IDH wild-type WHO grade II diffuse low-grade gliomas. A heterogeneous family with different outcomes. Systematic review and meta-analysis.

WHO grade II diffuse low-grade gliomas (DLGGs) were recently divided into sub-groups on the basis of their molecular profiles. IDH wild-type (IDH-wt) tumors seem to be associated with unfavorable prognoses due to biological similarities to glioblastomas. The authors performed a systematic review and meta-analysis of literature examining epidemiology, clinical characteristics, management, and the outcome of IDH-wt grade II DLGGs. According to PRISMA guidelines, a comprehensive review of studies published from January 2009 to October 2017 was carried out. The authors identified series that examined the prevalence rate, clinical and radiological characteristics, treatment, and outcome of IDH-wt DLGGs. Variables influencing outcomes were analyzed using a random-effects meta-analysis model. Finally, a meta-regression analysis was performed to examine the impact of therapeutic strategies on the effect-size. Twenty-two studies were included in this systematic review. The IDH-wt prevalence rate was 22.9% (95% CI 18.4-27.4%). The hazard ratio for this molecular subgroup in the DLGGs population was 3.46 (95% CI 2.24-5.36; p < 0.001), and the heterogeneity was significant (I = 85%, τ = 0.88) (HR range 1.28-376). Nonetheless, publication bias did not affect the analysis (p = 0.176). The meta-regression revealed that the extent of resection and post-operative chemotherapy affected the outcome in the IDH-wt subgroup (p < 0.001 and 0.015, respectively), with no significant association of the HR with the rate of RT or RT + CHT. The prevalence of IDH-wt tumors is approximately 23% of DLGGs. The absence of IDH mutation is associated with a heterogeneous outcome, and its therapeutic relevance for postoperative management remains unclear. Maximal surgical resection improves the overall survival in the DLGGs population, beyond molecular status. Further molecular stratification is needed to better understand IDH-wt behavior and therapeutic response.