BMJ oncology最新文献

{"title":"Improving patient understanding of GEP test results (IMPARTER4): an RCT.","authors":"Lesley Fallowfield, Ivonne Solis-Trapala, Rachel Starkings, Lucy Matthews, Shirley May, Valerie Jenkins","doi":"10.1136/bmjonc-2024-000689","DOIUrl":"10.1136/bmjonc-2024-000689","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Objective: </strong>Explaining gene expression profiling (GEP) test results to patients can be challenging. We examined the utility of two 8 min films about Oncotype DX and Prosigna to aid the knowledge and decision-making of women with early-stage oestrogen receptor positive (ER+) breast cancer.</p><p><strong>Methods and analysis: </strong>Patients awaiting GEP test results completed an anxiety questionnaire and the intolerance of uncertainty scale (IUS) before randomisation and divided into Group A (standard verbal and/or written hospital information) or Group B (standard information plus GEP film). Prior to results, they were interviewed about their GEP test knowledge and how the recurrence risk helps determine treatment options. After the results consultation, participants answered two further questionnaires. Participating clinicians completed IUS scales and reported their satisfaction with the results discussions.</p><p><strong>Results: </strong>230/251 patients completed the study (Group A (n=106) and Group B (n=124)). The total knowledge score was higher in Group B (estimated between groups mean difference of 2.5 (95% CI:1.7 to 3.4) p<0.001). Most treatment decisions adhered to recommended risk of recurrence thresholds, although patients with higher trait anxiety were more likely to make less apparently rational decisions OR=0.93 (95%CI 0.88 to 0.97) p=0.002 (163/230; 70.8% received ET alone; 65/230; 28% ET plus chemotherapy, and two sought second opinions). Clinicians reported slightly longer consultations for Group A participants who tended to ask more difficult and unexpected questions.</p><p><strong>Conclusion: </strong>Patients who received standard verbal and written information plus film had increased knowledge about GEP tests compared with standard information alone.</p><p><strong>Trial registration number: </strong>ISRCTN28497350.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000689"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TERT promoter mutations or protein overexpression define an aggressive subset with favourable immunotherapeutic response in advanced urothelial carcinoma.","authors":"Kaifeng Jin, Jingtong Xu, Lingkai Zhang, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Yawei Ding, Hailong Liu, Yuan Chang, Le Xu, Zewei Wang, Yu Zhu, Jiejie Xu","doi":"10.1136/bmjonc-2024-000586","DOIUrl":"10.1136/bmjonc-2024-000586","url":null,"abstract":"<p><strong>Objective: </strong>Telomerase reverse transcriptase (<i>TERT</i>) gene promoter mutation (TPM) is a key non-coding somatic alteration in urothelial carcinoma (UC) that plays a critical role in telomerase activation. Despite its importance, the prognostic value of TPM has shown mixed results in previous studies.</p><p><strong>Methods and analysis: </strong>This study included 155 UC patients from two local clinical centres and 1652 patients from four public datasets, along with matched clinical annotation. Immunohistochemistry of TERT and immune-related markers was performed on tissue microarrays, and transcriptomic and genomic data were analysed to evaluate immune microenvironment characteristics and mutational profiles associated with TPM. We assessed the association of TPM or TERT overexpression (OE) with clinical outcomes, genomics and immunological profiles across tumour stages.</p><p><strong>Results: </strong>In early-stage UC, TPM or TERT OE was not significantly associated with patient outcomes. However, in advanced urothelial carcinoma (aUC), TPM or TERT OE was linked to markedly worse overall survival (OS) and a poor response to platinum-based chemotherapy. Notably, despite this unfavourable prognosis, these patients exhibited a more favourable response to anti-PD-1/PD-L1 immunotherapy. aUC with TPM or TERT OE was characterised by an immune-evasive microenvironment, including infiltration of exhausted CD8⁺ T cells and elevated PD-1 and PD-L1 expression. Furthermore, genomic analysis further revealed a higher APOBEC mutational signature and a lower clock-like mutational signature in aUC with TPM or TERT OE.