Abstract
BACKGROUND: Despite improved overall survival outcomes, chemotherapy has brought concerns for heart disease-related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear. METHODS: We obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan-Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias. RESULTS: AA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736-0.83, P<0.001). For competing risk regression analysis, the cumulative incidence of HDRD in non-chemotherapy exceeded HDRD in the chemotherapy group (P<0.001) and multivariable analysis showed a lower HDRD risk in AA patients with chemotherapy (adjusted SHR=0.574, 95%CI=0.331-0.991, P=0.046). In the PSM-after cohort, there were no significant association between chemotherapy and the increased HDRD risk (adjusted SHR=0.595, 95%CI=0.316-1.122, P=0.11). Landmark analysis showed that AA patients who received chemotherapy had better heart disease-specific survival than those in the non-chemotherapy group (P=0.007) at the follow-up time points of 216 months. No difference was found when the follow-up time was more than 216 months. CONCLUSION: AA patients with chemotherapy are associated with a lower risk of HDRD compared with those without chemotherapy. Our findings may help clinicians make a decision about the management of AA patients and provide new and important evidence for applying chemotherapy in AA patients as the first-line treatment. However, more research is needed to confirm these findings and investigate the correlation of the risk of HDRD with different chemotherapy drugs and doses.