Risk and prognostic survival analysis of radiation-related second malignant neoplasms following radiotherapy for nasopharyngeal carcinoma: intensity-modulated radiotherapy and two-dimensional radiotherapy.

Abstract

To clarify the long-term risk and prognostic implications of second malignant neoplasms (SMNs) among nasopharyngeal carcinoma survivors in intensity-modulated radiotherapy (IMRT) and historical two-dimensional radiotherapy (2D-RT) cohorts. We extracted data from 8,032 and 39,118 initially diagnosed, non-metastatic NPC patients treated with IMRT ± chemotherapy and 2D-RT ± chemotherapy, respectively. Risk factors for SMN development in the IMRT cohort were evaluated using univariate and multivariable Cox proportional hazards models. Survival outcomes were assessed using the Kaplan-Meier method. Radiation-related SMNs occurred in 212 patients in the IMRT cohort and 247 patients in the historical 2D-RT cohort, corresponding to observed crude proportions of 3.49% and 0.63%, respectively. In the IMRT cohort, the 5-, 10-, and 15-year competing-risk cumulative incidences were 1.15%, 3.09%, and 6.66%, respectively. Median latency to SMN diagnosis was 7.3 years in the IMRT cohort and 9.5 years in the historical 2D-RT cohort. The oral cavity and sinonasal region were common SMN sites, and squamous cell carcinoma was the predominant histology. In multivariable Cox analysis within the IMRT cohort, male sex, age ≤ 50 years, and smoking history were independently associated with SMN development. Among patients with SMNs, 5-year overall survival was 38.6% in the IMRT cohort and 29.3% in the historical 2D-RT cohort. In this cross-era institutional study, the IMRT cohort showed a numerically higher observed crude incidence and shorter latency of radiation-related SMNs than the historical 2D-RT cohort. Male sex, younger age, and smoking history were independent risk factors for SMN development. Among patients who developed SMNs, observed overall survival estimates were higher in the IMRT cohort.