Outcome of young children with high‐grade glioma treated with irradiation‐avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials

Abstract

Purpose To report the final analysis of survival outcomes for children with newly diagnosed high-grade glioma (HGG) treated on the “Head Start” (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old. Patients and Methods Between 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients. Patients with predominantly brainstem tumors were excluded. Patients were to be treated with single induction chemotherapy regimen C, comprising four cycles of vincristine, carboplatin, and temozolomide. Following induction, patients underwent marrow-ablative chemotherapy and autologous hematopoietic cell rescue. Irradiation was used for patients with residual tumor after consolidation or >6 years old or at the time of tumor progression. Results The 5-year event-free survival (EFS) and overall survival (OS) for all HGG patients were 25 ± 8% and 36 ± 9%, respectively. The EFS at 5 years for patients with AA and GBM were 24 ± 11% and 30 ± 16%, respectively (P = 0.65). The OS at 5 years for patients with AA and GBM was 34 ± 12% and 35 ± 16%, respectively (P = 0.83). Children <36 months old experienced improved 5-year EFS and OS of 44 ± 17% and 63 ± 17%, compared with children 36–71 months old (31 ± 13% and 38 ± 14%) and children>72 months old (0% and 13 ± 12%). Conclusions Irradiation-avoiding treatment strategies should be evaluated further in young children with HGG given similar survival rates to older children receiving standard irradiation-containing therapies.

Regression of ETV6-NTRK3 Infantile Glioblastoma After First-Line Treatment With Larotrectinib

“… 8 , 9 , 11 Young children treated with cranial irradiation experience devastating neurocognitive sequelae and tumor recurrence; however, there is growing evidence that younger patients (< 36 months old) demonstrate longer event-free and overall survival when treated with single-cycle induction chemotherapy consisting of vincristine, carboplatin, and temozolomide. 12 However, progression-free survival rates remain poor for these patients, highlighting the need for new therapeutic options, including small molecules and/or immunotherapy alone or in combination with chemotherapy regimens. 13 Although the etiology and genomic drivers of glioblastoma are diverse, 14 - 16 a common finding in pediatric HGG, especially infantile HGGs, is the presence of fusions involving NTRK , ALK , and ROS1 , among others.…”

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

“…3 Many respond to chemotherapy, however RT is with-held due to the impact of radiation therapy in infants. 4 Treatment with RT may be used at recurrence, but with devastating sequelae. Progression following RT leads to a dismal outcome.…”

Tandem High-dose Chemotherapy without Craniospinal Irradiation in Treatment of Non-metastatic Malignant Brain Tumors in Very Young Children

“… 16 Several studies using HDCT/auto-SCT to minimize RT, including Head Start I-III and CCG 99703, have reported encouraging outcomes in very young patients with malignant brain tumors. 8 9 10 11 12 13 14 Previously, we also reported encouraging preliminary results of a single-arm trial using tandem HDCT/auto-SCT in very young children with malignant brain tumors. However, the number of enrolled patients was small, and the short follow-up duration prevented analysis of long-term late effects.…”

“… 5 6 7 Following success in high-risk neuroblastoma, studies have investigated the effectiveness of HDCT/auto-SCT in improving the prognosis of high-risk brain tumors and/or to avoid or minimize RT. 8 9 10 11 12 Recently, it has been demonstrated that further dose intensification by tandem HDCT/auto-SCT may further improve outcomes in patients with high-risk brain tumors. 13 14 …”