The Impact of Second Primary Malignancies on Head and Neck Cancer Survivors: A Nationwide Cohort Study

BACKGROUND: Head and neck cancer (HNC) is associated with a high rate of developing second primary malignancies(SPMs). But the impact on survival remains poorly understood before. Therefore, we want to estimate the impact of SPMs on HNC survivors. METHODS AND FINDINGS: Between 1986 and 2008, a total of 9,996 SPMs were recorded for 93,891 patients with an initial diagnosis of HNC by the Taiwan Cancer Registry. Patients were followed with national death registry database to 2011.Using the Kaplan–Meier method, a time-dependent covariate was employed to compare the survival rates between patients with and without SPMs. A Cox proportional hazards model that treated age and sex as confounders was used to examine the hazard ratios of SPMs. The relative survival rates were calculated using age- and sex-specific life tables for the population. Parametric mixture cure fraction models were then employed to estimate the percentage of cancer survivors who would be cured. Use of the Kaplan–Meier method showed that the crude survival rates differed significantly for patients with and patients without SPMs (log-rank test <0.01). For the results of Cox proportional hazards regression analysis, SPMs had a significant influence on survival rates with univariate (HR 2.59,95% CI 2.53to 2.65) and multivariate analysis (HR 2.34, 2.28 to 2.40). Patients with SPMs of nasopharyngeal carcinoma (NPC) had the highest cure rate at 39%, where as esophageal and lung cancer had the worst prognosis, with a cure rate of 11%. CONCLUSIONS: A worse prognosis was found for second primary cancer such as esophageal or lung cancer. Patients and healthcare providers must strongly consider and have a high clinical suspicion of these SPMs.