Risk Of Second Primary Tumors In Patients With Nasopharyngeal Carcinoma Following Definitive Intensity-Modulated Radiotherapy

Background: Second primary tumor (SPT) is a serious complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). This current study aimed to evaluate the incidence of SPT and the excess cancer risks in NPC patients treated with intensity-modulated radiotherapy (IMRT). Methods: Case records of 759 non-metastatic NPC patients who underwent definitive IMRT between February 2003 and September 2011 were reviewed. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed using the Cox proportional hazard model. Standardized incidence ratios (SIR) were calculated using age, gender and calendar year specific incidence rates from the Hong Kong Cancer Registry to quantify excess cancer risks compared with the general population. Results: The median follow-up was 7.5 years. Fifty-one SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. The 3-year, 5-year and 8-year cumulative SPT incidences were 1.0%, 3.7% and 7.7% respectively. Most common in-field SPTs were tongue cancers (31.8%) and sarcomas (31.8%). Median overall survival after diagnosis of SPT was 2.9 years. Age was the only independent factor associated with SPT development [Hazard ratio, 1.061; 95% confidence interval (CI), 1.029 – 1.094; p < 0.001]. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37 – 2.42). Significant excess risks were observed for sarcoma (SIR, 38.10; 95% CI, 16.41 – 75.06), tongue (SIR, 33.33; 95% CI, 13.36 – 68.67), oropharyngeal (SIR, 25.00; 95% CI, 2.81 – 90.25), prostate (SIR, 3.19; 95% CI, 1.17 – 6.95) and liver cancer (SIR, 2.80; 95% CI, 1.02 – 6.10). The excess risks were higher beyond 5 years of follow-up. Conclusions: High SPT incidence and excess cancer risks were observed after definitive IMRT for NPC, in particular for tumors arising within radiotherapy fields. SPT severely negates longevity of NPC survivors. High awareness is warranted for this lethal late complication in clinical follow-up. Legal entity responsible for the study: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Funding: None Disclosure: All authors have declared no conflicts of interest.