The risks and trends of cardiac-specific mortality associated with chemotherapy or radiotherapy in a large cohort of non-elderly patients with non-small cell lung cancer

BACKGROUND: Anticancer treatment-related heart events is a major concern. However, the frequent occurrence time of cardiac death and the association between cardiac-specific mortality (CSM) and various lung lobes among non-elderly non-small cell lung cancer (NSCLC) patients after chemotherapy or radiotherapy (RT) are uncertain. METHODS: Data of patients aged 20–59 years and diagnosed with NSCLC during 1975–2014 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We divided them into four groups: no chemotherapy or RT, chemotherapy-only, RT-only and chemoradiation therapy (CRT). The Fine and Gray model was applied to evaluate the risks; the cumulative curves of CSM were established by Gray’s test. Furthermore, the forest graphs delineated the hazards of different tumor subsites to CSM as the survival time prolonged. Eventually, we analyzed and elucidated the tendency of CSM decade by decade. RESULTS: We identified 121,302 patients and 3,423 died of heart diseases. In chemotherapy-only group, age, sex, race, marital status and surgery were significantly correlated to CSM while the subsite location of tumor was the key risk among RT-only patients. The hazard ratio (HR) of CSM was greatest in 2–5 years after RT (P=0.008, HR =2.30). CSMs of chemotherapy (P=0.130, HR =2.480) and CRT (P=0.028, HR =2.600) peaked in 1985–1994 and decreased sharply hereafter, whereas the CSMs of RT-only declined over time. CONCLUSIONS: The risks of CSM after chemotherapy were similar to the common hazards of heart diseases; tumor in the left-lower lobe was a remarkable risk for patients receiving RT-only and the frequent occurrence of cardiac death was from the second year after RT. The CSMs of chemotherapy and CRT culminated in 1985–1994 and then descended; it declined all the time in RT-only group.