Comment to the paper "The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brain stem glioma" by Burzynski et al.

Abstract

Comments The authors conducted a single-arm phase II study on antineoplaston (ANP) for the efficacy and safety in the treatment of recurrent pediatric diffuse intrinsic pontine tumors (RPDIPGs) by using a combination of A10 and AS2-1 in a group of 17 patients with mean age of 8.8 years at recurrence. The overall response rate (OR) was 29.5 % with complete response rate (CR) of 6 %, partial response rate (PR) of 23.5 %, stable disease (SD) of 11.8 %, progressive disease of 47 %, and acceptable toxicity. Counting from the first day of ANP administration, the 6-month progression-free survival was 35.3 % and 1-year overall survival was 29.4 % with one long-term survival for more than 15 years. However, the series was small and the enrollment of patients lasted from 1996 to 2006 [1]. In a recently reported series of 31 RPDIPG patients with mean age of 7.8 years at the start of the first treatment for tumor recurrence or progression, the results were as follows: no long-term survival, no CR, PR 12 %, SD 34 %, and PD 53%. The mean event-free survival (EFS) was 2 months. This study highlighted that repeat radiation to the primary tumor was most effective with mean EFS of 3.9 months [2]. Comparing with the treatment results of these two series for RPDIPGs and reports of clinical trials for diffuse intrinsic pontine tumors (DIPGs), although the series of ANP phase II study was small to conclude, the outcome seemed promising [1–3]. There has been a clinical question whether histological grading of DIPGs influences survival and if there are some other diffuse pontine lesions. Referring to a reported study of prognostic factors for DIPGs, stereotactic biopsy and histological diagnosis of high-grade or low-grade gliomas were available in 63 adults and 37 children. This study showed that histological grade was a significant prognostic factor in DIPGs with statistical significance in adult patients (p=0.0001), but there was no statistical significance in pediatric patients (p=0.0755). However, in children, the 1-year actuarial survival rate was higher in low-grade gliomas (80.4± 0.08 %) than high-grade gliomas (48.6±0.14 %). In the same study, the histological diagnosis of stereotactic biopsy of 142 brain stem lesions in adults and children, only 106 cases (74.6 %) were astrocytic tumors [4]. The same study group also reported the histological diagnosis of intrinsic brain stem tumors in children. Biopsies were performed in 44 children with intrinsic brain stem lesion. Histological diagnosis obtained in 41 (93.1 %) patients included 37 diffuse brain stem gliomas, 2 pilocytic astrocytomas, 1 ependymoma, and 1 ganglioglioma [5]. Roujeau et al. reported stereotactic biopsy of diffuse pontine lesions in 24 children. There were 22 highgrade infiltrative astrocytomas (WHO grade III and IV), 1 grade II astrocytoma, and 1 pilocytic astrocytoma [6]. In our unreported experience of biopsy of diffuse pontine tumors in children, the histological diagnosis obtained included five glioblastoma multiformes (GBMs), eight AAs, six astrocytomas, and three pilocytic astrocytomas. The proportion of highgrade and low-grade gliomas varies in different series. Diffuse pontine pilocytic astrocytoma can have long-term survival. There is also a possibility of other pathologies, higher in brain stem lesions in general and sporadic cases in diffuse pontine lesions. In the study series of APN in 17 patients, only four T.<T. Wong (*) Pediatric Neurosurgery, Division of Neurosurgery, Department of Surgery, Cheng Hsin General Hospital, Taipei, Taiwan e-mail: ttwong@vghtpe.gov.tw