European Journal of Cancer最新文献

{"title":"The role of IL-8 in cancer development and its impact on immunotherapy resistance","authors":"Clara Meier,&nbsp;Angela Brieger","doi":"10.1016/j.ejca.2025.115267","DOIUrl":"10.1016/j.ejca.2025.115267","url":null,"abstract":"<div><div>Tumors are structures of high complexity. Plurality of their structural and functional components - heterogeneity, diversity, directionality, interdependence and integration of signaling pathways - seem to follow isolated local rules, whereby a superordinate structure remains largely unknown. Understanding the complexity of cancer is the mainstay in finding determinants and developing effective therapies. Interleukin 8 (IL-8) is a potent pro-inflammatory chemokine that is significantly elevated in many different tumor entities. In contrast to its initially postulated anti-tumor properties, an increasing number of studies have been published in recent years linking this chemokine with tumor-promoting features and poor prognosis. This review summarizes the current state and diversity of the role of IL-8 in the development of cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115267"},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 2 study of futibatinib in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplifications","authors":"Taroh Satoh ,&nbsp;Philippe Barthélémy ,&nbsp;Lucia Nogova ,&nbsp;Kazunori Honda ,&nbsp;Hidekazu Hirano ,&nbsp;Keun-Wook Lee ,&nbsp;Sun Young Rha ,&nbsp;Min-Hee Ryu ,&nbsp;Joon Oh Park ,&nbsp;Toshihiko Doi ,&nbsp;Jaffer Ajani ,&nbsp;Nanae Hangai ,&nbsp;Jill Kremer ,&nbsp;Mark Mina ,&nbsp;Mei Liu ,&nbsp;Kohei Shitara","doi":"10.1016/j.ejca.2025.115262","DOIUrl":"10.1016/j.ejca.2025.115262","url":null,"abstract":"<div><h3>Background and aims</h3><div>Aberrant fibroblast growth factor receptor (FGFR)-driven signaling, predominantly arising from <em>FGFR2</em> amplification, plays a key role in gastric cancer pathogenesis. This open-label, phase 2 study evaluated the efficacy and safety of futibatinib, an irreversible FGFR1–4 inhibitor, in patients with gastric or gastroesophageal junction (GEJ) cancer harboring <em>FGFR2</em> amplifications.</div></div><div><h3>Methods</h3><div>Patients were treated with futibatinib 20 mg orally once daily in a 28-day cycle. The primary endpoint was objective response rate (ORR) per independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.</div></div><div><h3>Results</h3><div>Among 28 treated patients, the ORR per independent central review was 17.9 %, comprising five patients with a partial response (median duration of response, 3.9 months), and an additional nine patients with stable disease for a disease control rate of 50.0 %. Median PFS per independent central review and median OS were 2.9 and 5.9 months, respectively. The most common treatment-related adverse events (any grade) were hyperphosphatemia (89.3 %), decreased appetite (32.1 %), and increased aspartate aminotransferase (21.4 %). Only one (3.6 %) patient discontinued study treatment due to an adverse event.</div><div>Futibatinib demonstrated modest antitumor activity with a safety profile consistent with previous reports in patients with gastric or GEJ cancer harboring <em>FGFR2</em> amplifications, potentially warranting further investigation.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115262"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143300056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic and clinical significance of substantial lymphovascular space invasion in early-stage endometrial carcinoma","authors":"Zhuang Li ,&nbsp;Jiali Peng ,&nbsp;Bingxin Zhang ,&nbsp;Chen Zhao ,&nbsp;Zhongshao Chen ,&nbsp;Huimin Xiao ,&nbsp;Zhaoyang Zhang ,&nbsp;Xinyue Ma ,&nbsp;Feng Gao ,&nbsp;Rui Xin ,&nbsp;Wenwei Wang ,&nbsp;Shuaixin Wang ,&nbsp;Lingliya Tang ,&nbsp;Yawen Zhang ,&nbsp;Beihua Kong ,&nbsp;Li Li ,&nbsp;Aijun Yin","doi":"10.1016/j.ejca.2025.115258","DOIUrl":"10.1016/j.ejca.2025.115258","url":null,"abstract":"<div><h3>Objectives</h3><div>Substantial lymphovascular space invasion (LVSI) has been incorporated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma. This study aims to evaluate whether classifying LVSI into substantial LVSI (≥5 involved vessels) and no/focal LVSI (≤4 involved vessels) provides meaningful prognostic differentiation in early-stage endometrial carcinoma.