European Journal of Cancer最新文献

{"title":"Immunotherapy followed by cetuximab in locally advanced/metastatic cutaneous squamous cell carcinomas: the I-TACKLE trial","authors":"Paolo Bossi ,&nbsp;Andrea Alberti ,&nbsp;Cristiana Bergamini ,&nbsp;Carlo Resteghini ,&nbsp;Laura Deborah Locati ,&nbsp;Salvatore Alfieri ,&nbsp;Stefano Cavalieri ,&nbsp;Elena Colombo ,&nbsp;Cristina Gurizzan ,&nbsp;Luigi Lorini ,&nbsp;Valeria Tovazzi ,&nbsp;Manuel Zamparini ,&nbsp;Marco Ravanelli ,&nbsp;Paolo Antonio Ascierto ,&nbsp;Vittorio Rampinelli ,&nbsp;Alberto Grammatica ,&nbsp;Roberto Patuzzo ,&nbsp;Andrea Maurichi ,&nbsp;Lisa Francesca Licitra","doi":"10.1016/j.ejca.2025.115379","DOIUrl":"10.1016/j.ejca.2025.115379","url":null,"abstract":"<div><h3>Background</h3><div>Immunotherapy with pembrolizumab and cemiplimab achieves an overall response rate (ORR) of 34–51 % in locally advanced/metastatic (LA/M) cSCC, but primary and acquired resistance remains a challenge. This study evaluates whether adding cetuximab to pembrolizumab can overcome resistance by reducing immune escape.</div></div><div><h3>Patients and methods</h3><div>I-TACKLE is a phase II, open-label trial conducted at three Italian centers. Patients received intravenous pembrolizumab 200 mg every 3 weeks, and cetuximab was added in cases of stable disease or progression. The primary endpoint was cumulative ORR by a single agent or by combination strategy. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and response duration.</div></div><div><h3>Results</h3><div>From May 2019 to April 2021, 43 patients were enrolled and treated with pembrolizumab, and 23 received combination therapy. Median treatment durations were 3 months (pembrolizumab) and 4 months (combination). Cumulative ORR was 63 % [95 % CI 48–77], with 19/43 (44 %) responding to pembrolizumab and 8/21 (38 %) responding to the combination after resistance. Both patients experiencing an acquired resistance to pembrolizumab obtained partial response when cetuximab was introduced. Overall, 10/23 (44 %) responded to the combination. One-year PFS was 51 % with pembrolizumab and 42 % with combination therapy. Grade 3–4 treatment-related adverse events occurred in 7/43 (16 %) during pembrolizumab and 8/23 (35 %) during combination therapy, primarily dermatitis (30 %).</div></div><div><h3>Conclusions</h3><div>In LA/M cSCC, the addition of cetuximab to pembrolizumab reverts primary and acquired resistance with manageable toxicities. This sequential approach warrants further study.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115379"},"PeriodicalIF":7.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724816","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":"Primary mediastinal B-cell lymphoma (PMBCL): The LYSA pragmatic guidelines","authors":"Loïc Renaud ,&nbsp;Marie Donzel ,&nbsp;Justine Decroocq ,&nbsp;Pierre Decazes ,&nbsp;Jean Galtier ,&nbsp;Barbara Burroni ,&nbsp;Elena-Liana Veresezan ,&nbsp;Côme Sesboüé ,&nbsp;Peggy Dartigues ,&nbsp;Catherine Chassagne-Clément ,&nbsp;Laurent Martin ,&nbsp;Claire Mauduit ,&nbsp;Sophie Kaltenbach ,&nbsp;Dominique Penther ,&nbsp;Pascaline Etancelin ,&nbsp;David Sibon ,&nbsp;Sarah Bailly ,&nbsp;Valentine Martin ,&nbsp;Eric Durot ,&nbsp;Youlia Kirova ,&nbsp;Vincent Camus","doi":"10.1016/j.ejca.2025.115369","DOIUrl":"10.1016/j.ejca.2025.115369","url":null,"abstract":"<div><div>Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma with unique clinical, histopathological, and molecular characteristics. Despite its aggressive nature, PMBCL has a high cure rate when managed appropriately. Advances in the understanding of PMBCL biological characteristics, coupled with improvements in diagnostic tools and therapeutic approaches, have significantly improved patient outcomes in recent years. In this article, we present a set of pragmatic guidelines developed by the Lymphoma Study Association (LYSA) for the management of PMBCL. These guidelines address key aspects of diagnosis, staging, response evaluation, and treatment, integrating the latest evidence from clinical trials, expert consensus, and real-world practice. The aim of the guidelines is to provide clinicians with a clear, practical framework to optimize care for patients with PMBCL, ensuring that the best available evidence is translated into clinical practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115369"},"PeriodicalIF":7.