Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX

被引：5

作者：

Stoop, Thomas F. ^{[1
,2
,3
]}

Sugawara, Toshitaka ^{[1
,4
]}

Oba, Atsushi ^{[1
,4
,5
]}

Feld, Isabel M. ^{[2
,3
]}

van Roessel, Stijn ^{[2
,3
]}

van Veldhuisen, Eran ^{[2
,3
]}

Wu, Y. H. Andrew ^{[1
,6
,7
]}

Nishino, Jo ^{[8
]}

Ali, Mahsoem ^{[2
,3
]}

Alseidi, Adnan ^{[9
]}

Sauvanet, Alain ^{[10
]}

Mirabella, Antonello ^{[11
]}

Sa Cunha, Antonio ^{[12
]}

Kokkola, Arto ^{[13
]}

Groot Koerkamp, Bas ^{[14
]}

Pietrasz, Daniel ^{[12
]}

Kleive, Dyre ^{[15
]}

Butturini, Giovanni ^{[16
]}

Malleo, Giuseppe ^{[17
]}

van Laarhoven, Hanneke W. M. ^{[3
,18
]}

Frigerio, Isabella ^{[16
]}

Dembinski, Jeanne ^{[10
]}

He, Jin ^{[6
,7
]}

Gagniere, Johan ^{[19
]}

Kleeff, Joerg ^{[20
]}

Ramia, Jose M. ^{[21
]}

Roberts, Keith J. ^{[22
]}

Labori, Knut J. ^{[15
]}

Marino, Marco V. ^{[11
]}

Falconi, Massimo ^{[23
]}

Mortensen, Michael B. ^{[24
]}

Lesurtel, Mickael ^{[12
]}

Bonds, Morgan ^{[9
]}

Chatzizacharias, Nikolaos ^{[22
]}

Strobel, Oliver ^{[25
,26
]}

Turrini, Olivier ^{[27
]}

Griffin, Oonagh ^{[28
]}

Franklin, Oskar ^{[1
,29
]}

Pfeiffer, Per ^{[30
]}

Schulick, Richard D. ^{[1
]}

Salvia, Roberto ^{[17
]}

de Wilde, Roeland F. ^{[14
]}

Dokmak, Safi ^{[10
]}

Rodriguez Franco, Salvador ^{[1
]}

Augustinus, Simone ^{[2
,3
]}

Burgdorf, Stefan K. ^{[31
]}

Crippa, Stefano ^{[23
]}

Hackert, Thilo ^{[25
,32
]}

Tarvainen, Timo ^{[13
]}

Burns, William R. ^{[6
,7
]}

机构：

[1] Univ Colorado Anschutz Med Campus, Dept Surg, Div Surg Oncol, Aurora, CO USA

[2] Locat Univ Amsterdam, Dept Surg, Amsterdam UMC, Boelelaan 1117 ZH-7F, NL-1081 HV Amsterdam, Netherlands

[3] Canc Ctr Amsterdam, Amsterdam, Netherlands

[4] Tokyo Med & Dent Univ, Grad Sch Med, Dept Hepatobiliary & Pancreat Surg, Tokyo, Japan

[5] Canc Inst Hosp, Japanese Fdn Canc Res, Dept Hepatobiliary Pancreat Surg, Tokyo, Japan

[6] Johns Hopkins Univ, Sch Med, Div Hepatobiliary & Pancreat Surg, Baltimore, MD 21218 USA

[7] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[8] Natl Canc Ctr Japan, Res Inst, Div Bioinformat, Tokyo 1040045, Japan

[9] Virginia Mason Med Ctr, Dept Surg, Seattle, WA USA

[10] Univ Paris Cite, Beaujon Hosp, APHP, Dept HPB Surg & Liver Transplantat, Clichy, France

[11] Ospedali Riuniti Villa Sofia Cervello, UOC Otolaryngol, I-90146 Palermo, Italy

[12] Paris Saclay Univ, Paul Brousse Hosp, Liver Ctr Transplant, Dept Hepatobiliary Pancreat Surg, Villejuif, France

[13] Helsinki Univ Hosp, Univ Helsinki, Dept Vasc Surg, Helsinki, Finland

[14] Erasmus MC Canc Inst, Dept Surg, Rotterdam, Netherlands

[15] Univ Oslo, Inst Clin Med, Dept Hepatopancreato Biliary Surg, Oslo, Norway

[16] Pederzoli Hosp, Dept Gen Surg, Peschiera Del Garda, Italy

[17] Univ Verona Hosp Trust, Pancreas Inst, Dept Gen & Pancreat Surg, Verona, Italy

