BMJ oncology最新文献

{"title":"Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma.","authors":"Khalil Choucair, Andrew Elliott, Matthew James Oberley, Phillip Walker, April K Salama, Azhar Saeed, Hirva Mamdani, Dipesh Uprety, Wafik S El-Deiry, Himisha Beltran, Stephen V Liu, Chul Kim, Abdul Rafeh Naqash, Emil Lou, Lujia Chen, Anwaar Saeed","doi":"10.1136/bmjonc-2024-000551","DOIUrl":"10.1136/bmjonc-2024-000551","url":null,"abstract":"<p><strong>Objective: </strong>Cancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI in patients ≥80 years.</p><p><strong>Methods and analysis: </strong>We analysed tumour samples (n=24 123) from patients ≥80 (versus<80) with non-small cell lung cancer (NSCLC), melanoma (MEL), and renal cell cancer (RCC). Using gene expression deconvolution, we investigated differences in tumour microenvironment (TIME) composition. Then, using next-generation sequencing and programmed death-ligand 1 (PD-L1) assessment, we evaluated gene expression differences between age groups and across tumour types, with a focus on ageing-related processes such as DNA damage response (DDR), immune checkpoint (IC) and metabolism-related genes. In a subset of patients ≥80 (n=1013), gene clustering and differential gene expression analyses were carried out to identify potential tumour-type specific expression patterns in responders to ICI.</p><p><strong>Results: </strong>Significant differences in TIME composition were seen in patients with NSCLC and MEL. In patients ≥80, tumour mutational burden was lower in patients with NSCLC, higher in MEL and RCC had fewer PD-L1+tumours. DDR, IC and metabolism-related gene enrichments were distinct in patients ≥80. In patients ≥80 treated with ICIs (n=1013), there were no significant differences in survival between gene clusters, but differential gene expression analysis identified potential tumour-type specific expression patterns in responders.</p><p><strong>Conclusion: </strong>Our findings reveal tumour type-specific expression profiles, TIMEs and response signatures to ICIs in patients ≥80, supporting further biomarker investigations in this population.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000551"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070011","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":"Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil/Caelyx): an updated analysis and future perspective.","authors":"Alberto A Gabizon, Shira Gabizon-Peretz, Shadan Modaresahmadi, Ninh M La-Beck","doi":"10.1136/bmjonc-2024-000573","DOIUrl":"10.1136/bmjonc-2024-000573","url":null,"abstract":"<p><p>In 2025, it will be 30 years since the initial clinical approval of pegylated liposomal doxorubicin (PLD) by the Food and Drug Administration. PLD predated the field of nanomedicine and became a model nanomedicine setting key pharmacological principles (prolonged circulation, slow drug release and the enhanced permeability and retention (EPR) effect) for clinical application of other nano-drugs in cancer therapy. The impressive reduction of cardiotoxicity conferred by PLD is the most valuable clinical asset. While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breast cancer, it has not been extensively tested in primary (neoadjuvant) and adjuvant therapy and has not fulfilled the expectations from the results in animal models efficacy-wise. This discrepancy may be due to the large dose gap between mice and humans and the apparent variability of the EPR effect in human cancer. PLD is a complex product and we are still in a learning curve regarding a number of factors such as its interaction with the complement system and its immune modulatory properties, as well as its integration in multimodality therapy that may potentiate its value and role in cancer therapy.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000573"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070014","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":"Cancer incidence and competing mortality risk following 15 presenting symptoms in primary care: a population-based cohort study using electronic healthcare records.","authors":"Matthew E Barclay, Cristina Renzi, Hannah Harrison, Ana Torralbo, Becky White, Samantha Hiu Yan Ip, Juliet Usher-Smith, Jane Lange, Nora Pashayan, Spiros Denaxas, Angela M Wood, Antonis Antoniou, Georgios Lyratzopoulos","doi":"10.1136/bmjonc-2024-000500","DOIUrl":"10.1136/bmjonc-2024-000500","url":null,"abstract":"<p><strong>Objectives: </strong>Assessment of age, sex and smoking-specific risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms.</p><p><strong>Methods and analysis: </strong>Data on patients aged 30-99 in 2007-2017 were extracted from a UK primary care database (CPRD Gold), comprising a randomly selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump and post-menopausal bleed).Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality and to estimate cumulative incidence up to 12 months following index consultation.</p><p><strong>Results: </strong>Data included 1 622 419 patients, of whom 36 802 had a cancer diagnosis and 28 857 died without a cancer diagnosis within 12 months of the index.The risk of specific cancers exceeded the UK urgent referral risk threshold of 3% from a relatively young age for patients with red flag symptoms. For non-organ-specific symptoms, the risk of cancer at individual sites either did not reach the threshold at any age or reached it only in older patients.</p><p><strong>Conclusion: </strong>Patients with new-onset symptoms in primary care often have comparable risks of cancer diagnosis and non-cancer mortality. Non-organ-specific symptoms, in particular, are associated with elevated risk of cancer at multiple different sites. Management of symptomatic patients in primary care should be informed by the risk of different cancer types alongside mortality risk.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000500"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069493","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":"Which patients with symptoms should be referred urgently for investigation of suspected cancer?","authors":"Sarah F Moore","doi":"10.1136/bmjonc-2024-000640","DOIUrl":"10.1136/bmjonc-2024-000640","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000640"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070008","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":"From prediction to practice: mitigating bias and data shift in machine-learning models for chemotherapy-induced organ dysfunction across unseen cancers.","authors":"Matthew Watson, Pinkie Chambers, Luke Steventon, James Harmsworth King, Angelo Ercia, Heather Shaw, Noura Al Moubayed","doi":"10.1136/bmjonc-2024-000430","DOIUrl":"10.1136/bmjonc-2024-000430","url":null,"abstract":"<p><strong>Objectives: </strong>Routine monitoring of renal and hepatic function during chemotherapy ensures that treatment-related organ damage has not occurred and clearance of subsequent treatment is not hindered; however, frequency and timing are not optimal. Model bias and data heterogeneity concerns have hampered the ability of machine learning (ML) to be deployed into clinical practice. This study aims to develop models that could support individualised decisions on the timing of renal and hepatic monitoring while exploring the effect of data shift on model performance.</p><p><strong>Methods and analysis: </strong>We used retrospective data from three UK hospitals to develop and validate ML models predicting unacceptable rises in creatinine/bilirubin post cycle 3 for patients undergoing treatment for the following cancers: breast, colorectal, lung, ovarian and diffuse large B-cell lymphoma.</p><p><strong>Results: </strong>We extracted 3614 patients with no missing blood test data across cycles 1-6 of chemotherapy treatment. We improved on previous work by including predictions post cycle 3. Optimised for sensitivity, we achieve F2 scores of 0.7773 (bilirubin) and 0.6893 (creatinine) on unseen data. Performance is consistent on tumour types unseen during training (F2 bilirubin: 0.7423, F2 creatinine: 0.6820).</p><p><strong>Conclusion: </strong>Our technique highlights the effectiveness of ML in clinical settings, demonstrating the potential to improve the delivery of care. Notably, our ML models can generalise to unseen tumour types. We propose gold-standard bias mitigation steps for ML models: evaluation on multisite data, thorough patient population analysis, and both formalised bias measures and model performance comparisons on patient subgroups. We demonstrate that data aggregation techniques have unintended consequences on model bias.