541P - A multicenter study evaluating the clinical and molecular characteristics of adult patients with diffuse midline and non-midline K27M altered gliomas

Background

Diffuse midline high grade glioma (DMG), H3 K27-altered previously known as DMG H3 K27M-mutant can appear both in childhood and in adulthood and the presence of this mutation is a well-known marker for poor prognosis with a median survival of around 9 months regardless of the histologic appearance. The goal of this retrospective study is to describe our multi-institutional experience with the clinical and molecular characteristics of these tumors in adults.

Methods

We retrospectively reviewed the electronic medical records (EMR) of all consecutive adult patients that underwent a surgical procedure for glioma excision and whose tissue was tested for the K27M mutation either by next generation sequencing (NGS) or immunohistochemistry (IHC) at the three main sites of our institution (Florida, Minnesota, and Arizona) from inception of the EMR to date.

Results

A total of 245 adult patients were included in this study, 138 (56.32%) male and 107 (43.68%) female with a median age of 48.50 years. Of these, n=72 (29.39%) had a K27M alteration and n= 173 were K27M wt. The most frequent location for the K27M altered and the K27M wt was the thalamus (n=30, 41.67% and n=45, 22.5%). In the H3K27M-altered group, the main 3 treatments were TMZ + RT in n= 36 (13.2%), RT alone in n= 19 (7%) and TMZ + RT + Optune device in n= 3 (1.1%). In the H3K27M-wt group, n= 122 received TMZ + RT (80.26%), n= 13 received RT alone (8.55%), and palliative care in n= 17 (11.18%). When comparing K27M altered vs GBM, both groups had similar OS with 18 months (95% CI 14.24-21.76) and 16 months (95% CI 10.29-21.70, p=0.57). In a subanalysis according to the tumor localization, the midlines showed an OS of 19 months (95% CI 15.041-22.96) vs. 13 months for the non-midline group ([95% CI 15.04-22.96], p=0.56).NGS was done in 93 patients (38%). The most frequent gene alterations were the TERT promoter mutation n= 61 (65.59%), TP53 gene mutation n= 34 (33.34%), and NF1 mutation n=31 (30.39%) and PIK3CA gene mutation n= 26 (34.67%).

Conclusions

Our study shows similar results in terms of survival to those reported in the literature, however the molecular alterations found in NGS show a small proportion of possible molecular targets that could help in the treatment of patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.