The Christie School of Oncology: Christie Research Publications Repository
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The Birmingham mandible and midface rules: final data analysis
No full textHeuristics and predictor rules are a mainstay in the field of emergency medicine where the breadth of knowledge required of frontline staff can be significant. The Birmingham mandible and midface (BruMM) rules were previously developed to streamline decision making concerning plain film radiography in suspected facial fractures. Frontline clinicians within a large NHS foundation trust were asked to apply the BruMM rules to any suspected mandibular or zygomatic fracture, prompting them to consider plain film radiographs as the investigation of choice. Radiographs were then reviewed by members of the BruMM Rules Study Group to determine the presence or absence of fractures. Discriminant analysis was performed whereby binomial fracture outcomes were modelled using cross-validated least absolute shrinkage and selection operator (LASSO) regression. Custom analysis was then performed using a forward stepwise procedure, maximising the Jaccard index of a predictor against the target outcome. A total of 116 patients were recruited, of whom 28 (24.1%) demonstrated a fracture. Combining the results from the LASSO regression analysis and forward stepwise Jaccard procedure yielded a predictor rule with three mandibular and six zygomatic predictors. This composite BruMM-rules score demonstrated maximal sensitivity and specificity of 96.4% and 56.5%, respectively.Implementation of the BruMM rules in the current cohort would have avoided 49 plain film radiograph studies (43.4%), translating into potential cost savings of £8,356.86-£15,440.76 per annum
Comparative treatment planning of very high-energy electrons and photon volumetric modulated arc therapy: Optimising energy and beam parameters
No full textBACKGROUND: Very High-Energy Electron (VHEE) beams offer potential advantages over current clinical radiotherapy modalities due to their precise dose targeting and minimal peripheral dose spread, which is ideal for treating deep-seated tumours. To aid the development of clinical VHEE machines, this study adressed the need to identify optimum VHEE beam characteristics for tumours across various anatomical sites. MATERIALS AND METHODS: VHEE treatment planning employed matRad, an open-source treatment planning system, by adapting its proton pencil beam scanning implementation. VHEE beam characteristics were generated using TOPAS Monte Carlo simulations. A total of 820 plans were retrospectively created and analysed across 10 pelvic and 12 thoracic cases and compared against clinical photon VMAT plans to identify the most optimal VHEE beam configuration and energy requirement. RESULTS: VHEE plans outperformed photon VMAT in sparing organs-at-risk (OARs) while maintaining or improving target coverage. While 150 MeV served as the threshold for effectively treating deep-seated sites, 200 MeV was identified as a more optimal energy in the pelvis for achieving the best balance of penetration and sparing abutting OARs. Lower energies (70-110 MeV) also benefitted mid-to-superficial disease in the lung cohort. Typically, VHEE plans required 3-5 fields, and resulted in notable dose reductions to OARs across treatment sites, including: 22.5% reduction in rectal D(mean); 13.8% decrease in bladder D(mean); 8.2% reduction in heart D(mean); and a 24.4% decrease in lung V(20Gy). CONCLUSION: The study reinforces VHEE's potential in clinical settings, emphasising the need for varied energy ranges to enhance treatment flexibility and effectiveness
Cost-effectiveness of CA125- and age-informed risk-based triage for ovarian cancer detection in primary care
No full textBACKGROUND: In England, current practice is cancer antigen 125 (CA125) testing with pelvic ultrasound scan (USS) if CA125 is ≥35 U/mL for triage of women with suspected ovarian cancer (OC) in primary care. However, OC risk varies with CA125 level and age. The Ovatools model predicts OC risk based on age and CA125 levels to support primary care triage. METHODS: We evaluated five alternative triage pathways for suspected OC in primary care, using a decision model. Two CA125-USS sequential pathways used Ovatools risk: 1-3% (subsequent USS) and ≥3% (urgent referral), or age-adjusted CA125 thresholds equivalent to Ovatools risks. Three pathways involved concurrent CA125-USS testing, with referral if abnormal USS or one of the following: (1) Ovatools risk ≥3%, (2) CA125 above the equivalent age-adjusted threshold, or (3) CA125 ≥ 35 U/mL. Clinical and cost-effectiveness was compared against current practice for women over and under 50 years. RESULTS: All alternative pathways increased benefits at age ≥50 years, at additional cost. The incremental cost-effectiveness ratios for CA125-USS sequential pathways were below £30,000, dropping below £20,000 if the Ovatools threshold for USS increased to 1.2-1.4% risk. DISCUSSION: For women ≥50 years, the Ovatools and equivalent age-adjusted threshold sequential pathways are cost-effective compared to current practice
