Abstract Details

Title Clinical and Pathologic Determinants of Outcome for Non-Optic Pathway Gliomas in Adults with Neurofibromatosis Type 1

Topic Neuro-oncology

Presentation(s) S27 - Innovations in Neuro-oncology (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Background CNS malignancies are more common in people with NF1 than the general population. However, little is known about the clinical presentation, pathologic features, and treatment outcomes in NF1-associated gliomas.

Objective

Assess clinical course, histology, molecular features, and overall survival of adults with neurofibromatosis type 1 (NF1) and non-optic pathway gliomas (non-OPG).

Design/Methods Adults with NF1 and histologically confirmed non-OPG at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University Hospital were identified. Data on clinical presentation, histologic and molecular diagnostics, treatment, and survival were collected retrospectively. Central review of digitized pathology slides was performed by three neuropathologists.

Results

41 cases were identified. Most common presenting symptoms were headache, ataxia, visual concerns, sensory deficits, and dysphagia. Pathology slides were available for central review on 35 cases, diagnoses included: diffuse astrocytoma (9), glioblastoma (6), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), anaplastic astrocytoma (3), gliosarcoma (1), ganglioglioma (1), embryonal tumor (1), and diffuse midline glioma (1). Classification did not reach consensus in five cases. Most tumors (71%) were located in midline structures. Majority (80%) had biopsy or subtotal resection. IDH1 status was wildtype in 100% of 27 tested cases. MGMT promoter was unmethylated in 7/11 (64%) tested cases. In 10/41 cases comprehensive molecular testing was performed, common variants or amplifications were NF1, EGFR, ATRX, CDKN2A/B, P53, TERT, and MSH2/3. Similar to sporadic gliomas, patients with NF1-associated glioma were treated with surgery, radiation and/or chemotherapy. Despite young age (median 32 years) and favorable performance status (median 80%), the median overall survival was 23 months [2-109].

Conclusions Non-OPG in adults with NF1, including histologically low-grade tumors, often have a more aggressive course compared to patients with sporadic non-OPG. Standardized approaches to histologic diagnoses and molecular testing paired with outcome data is likely to improve prognostication, prioritization of treatment regimens, and recommended surveillance.

Authors/Disclosures
Anna Piotrowski, MD (Memorial Sloan Kettering Cancer Center) PRESENTER	Dr. Piotrowski has nothing to disclose.
	No disclosure on file
Rebecca M. Brown, MD, PhD (Memorial Sloan Kettering Cancer Center)	Dr. Brown has nothing to disclose.
Jose Diarte, MPH (Memorial Sloan Kettering Cancer Center)	Mr. Diarte has nothing to disclose.
	No disclosure on file
Tejus Bale (MSKCC)	No disclosure on file
	No disclosure on file
	No disclosure on file
Ingo K. Mellinghoff, MD, FACP (Memorial Sloan Kettering Cancer Center)	Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Agios. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Black Diamond Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Voyager Therapeutics . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kazia Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Agios. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Black Diamond Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Debiopharm Group. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Puma Biotechnology. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Voyager Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DC Europa Ltd. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kazia Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cardinal Health. Dr. Mellinghoff has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier . Dr. Mellinghoff has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ASCO/JCO. The institution of Dr. Mellinghoff has received research support from Amgen. The institution of Dr. Mellinghoff has received research support from General Electric. The institution of Dr. Mellinghoff has received research support from Lilly. The institution of Dr. Mellinghoff has received research support from Kazia Therapeutics. An immediate family member of Dr. Mellinghoff has received research support from Vigeo Therapeutics. The institution of an immediate family member of Dr. Mellinghoff has received research support from Samus Therapeutics. The institution of Dr. Mellinghoff has received research support from Erasca .
Jaishri Blakeley, MD, FAAN (Johns Hopkins University School of Medicine)	Dr. Blakeley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Springworks Therapeutics.
Carlos Ramos (Johns Hopkins University, School of Medicine)	No disclosure on file