Rituraj Upadhyay1, Kaiping Liao2, David R Grosshans3, Susan L McGovern3, Mary Frances McAleer3, Wafik Zaky4, Murali M Chintagumpala5, Anita Mahajan6, Debra Nana Yeboa3, Arnold C Paulino3,5. 1. Department of Radiation Oncology, The James Cancer Centre Ohio State University, Columbus, Ohio, USA. 2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 5. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA. 6. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
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.
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.
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