Background: FOLFOXIRI plus bevacizumab improved efficacies and increased some adverse events in untreated metastatic colorectal cancer (mCRC), compared with the doublet plus bevacizumab. The clinical outcomes of ramucirumab (RAM) in combination with FOLFIRI or FOLFOXIRI as a first-line treatment are unknown. In this randomized phase II study (WJOG9216G), we compared the efficacy and safety of these regimens to determine which is more promising.
Methods: Patients with untreated mCRC were randomly assigned to the FOLFIRI-RAM or FOLFOXIRI-RAM arms. The primary endpoint was a confirmed objective response rate (ORR), and secondary endpoints included early tumor shrinkage (ETS), progression-free survival (PFS), overall survival (OS), and safety.
Results: In total, 122 patients were randomized. The confirmed ORR was 59.3% and 60.3% in the FOLFIRI-RAM and FOLFOXIRI-RAM arms, respectively (odds ratio 1.04; P = 0.91). With a median follow-up period of 42.1 and 40.4 months, PFS was comparable between the FOLFIRI-RAM and FOLFOXIRI-RAM arms (median, 11.5 and 10.5 months). ETS rate (71.2% and 52.4%) and OS (median, 32.6 and 28.2 months) were significantly better in the FOLFIRI-RAM arm than in the FOLFOXIRI-RAM arm. The major grade ≥ 3 adverse events in the FOLFIRI-RAM and FOLFOXIRI-RAM arms were neutropenia (44.1% and 72.6%), anorexia (3.4% and 14.5%), and febrile neutropenia (3.4% and 11.3%).
Conclusions: FOLFOXIRI plus RAM was not superior to FOLFIRI plus RAM in terms of efficacy, including ORR, in patients with untreated mCRC. Instead, first-line FOLFIRI plus RAM showed clinical efficacy and safety profiles comparable to those of doublet chemotherapy plus bevacizumab.
{"title":"Randomized phase II study of FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment for metastatic colorectal cancer: WJOG9216G (RECAST).","authors":"Yosuke Kito, Kentaro Yamazaki, Hirokazu Shoji, Takeshi Yamada, Takahiro Tsushima, Seiichiro Mitani, Kazuhiro Shiraishi, Hisateru Yasui, Hiroki Hara, Kenro Hirata, Taito Esaki, Yudai Shinohara, Takao Tsuzuki, Shinya Kajiura, Toshiki Masuishi, Naoki Izawa, Eishi Baba, Kohei Murata, Naoya Akazawa, Yozo Suzuki, Hironaga Satake, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Hisato Kawakami, Shuichi Hironaka, Kei Muro","doi":"10.1016/j.ejca.2026.116688","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116688","url":null,"abstract":"<p><strong>Background: </strong>FOLFOXIRI plus bevacizumab improved efficacies and increased some adverse events in untreated metastatic colorectal cancer (mCRC), compared with the doublet plus bevacizumab. The clinical outcomes of ramucirumab (RAM) in combination with FOLFIRI or FOLFOXIRI as a first-line treatment are unknown. In this randomized phase II study (WJOG9216G), we compared the efficacy and safety of these regimens to determine which is more promising.</p><p><strong>Methods: </strong>Patients with untreated mCRC were randomly assigned to the FOLFIRI-RAM or FOLFOXIRI-RAM arms. The primary endpoint was a confirmed objective response rate (ORR), and secondary endpoints included early tumor shrinkage (ETS), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>In total, 122 patients were randomized. The confirmed ORR was 59.3% and 60.3% in the FOLFIRI-RAM and FOLFOXIRI-RAM arms, respectively (odds ratio 1.04; P = 0.91). With a median follow-up period of 42.1 and 40.4 months, PFS was comparable between the FOLFIRI-RAM and FOLFOXIRI-RAM arms (median, 11.5 and 10.5 months). ETS rate (71.2% and 52.4%) and OS (median, 32.6 and 28.2 months) were significantly better in the FOLFIRI-RAM arm than in the FOLFOXIRI-RAM arm. The major grade ≥ 3 adverse events in the FOLFIRI-RAM and FOLFOXIRI-RAM arms were neutropenia (44.1% and 72.6%), anorexia (3.4% and 14.5%), and febrile neutropenia (3.4% and 11.3%).</p><p><strong>Conclusions: </strong>FOLFOXIRI plus RAM was not superior to FOLFIRI plus RAM in terms of efficacy, including ORR, in patients with untreated mCRC. Instead, first-line FOLFIRI plus RAM showed clinical efficacy and safety profiles comparable to those of doublet chemotherapy plus bevacizumab.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"238 ","pages":"116688"},"PeriodicalIF":7.1,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1016/j.ejca.2026.116679
Xiangxue Wang, Liya Chen, Jingwen Sun, Sirvan Khalighi, Tanmoy Dam, Himanshu Maurya, Tilak Pathak, Cheng Lu, Shipra Gandhi, Sunil Badve, Shen Zhao, Wentao Yang, Jun Xu, Anant Madabhushi, Bolin Song
Purpose: We present MuTriM, a multimodal deep learning model integrating DCE-MRI and whole-slide pathology to predict survival and radiation benefit in breast cancer.
Patients and methods: MuTriM employs an attention-based cross-modal and cross-temporal fusion framework that concurrently integrates DCE-MRI radiomic features with pathomic features of cellular morphology on WSI. MuTriM was trained on the Fudan University Shanghai Cancer Center (FUSCC) cohort (N = 335) and externally tested on the TCGA cohort (N = 126) using matched DCE-MRI and WSI.
Results: MuTriM was prognostic of recurrence-free survival (RFS) in a subtype-agnostic setting (HR = 5.26, 95% CI, 1.69-16.4, p = 0.004; C-index = 0.75), outperforming unimodal models based on DCE-MRI alone (C-index = 0.65) or WSI alone (C-index = 0.70). MuTriM was also prognostic among HER2 + (HR = 6.82, 95% CI, 1.08-43.2, p = 0.04) and ER+ populations (HR = 4.61, 95% CI, 1.25-17.1, p = 0.02). A high MuTriM score was associated with improved RFS (HR = 0.15, 95% CI 0.03-0.87; P = 0.03), whereas a low MuTriM score showed no significant benefit (HR = 4.06, 95% CI 0.05-31; P = 0.53) (interaction P = 0.04). Transcriptomic analyses revealed that high-risk tumors showed suppressed cytotoxic T-cell activity and enrichment of extracellular matrix remodeling, neutrophil degranulation, and neuronal signaling, consistent with immune evasion. Upregulation of NRXN1, GABRA3, KCNK3, and KLK12 was linked to worse survival, whereas SYNGR3 and CD207 were associated with favorable outcomes.
