Pub Date : 2026-01-11DOI: 10.1016/j.ejca.2026.116231
Rachel Woodford , Sally Lord , Annelise Decaria , John Simes , Michael Friedlander , Ian C. Marschner , Chee Khoon Lee
Introduction
A considerable proportion of patients in ovarian cancer maintenance trials may be censored in progression-free survival (PFS) analyses, the primary study endpoint. Such censoring is often informative, reflecting discontinuation due to toxicity, preference, or early switch to alternative therapies, potentially biasing results toward overestimating PFS benefit. We aimed to quantify the impact of informative censoring on PFS in these trials.
Methods
Double-blind, placebo-controlled maintenance therapy trials were selected, and individual patient data reconstructed from published survival curves. A sensitivity analysis reclassified varying proportions of all censored events as progressions to model scenarios from 0 % to 100 % informative censoring. Hazard ratios (HRs) were re-estimated and compared with the originally reported values. Duration of therapy was compared with PFS.
Results
Twenty-two trial units (N = 8256) were included. Nineteen reported statistically significant results, falling to 14 (74 %) at the upper limit of analysis. HRs diminished progressively, with a 6 % reduction at 10 % censoring and 29 % at 100 %. In nine PARP inhibitor trials, treatment duration was shorter than PFS (mean of medians = 12.5 vs 17.6 months). Results were consistent when limited to PARP inhibitor studies. No correlation was observed between adverse events and censoring.
Conclusions
Informative censoring can substantially distort PFS benefit estimates in ovarian cancer maintenance trials. Transparent reporting of censoring rates and their causes is essential for meaningful clinical interpretation and should be standard in all randomised maintenance therapy trials.
{"title":"Informative censoring in maintenance therapy trials for advanced ovarian cancer: An empirical assessment of its impact on treatment benefit","authors":"Rachel Woodford , Sally Lord , Annelise Decaria , John Simes , Michael Friedlander , Ian C. Marschner , Chee Khoon Lee","doi":"10.1016/j.ejca.2026.116231","DOIUrl":"10.1016/j.ejca.2026.116231","url":null,"abstract":"<div><h3>Introduction</h3><div>A considerable proportion of patients in ovarian cancer maintenance trials may be censored in progression-free survival (PFS) analyses, the primary study endpoint. Such censoring is often informative, reflecting discontinuation due to toxicity, preference, or early switch to alternative therapies, potentially biasing results toward overestimating PFS benefit. We aimed to quantify the impact of informative censoring on PFS in these trials.</div></div><div><h3>Methods</h3><div>Double-blind, placebo-controlled maintenance therapy trials were selected, and individual patient data reconstructed from published survival curves. A sensitivity analysis reclassified varying proportions of all censored events as progressions to model scenarios from 0 % to 100 % informative censoring. Hazard ratios (HRs) were re-estimated and compared with the originally reported values. Duration of therapy was compared with PFS.</div></div><div><h3>Results</h3><div>Twenty-two trial units (N = 8256) were included. Nineteen reported statistically significant results, falling to 14 (74 %) at the upper limit of analysis. HRs diminished progressively, with a 6 % reduction at 10 % censoring and 29 % at 100 %. In nine PARP inhibitor trials, treatment duration was shorter than PFS (mean of medians = 12.5 vs 17.6 months). Results were consistent when limited to PARP inhibitor studies. No correlation was observed between adverse events and censoring.</div></div><div><h3>Conclusions</h3><div>Informative censoring can substantially distort PFS benefit estimates in ovarian cancer maintenance trials. Transparent reporting of censoring rates and their causes is essential for meaningful clinical interpretation and should be standard in all randomised maintenance therapy trials.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116231"},"PeriodicalIF":7.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975635","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 : 2026-01-11DOI: 10.1016/j.ejca.2026.116229
Nai-Jung Chiang , Yung-Yeh Su , I.-Wei Ho , Li-Yuan Bai , Chung-Pin Li , Jen-Shi Chen , Chin-Fu Hsiao , Hsiao-Hui Tsou , Chiun Hsu , Tai-Jan Chiu , Yao-Yu Hsieh , Kun-Ming Rau , Ching-Liang Ho , Yan-Shen Shan , Li-Tzong Chen
Objective
A multicenter, randomized phase II trial to compare two first-line triplet treatments for advanced pancreatic ductal adenocarcinoma (PDAC).
Methods
Patients with histologically confirmed advanced PDAC were randomized 1:1 to receive S-1/leucovorin plus oxaliplatin, and gemcitabine (SLOG) or modified FOLFIRINOX (mFOLFIRINOX). Tumor response was assessed every eight weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), safety and biomarker studies.
Results
A total of 129 patients (65 SLOG, 64 mFOLFIRINOX) were enrolled. After a median follow-up of 37.7 months, no significant differences were observed between the SLOG and mFOLFIRINOX arms in median PFS (7.5 vs. 6.5 months; p = 0.88), median OS (12.9 vs. 12.1 months), or objective response rate (38.5 % vs. 26.6 %). HRD (homologous recombination deficiency) mutations were found in 14 of 108 profiled patients (12.9 %). Patients with HRD mutations had significantly longer median PFS (11.9 vs. 7.0 months; p = 0.008) and OS (17.7 vs. 11.7 months; p = 0.036). The safety profiles differed: grade 3/4 neutropenia was significantly less common with SLOG (15.4 % vs. 53.1 %; p < 0.001), while SLOG had more grade 3/4 non-hematological toxicities.
Conclusion
SLOG did not demonstrate superiority in PFS over mFOLFIRINOX, and mFOLFIRINOX therefore remains as one of the preferred first-line standards. Given its lower incidence of severe neutropenia and its convenience with oral S-1, SLOG may warrant further investigation in selected Asian patients with advanced PDAC.
