Survival Benefit Associated With Resection of Locally Advanced Pancreatic Cancer After Upfront FOLFIRINOX Versus FOLFIRINOX Only: Multicenter Propensity Score-matched Analysis.
Antineoplastic Agents
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Female
Fluorouracil
/ therapeutic use
Follow-Up Studies
Humans
Irinotecan
/ therapeutic use
Leucovorin
/ therapeutic use
Male
Middle Aged
Neoplasm Staging
Netherlands
/ epidemiology
Oxaliplatin
/ therapeutic use
Pancreas
/ pathology
Pancreatectomy
/ methods
Pancreatic Neoplasms
/ diagnosis
Propensity Score
Prospective Studies
Survival Rate
/ trends
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
pubmed:
3
8
2021
medline:
23
11
2021
entrez:
2
8
2021
Statut:
ppublish
Résumé
This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection). Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking. Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015-December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS. Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222-0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01). Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
Sections du résumé
OBJECTIVE
This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection).
BACKGROUND
Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking.
METHODS
Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015-December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS.
RESULTS
Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222-0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01).
CONCLUSIONS
Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
Identifiants
pubmed: 34334641
doi: 10.1097/SLA.0000000000005120
pii: 00000658-202111000-00008
doi:
Substances chimiques
Antineoplastic Agents
0
folfirinox
0
Oxaliplatin
04ZR38536J
Irinotecan
7673326042
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
729-735Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Latenstein AEJ, van der Geest LGM, Bonsing BA, et al. Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma. Eur J Cancer 2020; 125:83–93.
Maggino L, Malleo G, Marchegiani G, et al. Outcomes of primary chemotherapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma. JAMA Surg 2019; 154:932–942.
Walma MS, Brada LJ, Patuleia SIS, et al. Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: a multicenter prospective cohort. Eur J Surg Oncol 2021; 47 (3 Pt B):699–707.
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; 17:801–810.
Hackert T, Sachsenmaier M, Hinz U, et al. Locally advanced pancreatic cancer: neoadjuvant therapy with Folfirinox results in resectability in 60% of the patients. Ann Surg 2016; 264:457–463.
Gemenetzis G, Groot VP, Blair AB, et al. Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection. Ann Surg 2019; 270:340–347.
Satoi S, Yamamoto T, Yamaki S, et al. Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 2020; 4:6–13.
Hartwig W, Gluth A, Hinz U, et al. Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg 2016; 103:1683–1694.
Hackert T. Surgery for pancreatic cancer after neoadjuvant treatment. Ann Gastroenterol Surg 2018; 2:413–418.
Rangelova E, Wefer A, Persson S, et al. Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single institution experience. Ann Surg 2021; 273:579–586.
Jegatheeswaran S, Baltatzis M, Jamdar S, et al. Superior mesenteric artery (SMA) resection during pancreatectomy for malignant disease of the pancreas: a systematic review. HPB (Oxford) 2017; 19:483–490.
Reni M, Zanon S, Balzano G, et al. Selecting patients for resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma. Ann Oncol 2017; 28 (11):2786–2792.
Strijker M, Mackay TM, Bonsing BA, et al. Establishing and coordinating a nationwide multidisciplinary study group: lessons learned by the Dutch Pancreatic Cancer Group. Ann Surg 2020; 271:e102–e104.
Versteijne E, van Eijck CH, Punt CJ, et al. Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials 2016; 17:127.
Springer International Publishing: American Joint Commission on Cancer, Amin M, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 2017.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228–247.
Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2017; 15:1028–1061.
Mattei A. Estimating and using propensity score in presence of missing background data: an application to assess the impact of childbearing on wellbeing. Stat Methods Appl 2009; 18:257–273.
Strobel O, Berens V, Hinz U, et al. Resection after neoadjuvant therapy for locally advanced, ‘unresectable’ pancreatic cancer. Surgery 2012; 152:S33–S42.
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; 22:295–301.
Cecchini M, Miccio JA, Pahade J, et al. A single-institution experience of induction 5-Fluorouracil, leucovorin, irinotecan, and oxaliplatin followed by surgery versus consolidative radiation for borderline and locally advanced unresectable pancreatic cancer. Pancreas 2020; 49:904–911.
Franck C, Canbay A, Malfertheiner P, et al. Maintenance therapy with FOLFIRI after FOLFIRINOX for advanced pancreatic ductal adenocarcinoma: a retrospective single-center analysis. J Oncol 2019; 2019:5832309.
Katz MHG, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012; 118:5749–5756.
Verbeke C, Lohr M, Karlsson JS, et al. Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. Cancer Treat Rev 2015; 41:17–26.
van Veldhuisen E, Walma MS, van Rijssen LB, et al. Added value of intra-operative ultrasound to determine the resectability of locally advanced pancreatic cancer following FOLFIRINOX chemotherapy (IMAGE): a prospective multicenter study. HPB (Oxford) 2019; 21:1385–1392.
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; 261:12–17.
Reames BN, Blair AB, Krell RW, et al. Management of locally advanced pancreatic cancer: results of an international survey of current practice. Ann Surg 2021; 273 (6):1173–1181.
Tsai S, George B, Wittmann D, et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer. Ann Surg 2020; 271:740–747.
Aoki S, Motoi F, Murakami Y, et al. Decreased serum carbohydrate antigen 19-9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients. BMC Cancer 2019; 19:252.
van Veldhuisen E, Vogel JA, Klompmaker S, et al. Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. HPB (Oxford) 2018; 20:605–611.
Hank T, Strobel O. Conversion surgery for advanced pancreatic cancer. J Clin Med 2019; 8 (11):1945.
van Roessel S, van Veldhuisen E, Klompmaker S, et al. Evaluation of adjuvant chemotherapy in patients with resected pancreatic cancer after neoadjuvant FOLFIRINOX treatment. JAMA Oncol 2020; 6:1733–1740.
Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, et al. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 2013; 31 (1):23–29.
Breen WG, Jethwa KR, Yu NY, et al. Patient-reported quality of life before and after chemoradiation for intact pancreas cancer: a prospective registry study. Pract Radiat Oncol 2020; 11 (1):e63–e69.
Franck C, Müller C, Rosania R, et al. Advanced pancreatic ductal adenocarcinoma: moving forward. Cancers (Basel) 2020; 12 (7):1955.
Eaton AA, Gonen M, Karanicolas P, et al. Health-related quality of life after pancreatectomy: results from a randomized controlled trial. Ann Surg Oncol 2016; 23:2137–2145.
Heerkens HD, van Berkel L, Tseng DSJ, et al. Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications. HPB (Oxford) 2018; 20:188–195.
Heerkens HD, Tseng DS, Lips IM, et al. Health-related quality of life after pancreatic resection for malignancy. Br J Surg 2016; 103:257–266.
Mbah N, Brown RE, St Hill CR, et al. Impact of post-operative complications on quality of life after pancreatectomy. JOP 2012; 13:387–393.
Laitinen I, Sand J, Peromaa P, et al. Quality of life in patients with pancreatic ductal adenocarcinoma undergoing pancreaticoduodenectomy. Pancreatology 2017; 17 (3):445–450.
Janssen QP, Buettner S, Suker M, et al. Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis. J Natl Cancer Inst 2019; 111:782–794.
Sugimoto M, Takahashi N, Farnell MB, et al. Survival benefit of neoadjuvant therapy in patients with non-metastatic pancreatic ductal adenocarcinoma: a propensity matching and intention-to-treat analysis. J Surg Oncol 2019; 120:976–984.
Michelakos T, Pergolini I, Castillo CF, et al. Predictors of resectability and survival in patients with borderline and locally advanced pancreatic cancer who underwent neoadjuvant treatment with FOLFIRINOX. Ann Surg 2019; 269:733–740.