The Christie School of Oncology: Christie Research Publications Repository
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Physical activity and mortality in melanoma patients within the Norwegian women and cancer study (NOWAC)
No full textPre- and post-diagnosis physical activity (PA) have been associated with decreased mortality and recurrence in cancer patients, but its effect is under-studied in patients with cutaneous melanoma. We investigated the association between pre-diagnosis PA (most recent level and long-term trajectories) and melanoma-specific, other-cause, and overall mortality. Additionally, PA levels before and after a melanoma diagnosis were compared. We used information at recruitment and follow-ups in the prospective population-based Norwegian Women and Cancer cohort linked to the Cancer Registry of Norway. In total 1829 women were diagnosed with a first primary melanoma in 1991─2020, aged 34-93 years. We used Cox regression adjusted for age at diagnosis, education, smoking status, region of residence, melanoma thickness, and summary stage. Most recent pre-diagnosis PA was non-significantly associated with lower risk of melanoma-specific mortality (hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.44─1.07, high vs. low) and significantly associated with other-cause (HR = 0.50, 95% CI = 0.28─0.89) and overall mortality (HR = 0.59, 95% CI = 0.42─0.82). Four pre-diagnosis PA trajectory classes were identified using a latent class mixed model (low, decreasing, moderate, and high). The PA trajectory classes were not significantly associated with melanoma-specific mortality. However, significantly decreased risks of other-cause (HR = 0.51, 95% CI = 0.30─0.87) and overall mortality (HR = 0.59, 95% CI = 0.42─0.84) were found in the moderate versus low class. Only 275 patients reported both pre- and post-diagnosis PA, and among those, 69% had a similar PA level before and after melanoma diagnosis. Our results suggest that pre-diagnosis PA reduces mortality in middle-aged Norwegian women with melanoma
Late-Onset Immune-Related Adverse Events in Patients with Advanced Melanoma: The LATENT Study
No full textBACKGROUND/OBJECTIVES: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked. METHODS: To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors. RESULTS: Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion. CONCLUSIONS: This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them
Reduced treatment response to inhaled corticosteroids in current smokers with COPD, regardless of blood eosinophil count: insights from the FLAME trial
No full textInhaled corticosteroids (ICSs) benefit patients with chronic obstructive pulmonary disease at high risk of exacerbations with raised blood eosinophil count (BEC). Emerging evidence suggests current smokers show a reduced response to ICS. This post-hoc analysis of the FLAME trial explored the impact of smoking status on the efficacy of long-acting beta-2 agonist (LABA)+ICS versus LABA+long-acting muscarinic antagonist (LAMA) for preventing exacerbations. Our findings indicate that LABA+LAMA is superior to LABA+ICS in preventing moderate to severe exacerbations in current smokers and inferior in ex-smokers with BEC ≥200 cells/µL. Smoking status significantly modifies ICS treatment effects on exacerbation outcomes, suggesting reduced ICS efficacy in current smokers, regardless of BEC
Radiation therapy in the management of muscle-invasive bladder cancer with carcinoma in situ: still a no go?
