The Christie School of Oncology: Christie Research Publications Repository
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Evolving treatment for advanced non-small cell lung cancer harbouring common EGFR activating mutations
No full textA clinically important subgroup of non-small cell lung cancer (NSCLC) is driven by common mutations in the epidermal growth factor receptor (EGFR). Over the past decade, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) have substantially improved clinical outcomes, although acquired resistance inevitably emerges. In particular, the third-generation TKI osimertinib has demonstrated superior progression-free survival (PFS) and overall survival (OS) compared to earlier-generation TKIs in the frontline setting, yet median OS remains approximately three years in pivotal trials. Efforts to extend disease control have led to various upfront intensification strategies, including combining EGFR TKIs with antiangiogenics or chemotherapy (e.g., the FLAURA-2 trial), and pairing novel bispecific antibodies such as amivantamab with third-generation TKIs. Upon progression on third-generation EGFR TKIs, platinum-based chemotherapy remains the standard second-line treatment, albeit with modest response rates. Emerging therapies targeting MET amplification (e.g., savolitinib plus osimertinib), leveraging antibody-drug conjugates (e.g., patritumab deruxtecan), or adding immunotherapy and antiangiogenics have shown preliminary promise in overcoming resistance. Ongoing trials are assessing optimal treatment sequencing and the use of circulating tumor DNA (ctDNA) to guide therapy escalation or de-escalation. Ultimately, the evolving landscape of EGFR-mutant NSCLC underscores the need for refined biomarker-driven approaches and personalized regimens to achieve further gains in survival. In this review, we discuss these strategies in detail, highlighting current evidence and future directions for EGFR-mutant NSCLC treatment
Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice
No full textIn the UK, most patients receive publicly funded medical care through the National Health Service (NHS), which funds tumour and/or germline testing for eligible patients with cancer to inform clinical management.Testing on tumour-derived DNA may identify putative heritable variants, with implications for the proband and their wider family, but is not a reliable substitute for germline genetic testing when hereditary cancer predisposition is suspected.The likelihood that a variant identified through tumour testing is of germline origin depends on multiple clinical and technical factors. Certain genotypes significantly influence a patient's cancer risk, and intervention in those carriers may facilitate cancer prevention or early detection, while other genotypes are associated with lower cancer risk, and associated intervention in such cases have limited clinical utility.We convened a national meeting of clinical cancer genetics and scientific leads to rationalise germline follow-up testing of variants identified through tumour-based testing. After contrasting potential approaches, implementation of an NHS-contextualised 'intermediate conservative' approach was agreed and refined by the authors, with the final pathway recirculated to the UK clinical and scientific community for consensus agreement and publication.We outline relevant patient, genetic and technical considerations informing likely origin of variants, a review of current relevant guidance and NHS laboratory practices and a workflow for laboratory and clinical teams to triage tumour-detected variants requiring onward germline follow-up. This approach aims to direct limited resources towards identifying germline variants associated with the greatest potential clinical impact, with a view to supporting more efficient and equitable delivery of genomic medicine in oncology
Consolidation thoracic radiotherapy after chemoimmunotherapy in ES-SCLC: A multicentric retrospective analysis
No full textBACKGROUND: The CREST trial established the benefit of consolidative thoracic radiotherapy (TRT) following first line (1L) chemotherapy in extensive-stage small cell lung cancer (ES-SCLC), demonstrating improved 2-year overall survival (OS). However, the role of TRT in the chemoimmunotherapy (CT-IO) era remains unclear, as TRT was excluded from registrational trials. METHODS: This retrospective study analysed consecutive patients (pts) with ES-SCLC treated with 1L CT-IO between January 2020 and January 2024 across 4 centres. Pts without radiological progression (PD) at their first post-treatment assessment were included. Intrathoracic recurrence rates, progression-free survival (PFS), and OS were compared between pts who received TRT and those who did not. RESULTS: 336 pts were identified, with 111 (33.0 %) receiving