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Rompen IF, Marchetti A, Levine J, Swett B, Galimberti V, Han J, Riachi ME, Habib JR, Imam R, Kaplan B, Sacks GD, Cao W, Wolfgang CL, Javed AA, Hewitt DB. Impact of resection margin status on recurrence and survival in patients with resectable, borderline resectable, and locally advanced pancreatic cancer. Surgery 2025; 180:109114. [PMID: 39798179 DOI: 10.1016/j.surg.2024.109114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 10/02/2024] [Accepted: 12/17/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND To improve outcomes for patients with pancreatic ductal adenocarcinoma, a complete resection is crucial. However, evidence regarding the impact of microscopically positive surgical margins (R1) on recurrence is conflicting due to varying definitions and limited populations of patients with borderline-resectable and locally advanced pancreatic cancer. Therefore, we aimed to determine the impact of the resection margin status on recurrence and survival in patients with pancreatic ductal adenocarcinoma stratified by local tumor stage. METHODS We performed a retrospective cohort study on patients with nonmetastatic pancreatic ductal adenocarcinoma undergoing pancreatectomy at a high-volume academic center (2012-2022). R1 was subclassified into microscopic invasion of the margin (R1 direct) or carcinoma present within 1 mm but not directly involving the margin (R1 <1 mm). Overall survival and time to recurrence were assessed by log-rank test and multivariable Cox regression. RESULTS Of 472 included patients, 154 (33%) had an R1 resection. Of those 50 (32%) had R1 <1 mm and 104 (68%) R1 direct. The most commonly involved margin was the uncinate (41%) followed by the pancreatic neck (16%) and vascular margins (9%). Overall, a stepwise shortening of time to recurrence and overall survival was observed with an increasing degree of margin involvement (median time to recurrence: R0 39.3 months, R1 <1 mm 16.0 months, and R1 direct 13.4 months, all comparisons P < .05). Multivariable analyses confirmed the independent prognostic value of R1 direct across all surgical stages. CONCLUSION The resection margin status portends an independent prognostic value. Moreover, this association persists in patients with borderline-resectable and locally advanced pancreatic cancer. Increasing the R0-resection rate is the most important potentially influenceable prognostic factor for improving surgery-related outcomes.
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Affiliation(s)
- Ingmar F Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY; Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. https://twitter.com/IngmarFRompen
| | - Alessio Marchetti
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY; Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. https://twitter.com/alemarche055
| | - Jonah Levine
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Benjamin Swett
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Veronica Galimberti
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Jane Han
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Mansour E Riachi
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Joseph R Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY. https://twitter.com/J_habib1
| | - Rami Imam
- Department of Pathology, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Brian Kaplan
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Greg D Sacks
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Wenqing Cao
- Department of Pathology, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Christopher L Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Ammar A Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY. https://twitter.com/ammar_asrar
| | - D Brock Hewitt
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY.
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Takamoto T, Nara S, Ban D, Mizui T, Miyata A, Esaki M. Neoadjuvant gemcitabine and S-1 in pancreatic ductal adenocarcinoma: Effects on nutritional status and pancreaticoduodenectomy outcomes. Surgery 2025; 180:109026. [PMID: 39740600 DOI: 10.1016/j.surg.2024.109026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/20/2024] [Accepted: 11/30/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND With the advent of improved chemotherapy options, neoadjuvant chemotherapy has gained acceptance as a multidisciplinary treatment approach for localized pancreatic ductal adenocarcinoma. This study aimed to clarify whether neoadjuvant chemotherapy with gemcitabine and S-1 influences preoperative nutritional status and postoperative outcomes, particularly in patients undergoing highly invasive pancreatic resection. METHODS Patients with resectable pancreatic ductal adenocarcinoma who underwent pancreaticoduodenectomy as upfront surgery or after neoadjuvant chemotherapy with gemcitabine and S-1 between January 2015 and December 2022 were assessed. In addition to perioperative surgical outcomes, preoperative nutritional status was evaluated using serum albumin, controlling nutritional status, and prognostic nutritional index. RESULTS A total of 158 patients who underwent upfront pancreaticoduodenectomy and 119 who received neoadjuvant chemotherapy with gemcitabine and S-1 before pancreaticoduodenectomy were evaluated. Preoperative nutritional assessments (serum albumin, controlling nutritional status score, and prognostic nutritional index) showed no significant differences between groups, either at the initial consultation or immediately before surgery. No significant differences were observed in postoperative outcomes, including blood loss, operation time, and morbidity. The neoadjuvant chemotherapy with gemcitabine and S-1 group had a significantly greater rate of negative tumor margins (R0 resection rate 86% vs 74%, P = .018), and improved overall survival (hazard ratio, 0.41; 95% confidence interval, 0.25-0.67, P < .001) compared with the upfront pancreaticoduodenectomy group. CONCLUSIONS Neoadjuvant chemotherapy with gemcitabine and S-1 does not adversely impact preoperative nutritional status and enhances the effectiveness of pancreaticoduodenectomy for resectable pancreatic ductal adenocarcinoma, leading to improved pathologically curative resection rates and overall survival.
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Affiliation(s)
- Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan.
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Akinori Miyata
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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Yun WG, Chae YS, Han Y, Jung HS, Cho YJ, Kang HC, Kwon W, Park JS, Chie EK, Jang JY. Efficacy of Neoadjuvant Radiotherapy After Chemotherapy and the Optimal Interval from Radiotherapy to Surgery for Borderline Resectable and Resectable Pancreatic Cancer. Ann Surg Oncol 2025; 32:2819-2829. [PMID: 39808212 PMCID: PMC11882644 DOI: 10.1245/s10434-024-16743-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 12/10/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Benefits of neoadjuvant treatment for pancreatic cancer with major vessel invasion has been demonstrated through randomized controlled trials; however, the optimal neoadjuvant treatment strategy remains controversial, especially for radiotherapy. Therefore, we aimed to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy and the optimal time interval to undergo surgery after radiotherapy in (borderline) resectable pancreatic cancer. METHODS Between 2013 and 2022, patients with (borderline) resectable pancreatic cancer with vessel contact who received 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan or gemcitabine and nanoparticle albumin-bound paclitaxel as initial treatment following surgery were included. Patients who received radiotherapy after chemotherapy and those who did not were matched using 1:1 nearest-neighbor propensity scores. Propensity scores were measured using the tumor size at initial image, duration of neoadjuvant chemotherapy, and responsiveness to neoadjuvant chemotherapy. RESULTS Of 212 patients, 166 patients were retrieved for the matched cohort. Patients who received radiotherapy had significantly better postoperative survival, local control, and R0 resection rates than those who did not. Furthermore, patients who underwent surgery within 4 weeks after completing radiotherapy had lower intraoperative blood loss and a clinically relevant postoperative pancreatic fistula rate than those who underwent surgery after more than 4 weeks. CONCLUSIONS In patients with (borderline) resectable pancreatic cancer with vessel contact who were scheduled for curative-intent surgery after neoadjuvant chemotherapy, additional radiotherapy was associated with better postoperative survival and local control. Furthermore, our findings suggested that scheduling surgery within 4 weeks following radiation therapy might enhance the perioperative outcomes.
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Affiliation(s)
- Won-Gun Yun
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Soo Chae
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Youngmin Han
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hye-Sol Jung
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Jae Cho
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Wooil Kwon
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Joon Seong Park
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
- Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Addeo P, Muzzolini M, Laurent C, Heyd B, Sauvanet A, Garnier J, Alfano MS, Gaujoux S, De Ponthaud C, Marchese U, Da Silva D, Buc E, Souche R, Fabre JM, Colombo PE, Ferre L, Foguenne M, Hubert C, El Amrani M, Truant S, Schwartz L, Regenet N, Dupre A, Brustia R, Cherif R, Navez J, Darnis B, Facy O, Grellet R, Piessen G, Veziant J, Rhaiem R, Kianmanesh R, Fernandez-De-Sevilla E, Gelli M, Taibi A, Georges P, Mabrut JY, Lesurtel M, Doussot A, Bachellier P. Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study. Ann Surg Oncol 2025; 32:2809-2818. [PMID: 39777595 DOI: 10.1245/s10434-024-16735-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). METHODS This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS. RESULTS There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9-177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4-NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00-6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27-5.41; p = 0.009). CONCLUSIONS Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy.
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Affiliation(s)
- Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
| | - Milena Muzzolini
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Christophe Laurent
- Department of Digestive Surgery, Centre Magellan-CHU Bordeaux, Bordeaux, France
| | - Bruno Heyd
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Alain Sauvanet
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Jonathan Garnier
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Marie Sophie Alfano
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Sebastien Gaujoux
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Charles De Ponthaud
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Doris Da Silva
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Emmanuel Buc
- Department of Digestive and Hepatobiliary Surgery-Liver Transplantation, University Hospital Clermont-Ferrand, Clermont-Ferrand, France
| | - Regis Souche
- Department of Surgery, Hopital Saint Eloi, Montpellier, France
| | | | - Pierre-Emanuel Colombo
- Department of Surgical Oncology, Institut du Cancer de Montpellier (ICM), Montpellier, France
| | - Lorenzo Ferre
- Department of Surgical Oncology, Institut du Cancer de Montpellier (ICM), Montpellier, France
| | - Maxime Foguenne
- Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Catherine Hubert
- Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Stephanie Truant
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Lilian Schwartz
- Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, Rouen, France
| | - Nicolas Regenet
- Department of Digestive Surgery, Nantes Hospital, Nantes, France
| | - Aurelien Dupre
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Rim Cherif
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Benjamin Darnis
- Department of Digestive Surgery, Clinique de La Sauvegarde, Lyon, France
| | - Olivier Facy
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Robin Grellet
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Julie Veziant
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Rami Rhaiem
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | | | | | - Abdelkader Taibi
- Department of Digestive Surgery, Dupuytren Limoges University Hospital, Limoges, France
| | - Pauline Georges
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Jean Yves Mabrut
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Mickael Lesurtel
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Alexandre Doussot
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
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Citterio D, Droz Dit Busset M, Sposito C, Mazzola M, Grandi S, Zironda A, Leoncini G, Simonotti N, Battiston C, Flores M, Ferrari G, Mazzaferro V. Prediction of early recurrence as a marker of surgical futility in pancreatic adenocarcinoma. Surg Oncol 2025; 59:102208. [PMID: 40086295 DOI: 10.1016/j.suronc.2025.102208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 02/06/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Long-term survival after resection for pancreatic ductal adenocarcinoma (PDAC) is impaired by very high recurrence rates. When recurrence occurs within 6 months (early recurrence: ER) the benefit of surgery is equivalent to palliative chemotherapy in unresectable patients. Therefore, ER is a surrogate of surgical futility in PDAC. MATERIALS AND METHODS To investigate predictive factors of ER and its impact on survival, a training and a validation cohort of prospectively collected patients who underwent surgery for resectable or borderline-resectable PDAC were analyzed in two independent Pancreas Units during the same period. Logistic regression model on the training cohort identified independent predictors of ER, used to build a prognostic risk-score then tested on the validation cohort. RESULTS Out of 176 patients in the training cohort, 21.6 % experienced ER, with significant impact on survival (OS: 9.7 months vs. 32.7 months for ER vs. late/no recurrence, respectively). At multivariable analysis, three independent risk factors for ER were identified: Ca19.9 > 100 U/mL, G3 tumors and lack of adjuvant chemotherapy. Based on such features the derived ER-score stratified three prognostic classes at incremental risk of ER (12 %, 35 % and 53 %) with different OS (31.1, 19.7 and 9.3 months, respectively, p < 0.001). The ER predictive score was then tested on a validation cohort of 242 patients, 22.3 % of whom underwent ER. Despite significant differences in tumor-related features, the score was able to discriminate among the predicted ER-risk classes (15 %, 27 % and 53 %, respectively) and forecast significantly different OS (5.8, 19 and 31.1 months, p > 0.001). The discriminative capability of the score in the two cohorts was similar (training AUC = 0.72 vs. validation AUC = 0.68, p = 0.28). CONCLUSION An externally validated clinical score, able to identify three prognostic classes at incremental risk of developing ER after resection of PDAC is provided. In patients at high risk of ER, prediction of surgical futility may help in decision-making.
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Affiliation(s)
- Davide Citterio
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Sposito
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy
| | - Michele Mazzola
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Samuele Grandi
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Andrea Zironda
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Giuseppe Leoncini
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Nicolò Simonotti
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Battiston
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Flores
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Giovanni Ferrari
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy.
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6
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Yin H, Xin Y, Yang J, Luo Q, Yang M, Sun J, Wang Y, Wang Q, Kalvakolanu DV, Guo B, Jiang W, Zhang L. Multifunctional nanozymes: Promising applications in clinical diagnosis and cancer treatment. Biosens Bioelectron 2025; 279:117383. [PMID: 40121930 DOI: 10.1016/j.bios.2025.117383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 02/09/2025] [Accepted: 03/14/2025] [Indexed: 03/25/2025]
Abstract
Cancer remains one of the greatest challenges in modern medicine. Traditional chemotherapy drugs often cause severe side effects, including nausea, vomiting, diarrhea, neurotoxicity, liver damage, and nephrotoxicity. In addition to these adverse effects, high recurrence and metastasis rates following treatment pose significant challenges for clinicians. There is an urgent need for novel therapeutic strategies to improve cancer treatment outcomes. In this context, nanozymes-artificial enzyme mimetics-have attracted considerable attention due to their unique advantages, including potent tumor-killing effects, enhanced biocompatibility, and reduced toxicity. Notably, nanozymes can dynamically monitor tumors through imaging and tracing. The multifunctional nanozyme (MN) is a promising research focus, integrating multiple catalytic activities, signal enhancement, sensing capabilities, and diverse modifications within a single nanozyme system. MNs can selectively target tumor regions, facilitating synergistic effects with other cancer therapies while enabling real-time imaging and tumor tracking. In this review, we first categorize MNs based on their composition and structural characteristics. We then discuss the primary mechanisms by which MNs exert their anticancer effects. Additionally, we review three types of MN biosensors and four MN-based therapeutic approaches applied in cancer treatment. Finally, we highlight the current challenges in MN research and provide an outlook on future developments in this field.
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Affiliation(s)
- Hailin Yin
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Yang Xin
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Jiaying Yang
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Qian Luo
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Mei Yang
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Jicheng Sun
- Department of Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China
| | - Yingtong Wang
- The Undergraduate Center of Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Qi Wang
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China
| | - Dhan V Kalvakolanu
- Greenebaum NCI Comprehensive Cancer Center, Department of Microbiology and Immunology, University of Maryland School Medicine, Baltimore, MD, USA
| | - Baofeng Guo
- Department of Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China
| | - Wei Jiang
- Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450052, China.
| | - Ling Zhang
- College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China.