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled patients with FIGO 2009 stage I–II endometrial carcinoma who underwent surgical staging between January 2013 and August 2020. LVSI was graded as no LVSI, focal LVSI (1–4 involved vessels), or substantial LVSI (≥5 involved vessels), following the World Health Organization 2020 definition.</div></div><div><h3>Results</h3><div>Among 1796 patients, 112 (6.2 %) had substantial LVSI, 170 (9.5 %) had focal LVSI, and 1514 (84.3 %) had no LVSI. The 5-year progression-free survival (PFS) rates were 81.7 % for substantial LVSI, 89.9 % for focal LVSI, and 95.0 % for no LVSI (<em>P</em> &lt; 0.001). Multivariate analysis found that substantial LVSI was an independent predictor of worse PFS (substantial vs. no LVSI: HR 2.49, <em>P</em> &lt; 0.001; substantial vs. focal LVSI: HR 1.90, <em>P</em> = 0.047). No statistically significant difference in PFS was observed between patients with focal LVSI and those with no LVSI (HR 1.31, <em>P</em> = 0.321). The overall survival (OS) analysis showed consistent results.</div></div><div><h3>Conclusions</h3><div>Substantial LVSI is an independent prognostic factor for PFS and OS in early-stage endometrial carcinoma, while focal LVSI shows similar outcomes to no LVSI. Our findings support the use of substantial LVSI (≥5 involved vessels) as a key determinant for risk stratification and staging, aligning with the FIGO 2023 staging system recommendations.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115258"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078965","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}

{"title":"Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma","authors":"Josephine G.M. Strijker ,&nbsp;Guillem Pascual-Pasto ,&nbsp;Grant P. Grothusen ,&nbsp;Yannine J. Kalmeijer ,&nbsp;Elisavet Kalaitsidou ,&nbsp;Chunlong Zhao ,&nbsp;Brendan McIntyre ,&nbsp;Stephanie Matlaga ,&nbsp;Lindy L. Visser ,&nbsp;Marta Barisa ,&nbsp;Courtney Himsworth ,&nbsp;Rivani Shah ,&nbsp;Henrike Muller ,&nbsp;Linda G. Schild ,&nbsp;Peter G. Hains ,&nbsp;Qing Zhong ,&nbsp;Roger R. Reddel ,&nbsp;Phillip J. Robinson ,&nbsp;Xavier Catena ,&nbsp;María S. Soengas ,&nbsp;Judith Wienke","doi":"10.1016/j.ejca.2025.115263","DOIUrl":"10.1016/j.ejca.2025.115263","url":null,"abstract":"<div><h3>Introduction</h3><div>Chimeric antigen receptor (CAR) T-cell therapy is a promising and innovative cancer therapy. However, immunosuppressive tumor microenvironments (TME) limit T cell persistence and durable efficacy. Here, we aimed to identify and target immunosuppressive factors in the TME of neuroblastoma, a pediatric extracranial solid tumor, to improve CAR-T efficacy.</div></div><div><h3>Methods</h3><div>Immunosuppressive factors were identified using a multi-omics approach, including single-cell RNA sequencing (scRNA-seq) of 24 neuroblastoma tumors, published bulk-RNA sequencing datasets, and mass-spectrometry of patient-derived tumoroid models. Candidate targets were validated with functional assays <em>in vitro</em> and <em>in vivo</em>. Protein degradation of the top immunosuppressive target by PROTAC technology was used to evaluate the effect on CAR T-cell activity.</div></div><div><h3>Results</h3><div>ScRNA-seq revealed 13 immunosuppressive interactions in the TME of neuroblastoma, two effectors of which, Midkine (MDK) and Macrophage Migration Inhibitory Factor (MIF), were validated as candidate targets across multiple published datasets. Both factors were among the top 6 % of most abundantly secreted factors by patient-derived tumoroid models, substantiating their potential relevance in the TME. <em>In vitro</em> and <em>in vivo</em> functional assays confirmed MIF to be a potent inhibitor of CAR T-cell activation and killing capacity. To translate these findings into a potentially clinically applicable treatment, we explored MIF targeting by PROTAC technology, which significantly enhanced activation of CAR T-cells targeting GPC2 and B7-H3.</div></div><div><h3>Conclusion</h3><div>By defining the immunosuppressive effects of neuroblastoma’s TME on CAR T-cell efficacy, revealing the pivotal role of MIF, we provide an analytic pipeline and therapeutic strategy for improving adoptive cell therapies for this pediatric malignancy and potentially other solid tumors.