Clinical outcome and molecular characterization of pediatric glioblastoma treated with postoperative radiotherapy with concurrent and adjuvant temozolomide: a single institutional study of 66 children

Abstract

Background Glioblastoma (GBM) in children is rare. Pediatric GBM have a distinct molecular profile as compared to adult GBM. There are relatively few studies of pediatric GBMs and no standard of care on adjuvant therapy. We aimed to evaluate the clinical outcome and molecular profile of pediatric GBM. Methods and Materials Between 2004 and 2013, 66 consecutive children with histologically proven GBM were identified from our database. The majority of the children underwent maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolomide. Immunohistochemical staining was performed for p53, MIB-1 labeling index, MGMT overexpression, and EGFR amplification and isocitrate dehydrogenase (IDH1) R132H point mutation. Survival and impact of possible prognostic factors on outcomes were analyzed. Result Median survival was 15 months. The overall survival rate at 1 year was 62%, at 2 years was 30%, and at 3 years was 27%. Patients with thalamic tumors (P < .001), incompletely resected tumors (P < .00001), and tumors with MIB-1 labeling index >25% (P < .002) had poor overall survival rates. p53 was overexpressed in 74% of patients, MGMT promoter methylation was seen in 37% of patients, IDH1 mutation was seen in 4% of patients, and no patients had EGFR amplification. MGMT methylation and p53 overexpression did not impact survival. Conclusions Clinical outcome of pediatric GBM is similar to that reported for adult GBM. The frequency of p53 overexpression is higher than in adult GBM, while MGMT methylation, IDH1 mutations and EGFR amplification is lower than in adult GBM. MGMT methylation and p53 expression status do not have any prognostic significance.

Contrast Enhancement Patterns in Pediatric Glioblastomas

“…In this study, the following genetic markers were evaluated: the IDH1 mutation was tested in 29 patients and was detected in 6. The IDH1 mutation is considered a strong predictor of a better outcome in adult GBMs and is found in most patients with secondary adult GBMs 11 . However, the IDH1 mutation is rare in pediatric high-grade gliomas 10 .…”

High-Grade Gliomas in Children—A Multi-Institutional Polish Study

“…Maximal safe resection is the first step of HHG treatment. Many retrospective series reported extent of resection (EOR) as the only one or one of the main prognostic factors influencing OS ( Table 4 ) [ 1 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 17 , 19 , 22 , 25 , 27 , 29 , 30 ]. Additionally, SEER analysis performed by Adams H. showed that gross total resection is independently associated with improved OS in GBM patients [ 34 ].…”

“…RT as adjuvant treatment (combined with CTH in some patients) was used in almost all of the studies. Doses prescribed were usually within the range of 54 to 60 Gy, given in 1.8 to 2 Gy fractions, and covered tumor (GTV), along with tumor bed and additional margins of 2 to 2.5 cm (CTV,PTV) [ 7 , 8 , 9 , 10 , 11 , 12 , 14 , 17 , 19 , 22 , 24 , 25 , 28 ]. Some authors limited the dose to 54 Gy in cases of children 6 years of age or younger, as well as included patients irradiated to only 45 Gy [ 6 , 17 , 27 , 30 ].…”

“…With only one prospective trial and few retrospective studies proving the benefit of temozolomide-based CTH, the value of this therapeutic agent is still a subject of discussion [ 6 , 7 , 8 , 9 , 10 ]. The use of adjuvant CTH after RT or radiochemotherapy (RCTH) and the sequence of treatment or total dose of RT also varied between the studies [ 1 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. The above-mentioned, together with the rarity of HGG diagnosis in the pediatric population, strongly calls for a multi-institutional analysis, such as the one presented in this article [ 32 , 33 , 34 , 35 ].…”

Therapeutic approach beyond conventional temozolomide for newly diagnosed glioblastoma: Review of the present evidence and future direction

“…However, recent series of pediatric GBM has reported encouraging results and manageable toxicity when treated with concurrent radiation and TMZ followed by maintenance TMZ. [36] Another series of 66 patients reported recently, [37] found the median survival to be 15 months when treated with the same schedule. In addition, MGMT methylation and p53 over expression was not shown to impact OS.…”