Quantifying the risk and dosimetric variables of symptomatic brainstem injury after proton beam radiation in pediatric brain tumors

Background Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT. Methods All patients <21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem. Results A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT was 6.3 years and median prescribed RT dose was 54Gy [RBE]. Fifteen patients (3.2%) developed SBI, at a median of 4 months after RT. Grades 2, 3, 4, and 5 brainstem injuries were seen in 7, 5, 1, and 2 patients respectively. Asymptomatic radiographic changes were seen in 51 patients (10.9%). SBI was significantly higher in patients with age <= 3 years, female gender, ATRT histology, patients receiving high-dose chemotherapy with stem cell rescue, and those not receiving craniospinal irradiation. Patients with SBI had a significantly higher V50-52. In 2014, our institution started using strict brainstem dose constraints (Dmax <= 57 Gy, Dmean <= 52.4 Gy, and V54 <= 10%). There was a trend towards decrease in SBI from 4.4% (2007-2013) to 1.5% (2014-2019) (P = .089) without affecting survival. Conclusion Our results suggest a low risk of SBI after PBT for pediatric brain tumors, comparable to photon therapy. A lower risk was seen after adopting strict brainstem dose constraints.