{"title":"SLOG versus modified FOLFIRINOX as first-line treatment for advanced pancreatic cancer: A randomized phase II trial (TCOG T5217)","authors":"Nai-Jung Chiang , Yung-Yeh Su , I.-Wei Ho , Li-Yuan Bai , Chung-Pin Li , Jen-Shi Chen , Chin-Fu Hsiao , Hsiao-Hui Tsou , Chiun Hsu , Tai-Jan Chiu , Yao-Yu Hsieh , Kun-Ming Rau , Ching-Liang Ho , Yan-Shen Shan , Li-Tzong Chen","doi":"10.1016/j.ejca.2026.116229","DOIUrl":"10.1016/j.ejca.2026.116229","url":null,"abstract":"<div><h3>Objective</h3><div>A multicenter, randomized phase II trial to compare two first-line triplet treatments for advanced pancreatic ductal adenocarcinoma (PDAC).</div></div><div><h3>Methods</h3><div>Patients with histologically confirmed advanced PDAC were randomized 1:1 to receive S-1/leucovorin plus oxaliplatin, and gemcitabine (SLOG) or modified FOLFIRINOX (mFOLFIRINOX). Tumor response was assessed every eight weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), safety and biomarker studies.</div></div><div><h3>Results</h3><div>A total of 129 patients (65 SLOG, 64 mFOLFIRINOX) were enrolled. After a median follow-up of 37.7 months, no significant differences were observed between the SLOG and mFOLFIRINOX arms in median PFS (7.5 vs. 6.5 months; p = 0.88), median OS (12.9 vs. 12.1 months), or objective response rate (38.5 % vs. 26.6 %). HRD (homologous recombination deficiency) mutations were found in 14 of 108 profiled patients (12.9 %). Patients with HRD mutations had significantly longer median PFS (11.9 vs. 7.0 months; p = 0.008) and OS (17.7 vs. 11.7 months; p = 0.036). The safety profiles differed: grade 3/4 neutropenia was significantly less common with SLOG (15.4 % vs. 53.1 %; p < 0.001), while SLOG had more grade 3/4 non-hematological toxicities.</div></div><div><h3>Conclusion</h3><div>SLOG did not demonstrate superiority in PFS over mFOLFIRINOX, and mFOLFIRINOX therefore remains as one of the preferred first-line standards. Given its lower incidence of severe neutropenia and its convenience with oral S-1, SLOG may warrant further investigation in selected Asian patients with advanced PDAC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116229"},"PeriodicalIF":7.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035752","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 : 2026-01-10DOI: 10.1016/j.ejca.2026.116228
Goh Eun Chung , Su Jong Yu , Jeayeon Park , Yoon Jun Kim , Jung-Hwan Yoon , Kyungdo Han , Eun Ju Cho
Background
Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent among young adults and may contribute to cancer development. However, the impact of longitudinal changes in MASLD status on cancer risk remains unclear. This study aimed to evaluate the association between changes in MASLD status and subsequent cancer incidence in young adults.
Methods
Adults aged 20–39 years who underwent two consecutive health screening examinations—one between 2009–2012 and another between 2011–2014—were identified from the Korean National Health Insurance Service database. Participants were classified into four groups based on changes in MASLD status: non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for the development of cancer.
Results
During a median follow-up of 10.6 years, 95,666 (2.7 %) of 3536,172 participants developed cancer. Compared with the non-MASLD group, the persistent MASLD group exhibited the highest overall cancer risk (HR = 1.15; 95 % CI = 1.13–1.18), followed by the incident MASLD group (HR = 1.03; 95 % CI = 1.00–1.06). The resolved MASLD group showed no significant difference in cancer risk (HR = 1.02; 95 % CI = 0.98–1.05). Persistent MASLD was further associated with elevated risks of laryngeal, biliary, renal, hepatic, pancreatic, and colorectal cancers. Among women, persistent MASLD was linked to higher risks of uterine corpus, cervical, and ovarian cancers.
Conclusions
Incident and persistent MASLD in young adults are associated with increased overall and site-specific cancer risks, whereas individuals whose MASLD improved showed no significant excess risk. Early identification and management of MASLD may help reduce future cancer burden.
代谢功能障碍相关的脂肪变性肝病（MASLD）在年轻人中越来越普遍，并可能导致癌症的发展。然而，MASLD状态的纵向变化对癌症风险的影响尚不清楚。本研究旨在评估年轻成人中MASLD状态变化与随后癌症发病率之间的关系。方法从韩国国民健康保险服务数据库中确定年龄在20-39岁的成年人，他们分别在2009-2012年和2011 - 2014年连续进行了两次健康筛查检查。参与者根据MASLD状态的变化分为四组：非MASLD、解决MASLD、事件MASLD和持续MASLD。采用Cox比例风险模型计算癌症发展的校正风险比（hr）和95% %置信区间（CIs）。在中位随访10.6年期间，3536,172名参与者中有95,666人（2.7% %）患上了癌症。与非MASLD组相比，持续性MASLD组的总体癌症风险最高（HR = 1.15; 95 % CI = 1.13-1.18），其次是偶发性MASLD组（HR = 1.03; 95 % CI = 1.00-1.06）。解决MASLD组的癌症风险无显著差异（HR = 1.02; 95 % CI = 0.98-1.05）。持续的MASLD与喉癌、胆癌、肾癌、肝癌、胰腺癌和结直肠癌的风险升高进一步相关。在女性中，持续的MASLD与子宫癌、宫颈癌和卵巢癌的高风险相关。结论：年轻成人的偶发性和持续性MASLD与整体和部位特异性癌症风险增加相关，而MASLD改善的个体没有明显的额外风险。早期发现和管理MASLD可能有助于减少未来的癌症负担。
{"title":"Associations between changes in MASLD status and cancer development in young adults: A nationwide cohort study","authors":"Goh Eun Chung , Su Jong Yu , Jeayeon Park , Yoon Jun Kim , Jung-Hwan Yoon , Kyungdo Han , Eun Ju Cho","doi":"10.1016/j.ejca.2026.116228","DOIUrl":"10.1016/j.ejca.2026.116228","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent among young adults and may contribute to cancer development. However, the impact of longitudinal changes in MASLD status on cancer risk remains unclear. This study aimed to evaluate the association between changes in MASLD status and subsequent cancer incidence in young adults.</div></div><div><h3>Methods</h3><div>Adults aged 20–39 years who underwent two consecutive health screening examinations—one between 2009–2012 and another between 2011–2014—were identified from the Korean National Health Insurance Service database. Participants were classified into four groups based on changes in MASLD status: non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for the development of cancer.</div></div><div><h3>Results</h3><div>During a median follow-up of 10.6 years, 95,666 (2.7 %) of 3536,172 participants developed cancer. Compared with the non-MASLD group, the persistent MASLD group exhibited the highest overall cancer risk (HR = 1.15; 95 % CI = 1.13–1.18), followed by the incident MASLD group (HR = 1.03; 95 % CI = 1.00–1.06). The resolved MASLD group showed no significant difference in cancer risk (HR = 1.02; 95 % CI = 0.98–1.05). Persistent MASLD was further associated with elevated risks of laryngeal, biliary, renal, hepatic, pancreatic, and colorectal cancers. Among women, persistent MASLD was linked to higher risks of uterine corpus, cervical, and ovarian cancers.</div></div><div><h3>Conclusions</h3><div>Incident and persistent MASLD in young adults are associated with increased overall and site-specific cancer risks, whereas individuals whose MASLD improved showed no significant excess risk. Early identification and management of MASLD may help reduce future cancer burden.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116228"},"PeriodicalIF":7.1,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950247","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 : 2026-01-09DOI: 10.1016/j.ejca.2026.116227
Alice Boilève , Léa Mercier , Baptiste Bonnet , Anthony Tarabay , Sarah Blanchet-Deverly , Antoine Hollebecque , Cristina Smolenschi , Marine Valéry , Matthieu Delaye , Thomas Pudlarz , Alina Fuerea , Valérie Boige , Jérome Durand-Labrunie , Maximiliano Gelli , Paul Beunon , Rémy Barbe , Aurélien Lambert , Michel Ducreux
Background
A better prognosis is suggested for lung-only metastases patients with pancreatic ductal adenocarcinoma (PDAC), yet biological/clinical underpinnings of organotropism in PDAC remain unclear. Study objective was to compare PDAC patients depending on their metastatic site with a special focus on “lung-only” metastases patients.
Methods
A retrospective analysis included all patients with metastatic PDAC between 2010 and 2022 in an academic-center. Lung-only patients were defined as patients with only lung metastases at diagnosis of metastases.
Results
Among 1012 patients, 109 (11 %) presented lung-only metastases, 506 patients (50 %) liver-only, 94 (9 %) peritoneal-only and 303 (30 %) other or multiple sites. Compared with others, lung-only patients were more frequently female (63 % vs. 46 %), older at metastatic diagnosis (median 66 vs. 63 years, p = 0.01), and less likely to have synchronous metastases (42 % vs. 69 %, p < 0.001).
ctDNA detection was lower in the lung-only group with less KRAS mutations and TP53 mutations detected with liquid biopsy (but no difference was observed using tumor tissue). Median OS was higher in the lung-only group with 28.7 months (95 %CI [23.3–38.6]) vs 13.5 months (95 %CI [12.4–14.6]) for liver-only group, 11.5 months (95 %CI [9.6–16.9]) for peritoneal-only group and 11.3 months (95 %CI [10.0–13.8]) for other patients (p < 0.0001). Among lung-only patients, local treatments (n = 15) had a positive prognostic impact.
Conclusions
Patients with lung-only metastases had a better OS than others, were more often women, and harbored less KRAS mutations. Our results argue in favor of PDAC with specific characteristics, especially a better prognosis, possibly further enhanced by the possibility to perform local treatments, and less detection of ctDNA.