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Duhn J, von Fritsch L, Bolm L, Braun R, Honselmann K, Litkevych S, Kist M, Deichmann S, Tol KKV, Franke B, Reinwald F, Sackmann A, Holleczek B, Krauß A, Klinkhammer-Schalke M, Zeissig SR, Keck T, Wellner UF, Abdalla TSA. Perioperative and oncologic outcomes after total pancreatectomy and pancreatoduodenectomy for pancreatic head adenocarcinoma-A propensity score-matched analysis from the German Cancer Registry Group. Surgery 2025; 181:109292. [PMID: 40101369 DOI: 10.1016/j.surg.2025.109292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/08/2025] [Accepted: 02/01/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND To compare perioperative morbidity and mortality in patients receiving pancreatoduodenectomy or total pancreatectomy for pancreatic head adenocarcinoma using German Cancer Registry data. METHODS Anonymized pooled data were retrieved from regional cancer registries participating in the German Cancer Registry Group of the Association of German Tumor Centers. Included were patients diagnosed with pancreatic head adenocarcinoma since 2016, receiving curative intent pancreatoduodenectomy or total pancreatectomy. Patients were propensity-score matched according to age, sex, and histopathology. Primary endpoints were 30- and 90-day postoperative mortality. Secondary endpoints were administration of adjuvant chemotherapy, long-term survival, and patterns of cancer recurrence. The data were analyzed using R. RESULTS In total, 756 patients per treatment group were matched for further analyses. R0-resection rate was comparable between pancreatoduodenectomy and total pancreatectomy (69.6 vs 73.4%, P = .154). The 30-day (9.5 vs 4.8%, P < .001) and 90-day postoperative mortality (18.0 vs 11.0%, P < .001) rates were significantly lower after pancreatoduodenectomy compared with total pancreatectomy. After pancreatoduodenectomy, more patients received adjuvant chemotherapy (43.6 vs 53.3%, P < .001) and time to adjuvant chemotherapy was shorter (60.1 vs 52.7 days, P = .002) compared with total pancreatectomy. Long-term overall survival was worse after total pancreatectomy (P < .001), also in patients receiving adjuvant chemotherapy (P = .019). The sites of recurrence were comparable between both groups (P = .274). CONCLUSION The results of this study show greater perioperative morbidity and mortality after total pancreatectomy compared with pancreatoduodenectomy for pancreatic head malignancy. Also, long-term survival was worse after total pancreatectomy. These results emphasize the role of pancreatoduodenectomy as a standard surgical procedure for pancreatic head adenocarcinoma and suggest that total pancreatectomy should only be performed in selected patients.
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Affiliation(s)
- Jannis Duhn
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Lennart von Fritsch
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Rüdiger Braun
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Kim Honselmann
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Stanislav Litkevych
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Markus Kist
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Steffen Deichmann
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Kees Kleihues-van Tol
- Network for Care, Quality and Research in Oncology, German Cancer Registry Group of the Association of German Tumor Centers (ADT), Berlin, Germany
| | - Bianca Franke
- Network for Care, Quality and Research in Oncology, German Cancer Registry Group of the Association of German Tumor Centers (ADT), Berlin, Germany
| | - Fabian Reinwald
- Cancer Registry of Rhineland-Palatinate in the Institute for Digital Health Data, Mainz, Germany
| | - Andrea Sackmann
- Hessian Cancer Registry, Hessian Office for Health and Care, Frankfurt, Germany
| | | | - Anna Krauß
- Cancer Registry Mecklenburg-Western Pomerania, Greifswald, Germany
| | - Monika Klinkhammer-Schalke
- Network for Care, Quality and Research in Oncology, German Cancer Registry Group of the Association of German Tumor Centers (ADT), Berlin, Germany
| | - Sylke R Zeissig
- Network for Care, Quality and Research in Oncology, German Cancer Registry Group of the Association of German Tumor Centers (ADT), Berlin, Germany; Institute of Clinical Epidemiology and Biometry (ICE-B), University of Würzburg, Würzburg, Germany
| | - Tobias Keck
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
| | - Ulrich F Wellner
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Thaer S A Abdalla
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
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8
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Sanford NN, Narang AK, Aguilera TA, Bassetti MF, Chuong MD, Erickson BA, Goodman KA, Herman JM, Intven M, Kilcoyne A, Kim H, Paulson E, Reyngold M, Tsai S, Tchelebi LT, Tuli R, Versteijne E, Wei AC, Wo JY, Zhang Y, Hong TS, Hall WA. NRG Oncology International Consensus Contouring Atlas on Target Volumes and Dosing Strategies for Dose-Escalated Pancreatic Cancer Radiation Therapy. Int J Radiat Oncol Biol Phys 2025; 121:918-929. [PMID: 39510320 DOI: 10.1016/j.ijrobp.2024.10.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/09/2024] [Accepted: 10/11/2024] [Indexed: 11/15/2024]
Abstract
PURPOSE Dose-escalated radiation therapy is increasingly used in the treatment of pancreatic cancer; however, approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiation therapy. METHODS AND MATERIALS An expert international panel comprising 15 radiation oncologists, 2 surgeons, and 1 radiologist was recruited. Participants used MimCloud software to contour high- and low-risk clinical target volumes (CTVs) on 3 pancreatic cancer cases: a borderline resectable head tumor, a locally advanced head tumor, and a medically inoperable tail tumor. Simultaneous Truth and Performance Level Estimation volumes were created, and contours were analyzed using Dice similarity coefficients. RESULTS The contoured gross tumor volume for the borderline head, locally advanced head, and unresectable tail tumor cases were 156.7, 58.2, and 9.0 cc, respectively, and the Dice similarity coefficients (SD) for the high- and low-risk CTV ranged from 0.45 to 0.82. Consensus volumes were agreed upon by authors. High-risk CTVs comprised the tumor plus abutting vessels. Low-risk CTVs started superiorly at (tail and distal body tumors) or 1 cm above (head, neck and proximal body tumors) the celiac takeoff and extended inferiorly to the superior mesenteric artery at the level of the first jejunal takeoff. For head, neck, and proximal body tumors, the lateral volume encompassed the entire pancreas head and 5 to 10 mm around the celiac, superior mesenteric artery, superior mesenteric vein, including the common hepatic artery and medial portal vein, consistent with a "Triangle" volume-based approach. For distal body and tail tumors, the entire tail was included, along with the splenic vessels and the takeoffs of celiac artery. CONCLUSIONS Through multidisciplinary collaboration, we created consensus contouring guidelines for dose-escalated pancreatic cancer radiation therapy. These volumes include not only gross disease, but also routine elective coverage, and can be used to standardize practice for future trials seeking to define the role of dose-escalated radiation therapy in pancreatic cancer.
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Affiliation(s)
- Nina N Sanford
- Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Amol K Narang
- Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Todd A Aguilera
- Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin
| | - Michael D Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida
| | - Beth A Erickson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joseph M Herman
- Northwell Health Cancer Institute, Department of Radiation Medicine, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY; Histosonics, Plymouth, Minnesota
| | - Martijn Intven
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Aoife Kilcoyne
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts
| | - Hyun Kim
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | - Eric Paulson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Marsha Reyngold
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Susan Tsai
- Department of Surgical Oncology, Ohio State University, Columbus, Ohio
| | - Leila T Tchelebi
- Northwell Health Cancer Institute, Department of Radiation Medicine, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY
| | - Richard Tuli
- Department of Radiation Oncology, University of South Florida, Morsani College of Medicine, Florida
| | - Eva Versteijne
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Alice C Wei
- Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Jennifer Y Wo
- Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ying Zhang
- Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Theodore S Hong
- Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William A Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
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9
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Hill CS, Parkinson R, Jaffee EM, Sugar E, Zheng L, Onners B, Weiss MJ, Wolfgang CL, Cameron JL, Pawlik TM, Rosati L, Le DT, Hacker-Prietz A, Lutz ER, Schulick R, Narang AK, Laheru DA, Herman JM. Phase 1 Study of Adjuvant Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Transduced Pancreatic Tumor Cell Vaccine, Low-Dose Cyclophosphamide, and Stereotactic Body Radiation Therapy Followed by FOLFIRINOX in High-Risk Resected Pancreatic Ductal Adenocarcinoma. Int J Radiat Oncol Biol Phys 2025; 121:930-941. [PMID: 39547453 DOI: 10.1016/j.ijrobp.2024.10.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 09/06/2024] [Accepted: 10/06/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE Local and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC. PATIENTS AND METHODS The study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full-dose FFX. After toxicity review, cohort 2 had SBRT and was switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression. RESULTS Nineteen patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after 2 cycles of mFFX. Median overall survival (OS)/disease-free survival (DFS) for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. One- and 2-year OS for cohort 3 was 83%/75%, respectively. At the last follow-up (median = x), 5 patients were alive (42%) in cohort 3. CONCLUSIONS This is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.
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Affiliation(s)
- Colin S Hill
- Laura and Issac Perlmutter Cancer Center at New York University, Department of Radiation Oncology, New York University Grossman School of Medicine, New York, New York
| | - Rose Parkinson
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elizabeth M Jaffee
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elizabeth Sugar
- Division of Biostatistics and Bioinformatics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Lei Zheng
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Beth Onners
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Matthew J Weiss
- Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York, New York
| | - Christopher L Wolfgang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, New York, University Grossman School of Medicine, New York, New York
| | - John L Cameron
- Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, Columbus, Ohio
| | - Lauren Rosati
- Department of Pediatrics, Heersink School of Medicine, University of Alabama, Birmingham, Alabama
| | - Dung T Le
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Amy Hacker-Prietz
- Department of Radiation Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Richard Schulick
- Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado; University of Colorado Cancer Center, Aurora, Colorado
| | - Amol K Narang
- Department of Radiation Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Daniel A Laheru
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | - Joseph M Herman
- Radiation Medicine, Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York, New York..
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10
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Wu HY, Tsou HH, Lu LS, Lee HL, Chiou JF, Ch'ang HJ. Role of Neoadjuvant Chemoradiation Therapy for Resectable and Borderline Resectable Pancreatic Adenocarcinoma-A Systematic Review and Meta-Analysis. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00175-0. [PMID: 40074045 DOI: 10.1016/j.ijrobp.2025.02.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/31/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND Randomized trials and meta-analyses have indicated longer survival with neoadjuvant than with adjuvant therapy in patients with resectable or borderline resectable (R/BR) pancreatic adenocarcinoma. Despite the efficacy of chemotherapy, the role of radiation therapy as an adjuvant or neoadjuvant treatment for patients with R/BR pancreatic adenocarcinoma remains unclear. In this systematic review and meta-analysis, we compared the benefits of additional chemoradiation therapy (CRT) to neoadjuvant chemotherapy (NAC) with NAC alone for R/BR pancreatic adenocarcinoma. METHODS AND MATERIALS A systematic literature search was conducted on Embase, Web of Science, PubMed, Cochrane, and Google Scholar. Median overall survival (OS) was the primary endpoint. Secondary endpoints included disease-free survival (DFS), resection rate, and R0 resection rate. RESULTS This review and meta-analysis included 31 prospective studies, of which 9 were randomized trials. In these studies, 658 patients from 14 study arms received NAC alone and 912 patients from 19 study arms received both NAC and CRT (NAC-CRT). The pooled median OS was 25.55 months (95% CI, 21.59-30.24 months) for NAC alone and 17.55 months (95% CI, 16.47-18.70 months; P < .0001) for NAC-CRT. The pooled R0 resection rate was higher with NAC-CRT (83.43%) than with NAC (69.97%; P < .0001). No significant difference was observed in DFS or resection rate between the 2 groups. In patients who received 5 or more cycles of initial chemotherapy, NAC-CRT was associated with longer OS than NAC (23.30 vs 21.85 months; P = .856). CONCLUSIONS NAC provides significantly longer OS than NAC-CRT to R/BR pancreatic adenocarcinoma. NAC-CRT is associated with a significantly improved R0 resection rate. This positive local effect of CRT can be translated to extended survival when 5 cycles or more of NAC are prescribed.
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Affiliation(s)
- Hsiao-Yu Wu
- Institute of Public Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Hsiao-Hui Tsou
- Institute of Public Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Long-Sheng Lu
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Hsin-Lun Lee
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Jeng Fong Chiou
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Hui-Ju Ch'ang
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Department of Oncology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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11
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Dickerson LD, Gittens J, Brunning C, Jackson R, Schmid MC, Mielgo A, Palmer D, Halloran CM, Ghaneh P. Neoadjuvant treatment versus upfront surgery in borderline resectable and resectable pancreatic ductal adenocarcinoma: meta-analysis. BJS Open 2025; 9:zrae172. [PMID: 40126570 PMCID: PMC11932015 DOI: 10.1093/bjsopen/zrae172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 11/25/2024] [Accepted: 12/25/2024] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Pancreatic cancer prognosis remains poor despite advances in adjuvant treatment. Neoadjuvant treatment may improve survival and disease-free survival. This meta-analysis evaluates the outcomes for patients with borderline-resectable (borderline-resectable pancreatic cancer) or resectable disease (resectable pancreatic cancer) in randomized trials of neoadjuvant therapy versus upfront surgery. METHODS The review was performed according to PRISMA guidance. Articles were included from the start of the database until 1 May 2024. The primary outcome was overall survival. Secondary outcomes were progression-free survival, resection rate, R0 rate, N0 rate, vascular resection rate, surgical complications, significant adverse events and rates of adjuvant therapy. Data was collected from study manuscripts or through individual patient-level data extraction. Meta-analysis was performed using a random-effects model with subgroup comparisons for resectability status (resectable pancreatic cancer versus borderline-resectable pancreatic cancer) and treatment modality (chemotherapy versus chemoradiotherapy). RESULTS Nine trials were included representing 1194 patients. Four trials recruited borderline-resectable pancreatic cancer, four resectable pancreatic cancer and one both. Four trials reported chemotherapy, four chemoradiotherapy and one both treatments. Neoadjuvant treatment improved overall survival (HR 0.73, 95% c.i. 0.55 to 0.98; P = 0.001) and progression-free survival (HR 0.80, 95% c.i. 0.65 to 0.99; P = 0.041). Subgroup analysis demonstrated neoadjuvant treatment improved overall survival for borderline-resectable pancreatic cancer (HR 0.60, 95% c.i. 0.38 to 0.96) but not resectable pancreatic cancer (HR 0.90, 95% c.i. 0.63 to 1.28). The overall resection rate was lower in neoadjuvant treatment (72.6% versus 80.6%, RR 0.94, 95% c.i. 0.89 to 0.99; P = 0.020). R0 rate (43.8% versus 23.0%, RR 1.35, 95% c.i. 1.16 to 1.57; P = 0.002) and N0 rate (30.9% versus 15.0%, RR 2.03, 95% c.i. 1.50 to 2.74; P = 0.001) was improved in neoadjuvant treatment. Significant adverse events occurred more frequently in neoadjuvant treatment (56.1% versus 27.0%, RR 1.92, 95% c.i. 1.28 to 1.89; P = 0.007). CONCLUSION Neoadjuvant treatment significantly improves survival in borderline-resectable pancreatic cancer but not resectable pancreatic cancer. It should be regarded as standard of care for these patients. Further work is needed to identify the optimum neoadjuvant regimen and a possible role in the treatment of resectable pancreatic cancer.