No full textBACKGROUND AND OBJECTIVE: This narrative review explores the impact of carcinoma in situ (CIS) on outcomes in muscle-invasive bladder cancer (MIBC) after trimodal therapy (TMT) comprising transurethral resection of bladder tumor, a radiosensitizing agent and radiation therapy (RT). There is limited and inconsistent evidence on the effect of CIS, often considered a contraindication to TMT, on treatment efficacy. METHODS: We reviewed studies evaluating the influence of TMT and RT alone on clinical outcomes in CIS-associated MIBC. Endpoints evaluated included complete response (CR) rates, overall survival (OS), disease-specific survival (DSS), and RT protocol variations, such as fractionation schedules, total doses, and the use of image-guided RT. KEY FINDINGS AND LIMITATIONS: Evidence from studies on RT alone is inconsistent, often because of outdated regimens and inadequate CIS evaluation. Retrospective TMT studies suggest that CIS does not significantly affect CR rates, although its impact on OS and DSS remains uncertain, particularly with suboptimal RT protocols. Emerging evidence supports continuous and moderately hypofractionated RT combined with image-guided RT as potential strategies to improve outcomes. Standardized definitions of extensive CIS and better patient selection are critical for optimizing bladder preservation strategies. CONCLUSIONS AND CLINICAL IMPLICATIONS: CIS presents significant challenges for TMT in MIBC, necessitating precise assessment, advanced RT techniques, and multidisciplinary collaboration. Novel therapies, including immunotherapy and intravesical agents, may further improve outcomes. Research into standardized protocols is essential to optimize treatment strategies
Optimizing risk-reducing surgery and aspirin decision aids for Lynch syndrome carriers using the person-based approach: A think-aloud interview study
No full textLynch syndrome 'carriers' carry a germline pathogenic variant conferring gene-, sex-, and organ-specific increased cancer risks. They are presented with difficult, interrelated choices over their lifetime. This study was part of a larger project to codesign a health intervention, Lynch Choices™ https://canchoose.org.uk to provide an information hub and decision support for carriers, their family members, and clinicians. This study aimed to answer the research question: What content, framing, and design elements of a decision aid for genetic cancer risk management are important to Lynch syndrome carriers? Adult carriers were invited to a think-aloud interview to hear their thoughts about a prototype version of Lynch Choices™ containing values-clarification exercises. The first half of interviews focused on the gynecological risk-reducing surgery and the second half on the aspirin decision aid. Twenty carriers (eight men) were interviewed, half of whom had a personal history of cancer. Iterative refinement of Lynch Choices™ content and design was completed between interviews using a transparent table of changes from the person-based approach. Following the interviews, reflexive thematic analysis was applied to the entire qualitative dataset. Three themes were constructed to guide further optimization and make recommendations for improved cancer risk communication in clinical practice. The three themes were: (1) Interpreting gene-specific cancer risks and 'What does it mean to me?'; (2) Words matter: Careful phrasing is important to feel understood; (3) Decision aids: They can help but might trigger emotions. Think-aloud interviews provided in-depth insight into the psychosocial context of carriers. This informed optimization of the decision aid to support engagement and promote shared decision making with healthcare professionals. The learning from this study had broader implications beyond decision aid development, to understanding preferences, needs, and experiences regarding genetic cancer risk communication and decision support
Efficacy, molecular and translational analysis of TP53-mutated HR-MDS with bexmarilimab and azacitidine: Updated results from the bexmab Phase 1/2 study
No full textAre we closing the gender gap in academic oncology? An observational study of gender disparities in participant engagement at the ASCO 2024 annual meeting
No full textOBJECTIVE: Despite global efforts, gender disparities in oncology may persist. Understanding these disparities within the context of major conferences can inform strategies to promote gender inclusiveness in the field. This study evaluates the participation of women and men at the American Society of Clinical Oncology (ASCO) 2024 congress, focusing on chairs, speakers and audience questioners. DESIGN: Observational study. SETTING: 152 recorded sessions of the ASCO 2024 annual meeting, one of the largest conferences in the field of oncology, available on the ASCO website. PARTICIPANTS: Individuals serving as chairs, speakers and audience members who asked questions. PRIMARY AND SECONDARY OUTCOME MEASURES: In this observational study, gender for chairs, speakers and audience questioners across 152 sessions of the ASCO 2024 congress was assessed by two independent reviewers using audio and video recordings. Speaking times for questions and responses were also evaluated. Statistical analyses, including χ(2) and unpaired t-tests, were conducted to analyse the data. RESULTS: Women were well represented as chairs (n=124) and speakers (n=402) in 66% and 95% of sessions, respectively. However, only 21% of questions from the audience were posed by women, while 37% of questions were asked by men and 42% online or by chairs/speakers. Women were more likely to pose questions when the sessions were chaired by women (71% vs 53%; p=0.047). There were no statistically significant gender disparities concerning speaking time (questions: p=0.30; responses: 0.53). The response dynamics indicated a pattern of gender homogeneity, with individuals more frequently responding to questions from their own gender. CONCLUSIONS: While the balanced representation of women in leadership roles at the ASCO 2024 congress reflects positive development in gender equality, disparities in active participation persist. These findings underscore the need for strategies that not only promote women in visible roles but also foster an environment that supports their active engagement in scientific discussions