Conclusion: By unifying radiology, pathology, and transcriptomics, MuTriM provides an interpretable multimodal framework for breast cancer prognosis and treatment guidance.
目的：我们提出了MuTriM，这是一个多模态深度学习模型，结合DCE-MRI和全切片病理来预测乳腺癌的生存和放疗获益。患者和方法：MuTriM采用基于注意力的跨模态和跨颞融合框架，同时整合DCE-MRI放射学特征和WSI细胞形态学的病理特征。MuTriM在复旦大学上海肿瘤中心（FUSCC）队列（N = 335）中进行训练，并在TCGA队列（N = 126）中使用匹配的DCE-MRI和WSI进行外部测试。结果：在亚型不确定的情况下，MuTriM是无复发生存（RFS）的预后（HR = 5.26, 95% CI, 1.69-16.4, p = 0.004;C-index = 0.75），优于单独基于DCE-MRI （C-index = 0.65）或单独基于WSI （C-index = 0.70）的单峰模型。MuTriM对HER2 + 人群（HR = 6.82, 95% CI, 1.08-43.2, p = 0.04）和ER+ 人群（HR = 4.61, 95% CI, 1.25-17.1, p = 0.02）的预后也有影响。较高的MuTriM评分与改善的RFS相关（HR = 0.15, 95% CI 0.03-0.87; P = 0.03），而较低的MuTriM评分没有显著的益处（HR = 4.06, 95% CI 0.05-31; P = 0.53）（相互作用P = 0.04）。转录组学分析显示，高危肿瘤显示细胞毒性t细胞活性受到抑制，细胞外基质重塑、中性粒细胞脱颗粒和神经元信号富集，与免疫逃避一致。NRXN1、GABRA3、KCNK3和KLK12的上调与较差的生存率相关，而SYNGR3和CD207与良好的预后相关。结论：通过统一放射学、病理学和转录组学，MuTriM为乳腺癌预后和治疗指导提供了一个可解释的多模式框架。
{"title":"MuTriM: A multiscale deep learning model integrating longitudinal radiomics and pathomic features for predicting recurrence and adjuvant radiation benefit in breast cancer.","authors":"Xiangxue Wang, Liya Chen, Jingwen Sun, Sirvan Khalighi, Tanmoy Dam, Himanshu Maurya, Tilak Pathak, Cheng Lu, Shipra Gandhi, Sunil Badve, Shen Zhao, Wentao Yang, Jun Xu, Anant Madabhushi, Bolin Song","doi":"10.1016/j.ejca.2026.116679","DOIUrl":"10.1016/j.ejca.2026.116679","url":null,"abstract":"<p><strong>Purpose: </strong>We present MuTriM, a multimodal deep learning model integrating DCE-MRI and whole-slide pathology to predict survival and radiation benefit in breast cancer.</p><p><strong>Patients and methods: </strong>MuTriM employs an attention-based cross-modal and cross-temporal fusion framework that concurrently integrates DCE-MRI radiomic features with pathomic features of cellular morphology on WSI. MuTriM was trained on the Fudan University Shanghai Cancer Center (FUSCC) cohort (N = 335) and externally tested on the TCGA cohort (N = 126) using matched DCE-MRI and WSI.</p><p><strong>Results: </strong>MuTriM was prognostic of recurrence-free survival (RFS) in a subtype-agnostic setting (HR = 5.26, 95% CI, 1.69-16.4, p = 0.004; C-index = 0.75), outperforming unimodal models based on DCE-MRI alone (C-index = 0.65) or WSI alone (C-index = 0.70). MuTriM was also prognostic among HER2 + (HR = 6.82, 95% CI, 1.08-43.2, p = 0.04) and ER+ populations (HR = 4.61, 95% CI, 1.25-17.1, p = 0.02). A high MuTriM score was associated with improved RFS (HR = 0.15, 95% CI 0.03-0.87; P = 0.03), whereas a low MuTriM score showed no significant benefit (HR = 4.06, 95% CI 0.05-31; P = 0.53) (interaction P = 0.04). Transcriptomic analyses revealed that high-risk tumors showed suppressed cytotoxic T-cell activity and enrichment of extracellular matrix remodeling, neutrophil degranulation, and neuronal signaling, consistent with immune evasion. Upregulation of NRXN1, GABRA3, KCNK3, and KLK12 was linked to worse survival, whereas SYNGR3 and CD207 were associated with favorable outcomes.</p><p><strong>Conclusion: </strong>By unifying radiology, pathology, and transcriptomics, MuTriM provides an interpretable multimodal framework for breast cancer prognosis and treatment guidance.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"238 ","pages":"116679"},"PeriodicalIF":7.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1016/j.ejca.2026.116677
Emma Nicklin, Christopher Bedding, Sara Alfieri, Giovanni Apolone, Volker Arndt, Nanne Bos, Anne Bredart, Cinzia Brunelli, Luana Caselli, Gennaro Ciliberto, Leslye Rojas-Concha, Norbert Couespel, Daniela Doege, Montse Ferrer, Maria Alice Franzoi, Laura Gangeri, Olatz Garin, Emma Gillanders, Mogens Groenvold, Caitriona Higgins, Esther C E de Jongh, Tapani Kalmi, Stein Kaasa, Claudio Lombardo, Elise Martin, Helle Pappot, Ricardo Pietrobon, Gabriella Pravettoni, Bianca Scacciati, Aude Sirven, Maike G Sweegers, Melissa S Y Thong, Hugo Vachon, Lonneke V van de Poll-Franse, Ines Vaz-Luis, Augusto Caraceni, Galina Velikova, Alexandra Gilbert
Purpose: The European Oncology Quality of Life (EUonQoL) project aims to develop a questionnaire toolkit (EUonQoL-Kit) to assess the quality of life (QoL) of cancer patients and survivors across Europe.
