European Journal of Cancer最新文献

Why are patients with non-small cell lung cancer in stage I-IIIA considered inoperable? A registry-based study from the capital region of Denmark 为什么I-IIIA期非小细胞肺癌患者不能手术？一项来自丹麦首都地区的基于登记的研究

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-15 DOI: 10.1016/j.ejca.2026.116246

Thomas Budolfsen , Rene Horsleben Petersen , Lars Borgbjerg Møller , Jette Brabrand , Zaigham Saghir , Morten Quist

Background

Surgical resection is first-line treatment for patients with stage I–IIIA non-small cell lung cancer (NSCLC), yet a substantial proportion are managed without surgery. The reasons for non-operative management and the role of objective functional assessment are insufficiently described.

Methods

This retrospective registry-based cohort study included patients diagnosed with stage I–IIIA NSCLC in 2022 in the Capital Region of Denmark. Data were retrieved from the Danish Lung Cancer Registry and electronic medical records. Patients were categorized into “Surgery” and “No surgery” groups. Demographic variables, lung function, ECOG performance status, comorbidities, and MDT justifications were extracted. Multivariable logistic regression identified factors associated with not receiving surgery, and one-year overall survival (OS) was estimated using Kaplan–Meier methods.

Results

Among 524 patients, 178 (34 %) did not undergo surgery. Non-surgical management was independently associated with age ≥ 80 years, stage IIIA disease, poorer ECOG performance status, comorbidities, and reduced or unregistered DLco, whereas FEV1 and DLco ≥ 80 % predicted were negatively associated. MDT justifications were low lung function or poor performance status (29.2 %), comorbidities (18.0 %), and N2 disease (11.8 %); in 19.7 % no justification was documented. No documentation of preoperative exercise testing was identified. One-year OS was higher after surgery than no surgery (95.7 % vs. 82.0 %), unadjusted.

Conclusions

One third of patients with stage I–IIIA NSCLC were treated without surgery, mainly due to impaired functional status, comorbidity, or advanced stage. The absence of documented exercise testing highlights a gap between guideline recommendations and clinical practice.

手术切除是I-IIIA期非小细胞肺癌（NSCLC）患者的一线治疗方法，但仍有相当一部分患者无需手术治疗。非手术治疗的原因和客观功能评估的作用描述不够充分。方法：这项基于登记的回顾性队列研究纳入了2022年丹麦首都地区诊断为I-IIIA期NSCLC的患者。数据从丹麦肺癌登记处和电子医疗记录中检索。患者分为“手术”组和“不手术”组。提取了人口统计学变量、肺功能、ECOG表现状态、合并症和MDT的理由。多变量逻辑回归确定了不接受手术的相关因素，并使用Kaplan-Meier方法估计了一年总生存期（OS）。结果524例患者中，178例（34% %）未行手术治疗。非手术治疗与年龄≥ 80岁、IIIA期疾病、较差的ECOG表现状态、合并症、DLco减少或未登记独立相关，而FEV1和DLco≥ 80 %预测为负相关。MDT的理由是肺功能低下或表现不佳（29.2% %）、合并症（18.0% %）和N2疾病（11.8% %）；19.7 %没有证明文件。未发现术前运动试验的记录。术后1年OS高于未手术（95.7% % vs. 82.0 %），未经调整。结论1 / 3的I-IIIA期NSCLC患者没有手术治疗，主要是由于功能状态受损、合并症或晚期。缺乏文献记载的运动试验突出了指南建议和临床实践之间的差距。

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引用次数: 0

Comprehensive review of pregnancy associated breast cancer: Clinical features, molecular characteristics and novel therapies 妊娠相关乳腺癌的临床特征、分子特征和新治疗方法综述

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-12 DOI: 10.1016/j.ejca.2026.116230

Alessandra Spata , Joana M. Ribeiro , Paolo Vigneri , Alberto Zambelli , Jean Zeghondy , Chayma Bousrih , Thomas Grinda , Alessandro Viansone , Alexandre J. Vivanti , Michaël Grynberg , Bruno Achutti Duso , Fabrice André , Barbara Pistilli , Elie Rassy

