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 Domingo 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 Sousa 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 João 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 Ángel 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 Strandberg 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 Sánchez 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":"新辅助治疗对左侧可切除胰腺癌患者的影响：一项国际多中心研究。","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 Domingo 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 Sousa 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 João 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 Ángel 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 Strandberg 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 Sánchez 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>Purpose: </strong>To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.</p><p><strong>Background: </strong>Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.</p><p><strong>Methods: </strong>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). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated.</p><p><strong>Results: </strong>Overall, 2,282 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 to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to 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 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 to 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":"{\"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 Domingo 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 Sousa 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 João 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 Ángel 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 Strandberg 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 Sánchez 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>Purpose: </strong>To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.</p><p><strong>Background: </strong>Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.</p><p><strong>Methods: </strong>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). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated.</p><p><strong>Results: </strong>Overall, 2,282 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 to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to 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 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 to 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}","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
摘要
目的：评估与前期手术相比，新辅助治疗与左侧可切除胰腺癌（RPC）患者总生存期（OS）的关系。背景：与右侧胰腺癌相比，左侧胰腺癌的OS更差。虽然新辅助治疗目前被认为对RPC患者无效，但目前的随机试验主要包括右侧RPC患者。方法：国际多中心回顾性研究，包括来自4大洲18个国家76个中心的左侧胰腺切除术后病理证实的RPC患者，无论是新辅助治疗还是前期手术。主要终点为诊断后的OS。采用时间相关的Cox回归分析来研究新辅助治疗与OS的关系，并在诊断时调整混杂因素。计算调整后的OS概率。结果：总体而言，2,282例左侧胰腺切除术后的RPC患者，其中290例（13%）接受了新辅助治疗。最常见的新辅助方案是(m)FOLFIRINOX（38%）和吉西他滨-nab-紫杉醇（22%）。前期手术后，72%的患者接受了辅助化疗，主要是单药方案（74%）。与术前相比，新辅助治疗与延长的OS相关（调整后的HR=0.69 [95%CI 0.58-0.83]），与术前相比，调整后的中位OS为53个月vs. 37个月（P=0.0003），调整后的5年OS率为47% vs. 35% （P=0.0001）。相互作用分析表明，在肿瘤较大（p互作用=0.003）和血清CA19-9较高（p互作用=0.005）的患者中，新辅助治疗的效果更强。相比之下，新辅助治疗对脾动脉（p相互作用=0.43）、脾静脉（p相互作用=0.30）、腹膜后（p相互作用=0.84）和多脏器（p相互作用=0.96）受累的效果没有增强。结论：与前期手术相比，左侧RPC患者的新辅助治疗与改善的OS相关。新辅助治疗的影响随着肿瘤大小和诊断时血清CA19-9的升高而增加。需要针对左侧RPC患者的新辅助治疗进行随机对照试验。
The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.
Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.
Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.
Methods: 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). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated.
Results: Overall, 2,282 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 to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction=0.003) and higher serum 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 to 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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