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Affiliation(s)
- Luke D Dickerson
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Pancreatobiliary Surgery Unit, Liverpool University Foundation Trust, Liverpool, UK
| | - Jayden Gittens
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Chris Brunning
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Richard Jackson
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Michael C Schmid
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Ainhoa Mielgo
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Daniel Palmer
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Department of Medical Oncology, Clatterbridge Cancer Centre, Liverpool, UK
| | - Christopher M Halloran
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Pancreatobiliary Surgery Unit, Liverpool University Foundation Trust, Liverpool, UK
| | - Paula Ghaneh
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Pancreatobiliary Surgery Unit, Liverpool University Foundation Trust, Liverpool, UK
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12
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Zhao Y, Yang Y, Zhang B, Cui H, Liu L, Wang R, Han Y, Zhu D, Ma W, Zhang X, Wang J, Xiong S, Bai S, Zhu X, Cheng B. Endoscopic Ultrasound-Guided Brachytherapy of Yttrium-90 Implantation Into Pancreas: A Dose-Escalation Pilot Study. MedComm (Beijing) 2025; 6:e70117. [PMID: 40008378 PMCID: PMC11850441 DOI: 10.1002/mco2.70117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 01/10/2025] [Accepted: 01/20/2025] [Indexed: 02/27/2025] Open
Abstract
Intratumoral brachytherapy enables higher dose treatment and reduces damage to adjacent tissues. We first validated the feasibility and safety of endoscopic ultrasound (EUS)-guided Yttrium-90 (90Y) microspheres implantation in a porcine model. Under EUS guidance, 90Y-loaded microspheres were implanted into the pancreas of 10 miniature pigs. The first pig was implanted with 10 MBq particles. Subsequently, nine pigs were sequentially included in the low- (20 MBq), medium- (40 MBq), and high-dose (60 MBq) groups. Positron emission tomography (PET)/CT imaging was used to check the occurrence of particle displacement postoperatively. After euthanasia, the pancreas and adjacent organs were excised for histological examination and residue radiation detection. The absorbed doses demonstrated safe in the porcine model were further in the xenograft model and KRASLSL/+Trp53FL/FLPtfqaCre/+ mouse model. EUS-guided implantations of 90Y-loaded microspheres were successful in all animals. Two pigs had mild serum amylase elevation in the high-dose group and the abnormal index returned to baseline without interventions. The volume of necrotic lesions ranged from 255.76 to 745.57 mm3. In KPC mouse model, PET/CT imaging demonstrated a significant decrease in maximum standardized uptake value (SUVmax) after 90Y implantation. EUS-guided 90Y-loaded carbon microsphere implantation could serve as a safe and feasible technique at ultrahigh dose for pancreatic cancer brachytherapy.
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Affiliation(s)
- Yuchong Zhao
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Yilei Yang
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Buchuan Zhang
- Department of Nuclear MedicineTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Haochen Cui
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Luyao Liu
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Ronghua Wang
- Department of SurgeryUniversity of Pittsburgh School of MedicinePittsburghPennsylvaniaUSA
| | - Yunfeng Han
- Department of Nuclear MedicineTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Dongling Zhu
- Department of Nuclear MedicineTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Wenliang Ma
- Chengdu New Radiomedicine Technology Co., LtdChengduChina
| | - Xinxing Zhang
- Chengdu New Radiomedicine Technology Co., LtdChengduChina
| | - Jinlin Wang
- Department of OncologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Si Xiong
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Shuya Bai
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Xiaohua Zhu
- Department of Nuclear MedicineTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Bin Cheng
- Department of Gastroenterology and HepatologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
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13
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Harrison J, Brauer DG. Updates in the Surgical Management of Pancreatic Ductal Adenocarcinoma. Gastroenterol Clin North Am 2025; 54:223-243. [PMID: 39880530 DOI: 10.1016/j.gtc.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Surgical management of pancreas cancer is complex, including the timing of surgery, surgical approach, intraoperative techniques, and postoperative management, which are reviewed in detail in this manuscript. Ultimately, referral to a high-volume pancreatic surgeon or pancreatic surgery center is critical to ensuring appropriate short-term and long-term outcomes.
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Affiliation(s)
- Julia Harrison
- Department of Surgery, University of Minnesota, 420 Delaware Street SE, MMC 195, Minneapolis, MN 55455, USA
| | - David G Brauer
- Department of Surgery, University of Minnesota, 420 Delaware Street SE, MMC 195, Minneapolis, MN 55455, USA.
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14
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Tang P, Zhang J, Zhou Q, Yi W, Wang H. Effect of Radiotherapy in Neoadjuvant Treatment of Borderline Resectable and Locally Advanced Pancreatic Cancer: A Systematic Review and Meta-analysis. Pancreas 2025; 54:e246-e254. [PMID: 39999316 DOI: 10.1097/mpa.0000000000002400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
BACKGROUND Pancreatic cancer is a malignant tumor with poor prognosis and bad curative effect. Previous studies did not confirm the role of radiotherapy in neoadjuvant treatment of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). By reviewing new findings reported in recent years, we conducted this study to evaluate the survival impact by comparing chemoradiotherapy (CRT) with chemotherapy alone. MATERIALS AND METHODS PubMed, Embase, MEDLINE, Web of Science, Scopus, and Cochrane Library were searched for studies reporting median overall survival (OS) in patients with BRPC or LAPC treated with neoadjuvant treatment. Secondary outcomes included progression-free survival (PFS) or disease-free survival (DFS) or recurrence-free survival (RFS) and R0 resection rate. RESULTS A total of 18 studies were included in the meta-analysis. OS (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.91, I2 = 61.7%) and PFS/DFS/RFS (HR = 0.72, 95% CI: 0.58-0.91, I2 = 52.3%) are both favored CRT. Although R0 resection rate was increased in CRT group, significant survival benefit of radiotherapy was found in LAPC and low resection rate subgroup in stratification analysis. Regression analysis showed that only tumor resectability was associated with OS. CONCLUSIONS For patients with LAPC and who are unlikely to receive resection, neoadjuvant radiotherapy seems to improve OS and PFS/DFS/RFS.
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Affiliation(s)
| | - Junfeng Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, China
| | - Qiang Zhou
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, China
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15
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Donadio MDS, de Jesus VHF. Stepped-wedge clinical trials in pancreatic cancer: a step backward in improving overall survival or a leap forward to enhance quality of care? Gland Surg 2025; 14:263-267. [PMID: 40115846 PMCID: PMC11921292 DOI: 10.21037/gs-24-472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 02/03/2025] [Indexed: 03/23/2025]
Affiliation(s)
| | - Victor Hugo Fonseca de Jesus
- Department of Gastrointestinal Medical Oncology, Oncoclínicas, Florianópolis, SC, Brazil
- Department of Medical Oncology, Centro de Pesquisas Oncológicas (CEPON), Florianópolis, SC, Brazil
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16
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Kersch CN, Grossberg AJ. Perioperative Radiation for Patients with Resectable Pancreatic Cancer: an Updated Review After the Initial RTOG 0848 Results. J Gastrointest Cancer 2025; 56:70. [PMID: 39987276 DOI: 10.1007/s12029-025-01185-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2025] [Indexed: 02/24/2025]
Abstract
PURPOSE Pancreatic cancer remains one of the most lethal malignancies, with limited long-term survival despite advances in treatment strategies. While surgical resection offers the best chance for cure in localized disease, high rates of recurrence underscore the need for effective adjuvant therapies. Over four decades, the role of adjuvant chemoradiation (CRT) has been the subject of significant debate, with numerous trials yielding mixed outcomes regarding its impact on survival. Improvements in chemotherapy regimens and radiotherapy techniques have prompted renewed efforts to define the value of CRT, particularly in comparison to chemotherapy alone. The recent initial results of RTOG 0848 mark a critical milestone in this ongoing discussion, providing contemporary evidence that challenges established assumptions and refines patient selection criteria. By identifying specific subgroups-such as lymph node-negative patients-which may benefit from CRT, the trial offers clarity while highlighting the limitations of CRT in other populations. METHODS Herein, we review prior prospective and retrospective trials that investigated the role of perioperative CRT, in particular radiation therapy, for resectable pancreatic cancer. RESULTS This review examines the trajectory of research on CRT in pancreatic cancer, assesses the implications of RTOG 0848 for current clinical practice, and underscores the importance of further studies to optimize the integration of multimodal therapy in the management of this aggressive disease. CONCLUSION The combination of results from RTOG 0848 in conjunction with the results of prior prospective and retrospective trials lend support for the use of adjuvant RT for patients with both lymph node-negative and lymph node-positive disease. However, several open questions remain about the role of this therapy in select patient cohorts, and whether neoadjuvant versus advent radiation is optimal.
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Affiliation(s)
- Cymon N Kersch
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Aaron J Grossberg
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, USA.
- Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University, Portland, OR, USA.
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, USA.
- Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
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17
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Chan AHY, Zhao Y, Tan HL, Chua DW, Ng KYY, Lee SY, Lee JJX, Tai D, Goh BKP, Koh YX. Clinical Outcomes of Neoadjuvant Therapy Versus Upfront Surgery in Resectable Pancreatic Cancer: Systematic Review and Meta-analysis of Latest Randomized Controlled Trials. Ann Surg Oncol 2025:10.1245/s10434-024-16674-y. [PMID: 39987384 DOI: 10.1245/s10434-024-16674-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 11/23/2024] [Indexed: 02/24/2025]
Abstract
BACKGROUND Survival and surgical benefits of neoadjuvant treatments (NAT) in resectable pancreatic cancer (RPC) remains unclear. The role of NAT in providing additional benefits to reduce biological aggressiveness and recurrence is worth elucidating. We assessed the latest randomized controlled trials (RCTs). METHODS A systematic review and meta-analysis was performed including trials published from inception to February 2024 to evaluate survival, surgical, and short-term oncological benefits with RCTs for RPC, comparing NAT with upfront surgery. RESULTS Eight RCTs with 982 patients were analyzed. RPC treated with NAT conferred better median disease-free survival (DFS) compared to upfront surgery (HR = 0.66, p = 0.01) with a significantly improved R0 resection (RR = 1.20, p = 0.04) and pN0 rate (RR = 1.68, p < 0.001). These benefits did not translate into overall survival benefits (HR = 0.81, p = 0.06). Postoperative major morbidity and mortality did not differ significantly between treatment approaches. No significant difference was noted in resection rate (RR = 0.95, p = 0.21). However, a significantly lower surgical exploration rate was exhibited in the NAT group (RR = 0.84, p = 0.007). CONCLUSION NAT conferred better DFS with significantly improved R0 resection rate and pN0 rate compared with upfront surgery. Our findings highlight the potential benefits of NAT in enhancing survival, surgical, and short-term oncological outcomes without increasing postoperative risks.
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Affiliation(s)
- Anna Ho Yin Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
| | - Yun Zhao
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Hwee Leong Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Darren Weiquan Chua
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Kennedy Yao Yi Ng
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Suat Ying Lee
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Joycelyn Jie Xin Lee
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - David Tai
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore.
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
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18
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Mauro A, Faverio C, Brizzi L, Mazza S, Scalvini D, Alfieri D, Cappellini A, Chicco F, Ciccioli C, Delogu C, Bardone M, Gallotti A, Pagani A, Torello Viera F, Anderloni A. Multidisciplinary Therapeutic Approaches to Pancreatic Cancer According to the Resectability Status. J Clin Med 2025; 14:1167. [PMID: 40004698 PMCID: PMC11856188 DOI: 10.3390/jcm14041167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/20/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, characterized by late diagnosis, rapid progression, and limited therapeutic options. Despite advancements, only 20% of patients are eligible for surgical resection at diagnosis, the sole curative treatment. Multidisciplinary evaluation is critical to optimize care, stratifying patients based on resectability into resectable, borderline resectable, locally advanced, and metastatic stages. Preoperative imaging, such as computed tomography (CT) and endoscopic ultrasound (EUS), remains central for staging, for vascular assessment, and tissue acquisition. Endoscopic and systemic approaches are pivotal for addressing complications like biliary obstruction and improving outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered for years the gold standard for biliary drainage, although EUS-guided drainage is increasingly utilized due to its efficacy in both resectable and unresectable disease. Systemic therapies play a key role in neoadjuvant, adjuvant, and palliative settings, with ongoing trials exploring their impact on survival and resectability chance. This review highlights the evolving multidisciplinary approaches tailored to the disease stage, focusing on biliary drainage techniques, systemic therapies, and their integration into comprehensive care pathways for PDAC. The continuous refinement of these strategies offers incremental survival benefits and underscores the importance of personalized, multidisciplinary management.
