|
1
|
Zhou Y, Liao S, You J. Pathological complete response after neoadjuvant therapy for pancreatic ductal adenocarcinoma does not equal cure. ANZ J Surg 2021; 91:E254-E259. [PMID: 33634945 DOI: 10.1111/ans.16665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/24/2021] [Accepted: 01/31/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND There is a scarcity of data about patients with pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant therapy before radical resection and achieved a pathological complete response (pCR). The aim of this study was to describe the recurrence and survival in this subset of patients. METHODS The Embase, Web of Science and PubMed databases were systematically searched for eligible studies published between January 2000 and August 2020. Clinicopathological data of individual patients with pCR after neoadjuvant therapy for PDAC were extracted, pooled and analysed. RESULTS A total of 87 patients were subject to analysis. The majority of patients were female (61.5%) with a median age of 64 (range 43-75) years. Among reported, 41.9% of patients received gemcitabine-based neoadjuvant chemotherapy, 33.7% received FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan and leucovorin)-based regimen and 24.4% received fluoropyrimidine drugs-based regimen. Preoperative radiation was administered to 78.8% of the patients. Twenty-nine (33.3%) patients developed disease recurrence during a median follow-up period of 22.4 (range 2-194) months. The median, 1-, 3- and 5-year overall survival rates were 105 months, 93.6%, 70.3% and 70.3%, respectively. CONCLUSION Despite the excellent long-term outcomes, a pCR does not equal cure because this cohort of patients still has a significant risk of recurrence.
Collapse
Affiliation(s)
- Yanming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China
| | - Shan Liao
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China
| | - Jun You
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China
| |
Collapse
|
|
2
|
Luu AM, Hoehn P, Vogel SR, Reinacher-Schick A, Munding J, Uhl W, Braumann C. Pathologic Complete Response of Pancreatic Cancer following Neoadjuvant FOLFIRINOX Treatment in Hepatic Metastasized Pancreatic Cancer. Visc Med 2019; 35:387-391. [PMID: 31934588 DOI: 10.1159/000497827] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 02/08/2019] [Indexed: 12/21/2022] Open
Abstract
Introduction Pancreatic cancer is a lethal disease and often asymptomatic. Therefore, it is most often diagnosed at an advanced stage. The standard approach in a metastasized tumor stage is palliative chemotherapy. However, the prognosis remains extremely poor. Case Report We present the case of a patient who was diagnosed with a cancer of the head of the pancreas with hepatic metastases. After receiving palliative intended chemotherapy with the FOLFIRINOX regimen, staging computed tomography revealed the disappearance of the liver metastases and local resectability of the pancreatic head tumor. The patient underwent an uneventful Whipple's procedure. Surprisingly, pathohistological investigation revealed a complete pathological response. Conclusion Pathological complete response after FOLFIRINOX treatment in hepatic metastasized pancreatic cancer is extremely rare. It enables surgical resection and increases the survival rate significantly.
Collapse
Affiliation(s)
- Andreas Minh Luu
- Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Philipp Hoehn
- Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Sina Rabea Vogel
- Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | | | - Johanna Munding
- Institute of Pathology, University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany
| | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Chris Braumann
- Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| |
Collapse
|
|
3
|
Luu AM, Herzog T, Hoehn P, Reinacher-Schick A, Munding J, Uhl W, Braumann C. FOLFIRINOX treatment leading to pathologic complete response of a locally advanced pancreatic cancer. J Gastrointest Oncol 2018; 9:E9-E12. [PMID: 29755782 DOI: 10.21037/jgo.2018.01.07] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Pancreatic cancer (PC) is a lethal disease with a poor prognosis. It is typically asymptomatic and therefore most often diagnosed at an advanced stage. A primary unresectable PC can become resectable in case of tumor regression turning palliative into neoadjuvant therapy. We present a 67-year old female patient who was diagnosed with a locally advanced adenocarcinoma of the pancreatic head. After receiving palliative intended chemotherapy with the FOLFIRINOX regimen, staging computed tomography revealed local resectability of the pancreatic head tumor. The patient underwent an uneventful total pancreatectomy. Pathohistological investigation revealed a pathologic complete response (pCR). pCR after FOLFIRINOX treatment in primary unresectable PC is extremely rare. It might enable surgical resection and can increase the survival rate.
