Skip to main content
Top
Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Pancreatic Tumors

Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort

Authors: Daniel Pietrasz, MD, Lysiane Marthey, MD, Mathilde Wagner, MD, Jean-Frédéric Blanc, MD, PhD, Christophe Laurent, MD, PhD, Olivier Turrini, MD, PhD, Jean Luc Raoul, MD, PhD, Eric Terrebonne, MD, Olivia Hentic, MD, Isabelle Trouilloud, MD, Romain Coriat, MD, PhD, Nicolas Regenet, MD, Pasquale Innominato, MD, Julien Taieb, MD, PhD, Antonio Sa Cunha, MD, PhD, Jean Baptiste Bachet, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

Login to get access

Abstract

Purpose

In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy.

Methods

We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review.

Results

Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1–30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035).

Conclusions

Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Eheman C, Henley SJ, Ballard-Barbash R, et al. Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012;118(9):2338–66.PubMedPubMedCentralCrossRef Eheman C, Henley SJ, Ballard-Barbash R, et al. Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012;118(9):2338–66.PubMedPubMedCentralCrossRef
2.
go back to reference Bouvier AM, Remontet L, Jougla E, et al. Incidence of gastrointestinal cancers in France. Gastroenterol Clin Biol. 2004;28(10):877–81.PubMedCrossRef Bouvier AM, Remontet L, Jougla E, et al. Incidence of gastrointestinal cancers in France. Gastroenterol Clin Biol. 2004;28(10):877–81.PubMedCrossRef
3.
go back to reference Coleman MP, Gatta G, Verdecchia A, et al. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Ann Oncol. 2003;14 Suppl 5:v128–49.PubMedCrossRef Coleman MP, Gatta G, Verdecchia A, et al. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Ann Oncol. 2003;14 Suppl 5:v128–49.PubMedCrossRef
4.
5.
go back to reference Delpero JR, Paye F, Bachellier P, Boyer JM. Cancer du pancréas Rapport présenté au 112e Congrés Français de Chirurgie 2010. 2010. Delpero JR, Paye F, Bachellier P, Boyer JM. Cancer du pancréas Rapport présenté au 112e Congrés Français de Chirurgie 2010. 2010.
6.
go back to reference Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206(5):833–46.PubMedCrossRef Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206(5):833–46.PubMedCrossRef
7.
go back to reference Katz MH, Crane CH, Varadhachary G. Management of borderline resectable pancreatic cancer. Semin Radiat Oncol. 2014;24(2):105–12.PubMedCrossRef Katz MH, Crane CH, Varadhachary G. Management of borderline resectable pancreatic cancer. Semin Radiat Oncol. 2014;24(2):105–12.PubMedCrossRef
8.
go back to reference Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.PubMedPubMedCentralCrossRef Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.PubMedPubMedCentralCrossRef
9.
go back to reference Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118(23):5749–56.PubMedCrossRef Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118(23):5749–56.PubMedCrossRef
10.
go back to reference Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, Group EGW. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii33–40.PubMedCrossRef Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, Group EGW. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii33–40.PubMedCrossRef
11.
go back to reference Philip PA, Mooney M, Jaffe D, et al. Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol. 2009;27(33):5660–9.PubMedCrossRef Philip PA, Mooney M, Jaffe D, et al. Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol. 2009;27(33):5660–9.PubMedCrossRef
12.
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.PubMedCrossRef Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.PubMedCrossRef
13.
go back to reference Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef
14.
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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
15.
16.
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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference Petrelli F, Coinu A, Borgonovo KF, et al. Resection rate with FOLFIRINOX-based neoadjuvant therapy in locally advanced/Borderline resectable pancreatic cancer: a pooled analysis of published data. Ann Oncol. 2014;25(Suppl 4):1. Petrelli F, Coinu A, Borgonovo KF, et al. Resection rate with FOLFIRINOX-based neoadjuvant therapy in locally advanced/Borderline resectable pancreatic cancer: a pooled analysis of published data. Ann Oncol. 2014;25(Suppl 4):1.
18.
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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2014. J Natl Compr Cancer Netw. 2014;12(8):1083–93. Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2014. J Natl Compr Cancer Netw. 2014;12(8):1083–93.
20.
go back to reference Pessaux P, Varma D, Arnaud JP. Pancreaticoduodenectomy: superior mesenteric artery first approach. J Gastrointest Surg. 2006;10(4):607–11.PubMedCrossRef Pessaux P, Varma D, Arnaud JP. Pancreaticoduodenectomy: superior mesenteric artery first approach. J Gastrointest Surg. 2006;10(4):607–11.PubMedCrossRef
21.
