Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/46365
Title: The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study
Authors: 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.
Sauvanet, A.
Serrablo, A.
Giani, A.
Giardino, A.
Zerbi, A.
Arshad, A.
Wijma, A. G.
Coratti, A.
Zironda, A.
Socratous, A.
Rojas, A.
Halimi, A.
Ejaz, A.
Oba, A.
Patel, B. Y.
Bjornsson, B.
Reames, B. N.
Tingstedt, B.
Goh, B. K. P.
Paya-Llorente, C.
Del Pozo, C. D.
Gonzalez-Abos, C.
Medin, C.
van Eijck, C. H. J.
de Ponthaud, C.
Takishita, C.
Schwabl, C.
Mansson, C.
Ricci, C.
Thiels, C. A.
Douchi, D.
Hughes, D. L.
Kilburn, D.
Flanking, D.
Kleive, D.
Silva, D. S.
Edil, B. H.
Pando, E.
Moltzer, E.
Kauffman, E. F.
Warren, E.
Bozkurt, E.
Sparrelid, E.
Thoma, E.
Verkolf, E.
Ausania, F.
Giannone, F.
Huttner, F. J.
Burdio, F.
Souche, F. R.
Berrevoet, F.
Daams, F.
Motoi, F.
Saliba, G.
Kazemier, G.
Roeyen, G.
Nappo, G.
Butturini, G.
Ferrari, G.
Fusai, G. Kito
Honda, G.
SERGEANT, Gregory 
Karteszi, H.
Takami, H.
Suto, H.
Matsumoto, I.
Mora-Oliver, I.
Frigerio, I.
Fabre, J. M.
Chen, J.
Sham, J. G.
Davide, J.
Urdzik, J.
de Martino, J.
Nielsen, K.
Okano, K.
Kamei, K.
Okada, K.
Tanaka, K.
Labori, K. J.
Goodsell, K. E.
Alberici, L.
Webber, L.
Kirkov, L.
de Franco, L.
Miyashita, M.
Maglione, M.
Gramellini, M.
Ramera, M.
Amaral, M. J.
Ramaekers, M.
Truty, M. J.
van Dam, M. A.
Stommel, M. W. J.
Petrikowski, M.
Imamura, M.
Hayashi, M.
D'Hondt, M.
Brunner, M.
Hogg, M. E.
Zhang, C.
Suarez-Munoz, M. A.
Luyer, M. D.
Unno, M.
Mizuma, M.
Janot, M.
Sahakyan, M. A.
Jamieson, N. B.
Busch, O. R.
Bilge, O.
Belyaev, O.
Franklin, O.
Sanchez-Velazquez, P.
Pessaux, P.
Holka, P. S.
Ghorbani, P.
Casadei, R.
Sartoris, R.
Schulick, R. D.
Grutzmann, R.
Sutcliffe, R.
Mata, R.
Patel, R. B.
Takahashi, R.
Franco, S. Rodriguez
Cabus, S. S.
Hirano, S.
Gaujoux, S.
Festen, S.
Kozono, S.
Maithel, S. K.
Chai, S. M.
Yamaki, S.
van Laarhoven, S.
Mieog, J. S. D.
Murakami, T.
Codjia, T.
Sumiyoshi, T.
Karsten, T. M.
Nakamura, T.
Sugawara, T.
Boggi, U.
Hartman, V.
de Meijer, V. E.
Bartholoma, W.
Kwon, W.
Koh, Y. X.
Cho, Y.
Takeyama, Y.
Inoue, Y.
Nagakawa, Y.
Kawamoto, Y.
Ome, Y.
Soonawalla, Z.
Uemura, K.
Wolfgang, C. L.
Jang, J. Y.
Padbury, R.
Satoi, S.
Messersmith, W.
Wilmink, J. W.
Abu Hilal, M.
Besselink, M. G.
Del Chiaro, M.
Issue Date: 2025
Publisher: ELSEVIER
Source: Annals of oncology, 36 (5) , p. 529 -542
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 (P-interaction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; P-interaction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P-interaction = 0.43), splenic vein (P-interaction = 0.30), retroperitoneal (P-interaction = 0.84), and multivisceral (P-interaction = 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.
Notes: Rangelova, E (corresponding author), Univ Gotenborg, Sahlgrenska Acad, Inst Clin Sci, Dept Upper Abdominal Surg, Bla Straket 5, S-41345 Gothenburg, Sweden.
elena.rangelova@gu.se
Keywords: pancreatic adenocarcinoma;pancreatic body/tail;resectable;neoadjuvant therapy;CA19-9;tumor size
Document URI: http://hdl.handle.net/1942/46365
ISSN: 0923-7534
e-ISSN: 1569-8041
DOI: 10.1016/j.annonc.2024.12.015
ISI #: 001498312500001
Rights: 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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