[18] Locat Univ Amsterdam, Dept Med Oncol, Amsterdam UMC, Amsterdam, Netherlands

[19] Besancon Univ Hosp, Dept Digest Surg & Liver Transplantat, Besancon, France

[20] Martin Luther Univ Halle Wittenberg, Dept Visceral Vasc & Endocrine Surg, Halle, Germany

[21] Hosp Gen Univ Alicante, Dept Thorac Surg, Alicante, Spain

[22] Univ Birmingham, Dept Vasc Surg, Dept Vasc Surg, Birmingham Clin Trials Unit, Birmingham, W Midlands, England

[23] Univ Vita Salute San Raffaele, San Raffaele Hosp, IRCCS, Milan, Italy

[24] Odense Univ Hosp, Odense Pancreas Ctr OPAC, Dept Surg, Odense, Denmark

[25] Heidelberg Univ Hosp, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany

[26] Med Univ Vienna, Dept Gen Surg, Div Visceral Surg, Vienna, Austria

[27] Aix Marseille Univ, Inst Paoli Calmettes, Dept Surg Oncol, CRCM, Marseille, France

[28] St Vincents Univ Hosp, Natl Surg Ctr Pancreat Canc, Dublin, Ireland

[29] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden

[30] Odense Univ Hosp, Dept Oncol, Odense, Denmark

[31] Copenhagen Univ Hosp, Dept Surg & Transplantat, Rigshospitalet, Copenhagen, Denmark

[32] Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany

[33] Univ Colorado, Dept Med, Div Med Oncol, Sch Med, Aurora, CO USA

来源：

JAMA ONCOLOGY | 2025年 / 11卷 / 03期

关键词：

OPEN-LABEL; CANCER; GEMCITABINE; SURVIVAL; THERAPY; PHASE-3;

D O I：

10.1001/jamaoncol.2024.5917

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Importance The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Objective To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Design, Setting, and Participants This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023. Exposures Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy. Main Outcomes and Measures The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS. Results Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03). Conclusions and Relevance In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.

引用

页码：276 / 287

页数：12

共 63 条

[21] Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy [J].

Hammad, Abdulrahman Y. Y. ;

Hodges, Jacob C. C. ;

AlMasri, Samer ;

Paniccia, Alessandro ;

Lee, Kenneth K. K. ;

Bahary, Nathan ;

Singhi, Aatur D. D. ;

Ellsworth, Susannah G. G. ;

Aldakkak, Mohammed ;

Evans, Douglas B. B. ;

Tsai, Susan ;

Zureikat, Amer .

JAMA SURGERY, 2023, 158 (01) :55-62

[22] Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy [J].

Ivey, Gabriel D. ;

Shoucair, Sami ;

Delitto, Daniel J. ;

Habib, Joseph R. ;

Kinny-Koster, Benedict ;

Shubert, Christopher R. ;

Lafaro, Kelly J. ;

Cameron, John L. ;

Burns, William R. ;

Burkhart, Richard A. ;

Thompson, Elizabeth L. ;

Narang, Amol ;

Zheng, Lei ;

Wolfgang, Christopher L. ;

He, Jin .

WORLD JOURNAL OF SURGERY, 2022, 46 (11) :2751-2759

[23] Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1) [J].

Janssen, Boris, V ;

van Roessel, Stijn ;

van Dieren, Susan ;

de Boer, Onno ;

Adsay, Volkan ;

Basturk, Olca ;

Brosens, Lodewijk ;

Campbell, Fiona ;

Chatterjee, Deyali ;

Chou, Angela ;

Doglioni, Claudio ;

Esposito, Irene ;

Feakins, Roger ;

Fuchs, Talia L. ;

Fukushima, Noriyoshi ;

Gill, Anthony J. ;

Hong, Seung-Mo ;

Hruban, Ralph H. ;

Kaplan, Jeffrey ;

Krasinkas, Alyssa ;

Luchini, Claudio ;

Shi, Chanjuan ;

Singhi, Aatur ;

Thompson, Elizabeth ;

Velthuysen, Marie-Louise F. ;

Besselink, Marc G. ;

Verheij, Joanne ;

Wang, Huamin ;

Verbeke, Caroline ;

Farina, Arantza .