go back to reference Sanjay P, Takaori K, Govil S, Shrikhande SV, Windsor JA. ‘Artery-first’ approaches to pancreatoduodenectomy. Br J Surg. 2012;99(8):1027–35.PubMedCrossRef Sanjay P, Takaori K, Govil S, Shrikhande SV, Windsor JA. ‘Artery-first’ approaches to pancreatoduodenectomy. Br J Surg. 2012;99(8):1027–35.PubMedCrossRef
22.
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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
23.
go back to reference Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8–13.PubMedCrossRef Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8–13.PubMedCrossRef
24.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.PubMedCrossRef Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.PubMedCrossRef
25.
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.PubMedCrossRef Staley CA, Cleary KR, Abbruzzese JL, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996;12(4):373–80.PubMedCrossRef
26.
go back to reference Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.PubMedCrossRef Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.PubMedCrossRef
27.
go back to reference Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs. observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308(2):147–56.PubMedCrossRef Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs. observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308(2):147–56.PubMedCrossRef
28.
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.PubMedCrossRef 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.PubMedCrossRef
29.
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):951–5.PubMedCrossRef Schlieman MG, Ho HS, Bold RJ. Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003;138(9):951–5.PubMedCrossRef
30.
go back to reference Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.PubMedPubMedCentralCrossRef Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.PubMedPubMedCentralCrossRef
31.
go back to reference Paniccia A, Edil BH, Schulick RD, et al. Neoadjuvant FOLFIRINOX application in borderline resectable pancreatic adenocarcinoma: a retrospective cohort study. Medicine. 2014;93(27):e198.PubMedPubMedCentralCrossRef Paniccia A, Edil BH, Schulick RD, et al. Neoadjuvant FOLFIRINOX application in borderline resectable pancreatic adenocarcinoma: a retrospective cohort study. Medicine. 2014;93(27):e198.PubMedPubMedCentralCrossRef
32.
go back to reference Cassinotto C, Mouries A, Lafourcade J-P, et al. Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology. 2014;273(1):108–16.PubMedCrossRef Cassinotto C, Mouries A, Lafourcade J-P, et al. Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology. 2014;273(1):108–16.PubMedCrossRef
33.
go back to reference Fong Y, Gonen M, Rubin D, Radzyner M, Brennan MF. Long-term survival is superior after resection for cancer in high-volume centers. Ann Surg. 2005;242(4):540–4.PubMedPubMedCentral Fong Y, Gonen M, Rubin D, Radzyner M, Brennan MF. Long-term survival is superior after resection for cancer in high-volume centers. Ann Surg. 2005;242(4):540–4.PubMedPubMedCentral
34.
go back to reference DeOliveira ML, Winter JM, Schafer M, et al. Assessment of complications after pancreatic surgery: a novel grading system applied to 633 patients undergoing pancreaticoduodenectomy. Ann Surg. 2006;244(6):931–7.PubMedPubMedCentralCrossRef DeOliveira ML, Winter JM, Schafer M, et al. Assessment of complications after pancreatic surgery: a novel grading system applied to 633 patients undergoing pancreaticoduodenectomy. Ann Surg. 2006;244(6):931–7.PubMedPubMedCentralCrossRef
36.
go back to reference Konstantinidis IT, Warshaw AL, Allen JN, et al. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg. 2013;257(4):731–6.PubMedCrossRef Konstantinidis IT, Warshaw AL, Allen JN, et al. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg. 2013;257(4):731–6.PubMedCrossRef
37.
go back to reference Delpero JR, Bachellier P, Regenet N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB. 2014;16(1):20–33.PubMedPubMedCentralCrossRef Delpero JR, Bachellier P, Regenet N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB. 2014;16(1):20–33.PubMedPubMedCentralCrossRef
38.
go back to reference Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150(3):466–73.PubMedPubMedCentralCrossRef Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150(3):466–73.PubMedPubMedCentralCrossRef
39.
go back to reference Chatterjee D, Katz MH, Rashid A, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118(12):3182–90.PubMedPubMedCentralCrossRef Chatterjee D, Katz MH, Rashid A, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118(12):3182–90.PubMedPubMedCentralCrossRef
40.
go back to reference Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44.PubMedCrossRef Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44.PubMedCrossRef
Metadata
Title
Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort
Authors
Daniel Pietrasz, MD
Lysiane Marthey, MD
Mathilde Wagner, MD
Jean-Frédéric Blanc, MD, PhD
Christophe Laurent, MD, PhD
Olivier Turrini, MD, PhD
Jean Luc Raoul, MD, PhD
Eric Terrebonne, MD
Olivia Hentic, MD
Isabelle Trouilloud, MD
Romain Coriat, MD, PhD
Nicolas Regenet, MD
Pasquale Innominato, MD
Julien Taieb, MD, PhD
Antonio Sa Cunha, MD, PhD
Jean Baptiste Bachet, MD, PhD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4783-x

Other articles of this Special Issue 3/2015

Annals of Surgical Oncology 3/2015 Go to the issue