Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini
{"title":"分子改变对接受顺铂、吉西他滨和杜伐单抗治疗的晚期胆道癌患者的影响：一个庞大的现实世界人群","authors":"Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini","doi":"10.1093/jnci/djaf155","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.</p><p><strong>Methods: </strong>Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.</p><p><strong>Results: </strong>The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.</p><p><strong>Conclusions: </strong>This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.\",\"authors\":\"Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini\",\"doi\":\"10.1093/jnci/djaf155\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background & aims: </strong>Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.</p><p><strong>Methods: </strong>Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.</p><p><strong>Results: </strong>The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.</p><p><strong>Conclusions: </strong>This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.</p>\",\"PeriodicalId\":14809,\"journal\":{\"name\":\"JNCI Journal of the National Cancer Institute\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":9.9000,\"publicationDate\":\"2025-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JNCI Journal of the National Cancer Institute\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jnci/djaf155\",\"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":"JNCI Journal of the National Cancer Institute","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jnci/djaf155","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
背景与目的：顺铂、吉西他滨和杜伐单抗（CGD）联合治疗是晚期胆道癌（BTC）的标准一线治疗方案。本研究旨在评估在现实世界的临床实践中，基因改变对晚期BTC患者接受CGD治疗的结果的影响。方法：来自11个国家（欧洲、美国和亚洲）39个中心的不可切除、局部晚期或转移性BTC患者接受CGD治疗，纳入本分析。结果：该队列包括513例晚期BTC患者。最常发生改变的5个基因是TP53（22.1%）、KRAS（13.7%）、CDKN2A/B（13.6%）、ARID1A（12.2%）和IDH1（9.2%）。在多变量分析中，SMAD4突变与改善的无进展生存期（PFS） （HR 0.49, p = 0.018）和总生存期（OS） （HR 0.11, p = 0.023）相关，而TP53突变与恶化的PFS （HR 1.62, p = 0.0047）和TERT突变与恶化的OS （HR 8.92, p = 0.0012）相关。没有其他基因组改变与结果显著相关。亚组分析显示，TP53突变对肝内胆管癌（iCCA）的PFS和OS有负面影响，而KRAS突变与肝外胆管癌（eCCA）的PFS较差相关。没有基因改变与胆囊癌的预后有关。结论：通过全面的分子分析，这项大规模分析支持SMAD4突变对PFS和OS的积极预后影响，并强调了TP53 （PFS）和TERT （OS）突变的负面预后作用，为BTC的个性化治疗策略提供了有价值的见解。
The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.
Background & aims: Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.
Methods: Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.
Results: The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.
Conclusions: This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.
期刊介绍：
The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