BRITISH JOURNAL OF SURGERY, 2023, 110 (01) :67-75

[24] Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial [J].

Janssen, Q. P. ;

van Dam, J. L. ;

Bonsing, B. A. ;

Bos, H. ;

Bosscha, K. P. ;

Coene, P. P. L. O. ;

van Eijck, C. H. J. ;

de Hingh, I. H. J. T. ;

Karsten, T. M. ;

van der Kolk, M. B. ;

Patijn, G. A. ;

Liem, M. S. L. ;

van Santvoort, H. C. ;

Loosveld, O. J. L. ;

De Vos-Geelen, J. ;

Zonderhuis, B. M. ;

Homs, M. Y., V ;

van Tienhoven, G. ;

Besselink, M. G. ;

Wilmink, J. W. ;

Koerkamp, B. Groot .

BMC CANCER, 2021, 21 (01)

[25] Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline [J].

Khorana, Alok A. ;

Mangu, Pamela B. ;

Berlin, Jordan ;

Engebretson, Anitra ;

Hong, Theodore S. ;

Maitra, Anirban ;

Mohile, Supriya G. ;

Mumber, Matthew ;

Schulick, Richard ;

Shapiro, Marc ;

Urba, Susan ;

Zeh, Herbert J. ;

Katz, Matthew H. G. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (21) :2541-+

[26] Total Neoadjuvant Therapy for Operable Pancreatic Cancer [J].

Kim, Rebecca Y. ;

Christians, Kathleen K. ;

Aldakkak, Mohammed ;

Clarke, Callisia N. ;

George, Ben ;

Kamgar, Mandana ;

Khan, Abdul H. ;

Kulkarni, Naveen ;

Hall, William A. ;

Erickson, Beth A. ;

Evans, Douglas B. ;

Tsai, Susan .

ANNALS OF SURGICAL ONCOLOGY, 2021, 28 (04) :2246-2256

[27] Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial [J].

Labori, Knut Jorgen ;

Bratlie, Svein Olav ;

Andersson, Bodil ;

Angelsen, Jon-Helge ;

Biorserud, Christina ;

Bjornsson, Bergthor ;

Bringeland, Erling Audun ;

Elander, Nils ;

Garresori, Herish ;

Gronbech, Jon Erik ;

Haux, Johan ;

Hemmingsson, Oskar ;

Liljefors, Maria Gustafsson ;

Myklebust, Tor Age ;

Nymo, Linn Save ;

Peltola, Katriina ;

Pfeiffer, Per ;

Sallinen, Ville ;

Sandstrom, Per ;

Sparrelid, Ernesto ;

Stenvold, Helge ;

Soreide, Kjetil ;

Tingstedt, Bobby ;

Verbeke, Caroline ;

Ohlund, Daniel ;

Klint, Leif ;

Dueland, Svein ;

Lassen, Kristoffer .

LANCET GASTROENTEROLOGY & HEPATOLOGY, 2024, 9 (03) :205-217

[28]

Lambert PC, 2023, STPM3 STATA MODULE F

[29] Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer [J].

Lee, B. ;

Lipton, L. ;

Cohen, J. ;

Tie, J. ;

Javed, A. A. ;

Li, L. ;

Goldstein, D. ;

Burge, M. ;

Cooray, P. ;

Nagrial, A. ;

Tebbutt, N. C. ;

Thomson, B. ;

Nikfarjam, M. ;

Harris, M. ;

Haydon, A. ;

Lawrence, B. ;

Tai, D. W. M. ;

Simons, K. ;

Lennon, A. M. ;

Wolfgang, C. L. ;

Tomasetti, C. ;

Papadopoulos, N. ;

Kinzler, K. W. ;

Vogelstein, B. ;

Gibbs, P. .

ANNALS OF ONCOLOGY, 2019, 30 (09) :1472-1478

[30] Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis [J].

Liao, Wei-Chih ;

Chien, Kuo-Liong ;

Lin, Yu-Lin ;

Wu, Ming-Shiang ;

Lin, Jaw-Town ;

Wang, Hsiu-Po ;

Tu, Yu-Kang .

LANCET ONCOLOGY, 2013, 14 (11) :1095-1103

← 1 2 3 4 5 6 7 →