Abstract Details

Title Clinical and pathological characteristics of 52 adults with H3 K27M-mutant diffuse midline gliomas at UCSF

Topic Neuro-oncology

Presentation(s) S14 - Translational and Clinical Advances in Neuro-oncology (1:33 PM-1:44 PM)

Poster/Presentation
Number 004

Background Histone H3.3 or H3.1-mutant protein is commonly expressed in pediatric and adult diffuse midline gliomas, including diffuse intrinsic pontine gliomas (DIPGs), and portends a poor prognosis. However, knowledge of the behavior of this tumor in adults and treatments offered is limited.

Objective To report the clinical experience and the natural history of "Diffuse midline glioma, H3-K27M-mutant" (DMG-H3K27M), a recently defined WHO grade IV tumor entity, in adults.

Design/Methods We retrospectively reviewed the pathology of all adult (age ≥ 18) DMG-H3K27Ms diagnosed at our institution either via H3-K27M-mutant-specific immunohistochemistry or via the UCSF500, a targeted next-generation sequencing panel that includes the H3F3A, HIST1H3B, and HIST1H3C genes. Treatment, outcome, and imaging characteristics were obtained.

Results

52 adults with DMG-H3K27M were identified. Median age was 34-years (range, 19-69). Tumor locations included diencephalon (thalamus/hypothalamus/basal ganglia, 31), spine (8), brainstem (including pons/cerebellum, 8) and other (including pineal region, insula/parietal/temporal lobes, 5). 35 patients had biopsy only. 36/44 tumors were contrast-enhancing. 46/46 tumors were IDH-wildtype. 26/47 were ATRX intact. 49 patients were included for survival analyses. Median OS was 30.5-months (95%CI 14.5-41.8) and median PFS was 11.6-months (95%CI 8.8-20.3). In those with available clinical treatment data, 39/40 received radiation at initial diagnosis (34 with concomitant, 27 with adjuvant temozolomide). 33 patients had data on progression, of whom 23 progressed at least once. Of treatments administered at progression, 14 received bevacizumab, 5 were re-treated with temozolomide, 18 received other chemotherapy, and 13 received ≥1 course of re-irradiation.

Conclusions While still poor overall, clinical outcomes of adults DMG-H3K27M is often better than that of pediatric DIPGs and tumors are more frequently located in the spine and diencephalon. This may reflect a different cell of origin or different biological differences. Further investigation of DMG-H3K27M in adults is warranted to study the genetic and epigenetic features of these tumors, as well optimal treatment strategies.

Authors/Disclosures
Robin A. Buerki, MD, PhD (University of California, San Francisco) PRESENTER	No disclosure on file
Sarah Lapointe, MD (CHUM)	Dr. Lapointe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion.
David Solomon, MD, PhD (Johns Hopkins Hospital)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Nancy Ann Oberheim Bush, MD, PhD (UCSF)	Dr. Oberheim Bush has nothing to disclose.
Jennie W. Taylor, MD (University of California, San Francisco)	Dr. Taylor has received personal compensation for serving as an employee of Servier. The institution of Dr. Taylor has received research support from BMS. The institution of Dr. Taylor has received research support from Servier. The institution of Dr. Taylor has received research support from Navio. Dr. Taylor has received research support from University of Colorado. Dr. Taylor has received research support from Mt Sinai University . Dr. Taylor has received publishing royalties from a publication relating to health care.
Nicholas A. Butowski, MD (UCSF)	No disclosure on file
	No disclosure on file
Jennifer L. Clarke, MD, MPH (UCSF)	The institution of Dr. Clarke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Agios. The institution of Dr. Clarke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier. The institution of Dr. Clarke has received research support from Agios. The institution of Dr. Clarke has received research support from Servier. The institution of Dr. Clarke has received research support from Merck.

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