Methods: The EUonQoL-Kit development used mixed-methods and a co-design approach. Data was collected in six countries (Denmark, France, Germany, Italy, Netherlands and UK). The target populations were patients in active treatment (A), survivors (B) and patients requiring palliative care (C). A review of existing QoL theoretical models produced an initial EUonQoL conceptual framework. Semi-structured interviews and a Delphi survey evaluated/modified the framework. Existing validated items were used to construct the toolkit, including Computer Adaptive Testing (CAT), where available. A usability study evaluated EUonQoL-Kit.v1. Data triangulation and consensus methodology guided EUonQoL-Kit.v2.
Results: The initial conceptual framework covered four multi-dimensional domains: physical, social and overall health, and psychological wellbeing. The interviews and Delphi survey included 75 and 155 participants, respectively. The domain 'healthcare experience' was identified and included in the framework. EUonQoL-Kit.v1 resulted in three static questionnaires, one for each target population (n items- A=75; B=67; C=79). Following usability testing with 53 participants, EUonQoL-Kit.v2 was produced via a multi-stakeholder consensus development panel, creating a shortened version (n items- A=50; B=50; C=44). Dynamic versions of these questionnaires were developed using the EORTC CAT Core system.
Conclusions: EUonQoL-Kit is a novel toolkit developed to assess QoL across the cancer continuum and inform health policy within Europe. Its psychometric properties are currently being evaluated using data collected on more than 4200 patients across 32 countries.
目的：欧洲肿瘤生活质量（EUonQoL）项目旨在开发一个问卷工具包（EUonQoL- kit）来评估整个欧洲癌症患者和幸存者的生活质量（QoL）。方法：采用混合方法和协同设计方法开发EUonQoL-Kit。数据收集于六个国家（丹麦、法国、德国、意大利、荷兰和英国）。目标人群为正在积极治疗的患者(A)、幸存者(B)和需要姑息治疗的患者(C)。对现有生活质量理论模型的回顾产生了最初的EUonQoL概念框架。半结构化访谈和德尔菲调查评估/修改了框架。现有的经过验证的项目被用来构建工具包，包括计算机自适应测试（CAT），如果可用的话。一项可用性研究评估了EUonQoL-Kit.v1。EUonQoL-Kit.v2采用数据三角测量和共识方法。结果：最初的概念框架涵盖了四个多维领域：身体健康、社会和整体健康以及心理健康。访谈和德尔菲调查分别包括75名和155名参与者。确定了“医疗保健经验”领域并将其包含在框架中。EUonQoL-Kit。v1产生三份静态问卷，每个目标人群一份（n项- A=75； B=67； C=79）。经过53位参与者的可用性测试，EUonQoL-Kit。v2是通过多方利益相关者共识开发小组制作的，创建了一个缩短版本（n项- a =50； B=50； C=44）。这些问卷的动态版本是使用EORTC CAT核心系统开发的。结论：EUonQoL-Kit是一种新的工具包，用于评估整个癌症连续体的生活质量，并为欧洲的卫生政策提供信息。目前正在使用从32个国家的4200多名患者收集的数据对其心理测量特性进行评估。
{"title":"The development of the European Toolkit for the self-assessment of quality of life across the cancer care continuum (EUonQoL-Kit).","authors":"Emma Nicklin, Christopher Bedding, Sara Alfieri, Giovanni Apolone, Volker Arndt, Nanne Bos, Anne Bredart, Cinzia Brunelli, Luana Caselli, Gennaro Ciliberto, Leslye Rojas-Concha, Norbert Couespel, Daniela Doege, Montse Ferrer, Maria Alice Franzoi, Laura Gangeri, Olatz Garin, Emma Gillanders, Mogens Groenvold, Caitriona Higgins, Esther C E de Jongh, Tapani Kalmi, Stein Kaasa, Claudio Lombardo, Elise Martin, Helle Pappot, Ricardo Pietrobon, Gabriella Pravettoni, Bianca Scacciati, Aude Sirven, Maike G Sweegers, Melissa S Y Thong, Hugo Vachon, Lonneke V van de Poll-Franse, Ines Vaz-Luis, Augusto Caraceni, Galina Velikova, Alexandra Gilbert","doi":"10.1016/j.ejca.2026.116677","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116677","url":null,"abstract":"<p><strong>Purpose: </strong>The European Oncology Quality of Life (EUonQoL) project aims to develop a questionnaire toolkit (EUonQoL-Kit) to assess the quality of life (QoL) of cancer patients and survivors across Europe.</p><p><strong>Methods: </strong>The EUonQoL-Kit development used mixed-methods and a co-design approach. Data was collected in six countries (Denmark, France, Germany, Italy, Netherlands and UK). The target populations were patients in active treatment (A), survivors (B) and patients requiring palliative care (C). A review of existing QoL theoretical models produced an initial EUonQoL conceptual framework. Semi-structured interviews and a Delphi survey evaluated/modified the framework. Existing validated items were used to construct the toolkit, including Computer Adaptive Testing (CAT), where available. A usability study evaluated EUonQoL-Kit.v1. Data triangulation and consensus methodology guided EUonQoL-Kit.v2.</p><p><strong>Results: </strong>The initial conceptual framework covered four multi-dimensional domains: physical, social and overall health, and psychological wellbeing. The interviews and Delphi survey included 75 and 155 participants, respectively. The domain 'healthcare experience' was identified and included in the framework. EUonQoL-Kit.v1 resulted in three static questionnaires, one for each target population (n items- A=75; B=67; C=79). Following usability testing with 53 participants, EUonQoL-Kit.v2 was produced via a multi-stakeholder consensus development panel, creating a shortened version (n items- A=50; B=50; C=44). Dynamic versions of these questionnaires were developed using the EORTC CAT Core system.</p><p><strong>Conclusions: </strong>EUonQoL-Kit is a novel toolkit developed to assess QoL across the cancer continuum and inform health policy within Europe. Its psychometric properties are currently being evaluated using data collected on more than 4200 patients across 32 countries.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"238 ","pages":"116677"},"PeriodicalIF":7.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Androgen-deprivation therapy (ADT) plus radiotherapy is a standard of care for men with high-risk localized prostate cancer (PC). Adding docetaxel in this setting demonstrated better relapse-free survival (RFS) but not survival. Few data are available on relapse patterns. Our aim was to investigate whether different patterns of relapses exist in men with high-risk localized PC.
