The Lancet Oncology最新文献

{"title":"Whole-genome sequencing in breast cancer: is it ready for clinical application?","authors":"Peter Savas, Sherene Loi","doi":"10.1016/s1470-2045(25)00428-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00428-0","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical potential of whole-genome data linked to mortality statistics in patients with breast cancer in the UK: a retrospective analysis","authors":"Daniella Black, Helen Ruth Davies, Gene Ching Chiek Koh, Lucia Chmelova, Marko Cubric, Georgia Chalivelaki Chan, Andrea Degasperi, Jan Czarnecki, Ping Jing Toong, Yasin Memari, James Whitworth, Salome Jingchen Zhao, Yogesh Kumar, Shadi Basyuni, Giuseppe Rinaldi, Scott Shooter, Vladyslav Dembrovskyi, Rosie Davies, Maria Chatzou Dunford, Ellen Copson, Serena Nik-Zainal","doi":"10.1016/s1470-2045(25)00400-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00400-0","url":null,"abstract":"<h3>Background</h3>Breast cancer is the most frequently diagnosed cancer in women. Survival is generally considered favourable, yet some patients remain at risk of early death. We aimed to assess whether comprehensive whole-genome sequencing (WGS) linked to mortality data could add prognostic value to existing clinical measures and identify patients who might respond to targeted therapeutics.<h3>Methods</h3>In this integrative, retrospective analysis, we analysed 2445 breast cancer tumours (any stage and molecular subtype) collected from 2403 patients recruited through 13 National Health Service Genomic Medicine Centres or hospitals in England affiliated to the 100 000 Genomes Project (100kGP) between 2012 and 2018. We linked 2208 (90%) cases with clinical data; mortality data were obtained for 1188 patients. Following high-depth WGS of tumour and matched normal DNA, we performed comprehensive WGS profiling seeking driver mutations, mutational signatures, and compound algorithmic scores for homologous recombination repair deficiency (HRD), mismatch repair deficiency, and tumour mutational burden. Data from 1803 additional patients with breast cancer from three independent cohorts were used to validate various findings. To evaluate the prognostic value of WGS features, we performed univariable and multivariable Cox regression on data from patients with stage I–III, ER-positive, HER2-negative breast cancer with a cancer-specific mortality endpoint (around 5-year follow-up).<h3>Findings</h3>Among 2445 tumours in the 100kGP breast cancer cohort, we observed genomic characteristics with immediate personalised medicine potential in 656 (26·8%), including features reporting HRD (298 [12·2%] total cases and 76 [6·3%] ER-positive, HER2-negative cases), highly individualised driver events, mutations underpinning resistance to endocrine therapy, and mutational signatures indicating therapeutic vulnerabilities. 373 (15·2%) cases had WGS features with potential for translational research, including compromised base excision repair and non-homologous end-joining dependency. Structural variation burden (hazard ratio 3·9 [95 CI% 2·4–6·2]; p<0·0001), high levels of APOBEC signatures (2·5 [1·6–4·1]; p<0·0001), and <em>TP53</em> drivers (3·9 [2·4–6·2]; p<0·0001) were independently prognostic of customary clinical measures (age at diagnosis, stage, and grade) in patients with ER-positive, HER2-negative breast cancer. We developed a prognosticator for ER-positive, HER2-negative breast cancer capable of identifying patients who require either increased intervention or therapy de-escalation, validating the framework in the independent Swedish Cancerome Analysis Network-Breast (SCAN-B) dataset.<h3>Interpretation</h3>We show that breast cancer genomes are rich in predictive and prognostic value. We propose a two-step model for effective clinical application. First, the identification of candidates for targeted therapies or clinical trials using highly individual","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New system to allow artificial intelligence clinical trials to take place across all UK NHS Trusts","authors":"Tony Kirby","doi":"10.1016/s1470-2045(25)00597-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00597-2","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term overall survival with dual CTLA-4 and PD-L1 or PD-1 blockade and biomarker-based subgroup analyses in patients with advanced non-small-cell lung cancer: a systematic review and reconstructed individual patient data meta-analysis","authors":"Alessandro Di Federico, Sara Stumpo, Francesco Mantuano, Andrea De Giglio, Francesca Lo Bianco, Federica Pecci, Joao V Alessi, Xinan Wang, Francesca Sperandi, Barbara Melotti, Francesco Gelsomino, Ferdinandos Skoulidis, Marina C Garassino, Solange Peters, Mark M Awad, Andrea Ardizzoni, Biagio Ricciuti","doi":"10.1016/s1470-2045(25)00429-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00429-2","url":null,"abstract":"<h3>Background</h3>Immune checkpoint inhibitors targeting PD-L1 or PD-1 as monotherapy or combined with CTLA-4 inhibitors or chemotherapy (or both) are the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, it remains unclear which patients benefit from the addition of CTLA-4 inhibitors. We aimed to evaluate whether dual checkpoint blockade with CTLA-4 and PD-L1 or PD-1 inhibitors provides similar efficacy to PD-L1 or PD-1 inhibitor monotherapy, or whether these strategies produce distinct outcomes across NSCLC subpopulations.<h3>Methods</h3>We conducted a search of PubMed, MEDLINE, and Embase for randomised phase 3 trials published from database inception to Nov 21, 2024, that investigated PD-L1 or PD-1 inhibitors, with or without CTLA-4 inhibitors, in patients with advanced NSCLC. We focused on studies reporting Kaplan–Meier survival data at 5 years or biomarker analyses based on PD-L1, <em>KRAS</em>, and <em>STK11</em> mutational status. Individual patient data were extracted from Kaplan–Meier curves with WebPlotDigitizer version 5 and reconstructed with the IPDfromKM method. The primary endpoint of the study was 5-year overall survival in the overall population and in subpopulations based on PD-L1 tumour proportion score (TPS), tumour histology, and mutational status (mutant vs wild-type) of <em>KRAS</em> and <em>STK11</em>. This study was registered with PROSPERO, CRD420251081707.