The Christie School of Oncology: Christie Research Publications Repository
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The care of older patients with cancer across the United Kingdom in 2024: a narrative review by the international society of geriatric oncology UK country group
No full textThe worldwide population is ageing, alongside an increase in cancer incidence rates. Over the past 10 years, there has been huge progress in the field of oncology with earlier diagnosis and an expansion of treatment options, leading to a growing number of older people living with cancer. That has meant that caring for older patients with cancer is now part of day-to-day oncology practices. This cohort often has geriatric syndromes and a higher prevalence of frailty and complex needs and preparing our clinical services to optimise care for these patients is essential. Whilst it is widely accepted that comprehensive geriatric assessments are of benefit to patients, only a small proportion of patients can access these through specialised teams during their cancer care. In the past few years there has been significant progress in this field throughout the United Kingdom (UK). The goal of this review is to inform other health care systems how to learn from what has been done in the UK. This paper provides an update from our previous review in 2020, detailing the new services being implemented and made available to patients and an expansion in the number of new pilot teams and research projects/trials throughout the four nations of the UK
Translation of PET radiotracers for cancer imaging: recommendations from the national cancer imaging translational accelerator (NCITA) consensus meeting
No full textBACKGROUND: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation. METHODS: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation. Panellists independently completed a consensus survey of 57 questions, rating each on a 9-point Likert scale. Subsequently, panellists attended a consensus meeting to discuss survey outcomes and readjust scores independently if desired. Survey items with median scores ≥ 7 were considered 'required/appropriate', ≤ 3 'not required/inappropriate', and 4-6 indicated 'uncertainty remained'. Consensus was determined as ~ 70% participant agreement on whether the item was 'required/appropriate' or 'not required/not appropriate'. RESULTS: Consensus was achieved for 38 of 57 (67%) survey questions related to preclinical and clinical methodologies, and stakeholder engagement. For evaluating established radiotracers in new cancer types, in vitro and preclinical studies were considered unnecessary, clinical pharmacokinetic studies were considered appropriate, and clinical dosimetry and biodistribution studies were considered unnecessary, if sufficient previous data existed. There was 'agreement without consensus' that clinical repeatability and reproducibility studies are required while 'uncertainty remained' regarding the need for comparison studies. For novel radiotracers, in vitro and preclinical studies, such as dosimetry and/or biodistribution studies and tumour histological assessment were considered appropriate, as well as comprehensive clinical validation. Conversely, preclinical reproducibility studies were considered unnecessary and 'uncertainties remained' regarding preclinical pharmacokinetic and repeatability evaluation. Other consensus areas included standardisation of clinical study protocols, streamlined regulatory frameworks and patient and public involvement. While a centralised UK clinical imaging research infrastructure and open access federated data repository were considered necessary, there was 'agreement without consensus' regarding the requirement for a centralised UK preclinical imaging infrastructure. CONCLUSIONS: We provide consensus-based recommendations, emphasising streamlined methodologies and regulatory frameworks, together with active stakeholder engagement, for improving PET radiotracer standardisation, reproducibility and clinical implementation in oncology
"Hadrontherapy for life" symposium, caen, march 10/11, 2025-strategy for the future-pancreatic cancer
No full textThe symposium"Hadrontherapy for Life," held in Caen, on February 10 and 11, 2025, brought together over 100 international experts of heavy ions particle therapy. Clinical aspects of current indications and future strategies were discussed. Pancreatic cancer that may reach the second cause of cancer mortality in the next decade, was prioritized. Stimulating clinical data accumulated in Japan and more recently in Europe suggest an important role for carbon ion radiotherapy (CIRT) in advanced presentations but also in a preoperative setting, at the price of acceptable toxicity. Biological aspects also plead for combinations of CIRT with bio or immune therapy
ESMO-magnitude of clinical benefit scale version 2.0 (ESMO-MCBS v2.0)
No full textBACKGROUND: The ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated tool to assess the magnitude of clinical benefit from new cancer therapies, with planned updates based upon recognition of new needs and shortcomings. This paper describes the development of ESMO-MCBS v2.0. METHODOLOGY: The revision process incorporates nine steps: (i) review of critiques and suggestions and identification of problems in the application of ESMO-MCBS v1.1; (ii) identification of shortcomings for revision in the upcoming version; (iii) drafting solutions addressing identified shortcomings; (iv) field-testing of solutions; (v) preparation of a near-final revised version for peer review for reasonableness by members of the ESMO Faculty and ESMO Guidelines Committee; (vi) amendments based on peer review for reasonableness; (vii) near-final review by members of the ESMO-MCBS Working Group; (viii) final amendments; (ix) final review and approval by members of