Differential responsiveness among "high risk" pediatric brain tumors in a pilot study of dose-intensive induction chemotherapy

Abstract

Background: These factors have been predictive for progressive disease on therapy (PDOT) among pediatric brain tumors: >1.5 cm(2) unresectable tumor, glioblastoma, supratentorial primitive neuroectodermal tumor, and metastatic medulloblastoma (MBL). This pilot study sought to correlate cytoreductive response with progression free survival.

Procedures: Four courses of cisplatinum, cyclophosphamide, etoposide, and vincristine preceded hyperfractionated radiotherapy (RT). Maintenance chemotherapy consisted of eight cycles of carboplatin, etoposide, and vincristine. Biopsy specimens were immunohistochemically studied for labeling index, hypoxia, and multidrug resistance proteins.

Results: Twenty newly diagnosed patients [nine primitive neuroectodermal tumors/MBL, one choroid plexus carcinoma, eight malignant gliomas, and two anaplastic ependymomas] were treated. Ten patients, who required neuraxis irradiation, constituted the "PNET" group. These demonstrated five complete and one partial response (PR), with an estimated median progression free survival of 44 months and median survival in excess of 53 months. Patients treated with involved field irradiation were designated the "Glioma" group. Induction chemotherapy produced partial and minor responses (MRs) among 5/10. Their estimated median progression free survival was 6.9 months (P = 0.035 relative to the PNET) with a median survival of 10.7 months (P = 0.04). Age, labeling index, the presence of hypoxia, and Pgp/MDR1 expression failed to discriminate between the two groups.

Conclusions: This induction regimen produced a cytoreductive response in 6/10 and achieved a significant improvement in progression free survival among 7/10 in the PNET group. Unfortunately, responses among Glioma patients did not translate into durable control. Expression of the biologic factors was similar between both groups and did not correlate with diagnosis or response.