The Christie School of Oncology: Christie Research Publications Repository
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Investigating the outcomes following oncovascular resection in advanced pelvic cancer: a systematic review
No full textValidating data from multiplex assays of variant effect: a CanVIG-UK national survey of NHS clinical scientists
No full textAdvances in technology have made it possible for multiplex assays of variant effect (MAVEs) to systematically generate functional data for thousands of genetic variants. Robust clinical validation and accessible online resources for MAVE data have previously been identified as barriers to the clinical adoption of new MAVEs. We delivered a survey during the November 2024 Cancer Variant Interpretation Group UK (CanVIG-UK) meeting comprising National Health Service (NHS) clinical scientists and clinical geneticists and received 46 responses from individuals regularly performing variant classification for diagnostic reporting. Only 35% reported they would accept clinical validation of the MAVE provided by the authors who conducted the assay; 20% reported they would attempt clinical validation themselves, and 61% would await clinical validation by a trusted central body. 72% reported they would use MAVE data ahead of a formal peer-reviewed publication if reviewed and clinically validated by a trusted central body. When scoring central bodies on a scale of 1-5 for confidence in their review and validation of MAVEs, CanVIG-UK (median = 5), variant curation expert panels (VCEPs; median = 5), and ClinGen SVI Functional Working Group (median = 4) all scored highly. Participants supported making variant-level data accessible via a relevant web resource (although the majority of participants expressed that additional assay-level or variant-level information would have a low likelihood of altering validation scores provided by a trusted central body). These findings, from a comparatively homogeneous clinical diagnostic group operating in a resource-constrained healthcare setting, indicate that clinical application of new MAVEs for variant classification will be delayed unless robust clinical validations are performed by a trusted central body and made readily accessible
Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304
No full textRelacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial
No full textBACKGROUND: Relacorilant, a first-in-class selective glucocorticoid receptor antagonist, increases a tumour's sensitivity to chemotherapy by reducing cortisol signalling. This study aimed to show whether the addition of relacorilant to nab-paclitaxel improves progression-free and overall survival in females with platinum-resistant ovarian cancer. METHODS: This randomised, controlled, open-label phase 3 trial (ROSELLA [GOG-3073/ENGOT-ov72]) was done at 117 hospitals and community oncology treatment centres in 14 countries across Australia, Europe, Latin America, North America, and South Korea. Patients had to be aged 18 years or older and had to have a confirmed diagnosis of platinum-resistant, epithelial (ie, high-grade serous, endometrioid, or carcinosarcoma with a ≥30% epithelial component) ovarian, primary peritoneal, or fallopian tube cancer; up to three previous lines of anticancer therapy and previous bevacizumab and disease progression or intolerance to the most recent therapy; measurable disease according to the Response Evaluation Criteria in Solid Tumours (RECIST; version 1.1); an Eastern Cooperative Oncology Group performance status of 0 or 1; and adequate organ function. Patients were assigned (1:1) to relacorilant (150 mg orally the day before, of, and after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m(2) intravenously on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel monotherapy (100 mg/m(2) intravenously on the aforementioned schedule). The dual primary endpoints were progression-free survival assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours (version 1.1) and overall survival, and were assessed in all randomly assigned patients by intention to treat. The safety population included all randomly assigned patients who received at least one dose of the assigned treatment. This trial was registered at ClinicalTrials.gov, NCT05257408, and is ongoing. FINDINGS: Between Jan 5, 2023, and April 8, 2024, 381 patients were randomly assigned to the combination group (n=188) or to the nab-paclitaxel monotherapy group (n=193). Patients receiving relacorilant plus nab-paclitaxel had a statistically significant improvement in progression-free survival assessed by blinded independent central review compared with those receiving nab-paclitaxel monotherapy (hazard ratio 0·70 [95% CI 0·54-0·91]; median 6·54 months [95% CI 5·55-7·43] vs 5·52 months [3·94-5·88]; stratified log-rank p=0·0076). At the planned interim analysis, there was a clinically meaningful difference in overall survival with the addition of relacorilant to nab-paclitaxel (0·69 [95% CI 0·52-0·92]; 15·97 months [95% CI 13·47-not reached] vs 11·50 months [10·02-13·57]; log-rank p=0·0121). Adverse events were similar across study groups when adjusted for nab-paclitaxel exposure; no new safety signals were observed. INTERPRETATION: The addition of relacorilant to nab-paclitaxel prolonged progression-free survival and interim results also showed an improvement in overall survival. Together, the results position the combination of relacorilant and nab-paclitaxel as a potential new standard treatment for patients with platinum-resistant ovarian cancer. FUNDING: Corcept Therapeutics
Feasibility, acceptability and clinical outcomes of a real-world, regional lung cancer prehabilitation programme for patients undergoing curative intent radiotherapy
