The Christie School of Oncology: Christie Research Publications Repository
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Preclinical characterisation of changes in cardiac function and circulating biomarkers following differential irradiation of thoracic volumes
No full textINTRODUCTION: The heart and lungs are critical organs at risk in patients receiving radiotherapy for thoracic tumours. Preclinical studies in rat models have provided evidence indicating consequential effects of lung radiation on the heart through vascular remodelling which leads to pulmonary arterial hypertension. In this study, we aimed to assess the impact of lung irradiation on a long-term model of cardiac base irradiation that recapitulates clinical observations of the heart base as a radiosensitive region and to understand relationships between cardiopulmonary irradiation and circulating cytokines profiles. METHODS: Female C57BL6J mice were irradiated under CT image-guidance targeting the heart base, right lung or co-irradiation of the heart base and the right lung. Mice were monitored by transthoracic echocardiography for 50-weeks after irradiation with lung histology and cytokine profiling at 10 and 50 weeks. RESULTS: Lung and heart co-irradiation leads to small changes in the cardiac function and histological changes in the right lung with distinct changes in serum cytokines for different irradiated volumes compared to heart irradiation. DISCUSSION: In contrast to previous studies in rat models, these data demonstrate a minimal contribution of lung irradiation to cardiac response in this model. Understanding the potential interplay between the heart and lungs is important in the context of optimising cardiac dose distributions that may increase lung doses and minimising the impact of lung dose on cardiac function
Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response
No full textNavitoclax (oral B-cell lymphoma-2 family protein inhibitor induces apoptosis of malignant cells in myelofibrosis (MF). We present pooled cohort 1 results from the phase 2 REFINE trial, which evaluated navitoclax plus ruxolitinib (NAV+RUX) for patients with relapsed/refractory MF with suboptimal response to RUX (≥10 mg twice daily stable dose for ≥12 weeks [cohort 1a] or ≥24 weeks [cohort 1b]). Cohort 1a received add-on NAV 50 mg/d, with escalation to ≤300 mg if platelet count was ≥75 × 10(9)/L. Cohort 1b received NAV 100 or 200 mg/d if platelet count was ≤150 or >150 × 10(9)/L, respectively. The primary end point was spleen volume reduction of ≥35% (SVR(35)) at week 24. Secondary end points included ≥50% total symptoms score (TSS(50)) reduction at week 24, bone marrow fibrosis (BMF) grade changes, anemia response, and safety. In total, 125 patients received ≥1 dose of NAV+RUX. With median follow-up of 21 months, SVR(35) rate was 23% at week 24 and 39% at any time on study (median duration: 11 months). TSS(50) rate was 24% at week 24 and 46% at any time on study. BMF improved by ≥1 grade, any time on study, in 39% of patients. Anemia responses were achieved in 23% of patients. Median overall and progression-free survival were 52.3 and 22.1 months, respectively. No new safety signals were observed. The most common adverse event was thrombocytopenia without clinically significant bleeding. NAV+RUX was tolerable and demonstrated early improvement in disease modification parameters in this difficult-to-treat population. This trial was registered at www.ClinicalTrials.gov as #NCT03222609
Molecular analysis of adolescent and young adult high grade gliomas in the SPECTA-AYA study: Poorly characterised tumours with frequent germline alterations
No full textBACKGROUND: Adolescent and young adult (AYA) high grade gliomas (HGG) have the worst survival of AYA malignancies yet are poorly represented in large-scale molecular datasets. METHODS: 50 AYAs aged 12-29 with newly diagnosed or recurrent HGG and other high risk central nervous system (CNS) tumours were prospectively recruited to the EORTC SPECTA platform study and underwent whole exome sequencing, RNA sequencing and methylation profiling, with central pathological review. Actionable mutations were reported and patients followed up for therapies and outcome. RESULTS: From 46 locally diagnosed HGGs and 4 other recurrent CNS tumours, molecular and pathology review resulted in histological grade re-classification (n = 10), diagnostic refinement (n = 9) and revised diagnoses (n = 12) in a substantial proportion. Pathogenic constitutional alterations were present in 14 % overall and were largely limited to cases with IDH-wildtype glioblastoma and paediatric-type diffuse HGGs. 91 % of HGGs had potentially actionable alterations affecting RAS/RAF/MAPK (60 %), PI3K/AKT/mTOR (27 %) and cell cycle genes (11 %). High tumour mutational burden (> 10 somatic non-synonymous mutations per Mb of genome targeted) was present in 12 % at diagnosis and 18 % at recurrence, all in histological grade 4 tumours. Ten patients' treatment was modified on the basis of molecular profile, of whom 5 remained on treatment at last follow-up. CONCLUSION: AYA HGGs comprise a diverse group of entities; accurate, molecularly-defined diagnosis is critical to direct primary treatment, determine risk of genetic predisposition and guide molecularly-directed therapy. Current services fail to routinely address diagnosis, personalised molecular profiling or investigation of therapeutic opportunities for this high risk, poor prognosis group of rare cancer patients
Risk of ovarian cancer in women with a pathogenic variant in NBN: a systematic review and meta-analysis in 38,330 patients
No full textSarcopenia does not predict increased acute or late radiotherapy related toxicities in prostate cancer patients
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Deep learning models for deriving optimised measures of fat and muscle mass from MRI
No full textFat and muscle mass are potential biomarkers of wellbeing and disease in oncology, but clinical measurement methods vary considerably. Here we evaluate the accuracy, precision and ability to track change for multiple deep learning (DL) models that quantify fat and muscle mass from abdominal MRI. Specifically, subcutaneous fat (SF), intra-abdominal fat (VF), external muscle (EM) and psoas muscle (PM) were evaluated using 15 convolutional neural network (CNN)-based and 4 transformer-based deep learning model architectures. There was negligible difference in the accuracy of human observers and all deep learning models in delineating SF or EM. Both of these tissues had excellent repeatability of their delineation. VF was measured most accurately by the human observers, then by CNN-based models, which outperformed transformer-based models. In distinction, PM delineation accuracy and repeatability was poor for all assessments. Repeatability limits of agreement determined when changes measured in individual patients were due to real change rather than test-retest variation. In summary, DL model accuracy and precision of delineating fat and muscle volumes varies between CNN-based and transformer-based models, between different tissues and in some cases with gender. These factors should be considered when investigators deploy deep learning methods to estimate biomarkers of fat and muscle mass
Overview of large-scale routine implementation of electronic patient-reported outcome measures (ePROMs) for patients with lung cancer
No full textExpanding global radiotherapy access via telemedicine
No full textAims: Cancer is a leading cause of death globally. Over 70% of the 10 million cancer deaths worldwide in 2020 occurred in low- and middle-income countries. Radiotherapy is an important cancer treatment, used in half of cancer patients. Significant global disparities in radiotherapy access exist, with low access in low- and middle-income countries. The benefits of tele-radiotherapy in low- and middle-income countries for expanding global radiotherapy access are yet to be fully realized. In this paper, we highlight potential applications of tele-radiotherapy in expanding access to high-quality radiotherapy in developing countries. Materials and Methods: We performed a literature search to retrieve studies involving telemedicine applications in radiotherapy to provide a comprehensive overview of the topic. PubMed database served as the main source for retrieving studies, using the following search terms: ('telemedicine', 'radiotherapy', 'telehealth', 'remote monitoring', 'oncology', and 'remote training'). Additional selected papers were obtained from Web of Science, and Google Scholar using the same search terms. Results: Telemedicine in radiotherapy has many applications. Virtual training could upgrade radiotherapy skills in low- and middle-income countries, enabling safe adoption of new radiotherapy techniques and quality assurance. Tele-radiotherapy consultations and patient follow-up could improve the efficiency of clinics while tele-radiotherapy planning and peer-review could enable equitable global access to radiotherapy expertise. Telemedicine could also facilitate wider global access to radiotherapy trials. While telemedicine in radiotherapy holds significant promise in improving global radiotherapy access, several barriers to its adoption exist. These include a lack of infrastructure, data security concerns, regulatory challenges, resistance from providers and patients, financial constraints, miscommunication during remote consultations, and lack of training. Conclusion: Tele-radiotherapy applications hold promise in providing solutions to overcome global radiotherapy access inequity but the benefits of teleradiotherapy in low- and middle-income countries are yet to be fully realized. (c) 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies