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Zhang Y, Xu M, Wang Y, Yu F, Chen X, Wang G, Zhao K, Yang H, Su X. Value of [ 18F]AlF-NOTA-FAPI-04 PET/CT for predicting pathological response and survival in patients with locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 2025:10.1007/s00259-025-07084-7. [PMID: 39820598 DOI: 10.1007/s00259-025-07084-7] [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: 09/21/2024] [Accepted: 01/10/2025] [Indexed: 01/19/2025]
Abstract
OBJECTIVES This study aimed to evaluate the predictive value of [18F]AlF-NOTA-FAPI-04 PET/CT for pathological response to neoadjuvant chemotherapy (NCT) and prognosis in patients with locally advanced pancreatic ductal adenocarcinoma (LAPDAC). METHODS This study included 34 patients with histopathologically and radiologically confirmed LAPDAC who received [18F]AlF-NOTA-FAPI-04 PET/CT scans before NCT. After 4-6 cycles of NCT, these patients underwent radical resection. Pathological response to NCT was assessed by pathological tumor regression grades (TRG) based on the Evans system. PET/CT parameters were evaluated for their association with TRG, recurrence-free survival (RFS) and overall survival (OS) after NCT, including the maximum standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) of primary tumor, total FAPI-avid pancreatic volume (FPV) and total pancreatic FAP expression (TPF) of total pancreas. RESULTS Of 34 patients with LAPDAC, 14 patients had a pathologic good response (PGR, Evans III-IV), and 20 patients had a pathologic poor response (PPR, Evans I-II). Both the primary tumor SUVmax, FTV and TLF, and total pancreas FPV and TPF in the PGR groups were significantly lower than those in the PPR groups. Furthermore, SUVmax and TLF were higher in poorly differentiated LAPDAC than in well-moderately differentiated neoplasms. The FTV, TLF, FPV and TPF were closely associated with RFS and OS. On multivariate analysis, patients with FTV > 54.21 and TLF > 290.21 had a worse RFS and OS, respectively (HR = 3.24, P = 0.014 and HR = 3.35, P = 0.019) and OS (HR = 7.35, P = 0.002 and HR = 7.09, P = 0.004) in LAPDAC after NCT. CONCLUSIONS The parameters of [18F]AlF-NOTA-FAPI-04 PET/CT had the excellent performance for predicting pathologic TRG after NCT in LAPDAC. FTV and TLF were independent postoperative prognostic factors for RFS and OS for LAPDAC.
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Affiliation(s)
- Yafei Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Mimi Xu
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Yu Wang
- Department of Pharmacy, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, China
| | - Fang Yu
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xinxin Chen
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Guangfa Wang
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Kui Zhao
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Hong Yang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
| | - Xinhui Su
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
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Wang F, Fan J, Lu F, Xu J, Zhang H, Han J, Chen J, Yu D. HIF-1α expression is associated with the pathological response to neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma patients and can be predicted using CECT features. Quant Imaging Med Surg 2025; 15:662-675. [PMID: 39839013 PMCID: PMC11744163 DOI: 10.21037/qims-24-103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 11/22/2024] [Indexed: 01/23/2025]
Abstract
Background Hypoxia-inducible factor-1-alpha (HIF-1α) has the potential to predict the neoadjuvant chemotherapy (NAC) response in pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the relationship between the pathological response and intratumoral HIF-1α expression in patients with PDAC receiving NAC, and investigate the predictive value of contrast-enhanced computed tomography (CECT) features in HIF-1α expression. Methods A total of 58 patients from three centers with pathologically confirmed PDAC who underwent NAC followed by surgery were retrospectively enrolled in this study. Immunohistochemistry was performed to detect intratumoral HIF-1α expression. The Chi-square test was used to evaluate the differences in intratumoral HIF-1α expression in PDAC responders and non-responders after NAC. Binary logistic regression and receiver operating characteristic (ROC) curves were used to determine the optimal correlation factors of different pathological responses in PDAC patients after NAC and to predict these factors using CECT features. Results Among the PDAC patients, 27 (46.55%) responders and 31 (53.45%) non-responders were identified via histopathological examination. Nuclear and cytoplasmic HIF-1α expression was significantly higher in the responders than the non-responders (P<0.001, P=0.036). However, HIF-1α expression in the stroma was not statistically significant (P=0.864). The multivariate logistic regression revealed that the %Δ carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and nuclear HIF-1α were independent predictors of different pathological responses [odds ratio (OR) =9.005, P=0.037; OR =0.005, P=0.044; OR =0.352, P=0.018, respectively]. The ROC curve showed that nuclear HIF-1α expression was the optimal associated predictor of the pathologic response (area under the curve =0.873, 95% confidence interval: 0.782-0.964). The multivariate logistic regression also showed that of the CECT characteristics, the (post-NAC - pre-NAC) arterial phase (AP) was an independent predictive indicator of nuclear HIF-1α expression (OR =1.012, P=0.020). Conclusions Nuclear HIF-1α was the best predictor of the pathological response in patients with PDAC after NAC, and it can be predicted using CT feature of the (post-NAC - pre-NAC) AP.
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Affiliation(s)
- Fangqing Wang
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Jinlei Fan
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Fei Lu
- School of Medical Imaging, Shandong Second Medical University, Weifang, China
| | - Janwei Xu
- Department of Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Hui Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Junqi Han
- Department of Breast Imaging, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jingjing Chen
- Department of Breast Imaging, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Dexin Yu
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
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Shi S, Ye L, Jin K, Yu X, Guo D, Wu W. The complement C3a/C3aR pathway is associated with treatment resistance to gemcitabine-based neoadjuvant therapy in pancreatic cancer. Comput Struct Biotechnol J 2024; 23:3634-3650. [PMID: 39469671 PMCID: PMC11513484 DOI: 10.1016/j.csbj.2024.09.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 09/21/2024] [Accepted: 09/27/2024] [Indexed: 10/30/2024] Open
Abstract
Gemcitabine is a standard first-line drug for pancreatic cancer chemotherapy. Nevertheless, gemcitabine resistance is common and significantly limits its therapeutic efficacy, impeding advancements in pancreatic cancer treatment. In this study, through a comprehensive analysis of gemcitabine-resistant cell lines and patient samples, 39 gemcitabine resistance-associated risk genes were identified, and two distinct gemcitabine response-related phenotypes were delineated. Through a combination of bioinformatics analysis and in vivo and in vitro experiments, we identified the C3a/C3aR signaling pathway as a pivotal player in the development of gemcitabine resistance in pancreatic cancer. We found that activation of the C3a/C3aR signaling pathway promoted the proliferation, migration and gemcitabine resistance of pancreatic cancer cells, while the C3aR antagonist SB290157 effectively counteracted these effects by impeding the activation of the C3a/C3aR pathway. Our study reveals the fundamental role of complement C3a in the progression of pancreatic cancer, suggesting that complement C3a may serve as a promising biomarker in pancreatic cancer.
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Affiliation(s)
- Saimeng Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Longyun Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Duancheng Guo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Weiding Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
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Fields BC, Tzeng CWD. Locally Advanced Pancreas Cancer, Is There a Role for Surgery? Surg Clin North Am 2024; 104:1017-1030. [PMID: 39237161 PMCID: PMC11748233 DOI: 10.1016/j.suc.2024.03.004] [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] [Indexed: 09/07/2024]
Abstract
Locally advanced pancreatic cancer (LAPC) represents a unique clinical scenario in which the tumor is considered localized but unresectable due to anatomic factors. Despite a consensus against upfront surgery, no standard approach to induction therapy exists for patients with LAPC. Extended systemic therapy has shown promise in establishing tumor response and remains the standard of care. While associated with improved local control, the timing and role of radiation therapy remain in question. Following adequate response to induction chemotherapy, a safe attempt at margin-negative resection can be considered. Special attention should be given to required vascular skeletonization and/or resection with reconstruction.
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Affiliation(s)
- Brittany C Fields
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA.
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Giuliante F, Panettieri E, Campisi A, Coppola A, Vellone M, De Rose AM, Ardito F. Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review. Int J Surg 2024; 110:6163-6169. [PMID: 38818688 PMCID: PMC11486948 DOI: 10.1097/js9.0000000000001665] [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: 12/30/2023] [Accepted: 05/09/2024] [Indexed: 06/01/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.
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Affiliation(s)
- Felice Giuliante
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Elena Panettieri
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Andrea Campisi
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | | | - Maria Vellone
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Agostino M. De Rose
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Francesco Ardito
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
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Akita H, Mukai Y, Kubo M, Takahashi H, Hasegawa S, Kitakaze M, Matsuura N, Masuike Y, Sugase T, Shinno N, Kanemura T, Hara H, Sueda T, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M, Wada H. A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer. Surgery 2024; 176:1215-1221. [PMID: 39079828 DOI: 10.1016/j.surg.2024.06.049] [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: 04/29/2024] [Revised: 05/28/2024] [Accepted: 06/23/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. METHOD We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). RESULTS Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. CONCLUSION A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.
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Affiliation(s)
- Hirofumi Akita
- Department of Surgery, Osaka International Cancer Institute, Japan.
| | - Yosuke Mukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Kubo
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | | | | | - Yasunori Masuike
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takahito Sugase
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Naoki Shinno
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takashi Kanemura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hisashi Hara
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Toshinori Sueda
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
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Habib JR, Javed AA, Wolfgang CL. The Significance of Circulating Tumor Cells in Pancreatic Cancer. Adv Surg 2024; 58:135-142. [PMID: 39089773 DOI: 10.1016/j.yasu.2024.05.001] [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: 08/04/2024]
Abstract
The notion that technically resectable pancreatic ductal adenocarcinoma presents as localized disease is now known to be inaccurate. Evidence supports that most patients have subclinical systemic dissemination at the time of diagnosis. It is now widely accepted that both a local and systemic component of disease coexist, each requiring treatment of improved survival and potential cure. The advent of multiagent chemotherapy regimens has resulted in a modest improvement in survival. Consequently, this article will emphasize the expanding potential and significance of circulating tumor cells in the prognostication and management of patients with pancreatic cancer.
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Affiliation(s)
- Joseph R Habib
- Department of Surgery, New York University Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Ammar A Javed
- Department of Surgery, New York University Langone Health, 550 First Avenue, New York, NY 10016, USA
| | - Christopher L Wolfgang
- Department of Surgery, New York University Langone Health, 550 First Avenue, New York, NY 10016, USA.
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Neibart SS, Moningi S, Jethwa KR. Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer. Clin Exp Gastroenterol 2024; 17:213-225. [PMID: 39050120 PMCID: PMC11268661 DOI: 10.2147/ceg.s341189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 05/28/2024] [Indexed: 07/27/2024] Open
Abstract
Introduction For patients with locally advanced pancreatic cancer (LAPC), who are candidates for radiation therapy, dose-escalated radiation therapy (RT) offers unique benefits over traditional radiation techniques. In this review, we present a historical perspective of dose-escalated RT for LAPC. We also outline advances in SBRT delivery, one form of dose escalation and a framework for selecting patients for treatment with SBRT. Results Techniques for delivering SBRT to patients with LAPC have evolved considerably, now allowing for dose-escalation and superior respiratory motion management. At the same time, advancements in systemic therapy, particularly the use of induction multiagent chemotherapy, have called into question which patients would benefit most from radiation therapy. Multidisciplinary assessment of patients with LAPC is critical to guide management and select patients for local therapy. Results from ongoing trials will establish if there is a role of dose-escalated SBRT after induction chemotherapy for carefully selected patients. Conclusion Patients with LAPC have more therapeutic options than ever before. Careful selection for SBRT may enhance patient outcomes, pending the maturation of pivotal clinical trials.
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Affiliation(s)
- Shane S Neibart
- Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Shalini Moningi
- Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
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Saúde-Conde R, El Ghali B, Navez J, Bouchart C, Van Laethem JL. Total Neoadjuvant Therapy in Localized Pancreatic Cancer: Is More Better? Cancers (Basel) 2024; 16:2423. [PMID: 39001485 PMCID: PMC11240662 DOI: 10.3390/cancers16132423] [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: 05/15/2024] [Revised: 06/24/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.
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Affiliation(s)
- Rita Saúde-Conde
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Benjelloun El Ghali
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hopital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Christelle Bouchart
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Jean-Luc Van Laethem
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
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Akumuo RC, Villano AM, Reddy SP, Devarajan K, Barrak D, Reddy SS. Type of neoadjuvant treatment strategy is associated with differential pathologic responses in pancreatic ductal adenocarcinoma. Am J Surg 2024; 232:9-14. [PMID: 37977978 DOI: 10.1016/j.amjsurg.2023.10.053] [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: 08/27/2023] [Revised: 10/21/2023] [Accepted: 10/30/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Tumor fibrosis after neoadjuvant treatment (NAT) for pancreatic ductal adenocarcinoma (PDAC) correlates with treatment response. Herein we assessed how different NAT strategies influence pathologic responses and survival. METHODS Patients with surgically resected PDAC who received NAT (1991-2020) were included. Descriptive statistics compared outcomes amongst fibrosis groups (none, minor <50 %, partial 51%-94 %, major ≥95 %) and NAT (chemotherapy alone, chemoradiation, or chemotherapy + chemoradiation (total neoadjuvant therapy, TNT)). RESULTS Patients with major fibrosis most often received TNT (65.8 %, p < 0.001). Major fibrosis was associated with the greatest rate of downstaging (77.8 %, p < 0.001), highest R0 margin rate (100 %, p < 0.01), and lowest mean positive lymph node ratio (0.80, p < 0.01). Amongst complete responders, 11/14 (78.6 %) received TNT. Median overall (66.3 months, p = 0.003) and disease-free (54.7months, p = 0.05) survival were highest with major fibrosis. CONCLUSIONS Major fibrosis and complete pathologic responses after NAT are most frequent with a TNT strategy and are associated with improved outcomes.
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Affiliation(s)
- Rita C Akumuo
- Department of Surgery, Temple University Hospital, Philadelphia, PA, USA; Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
| | - Anthony M Villano
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
| | - Sai P Reddy
- Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
| | - Karthik Devarajan
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Dany Barrak
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
| | - Sanjay S Reddy
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
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Cai W, Zhu Y, Teng Z, Li D, Cong R, Chen Z, Ma X, Zhao X. Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy. Insights Imaging 2024; 15:116. [PMID: 38735009 PMCID: PMC11089023 DOI: 10.1186/s13244-024-01689-6] [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: 11/14/2023] [Accepted: 04/03/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVES To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features. MATERIALS AND METHODS One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were used to evaluate the predictive performance of the scoring system. RESULTS Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001). CONCLUSION ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach. CRITICAL RELEVANCE STATEMENT The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis. KEY POINTS Predicting the progression of LAPC in patients receiving IORT is important. Our ECV-based scoring system can risk stratifying patients with initial SD. Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.
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Affiliation(s)
- Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongjian Zhu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ze Teng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rong Cong
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaowei Chen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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12
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Wang K, Karalis JD, Elamir A, Bifolco A, Wachsmann M, Capretti G, Spaggiari P, Enrico S, Balasubramanian K, Fatimah N, Pontecorvi G, Nebbia M, Yopp A, Kaza R, Pedrosa I, Zeh H, Polanco P, Zerbi A, Wang J, Aguilera T, Ligorio M. Delta Radiomic Features Predict Resection Margin Status and Overall Survival in Neoadjuvant-Treated Pancreatic Cancer Patients. Ann Surg Oncol 2024; 31:2608-2620. [PMID: 38151623 PMCID: PMC10908610 DOI: 10.1245/s10434-023-14805-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 12/06/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions. METHODS We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). Gross tumor volume was contoured from CT scans, and 257 radiomics features were extracted. DRFs were calculated by direct subtraction of pre/post-NAT radiomic features. Cox proportional models and binary prediction models, including/excluding clinical variables, were constructed to predict overall survival (OS), disease-free survival (DFS), and RMS. RESULTS The discovery and validation cohorts comprised 58 and 31 patients, respectively. Both cohorts had similar clinical characteristics, apart from differences in NAT (FOLFIRINOX vs. gemcitabine/nab-paclitaxel; p < 0.05) and type of surgery resections (pancreatoduodenectomy, distal or total pancreatectomy; p < 0.05). The model that combined clinical variables (pre-NAT carbohydrate antigen (CA) 19-9, the change in CA19-9 after NAT (∆CA19-9), and resectability status) and DRFs outperformed the clinical feature-based models and other radiomics feature-based models in predicting OS (UTSW: 0.73; Humanitas: 0.66), DFS (UTSW: 0.75; Humanitas: 0.64), and RMS (UTSW 0.73; Humanitas: 0.69). CONCLUSIONS Our externally validated, predictive/prognostic delta-radiomics models, which incorporate clinical variables, show promise in predicting the risk of predicting RMS in NAT-treated PDAC patients and their OS or DFS.
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Affiliation(s)
- Kai Wang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - John D Karalis
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ahmed Elamir
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Alessandro Bifolco
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Megan Wachsmann
- Department of Pathology, Veterans Affairs North Texas Health Care System, Dallas, TX, USA
| | - Giovanni Capretti
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Paola Spaggiari
- Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Sebastian Enrico
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | - Nafeesah Fatimah
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Giada Pontecorvi
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Martina Nebbia
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Adam Yopp
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ravi Kaza
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ivan Pedrosa
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Herbert Zeh
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Patricio Polanco
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Jing Wang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Todd Aguilera
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Matteo Ligorio
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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13
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Servin-Rojas M, Fong ZV, Fernandez-Del Castillo C, Ferrone CR, Lee H, Lopez-Verdugo F, Qiao G, Rocha-Castellanos DM, Lillemoe KD, Qadan M. Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma. Surgery 2024; 175:471-476. [PMID: 37949693 DOI: 10.1016/j.surg.2023.09.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/03/2023] [Accepted: 09/26/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.
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Affiliation(s)
- Maximiliano Servin-Rojas
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/servinrojasmd
| | - Zhi Ven Fong
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/zhivenfongmd
| | | | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/cferronemd
| | - Hang Lee
- Department of Biostatistics, Massachusetts General Hospital, Boston, MA
| | - Fidel Lopez-Verdugo
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/fidel_lv
| | - Guoliang Qiao
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Dario M Rocha-Castellanos
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/dariorochamd
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Boston, MA.
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14
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Shi S, Guo D, Ye L, Li T, Fei Q, Lin M, Yu X, Jin K, Wu W. Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer. Cell Death Dis 2023; 14:778. [PMID: 38012214 PMCID: PMC10682013 DOI: 10.1038/s41419-023-06313-x] [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: 07/09/2023] [Revised: 11/06/2023] [Accepted: 11/15/2023] [Indexed: 11/29/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tract tumor with limited clinical treatments. Transforming acidic coiled-coil-containing protein 3 (TACC3) is a component of the centrosome axis and a member of the TACC family, which affect mitosis and regulate chromosome stability and are involved in tumor development and progression. However, the role of TACC3 in PDAC remains elusive. In this study, by exploiting the TCGA database, we found that high TACC3 expression in PDAC is associated with poor prognosis. shRNA-mediated TACC3 knockdown caused S phase arrest of the cell cycle and inhibited proliferation in PDAC cell lines. Through RNA sequencing and protein co-immunoprecipitation combined with mass spectrometry, KIF11 was identified as a protein that interacts with TACC3. TACC3 stabilizes and regulates KIF11 protein expression levels in PDAC cells through physical interaction. Knockdown of TACC3 or KIF11 resulted in abnormal spindle formation during cell division both in vitro and in vivo. Pharmacological inhibition of TACC3 or KIF11 can suppress tumor cell proliferation and promote apoptosis. Our studies further demonstrated that high expression of TACC3 and KIF11 mediated the resistance of PDAC to gemcitabine, and deficiency of TACC3 or KIF11 increased the sensitivity of PDAC cells to chemotherapy. In conclusion, our study reveals the fundamental role of TACC3 expression in PDAC cell proliferation and chemoresistance, suggesting that TACC3 can be used as a molecular marker to evaluate the prognosis of PDAC.