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115263"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143098572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma","authors":"Jeremy Mo ,&nbsp;Anne Zaremba ,&nbsp;Andrisha-Jade Inderjeeth ,&nbsp;Perla El Zeinaty ,&nbsp;Ao Li ,&nbsp;Alexandre Wicky ,&nbsp;Nicholas Della Marta ,&nbsp;Caroline Gaudy Marqueste ,&nbsp;Ann-Sophie Bohne ,&nbsp;Margarida Matias ,&nbsp;Nicholas McNamee ,&nbsp;Lucia Festino ,&nbsp;Charley Chen ,&nbsp;Sydney Ch’ng ,&nbsp;Alexander C.J. van Akkooi ,&nbsp;Laetitia Da Meda ,&nbsp;John J. Park ,&nbsp;Paolo A. Ascierto ,&nbsp;Axel Hauschild ,&nbsp;Jenny H. Lee ,&nbsp;Ines Pires da Silva","doi":"10.1016/j.ejca.2025.115254","DOIUrl":"10.1016/j.ejca.2025.115254","url":null,"abstract":"<div><h3>Aim</h3><div>Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.</div></div><div><h3>Method</h3><div>This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy.</div></div><div><h3>Results</h3><div>One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median follow-up of 28.7 months (95 % CI: 21.4–38.3), ORR was 57.3 %, median DOR was 42.8 months (95 % CI, 25.8 – not reached (NR)), median PFS was 14 months (95 % CI, 8.1– 19.8), and median OS was 42.8 months (95 % CI, 30.3 – NR). One-hundred and eight patients (59 %) experienced progressive disease; 50 % (n = 54/108) with primary resistance and 26 % (n = 28/108) with secondary resistance. Fifty patients (27 %; n = 50/185) received subsequent systemic therapies (+/- local therapy) with response data; 18 (36 %; n = 18/50) received doublet platinum chemotherapy (ORR 67 %, DOR 5.0 months [95 % CI; 3.7 - NR]) and 16 (32 %; n = 16/50) were rechallenged with anti-PD-(L)1 (ORR 56 %, DOR 20.2 months [95 % CI; 8.3 - NR]).</div></div><div><h3>Conclusion</h3><div>The most common subsequent treatment for patients with primary resistance was chemotherapy, while those with secondary resistance most frequently underwent further anti-PD-(L)1 therapy in combination with other therapies. Despite both therapies demonstrating promising ORR, doublet platinum chemotherapy had a poorer DOR compared to anti-PD-(L)1 rechallenge.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"217 ","pages":"Article 115254"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058073","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}

{"title":"Stereotactic body radiotherapy for lung-only oligometastatic head and neck squamous cell carcinoma: Long-term clinical outcome and favorable predictive factors","authors":"Viola Salvestrini ,&nbsp;Ilaria Bonaparte ,&nbsp;Carlotta Becherini ,&nbsp;Isacco Desideri ,&nbsp;Saverio Caini ,&nbsp;Annarita Palomba ,&nbsp;Niccolò Bertini ,&nbsp;Chiara Mattioli ,&nbsp;Gabriele Simontacchi ,&nbsp;Giulio Francolini ,&nbsp;Daniela Greto ,&nbsp;Mauro Loi ,&nbsp;Vanessa Di Cataldo ,&nbsp;Lorenzo Livi ,&nbsp;Pierluigi Bonomo","doi":"10.1016/j.ejca.2025.115260","DOIUrl":"10.1016/j.ejca.2025.115260","url":null,"abstract":"<div><h3>Background</h3><div>Oligometastatic disease in head and neck squamous cell carcinoma (HNSCC) is a rare setting. Local ablative therapies are the most adopted strategies although no evidence-based recommendations are currently published. We report on long-term clinical outcomes of a cohort of HNSCC patients treated with stereotactic body radiotherapy (SBRT) for lung-only oligometastatic disease. <em>Material and Methods</em>: Eligible patients had 1–5 lung metastases. The oligometastatic pattern was classified as “de novo” or “induced oligoprogressive”. We evaluated time to progression (TTP) as the time from the last day of SBRT to disease progression or death from any cause. Predictive factors of better clinical outcome and survival analysis were performed. <em>Results</em>: A cohort of 50 patients (52 metastases) was retrospectively evaluated. The median age was 68 years and 45 patients had an ECOG PS 0–1. Oropharynx cancer was the primary tumor subsite in 20 patients and HPV positive status was reported in 13 patients. “De novo” oligometastatic pattern was observed for the majority of patients. After a median follow up of 24,5 months, median TTP and overall survival (OS) from the end of SBRT were 17 months and 46 months, respectively. The 2-years LC rates was 86 %. At univariate analysis, patients aged &gt; 70 years reported a better TTP (0.03). <em>Conclusion</em>: Our findings suggested that SBRT may improve clinical outcome prolonging time to progression in a properly selected cohort of HNSCC patients with lung-only oligometastatic disease. Distant metastases from HPV-related primary HNSCC should be tested for p16/HPV status.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115260"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143098574","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}