{"title":"Lung-only metastatic pancreatic cancer: Differences in patients ‘characteristics, molecular profile and survival","authors":"Alice Boilève , Léa Mercier , Baptiste Bonnet , Anthony Tarabay , Sarah Blanchet-Deverly , Antoine Hollebecque , Cristina Smolenschi , Marine Valéry , Matthieu Delaye , Thomas Pudlarz , Alina Fuerea , Valérie Boige , Jérome Durand-Labrunie , Maximiliano Gelli , Paul Beunon , Rémy Barbe , Aurélien Lambert , Michel Ducreux","doi":"10.1016/j.ejca.2026.116227","DOIUrl":"10.1016/j.ejca.2026.116227","url":null,"abstract":"<div><h3>Background</h3><div>A better prognosis is suggested for lung-only metastases patients with pancreatic ductal adenocarcinoma (PDAC), yet biological/clinical underpinnings of organotropism in PDAC remain unclear. Study objective was to compare PDAC patients depending on their metastatic site with a special focus on “lung-only” metastases patients.</div></div><div><h3>Methods</h3><div>A retrospective analysis included all patients with metastatic PDAC between 2010 and 2022 in an academic-center. Lung-only patients were defined as patients with only lung metastases at diagnosis of metastases.</div></div><div><h3>Results</h3><div>Among 1012 patients, 109 (11 %) presented lung-only metastases, 506 patients (50 %) liver-only, 94 (9 %) peritoneal-only and 303 (30 %) other or multiple sites. Compared with others, lung-only patients were more frequently female (63 % vs. 46 %), older at metastatic diagnosis (median 66 vs. 63 years, p = 0.01), and less likely to have synchronous metastases (42 % vs. 69 %, p < 0.001).</div><div>ctDNA detection was lower in the lung-only group with less <em>KRAS</em> mutations and <em>TP53</em> mutations detected with liquid biopsy (but no difference was observed using tumor tissue). Median OS was higher in the lung-only group with 28.7 months (95 %CI [23.3–38.6]) vs 13.5 months (95 %CI [12.4–14.6]) for liver-only group, 11.5 months (95 %CI [9.6–16.9]) for peritoneal-only group and 11.3 months (95 %CI [10.0–13.8]) for other patients (p < 0.0001). Among lung-only patients, local treatments (n = 15) had a positive prognostic impact.</div></div><div><h3>Conclusions</h3><div>Patients with lung-only metastases had a better OS than others, were more often women, and harbored less <em>KRAS</em> mutations. Our results argue in favor of PDAC with specific characteristics, especially a better prognosis, possibly further enhanced by the possibility to perform local treatments, and less detection of ctDNA.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116227"},"PeriodicalIF":7.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975634","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 : 2026-01-09DOI: 10.1016/j.ejca.2026.116226
Veronika I. Engele , Vassilios Vassiliou , Sally Wheelwright , Monika Sztankay , Chiara Puglisi , Katarzyna Pogoda , Rachel van Leeuwaarde , Eveline Bleiker , Hikmat Abdel-Razeq , Louis Fox , Anne Lanceley , Sandrine Dabakuyo , Vesna Bjelic-Radisic , Andrew Nordin , Georgios Ioannidis , Dagmara Kulís , Anne Brédart , Gunda Schwaninger , Juan I. Arraras , Bernhard Holzner , Anne S. Oberguggenberger
Background
The aim of this study is to develop a European Organisation of Research and Treatment of Cancer (EORTC) patient-reported outcome measure (PROM) to assess quality of life (QOL) in individuals diagnosed with a hereditary cancer predisposition syndrome (HCPS) with or without a previous cancer diagnosis. We report on content generation, questionnaire construction, and questionnaire evaluation of acceptability, comprehensiveness, and linguistic validity.
Methods
Following phase 1–3a of the EORTC Quality of Life Group module development guidelines, QOL issues were identified through a literature review and interviews with health-care professionals and individuals undergoing HCPS genetic counseling or testing. Based upon the results, a preliminary questionnaire was developed and pre-tested internationally for relevance, clarity, and linguistic appropriateness. Revisions were guided by qualitative feedback and predefined criteria.
Results
63 issues were identified from the literature and expanded to a 73-item questionnaire through interviews. Pre-testing of the questionnaire in 119 individuals (79.8 % female) across twelve centers in nine countries, including carriers of BRCA, Lynch syndrome, and Li-Fraumeni, showed limited applicability for those with negative or pending results. The target population was therefore refined to mutation carriers. Following item reduction, the final instrument comprised thirty validated and linguistically appropriate items.
Conclusion
The EORTC QLQ-HCR30 is relevant and applicable for assessing QOL in individuals diagnosed with a HCPS and is now ready for preliminary psychometric evaluation (phase 3b and 4).
{"title":"Assessing quality of life in individuals with hereditary cancer risk: Results from phases 1–3a of the EORTC QLQ-HCR30 questionnaire","authors":"Veronika I. Engele , Vassilios Vassiliou , Sally Wheelwright , Monika Sztankay , Chiara Puglisi , Katarzyna Pogoda , Rachel van Leeuwaarde , Eveline Bleiker , Hikmat Abdel-Razeq , Louis Fox , Anne Lanceley , Sandrine Dabakuyo , Vesna Bjelic-Radisic , Andrew Nordin , Georgios Ioannidis , Dagmara Kulís , Anne Brédart , Gunda Schwaninger , Juan I. Arraras , Bernhard Holzner , Anne S. Oberguggenberger","doi":"10.1016/j.ejca.2026.116226","DOIUrl":"10.1016/j.ejca.2026.116226","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study is to develop a European Organisation of Research and Treatment of Cancer (EORTC) patient-reported outcome measure (PROM) to assess quality of life (QOL) in individuals diagnosed with a hereditary cancer predisposition syndrome (HCPS) with or without a previous cancer diagnosis. We report on content generation, questionnaire construction, and questionnaire evaluation of acceptability, comprehensiveness, and linguistic validity.</div></div><div><h3>Methods</h3><div>Following phase 1–3a of the EORTC Quality of Life Group module development guidelines, QOL issues were identified through a literature review and interviews with health-care professionals and individuals undergoing HCPS genetic counseling or testing. Based upon the results, a preliminary questionnaire was developed and pre-tested internationally for relevance, clarity, and linguistic appropriateness. Revisions were guided by qualitative feedback and predefined criteria.</div></div><div><h3>Results</h3><div>63 issues were identified from the literature and expanded to a 73-item questionnaire through interviews. Pre-testing of the questionnaire in 119 individuals (79.8 % female) across twelve centers in nine countries, including carriers of BRCA, Lynch syndrome, and Li-Fraumeni, showed limited applicability for those with negative or pending results. The target population was therefore refined to mutation carriers. Following item reduction, the final instrument comprised thirty validated and linguistically appropriate items.</div></div><div><h3>Conclusion</h3><div>The EORTC QLQ-HCR30 is relevant and applicable for assessing QOL in individuals diagnosed with a HCPS and is now ready for preliminary psychometric evaluation (phase 3b and 4).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116226"},"PeriodicalIF":7.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975636","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 : 2026-01-09DOI: 10.1016/j.ejca.2026.116225
Emilie Le Rhun , Debaleena Sain , Martin van den Bent , Enrico Franceschi , Ghazaleh Tabatabai , Wolfgang Wick , Matthias Preusser , Thierry Gorlia , Michael Weller
Background
The use of proton pump inhibitors with strong aldehyde dehydrogenase 1A1-activating properties (PA-PPI) has recently been associated with inferior outcomes in patients with newly diagnosed glioblastoma. While the mechanisms mediating such outcome associations remain incompletely understood, no such data have been generated for patients with recurrent glioblastoma.
Materials and Methods
We conducted a pooled analysis of four clinical trials in the setting of first recurrence of glioblastoma: DIRECTOR (NCT00941460), EORTC 1410 (NCT02343406), EORTC 1608 (arm C) (NCT03224104), and EORTC 26034 (NCT00086879). We assessed PA-PPI use at baseline and at two defined landmarks, week 8 and week 16. Cox models were used to identify associations of PA-PPI use with outcome.
Results
On univariate analysis, PA-PPI use was associated with inferior overall survival, but not progression-free survival, at baseline and at both landmarks. However, PA-PPI use was no longer prognostic in multivariable analyses controlling for major prognostic factors. Omission of distinct prognostic factors from the multivariate Cox models revealed that steroid use made PA-PPI use insignificant. Indeed, PA-PPI use was associated with steroid use.
Discussion
The present analysis of prognostic outcome associations of PA-PPI use in patients with recurrent glioblastoma provides no evidence that PA-PPI use may compromise outcome in this setting. The disconnect between clear outcome associations in the first-line setting, without a link to MGMT promoter methylation, versus no associations in the recurrent setting may be linked to changing prescriptions patterns, but requires further studies. Since alternative medications are available, the indications for PA-PPI prescription should probably be narrowed in patients with glioblastoma.
{"title":"Association of proton pump inhibitor use with outcome of patients with recurrent glioblastoma","authors":"Emilie Le Rhun , Debaleena Sain , Martin van den Bent , Enrico Franceschi , Ghazaleh Tabatabai , Wolfgang Wick , Matthias Preusser , Thierry Gorlia , Michael Weller","doi":"10.1016/j.ejca.2026.116225","DOIUrl":"10.1016/j.ejca.2026.116225","url":null,"abstract":"<div><h3>Background</h3><div>The use of proton pump inhibitors with strong aldehyde dehydrogenase 1A1-activating properties (PA-PPI) has recently been associated with inferior outcomes in patients with newly diagnosed glioblastoma. While the mechanisms mediating such outcome associations remain incompletely understood, no such data have been generated for patients with recurrent glioblastoma.</div></div><div><h3>Materials and Methods</h3><div>We conducted a pooled analysis of four clinical trials in the setting of first recurrence of glioblastoma: DIRECTOR (NCT00941460), EORTC 1410 (NCT02343406), EORTC 1608 (arm C) (NCT03224104), and EORTC 26034 (NCT00086879). We assessed PA-PPI use at baseline and at two defined landmarks, week 8 and week 16. Cox models were used to identify associations of PA-PPI use with outcome.</div></div><div><h3>Results</h3><div>On univariate analysis, PA-PPI use was associated with inferior overall survival, but not progression-free survival, at baseline and at both landmarks. However, PA-PPI use was no longer prognostic in multivariable analyses controlling for major prognostic factors. Omission of distinct prognostic factors from the multivariate Cox models revealed that steroid use made PA-PPI use insignificant. Indeed, PA-PPI use was associated with steroid use.</div></div><div><h3>Discussion</h3><div>The present analysis of prognostic outcome associations of PA-PPI use in patients with recurrent glioblastoma provides no evidence that PA-PPI use may compromise outcome in this setting. The disconnect between clear outcome associations in the first-line setting, without a link to <em>MGMT</em> promoter methylation, versus no associations in the recurrent setting may be linked to changing prescriptions patterns, but requires further studies. Since alternative medications are available, the indications for PA-PPI prescription should probably be narrowed in patients with glioblastoma.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116225"},"PeriodicalIF":7.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976093","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 : 2026-01-07DOI: 10.1016/j.ejca.2026.116223
Suriya Baskar , Rishi R. Patel , Matthew T. Gao , Brandon E. Rose , Sawyer Bawek , Deepak Vadehra , Timothy J. Brown , Nicholas J. Hornstein , Udhayvir S. Grewal
Pancreatic acinar cell carcinoma (PACC) is a rare malignancy, accounting for less than 2 % of all pancreatic cancers that exhibits distinct clinical and molecular features compared to the more common pancreatic ductal adenocarcinoma (PDAC). Historically, treatment approaches for PACC have been adapted from PDAC due to limited available prospective and/or randomized data to guide management. However, the emergence of next-generation sequencing (NGS) has revealed a unique genomic landscape in PACC, creating new opportunities for precision oncology. Unlike PDAC, PACC typically lacks KRAS, TP53, and CDKN2A mutations and instead shows alterations in the Wnt/β-catenin pathway (APC, CTNNB1), homologous recombination repair (HRR) genes (e.g., BRCA1/2, ATM), and mismatch repair (MMR) genes, which may have potential therapeutic implications. Targeted therapies have demonstrated clinical benefit in select cases, including PARP inhibitors for HRR-deficient tumors and immune checkpoint inhibitors for microsatellite instability-high (MSI-H) or MMR-deficient PACC. Additional actionable alterations such as BRAF V600E mutations, NTRK fusions, and ALK rearrangements have responded to corresponding targeted agents. Though based primarily on limited reports, these observations support the utility of comprehensive molecular profiling in guiding therapy for PACC. Universal germline testing is also recommended, given the high prevalence of germline HRR mutations and its implications for treatment and familial risk. In summary, the potential for personalized cancer therapy is promising in PACC. The integration of molecular diagnostics into clinical care is essential for identifying therapeutic targets and optimizing outcomes; continued research and participation in genomically matched clinical trials are key to advancing treatment paradigms for this rare malignancy.