Collapse
Affiliation(s)
- Andreas Minh Luu
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Torsten Herzog
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Philipp Hoehn
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | | | - Johanna Munding
- Institute of Pathology, University-Hospital Bergmannsheil, Bochum, Germany
| | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Chris Braumann
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| |
Collapse
|
|
4
|
Trajkovic-Arsic M, Heid I, Steiger K, Gupta A, Fingerle A, Wörner C, Teichmann N, Sengkwawoh-Lueong S, Wenzel P, Beer AJ, Esposito I, Braren R, Siveke JT. Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma. Sci Rep 2017; 7:17038. [PMID: 29213099 PMCID: PMC5719052 DOI: 10.1038/s41598-017-16826-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 11/17/2017] [Indexed: 01/05/2023] Open
Abstract
Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.
Collapse
Affiliation(s)
- M Trajkovic-Arsic
- Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - I Heid
- Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - K Steiger
- Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany
| | - A Gupta
- 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - A Fingerle
- Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - C Wörner
- Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - N Teichmann
- 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - S Sengkwawoh-Lueong
- Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - P Wenzel
- 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - A J Beer
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
- Department of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany
| | - I Esposito
- Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany
| | - R Braren
- Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
| | - J T Siveke
- Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
- German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
| |
Collapse
|
|
5
|
Cloyd JM, Wang H, Egger ME, Tzeng CWD, Prakash LR, Maitra A, Varadhachary GR, Shroff R, Javle M, Fogelman D, Wolff RA, Overman MJ, Koay EJ, Das P, Herman JM, Kim MP, Vauthey JN, Aloia TA, Fleming JB, Lee JE, Katz MHG. Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. JAMA Surg 2017; 152:1048-1056. [PMID: 28700784 DOI: 10.1001/jamasurg.2017.2227] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Importance We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. Objective To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Design, Setting, and Participants Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015. Exposures Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%). Main Outcomes and Measures Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Results Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Conclusions and Relevance Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.
Collapse
Affiliation(s)
- Jordan M Cloyd
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Huamin Wang
- Department of Pathology; University of Texas MD Anderson Cancer Center, Houston
| | - Michael E Egger
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Laura R Prakash
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Anirban Maitra
- Department of Pathology; University of Texas MD Anderson Cancer Center, Houston
| | - Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Rachna Shroff
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - David Fogelman
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Eugene J Koay
- Department of Radiation Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Prajnan Das
- Department of Radiation Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Joseph M Herman
- Department of Radiation Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Michael P Kim
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Thomas A Aloia
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Jason B Fleming
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Jeffrey E Lee
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| | - Matthew H G Katz
- Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston
| |
Collapse
|
|
6
|
Gostimir M, Bennett S, Moyana T, Sekhon H, Martel G. Complete pathological response following neoadjuvant FOLFIRINOX in borderline resectable pancreatic cancer - a case report and review. BMC Cancer 2016; 16:786. [PMID: 27724927 PMCID: PMC5057443 DOI: 10.1186/s12885-016-2821-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Pancreatic cancer is among the top 5 most common cancers worldwide, but is particularly devastating due to its insidious nature. Complete surgical resection remains the only potential curative treatment, although only 20 % of patients present with a resectable tumor. Patients may alternatively present with borderline resectable pancreatic cancer or locally advanced pancreatic cancer and can be offered treatment with neoadjuvant intent. The effectiveness of these treatments is unclear and there is a paucity of data to suggest one optimal treatment approach. CASE PRESENTATION We describe a 61-year-old female who presented with a two-week history of obstructive jaundice in the context of vague abdominal pain that had been ongoing for years prior to her visit. CT scan of the abdomen confirmed a hypovascular mass in the uncinate process consistent with borderline resectable pancreatic cancer. Pancreatic adenocarcinoma was confirmed with endoscopic ultrasound guided fine-needle aspiration cytology. Following multidisciplinary discussion, it was recommended that she undergo treatment with FOLFIRINOX. After a total of 13 cycles, follow up CT revealed that the lesion had decreased in size and she was offered resection as a potentially curative treatment. She underwent pancreaticoduodenectomy. Final pathology report revealed no evidence of residual adenocarcinoma (ypT0 ypN0 (0/23)). The patient remains disease-free 15 months following surgery. CONCLUSION To date, there have been very few reports of a complete pathological response following neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer. This report describes a unique case of a complete pathological remission in a patient with borderline resectable pancreatic cancer following FOLFIRINOX therapy alone and adds to the growing base of evidence meriting the initiation of clinical trials to assess the efficacy of FOLFIRINOX in these subsets of pancreatic cancer.