Pregnancy-Associated Breast Cancer (PABC) accounts for pregnancy-related breast cancer (PrBC), occurring during pregnancy and the first postpartum year, and postpartum breast cancer (PPBC), arising up to 5–10 years after childbirth. It represents an increasingly oncological challenge as delayed childbearing trends extend maternal reproductive age. Occurring in approximately 1:3000 pregnancies, PABC accounts for 0.2–3.8 % of all breast cancer cases. PABC is often associated with aggressive clinic-biological characteristics, including higher prevalence of triple-negative subtypes, increased lymph node involvement, and more frequent advanced-stage presentation compared to age-matched non-pregnant controls. The complex mammary microenvironment during pregnancy, lactation, and postpartum involution undergoes extensive hormonal-driven remodeling that creates a biphasic landscape, initially providing a permissive environment for carcinogenesis while conferring long-term protective effects. The molecular mechanisms underlying this transformation remain incompletely understood and represent an active area of investigation. Molecular profiling of PABC reveals enhanced proliferative signaling pathways, metabolic reprogramming, tumor-promoting inflammatory responses, and compromised DNA damage repair mechanisms. While PABC shares similar genomic architecture with non-pregnancy-associated breast cancers, distinct gene expression signatures have been identified that may contribute to its aggressive phenotype. This comprehensive review examines the physiological breast changes occurring throughout the reproductive cycle and their relationship to PABC carcinogenesis. We analyze the molecular profile and clinicopathological features that distinguish PABC from conventional breast cancer, while addressing the therapeutic challenges posed by fetal safety considerations. Additionally, we evaluate the safety profiles of novel therapeutic agents during pregnancy and lactation, highlighting the critical need for new pregnancy-compatible treatment strategies.

妊娠相关乳腺癌（PABC）包括妊娠相关乳腺癌（PrBC），发生在怀孕期间和产后第一年，以及产后乳腺癌（PPBC），发生在分娩后5-10年。随着推迟生育的趋势延长了产妇的生育年龄，它代表着一个日益严峻的肿瘤挑战。PABC大约发生在1:30 000的怀孕中，占所有乳腺癌病例的0.2-3.8 %。PABC通常与侵袭性临床生物学特征相关，包括三阴性亚型的患病率较高，淋巴结累及增加，与年龄匹配的未怀孕对照组相比，更频繁出现晚期症状。在怀孕、哺乳期和产后复复期，复杂的乳房微环境经历了广泛的激素驱动的重塑，创造了一个双相景观，最初为致癌提供了一个宽松的环境，同时赋予了长期的保护作用。这种转化背后的分子机制仍然不完全清楚，是一个活跃的研究领域。PABC的分子图谱揭示了增殖性信号通路、代谢重编程、促肿瘤炎症反应和DNA损伤修复机制的增强。虽然PABC与非妊娠相关乳腺癌具有相似的基因组结构，但已确定的不同基因表达特征可能有助于其侵袭性表型。本文综述了在整个生殖周期中发生的乳腺生理变化及其与PABC致癌的关系。我们分析了区分PABC与传统乳腺癌的分子特征和临床病理特征，同时解决了胎儿安全考虑带来的治疗挑战。此外，我们评估了新型治疗药物在妊娠和哺乳期的安全性，强调了对新的妊娠相容治疗策略的迫切需要。

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引用次数: 0

Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan 针对肺癌间质性肺炎的驱动突变：日本的一项全国性研究

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-12 DOI: 10.1016/j.ejca.2026.116232

Satoshi Ikeda , Takashi Ogura , Toshihiro Misumi , Yasuhiko Nishioka , Seishu Hashimoto , Kazuya Ichikado , Aya Fukuizumi , Saori Takata , Taku Itoh , Yuki Sato , Kyoichi Okishio , Kazuhiro Yatera , Noriho Sakamoto , Motoyasu Kato , Ryota Kikuchi , Takayuki Honda , Naozumi Hashimoto , Koji Murakami , Takuma Isshiki , Mayuka Yamane , Kazuma Kishi

Introduction

Non-small cell lung cancer (NSCLC) patients with comorbid interstitial pneumonia (IP) are at high risk for drug-induced pneumonitis, and previous reports suggest a lower frequency of common driver mutations such as EGFR. This may discourage genetic testing, potentially overlooking prevalent, targetable mutations like KRAS, BRAF, and MET. This study aimed to elucidate the real-world status of genetic testing, the frequency of oncogenic drivers, and the safety and efficacy of targeted therapies in patients with NSCLC and comorbid IP.

Methods

This multicenter, retrospective study analyzed 1256 patients with advanced or recurrent NSCLC and comorbid chronic fibrosing IP from 37 Japanese institutions (Registry number: UMIN000055609).