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Affiliation(s)
- Aurelio Mauro
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Carlotta Faverio
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Leonardo Brizzi
- Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefano Mazza
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Davide Scalvini
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Daniele Alfieri
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Alessandro Cappellini
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Fabio Chicco
- Gastroenterology & Digestive Endoscopy Unit, AO Lodi, 26900 Lodi, Italy
| | - Carlo Ciccioli
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, 90133 Palermo, Italy
| | - Claudia Delogu
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Marco Bardone
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Anna Gallotti
- Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Anna Pagani
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Francesca Torello Viera
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
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19
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Hayat U, Croce PS, Saadeh A, Desai K, Appiah J, Khan S, Khan YI, Kumar K, Hanif A. Current and Emerging Treatment Options for Pancreatic Cancer: A Comprehensive Review. J Clin Med 2025; 14:1129. [PMID: 40004658 PMCID: PMC11856716 DOI: 10.3390/jcm14041129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of death worldwide, and its global burden has increased significantly over the past few years. The incidence of pancreatic cancer has also increased in the United States, and most of this increase is attributed to the population's aging process in addition to the rise in the prevalence of risk factors such as obesity, diabetes, smoking, and alcohol intake. Most patients with pancreatic cancer present with advanced unresectable or metastatic disease. Only a few patients present at an early stage with localized disease, and a multidisciplinary approach is required to maximize survival and outcomes. The surgical approach is an option for localized disease, and surgery's safety and efficacy have also been improved in recent years due to the increasing use of minimally invasive surgical techniques. Moreover, systematic chemotherapy has also been used and has had a significant impact on survival. More recently, neoadjuvant therapy has been used for pancreatic cancer along with radiation therapy, optimizing survival among those patients. Targeted therapies have been introduced based on genetic testing in metastatic pancreatic cancer and have shown promising results. Moreover, immune checkpoint inhibitors and targeted agents such as PARP inhibitors and vaccines have emerged with optimal results in terms of survival. To conclude, pancreatic cancer is considered a disease with poor long-term survival; however, recent developments in pharmacotherapy have changed its treatment and have improved outcomes with improved survival. Our review summarizes ongoing therapeutic options for local and metastatic pancreatic cancer. It also summarizes new state-of-the-art therapies that have emerged or are in trials, which can change the pancreatic cancer treatment perspective.
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Affiliation(s)
- Umar Hayat
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Phillip S. Croce
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Aseel Saadeh
- Department of Internal Medicine, Geisinger Medical Center, Danville, PA 18711, USA;
| | - Karna Desai
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - John Appiah
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Sidrah Khan
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Yakub I. Khan
- Department of Internal Medicine, Division of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (Y.I.K.); (K.K.)
| | - Kishore Kumar
- Department of Internal Medicine, Division of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (Y.I.K.); (K.K.)
| | - Ahmad Hanif
- Department of Internal Medicine, Division of Hematology/Oncology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA;
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20
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Basree MM, Witt JS, Uboha NV, Lubner M, Minter R, Weber S, Ronnekleiv-Kelly S, Abbott D, Kratz J, Patel M, Zafar SN, LoConte N, Lubner SJ, Deming D, Ritter MA, Mohindra P, Bassetti MF. Neoadjuvant SBRT plus Elective Nodal Irradiation with Concurrent Capecitabine for Patients with Resectable Pancreatic Cancer: Survival Analysis of a Prospective Phase 1 Trial. Pract Radiat Oncol 2025:S1879-8500(25)00011-6. [PMID: 39924052 DOI: 10.1016/j.prro.2025.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/22/2024] [Accepted: 01/08/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND AND PURPOSE Elective nodal irradiation (ENI) in resectable pancreatic cancer remains undefined, though occult nodal disease is common. This study investigated the use of neoadjuvant stereotactic body radiation therapy (SBRT) to primary disease with ENI, with concurrent capecitabine. Safety data for this protocol were previously reported. In this report, we provide an updated survival analysis. MATERIALS AND METHODS This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 - 2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine (1650 mg/m2). All patients received ENI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities. Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier (KM) curves were employed for survival analysis. RESULTS Of 17 enrolled patients, 16 were evaluable (94.1%). Thirteen (76.5%) proceeded to surgery. Median follow up was 28.0 months (1.7 - 71.9). Four patients (25.0%) received neoadjuvant chemotherapy and six (37.5%) received adjuvant chemotherapy. Pathologic nodal involvement (69.2%) was associated with a higher risk of any relapse (p<0.01) and distant metastasis (p=0.02). Local failure occurred in 4 (25%) patients with 2/4 of those failures occurring partially within the 25 Gy elective nodal field and 1/4 occurred in the 25 Gy elective nodal field and partially within the 35 Gy tumor field. The median overall survival (OS) and disease-free survival (DFS) were 31.1 months (range, 2.3 - 73.6) and 12.0 months (range, 0.4 - 71.9), respectively. Three-year OS and DFS were 50% and 31.3% overall, and 61.5% and 38.5% for the surgical cohort. Patients with pN+ had worse median OS (23.9 vs 69.3 months; p=0.002) and DFS (9.9 vs 58.9 months; p=0.002). No further radiation related toxicities were noted since the prior report. CONCLUSION Neoadjuvant SBRT to the primary tumor with ENI and radiosensitizing chemotherapy is a feasible approach that may improve outcomes in patients with resectable and borderline pancreatic cancer, despite high rates of pathological nodal involvement. Further investigation of this strategy is warranted in a larger cohort.
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Affiliation(s)
- Mustafa M Basree
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
| | - Jacob S Witt
- Cancer Care Specialists of Illinois/Cancer Care Center of O'Fallon, O'Fallon, IL, USA
| | - Nataliya V Uboha
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Meghan Lubner
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Rebecca Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sean Ronnekleiv-Kelly
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Daniel Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jeremy Kratz
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI
| | - Monica Patel
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Syed Nabeel Zafar
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Noelle LoConte
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sam J Lubner
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Dustin Deming
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Mark A Ritter
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Pranshu Mohindra
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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21
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Aberle MR, Coolsen MME, Wenmaekers G, Volmer L, Brecheisen R, van Dijk D, Wee L, Van Dam RM, de Vos-Geelen J, Rensen SS, Damink SWMO. Skeletal muscle is independently associated with grade 3-4 toxicity in advanced stage pancreatic ductal adenocarcinoma patients receiving chemotherapy. Clin Nutr ESPEN 2025; 65:134-143. [PMID: 39577693 DOI: 10.1016/j.clnesp.2024.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/06/2024] [Accepted: 11/09/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) are regularly treated with FOLFIRINOX, a chemotherapy regimen based on 5-fluorouracil, irinotecan and oxaliplatin, which is associated with high toxicity. Dosing of FOLFIRINOX is based on body surface area, risking under- or overdosing caused by altered pharmacokinetics due to interindividual differences in body composition. This study aimed to investigate the relationship between body composition and treatment toxicity in advanced stage PDAC patients treated with FOLFIRINOX. METHODS Data from patients treated at the Maastricht University Medical Centre + between 2012 and 2020 were collected retrospectively (n = 65). Skeletal muscle-, visceral adipose tissue, subcutaneous adipose tissue-, (SM-Index, VAT-Index, SAT-Index resp.) and Skeletal Muscle Radiation Attenuation (SM-RA) were calculated after segmentation of computed tomography (CT) images at the third lumbar level using a validated deep learning method. Lean body mass (LBM) was estimated using SM-Index. Toxicities were scored and grade 3-4 adverse events were considered dose-limiting toxicities (DLTs). RESULTS Sixty-seven DLTs were reported during the median follow-up of 51.4 (95%CI 39.2-63.7) weeks. Patients who experienced at least one DLT had significantly higher dose intensity per LBM for all separate cytotoxics of FOLFIRINOX. Independent prognostic factors for the number of DLTs per cycle were: sarcopenia (β = 0.292; 95%CI 0.013 to 0.065; p = 0.013), SM-Index change (% per 30 days, β = -0.045; 95%CI -0.079 to -0.011; p = 0.011), VAT-Index change (% per 30 days, β = -0.006; 95%CI -0.012 to 0.000; p = 0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80 % (β = -0.315; 95 % CI -0.543 to -0.087; p = 0.008). CONCLUSION Sarcopenia and early muscle and fat wasting during FOLFIRINOX treatment were associated with treatment-related toxicity, warranting exploration of body composition guided personalized dosing of chemotherapeutics to limit DLTs.
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Affiliation(s)
- Merel R Aberle
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Mariëlle M E Coolsen
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
| | - Gilles Wenmaekers
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Leroy Volmer
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Radiotherapy (MAASTRO), Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Ralph Brecheisen
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - David van Dijk
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Leonard Wee
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Radiotherapy (MAASTRO), Maastricht University Medical Centre+, Maastricht, the Netherlands; Clinical Data Science, Maastricht University, Maastricht, the Netherlands
| | - Ronald M Van Dam
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
| | - Judith de Vos-Geelen
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Medical Oncology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Sander S Rensen
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
| | - Steven W M Olde Damink
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of General, Visceral- and Transplantation Surgery, RWTH Aachen University, Germany
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22
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Manoukian P, Kuhnen LC, van Laarhoven HWM, Bijlsma MF. Association of epigenetic landscapes with heterogeneity and plasticity in pancreatic cancer. Crit Rev Oncol Hematol 2025; 206:104573. [PMID: 39581245 DOI: 10.1016/j.critrevonc.2024.104573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/13/2024] [Accepted: 11/17/2024] [Indexed: 11/26/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.
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Affiliation(s)
- Paul Manoukian
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
| | - Leo C Kuhnen
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands
| | - Hanneke W M van Laarhoven
- Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Maarten F Bijlsma
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands
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23
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Nooijen LE, de Boer MT, Braat AE, Dewulf M, den Dulk M, Hagendoorn J, Hoogwater FJH, Lam HD, Molenaar Q, Neumann U, Porte RJ, Swijnenburg RJ, Zonderhuis B, Kazemier G, Klümpen HJ, van Gulik T, Groot Koerkamp B, Erdmann JI. National consensus on a new resectability classification for perihilar cholangiocarcinoma - A modified Delphi method. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:107117. [PMID: 37880001 DOI: 10.1016/j.ejso.2023.107117] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 10/03/2023] [Accepted: 10/10/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study. METHOD Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed. RESULTS The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease. CONCLUSION This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.
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Affiliation(s)
- Lynn E Nooijen
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Marieke T de Boer
- University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands
| | | | - Maxime Dewulf
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | - Marcel den Dulk
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | | | | | - Hwai-Ding Lam
- LUMC, Department of Surgery, Leiden, the Netherlands
| | | | - Ulf Neumann
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | - Robert J Porte
- University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands
| | - Rutger-Jan Swijnenburg
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Babs Zonderhuis
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Geert Kazemier
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Heinz-Josef Klümpen
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Thomas van Gulik
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Bas Groot Koerkamp
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, the Netherlands
| | - Joris I Erdmann
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
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24
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Bonazzi VF, Aoude LG, Brosda S, Bradford JJ, Lonie JM, Loffler KA, Gartside MG, Patel K, Mukhopadhyay P, Keane C, Gebski V, Kench JG, Goldstein D, Waddell N, Barbour AP. C-reactive protein is a prognostic biomarker in pancreatic ductal adenocarcinoma patients. Asia Pac J Clin Oncol 2025; 21:77-86. [PMID: 37415393 PMCID: PMC11733851 DOI: 10.1111/ajco.13993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 04/04/2023] [Accepted: 06/26/2023] [Indexed: 07/08/2023]
Abstract
AIM The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes. The non-randomized Phase II study "Gemcitabine and Abraxane for resectable Pancreatic cancer" (GAP) demonstrated the feasibility of perioperative gemcitabine/abraxane. Long-term survival in PDAC requires an effective immune response; hence, we undertook this translational study of the GAP trial cohort to identify immune-oncology biomarkers for clinical use. METHODS We combined Nanostring nCounter technology with immunohistochemistry to investigate the correlation between gene expression and overall patient survival. Findings were investigated in samples from the International Cancer Genome Consortium (ICGC, n = 88) and the Australian Pancreatic Genome Initiative (APGI, n = 227). RESULTS We confirmed that human equilibrative nucleoside transporter 1 (hENT1) expression was not a prognostic marker in PDAC but patients with high levels of hENT1 were more likely to live longer than 24 months post-surgery. Additionally, CD274 (PD-L1) and two novel biomarkers of survival, cathepsin W (CTSW) and C-reactive protein (CRP), were identified in the GAP cohort (n = 19). CRP expression was confirmed in data from the ICGC. Although PD-L1 and CTSW proteins were not significant across all three cohorts, results show that low CRP mRNA and protein expression are associated with longer overall survival in all three patient groups. CONCLUSION PDAC patients with long survival have higher hENT1 expression levels. Furthermore, CRP expression is a biomarker of poor prognosis following perioperative chemotherapy and resection in PDAC patients and thus may be useful for identifying patients who could benefit from more aggressive adjuvant strategies.
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Affiliation(s)
- Vanessa F. Bonazzi
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - Lauren G. Aoude
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - Sandra Brosda
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - Julia J. Bradford
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - James M. Lonie
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - Kelly A. Loffler
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Michael G. Gartside
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | - Kalpana Patel
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
| | | | - Colm Keane
- Mater Research Institute‐UQSouth BrisbaneQueenslandAustralia
| | - Val Gebski
- NHMRC Clinical Trials CentreCamperdownNew South WalesAustralia
| | - James G. Kench
- Royal Prince Alfred HospitalCamperdownNew South WalesAustralia
- University of Sydney Central Clinical SchoolCamperdownNew South WalesAustralia
| | - David Goldstein
- University of NSW Prince of Wales Clinical SchoolRandwickNew South WalesAustralia
| | - Nicola Waddell
- QIMRBerghofer Medical Research InstituteHerstonQueenslandAustralia
| | - Andrew P. Barbour
- Frazer InstituteThe University of QueenslandWoolloongabbaQueenslandAustralia
- Princess Alexandra HospitalWoolloongabbaQueenslandAustralia
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25
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Al Masad Q, Sousa A, Pena P, Sammartino CJ, Somasundar P, Abdelfattah T, Espat NJ, Calvino AS, Kwon S. Relationship of Time to First Therapy and Survival Outcomes of Neoadjuvant Chemotherapy Versus Upfront Surgery Approach in Resectable Pancreatic Ductal Adenocarcinoma. J Surg Res 2025; 306:111-121. [PMID: 39754820 DOI: 10.1016/j.jss.2024.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/02/2024] [Accepted: 12/07/2024] [Indexed: 01/06/2025]
Abstract
INTRODUCTION Evidence demonstrating overall survival benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor. METHODS A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC followed by definitive surgery compared to upfront surgery on overall survival with and without TTFT. RESULTS Total of 43,174 patients were included-9874 patients with clinical stage T1 and 33,300 patients with T2 PDACs. There were increasing trends in the NAC approach from 2.9% in 2010 to more than 25% by 2020 and decreasing trends in the upfront surgery approach from 69.34% in 2010 to 31.87% by 2020. There were significant differences in TTFT according to the treatment choice with upfront surgery group having a significantly shorter TTFT-proportion of those receiving first treatment within the first week was 24.32% in the upfront surgery compared to 4.22% in the NAC group. In the adjusted cox regression without the TTFT variable, there was a 25% higher rate of death in the upfront surgery compared to the NAC group (hazard ratio 1.25, 95% confidence interval 1.19-1.30). When the adjusted regression was performed with addition of a TTFT interaction term, there was survival disadvantage of upfront surgery approach in patients whose TTFT occurred after 1 wk, but not in those with TTFT occurring in less than 1 wk (hazard ratio 1.01, 95% confidence interval 0.86-1.17). CONCLUSIONS Our study emphasizes the importance of incorporating TTFT variable when comparing NAC versus upfront surgery approach in PDAC. Future studies comparing NAC to upfront surgery in resectable PDAC should consider incorporating the TTFT variable.
