European Journal of Cancer最新文献_第4页

Associations between changes in MASLD status and cancer development in young adults: A nationwide cohort study 年轻人MASLD状态变化与癌症发展之间的关系：一项全国性队列研究

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-10 DOI: 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。

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引用次数: 0

Lung-only metastatic pancreatic cancer: Differences in patients ‘characteristics, molecular profile and survival 仅肺转移性胰腺癌：患者特征、分子谱和生存率的差异

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-09 DOI: 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.

胰腺导管腺癌（PDAC）仅肺转移患者预后较好，但PDAC嗜器官性的生物学/临床基础尚不清楚。研究目的是比较不同转移部位的PDAC患者，并特别关注“仅肺”转移患者。方法回顾性分析2010 - 2022年间某学术中心所有转移性PDAC患者。仅肺转移的患者定义为在诊断转移时仅肺转移的患者。结果1012例患者中，109例（11 %）仅肺转移，506例（50 %）仅肝转移，94例（9 %）仅腹膜转移，303例（30 %）其他或多部位转移。与其他患者相比，单纯肺部患者更多为女性（63 % vs. 46 %），转移诊断年龄较大（中位66岁vs. 63岁，p = 0.01），同步转移的可能性较小（42 % vs. 69 %,p <； 0.001）。仅肺组的ctDNA检测较低，液体活检检测到的KRAS突变和TP53突变较少（但使用肿瘤组织没有观察到差异）。单肺组的中位OS较高，为28.7个月（95 %CI[23.3-38.6]），单肝组为13.5个月（95 %CI[12.4-14.6]），单腹膜组为11.5个月（95 %CI[9.6-16.9]），其他患者为11.3个月（95 %CI [10.0-13.8]）（p <； 0.0001）。在仅肺部患者中，局部治疗（n = 15）对预后有积极影响。结论仅肺转移患者的OS优于其他患者，且多为女性，KRAS突变较少。我们的研究结果支持PDAC具有特定的特点，特别是预后更好，可能进一步增强了局部治疗的可能性，以及较少的ctDNA检测。

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引用次数: 0

Assessing quality of life in individuals with hereditary cancer risk: Results from phases 1–3a of the EORTC QLQ-HCR30 questionnaire 评估遗传癌症风险个体的生活质量：EORTC QLQ-HCR30问卷1-3a期结果

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-09 DOI: 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).

本研究的目的是开发一种欧洲癌症研究和治疗组织（EORTC）患者报告的结果测量（PROM），以评估有或没有既往癌症诊断的遗传癌症易感综合征（HCPS）个体的生活质量（QOL）。我们报告了内容生成、问卷构建以及问卷的可接受性、全面性和语言效度评估。方法遵循EORTC生活质量组模块开发指南的第1-3a阶段，通过文献综述和对卫生保健专业人员和接受HCPS遗传咨询或测试的个人的访谈来确定生活质量问题。根据调查结果，我们编制了一份初步调查问卷，并在国际上进行了相关性、清晰度和语言适当性的预测试。修订工作以定性反馈和预先确定的标准为指导。结果从文献中确定了63个问题，并通过访谈扩展为73个问题的问卷。在9个国家的12个中心对119名个体（79.8% %为女性）进行问卷预测试，包括BRCA、Lynch综合征和Li-Fraumeni携带者，结果显示对阴性或待测结果的适用性有限。因此，目标人群被细化为突变携带者。项目减少后，最后的文书包括30个经过验证和语言上适当的项目。结论EORTC QLQ-HCR30可用于评估HCPS患者的生活质量，目前已准备好进行初步心理测量评估（3b期和4期）。

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引用次数: 0

Association of proton pump inhibitor use with outcome of patients with recurrent glioblastoma 质子泵抑制剂的使用与复发性胶质母细胞瘤患者预后的关系

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-09 DOI: 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.

具有强乙醛脱氢酶1a1激活特性（PA-PPI）的质子泵抑制剂的使用最近与新诊断的胶质母细胞瘤患者的不良预后相关。虽然介导这种结果关联的机制仍然不完全清楚，但复发性胶质母细胞瘤患者没有这样的数据。材料和方法我们对四项首次复发胶质母细胞瘤的临床试验进行了汇总分析：DIRECTOR （NCT00941460）、EORTC 1410 （NCT02343406）、EORTC 1608 （C组）（NCT03224104）和EORTC 26034 （NCT00086879）。我们在基线和两个定义的里程碑（第8周和第16周）评估了PA-PPI的使用。Cox模型用于确定PA-PPI使用与预后的关系。结果单因素分析显示，在基线和两个指标上，PA-PPI的使用与较差的总生存期相关，但与无进展生存期无关。然而，在控制主要预后因素的多变量分析中，PA-PPI的使用不再具有预后作用。从多变量Cox模型中遗漏了不同的预后因素，表明类固醇的使用使得PA-PPI的使用无关紧要。事实上，PA-PPI的使用与类固醇的使用有关。目前对复发性胶质母细胞瘤患者使用PA-PPI与预后结果相关的分析没有提供证据表明在这种情况下使用PA-PPI可能会损害预后。一线环境中没有MGMT启动子甲基化的明确结果关联与复发环境中没有关联之间的脱节可能与改变处方模式有关，但需要进一步研究。由于有替代药物可用，在胶质母细胞瘤患者中，PA-PPI处方的适应症可能应该缩小。

{"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}

引用次数: 0

Precision oncology promise in the management of pancreatic acinar cell carcinoma 精确肿瘤学在胰腺腺泡细胞癌治疗中的前景

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-07 DOI: 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.