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Affiliation(s)
- Saimeng Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Duancheng Guo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Longyun Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Tianjiao Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Qinglin Fei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Mengxiong Lin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Weiding Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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15
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Khasawneh H, Ferreira Dalla Pria HR, Miranda J, Nevin R, Chhabra S, Hamdan D, Chakraborty J, Biachi de Castria T, Horvat N. CT Imaging Assessment of Pancreatic Adenocarcinoma Resectability after Neoadjuvant Therapy: Current Status and Perspective on the Use of Radiomics. J Clin Med 2023; 12:6821. [PMID: 37959287 PMCID: PMC10649102 DOI: 10.3390/jcm12216821] [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: 09/19/2023] [Revised: 10/13/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Pancreatic adenocarcinoma (PDAC) is the most common pancreatic cancer and is associated with poor prognosis, a high mortality rate, and a substantial number of healthy life years lost. Surgical resection is the primary treatment option for patients with resectable disease; however, only 10-20% of all patients with PDAC are eligible for resection at the time of diagnosis. In this context, neoadjuvant therapy has the potential to increase the number of patients who are eligible for resection, thereby improving the overall survival rate. For patients who undergo neoadjuvant therapy, computed tomography (CT) remains the primary imaging tool for assessing treatment response. Nevertheless, the interpretation of imaging findings in this context remains challenging, given the similarity between viable tumor and treatment-related changes following neoadjuvant therapy. In this review, following an overview of the various treatment options for PDAC according to its resectability status, we will describe the key challenges regarding CT-based evaluation of PDAC treatment response following neoadjuvant therapy, as well as summarize the literature on CT-based evaluation of PDAC treatment response, including the use of radiomics. Finally, we will outline key recommendations for the management of PDAC after neoadjuvant therapy, taking into consideration CT-based findings.
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Affiliation(s)
- Hala Khasawneh
- Department of Radiology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
| | | | - Joao Miranda
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
- Department of Radiology, University of Sao Paulo, R. Dr. Ovidio Pires de Campos, 75-Cerqueira Cesar, Sao Paulo 05403-010, SP, Brazil
| | - Rachel Nevin
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
| | - Shalini Chhabra
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
| | - Dina Hamdan
- Department of Radiology, The Mount Sinai Hospital, 1468 Madison Ave, New York, NY 10029, USA;
| | - Jayasree Chakraborty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA;
| | - Tiago Biachi de Castria
- Department of Gastrointestinal Oncology, Moffit Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA;
- Morsani College of Medicine, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
- Department of Radiology, University of Sao Paulo, R. Dr. Ovidio Pires de Campos, 75-Cerqueira Cesar, Sao Paulo 05403-010, SP, Brazil
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16
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Pedrazzoli S. Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor. J Clin Med 2023; 12:6461. [PMID: 37892599 PMCID: PMC10607532 DOI: 10.3390/jcm12206461] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality. METHODS This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients. RESULTS Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available. CONCLUSION In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.
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17
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Jan IS, Ch'ang HJ. Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy. Radiat Oncol 2023; 18:137. [PMID: 37596627 PMCID: PMC10439654 DOI: 10.1186/s13014-023-02328-y] [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: 03/28/2023] [Accepted: 08/03/2023] [Indexed: 08/20/2023] Open
Abstract
Despite combination chemotherapy demonstrating a positive effect on survival, the clinical outcomes of pancreatic adenocarcinoma (PDAC) remain poor. Radiotherapy was previously a component of the curative treatment of PDAC. Advances in imaging and computer sciences have enabled the prescription of higher dosage of radiation focused on tumours with minimal toxicity to normal tissue. However, the role of radiotherapy has not been established in the curative treatment of localized PDAC because of the conflicting results from large prospective trials. Most studies have demonstrated improved locoregional control but no survival benefit from additional chemoradiotherapy (CRT) in addition to chemotherapy for resectable, borderline or locally advanced PDAC. The improved locoregional control enabled by CRT does not cause extended survival because of rapid distant progression in a significant proportion of patients with PDAC. Several single-institute studies of prescribing intensive chemotherapy with modern ablative radiotherapy for locally advanced PDAC have demonstrated extended survival with an acceptable safety profile. In an analysis after long-term follow-up, the PREOPANC study demonstrated a survival benefit from neoadjuvant gemcitabine-based CRT in resected PDAC relative to upfront surgery followed by adjuvant gemcitabine only. These observations indicated that the role of radiotherapy in PDAC should be evaluated in a subgroup of patients without rapid distant progression because systemic therapy for PDAC remains underdeveloped. We reviewed critical imaging, tissue, liquid and clinical biomarkers to differentiate the heterogeneous biologic spectra of patients with PDAC to identify those who may benefit the most from local radiotherapy. Exclusion of patients with localised PDAC who develop distant progression in a short time and undergo extended upfront chemotherapy for over 4 months may enable the identification of a survival benefit of local radiotherapy. Though promising, the effectiveness of biomarkers must be validated in a multi-institutional prospective study of patients with PDAC receiving CRT or not receiving CRT.
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Affiliation(s)
- I-Shiow Jan
- Department of Laboratory Medicine, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Hui Ju Ch'ang
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
- Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
- Department of Radiation Oncology, Taipei Medical University, Taipei, Taiwan.
- Department of Oncology, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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18
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Katz MHG. Selective Not Routine Use. Int J Radiat Oncol Biol Phys 2023; 116:707. [PMID: 37355304 DOI: 10.1016/j.ijrobp.2023.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/14/2023] [Indexed: 06/26/2023]
Affiliation(s)
- Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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19
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Olivari A, Agnetti V, Garajová I. Focus on Therapeutic Options for Surgically Resectable Pancreatic Adenocarcinoma Based on Novel Biomarkers. Curr Oncol 2023; 30:6462-6472. [PMID: 37504335 PMCID: PMC10378659 DOI: 10.3390/curroncol30070475] [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: 05/30/2023] [Revised: 06/29/2023] [Accepted: 07/04/2023] [Indexed: 07/29/2023] Open
Abstract
Pancreatic ductal adenocarcinoma remains associated with a poor prognosis, even when diagnosed at an early stage. Consequently, it is imperative to carefully consider the available therapeutic options and tailor them based on clinically relevant biomarkers. In our comprehensive review, we specifically concentrated on the identification of novel predictive and prognostic markers that have the potential to be integrated into multiparametric scoring systems. These scoring systems aim to accurately predict the efficacy of neoadjuvant chemotherapy in surgically resectable pancreatic cancer cases. By identifying robust predictive markers, we can enhance our ability to select patients who are most likely to benefit from neoadjuvant chemotherapy. Furthermore, the identification of prognostic markers can provide valuable insights into the overall disease trajectory and inform treatment decisions. The development of multiparametric scoring systems that incorporate these markers holds great promise for optimizing the selection of patients for neoadjuvant chemotherapy, leading to improved outcomes in resectable pancreatic neoplasia. Continued research efforts are needed to validate and refine these markers and scoring systems, ultimately advancing the field of personalized medicine in pancreatic adenocarcinoma management.
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Affiliation(s)
- Alessandro Olivari
- Medical Oncology Unit, Parma University Hospital, Via Gramsci 14, 43125 Parma, Italy
| | - Virginia Agnetti
- Medical Oncology Unit, Parma University Hospital, Via Gramsci 14, 43125 Parma, Italy
| | - Ingrid Garajová
- Medical Oncology Unit, Parma University Hospital, Via Gramsci 14, 43125 Parma, Italy
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Hank T, Klaiber U, Hinz U, Schütte D, Leonhardt CS, Bergmann F, Hackert T, Jäger D, Büchler MW, Strobel O. Oncological Outcome of Conversion Surgery After Preoperative Chemotherapy for Metastatic Pancreatic Cancer. Ann Surg 2023; 277:e1089-e1098. [PMID: 35758505 PMCID: PMC10082047 DOI: 10.1097/sla.0000000000005481] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach. BACKGROUND The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear. METHODS Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed. RESULTS Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8 mo, P =0.024) as well as in ypM0 (29.1 vs 19.2 mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup. CONCLUSION In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.
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Affiliation(s)
- Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Denise Schütte
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Carl-Stephan Leonhardt
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Frank Bergmann
- Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
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21
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Heiselman JS, Ecker BL, Langdon-Embry L, O’Reilly EM, Miga MI, Jarnagin WR, Do RKG, Horvat N, Wei AC, Chakraborty J. Registration-based biomarkers for neoadjuvant treatment response of pancreatic cancer via longitudinal image registration. J Med Imaging (Bellingham) 2023; 10:036002. [PMID: 37274758 PMCID: PMC10237235 DOI: 10.1117/1.jmi.10.3.036002] [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: 11/23/2022] [Revised: 04/18/2023] [Accepted: 05/15/2023] [Indexed: 06/06/2023] Open
Abstract
Purpose Pancreatic ductal adenocarcinoma (PDAC) frequently presents as hypo- or iso-dense masses with poor contrast delineation from surrounding parenchyma, which decreases reproducibility of manual dimensional measurements obtained during conventional radiographic assessment of treatment response. Longitudinal registration between pre- and post-treatment images may produce imaging biomarkers that more reliably quantify treatment response across serial imaging. Approach Thirty patients who prospectively underwent a neoadjuvant chemotherapy regimen as part of a clinical trial were retrospectively analyzed in this study. Two image registration methods were applied to quantitatively assess longitudinal changes in tumor volume and tumor burden across the neoadjuvant treatment interval. Longitudinal registration errors of the pancreas were characterized, and registration-based treatment response measures were correlated to overall survival (OS) and recurrence-free survival (RFS) outcomes over 5-year follow-up. Corresponding biomarker assessments via manual tumor segmentation, the standardized response evaluation criteria in solid tumors (RECIST), and pathological examination of post-resection tissue samples were analyzed as clinical comparators. Results Average target registration errors were 2.56 ± 2.45 mm for a biomechanical image registration algorithm and 4.15 ± 3.63 mm for a diffeomorphic intensity-based algorithm, corresponding to 1-2 times voxel resolution. Cox proportional hazards analysis showed that registration-derived changes in tumor burden were significant predictors of OS and RFS, while none of the alternative comparators, including manual tumor segmentation, RECIST, or pathological variables were associated with consequential hazard ratios. Additional ROC analysis at 1-, 2-, 3-, and 5-year follow-up revealed that registration-derived changes in tumor burden between pre- and post-treatment imaging were better long-term predictors for OS and RFS than the clinical comparators. Conclusions Volumetric changes measured by longitudinal deformable image registration may yield imaging biomarkers to discriminate neoadjuvant treatment response in ill-defined tumors characteristic of PDAC. Registration-based biomarkers may help to overcome visual limits of radiographic evaluation to improve clinical outcome prediction and inform treatment selection.
