Effect of Treatment Modalities on Progression-Free Survival and Overall Survival in Molecularly Subtyped World Health Organization Grade II Diffuse Gliomas: A Systematic Review.

BACKGROUND

With the 2016 update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System incorporating molecular subtyping to histology, WHO grade II diffuse astrocytic and oligodendroglial tumors are subcategorized by distinct molecular markers. There are no reported systematic reviews quantifying differences in progression-free survival (PFS) and overall survival (OS) on the basis of molecular subtypes of WHO grade II diffuse gliomas, against the background of administered treatments.

METHODS

Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trails).

RESULTS

For OS, the first quartile (25%), median (50%), third quartile (75%), and 95% confidence interval, respectively, were identified (in months): astrocytoma-wild-type WHO II (A-wt II): 22.8, 32.2, 40.7, and 21.6-61.2; astrocytoma-mutant WHO II (A-mt II): 69.85, 115.2, 128.4, and 55.4-164.0; oligodendroglioma WHO II (OD-II): 106.3, 163.7, 213.3, and 67.3-235.4 (P value = 0.0002). For PFS, the 25th, 50th, and 75th percentiles, and 95% confidence interval, respectively, are as follows (in months): A-wt II: 6.90, 17.45, 19.57, and 3.00-23.69; A-mt II: 37.20, 43.20, 55.63, and 35.7-60.0; OD-II: 47.42, 59.2, 88.28, and 46.3-91.2 (P value = 0.015).

CONCLUSIONS

This seems to be the first systematic review of OS and PFS in patients with WHO grade II low-grade gliomas (LGGs), against treatment modalities, in molecularly stratified subsets introduced by the WHO 2016 classification of central nervous system tumors. Overall, A-wt II was confirmed to have a significantly shorter OS than did A-mt II; no significant difference was found between OS of OD-II with A-wt II and A-mt II. In addition, all 3 molecular subtypes were found to have statistically significant differences between PFS, with OD-II having a statistically better PFS than A-mt II. These data can provide valuable prognostic insight to patients and clinicians. In addition, assessing survival differences enhances understanding of treatment recommendations against molecular markers and may facilitate future clinical trial design.