{"title":"Precision oncology promise in the management of pancreatic acinar cell carcinoma","authors":"Suriya Baskar , Rishi R. Patel , Matthew T. Gao , Brandon E. Rose , Sawyer Bawek , Deepak Vadehra , Timothy J. Brown , Nicholas J. Hornstein , Udhayvir S. Grewal","doi":"10.1016/j.ejca.2026.116223","DOIUrl":"10.1016/j.ejca.2026.116223","url":null,"abstract":"<div><div>Pancreatic acinar cell carcinoma (PACC) is a rare malignancy, accounting for less than 2 % of all pancreatic cancers that exhibits distinct clinical and molecular features compared to the more common pancreatic ductal adenocarcinoma (PDAC). Historically, treatment approaches for PACC have been adapted from PDAC due to limited available prospective and/or randomized data to guide management. However, the emergence of next-generation sequencing (NGS) has revealed a unique genomic landscape in PACC, creating new opportunities for precision oncology. Unlike PDAC, PACC typically lacks <em>KRAS, TP53</em>, and <em>CDKN2A</em> mutations and instead shows alterations in the Wnt/β-catenin pathway (<em>APC, CTNNB1</em>), homologous recombination repair (HRR) genes (e.g., <em>BRCA1/2, ATM</em>), and mismatch repair (MMR) genes, which may have potential therapeutic implications. Targeted therapies have demonstrated clinical benefit in select cases, including PARP inhibitors for HRR-deficient tumors and immune checkpoint inhibitors for microsatellite instability-high (MSI-H) or MMR-deficient PACC. Additional actionable alterations such as <em>BRAF V600E</em> mutations, <em>NTRK</em> fusions, and <em>ALK</em> rearrangements have responded to corresponding targeted agents. Though based primarily on limited reports, these observations support the utility of comprehensive molecular profiling in guiding therapy for PACC. Universal germline testing is also recommended, given the high prevalence of germline HRR mutations and its implications for treatment and familial risk. In summary, the potential for personalized cancer therapy is promising in PACC. The integration of molecular diagnostics into clinical care is essential for identifying therapeutic targets and optimizing outcomes; continued research and participation in genomically matched clinical trials are key to advancing treatment paradigms for this rare malignancy.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116223"},"PeriodicalIF":7.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939726","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 : 2026-01-07DOI: 10.1016/j.ejca.2026.116221
Xinghao Ai , Renhua Guo , Liang Zhang , Jian Fang , Yiping Zhang , Jianhua Chen , Jun Zhao , Feng Ye , Shumei Wang , Meiqi Shi , Xinwei Zhang , Fang Zhang , Jiakui Li , Li Wang , Xuejie Guo , Lingmei Xu , Xianghui Duan , Yan Hu , Shun Lu
Background
To investigate the preclinical characterization of dirozalkib, a novel anaplastic lymphoma kinase (ALK) inhibitor, and its safety, pharmacokinetics, and preliminary antitumor activity in advanced non-small cell lung cancer (NSCLC).
Methods
The preclinical inhibitory effects of dirozalkib were evaluated in vitro and in vivo. The first-in-human phase I study (NCT05055232) enrolled patients with advanced NSCLC harboring ALK or ROS1 rearrangements. Participants received 50–600 mg/day dirozalkib following a 3 + 3 dose-escalation design with rapid titration, and 300–600 mg/day in the dose-expansion phase. The primary endpoint was safety.
Results
Dirozalkib demonstrated potent inhibition of ALK fusion-positive cell lines and common resistance mutations, and suppressed tumor growth in patient-derived and intracranial xenograft lung cancer models. No dose-limiting toxicities occurred, establishing 600 mg/day as the maximum tolerated dose. Among 114 patients enrolled, 55 (48.2 %) experienced grade ≥ 3 treatment-emergent adverse events, most commonly diarrhea (8.8 %). The objective response rate (ORR) among patients with ALK rearrangements was 47.4 % (9/19) and 46.3 % (38/82) in the dose-escalation and dose-expansion cohort (89.3 % in ALK inhibitor–naive patients receiving 500 mg/day). After a single dose of 50–600 mg dirozalkib, median time to maximum concentration ranged from 3 to 4 h. Cmax and area under the curve of dirozalkib increased near-dose-proportional, with a geometric mean terminal elimination half-life of 19.6–25.4 h.
Conclusions
Dirozalkib exhibited favorable safety, antitumor activity and pharmacokinetics in patients with advanced ALK-rearranged NSCLC. The recommended phase II dose was 500 mg/day.
Trial registration: Clinicaltrials.gov (NCT05055232) and Chinadrugtrials.org.cn (CTR20190984).