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000430"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069930","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":"Bedside implications of the use of surrogate endpoints in solid and haematological cancers: implications for our reliance on PFS, DFS, ORR, MRD and more.","authors":"Timothée Olivier, Alyson Haslam, Dagney Ochoa, Eduardo Fernandez, Vinay Prasad","doi":"10.1136/bmjonc-2024-000364","DOIUrl":"10.1136/bmjonc-2024-000364","url":null,"abstract":"<p><p>Clinical endpoints, such as overall survival, directly measure relevant outcomes. Surrogate endpoints, in contrast, are intermediate, stand-in measures of various tumour-related metrics and include tumour growth, tumour shrinkage, blood results, etc. Surrogates may be a time point measurement, that is, tumour shrinkage at some point (eg, response rate) or biomarker-assessed disease status, measured at given time points (eg, circulating tumour DNA, ctDNA). They can also be measured over time, as with progression-free survival, which is the time until a patient presents with either disease progression or death. Surrogates are increasingly used in trials supporting the marketing authorisation of novel oncology drugs. Yet, the trial-level correlation between surrogates and clinical endpoints-meaning to which extent an improvement in the surrogate predicts an improvement in the direct endpoint-is often moderate to low. Here, we provide a comprehensive classification of surrogate endpoints: time point measurements and time-to-event endpoints in solid and haematological malignancies. Also, we discuss an overlooked aspect of the use of surrogates: the limitations of surrogates outside trial settings, at the bedside. Surrogates can result in the inappropriate stopping or switching of therapy. Surrogates can be used to usher in new strategies (eg, ctDNA in adjuvant treatment of colon cancer), which may erode patient outcomes. In liquid malignancies, surrogates can mislead us to use novel drugs and replace proven standards of care with costly medications. Surrogates can lead one to intensify treatment without clear improvement and possibly worsening quality of life. Clinicians should be aware of the role of surrogates in the development and regulation of drugs and how their use can carry real-world, bedside implications.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000364"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069076","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":"Consideration of initial steps to implementation of prostate cancer screening following the EU recommendation.","authors":"Patricia Fitzpatrick","doi":"10.1136/bmjonc-2024-000579","DOIUrl":"10.1136/bmjonc-2024-000579","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000579"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069764","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 between socioeconomic factors and PSA testing in a population-based organised testing programme and routine healthcare: a register-based study of 50-year-old men.","authors":"Emil Järbur, Erik Holmberg, Thomas Björk-Eriksson, Ola Bratt, Rebecka Arnsrud Godtman","doi":"10.1136/bmjonc-2024-000400","DOIUrl":"10.1136/bmjonc-2024-000400","url":null,"abstract":"<p><strong>Objective: </strong>Population-based, organised prostate cancer testing (OPT) programmes were started in Sweden in 2020. The influence of socioeconomic factors on prostate cancer testing in this setting is not known. We examined associations between socioeconomic factors and (1) participation in OPT and (2) unorganised prostate-specific antigen (PSA) testing.</p><p><strong>Methods and analysis: </strong>Region Västra Götaland's OPT programme invited 21 174 men aged 50 years in 2020-2021. Regional data on unorganised testing in 2013-2014 of men aged 50-52 years were retrieved from Western Sweden Study of Opportunistic Prostate Cancer Screening database. Data on income, education, cohabitation and country of birth were collected from Statistic Sweden. Univariable and multivariable Poisson regression was used to calculate incidence rate ratios (IRRs) with CIs for PSA testing by socioeconomic category.</p><p><strong>Results: </strong>Participation in OPT was associated with all investigated socioeconomic factors; multivariable IRRs: low versus non-low income 0.63 (95% CI 0.58 to 0.68), single versus non-single household 0.78 (95% CI 0.75 to 0.81), low versus average education 0.84 (95% CI 0.78 to 0.90) and non-Nordic versus Nordic country of birth 0.88 (95% CI 0.84 to 0.92). Unorganised PSA testing was negatively associated with low income 0.83 (95% CI 0.78 to 0.90) and single household 0.87 (95% CI 0.82 to 0.92), but not with low education 1.00 (95% CI 0.92 to 1.08) or non-Nordic country of birth 0.98 (95% CI 0.91 to 1.06).</p><p><strong>Conclusion: </strong>Socioeconomic factors influenced PSA testing among 50-year-old men, both in an organised testing programme and in unorganised, clinical testing. An active offer of testing is not enough to achieve socioeconomic equality in the early detection of prostate cancer.