Effects of dosimetric inadequacy on local control and toxicities in the patients with T4 nasopharyngeal carcinoma extending into the intracranial space and treated with intensity-modulated radiotherapy plus chemotherapy

Abstract

BACKGROUND To protect neurological tissues, underdosing occurs in most cases of T4 nasopharyngeal carcinoma (NPC) with intracranial extension. In this study, we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy. METHODS We prospectively enrolled patients who had non-metastatic T4 NPC with intracranial extension treated between January 2009 and November 2013. The prescribed dose was 66.0-70.4 Gy to the primary planning target volume (primary gross tumor volume [GTVp; i.e., the nasopharyngeal tumor] + 5.0 mm). Dose-volume histogram parameters were calculated, including minimum point dose (Dmin) and dose to 95% of the target volume (D95). All patients received chemotherapy with the cisplatin, 5-fluorouracil, and docetaxel regimen. Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS In total, 41 patients were enrolled. The local partial response rate was 87.8% after induction chemotherapy. With a median follow-up of 51 months, 7 patients experienced failure in the nasopharynx; the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4% and 90.2%, respectively. The actual mean Dmin to the GTVp was 55.2 Gy (range 48.3-67.3 Gy), and D95 was 61.6 Gy (range 52.6-69.0 Gy). All doses received by neurological organs remained well within their dose constraints. No patients developed temporal lobe necrosis or other neurological dysfunctions. CONCLUSIONS With relative underdosed IMRT plus effective chemotherapy, the patients achieved satisfactory local control with few late toxicities of the central nervous system. Determining the acceptable extent of dosimetric inadequacy requires further exploration.