Collapse
Affiliation(s)
- Mišo Gostimir
- Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Sean Bennett
- Department of Surgery, Division of General Surgery, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Terence Moyana
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Harman Sekhon
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Guillaume Martel
- Department of Surgery, Liver and Pancreas Unit, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| |
Collapse
|
|
7
|
Sinn M, Bahra M, Denecke T, Travis S, Pelzer U, Riess H. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival. World J Gastrointest Oncol 2016; 8:248-57. [PMID: 26989460 PMCID: PMC4789610 DOI: 10.4251/wjgo.v8.i3.248] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 12/01/2015] [Accepted: 12/18/2015] [Indexed: 02/05/2023] Open
Abstract
Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.
Collapse
|
|
8
|
Silvestris N, Longo V, Cellini F, Reni M, Bittoni A, Cataldo I, Partelli S, Falconi M, Scarpa A, Brunetti O, Lorusso V, Santini D, Morganti A, Valentini V, Cascinu S. Neoadjuvant multimodal treatment of pancreatic ductal adenocarcinoma. Crit Rev Oncol Hematol 2015; 98:309-24. [PMID: 26653573 DOI: 10.1016/j.critrevonc.2015.11.016] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 09/14/2015] [Accepted: 11/19/2015] [Indexed: 02/07/2023] Open
Abstract
Treatment of pancreatic ductal adenocarcinoma (PDAC) is increasingly multidisciplinary, with neoadjuvant strategies (chemotherapy, radiation, and surgery) administered in patients with resectable, borderline resectable, or locally advanced disease. The rational supporting this management is the achievement of both higher margin-negative resections and conversion rates into potentially resectable disease and in vivo assessment of novel therapeutics. International guidelines suggest an initial staging of the disease followed by a multidisciplinary approach, even considering the lack of a treatment approach to be considered as standard in this setting. This review will focus on both literature data supporting these guidelines and on new opportunities related to current more active chemotherapy regimens. An analysis of the pathological assessment of response to therapy and the potential role of target therapies and translational biomarkers and ongoing clinical trials of significance will be discussed.
Collapse
Affiliation(s)
- Nicola Silvestris
- Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy.
