Pub Date : 2025-12-19DOI: 10.1016/j.ejca.2025.116195
Noah Zimmermann , Julian Kött , Tim Zell , Ali Zeinal Abedini , Chiara L. Blomen , Stella Belz , Benjamin Deitert , Isabel Heidrich , Glenn Geidel , Alessandra Rünger , Daniel J. Smit , Michael Weichenthal , Selma Ugurel , Ulrike Leiter , Carola Berking , Ralf Gutzmer , Dirk Schadendorf , Imke von Wasielewski , Peter Mohr , Friedegund Meier , Christoffer Gebhardt
Background
Targeted therapies (TT) improve outcomes in BRAF-mutant melanoma. Pre-clinical data suggest that anticoagulation (AC) and platelet aggregation inhibition (PAI) may have antitumoral effects. We evaluated the impact of concomitant AC or PAI on outcomes in patients receiving TT.
Methods
We analyzed 1296 patients with unresectable stage III-IV BRAF-mutant melanoma treated with BRAF plus MEK inhibitors (2016–2024) in the prospective multicenter ADOReg registry. Patients were categorized as receiving no antithrombotic therapy (ATT; n = 1125), PAI (n = 73; acetylsalicylic acid or clopidogrel), or AC (n = 98; direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonists).
Results
Median follow-up was 1.3 years. Compared with patients without ATT, those receiving AC had significantly improved 12-month progression-free survival (PFS; HR 0.55, 95 % CI 0.39–0.78, p = 0.001) and overall survival (OS; HR 0.35, 95 % CI 0.19–0.64, p = 0.001). Direct oral anticoagulants showed the most pronounced PFS benefit (HR 0.40, 95 % CI 0.25–0.64, p < 0.001). PAI was not associated with a significant difference in PFS, but multivariable Cox regression indicated a reduced hazard of death (HR 0.48, 95 % CI 0.27–0.87, p = 0.015).
Conclusion
Concomitant AC, particularly factor Xa-inhibiting direct oral anticoagulants, was associated with improved survival in melanoma patients undergoing TT. These findings support prospective trials evaluating AC as concomitant therapy in advanced melanoma.
背景:靶向治疗(TT)改善braf突变黑色素瘤的预后。临床前数据表明抗凝(AC)和血小板聚集抑制(PAI)可能具有抗肿瘤作用。我们评估了合并AC或PAI对接受TT患者预后的影响。方法:我们在前瞻性多中心ADOReg注册中分析了1296例不可切除的BRAF- iv期突变黑色素瘤患者,这些患者接受BRAF + MEK抑制剂治疗(2016-2024)。患者被分类为未接受抗血栓治疗(ATT; n = 1125)、PAI (n = 73;乙酰水杨酸或氯吡格雷)或AC (n = 98;直接口服抗凝剂、低分子肝素或维生素K拮抗剂)。结果:中位随访时间为1.3年。与没有ATT的患者相比,接受AC治疗的患者12个月无进展生存期(PFS; HR 0.55, 95% CI 0.39-0.78, p = 0.001)和总生存期(OS; HR 0.35, 95% CI 0.19-0.64, p = 0.001)显著改善。直接口服抗凝药物显示出最明显的PFS益处(HR 0.40, 95% CI 0.25-0.64, p )。结论:在接受TT治疗的黑色素瘤患者中,伴随AC治疗,尤其是抑制xa因子的直接口服抗凝药物,与生存率的提高有关。这些发现支持前瞻性试验评估AC作为晚期黑色素瘤的伴随治疗。
{"title":"Enhanced overall and progression-free survival in advanced melanoma patients undergoing targeted therapy alongside antithrombotic treatment – Insights from a multicenter study involving 1296 patients from the prospective skin cancer registry ADOReg","authors":"Noah Zimmermann , Julian Kött , Tim Zell , Ali Zeinal Abedini , Chiara L. Blomen , Stella Belz , Benjamin Deitert , Isabel Heidrich , Glenn Geidel , Alessandra Rünger , Daniel J. Smit , Michael Weichenthal , Selma Ugurel , Ulrike Leiter , Carola Berking , Ralf Gutzmer , Dirk Schadendorf , Imke von Wasielewski , Peter Mohr , Friedegund Meier , Christoffer Gebhardt","doi":"10.1016/j.ejca.2025.116195","DOIUrl":"10.1016/j.ejca.2025.116195","url":null,"abstract":"<div><h3>Background</h3><div>Targeted therapies (TT) improve outcomes in BRAF-mutant melanoma. Pre-clinical data suggest that anticoagulation (AC) and platelet aggregation inhibition (PAI) may have antitumoral effects. We evaluated the impact of concomitant AC or PAI on outcomes in patients receiving TT.