E Rangelova, T F Stoop, T M E van Ramshorst, M Ali, E A van Bodegraven, A A Javed, D Hashimoto, E Steyerberg, A Banerjee, A Jain, A Sauvanet, A Serrablo, A Giani, A Giardino, A Zerbi, A Arshad, A G Wijma, A Coratti, A Zironda, A Socratous, A Rojas, A Halimi, A Ejaz, A Oba, B Y Patel, B Björnsson, B N Reames, B Tingstedt, B K P Goh, C Payá-Llorente, C D Del Pozo, C González-Abós, C Medin, C H J van Eijck, C de Ponthaud, C Takishita, C Schwabl, C Månsson, C Ricci, C A Thiels, D Douchi, D L Hughes, D Kilburn, D Flanking, D Kleive, D S Silva, B H Edil, E Pando, E Moltzer, E F Kauffman, E Warren, E Bozkurt, E Sparrelid, E Thoma, E Verkolf, F Ausania, F Giannone, F J Hüttner, F Burdio, F R Souche, F Berrevoet, F Daams, F Motoi, G Saliba, G Kazemier, G Roeyen, G Nappo, G Butturini, G Ferrari, G Kito Fusai, G Honda, G Sergeant, H Karteszi, H Takami, H Suto, I Matsumoto, I Mora-Oliver, I Frigerio, J M Fabre, J Chen, J G Sham, J Davide, J Urdzik, J de Martino, K Nielsen, K Okano, K Kamei, K Okada, K Tanaka, K J Labori, K E Goodsell, L Alberici, L Webber, L Kirkov, L de Franco, M Miyashita, M Maglione, M Gramellini, M Ramera, M J Amaral, M Ramaekers, M J Truty, M A van Dam, M W J Stommel, M Petrikowski, M Imamura, M Hayashi, M D'Hondt, M Brunner, M E Hogg, C Zhang, M Á Suárez-Muñoz, M D Luyer, M Unno, M Mizuma, M Janot, M A Sahakyan, N B Jamieson, O R Busch, O Bilge, O Belyaev, O Franklin, P Sánchez-Velázquez, P Pessaux, P S Holka, P Ghorbani, R Casadei, R Sartoris, R D Schulick, R Grützmann, R Sutcliffe, R Mata, R B Patel, R Takahashi, S Rodriguez Franco, S S Cabús, S Hirano, S Gaujoux, S Festen, S Kozono, S K Maithel, S M Chai, S Yamaki, S van Laarhoven, J S D Mieog, T Murakami, T Codjia, T Sumiyoshi, T M Karsten, T Nakamura, T Sugawara, U Boggi, V Hartman, V E de Meijer, W Bartholomä, W Kwon, Y X Koh, Y Cho, Y Takeyama, Y Inoue, Y Nagakawa, Y Kawamoto, Y Ome, Z Soonawalla, K Uemura, C L Wolfgang, J Y Jang, R Padbury, S Satoi, W Messersmith, J W Wilmink, M Abu Hilal, M G Besselink, M Del Chiaro
{"title":"The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.","authors":"E Rangelova, T F Stoop, T M E van Ramshorst, M Ali, E A van Bodegraven, A A Javed, D Hashimoto, E Steyerberg, A Banerjee, A Jain, A Sauvanet, A Serrablo, A Giani, A Giardino, A Zerbi, A Arshad, A G Wijma, A Coratti, A Zironda, A Socratous, A Rojas, A Halimi, A Ejaz, A Oba, B Y Patel, B Björnsson, B N Reames, B Tingstedt, B K P Goh, C Payá-Llorente, C D Del Pozo, C González-Abós, C Medin, C H J van Eijck, C de Ponthaud, C Takishita, C Schwabl, C Månsson, C Ricci, C A Thiels, D Douchi, D L Hughes, D Kilburn, D Flanking, D Kleive, D S Silva, B H Edil, E Pando, E Moltzer, E F Kauffman, E Warren, E Bozkurt, E Sparrelid, E Thoma, E Verkolf, F Ausania, F Giannone, F J Hüttner, F Burdio, F R Souche, F Berrevoet, F Daams, F Motoi, G Saliba, G Kazemier, G Roeyen, G Nappo, G Butturini, G Ferrari, G Kito Fusai, G Honda, G Sergeant, H Karteszi, H Takami, H Suto, I Matsumoto, I Mora-Oliver, I Frigerio, J M Fabre, J Chen, J G Sham, J Davide, J Urdzik, J de Martino, K Nielsen, K Okano, K Kamei, K Okada, K Tanaka, K J Labori, K E Goodsell, L Alberici, L Webber, L Kirkov, L de Franco, M Miyashita, M Maglione, M Gramellini, M Ramera, M J Amaral, M Ramaekers, M J Truty, M A van Dam, M W J Stommel, M Petrikowski, M Imamura, M Hayashi, M D'Hondt, M Brunner, M E Hogg, C Zhang, M Á Suárez-Muñoz, M D Luyer, M Unno, M Mizuma, M Janot, M A Sahakyan, N B Jamieson, O R Busch, O Bilge, O Belyaev, O Franklin, P Sánchez-Velázquez, P Pessaux, P S Holka, P Ghorbani, R Casadei, R Sartoris, R D Schulick, R Grützmann, R Sutcliffe, R Mata, R B Patel, R Takahashi, S Rodriguez Franco, S S Cabús, S Hirano, S Gaujoux, S Festen, S Kozono, S K Maithel, S M Chai, S Yamaki, S van Laarhoven, J S D Mieog, T Murakami, T Codjia, T Sumiyoshi, T M Karsten, T Nakamura, T Sugawara, U Boggi, V Hartman, V E de Meijer, W Bartholomä, W Kwon, Y X Koh, Y Cho, Y Takeyama, Y Inoue, Y Nagakawa, Y Kawamoto, Y Ome, Z Soonawalla, K Uemura, C L Wolfgang, J Y Jang, R Padbury, S Satoi, W Messersmith, J W Wilmink, M Abu Hilal, M G Besselink, M Del Chiaro","doi":"10.1016/j.annonc.2024.12.015","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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<sub>interaction</sub> = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; P<sub>interaction</sub> = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P<sub>interaction</sub> = 0.43), splenic vein (P<sub>interaction</sub> = 0.30), retroperitoneal (P<sub>interaction</sub> = 0.84), and multivisceral (P<sub>interaction</sub> = 0.96) involvement.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7000,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.annonc.2024.12.015","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
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