</p><p><strong>Conclusion: </strong>In this retrospective study, TPM or TERT OE identifies a more aggressive subset of patients with poor OS and an immune-evasive microenvironment but a better response to immunotherapy in aUC.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000586"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveillance imaging: minimal evidence and forgotten harms.","authors":"Haydee Verduzco-Aguirre, Christopher M Booth, Brooke E Wilson","doi":"10.1136/bmjonc-2024-000724","DOIUrl":"10.1136/bmjonc-2024-000724","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000724"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review comparing surveillance recommendations for the detection of recurrence following surgery across 16 common cancer types.","authors":"Hannah Harrison, Bhumi K Shah, Faris Khan, Carley Batley, Chiara Re, Sabrina H Rossi, Georgia Stimpson, Eamonn Gilmore, Eleanor White, Sofia Kler-Sangha, Aufia Espressivo, Z Sienna Pan, Tanzil Rujeedawa, Benjamin W Lamb, Laura Succony, Shi Lam, Bincy M Zacharia, Rebecca Lucey, Alexander J P Fulton, Dimana Kaludova, Anita Balakrishnan, Juliet A Usher-Smith, Grant D Stewart","doi":"10.1136/bmjonc-2024-000627","DOIUrl":"10.1136/bmjonc-2024-000627","url":null,"abstract":"<p><strong>Objectives: </strong>Identify and compare guidelines making recommendations for surveillance to detect recurrence in 16 common solid cancers after initial curative treatment in asymptomatic patients.</p><p><strong>Methods and analysis: </strong>We conducted a systematic review, combining search results from two electronic databases, one guideline organisation website (NICE), expert consultation and manual searching. Screening and data extraction were carried out by multiple reviewers. We collected data from each guideline on recommendations for surveillance and the use of risk stratification. Findings were compared between cancer types and regions. Text mining was used to extract statements on the evidence for surveillance. A protocol was published on PROSPERO in 2021 (CRD42021289625).</p><p><strong>Results: </strong>We identified 123 guidelines across 16 cancer types. Almost all guidelines (n<i>=</i>115, 93.5%) recommend routine surveillance for recurrent disease in asymptomatic patients after initial treatment. Around half (n=59, 51.3%) recommend indefinite or lifelong surveillance. The most common modality of surveillance was cross-sectional imaging. Risk stratification of frequency, length and mode of surveillance was widespread, with most guidelines (n<i>=</i>92, 74.8%) recommending that surveillance be adapted based on patient risk. More than a third (n<i>=</i>50, 39.0%) gave incomplete or vague recommendations. For 14 cancers, we found statements indicating there is no evidence that surveillance improves survival.</p><p><strong>Conclusion: </strong>Although specific details of follow-up schedules vary, common challenges were identified across cancer types. These include heterogenous recommendations, vague or non-specific guidance and a lack of cited evidence supporting the use of surveillance to improve outcomes. Evidence generation in this area is challenging; however, increased availability to linked health records may provide a way forward.</p><p><strong>Prospero registration number: </strong>CRD42021289625.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000627"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of resection margin width on local recurrence following breast-conserving surgery and whole breast radiotherapy for pure ductal carcinoma in situ: a systematic review and meta-analysis.","authors":"Ahmed Ezzat, Dhurka Shanthakumar, Naomi Laskar, Ramsey I Cutress, Dimitri Hadjiminas, Michael Boland, Meera Joshi, Ronak Patel, Yasmin Grant, Ravi Naik, Nur Amalina Che Bakri, Saur Hajev, Hussein Elghazaly, Josephine Holt, Alfie Roddan, Susan Cleator, Ara Darzi, Hutan Ashrafian, Daniel R Leff","doi":"10.1136/bmjonc-2024-000633","DOIUrl":"10.1136/bmjonc-2024-000633","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to determine the impact of margin width and boost radiotherapy on the local recurrence risk of pure ductal carcinoma in situ (DCIS).</p><p><strong>Methods and analysis: </strong>This is a prospectively registered systematic review and meta-analysis reporting relative risk (RR), OR and HR margin width outcomes. Eligible studies included prospective and retrospective case series with defining margin widths and 48 months of minimum follow-up. All patients (100%) received adjuvant whole breast radiotherapy (WBRT).