Patients and methods: Prospective data from the GETUG12 phase 3 randomized controlled trial comparing ADT alone vs ADT + docetaxel and estramustine (DE) was examined. RFS (main endpoint) was analysed using parametric survival models and second event-free survival (SEFS) defined from biochemical progression (BP) was analysed using a competing-risk approach.
Results: Overall, 413 patients were randomized from 2002 to 2006, 206 treated with ADT and 207 with ADT+DE, in addition to local treatment. First analysis showed that the piecewise-exponential model with two time-intervals ([0-3[; ≥3 years) was the model that best characterized RFS with no time-dependent effect of risk factors and treatment. Second analyses limited to patients with a BP showed that the risk of a second event was significantly lower in patients with a longer time-interval from randomization to BP (hazard ratio (HR≥ 3 versus < 3 years): 0.49 [95% CI 0.30-0.79]). In competing-risk analysis, a significant and protective effect of this time-interval was observed for metastases (sub-HR≥ 3 versus < 3 years: 0.41 [0.23-0.73] accounting for salvage treatment.
Conclusion: Time-interval from randomization to BP is a major prognostic factor for developing local or distant recurrences for patients with high-risk localized PC.
背景：雄激素剥夺疗法（ADT）加放疗是治疗高危局限性前列腺癌（PC）的标准治疗方法。在这种情况下，添加多西他赛显示出更好的无复发生存期（RFS），但不是生存期。关于复发模式的数据很少。我们的目的是调查男性高危局限性PC患者是否存在不同的复发模式。患者和方法：来自GETUG12期随机对照试验的前瞻性数据，比较ADT单独与ADT + 多西他赛和estramusstine （DE）。使用参数生存模型分析RFS（主要终点），使用竞争风险方法分析由生化进展（BP）定义的第二无事件生存期（SEFS）。结果：总的来说，2002 - 2006年，413例患者被随机分组，除局部治疗外，206例接受ADT治疗，207例接受ADT+DE治疗。首先分析表明，具有两个时间间隔（[0-3]；≥3年）的分段指数模型是最能表征RFS的模型，不受危险因素和治疗的时间依赖性影响。第二项针对BP患者的分析显示，从随机分组到BP的时间间隔较长的患者发生第二次事件的风险显著降低（风险比（HR≥3 vs < 3年）：0.49 [95% CI 0.30-0.79]）。在竞争风险分析中，观察到这一时间间隔对转移瘤的显著保护作用(亚hr≥3 vs < 3年：0.41[0.23-0.73]，说明了抢救治疗。结论：从随机分组到血压的时间间隔是高危局限性PC患者发生局部或远处复发的主要预后因素。
{"title":"Survival modelling of relapse-free survival and competing-risk analysis in patients with high-risk localized prostate cancer treated in GETUG-12.","authors":"Cécile Vicier, Farah Erdogan, Nedjla Allouache, Remy Delva, Gwenaëlle Gravis, Frédéric Rolland, Frank Priou, Jean-Marc Ferrero, Nadine Houede, Loïc Mourey, Christine Theodore, Ivan Krakowski, Jean-François Berdah, Marjorie Baciuchka, Brigitte Laguerre, FlechonAude Fléchon, Marine Gross-Goupil, Isabelle Cojean-Zelek, Stéphane Oudard, Jean-Luc Labourey, Paule Chinet-Charrot, Eric Legouffe, Jean-Léon Lagrange, Claude Linassier, Gaël Deplanque, Philippe Beuzeboc, Jean-Louis Davin, Meryem Brihoum, Stéphane Culine, Karim Fizazi, Gwénaël Le Teuff","doi":"10.1016/j.ejca.2026.116678","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116678","url":null,"abstract":"<p><strong>Background: </strong>Androgen-deprivation therapy (ADT) plus radiotherapy is a standard of care for men with high-risk localized prostate cancer (PC). Adding docetaxel in this setting demonstrated better relapse-free survival (RFS) but not survival. Few data are available on relapse patterns. Our aim was to investigate whether different patterns of relapses exist in men with high-risk localized PC.</p><p><strong>Patients and methods: </strong>Prospective data from the GETUG12 phase 3 randomized controlled trial comparing ADT alone vs ADT + docetaxel and estramustine (DE) was examined. RFS (main endpoint) was analysed using parametric survival models and second event-free survival (SEFS) defined from biochemical progression (BP) was analysed using a competing-risk approach.</p><p><strong>Results: </strong>Overall, 413 patients were randomized from 2002 to 2006, 206 treated with ADT and 207 with ADT+DE, in addition to local treatment. First analysis showed that the piecewise-exponential model with two time-intervals ([0-3[; ≥3 years) was the model that best characterized RFS with no time-dependent effect of risk factors and treatment. Second analyses limited to patients with a BP showed that the risk of a second event was significantly lower in patients with a longer time-interval from randomization to BP (hazard ratio (HR<sub>≥ 3 versus < 3 years</sub>): 0.49 [95% CI 0.30-0.79]). In competing-risk analysis, a significant and protective effect of this time-interval was observed for metastases (sub-HR<sub>≥ 3 versus < 3 years</sub>: 0.41 [0.23-0.73] accounting for salvage treatment.</p><p><strong>Conclusion: </strong>Time-interval from randomization to BP is a major prognostic factor for developing local or distant recurrences for patients with high-risk localized PC.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"238 ","pages":"116678"},"PeriodicalIF":7.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1016/j.ejca.2026.116682
Arnaud Bayle, Julia Bonastre, Benjamin Besse, Antoine Italiano, Christophe Massard, Fabrice Barlesi
{"title":"Clinical utility of comprehensive genomic profiling: From evidence generation to sustainable access.","authors":"Arnaud Bayle, Julia Bonastre, Benjamin Besse, Antoine Italiano, Christophe Massard, Fabrice Barlesi","doi":"10.1016/j.ejca.2026.116682","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116682","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":" ","pages":"116682"},"PeriodicalIF":7.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11Epub Date: 2026-01-23DOI: 10.1016/j.ejca.2026.116251
Uri Galili , Yongxiang Zhao