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Affiliation(s)
- Jon S. Heiselman
- Memorial Sloan Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Unit, New York, New York, United States
- Vanderbilt University, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - Brett L. Ecker
- Rutgers Cancer Institute of New Jersey, Department of Surgery, New Brunswick, New Jersey, United States
| | - Liana Langdon-Embry
- Rutgers New Jersey Medical School, Cooperman Barnabas Medical Center, Livingston, New Jersey, United States
| | - Eileen M. O’Reilly
- Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, New York, United States
| | - Michael I. Miga
- Vanderbilt University, Department of Biomedical Engineering, Nashville, Tennessee, United States
| | - William R. Jarnagin
- Memorial Sloan Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Unit, New York, New York, United States
| | - Richard K. G. Do
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York, United States
| | - Natally Horvat
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, New York, United States
| | - Alice C. Wei
- Memorial Sloan Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Unit, New York, New York, United States
| | - Jayasree Chakraborty
- Memorial Sloan Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Unit, New York, New York, United States
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22
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Guggenberger KV, Bley TA, Held S, Keller R, Flemming S, Wiegering A, Germer CT, Kimmel B, Kunzmann V, Hartlapp I, Anger F. Predictive value of computed tomography on surgical resectability in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: Results from a prospective, multicentre phase 2 trial (NEOLAP-AIO-PAK-0113). Eur J Radiol 2023; 163:110834. [PMID: 37080059 DOI: 10.1016/j.ejrad.2023.110834] [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: 03/06/2023] [Revised: 04/05/2023] [Accepted: 04/07/2023] [Indexed: 04/22/2023]
Abstract
PURPOSE To assess the role of current imaging-based resectability criteria and the degree of radiological downsizing in locally advanced pancreatic adenocarcinoma (LAPC) after multiagent induction chemotherapy (ICT) in multicentre, open-label, randomized phase 2 trial. METHOD LAPC patients were prospectively treated with multiagent ICT followed by surgical exploration within the NEOLAP trial. All patients underwent CT scan at baseline and after ICT to assess resectability status according to national comprehensive cancer network guidelines (NCCN) criteria and response evaluation criteria in solid tumors (RECIST) at the local study center and retrospectively in a central review. Imaging results were compared in terms of local and central staging, downsizing and pathological resection status. RESULTS 83 patients were evaluable for central review of baseline and restaging imaging results. Downstaging by central review was rarely seen after multiagent ICT (7.7%), whereas tumor downsizing was documented frequently (any downsizing 90.4%, downsizing to partial response (PR) according to RECIST: 26.5%). Patients with any downsizing showed no significant different R0 resection rate (37.3%) as patients that fulfilled the criteria of PR (40.9%). The sensitivity of any downsizing for predicting R0 resection was 97% with a negative predictive value (NPV) of 0.88. ROC-analysis revealed that tumor downsizing was a predictor of R0 resection (AUC 0.647, p = 0.028) with a best cut-off value of 22.5% downsizing yielding a sensitivity of 65% and a specificity of 61%. CONCLUSIONS Imaging-based tumor downsizing and not downstaging can guide the selection of patients with a realistic chance of R0-resection in LAPC after multi-agent ICT.
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Affiliation(s)
- K V Guggenberger
- Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, Wuerzburg, Germany.
| | - T A Bley
- Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, Wuerzburg, Germany
| | - S Held
- Department of Biometrics, ClinAssess GmbH, Leverkusen, Germany
| | - R Keller
- Clinical Research, AIO Studien gGmbH, Berlin, Germany
| | - S Flemming
- Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - A Wiegering
- Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - C T Germer
- Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - B Kimmel
- Department of Internal Medicine II, Medical Oncology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany
| | - V Kunzmann
- Department of Internal Medicine II, Medical Oncology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany
| | - I Hartlapp
- Department of Internal Medicine II, Medical Oncology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany
| | - F Anger
- Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
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23
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Newhook TE, Vreeland TJ, Griffin JF, Tidwell RSS, Prakash LR, Koay EJ, Ludmir EB, Smaglo BG, Pant S, Overman M, Wolff RA, Ikoma N, Maxwell J, Kim MP, Lee JE, Katz MHG, Tzeng CWD. Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma. Ann Surg 2023; 277:484-490. [PMID: 36649067 DOI: 10.1097/sla.0000000000005184] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication. METHODS Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. RESULTS Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). CONCLUSIONS This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.
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Affiliation(s)
- Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | - Rebecca S S Tidwell
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eugene J Koay
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ethan B Ludmir
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brandon G Smaglo
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shubham Pant
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael Overman
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert A Wolff
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jessica Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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24
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Bao QR, Frigerio I, Tripepi M, Marletta S, Martignoni G, Giardino A, Regi P, Scopelliti F, Allegrini V, Girelli R, Pucciarelli S, Spolverato G, Butturini G. Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma. Pancreatology 2023; 23:266-274. [PMID: 36841686 DOI: 10.1016/j.pan.2023.02.005] [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: 10/27/2022] [Revised: 01/27/2023] [Accepted: 02/20/2023] [Indexed: 02/27/2023]
Abstract
BACKGROUND The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.
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Affiliation(s)
- Quoc Riccardo Bao
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy; General Surgery 3, Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Italy
| | - Isabella Frigerio
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
| | - Marzia Tripepi
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy; Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Stefano Marletta
- Pathology Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy; Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy
| | - Guido Martignoni
- Pathology Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Alessandro Giardino
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Paolo Regi
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Filippo Scopelliti
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Valentina Allegrini
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Roberto Girelli
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Salvatore Pucciarelli
- General Surgery 3, Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Italy
| | - Gaya Spolverato
- General Surgery 3, Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Italy
| | - Giovanni Butturini
- Hepatopancreatobiliary Surgery Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
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25
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Zaharia C, Søreide K. Call for better response evaluation after neoadjuvant therapy in pancreatic cancer. Br J Surg 2023; 110:294-296. [PMID: 36630676 PMCID: PMC10364493 DOI: 10.1093/bjs/znac452] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 12/09/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Claudia Zaharia
- Department of Pathology, Stavanger University Hospital, Stavanger, Norway.,Gastrointestinal and Translational Research Group, Stavanger University Hospital, Stavanger, Norway
| | - Kjetil Søreide
- Gastrointestinal and Translational Research Group, Stavanger University Hospital, Stavanger, Norway.,Department of Gastrointestinal Surgery, Hepatopancreatobiliary Unit, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical medicine, University of Bergen, Bergen, Norway
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26
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Saha A, Wadsley J, Sirohi B, Goody R, Anthony A, Perumal K, Ulahanan D, Collinson F. Can Concurrent Chemoradiotherapy Add Meaningful Benefit in Addition to Induction Chemotherapy in the Management of Borderline Resectable and Locally Advanced Pancreatic Cancer?: A Systematic Review. Pancreas 2023; 52:e7-e20. [PMID: 37378896 DOI: 10.1097/mpa.0000000000002215] [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: 06/29/2023]
Abstract
OBJECTIVES The role of concomitant chemoradiotherapy or radiotherapy (RT) after induction chemotherapy (IC) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma is debatable. This systematic review aimed to explore this. METHODS We searched PubMed, MEDLINE, EMBASE, and Cochrane database. Studies were selected reporting outcomes on resection rate, R0 resection, pathological response, radiological response, progression-free survival, overall survival, local control, morbidity, and mortality. RESULTS The search resulted in 6635 articles. After 2 rounds of screening, 34 publications were selected. We found 3 randomized controlled studies and 1 prospective cohort study, and the rest were retrospective studies. There is consistent evidence that addition of concomitant chemoradiotherapy or RT after IC improves pathological response and local control. There are conflicting results in terms of other outcomes. CONCLUSIONS Concomitant chemoradiotherapy or RT after IC improves local control and pathological response in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. The role of modern RT in improving other outcome requires further research.
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Affiliation(s)
- Animesh Saha
- From the Department of Radiation Oncology, Apollo Multispecilty Hospitals, Kolkata, India
| | - Jonathan Wadsley
- Department of Clinical Oncology, Weston Park Cancer Centre, Sheffield, United Kingdom
| | - Bhawna Sirohi
- Department of Medical Oncology, Apollo Proton Cancer Centre, Chennai, India
| | | | - Alan Anthony
- Medical Oncology, Leeds Cancer Center, Leeds, United Kingdom
| | | | - Danny Ulahanan
- Medical Oncology, Leeds Cancer Center, Leeds, United Kingdom
| | - Fiona Collinson
- Medical Oncology, Leeds Cancer Center, Leeds, United Kingdom
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27
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Maggino L, Malleo G, Crippa S, Belfiori G, Nobile S, Gasparini G, Lionetto G, Luchini C, Mattiolo P, Schiavo-Lena M, Doglioni C, Scarpa A, Bassi C, Falconi M, Salvia R. CA19.9 Response and Tumor Size Predict Recurrence Following Post-neoadjuvant Pancreatectomy in Initially Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2023; 30:207-219. [PMID: 36227391 PMCID: PMC9726670 DOI: 10.1245/s10434-022-12622-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 09/14/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Data on recurrence after post-neoadjuvant pancreatectomy are scant. This study investigated the incidence and pattern of recurrence in patients with initially resectable and borderline resectable pancreatic ductal adenocarcinoma who received post-neoadjuvant pancreatectomy. Furthermore, preoperative predictors of recurrence-free survival (RFS) and their interactions were determined. PATIENTS AND METHODS Patients undergoing post-neoadjuvant pancreatectomy at two academic facilities between 2013 and 2017 were analyzed using standard statistics. The possible interplay between preoperative parameters was scrutinized including interaction terms in multivariable Cox models. RESULTS Among 315 included patients, 152 (48.3%) were anatomically resectable. The median RFS was 15.7 months, with 1- and 3-year recurrence rates of 41.9% and 74.2%, respectively. Distant recurrence occurred in 83.3% of patients, with lung-only patterns exhibiting the most favorable prognostic outlook. Normal posttreatment CA19.9, ΔCA19.9 (both in patients with normal and elevated baseline levels), and posttreatment tumor size were associated with RFS. Critical thresholds for ΔCA19.9 and tumor size were set at 50% and 20 mm, respectively. Interaction between ΔCA19.9 and posttreatment CA19.9 suggested a significant risk reduction in patients with elevated values when ΔCA19.9 exceeded 50%. Moreover, posttreatment tumor size interacted with posttreatment CA19.9 and ΔCA19.9, suggesting an increased risk in the instance of elevated posttreatment CA19.9 values and a protective effect associated with CA19.9 response in patients with tumor size >20 mm. CONCLUSION Recurrence following post-neoadjuvant pancreatectomy is common. Preoperative tumor size <20 mm, normal posttreatment CA19.9 and ΔCA19.9 > 50% were associated with longer RFS. These variables should not be taken in isolation, as their interaction significantly modulates the recurrence risk.