| | - Vito Longo
- Medical Oncology Unit, 'Mons R Dimiccoli' Hospital, Barletta, Italy
| | - Francesco Cellini
- Radiation Oncology Department, Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Michele Reni
- Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Alessandro Bittoni
- Medical Oncology Clinic, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy
| | - Ivana Cataldo
- ARC-NET Research Centre, University of Verona, Italy
| | - Stefano Partelli
- Pancreatic Unit, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreatic Unit, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Aldo Scarpa
- ARC-NET Research Centre, University of Verona, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy
| | - Vito Lorusso
- Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy
| | - Daniele Santini
- Medical Oncology Unit, University Campus Biomedico, Roma, Italy
| | - Alessio Morganti
- Radiation Oncology Center, Dept. of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Italy
| | - Vincenzo Valentini
- Radiation Oncology Department, Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Stefano Cascinu
- Medical Oncology Clinic, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy
| |
Collapse
|
|
9
|
Marsh RDW, Talamonti MS, Katz MH, Herman JM. Pancreatic cancer and FOLFIRINOX: a new era and new questions. Cancer Med 2015; 4:853-63. [PMID: 25693729 PMCID: PMC4472208 DOI: 10.1002/cam4.433] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 01/10/2015] [Accepted: 01/12/2015] [Indexed: 12/24/2022] Open
Abstract
FOLFIRINOX (FFX) was introduced to clinical practice in 2010 following publication of the PRODIGE 4/ACCORD 11 study, which compared this novel regimen to gemcitabine in metastatic pancreatic cancer. Median overall survival, progression-free survival, and objective responses were all superior with FFX and there was improved time to definitive deterioration in quality of life. Despite initial concerns over toxicity, there has been rapid uptake of this regimen, both revolutionizing management and opening the door to innovative research. As experience with FFX has accrued, many questions have arisen including the management of toxicities, the impact of frequent modifications, the optimal number of cycles, integration with other regimens and modalities, interpretation of radiologic and serologic response, utility of molecular signatures, and potential benefit in unique clinical settings such as pre- and postsurgery. This review will closely examine these issues, not only to summarize current knowledge but also to fuel scientific debate.
Collapse
Affiliation(s)
- Robert De W Marsh
- Department of Medicine, NorthShore University HealthSystemEvanston, Illinois, 60201
| | - Mark S Talamonti
- Department of Surgery, NorthShore University HealthSystemEvanston, Illinois, 60201
| | - Matthew Harold Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer CenterHouston, Texas
| | - Joseph M Herman
- Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins HospitalBaltimore, Maryland
| |
Collapse
|
|
10
|
Sharma MB, Carus A, Sunde L, Hamilton-Dutoit S, Ladekarl M. BRCA-associated pancreatico-biliary neoplasms: Four cases illustrating the emerging clinical impact of genotyping. Acta Oncol 2015; 55:377-81. [PMID: 26004055 DOI: 10.3109/0284186x.2015.1044023] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
| | - Andreas Carus
- Department of Oncology, Aarhus University Hospital, Denmark
| | - Lone Sunde
- Department of Clinical Genetics, Aarhus University Hospital, Denmark
| | | | | |
Collapse
|
|
11
|
Prolonged Complete Response in a Patient with Metastatic Pancreatic Adenocarcinoma after FOLFIRINOX Chemotherapy and Maintenance with FOLFIRI. Case Rep Oncol Med 2015; 2015:659624. [PMID: 26090249 PMCID: PMC4454729 DOI: 10.1155/2015/659624] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 05/10/2015] [Indexed: 01/05/2023] Open
Abstract
Metastatic pancreatic adenocarcinoma confers a poor prognosis. Even with recent advances in the treatment of this disease with the introduction of two modestly effective chemotherapy regimens, complete responses are still very rare. Moreover, there are no published data on how to further manage the patients who achieve a sustained remission following treatment. Herein, we report the case of a patient with metastatic pancreatic adenocarcinoma who achieved a complete response lasting for more than three years after receiving induction chemotherapy with FOLFIRINOX followed by maintenance with FOLFIRI.
Collapse
|
|
12
|
Vaccaro V, Sperduti I, Vari S, Bria E, Melisi D, Garufi C, Nuzzo C, Scarpa A, Tortora G, Cognetti F, Reni M, Milella M. Metastatic pancreatic cancer: Is there a light at the end of the tunnel? World J Gastroenterol 2015; 21:4788-4801. [PMID: 25944992 PMCID: PMC4408451 DOI: 10.3748/wjg.v21.i16.4788] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 02/08/2015] [Accepted: 03/31/2015] [Indexed: 02/06/2023] Open
Abstract
Due to extremely poor prognosis, pancreatic cancer (PDAC) represents the fourth leading cause of cancer-related death in Western countries. For more than a decade, gemcitabine (Gem) has been the mainstay of first-line PDAC treatment. Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results. Recently, the field of systemic therapy of advanced PDAC is finally moving forward. Polychemotherapy has shown promise over single-agent Gem: regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control, although sometimes at the cost of poor tolerability. The PRODIGE 4/ACCORD 11 was the first phase III trial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX; however the less favorable safety profile and the characteristics of the enrolled population, restrict the use of FOLFIRINOX to young and fit PDAC patients. The nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells. Regardless of whether or not this is its main mechanisms of action, the combination of nab-Paclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints. Furthermore, recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC, particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control. Here, we provide an overview of recent advances in the systemic treatment of advanced PDAC, mostly focusing on recent findings that have set new standards in metastatic disease. Potential avenues for further development in the metastatic setting and current efforts to integrate new effective chemotherapy regimens in earlier stages of disease (neoadjuvant, adjuvant, and multimodal approaches in both resectable and unresectable patients) are also briefly discussed.