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724821","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":"Safety of accelerated infusion of nivolumab and pembrolizumab","authors":"Loes van Rijssen ,&nbsp;Iris E.C. Nagtegaal ,&nbsp;Floortje K. Ploos van Amstel ,&nbsp;Chantal M.L. Driessen ,&nbsp;Nielka P. van Erp ,&nbsp;Anja Timmer-Bonte ,&nbsp;Sarah R. Verhoeff","doi":"10.1016/j.ejca.2025.115373","DOIUrl":"10.1016/j.ejca.2025.115373","url":null,"abstract":"<div><div>Nivolumab and pembrolizumab are checkpoint inhibitors targeting programmed cell death-1, used for several types of cancer. The increased use of these drugs and the growing number of cancer patients place a significant burden on the hospital ward capacity. Safely reducing the infusion time of immune checkpoint inhibitors could improve capacity. The aim of this implementation project was to explore the safety of accelerated infusion time for nivolumab and pembrolizumab. Patients who received monotherapy nivolumab or pembrolizumab were included in the implementation project. The administration time according to label of nivolumab and pembrolizumab was reduced over 2–3 treatment cycles from 60 and 30–10 min. Vital signs were measured every 15 min from start until 30 min after completion of each administration. If a hypersensitivity reaction (HSR) occurred, infusion was interrupted, and its severity was graded. Between January 2023 and December 2024, 101 patients were enrolled (316 infusions). This included 72 patients with nivolumab and 29 with pembrolizumab treatment. Only grade 1 and 2 HSR were observed. In total 11 HSRs were observed during the administration of nivolumab. Nine HSRs occurred during the 30-minute and two during the 10-minute infusion. No HSR was recorded with pembrolizumab. The accelerated infusion of nivolumab and pembrolizumab in 10 min is safe and results in considerable time efficiency. This strategy is potentially feasible for more immune checkpoint inhibitors and should therefore be considered to facilitate the treatment of the increasing number of cancer patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115373"},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705916","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":"Induction chemotherapy followed by chemoradiation in locally advanced cervical cancer: Quality of life outcomes of the GCIG INTERLACE trial","authors":"G. Eminowicz ,&nbsp;S. Vaja ,&nbsp;D. Gallardo ,&nbsp;C. Kent ,&nbsp;M. Panades ,&nbsp;T. Mathew ,&nbsp;A. Anand ,&nbsp;J. Forrest ,&nbsp;M. Adusumalli ,&nbsp;A. Chan ,&nbsp;A.M. Hacker ,&nbsp;A. Hackshaw ,&nbsp;J.A. Ledermann ,&nbsp;M. McCormack","doi":"10.1016/j.ejca.2025.115375","DOIUrl":"10.1016/j.ejca.2025.115375","url":null,"abstract":"<div><h3>Aim</h3><div>Induction chemotherapy (IC) added to chemoradiation (CRT) in locally advanced cervical cancer (LACC) improves survival at the expense of adverse events (AEs), 99 % with IC/CRT vs 95 % CRT alone, 59 % vs 48 % G3/4 AEs. We investigated the impact of this on quality of life (QoL).</div></div><div><h3>Methods</h3><div>500 women with FIGO 2008 stage IB1 node positive, IB2, II, IIIB and IVA cervical carcinoma were randomised to CRT alone or IC (6 weeks carboplatin AUC2 paclitaxel 80mg/m²) followed by CRT. QoL questionnaires (EORTC QLQ-C30 v3, QLQ-CX24) were completed at baseline, D1 week 4 IC, D1 CRT, D1 week 3 CRT, 4 weeks post CRT and all follow up visits. Mixed modelling for repeated measures was used to compare the groups during trial treatment to 2 years follow up (adjusting for baseline).</div></div><div><h3>Results</h3><div>QoL (global health status, physical and social functioning) slightly worsened during IC and symptom experience slightly improved. Emotional functioning improved during IC.</div><div>Peripheral neuropathy was slightly worse with IC/CRT. Fatigue and nausea/vomiting worsened from baseline to week 4 IC whilst pain and diarrhoea improved, consistent with reported AEs. Over the whole period, mean differences for these symptoms between the treatment groups was small and not clinically significant and resolved by 12–18 months.</div><div>In all cases, mean score differences during trial treatment until 2 years post CRT showed only small differences (&lt;5 units) not meeting the threshold for clinical relevance.