Radiation dose to heart base linked with poorer survival in lung cancer patients

• A novel methodology for identifying dose-sensitive normal tissues is applied to the lung for the first time.
• We perform a voxel-by-voxel analysis, correlating dose in each voxel against overall survival in 1101 NSCLC patients.
• The base of the heart is identified as a dose-sensitive structure.
• Patients receiving more than 8.5 Gy to this region have significantly poorer survival, p < 0.001, hazard ratio 1.2.
• A hypothesis is generated to aid better targeting of future clinical studies.

BackgroundAdvances in radiotherapy (RT) have allowed an increased proportion of lung cancer patients to be treated curatively. High doses delivered to critical thoracic organs can result in excess mortality with tolerance doses poorly defined. This work presents a novel method of identifying anatomical dose-sensitive regions within the thorax.MethodsA high-resolution, normal-tissue dosimetric analysis was performed to identify regions in the heart that correlate with poorer survival. A total of 1101 patients treated with curative-intent RT were selected and all computed tomography imaging and dose distributions were deformed to a reference. Mean dose distributions were created for patients who survived versus those who did not at a set time point. Statistical significance of dose differences was investigated with permutation testing. The dose received by the most statistically significant region of the thorax was collected in all patients and included in a multivariate survival analysis.ResultsThe permutation testing showed a highly significant region across the base of the heart, where higher doses were associated with worse patient survival (p < 0.001). Cox-regression multivariate analysis showed region dose, tumour volume, performance status and nodal stage were significant factors associated with survival, whereas cardiac mean dose, V5 and V30 showed no significance. Survival curves, controlling for these factors, were plotted with patients receiving doses greater than 8.5 Gy to the identified region showing worse survival (log-rank p < 0.001, hazard ratio 1.2).ConclusionThe application of this novel methodology in lung cancer patients identifies the base of the heart as a dose-sensitive region for the first time.