The Christie School of Oncology: Christie Research Publications Repository
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Adjuvant immunotherapy in the modern management of resectable melanoma: current status and outlook to 2028
No full textBACKGROUND: Therapeutic advances have reshaped the treatment landscape for patients with resectable melanoma, particularly for those with stage IIB/C and stage III disease. In this article, we discuss the current status and future outlook of adjuvant immunotherapy for melanoma in Europe. RESULTS: Adjuvant immunotherapy offers significant benefits in terms of recurrence-free survival and distant metastasis-free survival. Uncertainties regarding overall survival (OS) benefits, however, remain. Trials such as Keynote-054, which are expected to provide crucial OS information, have delayed their final analyses until 2027. Additionally, real-world studies have raised questions about the correlation between recurrence-free survival/distant metastasis-free survival improvements observed in clinical trials and OS outcomes in routine clinical practice. These uncertainties have led to ongoing debates about the cost-effectiveness of adjuvant therapies, with disparities in reimbursement policies across Europe reflecting these concerns. CONCLUSION: Looking ahead to 2028, adjuvant immunotherapy will remain a key option of comprehensive melanoma care, particularly for patients with stage IIB/C and stage III with micrometastatic disease, where neoadjuvant immunotherapy is not feasible
Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer
No full textINTRODUCTION: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. METHODS: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. RESULTS: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. CONCLUSIONS: Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification
The effect of time from surgery to commencing adjuvant radiotherapy for patients with head and neck squamous cell carcinoma
No full textINTRODUCTION: Studies reported inferior outcomes when radiotherapy starts >6-8 weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6-8 weeks post-surgery. METHODS/MATERIALS: Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted. RESULTS: 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44 days (IQR: 14 days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95 % CI 0.99-1.02; p = 0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95 % CI 0.99-1.03; p = 0.5). CONCLUSION: Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6-8 weeks post-surgery and that no threshold is considered for patient selection
Cutaneous melanoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up
No full textMen's knowledge, attitudes, practices, cultural beliefs, and perceived risk and susceptibility regarding prostate cancer in the Vhembe District, Limpopo Province, South Africa
No full textBACKGROUND: Prostate cancer (PCa) awareness and knowledge among men in Vhembe District, Limpopo Province, South Africa, remain inadequately studied despite the high local burden of the disease. This study investigates the knowledge, attitudes, practices, cultural beliefs, and perceived risk of PCa among men aged 40 and above in selected villages under the Mphaphuli and Niani tribal authorities. METHODS: A quantitative survey was conducted with 431 men, utilizing a questionnaire adapted from the African Women Awareness of Cancer (AWACAN) tool. The questionnaire, translated into Tshivenda, assessed socio-demographic data, awareness, knowledge of risk factors and symptoms, health-seeking behavior, and barriers to seeking medical help. RESULTS: The study revealed that 51.3% of participants had heard of PCa, while 48.7% had not. Awareness varied significantly with age, relationship status, education level, and language. Older men and those with higher education levels were more knowledgeable about PCa. Clinics, hospitals, and media were the primary sources of information. Misconceptions about risk factors were prevalent, with 24.0% of men indicating a preference for traditional healers for PCa symptoms. Barriers to medical help included fear of the disease, procedural fears, and cultural taboos. Multivariate analysis identified significant factors associated with PCa knowledge, including age, language, access to tap water, and cell phone ownership. CONCLUSION: These findings underscore the importance of targeted educational interventions considering sociodemographic and cultural contexts. Future public health initiatives should focus on bridging the gap between traditional and modern medical practices to enhance health outcomes in the Vhembe District and similar settings
A stretchable and biomimetic polyurethane membrane for lung alveolar in vitro modelling
No full textThe lung alveolus constitutes a morphologically and mechanistically complex tissue that is constantly subjected to cyclic tension and exhibits unique elastic properties. Available materials used to mimic alveolar tissue often lack biomimicry and the mechanical properties required for cyclic tension. Here, we report a fully synthetic fibrous polyurethane scaffold that approximates tissue stiffness, is elastic under breathing simulations and supports long-term culture of alveolar epithelial-like cells. Using electrospinning a fibrous membrane of tuneable thickness, set fibre diameter and small pore size is prepared. When subjected to cyclic uniaxial tension the material retains its elasticity at both low and high frequency mimicking human and mouse breathing. Thanks to the small pore size, lung alveolar cells can be cultured on its apical surface forming an epithelial monolayer. This monolayer can be maintained long term (at least 15 days) and in an air-liquid interface. In the latter conditions, cells differentiate and exhibit expression of surfactant protein A, a constituent of the surfactant layer that plays a key role in lung physiology. Owing to its lung-mimicking characteristics, the electrospun membrane holds the potential to be adapted for breathing lung models
HORIZON-01: a phase I-III platform study evaluating the efficacy and safety of multiple therapies in patients with biomarker-defined locally advanced, unresectable stage III non-small cell lung cancer (NSCLC)
No full textUnresectable stage III non-small-cell lung cancer: state of the art and challenges
No full textDespite advances in immunotherapy, unresectable stage III non-small-cell lung cancer (NSCLC) remains a highly challenging disease, with only around one-third of patients remaining disease-free at 5 years. The PACIFIC trial established consolidation with the anti-PD-L1 antibody durvalumab after concurrent chemoradiotherapy as the standard-of-care approach. Furthermore, the LAURA trial has redefined the treatment of patients with stage III unresectable EGFR-mutant NSCLC, demonstrating unprecedented progression-free survival durations with osimertinib consolidation. Despite these advances, novel approaches are urgently needed. Circulating tumour DNA-based monitoring of minimal residual disease is emerging as a personalized method of tailoring treatment duration and escalation strategies. Novel radiotherapy techniques have the potential to provide synergy with immunotherapy while minimizing toxicities. Additionally, ongoing trials evaluating chemoimmunotherapy combinations adapted from the neoadjuvant setting with the potential for conversion to resectable disease might, in the near future, redefine the boundary of surgical resectability. In this Review, we describe the rapidly evolving field of unresectable stage III NSCLC, providing a state-of-the-art overview that includes challenging topics such as biomarkers, personalization of therapy and the role of immunotherapy rechallenge
