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 T₄ and two with T₃ 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 T₄ 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.