Session Item

There is emerging evidence that radiotherapy (RT) dose to cardiac substructures, specifically those located at the base of the heart, is associated with cardiac events and worse overall survival in lung cancer patients. Darby et al reported a linear relationship between excess major cardiac events and mean heart dose in patients with breast cancer. We investigated if a similar relationship exists for lung cancer patients treated with curative-intent RT, considering heart substructures dose.

2488 lung cancer patients treated between 2010-2016 at a single institute with radical RT (55/60-66Gy in 20/30-33 fractions) with or without chemotherapy were included. Primary endpoint was cardiac death (CD) occurring after day 1 of RT. Cause of death recorded on death certificates was categorised using WHO-ICD10 codes from Public Health England data. Pre-existing cardiac disease (PCD) prior to RT was collected from Hospital Episode Statistics data. For each patient, the planning CT scan was deformably registered (using NiftyReg non-rigid registration) to 6 template patients with a cardiac avoidance region (CAR) segmented by a radiation oncologist. CAR was defined in consensus with a cardiologist based on previous studies and included superior vena cava, right atrium, aortic root, and proximal segments of the coronary arteries. Mean CAR dose was calculated for all patients and averaged over the 6 sets. A nested case-control design was used, with cases being patients who died with a cardiac cause. Each case was matched with three controls according to age range, gender, PCD, tumor volume quartile, RT, and chemotherapy regimen. Rate ratios for CD were estimated with the use of conditional logistic regression after stratification. The rate of CD was modelled as bx, where x was the EQD2(α/β=3) dose to CAR (in Gy) and b (slope) was the percentage increase in the rate CD per Gy.

709 (28%) had PCD and 289 (12%) of the patients died with a cardiac cause. Median of the mean EQD2 dose to CAR was 9.9 Gy (range, 0.5-61.5) and 10.8 Gy (range, 0.5-58.7) for patients with and without PCD, respectively. The rate of CD increased by 2% for each 1 Gy increase in the mean radiation dose delivered to CAR (95% CI of slope, 1.9 to 2.1;p<0.001)(Fig.1). From conditional logistic regression, rate ratio for CD among patients with PCD was similar to those without PCD (RR=1.01, 95% CI, 0.74 to 1.36;p=0.97).

This study demonstrates that risk of CD increases with mean dose to CAR, mostly located at the base of the heart, by 2% per Gy. This study could not identify any apparent threshold for CD due to dose to CAR. The percentage increase in the risk of CD per Gy increase in the mean CAR dose was similar for patients with and without PCD. However, for a given dose to CAR, the absolute increase in the risk of CD for patients with PCD will be different due to baseline risk being different. A future study will evaluate the impact of reducing dose to CAR on lung cancer survival in our institution.