the ESMO-MCBS Working Group and the ESMO Executive Board. RESULTS: Seventeen issues for revision or amendment were considered, and 13 amendments were formulated to address identified shortcomings. In the curative setting, studies evaluated based on disease-free survival now credit improved time without treatment or disease even when overall survival is not significantly improved, and studies with small absolute gain in disease-free survival are credited more conservatively. Additionally, acute and persistent toxicity annotations are added. In the non-curative setting, the approach to crediting a difference in the tail of overall survival and progression-free survival curves is more statistically valid, and the toxicity evaluation has been revised. In peer review all amendments were found to be either reasonable or mostly reasonable. The amendments changed the scoring of 85/353 of evaluated studies. CONCLUSIONS: The amendments incorporated into ESMO-MCBS v2.0 change the scores of 13.6% of evaluated studies (10.5% downgraded, 3.1% upgraded) and add toxicity annotations to 45.5% of the studies in the curative setting, and improve its discriminatory capacity and utility
Identification of CENPB as a Novel Candidate Therapeutic Targets in Acute Myeloid Leukaemia (AML)
No full textThe effect of healthcare professional-implemented interventions on adherence to oral targeted therapy in patients with cancer: a systematic review and meta-analysis
No full textPURPOSE: This study investigated the impact of healthcare professional-led interventions on adherence to oral targeted therapy and identified the behavior change techniques (BCTs) underpinning the interventions. METHODS: A systematic search of MEDLINE, Embase, APA PsycInfo, CINAHL Plus, PubMed, and Web of Science up to July 2024 identified randomized controlled trials and cohort studies involving adult patients (≥ 18 years) with cancer on oral targeted therapy receiving healthcare professional-led interventions to improve adherence. Adherence-related outcomes, including proportions of patients continuing treatments or with a medication possession ratio (MPR) ≥ 90%, were compared between intervention and control (usual care) groups. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) and heterogeneity (I(2) statistic) were reported. Differences in median time to treatment discontinuation were calculated and synthesized where applicable. Interventions were categorized using the BCT taxonomy. RESULTS: This review included 11 studies (1,654 patients). The pooled results for proportions of patients continuing treatment (OR 17.91; 95%CI 3.18, 100.73; I(2) < 0.1%) or with an MPR ≥ 90% (OR 3.67; 95%CI 1.98, 6.80; I(2) < 0.1%) showed a significantly favorable outcome in the intervention group compared to the control group. In two studies, the median time to treatment discontinuation was longer in the intervention group than in the control group. The most commonly used BCTs were 'credible source' (n = 11), 'problem-solving' (n = 9), 'instruction on how to perform a behavior' (n = 9), and 'pharmacological support' (n = 8). CONCLUSION: Despite limited evidence, healthcare professional-led interventions significantly improve treatment adherence. Future studies should tailor strategies for individual needs and apply BCTs in designing effective interventions. PROSPERO registered: no. CRD42024571808
Multimodality curative-intent treatment in NSCLC: an unprecedented era of change 2017-2025
No full textCurative-intent multimodality treatment-combining local treatments such as surgery or radiotherapy with systemic therapy-is the cornerstone of care in stage II-III non-small cell lung cancer (NSCLC). Since 2017, the systemic therapy backbones with multimodality treatment have undergone a dramatic transformation, driven by a series of pivotal, practice-changing clinical trials. Immunotherapy and targeted therapies, previously confined to the advanced/metastatic setting, are now firmly embedded in curative-intent regimens. Maintenance immunotherapy following chemoradiation in unresectable stage III disease, adjuvant tyrosine kinase inhibitors in resected epidermal growth factor receptor/anaplastic lymphoma kinase-positive tumours, neoadjuvant and perioperative chemoimmunotherapy in resectable stage II/III NSCLC and adjuvant chemoimmunotherapy following resection have all become new standards of care.This state-of-the-art review synthesises the key evidence underpinning these developments, highlights their clinical implications and identifies challenges to implementation-particularly the need for redefined clinical pathways, accurate pretreatment staging, timely biomarker testing and coordinated multidisciplinary decision-making. A novel treatment algorithm is proposed to support clinicians in navigating these complex treatment choices.We conclude that immunotherapy and targeted agents have irrevocably altered curative-intent NSCLC care, establishing multiple new standards that sometimes overlap and compete. In the surgical multimodality treatment pathway, neoadjuvant and perioperative chemoimmunotherapy offers the opportunity to increase the uptake of systemic therapy in comparison to adjuvant therapy and is considered by these authors to represent the optimal treatment path for most patients.In this unprecedented era of therapeutic expansion, the greatest challenge is no longer the absence of effective treatments, but the complexity of selecting, sequencing and delivering them, as well as patient optimisation. Lung cancer services must evolve through proactive pathway redesign, integrated diagnostics and new models of multidisciplinary care. High-quality, biomarker-driven and patient-centred care is now achievable for many patients with stage II-III NSCLC-but it will require system-level adaptation to deliver it