</div></div><div><h3>Methods</h3><div>We analyzed 1296 patients with unresectable stage III-IV BRAF-mutant melanoma treated with BRAF plus MEK inhibitors (2016–2024) in the prospective multicenter ADOReg registry. Patients were categorized as receiving no antithrombotic therapy (ATT; n = 1125), PAI (n = 73; acetylsalicylic acid or clopidogrel), or AC (n = 98; direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonists).</div></div><div><h3>Results</h3><div>Median follow-up was 1.3 years. Compared with patients without ATT, those receiving AC had significantly improved 12-month progression-free survival (PFS; HR 0.55, 95 % CI 0.39–0.78, p = 0.001) and overall survival (OS; HR 0.35, 95 % CI 0.19–0.64, p = 0.001). Direct oral anticoagulants showed the most pronounced PFS benefit (HR 0.40, 95 % CI 0.25–0.64, p < 0.001). PAI was not associated with a significant difference in PFS, but multivariable Cox regression indicated a reduced hazard of death (HR 0.48, 95 % CI 0.27–0.87, p = 0.015).</div></div><div><h3>Conclusion</h3><div>Concomitant AC, particularly factor Xa-inhibiting direct oral anticoagulants, was associated with improved survival in melanoma patients undergoing TT. These findings support prospective trials evaluating AC as concomitant therapy in advanced melanoma.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116195"},"PeriodicalIF":7.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833441","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 : 2025-12-19DOI: 10.1016/j.ejca.2025.116194
Maria Vittoria Dieci , Grazia Vernaci , Chiara Colangelo , Emilio Bria , Davide Massa , Elisabetta Di Liso , Carlo Alberto Giorgi , Tommaso Giarratano , Davide Napetti , Giorgio Bonomi , Francesca Zanghì , Michele Bottosso , Elisabetta Lazzarini , Laura Santarelli , Andrea Boscolo Bragadin , Stefano Indraccolo , Valentina Guarneri
Background
Outcomes and characteristics of endocrine-resistant, PIK3CA-mutated HR+ /HER2- advanced breast cancer patients in real-world are poorly investigated.
Here, we explored the role of circulating PIK3CA mutations in endocrine-resistant patients in the ongoing prospective, multicentric CHAMBER study.
Methods
PIK3CA was analyzed by NGS panel covering the full exonic region of PIK3CA gene.
Endocrine resistance was defined as: i) primary: relapse during the first 2 years of adjuvant ET, or ii) secondary: relapse after 2 years of starting or within 1 year of completing ET.
Overall survival (OS) was calculated from the start of first-line to death from any cause. Progression free survival 1 (PFS1) was calculated from the start of first-line to progression or death.
Results
Among the overall CHAMBER population, 22 % patients met the criteria for endocrine-resistance (74/337).
The study population consisted in 95 % women and 5 % men; median age at diagnosis was 50 years (IQR 44–63); 75 % of the women was postmenopausal;86 % of the total population presented with a secondary endocrine-resistance, 64 % had visceral relapse, 74 % had less than 3 metastatic sites, 79 % had received first-line CDK4/6 inhibitor.
PIK3CA status was available for 63/74 pts, with a 29 % prevalence of mutation.
PIK3CAmut was a negative prognostic factor for OS (median 65 [wt] vs 36 months [mut], log-rank p 0.024 HR 2.61 [95 % CI 1.10–6.22]) and PFS1 (median 22 [wt] vs 10 months [mut], log-rank p 0.012, HR 2.24 [95 % CI 1.18–4.26]).
Conclusion
The co-occurrence of endocrine-resistance and PIK3CAmut identifies a population with unfavorable prognosis, reinforcing the rationale of escalated therapies.