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Affiliation(s)
- Qusai Al Masad
- Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island
| | - Aryanna Sousa
- Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island
| | - Paola Pena
- Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island
| | - Cara J Sammartino
- Department of Public Health, Johnson and Wales University, Providence, Rhode Island
| | - Ponnandai Somasundar
- Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island; Department of Surgery, Boston University Medical Center, Boston, Massachusetts; Roger Williams Cancer Outcomes Research and Equity (RWCORE) Center, Providence, Rhode Island
| | - Thaer Abdelfattah
- Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island
| | - N Joseph Espat
- Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island; Department of Surgery, Boston University Medical Center, Boston, Massachusetts; Roger Williams Cancer Outcomes Research and Equity (RWCORE) Center, Providence, Rhode Island
| | - Abdul S Calvino
- Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island; Department of Surgery, Boston University Medical Center, Boston, Massachusetts; Roger Williams Cancer Outcomes Research and Equity (RWCORE) Center, Providence, Rhode Island
| | - Steve Kwon
- Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island; Department of Surgery, Boston University Medical Center, Boston, Massachusetts; Roger Williams Cancer Outcomes Research and Equity (RWCORE) Center, Providence, Rhode Island.
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26
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Yamane K, Anazawa T, Nagai K, Kasai Y, Masui T, Izuwa A, Kurahashi K, Ishida S, Ogiso S, Yoshimura M, Iwai T, Matsubara J, Fukuda A, Isoda H, Hidaka Y, Ibi Y, Hatano E. Neoadjuvant Chemoradiotherapy Using Moderately Hypofractionated Intensity-Modulated Radiotherapy Versus Upfront Surgery for Resectable Pancreatic Cancer: A Retrospective Cohort Study. Ann Surg Oncol 2025:10.1245/s10434-025-16956-z. [PMID: 39893341 DOI: 10.1245/s10434-025-16956-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 01/16/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND The efficacy of neoadjuvant chemoradiotherapy for resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. This study was designed to evaluate neoadjuvant chemoradiotherapy by using intensity-modulated radiotherapy (NAC-IMRT) for R-PDAC compared with upfront surgery (UpS). METHODS Among 198 patients with R-PDAC who were indicated for resection between 2013 and 2021, 130 were included in this study after excluding patients who underwent neoadjuvant chemotherapy and did not meet the NAC-IMRT criteria (Eligible set). NAC-IMRT was planned for 58 patients, and UpS was planned for 72 patients. Additionally, in 105 patients who could undergo the planned treatment (As-treated set), the surgical, pathological, and oncological outcomes were evaluated. RESULTS In the Eligible set, median overall survival (OS) was 50.5 months with NAC-IMRT and 34.7 months with UpS and progression-free survival was 20.4 months with NAC-IMRT and 13.9 months with UpS. In the As-treated set, OS was longer in the NAC-IMRT group (66.7 months vs. 34.7 months, p = 0.007). On multivariate analysis, NAC-IMRT was identified as an independent factor for better OS (hazard ratio 0.617, 95% confidence interval 0.382-0.995, p = 0.047, in the Eligible set). The incidence of postoperative complications did not show a difference between the two groups, and NAC-IMRT suppressed local tumor invasion, including lymphatic, venous, perineural invasion, and lymph node metastases. CONCLUSIONS NAC-IMRT may offer superior survival outcomes and manageable toxicity in R-PDAC patients compared with upfront surgery. This study supports the efficacy and safety of NAC-IMRT and recommends its consideration in R-PDAC treatment protocols.
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Affiliation(s)
- Kei Yamane
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yosuke Kasai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Surgery, Kurashiki Central Hospital, Okayama, Japan
| | - Aya Izuwa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koki Kurahashi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ishida
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Iwai
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Junichi Matsubara
- Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroyoshi Isoda
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yu Hidaka
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yumiko Ibi
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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27
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Karam E, Rondé-Roupie C, Aussilhou B, Hentic O, Rebours V, Lesurtel M, Sauvanet A, Dokmak S. Laparoscopic pancreatoduodenectomy is safe for the treatment of pancreatic ductal adenocarcinoma treated by chemoradiotherapy compared with open pancreatoduodenectomy: A matched case-control study. Surgery 2025; 178:108892. [PMID: 39488453 DOI: 10.1016/j.surg.2024.09.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/12/2024] [Accepted: 09/29/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Few studies compared laparoscopic and open pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy. METHODS Retrospective cohort of patients who underwent laparoscopic or open pancreatoduodenectomy for resectable or borderline resectable pancreatic ductal adenocarcinoma after chemoradiotherapy between 2012 and 2023 was analyzed. Open pancreatoduodenectomy patients could theoretically benefit from the laparoscopic approach. We used a 1:2 (laparoscopic-to-open pancreatoduodenectomy) propensity score matching analysis stratified on age, gender, and body mass index. RESULTS We included 128 patients (33 laparoscopic and 95 open pancreatoduodenectomy), and after propensity score matching, 33 laparoscopic pancreatoduodenectomy and 66 open pancreatoduodenectomy were compared. There was no difference in demographic data except for lower tobacco use in laparoscopic pancreatoduodenectomy group (9% vs 30%, P = .023) with similar clinical presentation. Laparoscopic pancreatoduodenectomy compared to open pancreatoduodenectomy showed a longer median operative duration (380 vs 255 minutes, P < .001), shorter median length of resected vein (15 vs 23 mm, P = .01), longer median venous clamping time (29 vs 15 minutes, P = .005), similar median blood loss (300 vs 300 mL, P = .223), similar rate of hard pancreas (97% vs 85%, P = .094), and a larger median size of Wirsung duct (5 vs 4 mm, P = .02). Postoperative outcomes showed similar 90-day mortality rates (3% vs 3%, P > .99), Clavien-Dindo III-IV complications (6% vs 14%, P = .158), median lengths of hospital stay (12 vs 13 days, P = .409), and readmission rates (9% vs 18%, P = .366). Pathologic data showed similar R0 resection rates (88% vs 82%, P = .568). With a similar rate of adjuvant chemotherapy (P = .324) and shorter median follow-up with laparoscopic pancreatoduodenectomy (18 vs 34 months, P = .004), 3-year overall (P = .768) and disease-free (P = .839) survival rates were similar. CONCLUSION In selected patients, laparoscopic pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy appears to be safe and feasible when performed in experienced centers.
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Affiliation(s)
- Elias Karam
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France; Visceral Surgery Unit, Tours University Hospital, France
| | - Charlotte Rondé-Roupie
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France
| | - Béatrice Aussilhou
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France
| | - Olivia Hentic
- Department of Pancreatology, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France
| | - Vinciane Rebours
- Department of Pancreatology, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France; Université de Paris Cité, Paris, France
| | - Mickaël Lesurtel
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France; Université de Paris Cité, Paris, France
| | - Alain Sauvanet
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France; Université de Paris Cité, Paris, France
| | - Safi Dokmak
- Department of Hepato-biliary-Pancreatic Surgery and Liver Transplantation, APHP, Hôpital Beaujon, DMU DIGEST, Clichy, France; Université de Paris Cité, Paris, France; Centre de Recherche sur l'Inflammation, INSERM Unité Mixte de Recherche 1149, Clichy, France.
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28
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Nomura S, Masui T, Muto J, Hashida K, Kitagawa H, Fujinuma I, Kitamura K, Ogura T, Takahashi A, Kawamoto K. Is distal pancreatectomy the optimal surgical procedure for pancreatic neck cancer? Surgery 2025; 178:108930. [PMID: 39581786 DOI: 10.1016/j.surg.2024.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 09/26/2024] [Accepted: 10/15/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND The optimal resection for pancreatic neck cancer is challenging in clinical practice because we could dissect by pancreaticoduodenectomy or distal pancreatectomy. The purpose of this study was to evaluate the effectiveness of lymph node dissection and to help determine the optimal surgical treatment for pancreatic neck cancer. METHODS We retrospectively evaluated 462 patients with pancreatic cancer who underwent curative-intent pancreatectomy between 2012 and 2022, 35 of whom had pancreatic neck cancer without preoperative radiologic gastroduodenal artery contact. We analyzed the clinicopathological characteristics, lymph node metastasis stations, and the efficacy index of lymph node dissection, which was calculated by multiplying the frequency of lymph node metastasis to each station by the 5-year survival rate of patients with positive lymph nodes at each station. RESULTS The lymph node station with the greatest rate of metastasis was #11p (28.6%), followed by #8 (17.1%), #14 (14.3%), #13 (14.3%), #17 (9.5%), and #6 (4.8%). The efficacy indices of lymph node dissection were 14.3 for #11, 4.76 for #13, and 8.57 for #14. There were no significant differences in 5-year recurrence-free survival and 5-year overall survival between patients undergoing pancreaticoduodenectomy and those undergoing distal pancreatectomy (23.7% vs 54.7%, P = .142; 29.9% vs 51.1%, P = .179, respectively). Univariate survival analysis showed that tumor size ≥2 cm was associated with poor prognosis (hazard ratio, 3.842, P = .009). CONCLUSIONS PD with #11p lymph node dissection is preferable to DP in terms of survival benefit for pancreatic neck cancer with lymph node metastasis.
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Affiliation(s)
- Satoshi Nomura
- Department of Surgery, Kurashiki Central Hospital, Kurashiki, Japan; Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan. https://www.twitter.com/NomuraSat60488
| | - Toshihiko Masui
- Department of Surgery, Kurashiki Central Hospital, Kurashiki, Japan.
| | - Jun Muto
- Department of Surgery, Kurashiki Central Hospital, Kurashiki, Japan
| | - Kazuki Hashida
- Department of Surgery, Kurashiki Central Hospital, Kurashiki, Japan; Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | | | - Ibuki Fujinuma
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Kei Kitamura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Toshiro Ogura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Amane Takahashi
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
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29
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Jarvis M, Laing R, James A. Anaesthesia for pancreatic resection surgery: part 1. BJA Educ 2025; 25:57-64. [PMID: 39897427 PMCID: PMC11785549 DOI: 10.1016/j.bjae.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2024] [Indexed: 02/04/2025] Open
Affiliation(s)
- M.S. Jarvis
- University Hospitals of Derby and Burton, Derby, UK
| | - R.W. Laing
- University Hospitals of North Midlands, Stoke-on-Trent, UK
| | - A. James
- University Hospitals of North Midlands, Stoke-on-Trent, UK
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30
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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Rangelova E, Stoop TF, van Ramshorst TME, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BKP, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CHJ, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, Ramaekers M, Truty MJ, van Dam MA, Stommel MWJ, Petrikowski M, Imamura M, Hayashi M, D'Hondt M, Brunner M, Hogg ME, Zhang C, Suárez-Muñoz MÁ, Luyer MD, Unno M, Mizuma M, Janot M, Sahakyan MA, Jamieson NB, Busch OR, Bilge O, Belyaev O, Franklin O, Sánchez-Velázquez P, Pessaux P, Holka PS, Ghorbani P, Casadei R, Sartoris R, Schulick RD, Grützmann R, Sutcliffe R, Mata R, Patel RB, Takahashi R, Rodriguez Franco S, Cabús SS, Hirano S, Gaujoux S, Festen S, Kozono S, Maithel SK, Chai SM, Yamaki S, van Laarhoven S, Mieog JSD, Murakami T, Codjia T, Sumiyoshi T, Karsten TM, Nakamura T, Sugawara T, Boggi U, Hartman V, de Meijer VE, Bartholomä W, Kwon W, Koh YX, Cho Y, Takeyama Y, Inoue Y, Nagakawa Y, Kawamoto Y, Ome Y, Soonawalla Z, Uemura K, Wolfgang CL, Jang JY, Padbury R, Satoi S, Messersmith W, Wilmink JW, Abu Hilal M, Besselink MG, Del Chiaro M. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Ann Oncol 2025:S0923-7534(25)00004-3. [PMID: 39814200 DOI: 10.1016/j.annonc.2024.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/26/2024] [Accepted: 12/23/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. PATIENTS AND METHODS This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. RESULTS Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. CONCLUSIONS Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.
