Mean heart dose (MHD) was found to be insufficient to predict risk of major adverse cardiac events (MACE) among patients with locally advanced non-small cell lung cancer (NSCLC) undergoing thoracic radiotherapy, according to a retrospective study published in the International Journal of Radiation Oncology, Biology, Physics.

Radiation therapy is associated with an increased risk of MACE among patients with locally advanced NSCLC. Most studies have evaluated MHD to evaluate cardiac toxicity, but MHD is not a sufficient surrogate for coronary artery dose. The aim of this study was to evaluate the role of MHD and left anterior descending (LAD) dose in predicting the risk of MACE in this population.

The investigators conducted a retrospective study by analyzing data from 701 consecutive patients with stage II to III NSCLC who received thoracic radiotherapy at a single center between 2003 and 2014. Radiation therapy was delivered as definitive treatment concurrent with chemotherapy or as neoadjuvant or adjuvant therapy with or without chemotherapy.  MACE included cardiac death, unstable angina, myocardial infarction, heart failure hospitalization or urgent visit, or coronary revascularization.

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Although MHD and LAD V15Gy were significantly correlated (r=0.74; P <.0001), MHD attributed to 54.5% of the proportion of variance in LAD V15Gy, indicating it is not sufficient for prediction (R2=0.545). Discordance, which occurred when MHD and LAD V15Gy differed, was present among 23.1% of cases.

Among the entire cohort, the 2-year cumulative incidence of MACE was 5.7%. This value differed, however, when stratified by MHD/LAD dose groups. The highest risk was in the MHD low/LAD high dose group at 13.0%, followed by the MHD high/LAD high dose group at 7.6%, the MHD high/LAD low group at 4.2%, and the MHD low/LAD low group at 1.8%.

In a multivariate analysis, only patients in groups with low LAD dose were associated with a reduced risk for MACE, including patients in the MHD high/LAD low group (hazard ratio [HR], 0.34; 95% CI, 0.13-0.93; P =.036) and MHD low/LAD low group (HR, 0.24; 95% CI, 0.10-0.53; P <.001).

The authors concluded that “MHD is not sufficient to predict LAD V15Gy with confidence and that isolated low LAD V15Gy significantly reduces the risk of MACE.” They added that “These findings further question the validity of continued utilization of whole heart metrics to predict cardiac toxicity and similarly question reliance on MHD constraints in guidelines and clinical trials.”


Atkins KM, Bitterman DS, Chaunzwa TL, et al. Mean heart dose is an inadequate surrogate for left anterior descending coronary artery dose and the risk of major adverse cardiac events in lung cancer radiotherapy. Int J Rad Oncol Biol Phys. Published online March 10, 2021. doi:10.1016/j.ijrobp.2021.03.005