First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: a real-world survival analysis
No full textOBJECTIVES: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies. METHODS: We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8-77) and 67.3 % of the patients had an ECOG 0-1. With a median follow-up of 73.2 months (95 % CI 66.2-115.7) and 30.6 months (95 % CI 26.0-38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022). CONCLUSION: First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFR-mutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches
Clinical trials for patients with salivary gland cancers: A systematic review of worldwide registers and an evaluation of current challenges
No full textBACKGROUND: Clinical trials (CT) are crucial for generating scientific evidence and improving clinical outcomes, but they can be challenging in the context of rare cancers. Salivary gland cancers (SGC) are rare and heterogeneous tumors, without standard-of-care approved systemic therapies. We analyzed completed and ongoing CTs to assess the current state of clinical research activity in the field. METHODS: ClinicalTrials.gov, WHO-ICTRP, HealthCanadaCT were searched for antineoplastic pharmacological and interventional CT involving patients with SGC from the trials database creation until August 6th, 2024. CT characteristics and status were collected. RESULTS: 134 clinical trials met inclusion criteria. Of these, 78 % were sponsored by non-industry entities. 49 % were conducted at only one site, and 61 % at up to five centers. Only 25 trials (19 %) were multinational, being 15 industry-sponsored, a significantly higher proportion compared to non-industry-sponsored trials(p < 0.01). 16 % CTs were umbrella or basket, and 6 % were randomized, again predominantly industry-sponsored(p < 0.01). Regarding SGC-specific trials, 32 % were open to all patients with SGC, regardless of specific histology. Patients with adenoid cystic, salivary duct, and mucoepidermoid carcinoma had access to 92 %, 66 % and 62 % of trials, respectively. 88 % CT targeted palliative setting, and 38 % incorporated predictive biomarkers. Tyrosine kinase inhibitors were the most studied therapy(26 %), followed by immunotherapy(15 %), chemotherapy and antibody-drug conjugate(12 % each) and androgen-blockade(8 %), among others. CONCLUSION: Clinical research for patients with SGC relies mainly in non-industry organisations, most of them limited to run trials in one to five sites, in a single country. Further collaboration between investigators is needed, as well as reconsidering inclusion criteria and trial designs
Exploring consent to use real-world data in lung cancer radiotherapy: decision of a citizens' jury for an 'informed opt-out' approach (vol 33, pg 192, 2025)
No full textMetachronous colorectal cancer risks after extended or segmental resection in MLH1, MSH2, and MSH6 Lynch syndrome: multicentre study from the Prospective Lynch Syndrome Database
No full textThis first prospective observational study evaluates the impact of extended versus segmental colorectal surgery on the risk of metachronous colorectal cancer (CRC) in patients with Lynch syndrome, analyzing data from the Prospective Lynch Syndrome Database version 5. Extended resection significantly reduced the risk of metachronous CRC in path_MLH1, path_MSH2, and path_MSH6 carriers compared to segmental resection
A service evaluation into camera occlusion using Surface-Guided Radiotherapy (SGRT) for VMAT DIBH breast patients
No full textTivozanib monotherapy in the frontline setting for patients with metastatic renal cell carcinoma and favorable prognosis (vol 26, pg 1639, 2024)
No full textCancer of unknown primary: the hunt for its elusive tissue-of-origin - is it time to call off the search?
No full textCancer of Unknown Primary (CUP) is an heterogenous group of metastatic cancers, for which the primary site cannot be identified despite thorough diagnostic work-up. Whilst it is a relatively rare entity, its aggressive nature, together with the paucity of effective treatments, mean it has a disproportionately high mortality rate. Advances in genomic profiling have driven research in the area, but despite this, therapeutic options and prognosis remain poor. For many years, the primary focus in CUP has been improving identification of the tissue-of-origin (TOO), with the hope that site-specific therapy will improve survival outcomes. However, the lack of conclusive evidence to support this, as well as an emerging paradigm shift in how cancers should be classified, has reignited the debate surrounding the importance of TOO. Here, we provide a comprehensive review of the ongoing relevance of TOO, within both the CUP and wider oncology landscape