</div></div><div><h3>Conclusion</h3><div>IC added to CRT does not adversely impact QoL compared to CRT, either during IC, during CRT or later.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115375"},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697436","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":"Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial","authors":"John M. Kirkwood ,&nbsp;Peter Mohr ,&nbsp;Christoph Hoeller ,&nbsp;Jean-Jacques Grob ,&nbsp;Michele Del Vecchio ,&nbsp;Jennifer Lord-Bessen ,&nbsp;Swetha Srinivasan ,&nbsp;Ayman Nassar ,&nbsp;Federico Campigotto ,&nbsp;Hannah Fairbanks ,&nbsp;Fiona Taylor ,&nbsp;Rachael Lawrance ,&nbsp;Georgina V. Long ,&nbsp;Jeffrey Weber","doi":"10.1016/j.ejca.2025.115371","DOIUrl":"10.1016/j.ejca.2025.115371","url":null,"abstract":"<div><h3>Background</h3><div>In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K.</div></div><div><h3>Methods</h3><div>Change from baseline to week 53 in health-related quality of life (HRQoL), as measured using the EORTC QLQ-C30 and EQ-5D-5L utility index and visual analog scale (VAS), was compared between treatment groups using linear mixed-effect models. Time to confirmed deterioration (TTCD) in HRQoL was assessed using Cox regression. Bother from side effects, as measured by the FACIT-GP5, was descriptively compared between treatment groups.</div></div><div><h3>Results</h3><div>There were no clinically meaningful differences in change from baseline between treatment groups in EORTC QLQ-C30 subscales, including global health status (GHS)/quality of life (QoL; least squares mean [LSM] difference: −1.3; 95 % confidence interval [CI]: −2.9, 0.4), and EQ-5D-5L utility index (LSM difference: −0.011; 95 % CI: −0.025, 0.004) and VAS (LSM difference: −1.3; 95 % CI: −2.6, 0.0). There was no difference in TTCD for nivolumab versus placebo in EORTC QLQ-C30 GHS/QoL (hazard ratio [HR]: 1.10; 95 % CI: 0.88, 1.36) or EQ-5D-5L utility index (HR: 1.10; 95 % CI: 0.86, 1.42); however, TTCD in EQ-5D-5L VAS was longer with placebo (HR: 1.92; 95 % CI: 1.39, 2.64). Proportions of patients reporting severe side effect bother (“quite a bit”/“very much”) were minimal (nivolumab: 1 %–4 %; placebo: 0 %–2 %).</div></div><div><h3>Conclusions</h3><div>Patients with resected stage IIB/C melanoma treated with adjuvant nivolumab demonstrated stable HRQoL and minimal bother from side effects.</div></div><div><h3>Clinical Trial Information</h3><div>NCT04099251</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115371"},"PeriodicalIF":7.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697437","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":"Corrigendum to \"HER2 status and response to neoadjuvant anti-HER2 treatment among patients with breast cancer and Li-Fraumeni syndrome\" [Eur J Cancer 211 (2024) 114307].","authors":"Michele Bottosso, Renata L Sandoval, Benjamin Verret, Natalia Polidorio, Olivier Caron, Alessandra Gennari, Brittany L Bychkovsky, Sophie H Cahill, Maria I Achatz, Valentina Guarneri, Fabrice André, Judy E Garber","doi":"10.1016/j.ejca.2025.115370","DOIUrl":"https://doi.org/10.1016/j.ejca.2025.115370","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":" ","pages":"115370"},"PeriodicalIF":7.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663034","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":"First-line checkpoint inhibitor therapy in metastatic acral lentiginous melanoma compared to other types of cutaneous melanoma: A multicenter study from the prospective skin cancer registry ADOREG","authors":"Sören Reinhard ,&nbsp;Jochen Sven Utikal ,&nbsp;Anne Zaremba ,&nbsp;Georg Lodde ,&nbsp;Imke von Wasielewski ,&nbsp;Kai Christian Klespe ,&nbsp;Friedegund Meier ,&nbsp;Sebastian Haferkamp ,&nbsp;Katharina C. Kähler ,&nbsp;Rudolf Herbst ,&nbsp;Christoffer Gebhardt ,&nbsp;Anca Sindrilaru ,&nbsp;Edgar Dippel ,&nbsp;Yenny Angela ,&nbsp;Peter Mohr ,&nbsp;Claudia Pfoehler ,&nbsp;Andrea Forschner ,&nbsp;Martin Kaatz ,&nbsp;Beatrice Schell ,&nbsp;Anja Gesierich ,&nbsp;Henner Stege","doi":"10.1016/j.ejca.2025.115356","DOIUrl":"10.1016/j.ejca.2025.115356","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is the main cause of skin cancer-related death. Treatment with immune checkpoint inhibitors (CPI) has improved the prognosis in recent years. However, subtypes of melanoma differ in their response. Acral lentiginous melanoma (ALM) has a worse prognosis compared to cutaneous melanoma other than ALM (CM) and is therefore of particular relevance.