Spatial mapping of cardiac dose-survival associations in oesophageal radiotherapy.

Abstract

To investigate spatial associations between cardiac radiation dose and survival following radiotherapy for oesophageal cancer, and to assess whether a previously defined Cardiac Avoidance Area (CAA) from lung radiotherapy is relevant in this patient population. Patients treated with curative-intent radiotherapy for middle or lower oesophageal cancer between 2009 and 2024 were identified from a large institutional database. Planning CT images and dose distributions were deformably registered to a common reference anatomy for voxel-based analysis. Dose-survival associations were assessed voxel-wise by comparing dose between patients alive and deceased at 12 months, with permutation testing for multiple comparisons. Dose to the CAA was quantified, and survival was evaluated using Kaplan-Meier analysis and multivariable Cox regression including clinical covariates. A total of 452 patients were included. Voxel-based analysis identified a spatially localised heart region where higher radiation dose was significantly associated with poorer 12-month survival, exceeding the 99th percentile of permutation-derived significance. This region partially overlapped with the lung-derived CAA and the left atrium. A maximum CAA dose threshold of 43.5 Gy produced significant survival stratification, with improved median survival in patients receiving lower doses. Maximum CAA dose remained an independent predictor of survival on multivariable analysis. Image-based data mining identified a radiosensitive cardiac region associated with survival after oesophageal radiotherapy, overlapping the established CAA from lung cancer. These findings support the relevance of spatially defined cardiac dose metrics and suggest a potential role for targeted cardiac avoidance in oesophageal radiotherapy planning.