现实世界中,内分泌抵抗、pik3ca突变的HR+ /HER2晚期乳腺癌患者的结局和特征研究很少。在这里,我们在正在进行的前瞻性多中心CHAMBER研究中探讨了循环PIK3CA突变在内分泌抵抗患者中的作用。方法采用覆盖PIK3CA基因全外显子区域的NGS面板对spik3ca进行分析。内分泌抵抗被定义为:i)原发性:在辅助ET治疗的前2年内复发,或ii)继发性:在开始ET治疗后2年或完成ET治疗后1年内复发。总生存期(OS)从一线开始计算到任何原因死亡。从一线开始至进展或死亡计算无进展生存期1 (PFS1)。结果在总体CHAMBER人群中,22 %的患者符合内分泌抵抗标准(74/337)。研究人群包括95% %的女性和5% %的男性;诊断时中位年龄为50岁(IQR 44-63);75% %的妇女绝经后;86% %的患者出现继发性内分泌抵抗,64% %的患者内脏复发,74% %的患者转移部位少于3个,79% %的患者接受了一线CDK4/6抑制剂治疗。63/74名患者有PIK3CA状态,突变发生率为29% %。PIK3CAmut是OS(中位65 [wt] vs 36个月[mut], log-rank p 0.024 HR 2.61[95 % CI 1.10-6.22])和PFS1(中位22 [wt] vs 10个月[mut], log-rank p 0.012, HR 2.24[95 % CI 1.18-4.26])的负面预后因素。结论内分泌抵抗和PIK3CAmut的共同出现是一个预后不良的人群,加强了升级治疗的理由。
{"title":"PIK3CA mutations and first-line outcomes in endocrine-resistant HR+/HER2- metastatic breast cancer: A multicentric real-world study.","authors":"Maria Vittoria Dieci , Grazia Vernaci , Chiara Colangelo , Emilio Bria , Davide Massa , Elisabetta Di Liso , Carlo Alberto Giorgi , Tommaso Giarratano , Davide Napetti , Giorgio Bonomi , Francesca Zanghì , Michele Bottosso , Elisabetta Lazzarini , Laura Santarelli , Andrea Boscolo Bragadin , Stefano Indraccolo , Valentina Guarneri","doi":"10.1016/j.ejca.2025.116194","DOIUrl":"10.1016/j.ejca.2025.116194","url":null,"abstract":"<div><h3>Background</h3><div>Outcomes and characteristics of endocrine-resistant, PIK3CA-mutated HR+ /HER2- advanced breast cancer patients in real-world are poorly investigated.</div><div>Here, we explored the role of circulating PIK3CA mutations in endocrine-resistant patients in the ongoing prospective, multicentric CHAMBER study.</div></div><div><h3>Methods</h3><div>PIK3CA was analyzed by NGS panel covering the full exonic region of PIK3CA gene.</div><div>Endocrine resistance was defined as: i) primary: relapse during the first 2 years of adjuvant ET, or ii) secondary: relapse after 2 years of starting or within 1 year of completing ET.</div><div>Overall survival (OS) was calculated from the start of first-line to death from any cause. Progression free survival 1 (PFS1) was calculated from the start of first-line to progression or death.</div></div><div><h3>Results</h3><div>Among the overall CHAMBER population, 22 % patients met the criteria for endocrine-resistance (74/337).</div><div>The study population consisted in 95 % women and 5 % men; median age at diagnosis was 50 years (IQR 44–63); 75 % of the women was postmenopausal;86 % of the total population presented with a secondary endocrine-resistance, 64 % had visceral relapse, 74 % had less than 3 metastatic sites, 79 % had received first-line CDK4/6 inhibitor.</div><div>PIK3CA status was available for 63/74 pts, with a 29 % prevalence of mutation.</div><div>PIK3CAmut was a negative prognostic factor for OS (median 65 [wt] vs 36 months [mut], log-rank p 0.024 HR 2.61 [95 % CI 1.10–6.22]) and PFS1 (median 22 [wt] vs 10 months [mut], log-rank p 0.012, HR 2.24 [95 % CI 1.18–4.26]).</div></div><div><h3>Conclusion</h3><div>The co-occurrence of endocrine-resistance and PIK3CAmut identifies a population with unfavorable prognosis, reinforcing the rationale of escalated therapies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116194"},"PeriodicalIF":7.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801951","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 : 2025-12-18DOI: 10.1016/j.ejca.2025.116193
Xiao Zhang , Jiaolin Zhou , Jianhao Geng , Yongheng Li , Fei Huang , Wenlong Shu , Wei Fu , Xin Zhou , Guoju Wu , Wenzhuo Jia , Jian Cui , Zhenjun Wang , Jiagang Han , Bohao Shi , Lifeng Li , Jinqiu Rui , Huadan Xue , Ke Hu , Tao Xu , Weijie Chen , Guole Lin
Background
Accurate risk stratification is essential to optimize neoadjuvant therapy for locally advanced rectal cancer (LARC) in the era of precision medicine. This study assessed the feasibility and safety of a circulating tumor DNA (ctDNA)-guided neoadjuvant strategy.
Methods
This interim analysis included patients with mid-low rectal adenocarcinoma (cT3–4N0M0 or cT1–4N1–2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes.
Results
Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all p <0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3–4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (p = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment.
Conclusion
This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy.