{"title":"Preclinical characterization and first-in-human, phase I trial of the novel ALK inhibitor dirozalkib in advanced non-small cell lung cancer","authors":"Xinghao Ai , Renhua Guo , Liang Zhang , Jian Fang , Yiping Zhang , Jianhua Chen , Jun Zhao , Feng Ye , Shumei Wang , Meiqi Shi , Xinwei Zhang , Fang Zhang , Jiakui Li , Li Wang , Xuejie Guo , Lingmei Xu , Xianghui Duan , Yan Hu , Shun Lu","doi":"10.1016/j.ejca.2026.116221","DOIUrl":"10.1016/j.ejca.2026.116221","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the preclinical characterization of dirozalkib, a novel anaplastic lymphoma kinase (ALK) inhibitor, and its safety, pharmacokinetics, and preliminary antitumor activity in advanced non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>The preclinical inhibitory effects of dirozalkib were evaluated in vitro and in vivo. The first-in-human phase I study (NCT05055232) enrolled patients with advanced NSCLC harboring ALK or ROS1 rearrangements. Participants received 50–600 mg/day dirozalkib following a 3 + 3 dose-escalation design with rapid titration, and 300–600 mg/day in the dose-expansion phase. The primary endpoint was safety.</div></div><div><h3>Results</h3><div>Dirozalkib demonstrated potent inhibition of ALK fusion-positive cell lines and common resistance mutations, and suppressed tumor growth in patient-derived and intracranial xenograft lung cancer models. No dose-limiting toxicities occurred, establishing 600 mg/day as the maximum tolerated dose. Among 114 patients enrolled, 55 (48.2 %) experienced grade ≥ 3 treatment-emergent adverse events, most commonly diarrhea (8.8 %). The objective response rate (ORR) among patients with ALK rearrangements was 47.4 % (9/19) and 46.3 % (38/82) in the dose-escalation and dose-expansion cohort (89.3 % in ALK inhibitor–naive patients receiving 500 mg/day). After a single dose of 50–600 mg dirozalkib, median time to maximum concentration ranged from 3 to 4 h. C<sub>max</sub> and area under the curve of dirozalkib increased near-dose-proportional, with a geometric mean terminal elimination half-life of 19.6–25.4 h.</div></div><div><h3>Conclusions</h3><div>Dirozalkib exhibited favorable safety, antitumor activity and pharmacokinetics in patients with advanced ALK-rearranged NSCLC. The recommended phase II dose was 500 mg/day.</div><div><strong>Trial registration:</strong> Clinicaltrials.gov <strong>(</strong>NCT05055232) and Chinadrugtrials.org.cn (CTR20190984).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116221"},"PeriodicalIF":7.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975630","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}
Predicting chemosensitivity before treatment could help tailor neoadjuvant chemotherapy (NAC) in early breast cancer (eBC). Pathological complete response (pCR) is associated with better long term survival, but yet no robust baseline predictor is available.
Patients and methods
We developed Chemo-prAIdict Breast, a deep learning model using whole slide images (WSIs) of diagnostic biopsies to predict residual disease (RD) after NAC. Two large French cohorts were analyzed (n = 1140 initially included, 928 analyzed after selection): the prospective multicenter PRIMUNEO cohort (n = 500, 438 after selection) for training and internal validation, and the CGFL retrospective cohort (n = 640, 490 after selection) for independent external validation. Patients were stratified by molecular subtype: HER2-amplified (HER2 +), ER-positive/HER2-negative (ER+/HER2 −), and triple-negative (TN).
Results
In external validation, Chemo-prAIdict Breast outperformed standard clinicopathological features, achieving AUCs of 0.652 (p = 0.001) in HER2 + , 0.814 (p = 0.003) in ER+ /HER2 −, and 0.677 (p = 0.001) in TN tumors. Robustness was confirmed using paired consecutive biopsy sections from 421 patients: predictions were strongly correlated within patients (Pearson r = 0.933 for HER2 +, 0.932 for ER+/HER2 −, 0.939 for TN; all p < 0.001).
Conclusions
While prospective studies with modern treatment regimens are needed to establish clinical utility, Chemo-prAIdict Breast is a new tool for identifying eBC that are differentially sensitive to standard NAC, and could help to select the most appropriate treatment strategy in HER2 + , ER+ /HER2- and TN eBC.
{"title":"Chemo-prAIdict Breast: A deep learning solution for predicting residual disease on biopsies of breast cancer patients treated with neoadjuvant chemotherapy","authors":"Natalia Fernanda Valderrama , Louis-Oscar Morel , Daniel Tshokola Mweze , Valentin Derangère , Isabelle Desmoulins , Didier Mayeur , Courèche Kaderbhai , Silvia Ilie , Audrey Hennequin , Nicolas Roussot , Antony Bergeron , Françoise Beltjens , Carlo Pescia , Henri-Philippe Morel , Charles Coutant , Jens Rittscher , Laurent Arnould , Nathan Vinçon , Sylvain Ladoire","doi":"10.1016/j.ejca.2026.116222","DOIUrl":"10.1016/j.ejca.2026.116222","url":null,"abstract":"<div><h3>Background</h3><div>Predicting chemosensitivity before treatment could help tailor neoadjuvant chemotherapy (NAC) in early breast cancer (eBC). Pathological complete response (pCR) is associated with better long term survival, but yet no robust baseline predictor is available.</div></div><div><h3>Patients and methods</h3><div>We developed Chemo-prAIdict Breast, a deep learning model using whole slide images (WSIs) of diagnostic biopsies to predict residual disease (RD) after NAC. Two large French cohorts were analyzed (n = 1140 initially included, 928 analyzed after selection): the prospective multicenter PRIMUNEO cohort (n = 500, 438 after selection) for training and internal validation, and the CGFL retrospective cohort (n = 640, 490 after selection) for independent external validation. Patients were stratified by molecular subtype: HER2-amplified (HER2 +), ER-positive/HER2-negative (ER+/HER2 −), and triple-negative (TN).</div></div><div><h3>Results</h3><div>In external validation, <em>Chemo-prAIdict Breast</em> outperformed standard clinicopathological features, achieving AUCs of 0.652 (p = 0.001) in HER2 + , 0.814 (p = 0.003) in ER+ /HER2 −, and 0.677 (p = 0.001) in TN tumors. Robustness was confirmed using paired consecutive biopsy sections from 421 patients: predictions were strongly correlated within patients (Pearson r = 0.933 for HER2 +, 0.932 for ER+/HER2 −, 0.939 for TN; all p < 0.001).</div></div><div><h3>Conclusions</h3><div>While prospective studies with modern treatment regimens are needed to establish clinical utility, <em>Chemo-prAIdict Breast</em> is a new tool for identifying eBC that are differentially sensitive to standard NAC, and could help to select the most appropriate treatment strategy in HER2 + , ER+ /HER2- and TN eBC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116222"},"PeriodicalIF":7.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939725","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 : 2025-12-26DOI: 10.1016/j.ejca.2025.116202
J.C. Janssen , A.W. Schurink , C. Verhoef , E. Oomen-de Hoop , M.W.J. Louwman , D.J. Grünhagen , A.A.M. van der Veldt
Background
Adjuvant systemic therapy for resected stage III melanoma was introduced in clinical practice following the improved recurrence free survival in randomized controlled trials. However, after ten years of follow-up, adjuvant treatment with dabrafenib plus trametinib did not result in a significant improvement in overall survival (OS). Currently, OS data for adjuvant anti-PD1 therapy are still pending.