</div></div><div><h3>Aims</h3><div>To evaluate the efficacy of CPI in first-line treatment of patients with advanced ALM compared CM.</div></div><div><h3>Methods</h3><div>Retrospective analysis of patients with metastatic ALM (n = 45) or CM (n = 328) who received first-line CPI therapy from the multicenter prospective skin cancer registry ADOREG. Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>ALM patients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CM patients. Combined CPI was administered in 48.9 % ALM patients and 39.3 % of CM patients, while the remaining patients received PD-1 monotherapy. OS trended to be shorter in patients with ALM (18.1 vs. 43.8 months, p = 0.10) with no significant differences in PFS (7.0 vs. 11.5 months, p = 0.21). In patients with CM, median OS with combined CPI was not reached, whereas the median OS after PD-1 monotherapy was 37.8 months (p = 0.22). Conversely, in patients with ALM, OS with combined CPI was 17.8 months, compared to 26 months with PD-1 monotherapy (p = 0.15). There were no significant differences in BOR between patients with ALM or CM.</div></div><div><h3>Conclusion</h3><div>Analysis of this real-world cohort of patients with metastatic melanoma showed a trend towards poorer survival outcomes upon first-line treatment with CPI in ALM compared to cutaneous melanoma of other subtypes.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115356"},"PeriodicalIF":7.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686723","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":"Development of an artificial intelligence-generated, explainable treatment recommendation system for urothelial carcinoma and renal cell carcinoma to support multidisciplinary cancer conferences","authors":"Gregor Duwe ,&nbsp;Dominique Mercier ,&nbsp;Verena Kauth ,&nbsp;Kerstin Moench ,&nbsp;Vikas Rajashekar ,&nbsp;Markus Junker ,&nbsp;Andreas Dengel ,&nbsp;Axel Haferkamp ,&nbsp;Thomas Höfner","doi":"10.1016/j.ejca.2025.115367","DOIUrl":"10.1016/j.ejca.2025.115367","url":null,"abstract":"<div><h3>Background</h3><div>Decisions on the best available treatment in clinical oncology are based on expert opinions in multidisciplinary cancer conferences (MCC). Artificial intelligence (AI) could increase evidence-based treatment by generating additional treatment recommendations (TR). We aimed to develop such an AI system for urothelial carcinoma (UC) and renal cell carcinoma (RCC).</div></div><div><h3>Methods</h3><div>Comprehensive data of patients with histologically confirmed UC and RCC who received MCC recommendations in the years 2015 – 2022 were transformed into machine readable representations. Development of a two-step process to train a classifier to mimic TR was followed by identification of superordinate and detailed categories of TR. Machine learning (CatBoost, XGBoost, Random Forest) and deep learning (TabPFN, TabNet, SoftOrdering CNN, FCN) techniques were trained. Results were measured by F1-scores for accuracy weights.</div></div><div><h3>Results</h3><div>AI training was performed with 1617 (UC) and 880 (RCC) MCC recommendations (77 and 76 patient input parameters). The AI system generated fully automated TR with excellent F1-scores for UC (e.g. ‘Surgery’ 0.81, ‘Anti-cancer drug’ 0.83, ‘Gemcitabine/Cisplatin’ 0.88) and RCC (e.g. ‘Anti-cancer drug’ 0.92 ‘Nivolumab’ 0.78, ‘Pembrolizumab/Axitinib’ 0.89). Explainability is provided by clinical features and their importance score. Finally, TR and explainability were visualized on a dashboard.</div></div><div><h3>Conclusion</h3><div>This study demonstrates for the first time AI-generated, explainable TR in UC and RCC with excellent performance results as a potential support tool for high-quality, evidence-based TR in MCC. The comprehensive technical and clinical development sets global reference standards for future AI developments in MCC recommendations in clinical oncology. Next, prospective validation of the results is mandatory.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115367"},"PeriodicalIF":7.