Brainstem toxicity after proton or photon therapy in children with localized intracranial ependymoma

Abstract

Objectives Children's ependymomas achieve a 5-years local control rate of 50% with a standard post-operative dose of 59.4 Gy. To decrease the dose to normal tissue, proton bean therapy (PBT) is preferred when available. Recently, retrospective studies reported higher rates of radionecrosis on the brainstem after PBT than photon radiation therapy (XRT), leading several teams to decrease the dose to 54 Gy in PBT for posterior fossa ependymomas under 3 years old. The benefit-risk's balance of the dose reduction is unclear especially since the real incidence of clinically relevant brainstem's toxicity appears low.This prompt us to compare the incidence of clinical and imaging brainstem toxicity between XRT and PBT and to correlate them to the dosimetric datas in the retrospective PEPPI French cohort. Methods From 2001 to 2021, we studied the MRI brainstem's modification and clinical brainstem toxicity for patients ≤ 22 years old from 5 reference French centers treated with surgery and radiation therapy (RT) for a localized intracranial ependymoma. Pre operative, post operative and follow-up MRI during 18 months after RT were analyzed. Post-gadolinium T1, T2, FLAIR and diffusion weighted imaging were used. Results Eighty-three patients were included in the study, 42 patients were treated with PBT, 37 with XRT and 4 with both. Median follow-up was 5.6 years [95%CI: 4.8-6.2], the 5-years overall survival and progression free survival rates were respectively 86.1% [95%CI: 75.7-92.3] and 68.7% [95%CI: 56.4-78.3]. Neither clinical or MRI brainstem radionecrosis nor new or progressive brainstem symptoms were found. Four patients (whose two had received PBT) presented a punctiform brainstem enhancement with a median time of onset of 3.5 months [3.0-9.4] after RT and a median time of disappearance of 7.6 months [3.7-7.9]. Median brainstem mean dose was 47.2 Gy [45.3-53.2] for them and 48.5 Gy for the cohort. Conclusion Brainstem imaging change occurred in 4,8% of children in a large series including PBT. No radionecrosis nor symptomatic MRI change was found within the brainstem. The pursue of the study with the others French centers will strengthen our results. Children's ependymomas achieve a 5-years local control rate of 50% with a standard post-operative dose of 59.4 Gy. To decrease the dose to normal tissue, proton bean therapy (PBT) is preferred when available. Recently, retrospective studies reported higher rates of radionecrosis on the brainstem after PBT than photon radiation therapy (XRT), leading several teams to decrease the dose to 54 Gy in PBT for posterior fossa ependymomas under 3 years old. The benefit-risk's balance of the dose reduction is unclear especially since the real incidence of clinically relevant brainstem's toxicity appears low.This prompt us to compare the incidence of clinical and imaging brainstem toxicity between XRT and PBT and to correlate them to the dosimetric datas in the retrospective PEPPI French cohort. From 2001 to 2021, we studied the MRI brainstem's modification and clinical brainstem toxicity for patients ≤ 22 years old from 5 reference French centers treated with surgery and radiation therapy (RT) for a localized intracranial ependymoma. Pre operative, post operative and follow-up MRI during 18 months after RT were analyzed. Post-gadolinium T1, T2, FLAIR and diffusion weighted imaging were used. Eighty-three patients were included in the study, 42 patients were treated with PBT, 37 with XRT and 4 with both. Median follow-up was 5.6 years [95%CI: 4.8-6.2], the 5-years overall survival and progression free survival rates were respectively 86.1% [95%CI: 75.7-92.3] and 68.7% [95%CI: 56.4-78.3]. Neither clinical or MRI brainstem radionecrosis nor new or progressive brainstem symptoms were found. Four patients (whose two had received PBT) presented a punctiform brainstem enhancement with a median time of onset of 3.5 months [3.0-9.4] after RT and a median time of disappearance of 7.6 months [3.7-7.9]. Median brainstem mean dose was 47.2 Gy [45.3-53.2] for them and 48.5 Gy for the cohort. Brainstem imaging change occurred in 4,8% of children in a large series including PBT. No radionecrosis nor symptomatic MRI change was found within the brainstem. The pursue of the study with the others French centers will strengthen our results.