Methods
In this retrospective nationwide population-based study, the 4-year OS was compared between patients who were diagnosed with stage III melanoma before and after the introduction of adjuvant therapy in the Netherlands. Propensity score matching (PSM) for age, sex, and four melanoma substages (IIIA-D) was applied to ensure comparability between the pre-adjuvant cohort, comprising patients diagnosed in 2015–2017, and the post-adjuvant cohort with patients diagnosed in 2019–2020.
Results
A total of 2651 patients with stage III melanoma were included. The median follow-up for patients without an event was 89 months for the pre-adjuvant cohort and 49 months for the post-adjuvant cohort. After PSM, both cohorts consisted of 1215 patients. The 4-year OS rate was comparable between the pre-adjuvant and post-adjuvant adjuvant cohort (71.2 % vs. 73.8 %, HR=0.90, 95 % CI: 0.77–1.04). No significant difference in OS was observed between cohorts for the different substages of melanoma.
Discussion
This population-based analysis of patients with stage III melanoma demonstrated no significant 4-year OS benefit after the introduction of adjuvant therapy. Pending the OS results of the randomized trials, the potential benefits and risks of adjuvant therapy should be carefully weighed for patients with stage III melanoma.
背景：在随机对照试验中，随着无复发生存率的提高，辅助全身治疗被引入临床实践。然而，经过10年的随访，达非尼加曲美替尼的辅助治疗并没有导致总生存期（OS）的显著改善。目前，辅助抗pd1治疗的OS数据仍未公布。方法：在这项基于全国人群的回顾性研究中，比较了荷兰引入辅助治疗前后诊断为III期黑色素瘤患者的4年OS。使用年龄、性别和四个黑色素瘤亚期（IIIA-D）的倾向评分匹配（PSM）来确保2015-2017年诊断的辅助前队列与2019-2020年诊断的辅助后队列之间的可比性。结果：共纳入2651例III期黑色素瘤患者。无事件患者的中位随访时间在辅助治疗前为89个月，在辅助治疗后为49个月。在PSM后，两个队列包括1215名患者。辅助治疗前和辅助治疗后的4年OS率相当（71.2 % vs. 73.8 %，HR=0.90, 95 % CI: 0.77-1.04）。不同亚阶段黑色素瘤的OS在队列之间没有显著差异。讨论：这项基于人群的III期黑色素瘤患者分析显示，在引入辅助治疗后，4年生存率无显著改善。在随机试验的OS结果公布之前，应该仔细权衡III期黑色素瘤患者辅助治疗的潜在益处和风险。
{"title":"4-year overall survival after the introduction of adjuvant therapy for patients with stage III melanoma: A population-based study","authors":"J.C. Janssen , A.W. Schurink , C. Verhoef , E. Oomen-de Hoop , M.W.J. Louwman , D.J. Grünhagen , A.A.M. van der Veldt","doi":"10.1016/j.ejca.2025.116202","DOIUrl":"10.1016/j.ejca.2025.116202","url":null,"abstract":"<div><h3>Background</h3><div>Adjuvant systemic therapy for resected stage III melanoma was introduced in clinical practice following the improved recurrence free survival in randomized controlled trials. However, after ten years of follow-up, adjuvant treatment with dabrafenib plus trametinib did not result in a significant improvement in overall survival (OS). Currently, OS data for adjuvant anti-PD1 therapy are still pending.</div></div><div><h3>Methods</h3><div>In this retrospective nationwide population-based study, the 4-year OS was compared between patients who were diagnosed with stage III melanoma before and after the introduction of adjuvant therapy in the Netherlands. Propensity score matching (PSM) for age, sex, and four melanoma substages (IIIA-D) was applied to ensure comparability between the pre-adjuvant cohort, comprising patients diagnosed in 2015–2017, and the post-adjuvant cohort with patients diagnosed in 2019–2020.</div></div><div><h3>Results</h3><div>A total of 2651 patients with stage III melanoma were included. The median follow-up for patients without an event was 89 months for the pre-adjuvant cohort and 49 months for the post-adjuvant cohort. After PSM, both cohorts consisted of 1215 patients. The 4-year OS rate was comparable between the pre-adjuvant and post-adjuvant adjuvant cohort (71.2 % <em>vs.</em> 73.8 %, HR=0.90, 95 % CI: 0.77–1.04). No significant difference in OS was observed between cohorts for the different substages of melanoma.</div></div><div><h3>Discussion</h3><div>This population-based analysis of patients with stage III melanoma demonstrated no significant 4-year OS benefit after the introduction of adjuvant therapy. Pending the OS results of the randomized trials, the potential benefits and risks of adjuvant therapy should be carefully weighed for patients with stage III melanoma.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116202"},"PeriodicalIF":7.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877663","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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