Oncolytic-viruses (OV) decrease tumor-mass but are less successful in eliciting long-term protective immune-response against tumor-antigens (TAs), due to poor uptake of tumor-cells by antigen-presenting-cells (APCs). It is postulated that this anti-tumor immune-response may greatly increase with OV containing the GGTA1-gene (OV-GT). GGTA1 encodes α1,3galactosyltransferase that synthesizes α-gal epitopes which bind the abundant human natural anti-Gal antibody. Tumor-cells infected with OV-GT present α-gal epitopes and bind the anti-Gal antibody. This antigen/antibody interaction activates the complement-system which mediates killing of tumor-cells presenting α-gal epitopes. The generated complement cleavage peptides C5a and C3a byproducts chemotactically recruit APCs. These APCs extensively phagocytose anti-Gal opsonized tumor-cells, following binding of the antibody’s Fc portion to Fc-receptors on the APCs. The APCs transport TAs of internalized tumor-cells to lymph-nodes, process and present peptides of the processed TAs. These TA peptides activate TA specific T-cells including cytotoxic T-cells (CTL). Activated CTL proliferate, circulate and kill metastatic tumor-cells presenting TAs. It is suggested that Newcastle-disease-virus, used as an effective OV-GT (NDV-GT) mediates by this mechanism the observed complete elimination of hepatic-cell carcinoma metastases in cynomolgus monkeys. Furthermore, NDV-GT treated cancer-patients with advanced-disease demonstrated 90 % response of partial-remission, stable-disease, and one complete-remission. These findings suggest that the GGTA1-gene within various OV amplifies their therapeutic efficacy by converting infected tumor-cells into a therapeutic cancer vaccine.
{"title":"Potential induction of protective anti-tumor immune response in cancer patients by oncolytic viruses containing the GGTA1 gene","authors":"Uri Galili , Yongxiang Zhao","doi":"10.1016/j.ejca.2026.116251","DOIUrl":"10.1016/j.ejca.2026.116251","url":null,"abstract":"<div><div>Oncolytic-viruses (OV) decrease tumor-mass but are less successful in eliciting long-term protective immune-response against tumor-antigens (TAs), due to poor uptake of tumor-cells by antigen-presenting-cells (APCs). It is postulated that this anti-tumor immune-response may greatly increase with OV containing the <em>GGTA1</em>-gene (OV-GT). <em>GGTA1</em> encodes <em>α</em>1,3galactosyltransferase that synthesizes <em>α</em>-gal epitopes which bind the abundant human natural anti-Gal antibody. Tumor-cells infected with OV-GT present <em>α</em>-gal epitopes and bind the anti-Gal antibody. This antigen/antibody interaction activates the complement-system which mediates killing of tumor-cells presenting <em>α</em>-gal epitopes. The generated complement cleavage peptides C5a and C3a byproducts chemotactically recruit APCs. These APCs extensively phagocytose anti-Gal opsonized tumor-cells, following binding of the antibody’s Fc portion to Fc-receptors on the APCs. The APCs transport TAs of internalized tumor-cells to lymph-nodes, process and present peptides of the processed TAs. These TA peptides activate TA specific T-cells including cytotoxic T-cells (CTL). Activated CTL proliferate, circulate and kill metastatic tumor-cells presenting TAs. It is suggested that Newcastle-disease-virus, used as an effective OV-GT (NDV-GT) mediates by this mechanism the observed complete elimination of hepatic-cell carcinoma metastases in cynomolgus monkeys. Furthermore, NDV-GT treated cancer-patients with advanced-disease demonstrated 90 % response of partial-remission, stable-disease, and one complete-remission. These findings suggest that the <em>GGTA1-</em>gene within various OV amplifies their therapeutic efficacy by converting infected tumor-cells into a therapeutic cancer vaccine.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116251"},"PeriodicalIF":7.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovarian function suppression (OFS) combined with tamoxifen or aromatase inhibitor (AI) are standard treatment options for young women with hormone receptor-positive breast cancer. Suboptimal OFS may reduce the efficacy of the endocrine treatment (ET). This study evaluated factors associated with suboptimal OFS induced by gonadotropin-releasing hormone agonist (GnRHa).
Methods
PREFER (NCT02895165) and GIM 23-POSTER (NCT05730647) are multicentric Italian prospective, observational studies enrolling premenopausal women undergoing (neo)adjuvant chemotherapy and/or ET. The present analysis includes only patients enrolled at the coordinating center. Patients receiving ET with OFS were classified into suboptimal (estradiol >25.1 ng/L measured by chemiluminescent immunoassay or resumed menstruation) or adequate OFS.
Results
As of June 2024, 488 patients were enrolled (median follow-up: 44.4 months, IQR 20.6–84.0). Of 343 patients receiving adjuvant ET, 315 were in the adequately suppressed group and 28 in the suboptimal suppression group (of whom 55.9 % and 92.9 %, respectively, were receiving an AI). Clinical characteristics (age, BMI, baseline FSH, and estradiol levels) and previous chemotherapy (with or without concurrent GnRHa) showed no association with suboptimal OFS. Concurrent treatment with AI was the only factor significantly associated with suboptimal OFS (HR 12.83, 95 % CI 3.01–54.65; p = 0.001). The proportion of patients with suboptimal suppression was 5.1 % (95 % CI 3.2–8.2) in the first year of ET, rising to 10.5 % (95 % CI 7.1–15.4) within five years.
Conclusions
Approximately 10 % of premenopausal women receiving GnRHa as part of adjuvant ET did not achieve complete OFS. Use of AI was the only factor linked to suboptimal OFS.