Results

The rate of any genetic testing was 59.2 % (95 % confidence interval [CI], 56.5–62.0), with multigene testing performed in only 41.0 % (95 %CI, 38.3–43.8). Among patients with NSCLC undergoing multigene testing (N = 515), the most frequent mutations were KRAS (4.7 %; G12C, 1.9 %), followed by EGFR (2.9 %), BRAF V600E (1.6 %), and MET exon 14 skipping (1.6 %). The incidence of drug-induced pneumonitis was 0 % (0/6) for sotorasib, 50 % (4/8) for osimertinib, 33 % (1/3) for alectinib, and 25 % (1/4) for both dabrafenib plus trametinib and tepotinib. Patients with actionable oncogenic drivers receiving targeted therapy had the longest overall survival, followed by those not receiving it, and then driver-negative/unknown patients (median: 39.2, 24.0, and 13.8 months, respectively).

Conclusions

Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.

非小细胞肺癌（NSCLC）合并间质性肺炎（IP）的患者发生药物性肺炎的风险很高，以前的报道表明常见驱动突变（如EGFR）的频率较低。这可能会阻碍基因检测，可能会忽略普遍的、可靶向的突变，如KRAS、BRAF和MET。本研究旨在阐明基因检测的现实状况，致癌驱动因素的频率，以及靶向治疗在非小细胞肺癌和合并症IP患者中的安全性和有效性。方法这项多中心、回顾性研究分析了来自日本37家机构的1256例晚期或复发性非小细胞肺癌和共病性慢性纤维化IP患者（注册号：UMIN000055609）。结果任一基因检测的检出率为59.2% %(95% %可信区间[CI]， 56.5 ~ 62.0)，多基因检测的检出率仅为41.0% %（95% %CI, 38.3 ~ 43.8）。在接受多基因检测的NSCLC患者中（N = 515），最常见的突变是KRAS(4.7 %;G12C, 1.9 %)，其次是EGFR（2.9 %）、BRAF V600E（1.6 %）和MET外显子14跳变（1.6 %）。索托拉西布的药物性肺炎发生率为0 %(0/6)，奥西替尼为50 %(4/8)，阿勒替尼为33 %(1/3)，达非尼联合曲美替尼和替波替尼为25 %（1/4）。接受靶向治疗的可操作致癌驱动因素患者的总生存期最长，其次是未接受靶向治疗的患者，然后是驱动因素阴性/未知的患者（中位数分别为39.2个月、24.0个月和13.8个月）。结论多基因检测在该人群中未得到充分利用。虽然许多靶向治疗具有较高的肺炎风险，但sotorasib似乎相对安全。尽管存在风险，但识别和治疗可操作的致癌驱动因素可能提高生存率。

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引用次数: 0

Informative censoring in maintenance therapy trials for advanced ovarian cancer: An empirical assessment of its impact on treatment benefit 晚期卵巢癌维持治疗试验中的信息审查：对其治疗效果影响的经验评估

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2026-01-11 DOI: 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.

相当大比例的卵巢癌维持试验患者可能在无进展生存期（PFS）分析中被剔除，PFS是主要研究终点。这种审查通常是信息性的，反映了由于毒性、偏好或早期转向替代疗法而停止治疗，可能使结果偏向于高估PFS的益处。我们的目的是量化这些试验中信息审查对PFS的影响。方法选择双盲、安慰剂对照的维持治疗试验，根据已发表的生存曲线重建个体患者数据。敏感性分析将所有审查事件的不同比例重新分类为从0 %到100 %信息审查的模型情景的进展。重新估计危险比（hr），并与最初报告的值进行比较。将治疗时间与PFS进行比较。结果共纳入试验单位22个（N = 8256）。19例报告了统计上显著的结果，在分析的上限下降到14例（74 %）。hr逐渐降低，在10 %时降低6 %，在100 %时降低29 %。在9项PARP抑制剂试验中，治疗持续时间短于PFS（平均中位数= 12.5个月vs 17.6个月）。当仅限于PARP抑制剂研究时，结果是一致的。未观察到不良事件与审查之间的相关性。结论信息性审查会严重扭曲卵巢癌维持试验中PFS的获益估计。透明地报告审查率及其原因对于有意义的临床解释至关重要，应成为所有随机维持治疗试验的标准。

{"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}

引用次数: 0

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。

{"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}

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