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Affiliation(s)
- E Rangelova
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
| | - T F Stoop
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - T M E van Ramshorst
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy
| | - M Ali
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - E A van Bodegraven
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - A A Javed
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA
| | - D Hashimoto
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - E Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - A Banerjee
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - A Jain
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - A Sauvanet
- Department of HPB Surgery and Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - A Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - A Giani
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - A Giardino
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - A Zerbi
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - A Arshad
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - A G Wijma
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - A Coratti
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - A Zironda
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - A Socratous
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - A Rojas
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - A Halimi
- Department of Surgery, Umeå University, Umeå, Sweden; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - A Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - A Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - B Y Patel
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - B Björnsson
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
| | - B N Reames
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - B Tingstedt
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - B K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - C Payá-Llorente
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C D Del Pozo
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C González-Abós
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - C Medin
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - C H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - C de Ponthaud
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - C Takishita
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - C Schwabl
- Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
| | - C Månsson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - C Ricci
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - C A Thiels
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - D Douchi
- Department of Surgery, Tohoku University, Sendai, Japan
| | - D L Hughes
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - D Kilburn
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - D Flanking
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden
| | - D Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - D S Silva
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - B H Edil
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - E Pando
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - E Moltzer
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - E F Kauffman
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - E Warren
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - E Bozkurt
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - E Sparrelid
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - E Thoma
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - E Verkolf
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - F Ausania
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - F Giannone
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - F J Hüttner
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - F Burdio
- Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain
| | - F R Souche
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - F Berrevoet
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium
| | - F Daams
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - F Motoi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - G Saliba
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - G Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - G Roeyen
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - G Nappo
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - G Butturini
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - G Ferrari
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - G Kito Fusai
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - G Honda
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - G Sergeant
- Department of Abdominal Surgery, Jessa Hospital, Faculty of Medicine and Health Sciences, Universiteit Hasselt, Hasselt, Belgium
| | - H Karteszi
- Department of Radiology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - H Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - H Suto
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - I Matsumoto
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - I Mora-Oliver
- Department of Surgery, Liver and Pancreato-Biliary Unit, Hospital Clínico Universitario Valencia, Biomedical Research Institute, INCLIVA, Valencia, Spain
| | - I Frigerio
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - J M Fabre
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - J Chen
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - J G Sham
- Department of Surgery, University of Washington, Seattle, USA; Fred Hutchinson Cancer Center, Seattle, USA
| | - J Davide
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - J Urdzik
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - J de Martino
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - K Nielsen
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - K Okano
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - K Kamei
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - K Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - K Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - K J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - K E Goodsell
- Department of Surgery, University of Washington, Seattle, USA
| | - L Alberici
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - L Webber
- Department of Upper GI Surgery, Fiona Stanley Hospital, Perth, Austria
| | - L Kirkov
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - L de Franco
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - M Miyashita
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - M Maglione
- Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - M Gramellini
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - M Ramera
- Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - M J Amaral
- General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - M Ramaekers
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M J Truty
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - M A van Dam
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - M W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - M Petrikowski
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M Imamura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - M Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - M D'Hondt
- Department of Digestive and Hepatobiliary-Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - M Brunner
- Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
| | - M E Hogg
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - C Zhang
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - M Á Suárez-Muñoz
- HPB Surgical Unit, University Hospital Virgen de la Victoria, Málaga, Spain
| | - M D Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M Unno
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Mizuma
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Janot
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M A Sahakyan
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - N B Jamieson
- Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - O R Busch
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - O Bilge
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - O Belyaev
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - O Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Umeå University, Umeå, Sweden
| | - P Sánchez-Velázquez
- Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain
| | - P Pessaux
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - P S Holka
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - P Ghorbani
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - R Casadei
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - R Sartoris
- Department of Radiology, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - R D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - R Grützmann
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - R Sutcliffe
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - R Mata
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - R B Patel
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - R Takahashi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - S Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - S S Cabús
- Department of HPB Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - S Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - S Gaujoux
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - S Festen
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - S Kozono
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - S K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - S M Chai
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia
| | - S Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - S van Laarhoven
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of HPB Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - J S D Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - T Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - T Codjia
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - T Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - T M Karsten
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - T Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - T Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo
| | - U Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - V Hartman
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - V E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - W Bartholomä
- Department of Radiology, Linköping University, Linköping, Sweden
| | - W Kwon
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y X Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Y Cho
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y Takeyama
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - Y Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Y Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Y Kawamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Y Ome
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Z Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - K Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - C L Wolfgang
- Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA
| | - J Y Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - R Padbury
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - S Satoi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Kansai Medical University, Osaka, Japan
| | - W Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, USA
| | - J W Wilmink
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
| | - M Abu Hilal
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - M G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - M Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
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Madani SP, Mohseni A, Mirza-Aghazadeh-Attari M, Shahbazian H, Afyouni S, Borhani A, Zandieh G, Laheru D, Kamel IR. Role of volumetric tumor enhancement on CT in predicting overall survival in patients with unresectable pancreatic ductal adenocarcinoma. Clin Imaging 2025; 117:110365. [PMID: 39613522 DOI: 10.1016/j.clinimag.2024.110365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 11/06/2024] [Accepted: 11/18/2024] [Indexed: 12/01/2024]
Abstract
PURPOSE To assess the utility of volumetric tumor enhancement on CT to predict tumor treatment response and the overall survival (OS) of patients with PDAC undergoing FOLFIRINOX-based systemic chemotherapy. Additionally, we aim to explore the performance of a novel model that incorporates relevant volumetric CT-derived parameters to the established RECIST 1.1 in predicting both treatment response and OS. MATERIAL AND METHODS In this retrospective single-institution study, 127 patients with PDAC who received FOLFIRINOX neoadjuvant chemotherapy between December 2012 and November 2021 were included. Manual volumetric segmentation of the single largest tumor was performed on portal venous phase images. Total and enhancing tumor volumes were calculated. Response by RECIST 1.1 was compared to response by tumor volume and enhancing tumor volume on follow-up CT. RESULTS There was no association between overall survival and RECIST 1.1 (p-value = 0.284), volumetric RECIST (p-value = 0.402), and other volumetric CT variables, except for a percentage reduction in enhancing tumor volume (p-value = 0.043). Using univariate survival analysis for categorical thresholds defined by CART, the percentage change in enhancing tumor volume was associated with OS (p-value = 0.018). There was also a significant association between baseline enhancing tumor volume and OS (p-value <0.0001). Using these two categories, we defined a multivariable model associated with OS (p-value <0.0001). CONCLUSION Percentage reduction in enhancing tumor volume was related to OS in non-surgical PDAC patients treated with FOLFIRINOX chemotherapy and could potentially be incorporated into patient survival prediction models.
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Affiliation(s)
- Seyedeh Panid Madani
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Alireza Mohseni
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | | | - Haneyeh Shahbazian
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Shadi Afyouni
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Ali Borhani
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Ghazal Zandieh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Daniel Laheru
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Ihab R Kamel
- Department of Radiology, University of Colorado, Aurora, CO, USA.
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Mimori K, Fujii T, Sho M, Endo I, Shirabe K, Kitagawa Y. Interview with Prof. Dr. Jeffrey Drebin, President of the 2024 President Elect of the American Surgical Association. Ann Gastroenterol Surg 2025; 9:24-31. [PMID: 39759979 PMCID: PMC11693547 DOI: 10.1002/ags3.12882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 10/21/2024] [Indexed: 01/07/2025] Open
Affiliation(s)
- Koshi Mimori
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Tsutomu Fujii
- Department of Surgery and Science, Faculty of Medicine, Academic AssemblyUniversity of ToyamaToyamaJapan
| | - Masayuki Sho
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | - Itaru Endo
- Department of Gastroenterological SurgeryGraduate School of Medicine, Yokohama City UniversityYokohamaJapan
| | - Ken Shirabe
- Department of General Surgical ScienceGraduate School of Medicine, Gunma UniversityMaebashiJapan
| | - Yuko Kitagawa
- Department of SurgeryKeio University School of MedicineShinjukuJapan
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Janczewski LM, Visenio MR, Joung RHS, Yang AD, Odell DD, Danielson EC, Posner MC, Skolarus TA, Bentrem DJ, Bilimoria KY, Merkow RP. Assessment of intermediate-term mortality following pancreatectomy for cancer. J Natl Cancer Inst 2025; 117:49-57. [PMID: 39212612 PMCID: PMC11717425 DOI: 10.1093/jnci/djae215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/08/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Pancreatic cancer remains highly lethal, and resection represents the only chance for cure. Although patients are counseled regarding short-term (0-3 months) mortality, little is known about mortality 3-6 months (intermediate-term) following surgery. We assessed predictors of intermediate-term mortality, evaluated hospital-level variation, and developed a nomogram to predict intermediate-term mortality risk. METHODS Patients undergoing pancreatic cancer resection were identified from the National Cancer Database (2010-2020). Multivariable logistic regression identified predictors of intermediate-term mortality and assessed differences between short-term and intermediate-term mortality. Multinomial regression grouped by intermediate-term mortality quartiles evaluated hospital-level variation. A neural network model was constructed to predict intermediate-term mortality risk. All statistical tests were 2-sided. RESULTS Of 45 297 patients, 3974 (8.9%) died within 6 months of surgery of which 2216 (5.1%) were intermediate-term. Intermediate-term mortality was associated with increasing T category, positive nodes, lack of systemic therapy, and positive margins (all P < .05) compared with survival beyond 6 months. Compared with short-term mortality, intermediate-term mortality was associated with treatment at high-volume hospitals, positive nodes, neoadjuvant systemic therapy, adjuvant radiotherapy, and positive margins (all P < .05). Median intermediate-term mortality rate per hospital was 4.5% (interquartile range [IQR] = 2.6-6.5). Highest quartile hospitals had decreased odds of treatment with neoadjuvant systemic therapy, neoadjuvant radiotherapy, and adjuvant radiotherapy (all P < .05). The neural network nomogram was highly accurate (accuracy = 0.9499; area under the receiver operating characteristics curve = 0.7531) in predicting individualized intermediate-term mortality risk. CONCLUSION Nearly 10% of patients undergoing pancreatectomy for cancer died within 6 months, of which one-half occurred in the intermediate term. These data have real-world implications to improve shared decision making when discussing curative-intent pancreatectomy.
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Affiliation(s)
- Lauren M Janczewski
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Michael R Visenio
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Rachel Hae-Soo Joung
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Anthony D Yang
- Division of Surgical Oncology, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - David D Odell
- Division of Thoracic Surgery, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA
| | - Elizabeth C Danielson
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Mitchell C Posner
- Division of Surgical Oncology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Ted A Skolarus
- Department of Surgery, Urology Section, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - David J Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Karl Y Bilimoria
- Division of Surgical Oncology, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Ryan P Merkow
- Division of Surgical Oncology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
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Hashimoto D, Satoi S, Yamaki S, Nakayama S, Shibata N, Matsumura K, Miyazaki H, Matsui Y, Tsybulskyi D, Sang NT, Ikeura T, Kanai M, Sekimoto M. Neoadjuvant Treatment with Changes in Chemotherapy Regimens According to Carbohydrate Antigen 19-9 Level for Resectable/Borderline Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2025; 32:517-528. [PMID: 39433718 DOI: 10.1245/s10434-024-16361-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 09/28/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND The response of carbohydrate antigen (CA) 19-9 to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) may contribute to outcomes. This study aimed to investigate the effect of changes in NAT regimens based on CA19-9 level. METHODS This single-center retrospective study included patients with resectable/borderline resectable (R/BR)-PDAC undergoing NAT from 2008 to 2022. A CA19-9 level lower than 150 IU/mL after NAT was the criterion for resection. If the level did not decrease, the chemotherapy regimen was changed to satisfy the criterion. The patient cohort was divided into group A (satisfied criterion without changing chemotherapy), group B (did not receive chemotherapy change, could not satisfy the criterion), group C (received chemotherapy change, satisfied the criterion), and group D (received chemotherapy change, could not satisfy the criterion). RESULTS The study cohort included 283 patients. After first-line chemotherapy, 112 (39.6%) patients did not satisfy the criterion (groups B [n = 64], C [n = 32], and D [n = 16]). Of the 283 patients, 48 (17%) received a chemotherapy change (groups C and D). The patients in groups C and D showed significantly better overall survival (OS, 35.9 months) than the group B patients (25.7 months) (P = 0.035). The OS of the group C patients (63.8 months) was similar to the OS of the group A patients (n = 171: 56.3 months; P = 0.430). Multivariate analysis of the patients in groups B, C, and D identified chemotherapy change as an independent prognostic factor for OS and progression-free survival. CONCLUSION Changing the chemotherapy targeting the CA19-9 level can improve the outcome of R/BR-PDAC patients with poor biologic response to first-line NAT.
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Affiliation(s)
- Daisuke Hashimoto
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan.
- Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - So Yamaki
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Shinji Nakayama
- Third Department of Internal Medicine, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Nobuhiro Shibata
- Cancer Treatment Center, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Kazuki Matsumura
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Hidetaka Miyazaki
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Yuki Matsui
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Denys Tsybulskyi
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Nguyen Thanh Sang
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Masashi Kanai
- Cancer Treatment Center, Kansai Medical University, Hirakata City, Osaka, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata City, Osaka, Japan
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Marchese U, Lenne X, Naveendran G, Tzedakis S, Gaillard M, Richa Y, Boyer L, Theis D, Bruandet A, Truant S, Fuks D, El Amrani M. Nationwide analysis of one-year mortality following pancreatectomy in 17,183 patients with pancreatic cancer. HPB (Oxford) 2025; 27:123-129. [PMID: 39547905 DOI: 10.1016/j.hpb.2024.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/11/2024] [Accepted: 10/26/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND The use of 1-year mortality following pancreatectomy for PDAC as a measure of surgical quality has not been evaluated. We aim to i) assess the 1-year mortality rate following pancreatectomy for PDAC, and ii) identify patient and hospital characteristics associated with 1-year mortality. METHODS Data was extracted retrospectively from the French national medico-administrative database. The study included patients who underwent pancreatectomy for PDAC between January 2012 and December 2019. The primary outcome was 1-year postoperative mortality. Hospitals were classified based on volume (high (≥26 resections/year) and low volume (<26)). RESULTS Overall, 17,183 patients who underwent pancreatectomy for PDAC were included. The overall 90-day and 1-year mortalities were 6.5 % and 21.5 %, respectively. 1-year mortality varied significantly between low and high-volume hospitals (23.6 % vs. 18.6 %, respectively, p < 0.001). Older age, Charlson Comorbidity Index (CCI), readmission, major complications were predictive factors for 1-year mortality. Pancreatectomy in low volume hospitals increased the risk of 1-year mortality by 1.23-fold (OR = 1.23, 95 % CI [1.15-1.32], p < 0.001). CONCLUSION The overall 1-year mortality after pancreatectomy for PDAC was 21.5 %, and was higher in patients of older age, with higher comorbidities, who experienced major complications, and who did not receive adjuvant therapy. Management in high-volume centers decreased mortality rates, regardless of the patient's condition.
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Affiliation(s)
- Ugo Marchese
- Department of Digestive, HPB and Endocrine Surgery, Cochin Hospital, AP-HP Centre, 27 rue du Faubourg St Jacques, 75014, Paris, France; Université Paris Cité, 15 rue de l'école de Médecine, 75006, Paris, France.
| | - Xavier Lenne
- Département d'Information Médicale, CHRU de Lille, 2 Av. Oscar Lambret, 59000, Lille, France; Université de Lille, 42 rue Paul Duez, 59000, Lille, France
| | - Gaanan Naveendran
- Department of Digestive, HPB and Endocrine Surgery, Cochin Hospital, AP-HP Centre, 27 rue du Faubourg St Jacques, 75014, Paris, France; Université Paris Cité, 15 rue de l'école de Médecine, 75006, Paris, France
| | - Stylianos Tzedakis
- Department of Digestive, HPB and Endocrine Surgery, Cochin Hospital, AP-HP Centre, 27 rue du Faubourg St Jacques, 75014, Paris, France; Université Paris Cité, 15 rue de l'école de Médecine, 75006, Paris, France
| | - Martin Gaillard
- Department of Digestive, HPB and Endocrine Surgery, Cochin Hospital, AP-HP Centre, 27 rue du Faubourg St Jacques, 75014, Paris, France; Université Paris Cité, 15 rue de l'école de Médecine, 75006, Paris, France
| | - Yasmina Richa
- School of Medicine, University College Cork, Cork, Ireland
| | - Laurent Boyer
- Département d'Information Médicale, La Timone Hospital, 264 rue Saint-Pierre, 13005, Marseille, France; Université d'Aix-Marseille, Jardin du Pharo, 58 Boulevard Charles Livon, 13007, Marseille, France
| | - Didier Theis
- Département d'Information Médicale, CHRU de Lille, 2 Av. Oscar Lambret, 59000, Lille, France; Université de Lille, 42 rue Paul Duez, 59000, Lille, France
| | - Amelie Bruandet
- Département d'Information Médicale, CHRU de Lille, 2 Av. Oscar Lambret, 59000, Lille, France; Université de Lille, 42 rue Paul Duez, 59000, Lille, France
| | - Stephanie Truant
- Université de Lille, 42 rue Paul Duez, 59000, Lille, France; Department of digestive Surgery and Transplantation, CHRU de Lille, 2 Av. Oscar Lambret, 59000, Lille, France
| | - David Fuks
- Department of Digestive, HPB and Endocrine Surgery, Cochin Hospital, AP-HP Centre, 27 rue du Faubourg St Jacques, 75014, Paris, France; Université Paris Cité, 15 rue de l'école de Médecine, 75006, Paris, France
| | - Mehdi El Amrani
- Université de Lille, 42 rue Paul Duez, 59000, Lille, France; Department of digestive Surgery and Transplantation, CHRU de Lille, 2 Av. Oscar Lambret, 59000, Lille, France
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Ariake K, Mizuma M, Unno M, Satoi S, Yamamoto N, Hayashi M, Kawai M, Akita H, Toyoda E, Fujii T, Sasaki M, Hakamada K, Watanabe J, Hatano E, Hidaka M, Hirano S, Kurahara H, Matsumoto I, Honda G, Ogura T, Nakamura M, Endo I. Optimal treatment strategy for patients with pancreatic cancer having positive peritoneal cytology: A nationwide multicenter retrospective cohort study supervised by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2025; 32:69-81. [PMID: 39317950 PMCID: PMC11780303 DOI: 10.1002/jhbp.12074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
BACKGROUND The aim of this study was to determine the optimal treatment for patients with pancreatic cancer (PaCa) having positive peritoneal cytology (PPC). METHODS This multicenter retrospective study included patients with PPC treated at 78 high-volume centers between January 2012 and December 2020. Prognoses after resection (S-group) and initiation of nonsurgical treatment (N-group) were compared. Prognostic factors for survival in both groups were analyzed. Detailed characteristics of conversion surgery (CS) in the N-group were evaluated. RESULTS In total, 568 enrolled patients were classified into an S-group (n = 445) or an N-group (n = 123). Median survival times (MSTs) were 19.0 months and 19.3 months, respectively, with no significant difference in prognosis (p = .845). The intervenable prognostic factors for survival were adjuvant treatment in the S-group (p < .001) and CS in the N-group (p < .001). Following CS, the MST was prolonged to 45.6 months, and peritoneal or liver recurrence decreased considerably. CS can be expected if PPC is diagnosed before neoadjuvant treatment and when combination treatment is initiated. CONCLUSION Surgical resection may not be beneficial for improving survival when PPC is evident. Chemotherapy aiming for CS may be the optimal treatment for such patients.
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Affiliation(s)
- Kyohei Ariake
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
- Department of Gastroenterological SurgerySendai City Medical Center Sendai Open HospitalSendaiJapan
| | - Masamichi Mizuma
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Michiaki Unno
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Sohei Satoi
- Department of SurgeryKansai Medical UniversityHirakataJapan
| | - Naoto Yamamoto
- Department of Gastrointestinal SurgeryKanagawa Cancer CenterYokohamaJapan
| | - Masamichi Hayashi
- Department of Surgery, Graduate School of MedicineNagoya UniversityNagoyaJapan
| | - Manabu Kawai
- Second Department of SurgeryWakayama Medical University School of MedicineWakayamaJapan
| | - Hirofumi Akita
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Eiji Toyoda
- Department of SurgeryOtsu Red Cross HospitalOtsuJapan
| | - Tsutomu Fujii
- Department of Surgery and Science, Faculty of MedicineAcademic Assembly, University of ToyamaToyamaJapan
| | - Masaru Sasaki
- Department of SurgeryJA Hiroshima General HospitalHatsukaichiJapan
| | - Kenichi Hakamada
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
| | - Jota Watanabe
- Department of Gastrointestinal SurgeryEhime Prefectural Central HospitalMatsuyamaJapan
| | - Etsuro Hatano
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
| | - Masaaki Hidaka
- Department of Digestive and General SurgeryShimane University Faculty of MedicineIzumoJapan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery IIHokkaido University Faculty of MedicineSapporoJapan
| | - Hiroshi Kurahara
- Department of Digestive SurgeryKagoshima UniversityKagoshimaJapan
| | - Ippei Matsumoto
- Department of Surgery, Faculty of MedicineKindai UniversityOsakasayamaJapan
| | - Goro Honda
- Department of SurgeryInstitute of Gastroenterology, Tokyo Women's Medical UniversityTokyoJapan
| | - Toshiro Ogura
- Department of Gastroenterological SurgerySaitama Cancer CenterSaitamaJapan
| | - Masafumi Nakamura
- Department of Surgery and OncologyGraduate School of Medical Sciences, Kyushu UniversityFukuokaJapan
- Japanese Society of Hepato‐Biliary‐Pancreatic SurgeryTokyoJapan
| | - Itaru Endo
- Japanese Society of Hepato‐Biliary‐Pancreatic SurgeryTokyoJapan
- Department of Gastroenterological Surgery, Graduate School of MedicineYokohama City UniversityYokohamaJapan
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Di Y, Song J, Sun Z, Wang Y, Meng L. Nonsurgical pancreatic cancer: the role of radiotherapy in prolonging survival - a retrospective cohort study in the SEER database. Int J Surg 2025; 111:818-827. [PMID: 38920320 PMCID: PMC11745595 DOI: 10.1097/js9.0000000000001885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/17/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND Limited research has compared external beam radiotherapy (RT) to non-RT in patients with nonsurgical locally advanced pancreatic cancer (LAPC). Therefore, this study investigates the impact of RT on overall survival (OS) in patients with nonsurgical LAPC in a real-world context. METHODS The authors conducted an analysis of patients with nonsurgical LAPC using data from the Surveillance, Epidemiology, and End Results (SEER) database. This analysis involved the utilization of Kaplan-Meier survival curves and multivariable Cox regression analyses. RESULTS A total of 5413 individuals with nonsurgical LAPC were included in this analysis. Among them, 2320 (42.9%) received RT, while 3093 (57.1%) underwent non-RT treatment. The median OS was 12.0 months for the RT group and 9.0 months for the non-RT group, with a statistically significant difference ( P <0.001). Multivariate analysis revealed that RT had a statistically significant impact on OS (HR, 0.86; 95% CI: 0.81-0.91; P <0.001). Propensity score matching analysis confirmed a statistically significant association of RT with improved OS (HR, 0.84, 95% CI: 0.79-0.90; P <0.001). These results remained consistent after conducting sensitivity analyses, subgroup analyses, and propensity score matching. CONCLUSION The study findings suggest that RT could be advantageous for patients with nonsurgical LAPC. Further investigations are warranted to explore the relationship between RT and OS.
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Affiliation(s)
- Yupeng Di
- Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, People's Republic of China
| | - Jiazhao Song
- Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, People's Republic of China
| | - Zhijia Sun
- Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, People's Republic of China
| | - Yingjie Wang
- Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, People's Republic of China
| | - Lingling Meng
- Department of Radiation Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
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Shimane G, Kitago M, Endo Y, Aiura K, Yagi H, Abe Y, Hasegawa Y, Hori S, Tanaka M, Nakano Y, Fukada J, Masugi Y, Kitagawa Y. Efficacy and safety of neoadjuvant S-1-based chemoradiotherapy in resectable and borderline-resectable pancreatic cancer: a long-term follow-up study. World J Surg Oncol 2024; 22:336. [PMID: 39707428 DOI: 10.1186/s12957-024-03609-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 12/01/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND/OBJECTIVES This study aimed to evaluate the safety, efficacy, and long-term outcomes of S-1-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC). METHODS This retrospective study included patients with PDAC who underwent S-1-based NACRT at our institute between 2010 and 2017. RESULTS Forty patients were included in the study, including 15 (37.5%) with resectable PDAC and 25 (62.5%) with borderline-resectable PDAC. The NACRT completion and resection rates were 85.0% (n = 34) and 67.5% (n = 27), respectively. Several grade 3 adverse events were observed, including leukopenia (25.0%), anorexia (17.5%), neutropenia (10.0%), thrombocytopenia (7.5%), febrile neutropenia (2.5%), elevated aspartate aminotransferase/alanine aminotransferase (2.5%) levels, and hyponatremia (2.5%). The R0 resection rate was 70.4% (n = 19/27) in patients who underwent pancreatectomy. Grades 1, 2, and 3 according to the College of American Pathologists grading system were observed in 1 (3.7%), 12 (44.4%), and 14 (51.9%) patients, respectively. Over a median follow-up period of 32.9 months (interquartile range, 9.1-68.0), the 1-, 3-, and 5-year OS rates were 81.4%, 45.5%, and 30.3%, respectively, in the intention-to-treat analysis. In the curative-intent surgery cohort (n = 27), the 1-, 3-, and 5-year OS rates were 88.9%, 48.2%, and 37.0%, respectively. CONCLUSIONS S-1-based NACRT is safe and yields acceptable long-term outcomes for patients with resectable or borderline-resectable PDAC.
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Affiliation(s)
- Gaku Shimane
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan.
| | - Yutaka Endo
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Koichi Aiura
- Department of Surgery, Nippon Kokan Hospital, Kanagawa, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Masayuki Tanaka
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Junichi Fukada
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yohei Masugi
- Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi Shinjuku-Ku, Tokyo, 160-8582, Japan
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Litjens G, Nakamoto A, Brosens LAA, Maas MC, Scheenen TWJ, Zámecnik P, van Geenen EJM, Prokop M, van Laarhoven KJHM, Hermans JJ. Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma. Eur Radiol 2024; 34:7973-7984. [PMID: 38907886 PMCID: PMC11557713 DOI: 10.1007/s00330-024-10838-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/18/2024] [Accepted: 04/26/2024] [Indexed: 06/24/2024]
Abstract
OBJECTIVES To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.
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Affiliation(s)
- Geke Litjens
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Atsushi Nakamoto
- Department of Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Lodewijk A A Brosens
- Department of Pathology, Radboud University Medical Center, Nijmegen, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marnix C Maas
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tom W J Scheenen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Patrik Zámecnik
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Erwin J M van Geenen
- Department of Gastroenterology and Hepatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mathias Prokop
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Kees J H M van Laarhoven
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - John J Hermans
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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Chopra A, Gebran A, Khachfe H, Asmar RE, Nassour I, Narayanan S, AlMasri S, Singhi A, Lee K, Zureikat A, Paniccia A. Impact of Neoadjuvant Therapy on Oncological Outcomes of Patients With Distal Pancreatic Adenocarcinoma. J Surg Oncol 2024; 130:1579-1588. [PMID: 39348461 DOI: 10.1002/jso.27856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 07/27/2024] [Accepted: 08/18/2024] [Indexed: 10/02/2024]
Abstract
BACKGROUND Distal pancreatic ductal adenocarcinoma (D-PDAC) often presents at an advanced stage. The efficacy of neoadjuvant therapy (NAT) in improving outcomes for D-PDAC is not well-established. This study evaluates the impact of NAT on the oncological outcomes of patients with D-PDAC. METHODS A retrospective cohort study of consecutive patients with resectable and borderline-resectable D-PDAC treated at a single center from 2012 to 2020 was performed. Stratification was based on initial treatment-NAT or surgery first (SF). Survival analysis, following intention-to-treat framework, used Kaplan-Meier and Cox regression to assess NAT's impact on progression-free survival (PFS) and overall survival (OS) of D-PDAC. RESULTS Among 141 patients (median age 69.8 years, 51.8% females) included in the study, 71 (50.4%) received NAT and 70 (49.6%) were planned for SF. Patients receiving NAT were younger (65.9 vs. 72.6 years) and had higher incidence of borderline-resectable disease (31% vs. 4.3%) (both p < 0.05) than those undergoing SF. Thirteen patients (18.3%) undergoing NAT and five (7.1%) in SF group, failed to undergo resection. Univariate comparison showed no difference in the PFS (SF:13.97 vs. NAT:17.00 months, p = 0.6), and OS (SF:23.73 vs. NAT:32.53 months, p = 0.35). Multivariate Cox regression analysis noted significantly improved PFS (HR = 0.64, 95%CI = 0.42-0.96, p = 0.031) and OS (HR = 0.60, 95%CI = 0.39-0.93, p = 0.021) with NAT. CONCLUSION NAT is associated with improved PFS and OS in patients with -D-PDAC. Further randomized controlled trials are warranted to confirm these findings.
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Affiliation(s)
- Asmita Chopra
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Anthony Gebran
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Hussein Khachfe
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Rudy El Asmar
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ibrahim Nassour
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Sowmya Narayanan
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Samer AlMasri
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Aatur Singhi
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Hartog M, Beishuizen SJE, Togo R, van Bruchem‐Visser RL, van Eijck CHJ, Mattace‐Raso FUS, Pek CJ, de Wilde RF, Groot Koerkamp B, Polinder‐Bos HA. Comprehensive Geriatric Assessment, Treatment Decisions, and Outcomes in Older Patients Eligible for Pancreatic Surgery. J Surg Oncol 2024; 130:1643-1653. [PMID: 39290062 PMCID: PMC11849714 DOI: 10.1002/jso.27862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 07/08/2024] [Accepted: 08/18/2024] [Indexed: 09/19/2024]
Abstract
INTRODUCTION Periampullary cancer has a poor prognosis. Surgical resection is a potentially curative but high-risk treatment. Comprehensive geriatric assessment (CGA) can inform treatment decisions, but has not yet been evaluated in older patients eligible for pancreatic surgery. METHODS This prospective observational study included patients ≥ 70 years of age eligible for pancreatic surgery. Frailty was defined as impairment in at least two of five domains: somatic, psychological, functional, nutritional, and social. Outcomes included postoperative complications, functional decline, and mortality. RESULTS Of the 88 patients included, 87 had a complete CGA. Sixty-five patients (75%) were frail and 22 (25%) were non-frail. Frail patients were more likely to receive nonsurgical treatment (43.1% vs. 9.1% p = 0.004). Fifty-seven patients underwent surgery, of which 52 (59%) underwent pancreaticoduodenectomy. The incidence of postoperative delirium was three times higher in frail patients (29.7% vs. 0%, p = 0.005). The risk of mortality was three times higher in frail patients (HR: 3.36, 95% CI: 1.43-7.89, p = 0.006). CONCLUSION Frailty is common in older patients eligible for pancreatic surgery and is associated with treatment decision, a higher incidence of delirium and a three times higher risk of all-cause mortality. CGA can contribute to shared decision-making and optimize perioperative care in older patients.