胰腺腺泡细胞癌（PACC）是一种罕见的恶性肿瘤，占所有胰腺癌的不到2%，与更常见的胰腺导管腺癌（PDAC）相比，它具有独特的临床和分子特征。从历史上看，由于可用的前瞻性和/或随机数据有限，PACC的治疗方法已改编自PDAC。然而，下一代测序（NGS）的出现揭示了PACC中独特的基因组景观，为精确肿瘤学创造了新的机会。与PDAC不同，PACC通常缺乏KRAS、TP53和CDKN2A突变，而是显示Wnt/β-catenin通路（APC、CTNNB1）、同源重组修复（HRR）基因（如BRCA1/2、ATM）和错配修复（MMR）基因的改变，这可能具有潜在的治疗意义。靶向治疗已在特定病例中显示出临床益处，包括治疗hrr缺陷肿瘤的PARP抑制剂和治疗微卫星不稳定性高（MSI-H）或mmr缺陷PACC的免疫检查点抑制剂。其他可操作的改变，如BRAF V600E突变、NTRK融合和ALK重排对相应的靶向药物有反应。虽然主要基于有限的报告，但这些观察结果支持综合分子谱在指导PACC治疗中的效用。鉴于生殖系HRR突变的高流行率及其对治疗和家族风险的影响，还建议进行普遍的生殖系检测。总之，个性化癌症治疗的潜力在PACC中是有希望的。将分子诊断整合到临床护理中对于确定治疗靶点和优化结果至关重要；持续的研究和参与基因组匹配的临床试验是推进这种罕见恶性肿瘤治疗范例的关键。

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引用次数: 0

Preclinical characterization and first-in-human, phase I trial of the novel ALK inhibitor dirozalkib in advanced non-small cell lung cancer 新型ALK抑制剂dirozalkib治疗晚期非小细胞肺癌的临床前特征和首次人体I期试验

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-07 DOI: 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. C_max 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).

研究新型间变性淋巴瘤激酶（ALK）抑制剂dirozalkib的临床前特性、安全性、药代动力学和对晚期非小细胞肺癌（NSCLC）的初步抗肿瘤活性。方法对地罗唑布进行体外和体内的临床前抑制作用评价。第一项人体I期研究（NCT05055232）招募了携带ALK或ROS1重排的晚期NSCLC患者。参与者在3 + 3快速滴定剂量递增设计后接受50-600 mg/天的地罗扎基治疗，在剂量扩展阶段接受300-600 mg/天的治疗。主要终点是安全性。结果dirozalkib对ALK融合阳性细胞系和常见耐药突变有明显的抑制作用，抑制患者源性和颅内异种移植肺癌模型的肿瘤生长。没有发生剂量限制性毒性，确定600 mg/天为最大耐受剂量。在114名入组患者中，55名（48.2 %）出现≥ 3级治疗后出现的不良事件，最常见的是腹泻（8.8 %）。在剂量递增和剂量扩展组中，ALK重排患者的客观缓解率（ORR）分别为47.4 %（9/19）和46.3 % (38/82)（ALK抑制剂初始患者接受500 mg/d治疗的ORR为89.3% %）。单次给药50-600 mg地唑基布后，达到最大浓度的中位时间为3 - 4 h。Cmax和dirozalkib曲线下面积接近剂量正比增加，几何平均终端消除半衰期为19.6 ~ 25.4 h。结论dirozalkib在晚期alk重排NSCLC患者中具有良好的安全性、抗肿瘤活性和药代动力学。推荐的II期剂量为500mg /天。试验注册：Clinicaltrials.gov （NCT05055232）和chinadrutrials.org.cn （CTR20190984）。

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引用次数: 0

Chemo-prAIdict Breast: A deep learning solution for predicting residual disease on biopsies of breast cancer patients treated with neoadjuvant chemotherapy chemo - prodict Breast：一个深度学习解决方案，用于预测接受新辅助化疗的乳腺癌患者活检上的残留疾病

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-07 DOI: 10.1016/j.ejca.2026.116222

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

Background

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.