{"title":"Feasibility of ctDNA-guided precision neoadjuvant therapy in locally advanced rectal cancer: Insights from the ongoing CINTS-R trial","authors":"Xiao Zhang , Jiaolin Zhou , Jianhao Geng , Yongheng Li , Fei Huang , Wenlong Shu , Wei Fu , Xin Zhou , Guoju Wu , Wenzhuo Jia , Jian Cui , Zhenjun Wang , Jiagang Han , Bohao Shi , Lifeng Li , Jinqiu Rui , Huadan Xue , Ke Hu , Tao Xu , Weijie Chen , Guole Lin","doi":"10.1016/j.ejca.2025.116193","DOIUrl":"10.1016/j.ejca.2025.116193","url":null,"abstract":"<div><h3>Background</h3><div>Accurate risk stratification is essential to optimize neoadjuvant therapy for locally advanced rectal cancer (LARC) in the era of precision medicine. This study assessed the feasibility and safety of a circulating tumor DNA (ctDNA)-guided neoadjuvant strategy.</div></div><div><h3>Methods</h3><div>This interim analysis included patients with mid-low rectal adenocarcinoma (cT3–4N0M0 or cT1–4N1–2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes.</div></div><div><h3>Results</h3><div>Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all <em>p</em> <0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3–4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (<em>p</em> = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment.</div></div><div><h3>Conclusion</h3><div>This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov identifier: NCT05601505.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116193"},"PeriodicalIF":7.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801952","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 : 2025-12-18DOI: 10.1016/j.ejca.2025.116192
Anna-Klara Wiklund , Giola Santoni , Cecilia Radkiewicz , Shaohua Xie , Helgi Birgisson , Eivind Ness-Jensen , My von Euler-Chelpin , Joonas H. Kauppila , Jesper Lagergren
Objectives
Helicobacter pylori infection seems to increase the risk of developing pancreatic cancer, but it is unknown whether eradication treatment of this bacterium changes this risk. We hypothesized that the increased risk of pancreatic cancer among individuals infected with Helicobacter pylori decreases over time after eradication treatment.
Methods
This multinational and population-based cohort study, using prospectively collected nationwide register data from 1995 to 2019, included all adults who received eradication treatment for Helicobacter pylori in Denmark, Finland, Iceland, Norway, or Sweden. Standardized incidence ratios (SIR) with 95 % confidence intervals (95 %CI) were calculated by dividing the incidence rates of pancreatic cancer in the eradication treatment cohort by that of the entire populations of the corresponding age, sex, calendar year, and country. The main outcome was changes in SIR over time after eradication treatment.
Results
During up to 24 years of follow-up of 661,827 participants and 5494,255 person-years in the eradication treatment cohort, 2331 participants developed pancreatic cancer. The risk of pancreatic cancer was increased during the first 1–5 years after eradication treatment (SIR 1.14, 95 % CI 1.07–1.21), after which it decreased and became similar to the level of the background population 6–10 years (SIR 0.99, 95 % CI 0.92–1.07) and 11–24 years (SIR 1.00, 95 % CI 0.92–1.08) after eradication treatment.
Conclusion
The elevated risk of developing pancreatic cancer among individuals with Helicobacter pylori infection seems to decrease after eradication treatment, reaching the risk estimates of the background population.
目的幽门螺杆菌感染似乎会增加患胰腺癌的风险,但目前尚不清楚根除这种细菌的治疗是否会改变这种风险。我们假设,幽门螺杆菌感染者胰腺癌风险的增加在根除治疗后随着时间的推移而降低。方法:这项以人群为基础的跨国队列研究,使用1995年至2019年期间前瞻性收集的全国登记数据,包括丹麦、芬兰、冰岛、挪威或瑞典接受幽门螺杆菌根除治疗的所有成年人。通过将根除治疗队列中胰腺癌的发病率除以相应年龄、性别、日历年和国家的整个人群的发病率,计算出具有95 %置信区间(95 %CI)的标准化发病率(SIR)。主要结果是根除治疗后SIR随时间的变化。结果在长达24年的随访中,661,827名参与者和根除治疗队列的5494,255人年,2331名参与者发展为胰腺癌。胰腺癌的风险在根除治疗后的前1-5年增加(SIR 1.14, 95 % CI 1.07-1.21),之后降低并与根除治疗后6-10年(SIR 0.99, 95 % CI 0.92-1.07)和11-24年(SIR 1.00, 95 % CI 0.92-1.08)的背景人群水平相似。结论幽门螺杆菌感染个体在根除治疗后发生胰腺癌的风险降低,达到背景人群的风险估计。