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Affiliation(s)
- Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
| | - Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
| | - Stefano Crippa
- Unit of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Giulio Belfiori
- Unit of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Sara Nobile
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
| | - Giulia Gasparini
- Unit of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Gabriella Lionetto
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona Hospital Trust, Verona, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona Hospital Trust, Verona, Italy
| | - Marco Schiavo-Lena
- Division of Pathology, Pancreas Translational and Clinical Research Center, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Doglioni
- Division of Pathology, Pancreas Translational and Clinical Research Center, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
| | - Massimo Falconi
- Unit of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy
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28
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Cai W, Zhu Y, Teng Z, Li D, Feng Q, Jiang Z, Cong R, Chen Z, Liu S, Zhao X, Ma X. Combined CT and serum CA19-9 for stratifying risk for progression in patients with locally advanced pancreatic cancer receiving intraoperative radiotherapy. Front Oncol 2023; 13:1155555. [PMID: 37124483 PMCID: PMC10140514 DOI: 10.3389/fonc.2023.1155555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Background and purpose The aim of this study was to evaluate the significance of baseline computed tomography (CT) imaging features and carbohydrate antigen 19-9 (CA19-9) in predicting prognosis of locally advanced pancreatic cancer (LAPC) receiving intraoperative radiotherapy (IORT) and to establish a progression risk nomogram that helps to identify the potential beneficiary of IORT. Methods A total of 88 LAPC patients with IORT as their initial treatment were enrolled retrospectively. Clinical data and CT imaging features were analyzed. Cox regression analyses were performed to identify the independent risk factors for progression-free survival (PFS) and to establish a nomogram. A risk-score was calculated by the coefficients of the regression model to stratify the risk of progression. Results Multivariate analyses revealed that relative enhanced value in portal-venous phase (REV-PVP), peripancreatic fat infiltration, necrosis, and CA19-9 were significantly associated with PFS (all p < 0.05). The nomogram was constructed according to the above variables and showed a good performance in predicting the risk of progression with a concordance index (C-index) of 0.779. Our nomogram stratified patients with LAPC into low- and high-risk groups with distinct differences in progression after IORT (p < 0.001). Conclusion The integrated nomogram would help clinicians to identify appropriate patients who might benefit from IORT before treatment and to adapt an individualized treatment strategy.
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Affiliation(s)
- Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongjian Zhu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ze Teng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qinfu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhichao Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rong Cong
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaowei Chen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Siyun Liu
- Magnetic Resonance Imaging Research, General Electric Healthcare (China), Beijing, China
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Xiaohong Ma,
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DiPeri TP, Newhook TE, Prakash LR, Ikoma N, Maxwell JE, Kim MP, Lee JE, Katz MH, Tzeng CWD. Prognostic significance of preoperative and postoperative CA 19-9 normalization in pancreatic adenocarcinoma treated with neoadjuvant therapy or surgery first. J Surg Oncol 2022; 126:1021-1027. [PMID: 35726394 PMCID: PMC9547830 DOI: 10.1002/jso.26989] [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: 04/27/2022] [Revised: 06/08/2022] [Accepted: 06/11/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF). METHODS Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin <2 mg/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9. RESULTS In patients receiving NT, normal pre/postoperative CA19-9 ("NTnl/nl ") was associated with median RFS and OS (26 and 77mo), followed by those who normalized after surgery ("NTabnl/nl " 16 and 44mo). For SF patients, normal pre-/postoperative CA19-9 ("SFnl/nl ") was associated with median RFS and OS (115 and not estimable mo), followed by those who normalized after resection ("SFabnl/nl " 18 and 49mo). Groups "NTabnl/abnl " and "SFabnl/abnl " with elevated CA19-9 both before and after resection had the worst median RFS and OS durations. CONCLUSIONS While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of SF patients. NT should be considered in patients presenting with elevated CA19-9. If considering SF, ideal patients may include those with normal CA19-9 at presentation.
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Affiliation(s)
- Timothy P. DiPeri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Timothy E. Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Laura R. Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Jessica E. Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Michael P. Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Matthew H.G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Ching-Wei D. Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
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Lee W, Park HJ, Lee HJ, Jun E, Song KB, Hwang DW, Lee JH, Lim K, Kim N, Lee SS, Byun JH, Kim HJ, Kim SC. Preoperative data-based deep learning model for predicting postoperative survival in pancreatic cancer patients. Int J Surg 2022; 105:106851. [PMID: 36049618 DOI: 10.1016/j.ijsu.2022.106851] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 08/01/2022] [Accepted: 08/12/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis even after curative resection. A deep learning-based stratification of postoperative survival in the preoperative setting may aid the treatment decisions for improving prognosis. This study was aimed to develop a deep learning model based on preoperative data for predicting postoperative survival. METHODS The patients who underwent surgery for PDAC between January 2014 and May 2015. Clinical data-based machine learning models and computed tomography (CT) data-based deep learning models were developed separately, and ensemble learning was utilized to combine two models. The primary outcomes were the prediction of 2-year overall survival (OS) and 1-year recurrence-free survival (RFS). The model's performance was measured by area under the receiver operating curve (AUC) and was compared with that of American Joint Committee on Cancer (AJCC) 8th stage. RESULTS The median OS and RFS were 23 and 10 months in training dataset (n = 229), and 22 and 11 months in test dataset (n = 53), respectively. The AUC of the ensemble model for predicting 2-year OS and 1-year RFS in the test dataset was 0.76 and 0.74, respectively. The performance of the ensemble model was comparable to that of the AJCC in predicting 2-year OS (AUC, 0.67; P = 0.35) and superior to the AJCC in predicting 1-year RFS (AUC, 0.54; P = 0.049). CONCLUSION and relevance: Our ensemble model based on routine preoperative variables showed good performance for predicting prognosis for PDAC patients after surgery.
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Affiliation(s)
- Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hack-Jin Lee
- R&D Team, DoAI Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Kyongmook Lim
- R&D Team, DoAI Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
| | - Namkug Kim
- Department of Convergence Medicine and Radiology, Research Institute of Radiology and Institute of Biomedical Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seung Soo Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Jae Ho Byun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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31
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Seo YD, Katz MHG. Preoperative therapy for pancreatic adenocarcinoma-precision beyond anatomy. Cancer 2022; 128:3041-3056. [PMID: 35679197 DOI: 10.1002/cncr.34273] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/06/2022] [Accepted: 05/11/2022] [Indexed: 12/16/2022]
Abstract
Despite recent advances in the systemic treatment of gastrointestinal tumors, pancreatic adenocarcinoma (PDAC) remains a challenging disease, with 5-year survival just over 10%. Pancreatectomy in patients meeting defined anatomic criteria can result in cure; however, perioperative morbidity and mortality, as well as high rates of both local and distant recurrence even after "potentially curative" resection, have limited survival. Although perioperative chemotherapy has been shown to improve patients' longevity and chance for cure, debate continues about whether the preoperative or adjuvant approach is most effective in treatment of localized PDAC. Large, randomized multicenter trials in patients with resectable and borderline resectable PDAC have evaluated an evolving therapeutic landscape with mixed results. Importantly, these landmark studies share the fundamentally flawed assumption that tumor anatomical characteristics are an indicator of behavior and natural history. Concurrent biologic and translational research has revealed that rather than a single disease, PDAC represents a phenotypically variable group of malignancies arising in physiologically diverse patients. Ongoing novel trials have begun to capture this heterogeneity both in patient selection as well as the measurement of response by using genomic, transcriptional and radiomic markers. By moving away from classic anatomic descriptors to a more nuanced landscape of biomarkers predictive of tumor behavior and response, we can further refine the questions asked in preoperative trials and translate the answers to clinically meaningful precision therapy in localized PDAC.
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Affiliation(s)
- Y David Seo
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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32
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Hester CA, Perri G, Prakash LR, Maxwell JE, Ikoma N, Kim MP, Tzeng CWD, Smaglo B, Wolff R, Javle M, Overman MJ, Lee JE, Katz MHG. Radiographic and Serologic Response to First-Line Chemotherapy in Unresected Localized Pancreatic Cancer. J Natl Compr Canc Netw 2022; 20:887-897.e3. [PMID: 35948035 DOI: 10.6004/jnccn.2022.7018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 04/14/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND This study aimed to determine the clinical relevance of putative radiographic and serologic metrics of chemotherapy response in patients with localized pancreatic cancer (LPC) who do not undergo pancreatectomy. Studies evaluating the response of LPC to systemic chemotherapy have focused on histopathologic analyses of resected specimens, but such specimens are not available for patients who do not undergo resection. We previously showed that changes in tumor volume and CA 19-9 levels provide a clinical readout of histopathologic response to preoperative therapy. METHODS Our institutional database was searched for patients with LPC who were treated with first-line chemotherapy between January 2010 and December 2017 and did not undergo pancreatectomy. Radiographic response was measured using RECIST 1.1 and tumor volume. The volume of the primary tumor was compared between pretreatment and posttreatment images. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the pretreatment volume. Serologic response was measured by comparing pretreatment and posttreatment CA 19-9 levels. We established 3 response groups by combining these metrics: (1) best responders with a decline in %Δvol in the top quartile and in CA 19-9, (2) nonresponders with an increase in %Δvol and in CA 19-9, and (3) other patients. RESULTS This study included 329 patients. Individually, %Δvol and change in CA 19-9 were associated with overall survival (OS) (P≤.1), but RECIST 1.1 was not. In all, 73 patients (22%) were best responders, 42 (13%) were nonresponders, and there were 214 (65%) others. Best responders lived significantly longer than nonresponders and others (median OS, 24 vs 12 vs 17 months, respectively; P<.01). A multivariable model adjusting for type of chemotherapy regimen, number of chemotherapy doses, and receipt of radiotherapy showed that best responders had longer OS than did the other cohorts (hazard ratio [HR], 0.35; 95% CI, 0.21-0.58 for best responders, and HR, 0.55; 95% CI, 0.37-0.83 for others). CONCLUSIONS Changes in tumor volume and serum levels of CA 19-9-but not RECIST 1.1-represent reliable metrics of response to systemic chemotherapy. They can be used to counsel patients and families on survival expectations even if pancreatectomy is not performed.