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Affiliation(s)
- Marij Hartog
- Department of Internal MedicineDivision of Geriatric Medicine, Erasmus MC University Medical CenterRotterdamThe Netherlands
| | | | - Reon Togo
- Department of Internal MedicineDivision of Geriatric Medicine, Erasmus MC University Medical CenterRotterdamThe Netherlands
| | | | - Casper H. J. van Eijck
- Department of SurgeryErasmus MC Cancer Institute, Erasmus MC University Medical Center RotterdamRotterdamThe Netherlands
| | - Francesco U. S. Mattace‐Raso
- Department of Internal MedicineDivision of Geriatric Medicine, Erasmus MC University Medical CenterRotterdamThe Netherlands
| | - Chulja J. Pek
- Department of SurgeryErasmus MC Cancer Institute, Erasmus MC University Medical Center RotterdamRotterdamThe Netherlands
| | - Roeland F. de Wilde
- Department of SurgeryErasmus MC Cancer Institute, Erasmus MC University Medical Center RotterdamRotterdamThe Netherlands
| | - Bas Groot Koerkamp
- Department of SurgeryErasmus MC Cancer Institute, Erasmus MC University Medical Center RotterdamRotterdamThe Netherlands
| | - Harmke A. Polinder‐Bos
- Department of Internal MedicineDivision of Geriatric Medicine, Erasmus MC University Medical CenterRotterdamThe Netherlands
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AbiMansour JP, Martin JA. Biliary Endoscopic Retrograde Cholangiopancreatography. Gastroenterol Clin North Am 2024; 53:627-642. [PMID: 39489579 DOI: 10.1016/j.gtc.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Since inception in 1968, biliary endoscopic retrograde cholangiopancreatography (ERCP) has transformed into a highly effective, minimally invasive modality for the identification and treatment of a variety of biliary pathologies including benign, malignant, and iatrogenic diseases. The diagnostic role of ERCP has been largely replaced by high-quality imaging modalities including endoscopic ultrasound and magnetic resonance cholangiopancreatography. However, there continues to be significant demand for therapeutic procedures. This article reviews the general principles of ERCP, as well as common indications, contraindications, and potential adverse events with which endoscopists and referring physicians should be familiar.
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Affiliation(s)
- Jad P AbiMansour
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - John A Martin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
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Kinoshita S, Terai T, Nagai M, Nakamura K, Kohara Y, Yasuda S, Matsuo Y, Doi S, Sakata T, Migita K, Ouji-Sageshima N, Ito T, Sho M. Clinical significance and therapeutic implication of CD200 in pancreatic cancer. Pancreatology 2024; 24:1280-1287. [PMID: 39419752 DOI: 10.1016/j.pan.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 09/29/2024] [Accepted: 10/12/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND CD200, a negative regulator of T cells as well as a marker for cancer stem cells, represents a significant prognostic factor and potential therapeutic target in certain cancers. However, its clinical significance remains unknown in pancreatic ductal adenocarcinoma (PDAC). METHODS CD200 was assessed in 220 resected PDAC patients who underwent surgery with or without neoadjuvant chemoradiotherapy (NACRT). We examined the clinicopathological outcomes associated with CD200 and further assessed its clinical implications regarding immunological and cancer stem cell properties. RESULTS NACRT was associated with higher CD200 expression (66.4 % vs. 32.2 %, P < 0.001) compared to upfront surgery. CD200 was identified as an independent poor prognostic factor in NACRT (hazard ratio 1.90, 95 % confidence interval 1.12-3.23, P = 0.016), but not in upfront surgery patients. Post-recurrence survival was significantly worse in CD200+ patients compared to CD200- patients in the NACRT group, but there was no significant difference observed in the upfront surgery group. CD200 expression was correlated with significantly lower levels of CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes. Furthermore, the correlation of CD200 with pancreatic cancer stem cell markers CD44/CD24/ESA was stronger in irradiated human pancreatic cancer cells. CONCLUSIONS Our data underscore novel roles for CD200 in immune evasion as well as therapy resistance in pancreatic cancer. CD200 may represent a novel poor prognostic predictive factor and potential therapeutic target for PDAC with NACRT.
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Affiliation(s)
- Shoichi Kinoshita
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Taichi Terai
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Minako Nagai
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Kota Nakamura
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Yuichiro Kohara
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Satoshi Yasuda
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Yasuko Matsuo
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Shunsuke Doi
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Takeshi Sakata
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Kazuhiro Migita
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Noriko Ouji-Sageshima
- Department of Immunology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Toshihiro Ito
- Department of Immunology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
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Shin DH, Choi M, Rho SY, Hong SS, Kim SH, Hwang HK, Kang CM. Minimally invasive pancreatoduodenectomy with combined venous vascular resection: A comparative analysis with open approach. Ann Hepatobiliary Pancreat Surg 2024; 28:500-507. [PMID: 39314031 PMCID: PMC11599825 DOI: 10.14701/ahbps.24-082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 07/14/2024] [Accepted: 07/16/2024] [Indexed: 09/25/2024] Open
Abstract
Backgrounds/Aims This study aimed to compare the minimally invasive pancreatoduodenectomy with venous vascular resection (MI-PDVR) and open pancreatoduodenectomy with venous vascular resection (O-PDVR) for periampullary cancer. Methods Data of 124 patients who underwent PDVR (45 MI-PDVR, 79 O-PDVR) between January 1, 2016, and December 31, 2023, was retrospectively reviewed. Results MI-PDVR is significantly better than O-PDVR in terms of perioperative outcomes (median operation time [452.69 minutes vs. 543.91 minutes; p = 0.004], estimated blood loss [410.44 mL vs. 747.59 mL; p < 0.01], intraoperative transfusion rate [2 cases vs. 18 cases; p = 0.01], and hospital stay [18.16 days vs. 23.91 days; p = 0.008]). The complications until the discharge day showed no significant difference between the two groups (Clavien-Dindo < 3, 84.4% vs. 82.3%; Clavien-Dindo ≥ 3, 15.6% vs. 17.7%; p = 0.809). In terms of long-term oncological outcomes, there was no statistical difference in overall survival (OS, 51.55 months [95% CI: 35.95-67.14] vs. median 49.92 months [95% CI: 40.97-58.87]; p = 0.340) and disease-free survival (DFS, median 35.06 months [95% CI: 21.47-48.65] vs. median 38.77 months [95% CI: 29.80-47.75]; p = 0.585), between the two groups. Long-term oncological outcomes for subgroup analysis focusing on pancreatic ductal adenocarcinoma also showed no statistical differences in OS (40.86 months [95% CI: 34.45-47.27] vs. 48.48 months [95% CI: 38.16-58.59]; p = 0.270) and DFS (24.42 months [95% CI: 17.03-31.85] vs. 34.35 months, [95% CI: 25.44-43.27]; p = 0.740). Conclusions MI-PDVR can provide better perioperative outcomes than O-PDVR, and has similar oncological impact.
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Affiliation(s)
- Dong Hyun Shin
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Munseok Choi
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Seoung Yoon Rho
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Seung Soo Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hyun Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Bryant JM, Nakashima J, Khatri VM, Sinnamon AJ, Denbo JW, Hodul P, Malafa M, Hoffe S, Frakes JM. The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma. J Clin Med 2024; 13:6800. [PMID: 39597944 PMCID: PMC11594810 DOI: 10.3390/jcm13226800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/04/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. METHODS The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. RESULTS Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. CONCLUSIONS While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.
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Affiliation(s)
- John Michael Bryant
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Justyn Nakashima
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Vaseem M. Khatri
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Andrew J. Sinnamon
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Jason W. Denbo
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Pamela Hodul
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Mokenge Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Sarah Hoffe
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
| | - Jessica M. Frakes
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
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Kotb A, Hafeji Z, Jesry F, Lintern N, Pathak S, Smith AM, Lutchman KRD, de Bruin DM, Hurks R, Heger M, Khaled YS. Intra-Operative Tumour Detection and Staging in Pancreatic Cancer Surgery: An Integrative Review of Current Standards and Future Directions. Cancers (Basel) 2024; 16:3803. [PMID: 39594758 PMCID: PMC11592681 DOI: 10.3390/cancers16223803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 10/15/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Surgical resection for pancreatic ductal adenocarcinoma (PDAC) entails the excision of the primary tumour and regional lymphadenectomy. This traditional strategy is challenged by the high rate of early recurrence, suggesting inadequate disease staging. Novel methods of intra-operative staging are needed to allow surgical resection to be tailored to the disease's biology. METHODS A search of published articles on the PubMed and Embase databases was performed using the terms 'pancreas' OR 'pancreatic' AND 'intra-operative staging/detection' OR 'guided surgery'. Articles published between January 2000 and June 2023 were included. Technologies that offered intra-operative staging and tailored treatment were curated and summarised in the following integrative review. RESULTS lymph node (LN) mapping and radioimmunoguided surgery have shown promising results but lacked practicality to facilitate real-time intra-operative staging for PDAC. Fluorescence-guided surgery (FGS) offers high contrast and sensitivity, enabling the identification of cancerous tissue and positive LNs with improved precision following intravenous administration of a fluorescent agent. The unique properties of optical coherence tomography and ultrasound elastography lend themselves to be platforms for virtual biopsy intra-operatively. CONCLUSIONS Accurate intra-operative staging of PDAC, localisation of metastatic LNs, and identification of extra-pancreatic disease remain clinically unmet needs under current detection methods and staging standards. Tumour-specific FGS combined with other diagnostic and therapeutic modalities could improve tumour detection and staging in patients with PDAC.
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Affiliation(s)
- Ahmed Kotb
- Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK
| | - Zaynab Hafeji
- Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK
| | - Fadel Jesry
- Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK
| | - Nicole Lintern
- Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK
| | - Samir Pathak
- The Pancreato-Biliary Unit, St James’s University Teaching Hospital, Leeds LS9 7TF, UK
| | - Andrew M. Smith
- The Pancreato-Biliary Unit, St James’s University Teaching Hospital, Leeds LS9 7TF, UK
| | - Kishan R. D. Lutchman
- Department of Surgery, Amsterdam UMC, Location AMC, 1105 AZ Amsterdam, The Netherlands
- Department of Biomedical Engineering and Physics, Amsterdam UMC, Location AMC, 1105 AZ Amsterdam, The Netherlands
| | - Daniel M. de Bruin
- Department of Biomedical Engineering and Physics, Amsterdam UMC, Location AMC, 1105 AZ Amsterdam, The Netherlands
| | - Rob Hurks
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| | - Michal Heger
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing 314001, China
| | - Yazan S. Khaled
- Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK
- The Pancreato-Biliary Unit, St James’s University Teaching Hospital, Leeds LS9 7TF, UK
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Liu J, Sidiqi B, McComas K, Gogineni E, Andraos T, Crane CH, Chang DT, Goodman KA, Hall WA, Hoffe S, Mahadevan A, Narang AK, Lee P, Williams TM, Chuong MD. SBRT for Pancreatic Cancer: A Radiosurgery Society Case-Based Practical Guidelines to Challenging Cases. Pract Radiat Oncol 2024; 14:555-573. [PMID: 38986901 DOI: 10.1016/j.prro.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 06/17/2024] [Accepted: 06/21/2024] [Indexed: 07/12/2024]
Abstract
The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions.
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Affiliation(s)
- Jason Liu
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
| | - Baho Sidiqi
- Department of Radiation Oncology, Northwell Health Cancer Institute, New Hyde Park, New York
| | - Kyra McComas
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennesse
| | - Emile Gogineni
- Department of Radiation Oncology, Ohio State James Cancer Center, Columbus, Ohio
| | - Therese Andraos
- Department of Radiation Oncology, Ohio State James Cancer Center, Columbus, Ohio
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Daniel T Chang
- Department of Radiation Oncology, University of Michigan Health, Ann Arbor, Michigan
| | - Karyn A Goodman
- Department of Radiation Oncology, Mount Sinai Health, New York City, New York
| | - William A Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Sarah Hoffe
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Anand Mahadevan
- Department of Radiation Oncology, NYU Langone Health, New York City, New York
| | - Amol K Narang
- Department of Radiation Oncology, Johns Hopkins University Kimmel Cancer Center, Baltimore, Maryland
| | - Percy Lee
- Department of Radiation Oncology, City of Hope Lennar Cancer Center, Irvine, California
| | - Terence M Williams
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California
| | - Michael D Chuong
- Department of Radiation Oncology, Baptist Health South Florida, Miami, Florida
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49
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Ross SB, Popover J, Sucandy I, Christodoulou M, Pattilachan TM, Rosemurgy AS. The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma. Am Surg 2024; 90:3061-3073. [PMID: 38635295 DOI: 10.1177/00031348241248703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024]
Abstract
Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.
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Affiliation(s)
- Sharona B Ross
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
| | - Jesse Popover
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
| | - Iswanto Sucandy
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
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50
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Ueda H, Takahashi H, Sakaniwa R, Kitamura T, Kobayashi S, Tomimaru Y, Kubo M, Sasaki K, Iwagami Y, Yamada D, Asaoka T, Noda T, Shimizu J, Doki Y, Eguchi H. Preoperative treatment response prediction for pancreatic cancer by multiple microRNAs in plasma exosomes: Optimization using machine learning and network analysis. Pancreatology 2024; 24:1097-1106. [PMID: 39278808 DOI: 10.1016/j.pan.2024.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 08/28/2024] [Accepted: 09/10/2024] [Indexed: 09/18/2024]
Abstract
BACKGROUND/OBJECTIVES MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction. METHODS A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response. RESULTS In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders. CONCLUSIONS Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
| | - Ryoto Sakaniwa
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan
| | - Tetsuhisa Kitamura
- Environment Medicine, Department of Social Medicine, Division of Environment Medicine and Population Sciences, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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