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642419","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":"Update of the impact of menopausal hormone therapy on breast cancer risk","authors":"Heli Siitonen ,&nbsp;Johanna Joensuu ,&nbsp;Hanna Savolainen-Peltonen ,&nbsp;Mika Gissler ,&nbsp;Olavi Ylikorkala ,&nbsp;Tomi S. Mikkola","doi":"10.1016/j.ejca.2025.115340","DOIUrl":"10.1016/j.ejca.2025.115340","url":null,"abstract":"<div><h3>Background</h3><div>We assessed menopausal hormone therapy (MHT) -related invasive breast cancer (BC) risks among more recent MHT users to compare this data with older national and international data.</div></div><div><h3>Methods</h3><div>We identified in this nationwide cohort study MHT users (n = 357 928) in 1994–2019 from the medical reimbursement register and age-matched non-users (n = 351 735) from the national population register and followed them for the occurrence of invasive BC with the aid of the Finnish Cancer Registry. The unadjusted BC risks were calculated as odds ratios (ORs) and 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>During a median of 18 years and 13 million person-years, 23 571 MHT users (6.6 %) and 17 192 non-users (4.9 %) were diagnosed with invasive BC (p &lt; 0.001), and the median detection year was 2011. Ever use of estrogen-only therapy for 5–9 years (OR 1.61; 95 % CI 1.51–1.71) or tibolone for ≤ 10 years (1.30; 1.02–1.67) was accompanied by smaller risk elevations than use of estrogen-progestogen therapy (EPT) for the same duration (1.82; 1.76–1.88 and 1.98; 1.91–2.06). Dydrogesterone-EPT for 5–9 years was associated with a smaller risk increase (1.32; 1.12–1.55) than other EPT regimens (1.76–2.16; 1.62–2.30). The BC risks remained elevated 5–10 years after cessation of MHT with most of the regimens.</div></div><div><h3>Conclusions</h3><div>Despite possible changes towards safer MHT prescribing, our data collected largely in early millennium show at least as large BC risk elevations in MHT users as seen in older studies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115340"},"PeriodicalIF":7.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643025","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":"Radiation vs. trans-oral surgery for treatment de-escalation in HPV-related oropharyngeal cancers: Primary analysis of the ORATOR2 randomized trial","authors":"David A. Palma ,&nbsp;Eitan Prisman ,&nbsp;Eric Berthelet ,&nbsp;Eric Tran ,&nbsp;Sarah Hamilton ,&nbsp;Jonn Wu ,&nbsp;Antoine Eskander ,&nbsp;Kevin Higgins ,&nbsp;Irene Karam ,&nbsp;Ian Poon ,&nbsp;Zain Husain ,&nbsp;Danny Enepekides ,&nbsp;Michael Hier ,&nbsp;Keith Richardson ,&nbsp;Alex Mlynarek ,&nbsp;Stephanie Johnson-Obaseki ,&nbsp;Marc Gaudet ,&nbsp;Andrew Bayley ,&nbsp;Samuel Dowthwaite ,&nbsp;James E. Jackson ,&nbsp;Anthony C. Nichols","doi":"10.1016/j.ejca.2025.115343","DOIUrl":"10.1016/j.ejca.2025.115343","url":null,"abstract":"<div><h3>Background</h3><div>The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS).</div></div><div><h3>Patients and methods</h3><div>Patients with T1-T2 N0–2 HPV-related OPSCC were randomly assigned to primary RT (60 Gy with concurrent weekly cisplatin in node-positive) vs. TOS + neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94 % in each arm, compared to 84 %). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm.</div></div><div><h3>Results</h3><div>Sixty-one patients were randomized (n = 30 in RT arm and n = 31 in TOS+ND arm), with a median age of 62 years (IQR: 57–68). The majority were male (n = 51) and never-smokers (n = 31). Median follow-up was 3.7 years (IQR: 3.1–4.5 years). In the RT arm, the primary endpoint for acceptability was met (p = 0.008), and two-year OS was 100 % (95 % confidence interval [CI]: 100–100 %). In the TOS+ND arm, the primary endpoint was not met (p = 0.296) and two-year OS was 90 % (95 % CI: 71–97 %), significantly worse than the RT arm (p = 0.041). Two-year progression-free survival (PFS) were 100 % (95 % CI: 100–100 %) vs. 86 % (95 % CI: 67–95 %) respectively (p = 0.012). Mean (± SD) 2-year MDADI total scores were 89 ± 13 vs. 83 ± 11, respectively (p = 0.11), and grade 2–5 toxicity rates were similar (n = 21 vs. n = 24 respectively, p = 0.51), with no additional grade 5 events.</div></div><div><h3>Conclusion</h3><div>For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials.</div></div><div><h3>Trial Registration</h3><div>Clinicaltrials.gov NCT03210103.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115343"},"PeriodicalIF":7.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686722","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}