The Christie School of Oncology: Christie Research Publications Repository
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Incorporation of 8Gy total body irradiation into reduced intensity conditioning does not improve allogeneic transplant outcomes for high-risk adult acute lymphoblastic leukemia: Results from the randomised prospective phase 2 UK multicentre ALL-RIC impact study
No full textThe microbiome of pseudomyxoma peritonei: a scoping review
No full textThere is growing interest in the role of the microbiome in carcinogenesis, but few studies examine the microbiome of pseudomyxoma peritonei (PMP). This scoping review summarises the microorganisms identified in PMP samples and examines the evidence of their role in disease outcomes. The methodology was developed in accordance with the PRISMA-ScR framework and checklist. Nine relevant studies were included. Microbiological testing was performed on PMP samples from 85 patients. At the phylum level, Proteobacteria was detected in greatest relative abundance in tumour tissue, cellular and acellular mucin. The relative proportion of different phyla more closely resembled the gut microbiome in inflammatory bowel disease than in a healthy gut. High-grade specimens showed significantly higher bacterial density than low-grade specimens and non-neoplastic non-perforated appendix specimens. Survival data of 58 patients were published, correlating outcomes to pre-operative antibiotic administration. Observed differences were not statistically significant. There is evidence of an altered bacterial profile in PMP samples compared to a healthy gut microbiome, the significance of which is unclear. Significant methodological challenges remain in this field of study. This scoping review supports the need for further analysis of the PMP bacterial profile, using methodologies that incorporate controls and deliver taxonomic resolution at species level
Scaling for African inclusion in high-throughput whole cancer genome bioinformatic workflows
No full textSub-Saharan Africa is experiencing the highest mortality rates for several cancer types. While cancer research globally has entered the genomic era and advanced the deployment of precision oncology, Africa has largely been excluded and has received few benefits from tumour profiling. Through a thorough literature review, we identified only five whole cancer genome databases that include patients from Sub-Saharan Africa, covering four cancer types (breast, esophageal, prostate, and Burkitt lymphoma). Irrespective of cancer type, these studies report higher tumour genome instability, including African-specific cancer drivers and mutational signatures, suggesting unique contributory mechanisms at play. Reviewing bioinformatic tools applied to African databases, we carefully select a workflow suitable for large-scale African resources, which incorporates cohort-level data and a scalable design for time and computational efficiency. Using African genomic data, we demonstrate the scalability achieved by high-level parallelism through physical data or genomic interval chunking strategies. Furthermore, we provide a rationale for improving current workflows for African data, including the adoption of more genomic techniques and the prioritisation of African-derived datasets for diverse applications. Together, these enhancements and genomic scaling strategies serve as practical computational guidance, lowering technical barriers for future large-scale African-inclusive research and ultimately helping to reduce the disparity gap in cancer mortality rates across Sub-Saharan Africa
TOWARDS QUANTIFYING THE IMPACT OF HYPOFRACTIONATION VS. STANDARD RADIOTHERAPY TREATMENT REGIMENS FOR CANCER ON COSTS WORKFLOW AND THE ENVIRONMENT
No full textPatient experience assessment with serial sampling for research in rectal cancer radiotherapy trials: use of the Decision Regret Scale
No full textADSCaN: A Randomised Phase II study of Accelerated, Dose escalated, Sequential Chemo-radiotherapy in Non-Small Cell Lung Cancer. (ISRCTN47674500)
No full textRevealing the Drivers Underlying Distinct Evolutionary Trajectories in Lung Adenocarcinoma
No full textElucidating the evolution of cancers allows us to understand their key events, and the order in which they occur. To chart and interpret these evolutionary trajectories, we leverage whole-genome sequencing of lung tumours, including those from the largest cohort to date of lung cancers in subjects who have never smoked. Through ordering frequent genomic alterations, we discover three distinct evolutionary paths taken by lung adenocarcinomas; two dominated by tumours from people who have never smoked (NS-LUAD), and one followed by the vast majority of those who have smoked (S-LUAD). However, one in six NS-LUAD follow the smoking-dominant trajectory. These tumours, surprisingly, have fewer somatic alterations than the other NS-LUAD, and have shorter latency. They are strongly enriched for KRAS mutations. Our results suggest that gaining KRAS mutations allows these tumours to evolve more rapidly, acquiring a set of smoking-associated key alterations, with less need for genomic instability to progress. These tumours are three times more frequent in subjects of European vs. East Asian ancestry. These findings could shape clinical management strategies for lung adenocarcinoma patients, particularly for tumours driven by smoking-like evolutionary trajectories
Outcomes of mecom rearranged AML undergoing intensive chemotherapy in the NCRI AML17 and AML19 trials
No full textPatient-relevant outcomes from the phase III MARIPOSA-2 trial: amivantamab-chemotherapy versus chemotherapy in EGFR-mutant advanced non-small-cell lung cancer following disease progression on osimertinib
No full textOBJECTIVE: The MARIPOSA-2 study demonstrated improved progression-free survival with amivantamab and chemotherapy compared with chemotherapy alone in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC) with disease progression on or after treatment with osimertinib. This publication describes the results of patient-reported outcomes (PROs) measures and time to symptomatic progression (TTSP) for 2 treatment arms. METHODS: PRO instruments included the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire Core 30 (EORTC QLQ-C30), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8c, and the NSCLC Symptom Assessment Questionnaire. Changes from baseline were analyzed using mixed-effects models for repeated measures. Treatment comparisons were based on least-squares means. The hazard ratio for TTSP was estimated using a stratified Cox regression model with P value derived from a stratified log-rank test. RESULTS: Patients received amivantamab-chemotherapy (n = 131) or chemotherapy alone (n = 263). PRO scores were stable over time with little or no group differences in least-squares mean change from baseline. At 6 months postbaseline, 55.1% of patients in the amivantamab-chemotherapy arm reported improved or stable EORTC QLQ-C30 global health status/QoL scores compared with 29.1% in the chemotherapy arm. TTSP was prolonged for the amivantamab-chemotherapy treatment group versus chemotherapy alone (hazard ratio [HR] [95% CI], 0.73 [0.55-0.96]; nominal P = .0259). CONCLUSION: PRO results indicate that the clinical benefits of adding amivantamab to chemotherapy were achieved without compromising health-related QoL. Amivantamab-chemotherapy prolonged TTSP versus chemotherapy alone
Unravelling the impact of linear energy transfer on micronuclei induction from proton and photon irradiation
No full textMicronucleus (MN) formation has a strong link to radiation damage and is a common bio-dosimeter for acute radiation exposures. The percentage of cells containing MN (PCMN) has a strong relationship with dose, however variation between previous studies has made understanding the effect of linear energy transfer (LET) difficult. This study investigated the PCMN of seven cell lines in response to photon and proton irradiation at two different LETs (0.6 keV/ µm and 6.5 keV/ µm). MN production was scored via the cytokinesis block micronuclei assay. A linear relationship between dose and PCMN was noted for all cell lines and radiation types, with a large variability in the MN yield between cell lines. This dose-dependent increase in PCMN was independent of LET, with most cell lines showing similar responses to the radiation qualities. Overall, this data proposes a more complex relationship between dose, MN and LET