KEY POINTS
- Investigators examined long-term radiation-related second malignant neoplasms after nasopharyngeal carcinoma treatment using modern IMRT and a much larger historical 2D-RT cohort.
- The final IMRT analysis included 6,070 long-term survivors, among whom 212 second malignancies were identified, giving a crude observed proportion of 3.49%.
- Competing-risk cumulative incidence after IMRT increased substantially with time: 1.15% at 5 years, 3.09% at 10 years, and 6.66% at 15 years. Median latency to diagnosis was 7.3 years.
- The oral cavity was the most frequent anatomical site, accounting for 42.5% of second malignancies after IMRT; the tongue and sinonasal region were also prominent. Squamous cell carcinoma was the most common histology.
- Within the IMRT cohort, independent risk factors included male sex (HR 1.46), age ≤50 years (HR 1.43), and smoking history (HR 1.51).
- The historical 2D-RT dataset identified 247 radiation-related second malignancies among 39,118 initially treated patients, with a crude proportion of 0.63% and median latency of 9.5 years.
- Among patients who developed a second malignancy, 5-year overall survival was 38.6% after IMRT versus 29.3% in the historical 2D-RT cohort.
- The apparent crude excess after IMRT should not be interpreted as evidence that IMRT causes more second cancers. The cohorts came from different treatment eras, with differences in follow-up, diagnostic surveillance, systemic treatment, survival, and competing mortality.
CLINICAL TAKEAWAY
Second malignancy risk becomes increasingly relevant as NPC survival improves, reaching roughly 1 in 15 survivors by 15 years in this modern IMRT cohort. The data support long-term survivorship awareness, particularly in younger patients and smokers, but they cannot establish whether IMRT itself carries greater carcinogenic risk than historical 2D techniques.