Collapse
|
|
13
|
Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: Surgery is not enough. World J Gastroenterol 2015; 21:3157-3165. [PMID: 25805920 PMCID: PMC4363743 DOI: 10.3748/wjg.v21.i11.3157] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 12/19/2014] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of death in cancer and has a 5-year survival of < 5%. Only about 15% of the patients present with a resectable PDAC with potential to undergo “curative” surgery. After surgery, local and systemic recurrence, is though very common. The median survival of resected patients with adjuvant chemotherapy after surgery is only 20-23 mo. This underscores the significant need to improve PDAC management strategies. Increased survival rate is dependent on new breakthroughs in our understanding of not at least tumor biology. The aim of this review is to update and comment on recent knowledge concerning PDAC biology and new diagnostics and treatment modalities. One fundamental approach to improve survival rates is by earlier and improved diagnosis of the disease. In recent years, novel blood-based biomarkers have emerged based on genetic, epigenetic and protein changes in PDAC with very promising results. For biomarkers to enter clinical practice they need to have been developed using adequate control groups and provide high sensitivity and specificity and by this identify patients at risk already in a pre-symptomatic stage. Another way to improve outcomes, is by employing neoadjuvant treatments thereby increasing the number of resectable cases. Novel systemic treatment regimes like FOLFIRINOX and nab-paclitaxel have demonstrated improvements in prolonging survival in advanced cases, but long-term survival is still scarce. The future improved understanding of PDAC biology will inevitably render new treatment options directed against both the cancer cells and the surrounding microenvironment.
Collapse
MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Carcinoma, Pancreatic Ductal/blood
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Carcinoma, Pancreatic Ductal/therapy
- Chemotherapy, Adjuvant
- Early Detection of Cancer
- Humans
- Molecular Targeted Therapy
- Neoadjuvant Therapy/adverse effects
- Neoadjuvant Therapy/methods
- Neoplasm Recurrence, Local
- Neoplasm, Residual
- Pancreatectomy/adverse effects
- Pancreatic Neoplasms/blood
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Pancreatic Neoplasms/therapy
- Patient Selection
- Precision Medicine
- Predictive Value of Tests
- Risk Factors
- Time Factors
- Treatment Outcome
Collapse
|
|
14
|
Neofytou K, Giakoustidis A, Smyth EC, Cunningham D, Mudan S. A case of metastatic pancreatic adenocarcinoma with prolonged survival after combination of neoadjuvant FOLFIRINOX therapy and synchronous distal pancreatectomy and hepatectomy. J Surg Oncol 2014; 111:768-70. [PMID: 25556724 DOI: 10.1002/jso.23867] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Accepted: 11/17/2014] [Indexed: 12/19/2022]
Abstract
In this case report we detail the treatment of a patient with pancreatic ductal adenocarcinoma and a solitary liver metastasis who received nine cycles of FOLFIRINOX therapy with favourable response. The patient subsequently underwent synchronous distal pancreatectomy and hepatectomy with an R0 resection followed by three further cycles of FOLFIRINOX. At the last follow-up, 2 years from operation and 28 months from the diagnosis of metastatic pancreatic adenocarcinoma the patient remains disease free.