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Affiliation(s)
- Caitlin A Hester
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Giampaolo Perri
- Department of General and Pancreatic Surgery, University of Verona, Verona, Italy; and
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Brandon Smaglo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Claus A, Sweeney A, Sankepalle DM, Li B, Wong D, Xavierselvan M, Mallidi S. 3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors. Front Oncol 2022; 12:915319. [PMID: 35875138 PMCID: PMC9300843 DOI: 10.3389/fonc.2022.915319] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/24/2022] [Indexed: 01/27/2023] Open
Abstract
Pancreatic cancer is a disease with an incredibly poor survival rate. As only about 20% of patients are eligible for surgical resection, neoadjuvant treatments that can relieve symptoms and shrink tumors for surgical resection become critical. Many forms of treatments rely on increased vulnerability of cancerous cells, but tumors or regions within the tumors that may be hypoxic could be drug resistant. Particularly for neoadjuvant therapies such as the tyrosine kinase inhibitors utilized to shrink tumors, it is critical to monitor changes in vascular function and hypoxia to predict treatment efficacy. Current clinical imaging modalities used to obtain structural and functional information regarding hypoxia or oxygen saturation (StO2) do not provide sufficient depth penetration or require the use of exogenous contrast agents. Recently, ultrasound-guided photoacoustic imaging (US-PAI) has garnered significant popularity, as it can noninvasively provide multiparametric information on tumor vasculature and function without the need for contrast agents. Here, we built upon existing literature on US-PAI and demonstrate the importance of changes in StO2 values to predict treatment response, particularly tumor growth rate, when the outcomes are suboptimal. Specifically, we image xenograft mouse models of pancreatic adenocarcinoma treated with suboptimal doses of a tyrosine kinase inhibitor cabozantinib. We utilize the US-PAI data to develop a multivariate regression model that demonstrates that a therapy-induced reduction in tumor growth rate can be predicted with 100% positive predictive power and a moderate (58.33%) negative predictive power when a combination of pretreatment tumor volume and changes in StO2 values pretreatment and immediately posttreatment was employed. Overall, our study indicates that US-PAI has the potential to provide label-free surrogate imaging biomarkers that can predict tumor growth rate in suboptimal therapy.
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Turner KM, Delman AM, Kharofa JR, Smith MT, Choe KA, Olowokure O, Wilson GC, Patel SH, Sohal D, Ahmad SA. Radiation therapy in borderline resectable pancreatic cancer: A review. Surgery 2022; 172:284-290. [PMID: 35034793 DOI: 10.1016/j.surg.2021.12.013] [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: 10/07/2021] [Revised: 11/11/2021] [Accepted: 12/14/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Borderline resectable pancreatic cancer constitutes a complex clinical entity, presenting the clinician with a locally aggressive disease that has a proclivity for distant spread. The benefits of radiation therapy, such as improved local control and improved survival, have been questioned. In this review we seek to summarize the existing evidence on radiation therapy in borderline resectable pancreatic cancer and highlight future areas of research. METHODS A comprehensive review of PubMed for clinical studies reporting outcomes in borderline resectable pancreatic cancer was performed in June 2021, with an emphasis placed on prospective studies. RESULTS Radiologic "downstaging" in borderline resectable pancreatic cancer is a rare event, although some evidence shows increased clinical response to neoadjuvant chemotherapy over radiation therapy. Margin status seems to be equivalent between regimens that use neoadjuvant chemotherapy alone and regimens that include neoadjuvant radiation therapy. Local control in borderline resectable pancreatic cancer is likely improved with radiation therapy; however, the benefit of improved local control in a disease marked by systemic failure has been questioned. Although some studies have shown improved survival with radiation therapy, differences in the delivery and tolerance of chemotherapy between the neoadjuvant and adjuvant setting confound these results. When the evidence is evaluated as a whole, there is no clear survival benefit of radiation therapy in borderline resectable pancreatic cancer. CONCLUSION Once considered a staple of therapy, the role of radiation therapy in borderline resectable pancreatic cancer is evolving as systemic therapy regimens continues to improve. Increased clinical understanding of disease phenotype and response are needed to accurately tailor therapy for individual patients and to improve outcomes in this complex patient population.
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Affiliation(s)
- Kevin M Turner
- Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Aaron M Delman
- Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Jordan R Kharofa
- Department of Radiation Oncology, University of Cincinnati College of Medicine, OH
| | - Milton T Smith
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Kyuran A Choe
- Department of Radiology, University of Cincinnati College of Medicine, OH
| | - Olugbenga Olowokure
- Division of Hematology & Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Gregory C Wilson
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Davendra Sohal
- Division of Hematology & Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH.
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Jang JK, Choi SJ, Byun JH, Kim JH, Lee SS, Kim HJ, Yoo C, Kim KP, Hong SM, Seo DW, Hwang DW, Kim SC. Prediction of Margin-Negative Resection of Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy: Diagnostic Performance of NCCN Criteria for Resection vs. CT-Determined Resectability. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1025-1034. [PMID: 35658103 DOI: 10.1002/jhbp.1192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 04/12/2022] [Accepted: 04/17/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Accurate assessment of pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) is crucial. Recently, the NCCN introduced criteria for resection of PDAC following NAT. METHODS We analyzed 127 patients who underwent NAT and pancreatectomy for PDAC between January 2010 and March 2020. CT-determined resectability according to the NCCN guideline, and CA 19-9 level was evaluated before and after NAT. Diagnostic performance of the NCCN criteria for margin-negative (R0) resection was investigated and compared with CT alone. RESULTS R0 resection was achieved in 104 (81.9%) patients. After NAT, there were 30 (23.6%) resectable, 90 (70.9%) borderline resectable, and seven (5.5%) locally advanced tumors. Significantly decreased or stable CA 19-9 levels were noted in 114 (89.8%) patients. The sensitivity and specificity of the NCCN criteria were 87.5% (91/104) and 21.7% (5/23), respectively, which were significantly different from CT including only resectable PDAC (26.9% [28/104] and 91.3% [21/23]; p<0.001), but less prominently different from CT including resectable and borderline resectable PDAC (95.2% [99/104]; p=0.022 and 8.7% [2/23]; p=0.375). CONCLUSIONS The NCCN criteria for resection following NAT showed high sensitivity and low specificity for predicting R0 resection. It had supplementary benefit over CT alone, mainly in preventing underestimation of R0 resection.
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Affiliation(s)
- Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Se Jin Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Changhoon Yoo
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Dae Wook Hwang
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Song Cheol Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Taherian M, Wang H. Critical issues in pathologic evaluation of pancreatic ductal adenocarcinoma resected after neoadjuvant treatment: a narrative review. Chin Clin Oncol 2022; 11:21. [PMID: 35726190 PMCID: PMC9524072 DOI: 10.21037/cco-21-175] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 06/08/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND OBJECTIVE Preoperative neoadjuvant therapy (NAT) is increasingly used in the treatment of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Because NAT often induces heterogeneous tumor response and extensive fibrosis both in tumor and adjacent pancreatic tissue, pathologic assessment of posttherapy pancreatectomy specimens is challenging. A limited number of studies examined the optimal grossing and sampling methods, tumor response grading (TRG), and the prognostic value of posttherapy tumor (ypT) and lymph node (ypN) stages of treated PDAC patients. In this review, we will provide an overview of the current status and critical issues in pathologic evaluation of PDAC resected after NAT. METHODS In PubMed, Google Scholar and Web of Science, we reviewed existing English literature (published up to December 2021) highlighting the most recent ones using electronic databases and authors' experience to outline the challenging aspects and new perspectives on pathologic assessment of the treated PDAC. KEY CONTENT AND FINDINGS The recent recommendations from the Pancreatobiliary Pathology Society (PBPS) provide the much-needed guidelines for systematic and standardized pathologic evaluation and reporting of treated PDAC for optimal patient care. For treated PDAC, tumor size measured by gross and radiology is not reliable. Histologic validation of tumor size on consecutive mapping sections is recommended for accurate ypT stage. A tumor size of 1.0 cm seems to be a better cutoff for ypT2 for treated PDACs. The published data suggested that the MD Anderson Cancer Center (MDA) TRG system is easy to use, has a better interobserver agreement and better correlation with patient prognosis compared to the College of American Pathologists (CAP) and Evans grading systems and may be used as an alternative TRG system for the CAP cancer protocol. CONCLUSIONS Systemic and standardized grossing and sampling are essential for accurate pathologic evaluation and reporting for optimal care of PDAC patients who received NAT. Future studies on optimal sampling and integration of histopathology with artificial intelligence (AI), molecular and immunohistochemical markers are needed for better and personalized care of treated PDAC patients.
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Affiliation(s)
- Mehran Taherian
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Huamin Wang
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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37
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Labori KJ. Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives. Front Surg 2022; 9:839339. [PMID: 35548190 PMCID: PMC9082635 DOI: 10.3389/fsurg.2022.839339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/28/2022] [Indexed: 12/27/2022] Open
Abstract
Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.
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Affiliation(s)
- Knut Jørgen Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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38
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Murata Y, Mizuno S, Kishiwada M, Uchida K, Noguchi D, Gyoten K, Hayasaki A, Fujii T, Iizawa Y, Tanemura A, Kuriyama N, Sakurai H, Isaji S. Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma. Pancreatology 2021; 21:1482-1490. [PMID: 34452821 DOI: 10.1016/j.pan.2021.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 08/19/2021] [Accepted: 08/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined. OBJECTIVE To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC. METHODS The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis. RESULTS Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR. CONCLUSIONS pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.
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Affiliation(s)
- Yasuhiro Murata
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
| | - Shugo Mizuno
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Masashi Kishiwada
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Katsunori Uchida
- Department of the Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Daisuke Noguchi
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Kazuyuki Gyoten
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Aoi Hayasaki
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Takehiro Fujii
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Yusuke Iizawa
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Akihiro Tanemura
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Naohisa Kuriyama
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Hiroyuki Sakurai
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Shuji Isaji
- Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
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39
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Okada K, Uemura K, Kondo N, Sumiyoshi T, Seo S, Otsuka H, Serikawa M, Ishii Y, Tsuboi T, Murakami Y, Takahashi S. Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer. Langenbecks Arch Surg 2021; 407:623-632. [PMID: 34609618 DOI: 10.1007/s00423-021-02339-x] [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: 02/16/2021] [Accepted: 09/21/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. METHODS The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. RESULTS In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p < 0.001) were independent poor prognostic factors. The median serum carbohydrate antigen (CA) 19-9 level after NAT in N2 patients was 105 U/mL, which was significantly higher than that of patients with N0 (p = 0.004) and N1 (p = 0.008) status. CONCLUSION Patients with BR/LAPC who underwent surgery after NAT had significantly lower N2 status and better prognosis than patients who underwent UFS. Elevated CA19-9 levels after NAT indicated a higher nodal status.
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Affiliation(s)
- Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
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40
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Khachfe HH, Habib JR, Nassour I, Al Harthi S, Jamali FR. Borderline Resectable and Locally Advanced Pancreatic Cancers: A Review of Definitions, Diagnostics, Strategies for Treatment, and Future Directions. Pancreas 2021; 50:1243-1249. [PMID: 34860806 DOI: 10.1097/mpa.0000000000001924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
ABSTRACT Locally advanced and borderline resectable pancreatic cancers are being increasingly recognized as a result of significant improvements in imaging modalities. The main tools used in diagnosis of these tumors include endoscopic ultrasound, computed tomography, magnetic resonance imaging, and diagnostic laparoscopy. The definition of what constitutes a locally advanced or borderline resectable tumor is still controversial to this day. Borderline resectable tumors have been treated with neoadjuvant therapy approaches that aim at reducing tumor size, thus improving the chances of an R0 resection. Both chemotherapy and radiotherapy (solo or in combination) have been used in this setting. The main chemotherapy agents that have shown to increase resectability and survival are FOLFORINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine-nab-paclitaxel. Surgery on these tumors remains a significantly challenging task for pancreatic surgeons. More studies are needed to determine the best agents to be used in the neoadjuvant and adjuvant settings, biologic markers for prognostic and operative predictions, and validation of previously published retrospective results.
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Affiliation(s)
| | - Joseph R Habib
- Division of General Surgery, University of Maryland, Baltimore, MD
| | | | - Salem Al Harthi
- Division of General Surgery, University of Maryland, Baltimore, MD
| | - Faek R Jamali
- Department of General Surgery, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
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41
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Neoadjuvant Treatment Strategies in Resectable Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13184724. [PMID: 34572951 PMCID: PMC8469083 DOI: 10.3390/cancers13184724] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/15/2021] [Accepted: 09/15/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Only 10–20% of patients with newly diagnosed resectable pancreatic adenocarcinoma have potentially resectable disease. Upfront surgery is the gold standard, but it is rarely curative. After surgical extirpation of tumors, up to 80% of patients will develop cancer recurrence, and the initial relapse is metastatic in 50–70% of these patients. Adjuvant chemotherapy offers the best strategy to date to improve overall survival but faces real challenges; some patients will experience rapid disease progression within 3 months of surgery and patients who do not receive all planned cycles of chemotherapy have unfavourable oncological outcomes. The neoadjuvant approach is therefore logical but requires further investigation. This approach shows favourable trends regarding disease-free survival and overall survival but, in the absence of rigorous published phase III trials, is not validated to date. Here, we intend to provide a comprehensive analysis of the literature to provide direction for future studies. Abstract Complete surgical resection is the cornerstone of curative therapy for resectable pancreatic adenocarcinoma. Upfront surgery is the gold standard, but it is rarely curative. Neoadjuvant treatment is a logical option, as it may overcome some of the limitations of adjuvant therapy and has already shown some encouraging results. The main concern regarding neoadjuvant therapy is the risk of disease progression during chemotherapy, meaning the opportunity to undergo the intended curative surgery is missed. We reviewed all recent literature in the following areas: major surveys, retrospective studies, meta-analyses, and randomized trials. We then selected the ongoing trials that we believe are of interest in this field and report here the results of a comprehensive review of the literature. Meta-analyses and randomized trials suggest that neoadjuvant treatment has a positive effect. However, no study to date can be considered practice changing. We considered design, endpoints, inclusion criteria and results of available randomized trials. Neoadjuvant treatment appears to be at least a feasible strategy for patients with resectable pancreatic cancer.
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Gleeson EM, Leigh N, Golas BJ, Magge D, Sarpel U, Hiotis SP, Labow DM, Pintova S, Cohen NA. Adjuvant Chemotherapy Is Not Guided by Pathologic Treatment Effect After Neoadjuvant Chemotherapy in Pancreatic Cancer. Pancreas 2021; 50:1163-1168. [PMID: 34714279 DOI: 10.1097/mpa.0000000000001881] [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: 12/10/2022]
Abstract
OBJECTIVES Currently, there is no guidance for optimal adjuvant chemotherapy selection after pancreatectomy with a partial or poor response to neoadjuvant therapy. This study seeks to describe an institution's practice patterns of adjuvant chemotherapy selection after neoadjuvant therapy. METHODS Patients at a single institution receiving neoadjuvant chemotherapy followed by pancreatectomy for pancreatic cancer were reviewed. Patients enrolled in trials or without follow-up were excluded. Types of chemotherapy, the College of American Pathologists pathologic tumor response, and medical oncology plans were recorded. RESULTS Forty-one patients met inclusion criteria. Pathologic review of treatment effect demonstrated that 3 patients (7.3%) had complete pathologic response, 3 (7.3%) had near complete pathologic response, 16 (39%) had partial response, and 14 (34.1%) had poor/no response to neoadjuvant chemotherapy. Fourteen of the 30 patients with partial or poor response (46.7%) received an alternate adjuvant regimen. Pathologic response to neoadjuvant chemotherapy specifically guided therapy in 11 (30.5%) patients. CONCLUSIONS Despite 73.1% of patients with partial or poor response to neoadjuvant chemotherapy, only 46.7% received a different adjuvant regimen. Medical oncologists infrequently considered treatment effect when choosing adjuvant therapy. Pathologic response to neoadjuvant chemotherapy should be considered when selecting adjuvant chemotherapy.
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Affiliation(s)
| | - Natasha Leigh
- From the Division of Surgical Oncology, Department of Surgery
| | | | - Deepa Magge
- From the Division of Surgical Oncology, Department of Surgery
| | - Umut Sarpel
- From the Division of Surgical Oncology, Department of Surgery
| | - Spiros P Hiotis
- From the Division of Surgical Oncology, Department of Surgery
| | - Daniel M Labow
- From the Division of Surgical Oncology, Department of Surgery
| | - Sofya Pintova
- Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Noah A Cohen
- From the Division of Surgical Oncology, Department of Surgery
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43
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Hamad A, Brown ZJ, Ejaz AM, Dillhoff M, Cloyd JM. Neoadjuvant therapy for pancreatic ductal adenocarcinoma: Opportunities for personalized cancer care. World J Gastroenterol 2021; 27:4383-4394. [PMID: 34366611 PMCID: PMC8316910 DOI: 10.3748/wjg.v27.i27.4383] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/12/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is best treated in a multidisciplinary fashion using surgery, chemotherapy, and radiation. Adjuvant chemotherapy has shown to have a significant survival benefit in patients with resected PDAC. However, up to 50% of patients fail to receive adjuvant chemotherapy due to postoperative complications, poor patient performance status or early disease progression. In order to ensure the delivery of chemotherapy, an alternative strategy is to administer systemic treatment prior to surgery. Precision oncology refers to the application of diverse strategies to target therapies specific to characteristics of a patient’s cancer. While traditionally emphasized in selecting targeted therapies based on molecular, genetic, and radiographic biomarkers for patients with metastatic disease, the neoadjuvant setting is a prime opportunity to utilize personalized approaches. In this article, we describe the current evidence for the use of neoadjuvant therapy (NT) and highlight unique opportunities for personalized care in patients with PDAC undergoing NT.
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Affiliation(s)
- Ahmad Hamad
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43215, United States
| | - Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43215, United States
| | - Aslam M Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43215, United States
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43215, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43215, United States
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44
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McCarthy PM, Rendo MJ, Uy MD, Adams AM, O’Shea AE, Nelson DW, Fenderson JL, Cebe KM, Krell RW, Clifton GT, Peoples GE, Vreeland TJ. Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma. Onco Targets Ther 2021; 14:3537-3544. [PMID: 34103944 PMCID: PMC8179799 DOI: 10.2147/ott.s311661] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/05/2021] [Indexed: 01/11/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.
