ID #1054 Long-Term Survivors of Diffuse Hemispheric Glioma, H3 G34-mutant: Interim Assessment of a Multicentre Study
Cameron Crowell, Nikhil Mankuzhy, Pratiti Bandopadhayay, Sohil Patel, Daddy Mata-Mbemba, Michal Zapotocky, Mary-Pat Schlosser, Egiroh Omene, Sylvia Cheng, Jacquelyn Jones, Emily Lin, Olivia Vizzini, Sarah Lapointe, Romain Cayrol, Christina Coleman, Brandon Imber, Nikoleta Juretic, Matthias Karajannis, Keith Ligon, Nada Jabado, Craig ErkerAbstract
Background
Diffuse hemispheric glioma (DHG), H3 G34-mutant, is a malignancy of adolescent and young adults with poor prognosis. Long-term survival is uncommon, with only a few reports of patients surviving for extended periods.
Methods
We analyzed a retrospective multicentre cohort of 153 patients diagnosed with G34-mutant brain tumors to identify long-term survivors (LTS) defined as surviving 5 years or longer from diagnosis. Patients were diagnosed after January 1, 1995 and must have least one measure of survival or progression.
Results
Twelve patients (8%) in the cohort were LTS. Eight patients (67%) were younger than 18 years at time of diagnosis and nine (75%) were male. All patients presented with localized disease and were of the G34R mutation subtype. Molecular analysis demonstrated MGMT promoter methylation in 88% (7/8), ATRX loss in 78% (7/9), TP53 alterations in 91% (10/11), PDGFRA mutation was noted in 83% (5/6), PDGFRA amplification in 40% (2/5), and MYCN amplification in 14% (1/7). All received initial chemotherapy and irradiation. Regarding irradiation, 10 received focal radiation and one received craniospinal irradiation, and one unknown. All patients were treated with temozolomide-based chemotherapy, including four treated with the addition of CCNU and seven without. Median follow-up was 72 months (range, 67–81). At last follow-up, seven patients (58%) had died of disease, two (17%) were alive with disease, and three (25%) were alive without radiologic evidence of disease. Significant findings compared to non-LTS, LTS were more likely than STS to have initial GTR in 81% versus 39% and less likely to have deep structure involvement on MRI with 0% versus 26%.
Conclusions
Long-term survival in DHG, H3 G34 tumors is uncommon, characterized by G34R subtype, gross-total resection, lack of deep brain structure involvement, and use of multimodal therapy before disease progression. Additional radiographic and biological correlates are being explored.