Advantages and limitations of navigation-based multicriteria optimization (MCO) in selectively sparing pharyngeal constrictor muscles in head and neck radiotherapy treatment planning
No full textPURPOSE: Sparing pharyngeal constrictor muscles (PCMs) during radiotherapy improves patient-reported swallowing function. This study aimed to explore the feasibility of integrating knowledge-based planning (KBP) with multicriteria optimization (MCO) in Eclipse v18.0 to selectively spare PCM, quantify the required trade-off in prophylactic planning target volume (PTV54) coverage, and to evaluate MCO performance. METHOD: Ten patients previously planned with KBP for oropharyngeal cancer (65, 60, and 54 Gy in 30 fractions) were retrospectively re-planned. Clinical plans were further optimized using trade-off exploration in MCO, with a priority order: spinal cord and brainstem sparing, high-dose and intermediate-dose target coverage, PCM sparing, low-dose target coverage, parotids sparing, remaining organs at risk (OAR). Plans were evaluated based on planning target volumes dose metrics (D(50%), D(98%), and D(2%)), homogeneity index (HI), conformity index (CI), and maximum and mean doses to OARs, and paired t-tests were performed. Differences between navigated and deliverable plans were analyzed. One patient underwent 10 identical repeat plan generations. RESULTS: MCO reduced the average mean dose to the superior and middle PCM, inferior PCM, contralateral parotid, and larynx by 2.0, 3.4, 2.6, and 3.9 Gy, respectively (p < 0.05) but at the expense of HI and CI. No difference was observed in average PTV54 D(98%) between techniques; however, all clinical plans and seven MCO plans achieved D(98%) ≥ 95%, with three MCO plans modestly compromised (D(98%) 93.7%-94.6%). Dose metrics between navigated and deliverable plans differed by ≤0.7 Gy for mean doses and ≤1.8 Gy for maximum doses. Pareto surface generation was not repeatable. CONCLUSION: MCO effectively balances the trade-off between PCM sparing and low-dose target coverage. It may be a valuable tool in the context of personalized care
Radiotherapy for growing vestibular schwannomas
No full textIMPORTANCE: In the literature, there is a lack of data reporting tumor control rates after radiotherapy in actively growing vestibular schwannomas (VS). Data for this rarely studied population are needed. OBJECTIVE: To estimate tumor control rates in radiologically growing VS treated with first-line radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter cohort study used prospectively collected data from patients with growing unilateral VS treated first-line with radiotherapy between January 2000 and December 2023 from 8 tertiary referral skull base units. The data were analyzed in June 2025. EXPOSURES: Radiotherapy as an initial treatment for VS. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, ie VS growth postradiotherapy, which was predefined as an increase in maximum intracranial tumor diameter (ICTD) of 3 mm or greater within the first 2 years after radiotherapy or 2 mm or greater thereafter. Secondary outcomes were treatment failure based on different definitions of VS growth: (1) an increase in ICTD of 2 mm or greater, (2) an increase in ICTD of 3 mm or greater, and (3) conversion to surgery. RESULTS: A total of 1883 patients (975 female individuals [51.8%]; median age at diagnosis, 63 years [IQR, 53-71 years]) were included in the study. Using the primary definition of treatment failure (an increase in ICTD of ≥3 mm within the first 2 years postradiotherapy or ≥2 mm thereafter), the Kaplan-Meier estimate yielded a 10-year tumor control rate of 76.1% (95% CI, 72.7%-79.2%). For secondary outcome definitions, 10-year tumor control rates were 60.1% (95% CI, 57.5%-64.3%) for an ICTD increase of 2 mm or greater, 78.3% (95% CI, 75.0%-81.2%) for an increase of 3 mm or greater, and 92.6% (95% CI, 90.4%-94.3%) for conversion to surgery. Neither pretreatment tumor size nor tumor location (intracanalicular vs extracanalicular) were significantly associated with treatment failure. CONCLUSIONS AND RELEVANCE: The results of this cohort study provide tumor control outcomes for radiologically growing VS treated with radiotherapy using several clinically relevant definitions of growth. By focusing exclusively on this rarely isolated subgroup, the findings offer targeted data to potentially inform treatment expectations and future research
BRCA2 pre-mRNA differential 5' splicing: a rescue of functional protein properties from pathogenic gene variants and a lifeline for fanconi anemia D1 patients
No full textFanconi anemia (FA) is a DNA repair deficiency disorder associated with genomic and chromosomal instability and a high cancer risk. In a small percentage of cases, FA is caused by biallelic pathogenic variants (PVs) in the BRCA2/FANCD1 gene, defining the FA-D1 subtype. Experimental and epidemiologic data indicate that the complete absence of BRCA2 is incompatible with viability. Therefore, cells from individuals affected with FA caused by biallelic BRCA2 PVs must have a residual BRCA2 function. This activity may be maintained through hypomorphic missense mutations, translation termination-reinitiation associated with a translational stop mutation, or other non-canonical or uncommon translation initiation and elongation events. In some cases, however, residual BRCA2 function is provided by alternatively or aberrantly spliced BRCA2 transcripts. Here, we review and debate aspects of the contribution of splicing in the 5' segment to BRCA2 functions in the context of PVs affecting this largely intrinsically disordered protein region, with a focus on recent findings in individuals with FA-D1. In this Perspective, we also discuss some of the broader biological implications and open questions that arise from considering 5'-terminal BRCA2 splicing in light of old and new findings from FA-D1 patients and beyond