{"title":"Association of pregnancy with tumour progression in patients with glioma","authors":"Annette Leibetseder ,&nbsp;Maximilian J. Mair ,&nbsp;Anika Simonovska Serra ,&nbsp;Zoltan Spiro ,&nbsp;Martin Aichholzer ,&nbsp;Georg Widhalm ,&nbsp;Franziska Eckert ,&nbsp;Adelheid Wöhrer ,&nbsp;Raimund Helbok ,&nbsp;Serge Weis ,&nbsp;Matthias Preusser ,&nbsp;Josef Pichler ,&nbsp;Anna Sophie Berghoff","doi":"10.1016/j.ejca.2025.115259","DOIUrl":"10.1016/j.ejca.2025.115259","url":null,"abstract":"<div><h3>Background</h3><div>A significant proportion of women in reproductive age are diagnosed with diffuse gliomas, resulting in the need to address the safety of pregnancy in patient consultation. However, data on glioma progression after and during pregnancy are sparse and controversial.</div></div><div><h3>Methods</h3><div>Female adult patients in their reproductive years (≥18 years and &lt;46 years) with histological diagnosis of glioma between 01/01/2000 and 01/12/2019 from 2 academic centers have been included in the study. Re-classification according to the 2021 WHO classification of CNS tumours was performed. The cohort was divided into 3 groups, defined as (A) nulliparae, (B) primi-/multiparae before glioma diagnosis, and (C) primi-/multiparae after glioma diagnosis. Survival analyses were performed in a time-dependent manner with parity as time-dependent covariate.</div></div><div><h3>Results</h3><div>159/368 females met our inclusion criteria, resulting in 47 (29.6 %) nulliparae, 88 (55.3 %) primi-/multiparae before glioma diagnosis and 24 (15.1 %) primi-/multiparae after glioma diagnosis. Median follow-up was 127.4 months (range 0.7–341.9), and median overall survival and progression free survival were 247.6 months (range 0.4–269.1) and 67.9 months (range 0.7–341.9), respectively. Overall, 113/159 (71.1 %) patients had tumour progression and 53/159 (33.3 %) deceased. In total, 57.4 % of the nullipara, 76.1 % of the primi-/multipara before glioma diagnosis and 79.1 % of the primi-/multipara after glioma diagnosis groups experienced tumour progression (p &gt; 0.05). In multivariate time-dependent analysis, primi-/multiparae after glioma diagnosis presented with shorter progression free (HR 2.45, p = 0.0079), but not overall survival (HR 0.54, p &gt; 0.05) in comparison to the other two groups.</div></div><div><h3>Conclusion</h3><div>Pregnancy after glioma diagnosis was associated with shorter progression free survival. Longer follow-up as well as larger cohorts are needed to investigate a potential impact on overall survival.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115259"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402702","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}

{"title":"Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: A phase 2 trial","authors":"Jérôme Doyen ,&nbsp;Anne Dompmartin ,&nbsp;Coralie Cruzel ,&nbsp;Dinu Stefan ,&nbsp;Jean-Philippe Arnault ,&nbsp;Alexandre Coutte ,&nbsp;Alexandra Picard-Gauci ,&nbsp;Sandrine Mansard ,&nbsp;Baptiste Gleyzolle ,&nbsp;Eric Fontas ,&nbsp;Elodie Long-Mira ,&nbsp;Xavier Mirabel ,&nbsp;Laurent Mortier ,&nbsp;Henri Montaudié","doi":"10.1016/j.ejca.2025.115256","DOIUrl":"10.1016/j.ejca.2025.115256","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma.</div></div><div><h3>Methods</h3><div>This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-naïve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy × 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1-year overall survival (OS).</div></div><div><h3>Results</h3><div>This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3–43.8) months. The median age was 68 (35–95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were <em>BRAF</em>-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (<em>P</em> = 0.22 and <em>P</em> = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twenty-seven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; <em>P</em> = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3–4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5).</div></div><div><h3>Conclusions</h3><div>Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"217 ","pages":"Article 115256"},"PeriodicalIF":7.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045514","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}

