Protocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia.

INTRODUCTION: A coronary artery calcium (CAC) CT scan can identify calcified plaque and predict risk of future cardiac events. Cancer survivors undergoing thoracic radiotherapy routinely undergo a planning CT scan, which presents a unique opportunity to use already obtained medical imaging to identify those at the highest risk of cardiac events. While radiation therapy is an important modality for many cancer treatments, radiation dose to the heart in thoracic radiotherapy leads to cardiotoxicity and may accelerate pre-existing atherosclerosis. The primary aims of this study are to investigate the feasibility of using CAC scores calculated on thoracic radiotherapy planning CT scans to identify a subset of cancer survivors at an increased risk of future cardiac events, and to establish and evaluate a referral pathway for assessment and management in a cardio-oncology clinic. An optional substudy aims to investigate using abdominal aortic calcification (AAC) as a practical, low-radiation alternative to CAC to evaluate and monitor vascular health. METHODS AND ANALYSIS: This is an observational, prospective study in a minimum of 100 cancer survivors commencing radiotherapy. Participants will have CAC scored from thoracic radiotherapy planning CT scans. Those identified as high risk (CAC score>0) will be referred to a cardio-oncology clinic. Feasibility, determined by adherence to the recommended pathway, and impact on quality of life and anxiety measured via questionnaire, will be assessed. Participants in Western Australia will be invited to participate in a 12-month observational pilot substudy, investigating lifestyle behaviours and the use of a dual-energy X-ray absorptiometry machine to measure musculoskeletal health and AAC. ETHICS AND DISSEMINATION: Ethics approval has been obtained from St Vincent's Hospital, Sydney (Project number 2021/ETH11847), GenesisCare and Edith Cowan University (2022-03326-DALLAVIA). Study results will be reported in peer-reviewed academic journals, at scientific conferences, and at clinical forums, irrespective of the results observed. TRIAL REGISTRATION NUMBER: ACTRN12621001343897.

Correlation between initial tumour volume and treatment duration on Dabrafenib: observation study of subjects with BRAF mutant melanoma on the BRF112680 trial.

BACKGROUND: Planar-based measurements of lesions in metastatic melanoma have limitations in estimating tumor burden of a patient and in predicting response to treatment. Volumetric imaging might add predictive value to Response criteria in Solid Tumor (RECIST)-measurement. Based on clinical observations, we explored the association between baseline tumor volume (TV) and duration of treatment with dabrafenib in patients with metastatic melanoma. We have also explored the prognostic value of TV for overall survival (OS) and progression free survival (PFS). METHODS: This is a retrospective, chart-review of primary source documents and medical imaging of a cohort of patients participating in the BRF112680 phase 1 clinical trial at the Prince of Wales Hospital. TV was quantified by contouring all the measurable baseline target lesions in the standard manner for radiation planning using Voxxar™ software. We used Cox regression models to analyse associations between TV and duration of treatment with dabrafenib and between TV, PFS and OS. RESULTS: Among 13 patients of BRAF 112680 trial, 10 were included in the retrospective analysis. Target lesion sum volume ranged from 0.3 to 1065.5 cm3 (cc), with a median of 27.5 cc. The median PFS and OS were 420 days (range 109-1765) and 1680 days (range 390-2940), respectively. The initial TV was inversely correlated with duration of treatment with dabrafenib (rho - 0.6; P 0.03). In multivariate analysis, TV was a predictor for OS (HR 2.81 CI 1.06-6.19) and PFS (8.76 (CI 1.05-43.58). Patients with tumour volume above the median had significantly lower OS of 6-months compared to 56-months survival for patients with smaller volumes; P = 0.019. CONCLUSIONS: TV is a predictor for treatment duration and is prognostic of OS and PFS in patients with metastatic melanoma. These findings need to be validated prospectively in clinical trials.