No full textINTRODUCTION: Prehabilitation improves both physiological measurements and clinical outcomes for patients undergoing surgery for lung cancer. The feasibility, acceptability and efficacy of prehabilitation for patients having curative-intent radiotherapy for lung cancer is uncertain. METHODS: Prehab4Cancer (P4C) is a regional, community-based prehabilitation service for patients with cancer in Greater Manchester in the United Kingdom. We present an evaluation of the P4C service for patients undergoing curative-intent radiotherapy for lung cancer over a 2-year period. Feasibility was evaluated against prespecified key performance indicators. Objective physiological and subjective functional assessments were recorded before and after completion. Effects on mortality in comparison to a non-prehab cohort were assessed in an exploratory regression analysis. RESULTS: A total of 381 patients were referred to P4C via a web-based portal. 86 % (329/381) were contacted by phone and 73 % (279/381) completed an initial assessment. 45 % (172/381) completed the prehab programme with a median of 7 (IQR 3-11) sessions during a median time to commencing treatment of 23 days (IQR 16-34). Median time from referral to assessment was 4 days (IQR 3-6) and 86 % (239/279) were completed within 7 days of referral. Six-Minute Walk Tests improved by an average of 30 m (95 % CI 20.6-41 m, p = <0.001). 16 % (n = 21/132) of participants initially score 'Medium' or 'High' on IPAQ for weekly physical activity, improving to 52 % (n = 66/132) on programme completion. Participants had a median reduction in score of -2.5 (95 % CI -3.0 to -1.5) in WHODAS 2.0. There was an 8 % reduction in 1-year mortality in patients completing prehab (11 %, 17/160) vs those that did not complete prehab (19 %, 30/158, OR 0.5, 95 % CI 0.24-1.00, p = 0.054) after adjustment for age, gender, performance status and cancer staging. CONCLUSIONS: The P4C programme has demonstrated feasibility, acceptability and effectiveness in patients with lung cancer undergoing curative-intent radiotherapy
Osimertinib efficacy in advanced NSCLC patients with PACC and classical-like EGFR mutations: a retrospective analysis from The Christie
No full textStreamlining cancer pathways: minimising delays to referrals for physiological assessment & prehabilitation
No full textNovel methodologies for clinical research in radiation oncology: time to think outside of the box? a narrative review
No full textBACKGROUND: Traditional randomised controlled trials (RCTs) are foundational to clinical research, yet in radiation oncology, their limitations are increasingly evident. Rapid technological innovation, complex treatment protocols, and diverse patient populations challenge the feasibility, generalisability, and timeliness of RCTs. This has prompted exploration of alternative methodologies that better align with real-world practice and patient-centred care. METHODS: This narrative review was developed following a joint ESTRO-EORTC session at the May 2025 ESTRO meeting. It synthesises expert perspectives and recent literature to examine the limitations of RCTs and the potential of alternative designs, including real-world evidence (RWE), pragmatic trials, and Trials within Cohorts (TwiCs). FINDINGS: RCTs in radiation oncology face challenges including high cost, recruitment barriers, limited external validity, and ethical constraints. RWE, derived from registries and electronic health records, is increasingly used for regulatory decisions and post-market surveillance, though concerns about data quality and bias remain. Pragmatic trials offer inclusive, flexible designs that reflect routine care, but require robust infrastructure and statistical methods. TwiCs embed randomisation within observational cohorts, improving recruitment and reducing burden, yet raise ethical and methodological concerns. Examples such as OligoCARE, RAPID-RT and SPRINT illustrate how these designs can support scalable, patient-centred research. CONCLUSION: To advance societal sustainability and equity in radiation oncology, methodological pluralism is essential. RWE, pragmatic trials, and TwiCs offer promising alternatives to traditional RCTs, enabling more responsive and inclusive research. Their success depends on investment in infrastructure, training, and ethical frameworks that support transparency and trust
Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial
No full textAt the first interim analysis of the phase 3 KEYNOTE-426 trial, first-line pembrolizumab plus axitinib showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) over sunitinib for advanced renal cell carcinoma (RCC). To assess long-term durability of clinical outcomes and elucidate predictive biomarkers for RCC, we performed efficacy and prespecified exploratory biomarker analyses from KEYNOTE-426 with ≥5 years of follow-up. Pembrolizumab plus axitinib showed sustained benefits in OS (hazard ratio: 0.84; 95% confidence interval: 0.71-0.99), PFS (hazard ratio: 0.69; 95% confidence interval: 0.59-0.81) and ORR (60.6% versus 39.6%) compared to sunitinib. An 18-gene T-cell-inflamed gene expression profile (Tcell(inf)GEP) was positively associated with OS (P = 0.002), PFS (P < 0.0001) and ORR (P < 0.0001) within the pembrolizumab plus axitinib arm. An angiogenesis signature was positively associated with OS (P = 0.004) within the pembrolizumab plus axitinib arm and with OS (P < 0.0001), PFS (P < 0.001) and ORR (P = 0.002) within the sunitinib arm. Across arms, programmed cell death ligand 1 combined positive score was only associated (negatively) with OS within the sunitinib arm (P = 0.025). Additionally, PBRM1 (polybromo-1) mutation had a positive association with ORR (P = 0.002) within the pembrolizumab plus axitinib arm. Within the sunitinib arm, OS was positively associated with VHL (von Hippel-Lindau tumor suppressor gene) (P = 0.040) and PBRM1 (P = 0.010) mutations and was negatively associated with BAP1 (BRCA1-associated protein 1) mutation (P = 0.019). Results showed a sustained clinical benefit with pembrolizumab plus axitinib over sunitinib and provide valuable information on biomarkers for immunotherapy-based treatment combinations in advanced RCC. Prospective clinical investigations are needed for biomarker-directed treatment for advanced RCC. ClinicalTrials.gov identifier: NCT02853331