Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment

Published on Nov 1, 2020in JAMA Oncology31.777
· DOI :10.1001/JAMAONCOL.2020.3537
Stijn van Roessel9
Estimated H-index: 9
(UvA: University of Amsterdam),
Eran van Veldhuisen8
Estimated H-index: 8
(UvA: University of Amsterdam)
+ 41 AuthorsMarc G. Besselink88
Estimated H-index: 88
(UvA: University of Amsterdam)
Importance The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear. Objective To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment. Design, Setting, and Participants This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded. Exposures The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise. Results We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28;P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75];P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10;P = .73). Conclusions and Relevance These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.
OBJECTIVE: We sought to determine whether postoperative chemotherapy after preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) prolongs survival. BACKGROUND: Data to support administering postoperative chemotherapy to patients who received preoperative therapy are lacking. METHODS: All patients with PDAC who underwent pancreatectomy after preoperative therapy between 2010 and July 2017 at The University of Texas MD Anderson Cancer Center were identified. To contro...
#1Eva Versteijne (UvA: University of Amsterdam)H-Index: 11
#2Mustafa Suker (EUR: Erasmus University Rotterdam)H-Index: 13
Last. Geertjan van Tienhoven (UvA: University of Amsterdam)H-Index: 33
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PURPOSEPreoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.PATIENTS AND METHODSIn th...
Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. Primary endpoint was overall survival (OS). Secondary endpoi...
#1Louise Skau Rasmussen (AAU: Aalborg University)H-Index: 5
#2Benny VittrupH-Index: 1
Last. Claus Wilki Fristrup (OUH: Odense University Hospital)H-Index: 14
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Background: Adjuvant chemotherapy following curative resection is the standard treatment for pancreatic adenocarcinoma (PC). Randomized clinical trials using gemcitabine have shown a median overall survival (mOS) of 2 years and a 5-year survival rate of 15-20%. However, the effect of gemcitabine outside these trials is less clear. We examined the effect of postoperative gemcitabine on survival in an unselected cohort of patients receiving curative resection for PC in Denmark during a five-year p...
#1Fuyuhiko Motoi (Tohoku University)H-Index: 41
#2Tomoo KosugeH-Index: 86
Last. Michiaki Unno (Tohoku University)H-Index: 69
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: A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with ...
#1Daniel Pietrasz (University of Paris)H-Index: 8
#2Olivier TurriniH-Index: 37
Last. Antonio Sa Cunha (Université Paris-Saclay)H-Index: 33
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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.
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#2Kimberly D. Miller (ACS: American Cancer Society)H-Index: 29
Last. Ahmedin Jemal (ACS: American Cancer Society)H-Index: 139
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: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the Nati...
#1Thierry ConroyH-Index: 52
#2Pascal HammelH-Index: 87
Last. James Joseph Biagi (University of Lorraine)H-Index: 19
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Abstract Background Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall surviv...
#7Do-Youn Oh (Seoul National University Hospital)H-Index: 41
Objective:This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC.Summary Background Data:Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence e
#1Eva VersteijneH-Index: 11
#2J.A. VogelH-Index: 3
Last. G. van TienhovenH-Index: 24
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markdownabstractBackground: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. Methods: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intenti...
Cited By16
#1Tzu-Pin Lu (NTU: National Taiwan University)H-Index: 19
#2Chien-Hui Wu (NTU: National Taiwan University)H-Index: 3
Last. Yu-Wen Tien (NTU: National Taiwan University)H-Index: 26
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Pancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pan...
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#2Piera Leon (University of Montpellier)H-Index: 3
Last. Fabrizio Panaro (University of Montpellier)H-Index: 21
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INTRODUCTION 'Brittle Diabetes' (BD) is a life-threatening metabolic complication after total pancreatectomy (TP). More than 500 Intraportal islet autotransplantation (IAT) have been performed to prevent this complication, with almost 70% insulin independence after 3 years. Even when insulin independence was not achieved, IAT successfully prevented severe hypoglycemia. Currently, preliminary results for oncologic situations are promising, but their oncological outcomes are still a matter of deba...
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#2Lois A. Daamen (UU: Utrecht University)H-Index: 7
Last. Gijs A. PatijnH-Index: 15
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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 re...
#1Koji Kubota (Shinshu University)H-Index: 5
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BACKGROUND Although various biomarkers are useful in predicting cancer prognosis, the most effective preoperative systemic biomarkers for pancreatic ductal adenocarcinoma (PDAC) have not been established. This study aimed to evaluate whether the lymphocyte-to-monocyte ratio (LMR) can predict the long-term outcomes for patients who were to undergo surgical resection of PDAC. METHODS The study involved 170 patients with PDAC who underwent resection. Multivariate analysis was performed to identify ...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite surgical and pharmacological progresses in the latest years. High potential for metastasis is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underneath pathological processes. However, nowadays the research is focusing on the search of personalized approach also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investig...
#1Kung-Kai Kuo (KMU: Kaohsiung Medical University)H-Index: 22
#2Pi-Jung Hsiao (ISU: I-Shou University)H-Index: 2
Last. Kohsuke Kato (University of Tsukuba)H-Index: 10
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The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore,...
Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) ...
Background: Chemotherapy is suggested to use in all stages of pancreatic cancer. Is it reasonable to recommend chemotherapy for all PDAC patients? It is necessary to distinguish low-risk PDAC patients underwent pancreatectomy, who may not lose survival time due to missed chemotherapy and not need to endure pain, nausea, tiredness, drowsiness, and breath shortness caused by chemotherapy. Methods: Nomograms were constructed with basis from the multivariate Cox regression analysis. X-tile software ...
#1Erin P Ward (MCW: Medical College of Wisconsin)H-Index: 1
#2Douglas B. Evans (MCW: Medical College of Wisconsin)H-Index: 117
Last. Susan Tsai (MCW: Medical College of Wisconsin)H-Index: 33
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Treatment of localized pancreatic cancer has also evolved to prioritize preoperative (neoadjuvant) multimodality therapy over a surgery-first approach. Given the complexities of pancreatic cancer staging and the challenge of delivering multiple treatment modalities (chemotherapy, radiation therapy, and surgery), an experienced and highly integrated multidisciplinary team is necessary to achieve the best outcomes. In this review, we will discuss our institutional experience with neoadjuvant thera...
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