目的：卵巢功能抑制（OFS）联合他莫昔芬或芳香化酶抑制剂（AI）是年轻女性激素受体阳性乳腺癌的标准治疗选择。不理想的OFS可能会降低内分泌治疗（ET）的疗效。本研究评估了与促性腺激素释放激素激动剂（GnRHa）诱导的次优OFS相关的因素。方法：PREFER （NCT02895165）和GIM 23-POSTER （NCT05730647）是意大利多中心前瞻性观察性研究，纳入了接受（新）辅助化疗和/或ET的绝经前妇女。本分析仅包括在协调中心登记的患者。接受ET治疗的患者将OFS分为次优（雌二醇浓度为25.1 ng/L，化学发光免疫测定或月经恢复）或充分OFS。结果：截至2024年6月，纳入488例患者（中位随访44.4个月，IQR为20.6-84.0）。在343例接受辅助ET的患者中，315例在充分抑制组，28例在次优抑制组（其中55.9% %和92.9 %分别接受了AI）。临床特征（年龄、BMI、基线FSH和雌二醇水平）和既往化疗（伴有或不伴有GnRHa）显示与次优OFS无关。与AI同时治疗是唯一与次优OFS显著相关的因素（HR 12.83, 95 % CI 3.01-54.65; p = 0.001）。在ET治疗的第一年，亚理想抑制的患者比例为5.1% %(95% % CI 3.2-8.2)，五年内上升到10.2% %（95% % CI 7.1-15.4）。结论：大约10% %的绝经前妇女接受GnRHa作为辅助ET的一部分没有达到完全的OFS。人工智能的使用是导致OFS不理想的唯一因素。
{"title":"Comparison of suboptimal versus adequate ovarian function suppression in premenopausal women with early breast cancer treated with adjuvant endocrine therapy: An exploratory analysis of two prospective studies","authors":"Simone Nardin , Marco Bruzzone , Luca Arecco , Edoardo Chiappe , Chiara Lanzavecchia , Tommaso Ruelle , Irene Giannubilo , Maria Grazia Razeti , Roberto Borea , Lucrezia Barcellini , Francesca Bruzzone , Arianna Daneri , Chiara Molinelli , Davide Soldato , Alessia Levaggi , Claudia Bighin , Valentina Barbero , Silvia Ottonello , Graziana Scavone , Piero Fregatti , Francesca Poggio","doi":"10.1016/j.ejca.2026.116266","DOIUrl":"10.1016/j.ejca.2026.116266","url":null,"abstract":"<div><h3>Purpose</h3><div>Ovarian function suppression (OFS) combined with tamoxifen or aromatase inhibitor (AI) are standard treatment options for young women with hormone receptor-positive breast cancer. Suboptimal OFS may reduce the efficacy of the endocrine treatment (ET). This study evaluated factors associated with suboptimal OFS induced by gonadotropin-releasing hormone agonist (GnRHa).</div></div><div><h3>Methods</h3><div>PREFER (NCT02895165) and GIM 23-POSTER (NCT05730647) are multicentric Italian prospective, observational studies enrolling premenopausal women undergoing (neo)adjuvant chemotherapy and/or ET. The present analysis includes only patients enrolled at the coordinating center. Patients receiving ET with OFS were classified into suboptimal (estradiol >25.1 ng/L measured by chemiluminescent immunoassay or resumed menstruation) or adequate OFS.</div></div><div><h3>Results</h3><div>As of June 2024, 488 patients were enrolled (median follow-up: 44.4 months, IQR 20.6–84.0). Of 343 patients receiving adjuvant ET, 315 were in the adequately suppressed group and 28 in the suboptimal suppression group (of whom 55.9 % and 92.9 %, respectively, were receiving an AI). Clinical characteristics (age, BMI, baseline FSH, and estradiol levels) and previous chemotherapy (with or without concurrent GnRHa) showed no association with suboptimal OFS. Concurrent treatment with AI was the only factor significantly associated with suboptimal OFS (HR 12.83, 95 % CI 3.01–54.65; p = 0.001). The proportion of patients with suboptimal suppression was 5.1 % (95 % CI 3.2–8.2) in the first year of ET, rising to 10.5 % (95 % CI 7.1–15.4) within five years.</div></div><div><h3>Conclusions</h3><div>Approximately 10 % of premenopausal women receiving GnRHa as part of adjuvant ET did not achieve complete OFS. Use of AI was the only factor linked to suboptimal OFS.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116266"},"PeriodicalIF":7.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11Epub Date: 2026-02-04DOI: 10.1016/j.ejca.2026.116256
Wilfried Ernst Erich Eberhardt , Christina Schulte , Christoph Pöttgen , Thomas Christoph Gauler , Godehard Friedel , Hans-Georg Kopp , Berthold Fischer , Heinz Schmidtberger , Martin Kimmich , Wilfried Budach , Sebastian Cordes , Martin Metzenmacher , Gregor Zaun , Rodrigo Hepp de Los Rios , Werner Spengler , Claus Belka , Stephan Welter , Diana Luetke-Brintrup , Nika Guberina , Maja Guberina , Martin Stuschke
Introduction
More stage III non-small-cell lung cancer patients experience long-term survival (OS). ESPATUE-trial looked at surgery versus boost-radiochemotherapy following induction chemotherapy, consisting of three cycles of cisplatin 50 mg/m2 on days 1 and 8 and paclitaxel 175 mg/m2 on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m2 on days 2 and 9, and concurrent vinorelbine 20 mg/m2 on days 2 and 9 (Eberhardt et al, J Clin Oncol 2015). Here, we update 10-years-OS and report competing-risks-of-deaths.
Methods
Complete trial design has been published. We updated OS for patients still alive at 2/2022. Patients were followed up on a yearly basis and showed up to get follow-up imaging and reevaluation.
Results
From 1/2004 until 1/2013 246 patients medically and functionally operable were enrolled. Following induction 161 considered resectable were randomized to radiochemotherapy-boost(arm 1/A;n = 80) or definitive surgery(arm 2/B;n = 81).The median time from randomization to last evaluation was 145.1 months(interquartile range 121.5–197.8). Patients in the arm that included surgery(B) had a 10-year overall survival rate of 29.9 %(20.2–40.3) and those with radiochemotherapy(A) a rate of 28.3 %(18.8–38.5; p = 0.70 log rank). Rates of progression-free survival, death from second priomary lung cancer, death from first lung cancer, treatment related death, death from second cancer without lung cancer were comparable in both study arms
Conclusions
Long-term survival serves as baseline information for ongoing immunotherapy-based stage III protocols. No significant differences between local modalities radiochemotherapy and surgery were observed. A competing-risk-of-deaths-analysis showed no relevant preference for one arm. Death from comorbidities and death from second lung cancer remain relevant long-term-risks.
