Background: Nasopharyngeal cancers (NPCs) have an estimated incidence of 0.5 to 2 cases per 100,000 in the United States. Treatment of NPC with combination chemoradiotherapy has resulted in an 18% increase in 5-year overall survival in the US. It is essential to focus on the developments of second primary malignancies (SPMs) with improved survival. We aim to analyze the risk of SPMs among NPC survivors in this study. Methods: We estimated the incidence of SPMs among two-month survivors of NPC using the Surveillance, Epidemiology, and End Results (SEER)-18 registries between 2006 to 2018. The risk of SPMs was calculated using standardized incidence ratios (SIRs). Results: We included 7,560 patients with NPC in this study. The median age of diagnosis was 56 yrs (range 0 to 85 yrs). The median follow-up duration was 33 months (range 0 to 155 months). The median time for SPM development from initial diagnosis was 41 months (range 2 to 140 months). A total of 367 (5%) patients developed 398 SPMs at the last follow-up, of which 89% were solid organ malignancies, and 11% were hematologic neoplasms. The SPM risk for cohort was significantly elevated (SIR = 1.88, 95% confidence interval [CI] = 1.7 to 2.07) compared with the general population. The SIR was slightly higher in males (SIR = 1.90, 95% CI = 1.69 to 2.13) compared to females (SIR = 1.81, 95% CI = 1.48 to 2.20). The SIR according to age groups were as follows: age < 65 years (SIR = 2.03, 95% CI = 1.79 to 2.29), age > 65 years (SIR = 1.65, 95% CI = 1.38 to 1.94). Sites with highest risk included the nose, nasal cavity, and middle ear (SIR = 22.98, 95% CI = 9.92 to 45.27), nasopharynx (SIR = 17.28, 95% CI = 8.93 to 30.19), oral cavity and pharynx (SIR = 10.07, 95% CI = 7.81 to 12.79), esophagus (SIR = 3.97, 95% CI = 1.9 to 7.29), lung and bronchus (SIR = 3.53, 95% CI = 2.86 to 4.32), and liver (SIR = 3.05, 95% CI = 1.86 to 4.71) (Table). The risk of malignancies of the esophagus and lung were higher within the first year of diagnosis of NPC. The risk of malignancies of the nasopharynx, oral and nasal cavity, and liver was higher after one year of latency and remained statistically significantly elevated throughout the follow-up period. Conclusions: Our study reveals that patients with NPC are at higher risk of SPMs than the general population, most notably in the oral and nasal cavity, nasopharynx, esophagus, and lungs. These patients may benefit from cancer-specific screening during follow-up.

The data highlights only statistically significant SIR. *P-value < 0.05 for all.