{"title":"Risk of pancreatic cancer after eradication treatment of Helicobacter pylori","authors":"Anna-Klara Wiklund , Giola Santoni , Cecilia Radkiewicz , Shaohua Xie , Helgi Birgisson , Eivind Ness-Jensen , My von Euler-Chelpin , Joonas H. Kauppila , Jesper Lagergren","doi":"10.1016/j.ejca.2025.116192","DOIUrl":"10.1016/j.ejca.2025.116192","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Helicobacter pylori</em> infection seems to increase the risk of developing pancreatic cancer, but it is unknown whether eradication treatment of this bacterium changes this risk. We hypothesized that the increased risk of pancreatic cancer among individuals infected with <em>Helicobacter pylori</em> decreases over time after eradication treatment.</div></div><div><h3>Methods</h3><div>This multinational and population-based cohort study, using prospectively collected nationwide register data from 1995 to 2019, included all adults who received eradication treatment for <em>Helicobacter pylori</em> in Denmark, Finland, Iceland, Norway, or Sweden. Standardized incidence ratios (SIR) with 95 % confidence intervals (95 %CI) were calculated by dividing the incidence rates of pancreatic cancer in the eradication treatment cohort by that of the entire populations of the corresponding age, sex, calendar year, and country. The main outcome was changes in SIR over time after eradication treatment.</div></div><div><h3>Results</h3><div>During up to 24 years of follow-up of 661,827 participants and 5494,255 person-years in the eradication treatment cohort, 2331 participants developed pancreatic cancer. The risk of pancreatic cancer was increased during the first 1–5 years after eradication treatment (SIR 1.14, 95 % CI 1.07–1.21), after which it decreased and became similar to the level of the background population 6–10 years (SIR 0.99, 95 % CI 0.92–1.07) and 11–24 years (SIR 1.00, 95 % CI 0.92–1.08) after eradication treatment.</div></div><div><h3>Conclusion</h3><div>The elevated risk of developing pancreatic cancer among individuals with <em>Helicobacter pylori</em> infection seems to decrease after eradication treatment, reaching the risk estimates of the background population.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"233 ","pages":"Article 116192"},"PeriodicalIF":7.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788072","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 : 2025-12-18DOI: 10.1016/j.ejca.2025.116190
Luca Carlofrancesco Ammoni , Valentina Cortesi , Paolo Borghetti , Alice Baggi , Camilla Vultaggio , Vito Amoroso , Giorgio Facheris , Mattia Facchetti , Susanna Bianchi , Marta Laganà , Deborah Cosentini , Daniela Nonnis , Stefano Maria Magrini , Alfredo Berruti , Salvatore Grisanti
Background
Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma of the lung (LCNEC) are the deadliest forms of lung cancer with dismal prognosis. Recent evidence suggests that, beyond cigarette smoke, air pollution can have a role in the pathogenesis of non-small cell lung cancer (NSCLC) and is associated with poorer survival. However, whether air pollutants exposure could affect survival outcomes in SCLC/LCNEC is unknown.
Methods
We retrospectively analysed data from SCLC/LCNEC cases observed in the province of Brescia province Brescia between 2017 and 2021. Air pollutants mean concentrations were calculated during the same timeframe and the Brescia province was divided in six subareas dichotomized into lightly and heavily polluted areas based on the mean PM2.5 concentrations. Primary endpoint was to determine the impact of air pollutants exposure on SCLC/LCNEC overall survival (OS). Additionally, we explored the distribution of SCLC/LCNEC across the subareas classified for different air pollutants concentrations.
Findings
We observed 221 cases of SCLC/LCNEC, accounting for about 18 % of new lung cancer cases. Residency in heavily polluted areas (HR 1.51, p = 0.03) and extensive stage disease at diagnosis (HR 2.47, p = 0.0001) emerged as independent factors for poorer survival. Exploratory analyses showed an association between the distribution of SCLC/LCNEC cases and higher PM10 and NO2 concentrations (OR 1.16, p < 0.001 and OR 1.46, p < 0.001, respectively).
Interpretation
These results indicate that long-term exposure to high levels of PM2.5 represent an independent unfavourable prognostic factor for SCLC/LCNEC. Our data suggest that air pollution may also favour the onset of these malignant diseases. Case-control studies are warranted to confirm these preliminary results.
