European Journal of Cancer最新文献

{"title":"CAR-T cell therapy for patients with extramedullary multiple myeloma：Opportunities and challenges","authors":"Yin Wang ,&nbsp;Xiaoli Hu ,&nbsp;Juan Du ,&nbsp;Bei Liu","doi":"10.1016/j.ejca.2025.115374","DOIUrl":"10.1016/j.ejca.2025.115374","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a hematological malignancy characterized by abnormal proliferation of clonal plasma cells, which is usually confined to the bone marrow (BM). But some malignant plasma cells grow independently of the BM, called extramedullary disease (EMD). With the clinical application of proteasome inhibitors, immunomodulators, monoclonal antibodies, and hematopoietic stem cell transplantation, the overall survival of MM patients has been significantly improved, but the survival of patients with EMD is still worse than that of non-EMD patients. There are currently no specific treatment options for EMD. chimeric antigen receptor T (CAR-T) cell therapy has brought a new era of immunotherapy. The application of CAR-T has significantly benefited many MM patients, and CAR-T may be a new hope for patients with EMD in the future. This review retrospectively summarizes the mechanism and prognosis of EMD, focusing on the application and potential of CAR-T in the treatment of EMD. It is hoped that this review can provide ideas for the treatment of EMD with CAR-T in the future.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115374"},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768646","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":"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":"Reduction in surgical interventions in melanoma","authors":"Alexander C.J. van Akkooi ,&nbsp;Alexander M.M. Eggermont","doi":"10.1016/j.ejca.2025.115376","DOIUrl":"10.1016/j.ejca.2025.115376","url":null,"abstract":"<div><div>Melanoma surgery has evolved from elective lymph node dissection (ELND) to sentinel lymph node biopsy (SLNB) and wide local excision (WLE) margins have come down from 5 cm to nowadays 1 – 2 cm. Recent studies have illustrated the low frequency of residual tumour cells in WLE specimen, particularly for pT2 or lower tumours, where 97 % of patients cannot benefit from WLE. Moreover, a cohort of completely excised primary melanomas did not seem to have inferior clinical outcomes to those who did undergo WLE. Biomarkers, such as clinicopathological gene expression profilers (CP-GEP), can stratify high- and low-risk disease and make therapy decisions, in particular in clinical stage I/II melanoma and make sentinel lymph node biopsy (SLNB) largely redundant. Also SLNB needs to be reconsidered due to the lack of a clear overall survival benefit for adjuvant therapy in stage III. Moreover SLNB is redundant in stage IIB/C for decision making on adjuvant anti-PD1 therapy. Moreover the superiority of neo-adjuvant to salvage patients with macroscopic stage III over adjuvant therapy leads to sharp reduction of therapeutic lymph node dissections (TLND). Overall, the major impact of current developments is that SLNB might soon become obsolete and may be replaced by standard CP-GEP testing of the primary for clinical management, reduction of surgical interventions and simplification of follow up schedules in low risk patients. Thus, we are on the eve of a significant reduction in surgical interventions for melanoma that will come in the upcoming years.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115376"},"PeriodicalIF":7.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771624","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":"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 ,&nbsp;Renata L. Sandoval ,&nbsp;Benjamin Verret ,&nbsp;Natalia Polidorio ,&nbsp;Olivier Caron ,&nbsp;Alessandra Gennari ,&nbsp;Brittany L. Bychkovsky ,&nbsp;Sophie H. Cahill ,&nbsp;Maria I. Achatz ,&nbsp;Valentina Guarneri ,&nbsp;Fabrice André ,&nbsp;Judy E. Garber","doi":"10.1016/j.ejca.2025.115370","DOIUrl":"10.1016/j.ejca.2025.115370","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 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":"Conference on challenges in sarcoma (CCS) 2024: Expert opinions on non-evidence-based management aspects","authors":"Silvia Hofer ,&nbsp;Chantal Pauli ,&nbsp;Beata Bode ,&nbsp;Sylvie Bonvalot ,&nbsp;Christina Fotopoulou ,&nbsp;Hans Gelderblom ,&nbsp;Rick L Haas ,&nbsp;Jendrik Hardes ,&nbsp;Peter Hohenberger ,&nbsp;Jens Jakob ,&nbsp;Wolfgang G Kunz ,&nbsp;Andreas Leithner ,&nbsp;Bernadette Liegl-Atzwanger ,&nbsp;Lars H Lindner ,&nbsp;Aisha B Miah ,&nbsp;Peter Reichardt ,&nbsp;Piotr Rutkowski ,&nbsp;Benedikt M Schaarschmidt ,&nbsp;Katrin Scheinemann ,&nbsp;Joanna Szkandera ,&nbsp;Christian Rothermundt","doi":"10.1016/j.ejca.2025.115368","DOIUrl":"10.1016/j.ejca.2025.115368","url":null,"abstract":"<div><h3>Background</h3><div>Soft tissue sarcomas (STS) and other mesenchymal tumours belong to rare, heterogeneous neoplasms with over 150 subtypes that pose significant challenges in diagnosis and clinical decision making. While guidelines address evidence-based diagnostic and therapeutic procedures, clinical situations and scenarios without evidence remain controversial in daily practice. The 2024 Conference on Challenges in Sarcoma (CCS2024) aimed to narrow these gaps with the support of an international and multidisciplinary panel of sarcoma experts.</div></div><div><h3>Methods</h3><div>A Delphi process identified 200 controversial questions across eight prioritised clinical scenarios, including tenosynovial giant cell tumour, synovial sarcoma of the extremities, retroperitoneal sarcomas, angiosarcoma, phyllodes tumour, malignant peripheral nerve sheath tumour, uterine leiomyosarcoma, and atypical lipomatous tumour.</div></div><div><h3>Results</h3><div>Sixty-four experts discussed 141 controversies during the conference and reached strong consensus (&gt; 90 %) on 24 and consensus (&gt; 75 %) on 45 key diagnostic and therapeutic issues, while unresolved controversies emphasized the need for further research.</div></div><div><h3>Conclusions</h3><div>CCS2024 provides a framework for clinical decision making and underscores the importance of consensus-driven approaches in the treatment of rare and complex malignancies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115368"},"PeriodicalIF":7.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768643","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}