Nasopharyngeal carcinoma radiation-induced sarcoma in the skull base: a retrospective follow-up cohort study

Abstract Background Radiation-induced sarcoma (RIS) is a rare, fatal late complication of radiotherapy for nasopharyngeal carcinoma (NPC), particularly in the anatomically complex skull base region. Despite the high radiotherapy doses delivered to this area in NPC treatment, epidemiological features and risk factors for skull base NPC-RIS remain poorly defined, and systematic studies are lacking. Therefore, this study aimed to investigate the clinical characteristics and outcomes of skull base NPC-RIS. Methods This retrospective multicenter case series analyzed seven patients with pathologically confirmed skull base NPC-RIS and compared them to two control cohorts: recurrent NPC and primary T3/T4 NPC. The inclusion criteria were a primary NPC diagnosis, prior radiotherapy, new sarcoma within/adjacent to the radiation field meeting the modified Cahan criteria, and complete data. Clinical, imaging, and histopathological data were collected. The tumor location relative to the original radiation field and latency periods were analyzed. Results All seven NPC-RIS tumors occurred in the skull base, originating within prior high-dose fields. All RIS were noted in patients initially with T3-4 nasopharyngeal carcinoma. The pathological types were predominantly fibrosarcoma/osteosarcoma. Patients with NPC-RIS had significantly worse survival than those with recurrent NPC and primary T3/T4 NPC. Key distinguishing features of NPC-RIS included younger age at initial radiotherapy, significantly longer latency to onset than recurrence NPC, and tumors arising outside the original NPC site but within the irradiated field. Conclusion Younger age at radiotherapy was a key risk factor. Long latency and tumor location outside the primary NPC site, but within the radiation field, are critical diagnostic indicators. Management mandates lifelong surveillance for NPC survivors and prompt biopsy of new lesions in irradiated fields.