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Affiliation(s)
| | - Matthew J Rendo
- Department of Hematology and Oncology, Brooke Army Medical Center, San Antonio, TX, USA
| | - Matthew D Uy
- Department of Pathology, Brooke Army Medical Center, San Antonio, TX, USA
| | - Alexandra M Adams
- Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA
| | - Anne E O’Shea
- Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA
| | | | - Joshua L Fenderson
- Department of Hematology and Oncology, Brooke Army Medical Center, San Antonio, TX, USA
| | - Katherine M Cebe
- Department of Pathology, Brooke Army Medical Center, San Antonio, TX, USA
| | - Robert W Krell
- Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA
| | - Guy T Clifton
- Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA
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45
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Hester CA, Katz MHG. Thumbprinting Locally Advanced Pancreatic Cancer: Have We Developed the Optimal Staging System? Ann Surg Oncol 2021; 28:5808-5810. [PMID: 34019183 DOI: 10.1245/s10434-021-10181-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 05/07/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Caitlin A Hester
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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46
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Feng Z, Li K, Lou J, Wu Y, Peng C. An EMT-Related Gene Signature for Predicting Response to Adjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma. Front Cell Dev Biol 2021; 9:665161. [PMID: 33996821 PMCID: PMC8119901 DOI: 10.3389/fcell.2021.665161] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022] Open
Abstract
Background For pancreatic ductal adenocarcinoma (PDAC) patients, chemotherapy failure is the major reason for postoperative recurrence and poor outcomes. Establishment of novel biomarkers and models for predicting chemotherapeutic efficacy may provide survival benefits by tailoring treatments. Methods Univariate cox regression analysis was employed to identify EMT-related genes with prognostic potential for DFS. These genes were subsequently submitted to LASSO regression analysis and multivariate cox regression analysis to identify an optimal gene signature in TCGA training cohort. The predictive accuracy was assessed by Kaplan–Meier (K-M), receiver operating characteristic (ROC) and calibration curves and was validated in PACA-CA cohort and our local cohort. Pathway enrichment and function annotation analyses were conducted to illuminate the biological implication of this risk signature. Results LASSO and multivariate Cox regression analyses selected an 8-gene signature comprised DLX2, FGF9, IL6R, ITGB6, MYC, LGR5, S100A2, and TNFSF12. The signature had the capability to classify PDAC patients with different DFS, both in the training and validation cohorts. It provided improved DFS prediction compared with clinical indicators. This signature was associated with several cancer-related pathways. In addition, the signature could also predict the response to immune-checkpoint inhibitors (ICIs)-based immunotherapy. Conclusion We established a novel EMT-related gene signature that was capable of predicting therapeutic response to adjuvant chemotherapy and immunotherapy. This signature might facilitate individualized treatment and appropriate management of PDAC patients.
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Affiliation(s)
- Zengyu Feng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Kexian Li
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianyao Lou
- Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yulian Wu
- Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chenghong Peng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Radiotherapy for Resectable and Borderline Resectable Pancreas Cancer: When and Why? J Gastrointest Surg 2021; 25:843-848. [PMID: 33205307 DOI: 10.1007/s11605-020-04838-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 10/17/2020] [Indexed: 01/31/2023]
Abstract
The role of (chemo) radiation in the perioperative management of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma is controversial. Herein, we review and interpret existing data relating to the ability of (chemo) radiation to "downstage" pancreatic tumors, delay recurrence, and prolong patients' survival. In sum, the evidence suggests that while neoadjuvant (chemo) radiation may impact pathologic metrics favorably, it rarely converts anatomically unresectable tumors to resectable ones. And while data do support the ability of (chemo)radiation to delay cancer progression, its ability to prolong longevity has not been confirmed. It is possible that (chemo)radiation is effective in prolonging the survival of select patients, but to date, this cohort remains undefined due to heterogeneity in both the populations studied and the regimens used to treat them. Based on our interpretation of existing data, we currently administer neoadjuvant and adjuvant (chemo)radiation selectively to patients with localized pancreatic cancer who we consider at highest risk for local progression. We may also use it as an alternative to pancreatectomy in patients who are poor candidates for surgery. Ultimately, the role of (chemo)radiation in these settings is evolving. Better studies of patients most likely to benefit from its local effects are necessary to clearly define its place within the perioperative treatment algorithms used for patients with localized pancreatic cancer.
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Perri G, Prakash L, Qiao W, Varadhachary GR, Wolff R, Fogelman D, Overman M, Pant S, Javle M, Koay EJ, Herman J, Kim M, Ikoma N, Tzeng CW, Lee JE, Katz MHG. Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. JAMA Surg 2021; 155:832-839. [PMID: 32667641 DOI: 10.1001/jamasurg.2020.2286] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel (GA) are first-line chemotherapy regimens for pancreatic cancer. Their relative efficacy in the setting of localized disease is unknown. Objective To evaluate radiographic and serologic measures of responses associated with first-line chemotherapy with FOLFIRINOX or GA, and to determine the association between these drug regimens, putative measures of response, and survival. Design, Setting, and Participants This case series assessed 485 consecutive patients who were diagnosed as having previously untreated localized pancreatic ductal adenocarcinoma at The University of Texas MD Anderson Cancer Center between January 1, 2010, and December 31, 2017, and who received at least 3 cycles of first-line chemotherapy with FOLFIRINOX or GA. The median (range) follow-up duration was 33 (2-28) months. Exposures Administration of FOLFIRINOX (285 patients [59%]) or GA (200 patients [41%]) as first-line chemotherapy. Main Outcomes and Measures Resection rate, radiographic metrics (Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1, and change in tumor volume or anatomic staging), a serologic metric (serum cancer antigen 19-9 level), and overall survival after administration of first-line chemotherapy. Results In total, 485 patients (266 [55%] male) were included in the analysis. Patients treated with FOLFIRINOX were generally younger (median [range] age at diagnosis: 61 [30-81] vs 71 [36-89] years; P = .001) and had better performance status as indicated by the Eastern Cooperative Oncology Group scale (range 0-4, with lower numbers representing better performance) score of 2 or lower (274 patients [96%] vs 165 patients [82%] P = .001) but more invasive tumors than patients who received GA (91 [32%] vs 90 [45%] resectable tumors; P = .01). After propensity score matching to control for these biases, many objective serologic and radiographic metrics of response associated with administration of FOLFIRINOX or GA-including low rates of local tumor downstaging-did not differ. However, RECIST partial response was more common among patients treated with FOLFIRINOX (27 of 140 patients [19%]) than with GA (8 of 140 patients [6%]; P = .001). Moreover, (chemo)radiation (50% vs 34%; P = .001) was more commonly administered to and pancreatectomy (27% vs 16%; P = .01) was subsequently performed more frequently for patients initially treated with FOLFIRINOX. The overall survival duration of patients treated with either regimen was similar (hazard ratio, 1.48; 95% CI, 0.97-2.26; P = .07). Conclusions and Relevance In this cohort of patients with localized pancreatic adenocarcinoma who received FOLFIRINOX or GA as their first line of therapy, FOLFIRINOX was associated with higher rates of RECIST partial response and subsequent pancreatectomy than GA, but the overall survival associated with these regimens was similar.
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Affiliation(s)
- Giampaolo Perri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Laura Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Wei Qiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston
| | - Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - David Fogelman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Michael Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Shubham Pant
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Joseph Herman
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Michael Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
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Wei D, Zaid MM, Katz MH, Prakash LR, Kim M, Tzeng CWD, Lee JE, Agrawal A, Rashid A, Wang H, Varadhachary G, Wolff RA, Tamm EP, Bhosale PR, Maitra A, Koay EJ, Wang H. Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma. Pancreatology 2021; 21:200-207. [PMID: 33221151 PMCID: PMC7855532 DOI: 10.1016/j.pan.2020.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 11/04/2020] [Accepted: 11/08/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Tumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival. MATERIALS AND METHODS Retrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant. RESULTS As a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P < 0.001) and RadV (δ: 0.63, p < 0.0001). However, there was no correlation between RadL and pathologic tumor size in patients with ypT0 and those with pathologic tumor size of ≤1.0 cm. Post-therapy RTS and RadV group correlated with ypT stage, tumor response grades using either CAP or MDA grading system, distance of superior mesenteric artery margin and tumor recurrence/metastasis. CONCLUSION Although RadL tends to understage ypT in PDAC patients who had no radiologically detectable tumor or small tumors (RTS0 or RTS1), radiologic measurement of post-therapy tumor size may be used as a marker for the pathologic tumor staging and tumor response to neoadjuvant therapy.
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Affiliation(s)
- Dongguang Wei
- Department of Anatomical Pathology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Mohamed M Zaid
- Department of Radiation Oncology, University of Texas, Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Matthew H Katz
- Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Laura R Prakash
- Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Michael Kim
- Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Anshuman Agrawal
- Department of Radiation Oncology, University of Texas, Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Asif Rashid
- Department of Anatomical Pathology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Hua Wang
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Gauri Varadhachary
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Eric P Tamm
- Department of Diagnostic Radiology, University of Texas MD Anderson, Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Priya R Bhosale
- Department of Diagnostic Radiology, University of Texas MD Anderson, Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Anirban Maitra
- Department of Anatomical Pathology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA; Department of Translational Molecular Pathology, University of Texas MD, Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Eugene J Koay
- Department of Radiation Oncology, University of Texas, Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA.
| | - Huamin Wang
- Department of Anatomical Pathology, University of Texas, MD Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA; Department of Translational Molecular Pathology, University of Texas MD, Anderson Cancer Center, 515 Holcombe Blvd, Houston, TX, 77030, USA.
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Watson MD, Baimas-George MR, Murphy KJ, Pickens RC, Iannitti DA, Martinie JB, Baker EH, Vrochides D, Ocuin LM. Pure and Hybrid Deep Learning Models can Predict Pathologic Tumor Response to Neoadjuvant Therapy in Pancreatic Adenocarcinoma: A Pilot Study. Am Surg 2020; 87:1901-1909. [PMID: 33381979 DOI: 10.1177/0003134820982557] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant therapy may improve survival of patients with pancreatic adenocarcinoma; however, determining response to therapy is difficult. Artificial intelligence allows for novel analysis of images. We hypothesized that a deep learning model can predict tumor response to NAC. METHODS Patients with pancreatic cancer receiving neoadjuvant therapy prior to pancreatoduodenectomy were identified between November 2009 and January 2018. The College of American Pathologists Tumor Regression Grades 0-2 were defined as pathologic response (PR) and grade 3 as no response (NR). Axial images from preoperative computed tomography scans were used to create a 5-layer convolutional neural network and LeNet deep learning model to predict PRs. The hybrid model incorporated decrease in carbohydrate antigen 19-9 (CA19-9) of 10%. Accuracy was determined by area under the curve. RESULTS A total of 81 patients were included in the study. Patients were divided between PR (333 images) and NR (443 images). The pure model had an area under the curve (AUC) of .738 (P < .001), whereas the hybrid model had an AUC of .785 (P < .001). CA19-9 decrease alone was a poor predictor of response with an AUC of .564 (P = .096). CONCLUSIONS A deep learning model can predict pathologic tumor response to neoadjuvant therapy for patients with pancreatic adenocarcinoma and the model is improved with the incorporation of decreases in serum CA19-9. Further model development is needed before clinical application.
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Affiliation(s)
- Michael D Watson
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Maria R Baimas-George
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Keith J Murphy
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Ryan C Pickens
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - David A Iannitti
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - John B Martinie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Erin H Baker
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Dionisios Vrochides
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Lee M Ocuin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
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