{"title":"Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial","authors":"O. Metzger Filho ,&nbsp;F. Cardoso ,&nbsp;C. Poncet ,&nbsp;C. Desmedt ,&nbsp;S. Linn ,&nbsp;J. Wesseling ,&nbsp;F. Hilbers ,&nbsp;S. Delaloge ,&nbsp;J.-Y. Pierga ,&nbsp;E. Brain ,&nbsp;S. Vrijaldenhoven ,&nbsp;P.A. Neijenhuis ,&nbsp;E.J.Th Rutgers ,&nbsp;M. Piccart ,&nbsp;L.J. van ’t Veer ,&nbsp;G. Viale","doi":"10.1016/j.ejca.2025.115222","DOIUrl":"10.1016/j.ejca.2025.115222","url":null,"abstract":"<div><h3>Background</h3><div>Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.</div></div><div><h3>Patients and methods</h3><div>Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk. Survival outcomes at 8.7 years median follow-up by 70-gene signature were compared between NST and ILC for Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS) and Overall Survival (OS).</div></div><div><h3>Results</h3><div>5313 patients were ILC (n = 487) or NST (n = 4826). ILC was further classified into classic ILC (n = 255) or ILC variants (n = 232). The 70-gene signature classified 16.2 % of ILC and 39.1 % of NST as genomic high-risk (gH). Survival outcomes for ILC vs. NST revealed similar estimates according to genomic risk overall and across subsets. The 70-gene signature classified 10.2 % of classic ILC and 22.8 % of ILC variants as gH. 5-yr DFS estimates for ILC variants 88.4 % (95 %CI: 83.1–92.1) was inferior to classic ILC 93.0 % (95 %CI: 88.7–95.7).</div></div><div><h3>Conclusions</h3><div>Sixteen percent of ILC were classified high genomic risk by the 70-gene signature, with unfavorable survival outcomes. Survival estimates were similar for patients with ILC and NST classified as either low- or high-genomic risk, suggesting that the 70-gene signature also has prognostic value in ILC and may be a clinically useful tool for adjuvant treatment decision-making in ILC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"217 ","pages":"Article 115222"},"PeriodicalIF":7.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045839","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}

{"title":"Prolgolimab with chemotherapy as first-line treatment for advanced non-squamous non-small-cell lung cancer","authors":"K. Laktionov ,&nbsp;A. Smolin ,&nbsp;D. Stroyakovskiy ,&nbsp;V. Moiseenko ,&nbsp;M. Dvorkin ,&nbsp;T. Andabekov ,&nbsp;Y. Cheng ,&nbsp;B. Liu ,&nbsp;V. Kozlov ,&nbsp;S. Odintsova ,&nbsp;S. Dvoretsky ,&nbsp;A. Mochalova ,&nbsp;M. Urda ,&nbsp;T. Yi ,&nbsp;X. Li ,&nbsp;U. László ,&nbsp;V. Müller ,&nbsp;K. Bogos ,&nbsp;N. Fadeeva ,&nbsp;G. Musaev ,&nbsp;F. Kryukov","doi":"10.1016/j.ejca.2025.115255","DOIUrl":"10.1016/j.ejca.2025.115255","url":null,"abstract":"<div><h3>Background</h3><div>Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing ‘LALA’ mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months). The primary endpoint was overall survival (OS).</div></div><div><h3>Results</h3><div>After a median follow-up of 18 months, the median OS was not reached (95 % CI, 22.28 – NA) in the prolgolimab-combination group vs 14.6 months (95 % CI, 11.73 – 19.15) in the placebo-combination group (HR, 0.51; 95 % CI, 0.35 – 0.73, p = 0.0001). The OS improvement was independent of PD-L1 status. Median progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was 7.7 months in the prolgolimab-combination group and 5.5 months in the placebo-combination group (HR, 0.65; 95 % CI, 0.49 – 0.85, p = 0.0004). The only adverse events that were reported in at least 10 % of the patients that were significantly more frequent in the prolgolimab-combination group were blood creatinine increased and dyspnoea.</div></div><div><h3>Conclusion</h3><div>Among patients with advanced NSCLC the addition of prolgolimab to pemetrexed and a platinum-based drug increased OS and PFS, with no new safety concerns. This benefit was retained in patients with PD-L1 negative tumors. (ClinicalTrials.gov, NCT03912389)</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"217 ","pages":"Article 115255"},"PeriodicalIF":7.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064477","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}