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dc.contributor.authorMcWilliam, Alan
dc.contributor.authorAbravan, Azadeh
dc.contributor.authorBanfill, Kathryn
dc.contributor.authorFaivre-Finn, Corinne
dc.contributor.authorvan Herk, Marcel
dc.date.accessioned2022-01-11T11:59:35Z
dc.date.available2022-01-11T11:59:35Z
dc.date.issued2021en
dc.identifier.citationMcWilliam A, Abravan A, Banfill K, Faivre-Finn C, van Herk M. Demystifying Cardiac Dose in RTOG-0617. International Journal of Radiation Oncology Biology Physics. 2021;111(3):S125-S.en
dc.identifier.urihttp://hdl.handle.net/10541/624819
dc.description.abstractPurpose/Objective(s): The RTOG-0617 trial presented worse overall survival for patients with lung cancer treated in the high-dose 74 Gy arm compared to those treated with 60Gy. In multi-variable models, whole heart volumetric dose parameters (volume of heart receiving at least 5Gy and 30Gy), and the high-dose treatment arm was found to be associated with survival, rescinding dose escalation. In this abstract, we repeat this survival analysis, but consider cardiac sub-regions to find an explanation for the counterintuitive survival difference observed between the treatment arms. Materials/Methods: Voxel-wise analysis was performed on dose distributions spatially normalized onto a template patient anatomy. Permutation testing assessed significance, identifying anatomical regions where dose was associated with overall survival. Dose to the identified cardiac sub-region was included in multi-variable modelling. Clinical and dosimetric variables were bootstrapped 500 times into an elastic-net variable selection model to identify variables associated with survival. Variable importance was assessed by (1) magnitude of model coefficients and (2) frequency of selection. Next, multi-variable Cox regression survival models were created to assess significance of dose to the identified cardiac region compared to v5 and v30 parameters used previously. Results: A total of 488 patients, with accurate dose mapping, were included in the voxel-wise analysis. A significance region (P < 0.001) was identified in the base of the heart, centered over the origin of the left coronary artery and atrioventricular node, with median dose 9.5 Gy (high dose arm 10.2 Gy, low dose arm 9.1 Gy). Bootstrapping of clinical variables identified mean lung dose (selected 99%), treatment arm (65%), log tumor volume (66%) and heart region dose (62%) as most important factors associated with survival (v5 and v30 selected < 10%). Multi-variable models included mean lung dose, log tumor volume, age, gender, treatment arm, performance status, smoking history, PET staging and histology and either heart v5, v30 or the identified heart region dose. Heart v5 and v30 were not found to be associated with survival, with treatment arm (P < 0.05) and log tumor volume (P < 0.02) being significant. However, heart region dose was significant (P = 0.02), along with log tumor volume (P = 0.03). Other parameters, including treatment arm were not significant. Conclusion: These results show that dose to cardiac sub-regions is more strongly association with overall survival than whole heart dose parameters. Variable selection showed the importance to include mean lung dose, suggesting an interplay between lung and cardiac dose. The treatment arm effect observed in RTOG-0617 lost its significant once the identified base of heart region dose was included into the model. Our results suggest that the worse survival of the high dose arm in RTOG617 could be explained by the dose delivered to the base of the hearten
dc.language.isoenen
dc.titleDemystifying cardiac dose in RTOG-0617en
dc.typeMeetings and Proceedingsen
dc.contributor.departmentDivision of Cancer Sciences, School of Medical Sciences,Faculty of Biology, Medicine and Health, University of Manchester, Manchesteren
dc.identifier.journalInternational Journal of Radiation Oncology Biology Physicsen
dc.description.noteen]


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