{"title":"Ten-year overall survival in resectable stage-III NSCLC - Results of the randomized ESPATUE trial – Long-term survival and competing risk analysis","authors":"Wilfried Ernst Erich Eberhardt , Christina Schulte , Christoph Pöttgen , Thomas Christoph Gauler , Godehard Friedel , Hans-Georg Kopp , Berthold Fischer , Heinz Schmidtberger , Martin Kimmich , Wilfried Budach , Sebastian Cordes , Martin Metzenmacher , Gregor Zaun , Rodrigo Hepp de Los Rios , Werner Spengler , Claus Belka , Stephan Welter , Diana Luetke-Brintrup , Nika Guberina , Maja Guberina , Martin Stuschke","doi":"10.1016/j.ejca.2026.116256","DOIUrl":"10.1016/j.ejca.2026.116256","url":null,"abstract":"<div><h3>Introduction</h3><div>More stage III non-small-cell lung cancer patients experience long-term survival (OS). ESPATUE-trial looked at surgery versus boost-radiochemotherapy following induction chemotherapy, consisting of three cycles of cisplatin 50 mg/m<sup>2</sup> on days 1 and 8 and paclitaxel 175 mg/m<sup>2</sup> on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m<sup>2</sup> on days 2 and 9, and concurrent vinorelbine 20 mg/m<sup>2</sup> on days 2 and 9 (Eberhardt et al, J Clin Oncol 2015). Here, we update 10-years-OS and report competing-risks-of-deaths.</div></div><div><h3>Methods</h3><div>Complete trial design has been published. We updated OS for patients still alive at 2/2022. Patients were followed up on a yearly basis and showed up to get follow-up imaging and reevaluation.</div></div><div><h3>Results</h3><div>From 1/2004 until 1/2013 246 patients medically and functionally operable were enrolled. Following induction 161 considered resectable were randomized to radiochemotherapy-boost(arm 1/A;n = 80) or definitive surgery(arm 2/B;n = 81).The median time from randomization to last evaluation was 145.1 months(interquartile range 121.5–197.8). Patients in the arm that included surgery(B) had a 10-year overall survival rate of 29.9 %(20.2–40.3) and those with radiochemotherapy(A) a rate of 28.3 %(18.8–38.5; p = 0.70 log rank). Rates of progression-free survival, death from second priomary lung cancer, death from first lung cancer, treatment related death, death from second cancer without lung cancer were comparable in both study arms</div></div><div><h3>Conclusions</h3><div>Long-term survival serves as baseline information for ongoing immunotherapy-based stage III protocols. No significant differences between local modalities radiochemotherapy and surgery were observed. A competing-risk-of-deaths-analysis showed no relevant preference for one arm. Death from comorbidities and death from second lung cancer remain relevant long-term-risks.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116256"},"PeriodicalIF":7.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11Epub Date: 2026-01-29DOI: 10.1016/j.ejca.2026.116261
Sara Nyback , Inger Sundström Poromaa , Henrik Lindman , Angelica Lindén Hirschberg , Helena Kopp Kallner , Anna Wikman , Theodora Kunovac Kallak
Background
There is a great need for non-estrogenic treatment of vulvovaginal atrophy (VVA) symptoms affecting sexual function and quality of life. Women with breast cancer on anti-estrogenic therapy are particularly vulnerable and in need of help. The primary aim of this proof-of-concept trial was to evaluate the efficacy of vaginal tamoxifen in reducing the most troublesome VVA symptom.
Methods
In this randomized, double blind, placebo-controlled study, 115 postmenopausal women, with or without breast cancer, were randomized to 20 mg vaginal tamoxifen once weekly or placebo (1:1). Follow-up after one and three-months of treatment, included self-reported VVA symptoms on the Endocrine Symptom Subscale of FACT-B, and gynecologic exams for VVA score and measurement of vaginal pH and endometrial thickness.
Findings
After three months, 37 (68.6 %) of women on vaginal tamoxifen reported their most troublesome VVA symptom to be mild or not present at all, whereas corresponding number in the placebo group was 5 (9.1 %), p < 0.001. Expressed as odds, women on vaginal tamoxifen were more likely to report no or minor symptoms after three-months, OR 21.76 (95 % CI 7.36 – 64.3). The improvement in self-reported outcomes was accompanied by improvements in VVA scores and vaginal pH, p < 0.001.
Interpretation
This study has demonstrated that more than two-thirds of the women on vaginal tamoxifen improved in their most troublesome VVA symptom. This is likely due to a tamoxifen-induced estrogen agonistic effects in vagina in a low-estrogen environment. While findings are promising, further studies on improved vaginal administration and endometrial safety concerns are needed.
{"title":"Vaginal tamoxifen – A potential treatment option for vaginal atrophy symptoms in postmenopausal women who cannot use estrogen","authors":"Sara Nyback , Inger Sundström Poromaa , Henrik Lindman , Angelica Lindén Hirschberg , Helena Kopp Kallner , Anna Wikman , Theodora Kunovac Kallak","doi":"10.1016/j.ejca.2026.116261","DOIUrl":"10.1016/j.ejca.2026.116261","url":null,"abstract":"<div><h3>Background</h3><div>There is a great need for non-estrogenic treatment of vulvovaginal atrophy (VVA) symptoms affecting sexual function and quality of life. Women with breast cancer on anti-estrogenic therapy are particularly vulnerable and in need of help. The primary aim of this proof-of-concept trial was to evaluate the efficacy of vaginal tamoxifen in reducing the most troublesome VVA symptom.</div></div><div><h3>Methods</h3><div>In this randomized, double blind, placebo-controlled study, 115 postmenopausal women, with or without breast cancer, were randomized to 20 mg vaginal tamoxifen once weekly or placebo (1:1). Follow-up after one and three-months of treatment, included self-reported VVA symptoms on the Endocrine Symptom Subscale of FACT-B, and gynecologic exams for VVA score and measurement of vaginal pH and endometrial thickness.</div></div><div><h3>Findings</h3><div>After three months, 37 (68.6 %) of women on vaginal tamoxifen reported their most troublesome VVA symptom to be mild or not present at all, whereas corresponding number in the placebo group was 5 (9.1 %), p < 0.001. Expressed as odds, women on vaginal tamoxifen were more likely to report no or minor symptoms after three-months, OR 21.76 (95 % CI 7.36 – 64.3). The improvement in self-reported outcomes was accompanied by improvements in VVA scores and vaginal pH, p < 0.001.</div></div><div><h3>Interpretation</h3><div>This study has demonstrated that more than two-thirds of the women on vaginal tamoxifen improved in their most troublesome VVA symptom. This is likely due to a tamoxifen-induced estrogen agonistic effects in vagina in a low-estrogen environment. While findings are promising, further studies on improved vaginal administration and endometrial safety concerns are needed.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116261"},"PeriodicalIF":7.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11Epub Date: 2026-01-30DOI: 10.1016/j.ejca.2026.116258
Mélanie Dos Santos , Justine Lequesne , Guillaume Piessen , Alexandra Leconte , Rosine Guimbaud , Simon Pernot , Olivier Bouche , Sandrine Hiret , Emilie Soularue , David Tougeron , Laetitia Dahan , Samuel Le Sourd , Christophe Borg , Emmanuelle Samalin , Stéphane Corbinais , Aurélie Parzy , Jean-Marc Guilloit , Sharmini Varatharajah , Pierre-Emmanuel Brachet , Marine Dorbeau , Bénédicte Clarisse
Purpose
Perioperative chemotherapy with FLOT is a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. This trial evaluated the anti–PD-1 monoclonal antibody spartalizumab combined with FLOT as perioperative treatment for resectable patients.
Patients and Methods
GASPAR is a multicenter, single-arm, Simon two-stage phase 2 trial. Patients with untreated localized gastric or GEJ adenocarcinoma considered resectable (≥ cT2 or cN+) received 4 pre- and post-operative cycles of FLOT and 2 pre- and post-operative cycles of spartalizumab. The main endpoint was the rate of pathological complete regression (pCR) according to the Becker criteria, requiring 67 patients (H0/H1 =10/23 %, α=5 %, β=20 %).
Results
Overall, 68 patients were included: men (78 %), median age 63 years [range 31–79], cT3 51 %, GEJ 60 %, cN+ 58 %. Treatment was started in 67 patients. Delayed FLOT administration for toxicity and dose reduction concerned 14 (21 %) and 28 (42 %) patients, respectively. Surgery was R0 in 62 (95 %) of the patients operated on. Among 64 patients assessable for efficacy, pCR was observed in 20 patients (31 %), and major pathological response in 12 patients (19 %), meaning a major response rate of 50 %. Five patients developed grade 3 immune-mediated adverse events. One death related to pneumocystis occurred. Severe post-surgery complications occurred in 15 patients (23 %). After a median follow-up of 30 months [range 4–42], OS and DFS at 2 years were 86 % [77.8–94.9] and 77.5 % [68.1–88.2], respectively.
Conclusions
Spartalizumab combined with FLOT shows high efficacy as perioperative treatment in patients with resectable gastric cancer, and an acceptable safety profile.
{"title":"Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): Results from the GASPAR phase 2 study","authors":"Mélanie Dos Santos , Justine Lequesne , Guillaume Piessen , Alexandra Leconte , Rosine Guimbaud , Simon Pernot , Olivier Bouche , Sandrine Hiret , Emilie Soularue , David Tougeron , Laetitia Dahan , Samuel Le Sourd , Christophe Borg , Emmanuelle Samalin , Stéphane Corbinais , Aurélie Parzy , Jean-Marc Guilloit , Sharmini Varatharajah , Pierre-Emmanuel Brachet , Marine Dorbeau , Bénédicte Clarisse","doi":"10.1016/j.ejca.2026.116258","DOIUrl":"10.1016/j.ejca.2026.116258","url":null,"abstract":"<div><h3>Purpose</h3><div>Perioperative chemotherapy with FLOT is a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. This trial evaluated the anti–PD-1 monoclonal antibody spartalizumab combined with FLOT as perioperative treatment for resectable patients.</div></div><div><h3>Patients and Methods</h3><div>GASPAR is a multicenter, single-arm, Simon two-stage phase 2 trial. Patients with untreated localized gastric or GEJ adenocarcinoma considered resectable (≥ cT2 or cN+) received 4 pre- and post-operative cycles of FLOT and 2 pre- and post-operative cycles of spartalizumab. The main endpoint was the rate of pathological complete regression (pCR) according to the Becker criteria, requiring 67 patients (H0/H1 =10/23 %, α=5 %, β=20 %).</div></div><div><h3>Results</h3><div>Overall, 68 patients were included: men (78 %), median age 63 years [range 31–79], cT3 51 %, GEJ 60 %, cN+ 58 %. Treatment was started in 67 patients. Delayed FLOT administration for toxicity and dose reduction concerned 14 (21 %) and 28 (42 %) patients, respectively. Surgery was R0 in 62 (95 %) of the patients operated on. Among 64 patients assessable for efficacy, pCR was observed in 20 patients (31 %), and major pathological response in 12 patients (19 %), meaning a major response rate of 50 %. Five patients developed grade 3 immune-mediated adverse events. One death related to pneumocystis occurred. Severe post-surgery complications occurred in 15 patients (23 %). After a median follow-up of 30 months [range 4–42], OS and DFS at 2 years were 86 % [77.8–94.9] and 77.5 % [68.1–88.2], respectively.</div></div><div><h3>Conclusions</h3><div>Spartalizumab combined with FLOT shows high efficacy as perioperative treatment in patients with resectable gastric cancer, and an acceptable safety profile.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov Identifier: NCT04736485</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116258"},"PeriodicalIF":7.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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