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Abstract
Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Affiliations

Yejin Kim 1 2, Gowoon Yang 1 3, Jaewon Oh 4, Seo-Yeon Gwak 4, Kyung Hwan Kim 5, Joongyo Lee 6, Jin Sung Kim 1, Chang Geol Lee 1, Jaeho Cho 1, Bonnie Ky 7, Hong In Yoon 1, Clemens Grassberger 2
1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, The Republic of Korea.
2Department of Radiation Oncology, University of Washington, Fred Hutch Cancer Center, Seattle, Washington, the United States of America.
3Department of Radiation Oncology, Cha University Ilsan Cha Hospital, Cha University School of Medicine, Ilsan, The Republic of Korea.
4Severance Cardiovascular Hospital and Cardiovascular Research Institute, Cardiology Division, Yonsei University College of Medicine, Seoul, The Republic of Korea.
5Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, The Republic of Korea.
6Department of Radiation Oncology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
7Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, the United States of America.