背景：在治疗前预测化疗敏感性有助于在早期乳腺癌（eBC）中量身定制新辅助化疗（NAC）。病理完全缓解（pCR）与较好的长期生存相关，但目前还没有可靠的基线预测指标。患者和方法我们开发了chemo - prodict Breast，这是一种使用诊断活检的全切片图像（wsi）预测NAC后残留疾病（RD）的深度学习模型。我们分析了两个大型法国队列（n = 最初纳入的1140个，选择后分析的928个）：前瞻性多中心PRIMUNEO队列（n = 500，选择后分析的438个）用于训练和内部验证，CGFL回顾性队列（n = 640，选择后分析的490）用于独立的外部验证。患者按分子亚型进行分层：HER2扩增（HER2 +），ER阳性/HER2阴性（ER+/HER2 −）和三阴性（TN）。ResultsIn外部验证,Chemo-prAIdict乳房比标准的临床病理的特点,实现auc为0.652 (p = 0.001)在HER2 + ,0.814 (p = 0.003)ER + / HER2 −,和0.677 (p = 0.001)TN肿瘤。通过对421例患者的连续活检切片证实了稳健性：患者内部的预测具有很强的相关性（HER2 +的Pearson r = 0.933，ER+/HER2 −的Pearson r 0.932， TN的Pearson r 0.939；所有p <； 0.001）。结论虽然需要对现代治疗方案进行前瞻性研究以建立临床应用，但chemo - prodict Breast是一种识别对标准NAC差异敏感的eBC的新工具，可以帮助HER2 + ，ER+ /HER2-和TN eBC选择最合适的治疗策略。

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引用次数: 0

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-01

引用次数: 0

4-year overall survival after the introduction of adjuvant therapy for patients with stage III melanoma: A population-based study III期黑色素瘤患者引入辅助治疗后的4年总生存率：一项基于人群的研究

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-12-26 DOI: 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。

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引用次数: 0

Five-year survival after introduction of adjuvant treatment in stage III melanoma: A nationwide registry-based study III期黑色素瘤引入辅助治疗后的5年生存率：一项基于全国登记的研究。

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-12-26 DOI: 10.1016/j.ejca.2025.116201

Hildur Helgadottir , Lars Ny , Gustav J. Ullenhag , Rasmus Mikiver , Karolin Isaksson , Roger Olofsson Bagge

Background

In patients with stage III cutaneous melanoma, adjuvant treatments with PD-1 and BRAF+MEK inhibitors were approved based on improved recurrence-free survival. However, as the treatments have significant side effects and costs, the effect on overall survival remains a matter of great importance.

Methods

Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with stage IIIB-D melanoma in 2016–2020. Patients under the age of 75 years, that had a positive sentinel lymph node (SLN) were included. Patients were divided into two cohorts, depending on if the SLN biopsy was performed before or from September 2018 (pre- and post-cohort), based on the timepoint when adjuvant treatment was introduced. Patients were followed for survival until the end of 2024.

Results

The five-year overall survival rates were, 67.3 % (95 % CI 62.0–72.9) in the pre-cohort (n = 287) and 70.1 % (95 % CI 65.3–75.2) in the post-cohort (n = 349), with hazard ratio adjusted for age, sex and tumor stage of 0.96 (95 % CI 0.73–1.27), P=0.791. In the post-cohort 72.8 % received adjuvant treatment, the majority with PD-1 inhibitors where treatment exposure was highest in those < 60 years (80.2 %), males (78.3 %) and those having thicker primary melanomas (75.4 %). No significant overall or melanoma-specific survival differences were observed when comparing the pre- and the post-cohort in different subgroups.

Conclusions

In this nationwide, population and registry-based study there was no overall survival benefit observed five years after the introduction of adjuvant treatment for patients with stage III melanoma. These findings encourage a careful assessment of the current recommendation on adjuvant treatment.

背景：在III期皮肤黑色素瘤患者中，基于改善的无复发生存期，PD-1和BRAF+MEK抑制剂的辅助治疗被批准。然而，由于治疗有明显的副作用和成本，对总体生存的影响仍然是一个非常重要的问题。方法：从瑞典黑色素瘤登记处获得2016-2020年诊断为IIIB-D期黑色素瘤患者的临床和组织病理学参数。年龄在75岁以下，前哨淋巴结（SLN）阳性的患者也包括在内。根据引入辅助治疗的时间点，根据SLN活检是在2018年9月之前还是之后进行的（队列前和队列后），将患者分为两个队列。研究人员对患者进行了随访，直至2024年底。结果:5年总体生存率,67.3 %(95 %可信区间62.0 - -72.9)在pre-cohort (n = 287)和70.1 %(95 %可信区间65.3 - -75.2)在post-cohort (n = 349),与风险比调整年龄、性别和肿瘤阶段0.96(95 %可信区间0.73 - -1.27),P = 0.791。在队列后，72.8% %的患者接受了辅助治疗，其中大多数患者接受了PD-1抑制剂，治疗暴露率最高。结论：在这项全国性的、基于人口和登记的研究中，III期黑色素瘤患者在引入辅助治疗5年后没有观察到总体生存获益。这些发现鼓励对目前推荐的辅助治疗进行仔细评估。

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引用次数: 0