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

Annals of Surgical Oncology volume 26, pages 109–117 (2019)Cite this article

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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References

  1. Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma. J Natl Compr Cancer Netw JNCCN. 2017;15(8):1028–61.

    Article  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. Edge SB, Compton CC. The AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  23. Staley CA, Cleary KR, Abbruzzese JL, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996;12(4):373–80.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. 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).

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sadot E, Doussot A, O’Reilly EM, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512–21.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 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.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

Daniel Pietrasz, Jean-Baptiste Bachet and Antonio Sa Cunha have full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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Author notes

  1. Jean Baptiste Bachet and Antonio Sa Cunha have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepato-Bilio-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France

    Daniel Pietrasz MD & Antonio Sa Cunha MD, PhD

  2. Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris 06, France

    Daniel Pietrasz MD & Jean-Christophe Vaillant MD, PhD

  3. Surgical Oncology Department, Institut Paoli Calmette, Marseille, France

    Olivier Turrini MD, PhD & Jean-Robert Delpero MD

  4. Departement of Radiotherapy, Hopital Haut Lévêque, CHU de Bordeaux, Pessac, France

    Véronique Vendrely MD

  5. Radiation Oncology, Pitié-Salpêtrière Hospital, Paris, France

    Jean-Marc Simon MD

  6. Pancreato-Gastroenterology Department, Beaujon Hospital, Clichy, France

    Olivia Hentic MD

  7. Gastroenterology Unit, Cochin Hospital, Paris, France

    Romain Coriat MD, PhD

  8. Institut du Cancer de Montpellier, Montpellier, France

    Fabienne Portales MD

  9. CHU Estaing, Service de Chirurgie Digestive, Université Clermont Auvergne, Clermont-Ferrand, France

    Bertrand Le Roy MD

  10. Hepatogastroenterology and Digestive Oncology Department, Georges Pompidou Hospital, Paris, France

    Julien Taieb MD, PhD

  11. Department of Digestive Surgery, Nantes Hospital, Nantes, France

    Nicolas Regenet MD

  12. Surgical Oncology Department, Gustave Roussy, Villejuif, France

    Diane Goere MD, PhD

  13. Department of Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France

    Pascal Artru MD

  14. Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Est Parisien, Assistance Publique-Hôpitaux de Paris, Paris, France

    Florence Huguet MD, PhD

  15. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Haut Lévêque, CHU de Bordeaux, Pessac, France

    Christophe Laurent MD, PhD

  16. Department of Digestive Surgery and Transplantation, Beaujon Hospital, Clichy, France

    Alain Sauvanet MD, PhD

  17. Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris, France

    Jean Baptiste Bachet MD, PhD

Authors
  1. Daniel Pietrasz MD
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  2. Olivier Turrini MD, PhD
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  3. Véronique Vendrely MD
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  4. Jean-Marc Simon MD
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  5. Olivia Hentic MD
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  6. Romain Coriat MD, PhD
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  7. Fabienne Portales MD
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  8. Bertrand Le Roy MD
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  9. Julien Taieb MD, PhD
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  10. Nicolas Regenet MD
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  11. Diane Goere MD, PhD
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  12. Pascal Artru MD
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  13. Jean-Christophe Vaillant MD, PhD
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  14. Florence Huguet MD, PhD
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  15. Christophe Laurent MD, PhD
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  16. Alain Sauvanet MD, PhD
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  17. Jean-Robert Delpero MD
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  18. Jean Baptiste Bachet MD, PhD
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  19. Antonio Sa Cunha MD, PhD
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Corresponding author

Correspondence to Daniel Pietrasz MD.

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Disclosure

The authors declare that they have nothing to disclose.

Clinical Investigators Who Collected Data, Provided, and Cared for Study Patients

Aparicio Thomas, MD, PhD (Avicenne Hospital, Bobigny, France); Berger Anne, MD, PhD (Georges Pompidou European Hospital, Paris, France); Bourdariat Raphaël, MD (Jean Mermoz Hospital, Lyon, France); Blanc Jean-Frédéric (Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France); Chiche Laurence, MD, PhD (Bordeaux South Hospital, Bordeaux, France); Colombo Pierre Emmanuel, MD, PhD (Institut Régional du Cancer ICM, Montpellier, France); Dousset Bertrand, MD, PhD (Cochin Hospital, Paris, France); Drubay Vincent, MD (CHU Lille, Lille, France); Francois Eric, MD (Nice Hospital, Nice, France); Gilabert Marine, MD, PhD (Institut Paoli Calmette, Marseille, France); Hammel Pascal, MD, PhD (Beaujon Hospital, Clichy, France); Lecaille Cédric, MD (Bordeaux North Hospital, Bordeaux, France); Malka David (Gustave Roussy, Villejuif, France); Manfredi Sylvain, MD (Rennes Hospital, Rennes, France); Marthey Lysiane (Kremlin Bicêtre Hospital, Le Kremlin Bicêtre, France); Meunier Bernard, MD, PhD (Rennes Hospital, Rennes, France); Morere François (Paul Brousse Hospital, Villejuif France); Paye François, MD, PhD (Saint-Antoine Hospital, Paris, France); Penna Christophe (Kremlin Bicêtre Hospital, Kremlin Bicêtre, France); Pezet Denis, MD, PhD (CHU Estaing, Clermont Ferrand, France); Piessen Guillaume (CHU Lille, Lille, France); Pittau Gabriella, MD (Paul Brousse Hospiral, Villejuif France); Pointet Anne Laure, MD (Georges Pompidou European Hospital, Paris, France); Schwarz Lilian, MD (Rouen Hospital, Rouen, France); Smith Denis (Bordeaux Saint-André Hospital, Bordeaux, France); Soularue Emilie, MD (Kremlin Bicêtre Hospital, Kremlin Bicêtre, France).

Additional information

The AGEO and FRENCH associations supported this study.

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Pietrasz, D., Turrini, O., Vendrely, V. et al. How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort. Ann Surg Oncol 26, 109–117 (2019). https://doi.org/10.1245/s10434-018-6931-6

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  • DOI: https://doi.org/10.1245/s10434-018-6931-6

Keywords

  • FOLFIRINOX (FLX)
  • Chemoradiotherapy (CRT)
  • Additional CRT
  • Major Pathologic Response
  • Preoperative Chemoradiotherapy