TRT. Pts who received TRT had a lower rate of intrathoracic PD compared to those who did not (40.5 % vs 57.8 %, p = 0.003). Among those with intrathoracic PD despite TRT, only 21 (24.1 %) experienced PD within the radiation field. With a median follow-up of 31.3 months, pts who received TRT showed improved PFS (HR 0.89, p = 0.363) and OS (HR 0.82, p = 0.142), although not statistically significant. Multivariate analysis identified baseline liver metastases (LM) and stable disease after CT-IO as independent predictors of shorter PFS. Subgroup analysis revealed a longer PFS for pts receiving higher TRT doses (≥45 Gy vs <45 Gy) and those without LM. CONCLUSIONS: In this series, TRT following 1 L CT-IO significantly improved intrathoracic control, although it did not translate into significantly better survival outcomes. Prospective trials are warranted to evaluate the impact of TRT on quality of life and survival
A therapeutic radiographer perspective of concurrent chemoradiotherapy for non-small cell lung cancer in the UK
No full textClinical characteristics, healthcare resource use, and survival outcomes among patients with advanced NSCLC tested for KRAS mutations in France, the United Kingdom, and Switzerland
No full textObjectiveTo evaluate real-world patient characteristics, healthcare resource use (HRU), and clinical outcomes among patients with advanced or metastatic (A/M) non-small cell lung cancer (NSCLC) stratified by KRAS mutation status (KRAS G12C, KRAS non-G12C, and KRAS wild-type[WT]).MethodsThis retrospective chart review included adults with A/M NSCLC and known KRAS status who received second- or third-line non-targeted therapy (index therapy) in France, the UK, or Switzerland. Patient characteristics, HRU, and key clinical outcomes-including time to treatment discontinuation (TTD), progression-free survival (PFS), and overall survival (OS)-were analyzed using the Kaplan-Meier method and log-rank methods. Exploratory multivariate Cox models adjusted for clinical covariates.ResultsThe study included 211 patients (France: 192, UK: 13, Switzerland: 6), with 53.1% having KRAS G12C, 21.8% KRAS non-G12C, and 25.1% KRAS WT NSCLC. Median age was 66 years; 62.1% were male, and 95.8% were current/former smokers. Baseline characteristics were comparable across KRAS subgroups. HRU was high, including 125 unplanned healthcare provider visits, primarily to general practitioners (42.4%) and specialists (24.0%). Hospitalization was frequent (70.1% of patients), with 40.8% experiencing unplanned admissions, largely due to disease complications (54.2%) and grade 3/4 adverse events (24.4%). Median TTD, PFS, and OS were comparable across KRAS subgroups for second-line (4.4-4.7 months, 5.3-6.3 months, and 11.2-15.0 months) and third-line (3.2-4.1 months, 3.4-5.2 months, and 5.1-9.2 months) therapy. Multivariate analysis showed that KRAS status, performance status, histology, and comorbidities were not significantly associated with survival outcomes.ConclusionsPatients with advanced NSCLC, regardless of KRAS mutation status, experience a substantial disease burden, frequent hospitalizations, and poor clinical outcomes. These findings highlight the urgent need for more effective treatment options for advanced NSCLC, including therapies tailored to KRAS-mutated disease
Androgen suppression, PSA response, toxicity and longer-term outcomes with transdermal oestradiol (tE2) patches compared with LHRH analogues for the treatment of locally advanced prostate cancer, the phase III PATCH (NCT00303784) and STAMPEDE (NCT00268476) trials
No full textPatient and tumour factors influencing length of sarcoma diagnostic trajectory intervals: first results from the international QUEST study
No full textRe: Bridging gaps in remote cancer care: commentary on the adjuvant abemaciclib monitoring model
No full textReal-world reirradiation treatment and disease characteristics: interim analysis of the prospective observational E2-RADIatE ReCare cohort
No full textObesity management for patients with coronary artery disease and heart failure
No full textObesity is causally linked to heart disease directly by triggering various adverse pathophysiological changes and indirectly through convergent risk factors such as type 2 diabetes, hypertension, dyslipidemia, and sleep disorder. Weight reduction is an important intervention for obesity-related cardiomyopathy, and antiobesity medications that target both obesity and heart failure (HF), particularly sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists, have a role in treatment. Bariatric surgery offers a viable treatment option for patients with severe obesity associated with coronary artery disease and HF but requires careful patient selection, preoperative optimization, choice of procedure, and postoperative management to minimize risks