The Christie School of Oncology: Christie Research Publications Repository
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Long-term outcomes of HDR monotherapy with a single fraction of 19 Gy for localized prostate cancer: A multicentered retrospective analysis
No full textLandscape of paediatric oncology clinical trials in Asia
No full textIn this second paper of a Series on childhood cancer in Asia, we provide an overview on the Paediatric Oncology Clinical Trials in Asia. Asia with a population of 4.7 billion constitutes about 60% of the world's population. The continent accounts for about half of the global paediatric cancer burden. Many Asian countries have consequently formed national professional societies in childhood cancer. Multicentre clinical trials are pivotal in advancing survival outcomes in paediatric oncology. The continent's diverse socioeconomic conditions may account for significant disparities in the development of such trials. However some countries with good financial resources are relatively deficient in developing clinical trials. In general, the countries show three distinct levels of clinical trials development: established, emerging and nascent. This article reports the landscape of multicentre clinical trials in Asia and the hurdles that clinicians face to actively engage in quality research and clinical trials. Although a 'one-size-fits-all' approach is not feasible, the successful development of clinical trials systems in some countries can offer valuable lessons and insights for others. This is the second in a Series of three papers on childhood cancer in Asia (Paper 3 appears in The Lancet Child and Adolescence Health)
Real-world post-progression outcomes for EGFR-mutant advanced NSCLC patients treated with first-line osimertinib. A single-institution series from The Christie
No full textMagnetisMM-3: long-term update and outcomes of less frequent dosing of elranatamab in relapsed/refractory multiple myeloma
No full textMethylation reprogramming associated with aggressive prostate cancer and ancestral disparities
No full textAfrican men are disproportionately impacted by aggressive prostate cancer (PCa). Key to this disparity both genetic and environmental factors, alluding to epigenetic modifications. However, African-inclusive prostate tumour DNA methylation studies are lacking. Assembling a multi-geo-ancestral prostate tissue cohort, including men with (57 African, 48 European, 23 Asian) or without (65 African) PCa, we interrogate for genome-wide differential methylation. Overall, methylation appears to be driven by ancestry over geography (152 southern Africa, 41 Australia). African tumours show substantial heterogeneity, with universal hypermethylation indicating epigenetic silencing, encompassing PCa suppressor genes and enhancer-targeted binding motifs. Conversely, African tumour-associated heterochromatic hypomethylation suggests permissive chromatin remodelling, with developmental pathway activation via enhancer targets. Taken together, we show methylation aberrations favour metastatic growth, genomic instability and disease aggressiveness in African tumours, which we hypothesise is driven by extensive plasticity of intergenic regulatory regions
A phase 2 study of pemigatinib for pre-treated glioblastoma or other gliomas with activating FGFR1-3 alterations: Results from FIGHT-209
No full textIdentifying best practices for RTTs and dosimetrists: a delphi consensus study on standardizing workflow steps
No full textHealth-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study
No full textBACKGROUND & AIMS: In the randomized, double-blind, phase III KEYNOTE-966 trial, the addition of pembrolizumab to gemcitabine and cisplatin (GemCis) led to a significant improvement in overall survival vs. GemCis alone for the first-line treatment of advanced biliary tract cancer (BTC). Herein, we present the prespecified health-related quality of life (HRQoL) outcomes from KEYNOTE-966. METHODS: HRQoL was assessed using the EORTC Core Quality of Life Questionnaire (QLQ-C30), EORTC QLQ-BIL21, and EQ-5D-5L questionnaires. Data from the latest time point with ≥60% completion and ≥80% compliance (week 18) were compared to baseline. Least squares means for change from baseline to week 18 were compared using a constrained longitudinal analysis model in six prespecified domains: QLQ-C30 global health status/quality of life, physical functioning, and role functioning; QLQ-BIL21 pain and jaundice scores, and EQ-5D-5L visual analogue score. The analysis population was all treated participants with ≥1 completed HRQoL assessment. Between-arm difference in time to confirmed deterioration was assessed using a stratified Cox proportional hazards model with randomization stratification factors. RESULTS: In KEYNOTE-966, 1,069 participants were randomized (533 to the GemCis+pembrolizumab arm and 536 to the GemCis+placebo arm). Questionnaire compliance was >87% from baseline to week 18 in both arms. Least squares means changes from baseline to week 18 were similar between arms for all prespecified domains. Time to confirmed deterioration estimates were also similar between arms, including for global health status/quality of life (median not reached [NR] in the pembrolizumab arm vs. 21.2 months in the placebo arm; hazard ratio [HR] 0.86, 95% CI 0.70-1.07); jaundice (NR vs. NR; HR 1.20, 95% CI 0.94-1.54), and pain (NR vs. NR; HR 0.79, 95% CI 0.59-1.05). CONCLUSION: HRQoL was maintained after adding pembrolizumab to GemCis, further supporting this regimen as a first-line treatment option for advanced BTC. IMPACT AND IMPLICATIONS: Biliary tract cancer (BTC) is often diagnosed at late stages because most patients do not present with disease-specific symptoms. Compared with the general population, patients with advanced BTC report worse physical, emotional, and functional well-being. In KEYNOTE-966, adding the PD-1 (programmed cell death protein 1) inhibitor pembrolizumab to gemcitabine and cisplatin as first-line therapy for participants with advanced BTC produced a statistically significant and clinically meaningful improvement in overall survival. The prespecified patient-reported outcome results from KEYNOTE-966 presented herein demonstrated that health-related quality of life was maintained after adding pembrolizumab to gemcitabine and cisplatin, further supporting this regimen as a first-line treatment option for advanced BTC. CLINICAL TRIAL REGISTRATION: NCT04924062