背景:小细胞肺癌(SCLC)和大细胞神经内分泌癌(LCNEC)是最致命的肺癌,预后较差。最近的证据表明,除了香烟烟雾,空气污染还可能在非小细胞肺癌(NSCLC)的发病机制中发挥作用,并与较差的生存率相关。然而,空气污染物暴露是否会影响SCLC/LCNEC患者的生存结局尚不清楚。方法:回顾性分析布雷西亚省2017年至2021年间观察到的SCLC/LCNEC病例数据。计算了同一时间段内空气污染物的平均浓度,并根据PM2.5的平均浓度将布雷西亚省划分为六个分区,分为轻污染区和重污染区。主要终点是确定空气污染物暴露对SCLC/LCNEC总生存期(OS)的影响。此外,我们还探讨了SCLC/LCNEC在不同空气污染物浓度分类的子区域中的分布。结果:我们观察到221例SCLC/LCNEC,约占肺癌新发病例的18% %。居住在重污染地区(HR 1.51, p = 0.03)和诊断时疾病分期广泛(HR 2.47, p = 0.0001)成为较差生存率的独立因素。探索性分析显示SCLC/LCNEC病例的分布与较高的PM10和NO2浓度之间存在关联(OR 1.16, p )。解释:这些结果表明,长期暴露于高水平的PM2.5是SCLC/LCNEC的一个独立的不利预后因素。我们的数据表明,空气污染也可能有利于这些恶性疾病的发病。有必要进行病例对照研究来证实这些初步结果。
{"title":"Ambient air pollution and survival in SCLC/LCNEC: Analysis of a single centre retrospective cohort","authors":"Luca Carlofrancesco Ammoni , Valentina Cortesi , Paolo Borghetti , Alice Baggi , Camilla Vultaggio , Vito Amoroso , Giorgio Facheris , Mattia Facchetti , Susanna Bianchi , Marta Laganà , Deborah Cosentini , Daniela Nonnis , Stefano Maria Magrini , Alfredo Berruti , Salvatore Grisanti","doi":"10.1016/j.ejca.2025.116190","DOIUrl":"10.1016/j.ejca.2025.116190","url":null,"abstract":"<div><h3>Background</h3><div>Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma of the lung (LCNEC) are the deadliest forms of lung cancer with dismal prognosis. Recent evidence suggests that, beyond cigarette smoke, air pollution can have a role in the pathogenesis of non-small cell lung cancer (NSCLC) and is associated with poorer survival. However, whether air pollutants exposure could affect survival outcomes in SCLC/LCNEC is unknown.</div></div><div><h3>Methods</h3><div>We retrospectively analysed data from SCLC/LCNEC cases observed in the province of Brescia province Brescia between 2017 and 2021. Air pollutants mean concentrations were calculated during the same timeframe and the Brescia province was divided in six subareas dichotomized into lightly and heavily polluted areas based on the mean PM<sub>2.5</sub> concentrations. Primary endpoint was to determine the impact of air pollutants exposure on SCLC/LCNEC overall survival (OS). Additionally, we explored the distribution of SCLC/LCNEC across the subareas classified for different air pollutants concentrations.</div></div><div><h3>Findings</h3><div>We observed 221 cases of SCLC/LCNEC, accounting for about 18 % of new lung cancer cases. Residency in heavily polluted areas (HR 1.51, p = 0.03) and extensive stage disease at diagnosis (HR 2.47, p = 0.0001) emerged as independent factors for poorer survival. Exploratory analyses showed an association between the distribution of SCLC/LCNEC cases and higher PM<sub>10</sub> and NO<sub>2</sub> concentrations (OR 1.16, p < 0.001 and OR 1.46, p < 0.001, respectively).</div></div><div><h3>Interpretation</h3><div>These results indicate that long-term exposure to high levels of PM<sub>2.5</sub> represent an independent unfavourable prognostic factor for SCLC/LCNEC. Our data suggest that air pollution may also favour the onset of these malignant diseases. Case-control studies are warranted to confirm these preliminary results.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116190"},"PeriodicalIF":7.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862298","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 : 2025-12-17DOI: 10.1016/j.ejca.2025.116189
François Schneider , Haotian Chen , Uwe Pelzer , Richard G. Compton , Gregor Duwe , Mihnea P. Dragomir , Georg Hilfenhaus , Loredana Vecchione , Annabel Alig , Matthäus Felsenstein , Markus Lerchbaumer , Damian T. Rieke , Marcus Bahra , Ralf Kutsche , Kristina Tschulik , Sebastian Stintzing , Ulrich Keilholz , Christopher C.M. Neumann
Background
Pancreatic adenocarcinoma (PDAC) remains one of the most lethal types of cancer, characterized by its unspecific symptoms, aggressive nature and late-stage diagnosis.
Patients and methods
In this study, Machine Learning (ML) models were trained and applied on the largest international, monocentric database, comprising over 23 clinical variables from 1040 PDAC patients. In this study, the potential of ML models was assessed for the 1-year survival rate, metastatic M0/M1 status and therapy-dependent survival time generating predictive and prognostic ML-based biomarkers.
Results
Consistent predictive performance was achieved for the 1-year survival rate (accuracy, internal/external cohort 72 % / 70 %) and radiological metastatic M0/M1 status (Accuracy, internal/external cohort 79 % / 72 %). Moreover, distinct ML-based survival models were trained for approved first-line adjuvant and palliative chemotherapy regimen (mFOLFIRINOX, gemcitabine with or without nab-paclitaxel) across resected (C-index = 0.60), locally advanced (C-index = 0.71) and metastatic (C-index = 0.71) PDAC subgroups, demonstrating that predictive performance is best for palliative regimens.
