Second malignant tumors in chinese patients with nasopharyngeal carcinoma following radiotherapy

Purpose: To define the incidence and pattern of second malignant tumors (SMTs) in Chinese patients with nasopharyngeal carcinoma (NPC) following irradiation and explore the possible correlation between SMTs and NPC. Material and method: From January 1979 to December 1993, a total of 1562 patients without previous malignant history had diagnoses of nasopharyngeal carcinoma (NPC) and received radiotherapy at the Chang Gung Memorial Hospital. The mean age at diagnosis was 46.3 years (range 10-81) and the ratio of male to female was 2.7:1. All except 13 patients with distant metastases at presentation were treated with radical radiotherapy (46.8 Gy at least). Patients with T4 and/or N3 lesions might receive neoadjuvent chemotherapy. SMTs were identified with the criteria provided by Warren and Gates. All SMTs had tissue proof except one hepatocellular carcinoma, it was diagnosed by image and AFP > 10000. Result: There were 39 (2.5%) patients developed SMTs during 7164 person-years of follow-up, triple cancer was identified in one patient. As shown in table 1, the relative risk (RR) of total cancer incidence was significantly higher than expected in general population after age- and sex-adjustment. In consideration of anatomical distribution, the significant increase of RR was found in the head and neck (H and N) cancer (RR=29.1), lymphoma/leukemia (RR=8) and gastric cancer (RR=4.2). In 18 cases of H and N cancers, most occurred inside the previous RT field and were squamous cell carcinoma, only 4 cases were soft tissue sarcoma which might be induced by irradiation. In 7 cases of gastric cancer, 6 were adenocarcinoma and one was small cell carcinoma. The time of occurrence of SMTs was different between H and N and other cancers. 71.4% SMTs other than H and N cancer occurred during the first 2 years post-radiation, but 88.9% H and N cancer developed after 2 years. Conclusion: Our study shows a preferential occurrence of H and N cancers, lymphoma/leukemia and gastric cancers in Chinese NPC patients following radiotherapy. Although the mechanism is unclear, some factors like viral infection, ionizing radiation were suspected to be involved in part of these association. Since Epstein-Barr virus (EBV) was detected in more than 90% of NPC and 11% of gastric cancer in Taiwan and it was reported to be related with some other cancers, we are conducting studies to verify whether EBV can be detected in the specimen of SMTs