</p><p><strong>Results: </strong>A total of 40 265 patients with pure DCIS in 31 studies were included. ORs and RR were calculated from 15 studies in 12 519 patients, and HRs were calculated from 12 studies in 12 946 patients. Local recurrence was significantly greater with narrower 'close' margins; 0.1-1 mm versus >1 mm in RR (2.88, 95% CI 1.86 to 3.90; p<0.05), OR (4.82, 95% CI 2.45 to 9.48; p<0.05) and HR analysis (1.34, 95% CI 1.01 to 1.67; p<0.05). Compared with margins >2 mm, significantly greater local recurrence was observed in margins 0.1-2 mm in RR (1.72, 95% CI 1.09 to 2.35; p<0.05) and OR (4.43, 95% CI 3.02 to 6.50; p<0.05). Comparing 0.1-1 mm versus >1 mm and 0.1-2 mm versus >2 mm, differences in local recurrence were not statistically significant, once adjusted for boost radiotherapy.</p><p><strong>Conclusions: </strong>In pure DCIS with WBRT, the local recurrence risk reduces as margin width increases up to 2 mm. The strength of the recommendation for a minimum clear margin of 2 mm is limited by a lack of data comparing 1.1-2 mm with >2 mm. The association between recurrence and close margins is not significant following boost radiotherapy, suggesting a possible alternative to re-excision in patients with close margins <2 mm.</p><p><strong>Systematic review registration: </strong>CRD42022308524.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000633"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of prostate cancer in men with testosterone deficiency and a family history of prostate cancer receiving testosterone therapy: a comparative study.","authors":"Edoardo Pozzi, Corey A Able, Taylor Kohn, Bruce R Kava, Francesco Montorsi, Andrea Salonia","doi":"10.1136/bmjonc-2024-000520","DOIUrl":"10.1136/bmjonc-2024-000520","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the incidence of any PCa diagnosis in men with testosterone deficiency (TD) who have a family history of PCa and were prescribed TTh compared with a control cohort of men with TD with a family history of PCa but who were not prescribed TTh, over a period of 10 years.</p><p><strong>Methods and analysis: </strong>Retrospective cohort study using data from 1 January 2012 to 7 March 2024 (TriNetX database). After meeting the inclusion criteria, 3041 men were analysed: 628 with family history of PCa and TD who received TTh, and 2413 who did not. We used propensity score matching to balance baseline characteristics between cohorts. The main outcomes were the risk of any PCa diagnosis and any active treatment (including radical prostatectomy, androgen deprivation therapy, brachytherapy, radiation and cryoablation) among men with TD who received TTh versus a matched cohort who did not.</p><p><strong>Results: </strong>Over 10 years, the risk of PCa diagnosis did not significantly differ between men who received TTh (6.26%) and those who did not (5.46%), HR 0.81, 95% CI 0.51 to 1.28. Similarly, no significant difference was found in the risk of receiving any active treatment for PCa between those who received TTh (2.73%) and those who did not (3.69%), HR 0.55, 95% CI 0.29 to 1.03.</p><p><strong>Conclusions: </strong>Men with TD and a family history of PCa who were prescribed TTh showed comparable risks of being diagnosed with PCa or receiving any active treatment for PCa, relative to men with analogous TD and family history, but who did not receive TTh.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000520"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy response in immunosuppressed patients with Merkel cell carcinoma: analysis of 183 patients.","authors":"Emily Gong, Lauren Zawacki, Xinyi Fan, Daniel S Hippe, Ankita A Menon, Allison J Remington, Kristina Lachance, Tomoko Akaike, Lisa Tachiki, Song Y Park, Paul Nghiem","doi":"10.1136/bmjonc-2024-000654","DOIUrl":"10.1136/bmjonc-2024-000654","url":null,"abstract":"<p><strong>Objective: </strong>Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor outcomes in immunosuppressed patients. While immune checkpoint inhibitors (ICIs) achieve ~60% response rates in immunocompetent MCC patients, their efficacy in immunosuppressed patients remains unclear due to exclusion from trials. This study compares ICI outcomes, safety and the impact of immunosuppression subtypes between these groups.