The Christie School of Oncology: Christie Research Publications Repository
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Defining the dose-volume constraints for the UK PROTIEUS oesophagus trial-ensuring a fair comparison between photons and protons
No full textAn introduction to pragmatic trials in lung cancer research: A multi-faceted approach
No full textPragmatic clinical trials (PTs) are increasingly recognised as a key methodology in lung cancer research, designed to evaluate the effectiveness of interventions in routine clinical settings. In contrast to traditional randomised controlled trials (RCTs), which involve highly selected patient populations under ideal conditions, PTs enrol broader, more representative cohorts, use streamlined trial procedures, and focus on outcomes that reflect patient-centred priorities. This enhances the generalisability of the results and supports evidence-based, joint decision-making between patients and clinicians. PTs offer a more sustainable and scalable path to generate clinically meaningful evidence that improves the quality of patient care and can address longstanding evidence gaps in the management of patients with lung cancer. This narrative review outlines the main features of PTs, highlighting the PRECIS-2 tool as a framework to design and evaluate the degree of pragmatism of a trial. Common challenges in clinical trial design - including recruitment of participants, informed consent, selection of appropriate clinical endpoints, data quality - are discussed alongside practical solutions. The emerging role of PTs in generating regulatory-grade evidence and the impact of PTs on clinical guidelines is discussed. Ongoing PTs are outlined, which demonstrate how pragmatic methodologies can be used to the evaluate screening interventions, therapeutic strategies and models of care delivery across a range of clinical settings
Treatment strategies with electrochemotherapy for limb in-transit melanoma: real-world outcomes from a European, retrospective, cohort study
No full textBackground: This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). Methods: We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT). Results: 452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had <= 10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1-8). CR rate in treatment-na & iuml;ve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. Conclusions: Among patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support
Molecular targeted maintenance therapy versus standard of care in advanced biliary cancer: an international, randomised, controlled, open-label, phase III umbrella trial (SAFIR-ABC10dPrecision Medicine)
No full textBackground: Advanced biliary tract cancers (ABCs) are a heterogeneous group of rare malignancies of the bile ducts and gall-bladder with a poor prognosis and limited treatment options. Cisplatinegemcitabine (CISGEM) chemotherapy plus immunotherapy (durvalumab or pembrolizumab) is the current first-line standard of care (1L-SoC). ABCs frequently harbour actionable molecular alterations that suggest a high potential for benefit from molecular targeted therapies (MTTs). However, the assessment of potential first-line MTT treatments is hindered by the scarcity of ABCs harbouring a specific alteration and the time required to carry out tumour molecular profiling. Materials and methods: We detail here the design of SAFIR-ABC10, an international, randomised, phase III umbrella trial comparing the efficacy of sequential matched targeted therapy after four cycles (12 weeks) of 1L-SoC versus continued 1L-SoC in patients with ABC and an actionable molecular alteration [European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I or II]. The primary study endpoint is progression-free survival. Besides initial tumour and circulating DNA next-generation sequencing analysis, sequential blood and tumour sampling will be carried out to identify biomarkers of prognosis, response and acquired resistance. Perspectives: SAFIR-ABC10 is, to our knowledge, the first randomised, umbrella trial assessing the concept of precision medicine in ABC, the ideal setting for addressing this question with a high rate of targetable alterations
Correlation between immune-related adverse events (irAEs) and survival outcomes in extensive-stage small cell lung cancer (ES-SCLC) patients (pts) treated with chemoimmunotherapy (CT-IO)
No full textPreferences between three options for androgen deprivation therapy: a focus group study
No full textOBJECTIVES: Androgen deprivation therapy (ADT) forms the mainstay of treatment for advanced prostate cancer. Traditionally administered as a luteinising hormone-releasing hormone (LHRH) agonist depot injection, newer options for ADT include transdermal oestradiol patches (tE2) or oral LHRH antagonists. This study aimed to identify whether this is an important choice for men, which treatment men would choose if offered either LHRH agonist injections, tE2 patches or oral LHRH antagonists as ADT, and to explore the factors influencing this decision. SUBJECTS, PATIENTS, AND METHODS: Five focus groups were conducted. A total of 24 men from around the UK participated in discussions, of whom 10 had never had prostate cancer and 14 had early prostate cancer but had not received ADT. Focus groups were co-facilitated with patient and public involvement representatives. Transcripts were analysed using a critical realist thematic analysis approach. RESULTS: Participants reported that having a choice of ADT is important and being involved in making treatment decisions can help men maintain an element of control. Most men expressed a preference to avoid ADT with LHRH agonist injections; 14 of the 24 men reported they would choose an oral LHRH antagonist, eight reported they would choose tE2 patches, and two that they would choose LHRH agonist injections. Participants reported a large number of factors that influenced their treatment choice that were grouped into: (i) side-effects of treatment, (ii) logistical aspects, and (iii) advice from trusted others. Personal preferences between different types of ADT were based on factors that participants identified as important to them, this prioritisation of factors was influenced by participants' past experiences, current health beliefs, and future expectations. CONCLUSIONS: Men wish to have choice of ADT, and many would not choose LHRH agonists injections if there were other ADT options available. This should be considered, as reimbursement committees and guideline-makers consider the role of alternative ADT strategies
Frailty and outcomes in adults undergoing systemic anticancer treatment: a systematic review and meta-analysis
No full textBACKGROUND: It is increasingly recognized that frailty should be assessed and considered in treatment decision making in patients with cancer. This review and meta-analysis synthesizes existing evidence evaluating the association between baseline frailty and systemic anticancer treatment outcomes in adults with cancer. METHODS: Five databases were systematically searched from database inception to January 2023 to identify prognostic factor studies (cohort or case-control design) reporting the associations between validated frailty assessments (pretreatment) and follow-up outcomes in adults with solid-organ malignancy undergoing systemic anticancer treatment. Risk of bias was assessed via Quality of Prognosis Studies in Systematic Reviews tool. Where appropriate, associations between frailty and outcomes (survival, toxicity, treatment tolerance, functional decline/quality of life, and hospitalization) were synthesized in meta-analysis and presented as forest plots. RESULTS: A total of 58 studies met inclusion criteria. They were undertaken in a range of tumor sites and mainly in older patients and advanced and/or palliative disease settings. Most had low or moderate risk of bias. Nine frailty assessment tools were evaluated. Four outcomes were synthesized in meta-analysis, which demonstrated the prognostic value of 2 tools: Geriatric-8 (survival, treatment tolerance, hospitalization) and Vulnerable Elders Survey-13 (survival, toxicity, treatment tolerance). Overall pooled estimates indicate that frailty conveys an increased risk of mortality (hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.41 to 2.00), toxicity (odds ratio [OR] 1.83, 95% CI = 1.24 to 2.68), treatment intolerance (OR = 1.68, 95% CI = 1.32 to 2.12), and hospitalization (OR = 1.94, 95% CI = 1.32 to 2.83). CONCLUSION: Simple, brief frailty assessments including Geriatric-8 and Vulnerable Elders Survey-13 are prognostic for a range of important outcomes in patients undergoing systemic anticancer treatment. Risk estimates should be used to support shared decision making
Oncology professionals' perceptions and recommendations to improve well-being and health at work in times of crisis: qualitative thematic analysis from the ESMO Resilience Task Force survey series
No full textBACKGROUND: The European Society for Medical Oncology (ESMO) Resilience Task Force (RTF) was established to address burnout and well-being issues among oncology professionals. In this article, we present findings on shared perceptions and recommendations to support and improve oncology professionals' well-being and health at work. MATERIALS AND METHODS: Inductive thematic analysis of qualitative responses from three global ESMO RTF surveys (2020-2021) was conducted using Braun and Clarke's six-step approach. Open-ended questions elicited suggestions, including descriptions of 'pleasant physical working conditions' in the third survey. Respondents (n = 989) were gender-balanced, from 90 countries, with half practising in Europe. Most were of white ethnicity, worked in medical oncology, and had over 10 years of experience. RESULTS: Six main themes described help and support needs from oncology professionals: training, education, information and learning; well-being; activism and advocacy; financial support; safety; and opportunities and career. Six additional themes described factors contributing to a 'pleasant physical working environment': physical working environment; working conditions and job role; safety; well-being and coping; working relations and support from others; and career and professional development. CONCLUSIONS: This is the largest global qualitative analysis of oncology professionals' needs during the coronavirus disease 2019 (COVID-19) pandemic, offering actionable recommendations for ESMO and other stakeholders to address work-related issues. Addressing these needs can foster resilience, improve working conditions, and promote better health and well-being
Value of hospital administrative data linked to national cancer registry records to identify metastatic disease at time of primary diagnosis in colorectal cancer patients: a study using national data in England
No full textBACKGROUND: Routinely collected data are increasingly being used for cancer research and health service evaluation. For both purposes, accurately identifying metastatic disease at diagnosis is essential. We developed an approach to identify metastatic disease at time of primary diagnosis according to national hospital administrative data (HAD) in patients identified with colorectal cancer (CRC) in the English national cancer registry (CR). METHODS: A national cohort of CRC patients diagnosed between 2013 and 2018 in England identified in CR data were linked to HAD. Metastatic disease was assumed to be present at diagnosis according to HAD if at least one of a set of pre-specified diagnostic ICD-10 codes appeared in a record of a hospital admission between one month before and six months after CRC diagnosis date. RESULTS: Of 186,236 patients, 40,421 (21.7%) had metastatic cancer according to HAD, 42,843 (23.0%) according to CR data, 49,827 (26.8%) according to either data source, and 33,437 (18.0%) according to both. Metastatic information was missing in CR data in 14,065 patients and 1,930 of these (13.7%) had metastatic cancer according to HAD. 1-year mortality was 59.3% (95%-CI: 58.8 - 59.8%) in patients with metastatic disease and 7.4% (7.2 - 7.5%) in patients without if HAD and CR data agreed. Mortality fell between these results if HAD and CR data disagreed. High mortality was seen in patients with missing metastatic data in the CR: 74.4% (72.4 - 76.3%) in patients with metastatic disease and 45.2% (44.3-46.1%) in patients without metastatic disease according to HAD. CONCLUSIONS: HAD should be linked to CR data to provide more accurate information on metastatic CRC at diagnosis including sites of metastasis. Linkage to HAD increased the number of patients identified with metastatic CRC by 14%, compared to CR data alone. Patients with metastatic disease at diagnosis in either data source had mortality outcomes expected for patients with metastatic cancer. CRC patients with missing metastasis data in CR data are likely to have metastatic disease and linkage to HAD provides important prognostic information