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Cardiac Radiation Dose and Lung Cancer Mortality
Study Questions:
Is cardiac radiation dose a predictor of major adverse cardiac events (MACE), oncology clinical trial common terminology criteria for adverse events (CTCAE), and all-cause mortality (ACM)?
Methods:
In this retrospective, single-center study of 748 patients with stage II or III non–small cell lung cancer (NSCLC) who underwent radiotherapy (RT) (mean age 65 years, 49% women, 36% with pre-existing coronary heart disease [CHD]), the authors examined the impact of baseline CHD, RT technique, and dose on MACE, ACM, and CTCAE.
Results:
There was no significant difference in RT technique and dose between patients with and without pre-existing CHD. Median follow-up time was 20 months, with 10% (n = 77) of patients meeting at ≥1 MACE, 71% (n = 533) dying, and 32% (n = 240) having a grade 3 CTCAE. Overall, patients with pre-existing CHD had worse outcomes compared to those without CHD. In multivariable analysis, a 1 Gy increase in mean heart dose (MHD) was associated with a 5% increase in risk of MACE, 2% increase in ACM, and 3% increase in CTCAE. There was no MHD threshold below which risk was decreased. Interestingly, the increase in risk related to MHD was noted only in patients without pre-existing CHD.
Conclusions:
Higher cardiac radiation dose is associated with worse outcomes in patients with NSCLC.
Perspective:
The findings from this well-characterized cohort are thought provoking to say the least. The study corroborates findings from prior smaller studies and highlights minimizing RT doses to <10 Gy as a potential approach to decreasing risk of adverse outcomes. One unexpected finding was that the association between MHD and outcomes was limited to the subgroup without pre-existing CHD. The authors astutely explain that this difference is potentially due to the elevated baseline risk in patients with CHD surpassing an observable dose-response relationship between MHD and outcomes. While possible, one cannot preclude potential confounding factors in the absence of a randomized study. Overall prognosis in patients with NSCLC is poor, with death from noncardiovascular causes significantly outweighing cardiovascular events, as noted in this study. Recommendations to reduce RT dose must account for the potential decrease in the effectiveness of cancer therapy and its impact on subsequent outcomes.
Clinical Topics: Cardio-Oncology, Noninvasive Imaging, Prevention
Keywords: Carcinoma, Non-Small-Cell Lung, Cardiotoxicity, Coronary Disease, Diagnostic Imaging, Lung Neoplasms, Radiation Dosage, Radiotherapy, Risk, Secondary Prevention, Treatment Outcome
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