Collapse
Affiliation(s)
- Kyriakos Neofytou
- Department of Academic Surgery, Royal Marsden Hospital, London, United Kingdom
| | | | | | | | | |
Collapse
|
|
15
|
Viúdez A, Ramírez N, Hernández-García I, Carvalho F, Vera R, Hidalgo M. Nab-paclitaxel: A flattering facelift. Crit Rev Oncol Hematol 2014; 92:166-80. [DOI: 10.1016/j.critrevonc.2014.06.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 06/03/2014] [Accepted: 06/20/2014] [Indexed: 12/21/2022] Open
|
|
16
|
Kotopoulis S, Delalande A, Popa M, Mamaeva V, Dimcevski G, Gilja OH, Postema M, Gjertsen BT, McCormack E. Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft. Mol Imaging Biol 2014; 16:53-62. [PMID: 23877869 DOI: 10.1007/s11307-013-0672-5] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
PURPOSE Adenocarcinoma of the pancreas remains one of the most lethal human cancers. The high mortality rates associated with this form of cancer are subsequent to late-stage clinical presentation and diagnosis, when surgery is rarely possible and of modest chemotherapeutic impact. Survival rates following diagnosis with advanced pancreatic cancer are very low; typical mortality rates of 50% are expected within 3 months of diagnosis. However, adjuvant chemotherapy improves the prognosis of patients even after palliative surgery, and successful newer neoadjuvant chemotherapeutical modalities have recently been reported. For patients whose tumours appear unresectable, chemotherapy remains the only option. During the past two decades, the nucleoside analogue gemcitabine has become the first-line chemotherapy for pancreatic adenocarcinoma. In this study, we aim to increase the delivery of gemcitabine to pancreatic tumours by exploring the effect of sonoporation for localised drug delivery of gemcitabine in an orthotopic xenograft mouse model of pancreatic cancer. EXPERIMENTAL DESIGN An orthotopic xenograft mouse model of luciferase expressing MIA PaCa-2 cells was developed, exhibiting disease development similar to human pancreatic adenocarcinoma. Subsequently, two groups of mice were treated with gemcitabine alone and gemcitabine combined with sonoporation; saline-treated mice were used as a control group. A custom-made focused ultrasound transducer using clinically safe acoustic conditions in combination with SonoVue® ultrasound contrast agent was used to induce sonoporation in the localised region of the primary tumour only. Whole-body disease development was measured using bioluminescence imaging, and primary tumour development was measured using 3D ultrasound. RESULTS Following just two treatments combining sonoporation and gemcitabine, primary tumour volumes were significantly lower than control groups. Additional therapy dramatically inhibited primary tumour growth throughout the course of the disease, with median survival increases of up to 10% demonstrated in comparison to the control groups. CONCLUSION Combined sonoporation and gemcitabine therapy significantly impedes primary tumour development in an orthotopic xenograft model of human pancreatic cancer, suggesting additional clinical benefits for patients treated with gemcitabine in combination with sonoporation.
Collapse
Affiliation(s)
- Spiros Kotopoulis
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Jonas Liesvei 65, 5021, Bergen, Norway
| | | | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Kelly CM, El Bassiouni M, Bennett MW, Crush L, McEneaney P, O'Suilleabhain C, Power DG. Borderline resectable pancreatic adenocarcinoma, is conversion therapy realistic? Acta Oncol 2014; 53:1268-71. [PMID: 24739060 DOI: 10.3109/0284186x.2014.887856] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Ciara M Kelly
- Department of Medical Oncology, Mercy University Hospital , Cork , Ireland
| | | | | | | | | | | | | |
Collapse
|
|
18
|
A R0 resection case of initially unresectable metastatic pancreatic cancer downstaged by FOLFIRINOX therapy. Pancreas 2014; 43:972-4. [PMID: 25010709 DOI: 10.1097/mpa.0000000000000139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
|
|
19
|
Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature. Pancreatology 2014; 14:425-30. [PMID: 25278312 DOI: 10.1016/j.pan.2014.07.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 06/14/2014] [Accepted: 07/07/2014] [Indexed: 02/08/2023]
Abstract
Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.
Collapse
|