Systematic Review and Individual Patient Data Analysis of Uncommon Variants of Glioblastoma: An Analysis of 196 Cases

Objectives: Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior. Materials: We conducted a systematic review and individual patient data analysis of these rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1 st 2016 published in English language and collected data regarding age, sex, subtype and treatment received, Progression Free Survival (PFS), Overall Survival (OS). Statistical Package for social sciences (SPSS) v16 software was used for all statistical analysis. Results: We retrieved data of 196 patients with rare GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBM-SC (9%) and GBM-E (8%). Median age at diagnosis was 38, 40, 43.5, 69.5 and 18 years, respectively. Male: female ratio was 2:1 for GBM-E, and 1:3 for GBM-SC. Maximal safe resection followed by adjuvant local radiation was used for most of the patients. However, 6 patients with GBM-PNET, 3 each of GBM-E, GBM-SC received adjuvant craniospinal radiation. Out of 88 patients who received chemotherapy, 64 received Temozolomide alone or combination chemotherapy containing Temozolomide. Median PFS and OS for the entire cohort were 9 and 16 months. In univariate analysis, patient with a Gross Total Resection had significantly better PFS and OS compared to those with a Sub Total Resection [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET, GBM-GC, GBM-SC, GBM-R and GBM-E were 32, 18.3, 11, 12 and 7.7 months, respectively (P = 0.001). Interestingly, 31.3%, 37.8% of patients with GBM-E, GBM-R had CSF dissemination. Conclusion: Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination.