The risk of second primary tumors in patients with nasopharyngeal carcinoma after definitive radiotherapy




Second primary tumors (SPTs) have a substantial impact on survival in cancer patients. However, risk factors for SPTs have not been documented well, especially in nasopharyngeal carcinoma (NPC). The objective of this retrospective analysis was to evaluate such risks in patients with NPC after they received definitive radiation treatment.


Three hundred twenty-six consecutive patients with pathologically confirmed, nonmetastatic, undifferentiated NPC who received treatment between January 1, 1994 and December 30, 1995 were analyzed. All patients were restaged in accordance with the 2002 American Joint Committee on Cancer staging classification. There were 18 patients (5.5%) with Stage I NPC, 152 patients (46.6%) with Stage II NPC, 101 patients (31.0%) with Stage III NPC, and 55 patients (16.9%) with Stage IVA or IVB NPC at initial diagnosis. All patients received definitive radiotherapy with either Cobalt-60 or megavoltage therapy. High-dose-rate brachytherapy was given to 23 patients either as part of their primary treatment or as adjuvant treatment for residual lesions.


The median follow-up for all patients was 5.6 years (range, 1.0–8.0 years). Seventeen patients (5.2%) developed SPTs, for an average annual rate of 1.0%, and the 5-year cumulative incidence was 5.8%. Six SPTs were located within the radiation field. The cumulative incidence of in-field SPTs was 0.35% at 3 years and 1.2% at 5 years, and the average annual rate was 0.35%. Eleven patients (64.7%) had tumors of the upper aerodigestive tract (UADT). Among the 14 SPTs that occurred within 5 years after radiotherapy, only 3 tumors (21.4%) occurred within the radiation field. In contrast, all 3 SPTs that occurred >5 years after radiotherapy occurred within the radiation field (P = .029). Multivariate analysis showed that age was the only independent risk factor for developing SPTs after RT for NPC. Advanced age (age ≥50 years) was associated with a 37% increased risk of developing SPTs (relative risk, 1.367; 95% confidence interval, 1.067–1.1753; P = .014). Other factors, including gender, tumor or lymph node classification, chemotherapy, total radiation dose to the nasopharynx, reirradiation, and adjuvant brachytherapy did not influence the risk of SPTs.


SPTs in patients with NPC occurred preferentially in the UADT and tended to develop within the irradiated field >5 years after patients received radiation. Older patients with NPC (age ≥50 years) may be at increased risk. Further studies with larger samples and longer follow-up will be needed to confirm these findings. Cancer 2006. © 2006 American Cancer Society.