The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study
Rangelova, E Stoop, T F van Ramshorst, T M E Ali, M van Bodegraven, E A Javed, A A Hashimoto, D Steyerberg, E Banerjee, A Jain, A
Rangelova, E
Stoop, T F
van Ramshorst, T M E
Ali, M
van Bodegraven, E A
Javed, A A
Hashimoto, D
Steyerberg, E
Banerjee, A
Jain, A
Affiliation
Sahlgrenska University Hospital; University of Gothenburg; Amsterdam UMC; Cancer Center Amsterdam; University of Colorado; Instituto Ospedaliero; New York University Medical Center; Kansai Medical University; Leiden University Medical Center; Royal Free London NHS Foundation Trust; University of Oklahoma; Assistance Publique Hopitaux de Paris; University of Paris Cité; Miguel Servet University Hospital; ASST Grande Ospedale Metropolitano Niguarda; Pederzoli Hospital; Humanitas University; Humanitas Clinical and Research Center; University Hospitals Southampton NHS Trust; University of Groningen; University Medical Center Groningen; Misericordia Hospital; Mayo Clinic; NorthShore University Health System; Umeå University; Karolinska Institutet; Karolinska University Hospital; Ohio State University; Tokyo Medical and Dental University; Cancer Institute Hospital Japanese Foundation for Cancer Research; Linköping University Hospital; University of Nebraska Medical Center; Lund University; Skåne University Hospital; Singapore General Hospital; National Cancer Centre Singapore; Hospital Doctor Peset; Hospital Clinic de Barcelona; Emory University; Erasmus MC Cancer Institute; Sorbonne University; Medical University Innsbruck; Uppsala University; University of Bologna; Azienda Ospedaliero Universitaria di Bologna; Tohoku University; Oxford Radcliffe Hospitals NHS Foundation Trust; Flinders Medical Centre; Oslo University Hospital; Centro Hospitalar Universitário de Santo António; Universitat Autónoma de Barcelona; Hospital Universitari Vall d'Hebron; Radboud University Medical Center; University of Pisa; Koç University; Ulm University Hospital; Instituto de Investigaciones Biomédicas August Pi I Sunyer; University Hospital of Strasbourg; University Pompeu-Fabra; University of Montpellier; Centre Hospitalier Universitaire Montpellier; Ghent University Hospital; Yamagata University; University Hospital Antwerp; Tokyo Women's Medical University; Universiteit Hasselt; Jessa Hospital; University Hospitals Bristol and Weston NHS Foundation Trust; Nagoya University; Kagawa University; Kindai University; Hospital Clínico Universitario Valencia; University of Washington; Fred Hutchinson Cancer Center; University Hospitals Birmingham NHS Foundation Trust; Hiroshima University; Hokkaido University; University of Oslo; Fiona Stanley Hospital; Cancer Institute Hospital Japanese Foundation for Cancer Research; Medical University of Innsbruck; University of Brescia; Centro Hospitalar e Universitário de Coimbra; University of Coimbra; Catharina Hospital; St. Josef Hospital; Ruhr University Bochum; Sapporo Medical University; Groeninge Hospital; Universitätsklinikum Erlangen; Friedrich-Alexander-Universität Erlangen Nürnberg; University Hospital Virgen de la Victoria; University of Glasgow; University of Paris Cité; Hospital de la Santa Creu i Sant Pau; PathWest Laboratory Medicine; University Hospitals Bristol and Weston NHS Foundation Trust; Rouen University Hospital; Linköping University; Seoul National University Hospital
Other Contributors
Michalski, C W
de Wilde, R F
Tufekci, T
Ishida, H
Dennahy, I S
Carter, J A
Olapo, J S
Caldera, M
Mazzola, M
Oshima, M
Tanaka, N
Choi, S H
Sato, S
Sugawara, S
Abadia-Forcen, T
Pawlik, T M
Kimura, Y
de Wilde, R F
Tufekci, T
Ishida, H
Dennahy, I S
Carter, J A
Olapo, J S
Caldera, M
Mazzola, M
Oshima, M
Tanaka, N
Choi, S H
Sato, S
Sugawara, S
Abadia-Forcen, T
Pawlik, T M
Kimura, Y
Publication date
2025-01-13
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Abstract
Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery.
Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated.
Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement.
Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.
Citation
Rangelova E, Stoop TF, van Ramshorst TME, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BKP, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CHJ, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, Ramaekers M, Truty MJ, van Dam MA, Stommel MWJ, Petrikowski M, Imamura M, Hayashi M, D'Hondt M, Brunner M, Hogg ME, Zhang C, Suárez-Muñoz MÁ, Luyer MD, Unno M, Mizuma M, Janot M, Sahakyan MA, Jamieson NB, Busch OR, Bilge O, Belyaev O, Franklin O, Sánchez-Velázquez P, Pessaux P, Holka PS, Ghorbani P, Casadei R, Sartoris R, Schulick RD, Grützmann R, Sutcliffe R, Mata R, Patel RB, Takahashi R, Rodriguez Franco S, Cabús SS, Hirano S, Gaujoux S, Festen S, Kozono S, Maithel SK, Chai SM, Yamaki S, van Laarhoven S, Mieog JSD, Murakami T, Codjia T, Sumiyoshi T, Karsten TM, Nakamura T, Sugawara T, Boggi U, Hartman V, de Meijer VE, Bartholomä W, Kwon W, Koh YX, Cho Y, Takeyama Y, Inoue Y, Nagakawa Y, Kawamoto Y, Ome Y, Soonawalla Z, Uemura K, Wolfgang CL, Jang JY, Padbury R, Satoi S, Messersmith W, Wilmink JW, Abu Hilal M, Besselink MG, Del Chiaro M; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS); International Consortium on Advanced Pancreatic Surgery. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Ann Oncol. 2025 May;36(5):529-542. doi: 10.1016/j.annonc.2024.12.015. Epub 2025 Jan 13.
Type
Journal Article