A retrospective dosimetry study of intensity-modulated radiotherapy for nasopharyngeal carcinoma: radiation-induced brainstem injury and dose-volume analysis

Background: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. Methods: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. Results: The median follow-up duration was 56 months (range, 3-141 months), and six with T-4 and two with T-3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T-4 stage, D-2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), D-max (the maximum point dose), D-1%, D-0.1cc (the top dose delivered to a 0.1-ml volume), and D-1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D-2% and the D-max, D-1%, D-0.1cc, and D-1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. Conclusions: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.