<h3>Findings</h3>The initial search yielded 1026 results, and six randomised clinical trials met the eligibility criteria and were included. Among the 2881 patients eligible for analysis (838 [29·1%] female and 2043 [70·9%] male), 1282 received dual CTLA-4 and PD-L1 or PD-1 blockade and 1599 received single PD-L1 or PD-1 blockade. Patients treated with dual CTLA-4 and PD-L1 or PD-1 blockade had similar median overall survival compared with those treated with single PD-L1 or PD-1 inhibition (16·1 months [95% CI 15·0–17·8] <em>vs</em> 16·9 months [15·5–18·3]; HR 0·95 [95% CI 0·87–1·03], p=0·19). Median overall survival was significantly longer with dual CTLA-4 and PD-L1 or PD-1 blockade among patients with PD-L1 TPS less than 1% versus those treated with single PD-L1 or PD-1 inhibition (15·5 months [95% CI 13·6–18·5] <em>vs</em> 14·5 months [13·4–15·9]; HR 0·85 [95% CI 0·74–0·98], p=0·021), with 5-year overall survival rates of 16·6% (95% CI 13·4–20·6) versus 9·3% (7·0–12·3), respectively. Median overall survival in patients with tumours harbouring <em>STK11</em> mutations was also significantly longer with dual CTLA-4 and PD-L1 or PD-1 blockade compared with single PD-L1 or PD-1 inhibition (13·9 months [95% CI 9·8–20·8] <em>vs</em> 7·8 months [6·4–12·9]; HR 0·67 [95% CI 0·49–0·91], p=0·012). However, no significant differences in overall survival were found between treatment groups by tumour histology (squamous <em>vs</em> non-squamous NSCLC) or by <em>KRAS</em> mutational status.<h3>Interpretation</h3>Compared with single PD-L1 ","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing patient-centred CINV care: gaps in olanzapine trial design – Authors’ reply","authors":"Mitsue Saito, Hirotoshi Iihara","doi":"10.1016/s1470-2045(25)00547-9","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00547-9","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity assessment bias in the PACE-C trial – Authors' reply","authors":"Alison C Tree, Emma Hall, Nicholas vas As","doi":"10.1016/s1470-2045(25)00536-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00536-4","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"1152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing patient-centred CINV care: gaps in olanzapine trial design","authors":"Man Sun, Dan Zang, Jun Chen","doi":"10.1016/s1470-2045(25)00433-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00433-4","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Oncol 2025; 26: 1067–80","authors":"","doi":"10.1016/s1470-2045(25)00488-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00488-7","url":null,"abstract":"<em>Hungria V, Robak P, Hus M, et al. Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial.</em> Lancet Oncol <em>2025; <strong>26:</strong> 1067–80</em>—In this Article, the affiliation for Prof Marek Hus and Michał Mielink should have been “Medical University of Lublin”. This correction has been made to the online version as of Sept 29, 2025.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Between the lines: an oncology diary no one assigned","authors":"Vangipuram Harshil Sai","doi":"10.1016/s1470-2045(25)00342-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00342-0","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Prologue</h2>It was a quiet summer, and I was determined to switch off—no clinics, no case logs, just rest. One afternoon, while unpacking a forgotten tote bag, I came across the black diary I had carried through my oncology postings. I opened it casually, not expecting much. But the pages pulled me back to bed 32, where Meena once lay. To questions I still could not answer and to moments I had never spoken about. I did not find case summaries. I found pieces of myself I had left behind.That summer, I</section></section><section><section><section><h2>The prognosis conversation</h2>Mr Iqbal was aged 83 years—a retired Urdu teacher with a dignified stillness about him. His history read like a ticking clock: stented triple-vessel coronary disease, diabetic nephropathy with chronic renal failure, and hypertensive cardiomegaly. He walked daily to the mosque until his speech began to slur and his left hand lost subtlety. An MRI revealed an advanced, infiltrative insular glioma; non-resectable, poorly accessible, and silently devastating.The oncology consultant offered</section></section></section><section><section><h2>The diary: my quiet curriculum</h2>Hospitals have official curricula: anatomy labs, clinical skills, and pharmacology. But beneath all that runs a quieter syllabus, one without PowerPoints or page numbers. I found mine in the pages of a small black diary tucked into my coat pocket.It began as scribbles, quick notes between rounds, fragments of feeling I did not know where else to put. Over time, they became confessions. No one teaches you how to carry a patient's silence or what to do with the guilt that seeps in after loss.That</section></section><section><section><h2>Epilogue: the diary revisited</h2>Weeks later, bed 32 was empty.The sheets had been changed. The monitor unplugged. The drip stand stood like a question mark beside the bed. But Meena's absence felt louder than any alarm. The new patient in that bed had no idea whose silence they had inherited.That night, I flipped through my diary and found the last line I had written about Meena:“Her pain seemed bigger than her body. But she smiled when I said she looked strong. Maybe we both lied a little. Maybe lying was mercy”.For my final</section></section>","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour genetics and thyroid cancer staging: a balancing act","authors":"Susan C Pitt, Megan Haymart","doi":"10.1016/s1470-2045(25)00424-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00424-3","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}