Effect of immunotherapy combined with chemotherapy with or without thoracic radiotherapy on markers of myocardial injury in patients with thoracic tumors.
Authors: Zhu Zihao , Xu Qicen , Yu Hongliang , Zhang Qian , Jiang Ning , Zhan Liangliang , Zong Dan , Wu Jianfeng , He Xia , Peng Wei , Li Xingwang , Wang Li , Shi Meiqi , Zhu Xiangzhi , Chen Cheng 
Published: June 2023

e14624

Background: Thoracic radiotherapy (TRT) is widely used in the treatment of thoracic tumors (TTs) including esophageal and lung cancers. Previous studies suggest that it may increase the risk of myocardial injury. The use of immune checkpoint inhibitors combined with chemotherapy (ICC) in TTs is becoming prevalent, and immune myocarditis is of interest to clinicians. Markers of myocardial injury (MMIs) (e.g., cTnT, CK-MB) have been used with high sensitivity and specificity for the diagnosis of immune myocarditis. Previous studies have focused on severe immune myocarditis due to its high lethality, and less attention has been paid to myocarditis with mildly elevated MMIs. However, ICC are increasingly being used in the treatment of earlier-stage TTs (e.g., neoadjuvant treatment of NSCLC), so the safety of treatment is particularly crucial. The main objective of this study was to analyze the effect of ICC with or without TRT on the MMIs in patients with TTs. Methods: This is a single-center retrospective study with the following main inclusion criteria: 1, pathologically confirmed esophageal and lung cancers only; 2, treated with ICC; 3, presence of comparable serial MMIs results from 1 week prior to the start of treatment to 12 weeks after the end of treatment; 4, TRT allowed in the same period. Primary exclusion criteria: 1，Elevation of MMIs occurs before ICC. 2，For patients who have received TRT, MMIs elevated before radiotherapy. As Chinese Society of Clinical Oncology PD-1 treatment-related myocarditis diagnostic criteria, cTnT was defined as elevated when it was significantly higher than baseline (20 μg/mL) and CK-MB was defined as elevated when it was 2.5 times higher than the upper limit of normal (≥62.5 U/L); Elevation of cTnT and CK-MB after treatment was used as the primary observation and a chi-square test was performed using the SPSS version 25. Results: This study investigated patient data from Jan 1st,2019 to Sep 20th,2022 for a total of 196 patients with esophageal squamous cancer and 298 patients with lung cancer (SCLC vs NSCLC = 13:285) who met the enrollment criteria. The median age was 64 years (29-89 years), male vs female = 406:88. 256 patients received ICC plus radiotherapy (Group A) and 238 patients without radiotherapy (Group B). The median dose of TRT was 50.4 Gy (12 - 60 Gy). The median cycles of use of Immune checkpoint inhibitors (including PD-1 and PD-L1 inhibitors) was 5 (1- 43). The proportion of all patients with post-treatment elevations of cTnT was 12.2% (29/238), including 11.9% (13/109) and 12.4% (16/129) in group A and B, p > 0.05. The whole proportion of patients with elevated CK-MB was 2.7% (13/473), including 3.2% (8/251) and 2.3% (5/222) in group A and B, p > 0.05. Conclusions: Elevated MMIs were common after the use of ICC in patients with TTs with or without radiotherapy, and TRT did not increase the risk of elevation of MMIs.