Cardiotoxicity in Patients With Lung Cancer Receiving Thoracic Radiotherapy and Immune-Checkpoint Therapy

Abstract

Immune checkpoint inhibitors (ICIs) have been widely adapted as part of the treatment of locally advance and metastatic lung cancer. ICIs can lead to severe immunogenic related cardiotoxicities, however, the overall cardiotoxic profile of these agents when combined with thoracic radiation therapy is not well defined. Here, we assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.Retrospective data was collected on Stage III-IV small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients who received ICIs between 2015 and 2018 at a large academic tertiary care hospital. All cardiotoxicities associated with ICI were assessed by a cardiologist and in correlation with history of thoracic radiotherapy (RT), the timing of RT in relation to ICI, and the mean RT heart dose. Multivariate analysis was performed on multiple logistic regression including the Framingham risk score and steroid use during the ICI therapy.Of 194 ICI-treated patients evaluated, 66 (34.02%) and 128 (65.98%) had Stage III and IV SCLC or NSCLC, respectively, the median age was 64 years (range, 36-88), and 42.47% were female. Within the total cohort, 55.2% (n = 107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (P = 0.87). There were 38 patients who received RT concurrently with ICI and did not develop any cardiotoxicity whereas cardiotoxicity was observed in 14.1% (n = 22/156) of those who did not receive concurrent RT (univariate, P = 0.030; multivariate, P = 0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy. Univariate analysis suggests a potential cardioprotective effect of thoracic RT with ICI's, which may be due to modulation of the immune response through reduction of lymphocytes involved in autoimmune processes. A larger cohort study will be conducted to further evaluate this potential cardioprotective effect.