Chemotherapy

For patients with diffuse pediatric-type high-grade glioma, H3-wild type and IDH-wild type, the benefit from radiation therapy with adjuvant chemotherapy compared with radiation therapy alone has not been formally proven in a randomized prospective trial. However, the aggregate data from numerous nonrandomized prospective clinical trials for children with high-grade gliomas suggest a benefit from alkylating chemotherapy, similar to adults with primary glioblastoma. Therefore, adjuvant therapy with a combination of radiation therapy and alkylating chemotherapy can be considered standard of care. Commonly used chemotherapy regimens include temozolomide alone or in combination with lomustine.[5,6]

Prospective, randomized clinical trials in adults with primary glioblastoma have established MGMT promoter hypermethylation as an independent prognostic biomarker regardless of therapy, as well as a predictive biomarker for benefit from temozolomide.[35,36] However, in children with diffuse pediatric-type high-grade glioma, H3-wild type and IDH-wild type, MGMT promoter methylation status is not prognostic,[8,37] and its predictive value for benefit from alkylator chemotherapy is unknown given the lack of applicable randomized data.

In a prospective randomized trial, the use of adjuvant bevacizumab after radiation therapy did not prolong overall survival (OS) or progression-free survival (PFS) in pediatric patients with newly diagnosed high-grade gliomas.[7]

No chemotherapy (including neoadjuvant, concurrent, postradiation chemotherapy) or immunotherapy strategy, when added to radiation therapy, has led to long-term survival for children with DIPGs.[38-40]; [41][Level of evidence B4] This includes therapy using high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue, which has been shown to be ineffective in extending survival.[42] However, similar to the treatment of other brain tumors, radiation therapy is generally omitted for infants with DIPGs, and chemotherapy-only approaches are used. Published data supporting the utility of this approach are lacking.

Children with infant-type hemispheric gliomas have been categorized into three groups.[43] Group 1 tumors include high-grade gliomas that are hemispheric and receptor tyrosine kinase (RTK) driven, including ALK, NTRK, ROS1, and MET gene fusions. Previously, infants with such tumors were treated with adjuvant multiagent chemotherapy instead of radiation therapy, with relatively favorable outcomes.[9,44]