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000400"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070030","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":"Circulating tumour cell clusters: isolation, biological significance and therapeutic implications.","authors":"Yufan Yang, Guanyin Huang, Jingru Lian, Chunhao Long, Boxi Zhao, Xuefei Liu, Binyu Zhang, Weijian Ye, Junhao Chen, Longxiang Du, Zhuofeng Jiang, Jialing Liu, Jianglin Zhang, Chengzhi Hu, Qingfeng Chen, Xin Hong","doi":"10.1136/bmjonc-2024-000437","DOIUrl":"10.1136/bmjonc-2024-000437","url":null,"abstract":"<p><p>Circulating tumour cells (CTCs) and CTC clusters are considered metastatic precursors due to their ability to seed distant metastasis. However, navigating the bloodstream presents a significant challenge for CTCs, as they must endure fluid shear forces and resist detachment-induced anoikis. Consequently, while a large number of cells from the primary tumour may enter the circulation, only a tiny fraction will result in metastasis. Nevertheless, the metastatic potency dramatically increases when CTCs travel in conjunction with other cell types to form CTC clusters, including neutrophils, myeloid-derived suppressor cells, macrophages, platelets, cancer-associated fibroblasts and red blood cells found in circulation. Such heterotypic CTC clustering events have been identified in a variety of cancer types and may serve as intriguing therapeutic targets and novel biomarkers for liquid biopsy. This review summarises recent advances in microfluidic technologies designed for the isolation of CTC clusters and explores the biological properties of distinct types of CTC clusters within the circulatory system. Investigation of the mechanisms of CTC cluster-blood microenvironment interactions may offer a promising avenue for gaining fresh insights into CTC cluster-mediated metastatic progression and reveal potential opportunities for devising personalised antimetastasis treatments.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000437"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069747","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":"UK national observational cohort study investigating Tolerance of Anti-cancer Systemic Therapy in the Elderly: the TOASTIE study.","authors":"Mark A Baxter, Michael Rowe, Kieran Zucker, Adam L Peters, Maria Rohan, Alexandra Marsh, Abigail L Gee, Gemma Quesne, Jonny Heseltine, Rachel Prichard, Deborah Scott, Conor O'Neill, Clair Brunner, Joni Howells, Veronica Conteh, Avinash Aujayeb, Xiangfei Yan, Lisa J Rodgers, Sally Martin, Helen Dearden","doi":"10.1136/bmjonc-2024-000459","DOIUrl":"10.1136/bmjonc-2024-000459","url":null,"abstract":"<p><strong>Objective: </strong>The Cancer and Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation study results have varied. The Tolerance of Anti-cancer Systemic Therapy in the Elderly study sought to evaluate the CARG score prospectively in a chemotherapy-naïve UK population.</p><p><strong>Methods and analysis: </strong>This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line chemotherapy for any solid organ malignancy or setting. Baseline demographics and established frailty measures were recorded. Follow-up data including toxicity and hospital admissions were collected retrospectively. Baseline CARG score predictive ability was assessed.</p><p><strong>Results: </strong>339 patients were recruited from 19 centres; median age 73 years (range 65-92), 51.9% male and 54.9% gastrointestinal primary. At baseline, 85% of patients were of Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, with median Rockwood Clinical Frailty Scale (CFS) 3 (range 0-8).314 (92.6%) patients had follow-up data; 69 (22.3%) patients experienced Common Terminology for Cancer Adverse Events grade ≥3 toxicity and 84 (27%) required hospital admission during treatment.Increasing CARG risk groups had increased grade ≥3 toxicity (low 19.6%, medium 22.2%, high 28.2%); however, this was non-significant with no evidence of robust predictive performance. Predictive performance of CFS and ECOG PS was superior to CARG. Importantly, patient and clinician perceptions of toxicity risk differed significantly.</p><p><strong>Conclusions: </strong>In older UK patients with cancer commencing chemotherapy, baseline frailty was prevalent. CARG score did not robustly discriminate or predict high-grade toxicity risk. ECOG and CFS showed superior, although limited, ability to predict and discriminate. This study highlights the need for the development of tools that better predict toxicity in this population.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000459"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069968","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}