A combined case-control and cohort study design: When to start alert for Cerebrovascular disease, Heart disease, and Hypertension (CHH)-specific death associated with lung cancer treatment?

Background : During the early stages after diagnosis, the time impact of radiotherapy and chemotherapy on the occurrence of fatal cardiac disease in lung cancer patients has received limited research attention. Patients and methods : Lung cancer patient data was obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Propensity-score matching methods were employed to equalize baseline confounding. The training set was utilized to construct a time-dependent (time cut = 6 months) Cox regression model and a Random survival forest model, whereas the test set was employed for model validation. The discrimination and accuracy of the model were assessed using the Concordance Index and the Integrated Brier score. Results : A total of 49,294 patients diagnosed with lung cancer between 2018 and 2019 were included in the analysis. Propensity score-matched analyses, accounting for important confounding covariates, demonstrated that patients who received CT only, RT only, or CT plus RT had significantly improved CHH-specific survival compared to those who did not receive CT and RT (P <0.001). Cox regression analysis indicated that within the first 6 months, RT and CT (P <0.001) independently acted as protective factors against CHH-specific mortality, while RT plus CT (P <0.001) was identified as an independent risk factor. At 6 months or later, RT (P <0.05) emerged as an independent risk factor, while the impact of CT on CHH-specific mortality became statistically insignificant compared to the initial six months. The results of the Rsf analysis indicated that the variables in descending order of importance were CT, RT, and CT plus RT. Additionally, independent risk factors included the year of diagnosis, T4, Stage Group, and Msite brain (P <0.05). Conclusions : These findings establish a critical time frame to raise awareness regarding the risk of CHH-specific death in lung cancer during the early post-diagnostic period.