Impact of mean heart dose on mortality after high-dose radiotherapy for lung cancer

Background: Cardiovascular complications represent an important late adverse effect of thoracic radiotherapy in patients with lung cancer. Mean heart dose (MHD) is a commonly used dosimetric parameter in radiotherapy planning; however, the optimal threshold associated with patient survival has not yet been clearly defined. The aim of this study was to evaluate the impact of MHD on overall survival following high-dose radiotherapy for lung cancer. Methods: We retrospectively analysed patients with lung cancer treated with thoracic radiotherapy at the Institute of Oncology Ljubljana between 2018 and 2022. Clinical characteristics, treatment data, and dosimetric parameters from radiotherapy plans were analysed. Mean heart dose was evaluated in 5-Gy increments. Overall survival was estimated using the Kaplan-Meier method, and the impact of individual variables was assessed using Cox regression analysis. Results: A total of 460 patients were included in the analysis. The mean age was 66 years, and the majority of patients had locally advanced disease (stage III). With a median follow-up of 28.5 months, the median overall survival was 28.3 months (95% CI 25.2- 31.6). The mean heart dose was 9.09 Gy (range 0.05-34.79 Gy). When comparing groups according to the MHD threshold of 20 Gy, patients with MHD < 20 Gy had longer survival (31.1 months; 95% CI 26.7-35.4) compared with patients with MHD ≥ 20 Gy (23.5 months; 95% CI 16.2-30.8; p = 0.020). In multivariable analysis, MHD ≥ 20 Gy was independently associated with worse overall survival (HR 1.54; 95% CI 1.12-2.11; p = 0.008). Age ≥ 65 years (HR 1.66; p < 0.001) and poorer performance status (HR 2.02; p < 0.001) were also significant prognostic factors. Conclusion: Mean heart dose represents an important prognostic factor in lung cancer radiotherapy. Our results show that MHD < 20 Gy is associated with improved overall survival, supporting the use of this constraint in high-dose radiotherapy planning for lung cancer. Further analyses of radiation dose to individual cardiac substructures may help identify critical cardiac regions and improve individualized radiotherapy planning.