Abstract
BackgroundRadiation 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.MethodsA 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.ResultsThe 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, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc 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.ConclusionsRadiotherapy-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.
Highlights
Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and causes transient as well as long-term complications
The incidence of Radiation-induced brain necrosis (RN) has been demonstrated to directly correlate with the modality of radiation therapy, which was suggested in previous studies; there is a lower occurrence in patients treated with intensity-modulated radiotherapy (IMRT) [3]
Both studies [10, 11] showed that brainstem injuries are related to targets that are larger and closer to the brainstem, which is similar to our results, but there was no statistical difference between patients with T3 and other cases, which may be due to the low rate of brainstem injury
Summary
Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and causes transient as well as long-term complications. The relationship between brainstem injury and radiation volume dose is unknown. We found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. Radiation therapy is the standard radical treatment for NPC and causes transient as well as long-term complications [2]. The incidence of RN has been demonstrated to directly correlate with the modality of radiation therapy, which was suggested in previous studies; there is a lower occurrence in patients treated with intensity-modulated radiotherapy (IMRT) [3]. There are other factors that may influence the incidence and severity of radiation-induced brainstem injury, for example, long-term close follow-up, the proper diagnostic modality, and independent image interpretation. We try to identify the relationship between the incidence of brainstem injury and radiation dose to improve the understanding of brainstem protection
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