Conclusions
The models developed in this study may serve as a foundation for supporting tumor board decisions and demonstrate that personalized, ML-based therapy concepts are feasible in the near future. In addition, the models proposed in this study are helpful for generating ML-based synthetic control arms in future clinical trials.
{"title":"The basis for future personalized therapy approaches – Machine learning-generated 1-year survival rate, metastatic status and therapy-dependent survival in pancreatic cancer patients","authors":"François Schneider , Haotian Chen , Uwe Pelzer , Richard G. Compton , Gregor Duwe , Mihnea P. Dragomir , Georg Hilfenhaus , Loredana Vecchione , Annabel Alig , Matthäus Felsenstein , Markus Lerchbaumer , Damian T. Rieke , Marcus Bahra , Ralf Kutsche , Kristina Tschulik , Sebastian Stintzing , Ulrich Keilholz , Christopher C.M. Neumann","doi":"10.1016/j.ejca.2025.116189","DOIUrl":"10.1016/j.ejca.2025.116189","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic adenocarcinoma (PDAC) remains one of the most lethal types of cancer, characterized by its unspecific symptoms, aggressive nature and late-stage diagnosis.</div></div><div><h3>Patients and methods</h3><div>In this study, Machine Learning (ML) models were trained and applied on the largest international, monocentric database, comprising over 23 clinical variables from 1040 PDAC patients. In this study, the potential of ML models was assessed for the 1-year survival rate, metastatic M0/M1 status and therapy-dependent survival time generating predictive and prognostic ML-based biomarkers.</div></div><div><h3>Results</h3><div>Consistent predictive performance was achieved for the 1-year survival rate (accuracy, internal/external cohort 72 % / 70 %) and radiological metastatic M0/M1 status (Accuracy, internal/external cohort 79 % / 72 %). Moreover, distinct ML-based survival models were trained for approved first-line adjuvant and palliative chemotherapy regimen (mFOLFIRINOX, gemcitabine with or without nab-paclitaxel) across resected (C-index = 0.60), locally advanced (C-index = 0.71) and metastatic (C-index = 0.71) PDAC subgroups, demonstrating that predictive performance is best for palliative regimens.</div></div><div><h3>Conclusions</h3><div>The models developed in this study may serve as a foundation for supporting tumor board decisions and demonstrate that personalized, ML-based therapy concepts are feasible in the near future. In addition, the models proposed in this study are helpful for generating ML-based synthetic control arms in future clinical trials.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116189"},"PeriodicalIF":7.1,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862289","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 : 2025-12-17DOI: 10.1016/j.ejca.2025.116169
Han-Jie Long, Gui Yang , Qi-Wei Liang
{"title":"Letter re: Patient-related prognostic factors in older adults with head and neck cancer: The EGeSOR clinical trial\"","authors":"Han-Jie Long, Gui Yang , Qi-Wei Liang","doi":"10.1016/j.ejca.2025.116169","DOIUrl":"10.1016/j.ejca.2025.116169","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"234 ","pages":"Article 116169"},"PeriodicalIF":7.1,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827014","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 : 2025-12-13DOI: 10.1016/j.ejca.2025.116170
Charlotte Lafont, Elena Paillaud, Lydia Brugel, Florence Canouï-Poitrine
{"title":"Response to letter Re: “Patient-related prognostic factors in older adults with head and neck cancer: The EGeSOR clinical trial”.","authors":"Charlotte Lafont, Elena Paillaud, Lydia Brugel, Florence Canouï-Poitrine","doi":"10.1016/j.ejca.2025.116170","DOIUrl":"10.1016/j.ejca.2025.116170","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"233 ","pages":"Article 116170"},"PeriodicalIF":7.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780430","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 : 2025-12-12DOI: 10.1016/j.ejca.2025.116182
Jannek Brauer , Daniel Scheidet , Sebastian Romann , Christina Zehender , Jessica Hassel , Norbert Frey , Lorenz H. Lehmann
Background
BRAF/MEK inhibitors are a cornerstone of the therapy of BRAF-mutant cancers. Despite frequent use, the incidence of cardiovascular side effects is still unclear. Data on cancer therapy-related cardiac dysfunction (CTRCD), particularly using contemporary biomarker-inclusive definitions, remain limited.
Objectives
To assess the incidence and risk factors of CTRCD in patients receiving BRAF/MEK inhibitors, using the International Cardio-Oncology Society (ICOS) definitions, which include cardiac imaging and biomarker assessments.
