Consolidation ICIs Alter cardiac subregion radiosensitivity in NSCLC patients treated with Chemo-Radiotherapy

he addition of immune checkpoint inhibitor (ICI) as consolidation therapy after chemoradiation (CRT) has improved survival rates in non-small cell lung cancer (NSCLC) patients. However, the cardiotoxicity of CRT combined with ICI remains underexplored. This study assesses if ICI exposure alters the critical cardiac subregion linked to radiation-induced heart disease (RIHD) following CRT.

We conducted a retrospective analysis of 321 locally advanced NSCLC patients treated with definitive CRT from August 2008 to December 2019, including 67 who received consolidation ICI. Cardiac contours include the entire heart, chambers, major coronary arteries, and conduction nodes. The primary endpoint was RIHD, defined as a major adverse cardiac event and atrial fibrillation. We used Fine-Gray analysis to investigate associations between RIHD and mean doses to cardiac subregions.

In total, 53 patients (18.4 %) developed RIHD, with no significant difference between CRT and CRT + ICI groups. Doses to cardiac subregions were similar between the groups. In the CRT group, multivariable analysis shows that dose to the base of the heart, especially the sinoatrial node (SAN), correlated with increased RIHD risk (HR = 1.02 per 1 Gy, 95 %CI [1.01-1.03], p < 0.001). In the CRT + IO group, the left ventricle (LV) dose was a significant predictor (1.06 [1.06-1.1], p = 0.006).

Doses to the SAN and the base of the heart correlate with RIHD in CRT patients, while doses to LV in CRT + ICI patients. While the 2-6 % increased risk per Gy seems modest, it is clinically significant as the subregions, being small structures, can potentially be completely spared with a carefully optimized plan.