Gliomatosis, to Be or Not to Cerebri? (P6.299)

Background: Gliomatosis cerebri (GC) has been debated as a pathologic entity sui generis versus a simple imaging and histologic pattern. Whereas the World Health Organization (WHO) 2000 classification considered GC a distinct tumor entity, WHO 2007 downgraded GC to a diffuse glioma pattern of extensive CNS infiltration, mostly of astrocytic phenotype involving at least three cerebral lobes, and the forthcoming WHO 2016 will further downgrade GC by removing the chapter. Tumors with distinctive GC presentation have been proven to be molecularly heterogeneous; however, paucity of data defining the pathophysiology and genetic driver(s) of this extensive diffuse infiltration pattern beleaguers the clinicians’ treatment planning. The GC literature is limited to retrospective studies and expert reviews, with only one ongoing phase II trial evaluating the use of dose-dense temozolomide. Methods: We reviewed 32 primary GC cases (2011-2014) to compare patient demographic, clinical, radiographic, molecular, tissue pathology, and survival data. Results: We found the major histologic phenotype was diffuse astrocytoma WHO grades II-IV (n=28,87[percnt]; grade II, n=10; grade III, n=8; and grade IV, n=10), and noted predominant temporal lobe involvement (n=25,78[percnt]). Treatment varied depending on histologic grade. The overall survival for astrocytic vs oligodendroglial tumors was 11.5 months versus 42 months respectively. Patients with IDH mutation (n=6) fared better, with median survival >33 months, consistent with previous reports. Interestingly, we identified two distinct populations of GC patients, one (n=7, 22[percnt]) with a 10-year-prior history of unrelated malignancies, and another (n=10, 31[percnt]) with systemic allergy/auto-immune diseases. Patients in both groups exhibited a predilection for infiltrating disease involvement of the posterior cerebrum. Conclusions: The clinical challenge to treat patients with extensive, diffuse infiltration of molecularly-diverse gliomas is as yet unmet. Uncovering the drivers of this condition may come with a deeper understanding of patient genetic and tumor microenvironmental predispositions toward the diffuse GC infiltrating pattern. Disclosure: Dr. Gatson has nothing to disclose. Dr. Kamiya Matsuoka has nothing to disclose. Dr. Rodriguez-Linares has nothing to disclose. Dr. Pillainayagam has nothing to disclose. Dr. Cachia has nothing to disclose. Dr. Daher has nothing to disclose. Dr. Chi has nothing to disclose. Dr. Weinberg has nothing to disclose. Dr. Tremont has nothing to disclose. Dr. Fuller has nothing to disclose. Dr. De Groot has received personal compensation for activities with Foundation Medicine, Genentech, Novartis, Celldex, Roche, MundiPharma EDO, VBL Therapeutics, and Deciphera Pharmaceuticals. Dr. De Groot has received research support from Sanofi-Aventis, Dr. Loghin has nothing to disclose.