</p><p><strong>Methods and analysis: </strong>This retrospective study analysed 183 advanced MCC patients on first-line ICIs from a Seattle-based data repository. Of these, 147 were immunocompetent, and 36 were immunosuppressed (chronic lymphocytic leukaemia (CLL) n=10, autoimmune disorders n=10, other haematologic malignancies n=9, solid organ transplants n=4 and HIV/AIDS n=3). Outcomes included objective response rate, disease progression, MCC-specific and overall survival probability, adjusted for age, sex and stage at ICI initiation.</p><p><strong>Results: </strong>Initial ICI response rates at 6 months were 50% in immunosuppressed and 61.5% in immunocompetent patients (HR=0.71, p=0.17). Immunosuppressed patients had higher risks of disease progression (2 years: 53.9% vs 42.1%, HR=1.65, p=0.05) and MCC-specific mortality (2 years: 38.7% vs 24.4%, HR=1.85, p=0.04). CLL patients (n=10) had a particularly low response rate (response rate: 20.0% vs 61.5%, HR=0.18, p=0.02) and high progression risk (2 years: 80.0% vs 42.1%, HR=4.09, p=0.01). Immunosuppressed patients faced higher rates of ICI toxicity (6-month risk: 51.6% vs 36.6%, HR=1.79, p=0.03).</p><p><strong>Conclusions: </strong>ICIs provide meaningful benefits to immunosuppressed MCC patients, though their response rates are lower, and progression risk is higher compared with immunocompetent patients.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000654"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Checkpoint inhibitor therapy in immunosuppressed patients with Merkel cell carcinoma: not all immunosuppression is created equal.","authors":"Andrew S Brohl","doi":"10.1136/bmjonc-2024-000695","DOIUrl":"10.1136/bmjonc-2024-000695","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000695"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluating testosterone therapy: new insights for men with familial prostate cancer risk.","authors":"Omer Onur Cakir, Fabio Castiglione","doi":"10.1136/bmjonc-2024-000635","DOIUrl":"10.1136/bmjonc-2024-000635","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000635"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of DNA methylation in breast tumour subtypes with parity and breastfeeding in a cohort of 1459 Black women: implications for public health.","authors":"Christine B Ambrosone, Song Yao, Mark D Long, Chunyu Liu, Jianhong Chen, Warren Davis, Gary Zirpoli, Rochelle Payne-Ondracek, Thaer Khoury, Zhihong Gong, Qiang Hu, Sirinapa Szewczyk, Angela R Omilian, Elisa V Bandera, Song Liu, Lawrence Kushi, Michael J Higgins, Julie R Palmer","doi":"10.1136/bmjonc-2024-000675","DOIUrl":"10.1136/bmjonc-2024-000675","url":null,"abstract":"<p><strong>Objective: </strong>Having children reduces risk of breast cancer overall, but parity without breastfeeding, more prevalent among black women, increases risk of poor-prognosis oestrogen receptor negative (ER-) breast cancer. We investigated if relationships between parity, breastfeeding and ER subtypes result from epigenetic programming, potentially steering breast progenitor cells to a basal-like phenotype.</p><p><strong>Methods and analysis: </strong>The Illumina MethylationEPIC platform was used to assess genome-wide methylation in formalin-fixed, paraffin-embedded tumours from 1459 Black women with breast cancer. Methylation was evaluated in relation to parity, breastfeeding and breast cancer subtypes in a case-only analysis, with methylation-gene expression pairs tested in a subset of cases. We then performed functional enrichment analysis for probes significantly associated with parity and breastfeeding.</p><p><strong>Results: </strong>Among women who did not breastfeed (n=634), there were 500 significant (p<1e-5) differentially methylated loci (DML) by parity, compared with only five DMLs among women who had breastfed their children (n=568). One of the top DML genes was <i>FOXA1</i>, pivotal in governing the luminal lineage of progenitor cells, with a statistically significant interaction (p=0.04) for number of births and breastfeeding. Associations were strongest for ER- disease.</p><p><strong>Conclusion: </strong>In this large study of Black women with breast cancer, we elucidated biological pathways for the observed associations between parity without breastfeeding and breast cancer subtypes, revealing distinct molecular alterations in breast DNA, particularly for ER- tumours. Black women in the USA tend to have more children and are less likely to breastfeed; their breast cancer risk may be reduced by societal systems that promote and support breastfeeding.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000675"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}