Methods
A total of 75 patients treated with BRAF/MEK inhibitors underwent prospective cardiotoxicity monitoring with two follow-up visits at 90 days (IQR 36–137 days) and 199 days (IQR 115–266 days). Standardized evaluations included echocardiography with global longitudinal strain (GLS), high-sensitivity cardiac troponin T (hs-cTnT), and NT-proBNP measurements at baseline and follow-up visits. CTRCD was classified according to ICOS criteria. Baseline risk was stratified by European Society of Cardiology (ESC) risk categories.
Results
CTRCD occurred in 33 of 75 patients (44 %), with 17 % classified as mild, 23 % moderate, and 4 % severe. Baseline age, sex, BMI, and most cardiovascular risk factors were not significantly associated with CTRCD. Coronary artery disease was the only baseline variable associated with increased CTRCD (OR 11.0, p = 0.029; univariate analysis), whereas elevated hs-cTnT, NT-proBNP, or reduced LVEF at baseline were not predictive. Absolute CTRCD numbers were highest in the high ESC-defined cardiovascular risk category group, while incidence peaked in the low-risk group. Other cardiac complications occurred in 41 patients (55 %).
Conclusions
CTRCD is frequent among patients treated with BRAF/MEK inhibitors. Traditional cardiovascular risk factors were not predictive, although coronary artery disease emerged as a strong risk marker. These findings highlight the need for dynamic surveillance strategies.
{"title":"Cardiotoxic effects of BRAF/MEK inhibition: An observational study","authors":"Jannek Brauer , Daniel Scheidet , Sebastian Romann , Christina Zehender , Jessica Hassel , Norbert Frey , Lorenz H. Lehmann","doi":"10.1016/j.ejca.2025.116182","DOIUrl":"10.1016/j.ejca.2025.116182","url":null,"abstract":"<div><h3>Background</h3><div>BRAF/MEK inhibitors are a cornerstone of the therapy of BRAF-mutant cancers. Despite frequent use, the incidence of cardiovascular side effects is still unclear. Data on cancer therapy-related cardiac dysfunction (CTRCD), particularly using contemporary biomarker-inclusive definitions, remain limited.</div></div><div><h3>Objectives</h3><div>To assess the incidence and risk factors of CTRCD in patients receiving BRAF/MEK inhibitors, using the International Cardio-Oncology Society (ICOS) definitions, which include cardiac imaging and biomarker assessments.</div></div><div><h3>Methods</h3><div>A total of 75 patients treated with BRAF/MEK inhibitors underwent prospective cardiotoxicity monitoring with two follow-up visits at 90 days (IQR 36–137 days) and 199 days (IQR 115–266 days). Standardized evaluations included echocardiography with global longitudinal strain (GLS), high-sensitivity cardiac troponin T (hs-cTnT), and NT-proBNP measurements at baseline and follow-up visits. CTRCD was classified according to ICOS criteria. Baseline risk was stratified by European Society of Cardiology (ESC) risk categories.</div></div><div><h3>Results</h3><div>CTRCD occurred in 33 of 75 patients (44 %), with 17 % classified as mild, 23 % moderate, and 4 % severe. Baseline age, sex, BMI, and most cardiovascular risk factors were not significantly associated with CTRCD. Coronary artery disease was the only baseline variable associated with increased CTRCD (OR 11.0, p = 0.029; univariate analysis), whereas elevated hs-cTnT, NT-proBNP, or reduced LVEF at baseline were not predictive. Absolute CTRCD numbers were highest in the high ESC-defined cardiovascular risk category group, while incidence peaked in the low-risk group. Other cardiac complications occurred in 41 patients (55 %).</div></div><div><h3>Conclusions</h3><div>CTRCD is frequent among patients treated with BRAF/MEK inhibitors. Traditional cardiovascular risk factors were not predictive, although coronary artery disease emerged as a strong risk marker. These findings highlight the need for dynamic surveillance strategies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"233 ","pages":"Article 116182"},"PeriodicalIF":7.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788030","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 : 2025-12-11DOI: 10.1016/j.ejca.2025.116171
Van Tai Nguyen , Rufina Binoy, Foteini Kalofonou, Michael Davidson, Mary O’Brien
{"title":"Review and comment on the retrospective analyses of the effect of immunotherapy-infusion time of day on outcome in patients with advanced non-small cell lung cancer","authors":"Van Tai Nguyen , Rufina Binoy, Foteini Kalofonou, Michael Davidson, Mary O’Brien","doi":"10.1016/j.ejca.2025.116171","DOIUrl":"10.1016/j.ejca.2025.116171","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"233 ","pages":"Article 116171"},"PeriodicalIF":7.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773938","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}