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Published in: Annals of Surgical Oncology 1/2019

01-01-2019 | Pancreatic Tumors

How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort

Authors: Daniel Pietrasz, MD, Olivier Turrini, MD, PhD, Véronique Vendrely, MD, Jean-Marc Simon, MD, Olivia Hentic, MD, Romain Coriat, MD, PhD, Fabienne Portales, MD, Bertrand Le Roy, MD, Julien Taieb, MD, PhD, Nicolas Regenet, MD, Diane Goere, MD, PhD, Pascal Artru, MD, Jean-Christophe Vaillant, MD, PhD, Florence Huguet, MD, PhD, Christophe Laurent, MD, PhD, Alain Sauvanet, MD, PhD, Jean-Robert Delpero, MD, Jean Baptiste Bachet, MD, PhD, Antonio Sa Cunha, MD, PhD

Published in: Annals of Surgical Oncology | Issue 1/2019

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Abstract

Background

Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX.

Patients and Methods

Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups).

Results

Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1–30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007).

Conclusions

Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.
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Literature
1.
go back to reference Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma. J Natl Compr Cancer Netw JNCCN. 2017;15(8):1028–61.CrossRef Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma. J Natl Compr Cancer Netw JNCCN. 2017;15(8):1028–61.CrossRef
2.
go back to reference Isaji S, Mizuno S, Windsor JA, et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018;18(1):2–11.CrossRefPubMed Isaji S, Mizuno S, Windsor JA, et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018;18(1):2–11.CrossRefPubMed
3.
go back to reference Burris HA, 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–13.CrossRefPubMed Burris HA, 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–13.CrossRefPubMed
4.
go back to reference Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMed
5.
go back to reference Christians KK, Tsai S, Mahmoud A, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014;19(3):266–74.CrossRefPubMedPubMedCentral Christians KK, Tsai S, Mahmoud A, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014;19(3):266–74.CrossRefPubMedPubMedCentral
6.
go back to reference Faris JE, Blaszkowsky LS, McDermott S, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist. 2013;18(5):543–8.CrossRefPubMedPubMedCentral Faris JE, Blaszkowsky LS, McDermott S, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist. 2013;18(5):543–8.CrossRefPubMedPubMedCentral
7.
go back to reference Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295–301.CrossRefPubMed Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295–301.CrossRefPubMed
8.
go back to reference Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22(4):1153–9.CrossRefPubMed Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22(4):1153–9.CrossRefPubMed
9.
go back to reference Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705–10.CrossRefPubMed Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705–10.CrossRefPubMed
10.
go back to reference Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK. Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial. J Can Assoc Radiol. 1981;32(3):164–5.PubMed Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK. Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial. J Can Assoc Radiol. 1981;32(3):164–5.PubMed
11.
go back to reference Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG. Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil—an Eastern Cooperative Oncology Group study. J Clin Oncol. 1985;3(3):373–8.CrossRefPubMed Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG. Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil—an Eastern Cooperative Oncology Group study. J Clin Oncol. 1985;3(3):373–8.CrossRefPubMed
12.
go back to reference Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000–01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592–9.CrossRefPubMed Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000–01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592–9.CrossRefPubMed
13.
go back to reference Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988;80(10):751–5.CrossRef Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988;80(10):751–5.CrossRef
14.
go back to reference Loehrer PJ, Sr., Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105–12.CrossRefPubMedPubMedCentral Loehrer PJ, Sr., Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105–12.CrossRefPubMedPubMedCentral
15.
go back to reference Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844–53.CrossRef Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844–53.CrossRef
16.
go back to reference Pietrasz D, Marthey L, Wagner M, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22 Suppl 3:1196–205.CrossRef Pietrasz D, Marthey L, Wagner M, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22 Suppl 3:1196–205.CrossRef
17.
go back to reference Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10.CrossRefPubMedPubMedCentral Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10.CrossRefPubMedPubMedCentral
18.
go back to reference Huguet F, Goodman KA, Azria D, Racadot S, Abrams RA. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American–French consensus recommendations. Int J Radiat Oncol Biol Phys. 2012;83(5):1355–64.CrossRefPubMed Huguet F, Goodman KA, Azria D, Racadot S, Abrams RA. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American–French consensus recommendations. Int J Radiat Oncol Biol Phys. 2012;83(5):1355–64.CrossRefPubMed
19.
go back to reference Evans DB, George B, Tsai S. Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy. Ann Surg Oncol. 2015;22(11):3409–13.CrossRefPubMed Evans DB, George B, Tsai S. Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy. Ann Surg Oncol. 2015;22(11):3409–13.CrossRefPubMed
20.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral
21.
go back to reference Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91.CrossRefPubMed Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91.CrossRefPubMed
22.
go back to reference Edge SB, Compton CC. The AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed Edge SB, Compton CC. The AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed
23.
go back to reference Staley CA, Cleary KR, Abbruzzese JL, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996;12(4):373–80.CrossRefPubMed Staley CA, Cleary KR, Abbruzzese JL, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996;12(4):373–80.CrossRefPubMed
24.
go back to reference Bonnetain F, Bonsing B, Conroy T, et al. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). Eur J Cancer. 2014;50(17):2983–93.CrossRefPubMed Bonnetain F, Bonsing B, Conroy T, et al. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). Eur J Cancer. 2014;50(17):2983–93.CrossRefPubMed
25.
go back to reference Schlieman MG, Ho HS, Bold RJ. Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003;138(9):951–6 (discussion 955–956).CrossRefPubMed Schlieman MG, Ho HS, Bold RJ. Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003;138(9):951–6 (discussion 955956).CrossRefPubMed
26.
go back to reference Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.CrossRefPubMedPubMedCentral Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.CrossRefPubMedPubMedCentral
27.
28.
go back to reference He J, Blair AB, Groot VP, et al. Is a pathological complete response following neoadjuvant chemoradiation associated with prolonged survival in patients with pancreatic cancer? Ann Surg. 2018;268(1):1–8.CrossRefPubMedPubMedCentral He J, Blair AB, Groot VP, et al. Is a pathological complete response following neoadjuvant chemoradiation associated with prolonged survival in patients with pancreatic cancer? Ann Surg. 2018;268(1):1–8.CrossRefPubMedPubMedCentral
Metadata
Title
How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort
Authors
Daniel Pietrasz, MD
Olivier Turrini, MD, PhD
Véronique Vendrely, MD
Jean-Marc Simon, MD
Olivia Hentic, MD
Romain Coriat, MD, PhD
Fabienne Portales, MD
Bertrand Le Roy, MD
Julien Taieb, MD, PhD
Nicolas Regenet, MD
Diane Goere, MD, PhD
Pascal Artru, MD
Jean-Christophe Vaillant, MD, PhD
Florence Huguet, MD, PhD
Christophe Laurent, MD, PhD
Alain Sauvanet, MD, PhD
Jean-Robert Delpero, MD
Jean Baptiste Bachet, MD, PhD
Antonio Sa Cunha, MD, PhD
Publication date
01-01-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 1/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6931-6

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