Somatic POLE Mutation and Ultra-Hypermutated Genotype in a De Novo High-Grade, Isocitrate Dehydrogenase Wild-Type Glioma: Treatment Implications.

Pembrolizumab leads to a durable response in ultra-hypermutated, high-grade, glioma.

Therapeutic options for primary meningeal angiosarcoma: A case report.

BACKGROUND: Primary angiosarcoma (AS) of the central nervous system (PACNS) is an extremely rare malignancy. The meninges represent an uncommon site of origin of PACNS. This report describes a recurrent meningeal PACNS treated with surgery, radiotherapy, stereotactic radiosurgery, and paclitaxel at different stages of the disease. CASE DESCRIPTION: A 36-year-old Asian male presented to our facility with a 4-month history of worsening headaches and complete right homonymous hemianopia. Neuroimaging revealed a left occipital lobe hematome with an underlying left tentorial tumor. After subtotal resection, neuropathological examination revealed features of a malignant endothelial cell AS. He received a course of adjuvant radiation therapy but experienced disease progression. He subsequently received additional stereotactic radiosurgery followed by weekly paclitaxel. Magnetic resonance imaging during the course of treatment revealed stable disease until patient died following another progression of his tumor. CONCLUSION: This case of a meningeal PACNS highlights the importance of considering this entity in the face of a malignant lesion presenting with intracranial hemorrhagic activity. Our observations suggest that the use of paclitaxel provided a modest clinical response in PACNS, highlighting the need to consider a combined approach structured mainly on surgery and radiotherapy. Stereotactic radiosurgery appears to be a promising treatment option.

Textiloma Mimicking a Recurrent High-Grade Astrocytoma: A Case Report.

Introduction Textiloma (Txm) is a nonmedical term that has been given to foreign body-related inflammatory pseudotumor arising from retained nonabsorbable cotton matrix that is either inadvertently or deliberately left behind during surgery, which may trigger an inflammatory reaction. This report describes a case of Txm mimicking a recurrent high-grade astrocytoma. Case Report We, here, present the case of a 69-year-old female with a 6-month history of progressive left-sided weakness. Neuroimaging studies revealed a large nonenhancing mass in the right frontoparietal lobe. Pathology reported a World Health Organization tumor classification grade II, diffuse astrocytoma. After surgical intervention, external beam radiation was given to the remaining areas of residual tumor. Routine magnetic resonance imaging (MRI) revealed a nodular area of contrast enhancement in the dorsal and inferior margin of the biopsy tract, growing between interval scans, and perfusion-weighted imaging parameters were elevated being clinically asymptomatic. She underwent a complete resection of this area of interest and pathology returned as a Txm with Surgicel fibers. Conclusion After treatment of a neoplasm, if unexpected clinical or imaging evidence of recurrence is present, a foreign body reaction to hemostatic material used during the initial surgery should be included in the differential diagnosis.

Phase 1 lead-in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma.

BACKGROUND: Repurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations of these agents with temozolomide (TMZ). METHODS: Adults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin. Dose-limiting toxicities (DLTs) were determined, using a 3 + 3 study design. RESULTS: Of 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2-year survival rate was 43%. CONCLUSIONS: Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.

Personalized Treatment for a Patient With a BRAF V600E Mutation Using Dabrafenib and a Tumor Treatment Fields Device in a High-Grade Glioma Arising From Ganglioglioma.

BACKGROUND: Gangliogliomas are slow-growing, low-grade central nervous system tumors affecting children and young adults. However, some patients will experience tumor recurrence and/or malignant progression. This article reports on the clinical history, molecular findings, and treatment response in a patient with BRAF V600-mutated high-grade glioma arising from ganglioglioma. METHODS: Hematoxylin-eosin staining and comprehensive genomic profiling via Foundation One were performed on the tumor sample from a male patient undergoing treatment at the Department of Neuro-Oncology at Baylor University Medical Center. RESULTS: The patient was eligible for participation in a clinical trial (ClinicalTrials.gov identifier: NCT00916409) of a tumor treatment fields (TTFields) device, NovoTTF-100A, with concurrent radiation and chemotherapy (CCRT). His disease relapsed 4 months after completion of his CCRT, with MRI showing areas of enhancement. Temozolomide was discontinued and he was offered dabrafenib, an oral selective inhibitor of BRAF V600E, with continued use of NovoTTF. At the time of this report, after 2 years of treatment with dabrafenib and TTFields, the patient shows a durable complete response in all areas with no active lesions or new areas of enhancement. CONCLUSIONS: This report suggests that TTFields delivered in combination with targeted therapy dabrafenib yielded a remarkable clinical and radiologic response in this recurrent high-grade glioma. Targeted therapy matched to genomic alterations combined with TTFields treatment could provide clinical benefit and should be prospectively explored in the near future.

Adult brainstem gliomas: Correlation of clinical and molecular features.

BACKGROUND: Brainstem gliomas are rare in adults and overall have superior survival outcomes compared to pediatric brainstem gliomas. PATIENTS AND METHODS: We conducted a retrospective data and tissue analysis of all adult patients (≥ 18 years old) with World Health Organization (WHO) Grade II, III, and IV brainstem gliomas in the University of Texas MD Anderson Cancer Center institutional database from 1990 to 2012. RESULTS: We identified 143 cases in adults ages 18 and over. There were 28 glioblastomas, 43 anaplastic astrocytomas, 15 diffuse astrocytomas, and 11 gliomas not otherwise specified, and in 46 cases the diagnosis was made radiographically. 128 (89.5%) cases were classified radiographically as diffuse and of the focal tumors, 9 of the 15 were WHO Grade III or IV tumors. Increasing tumor grade and contrast enhancement were associated with significantly reduced overall survival. The median overall survival for the entire cohort was 32.1 months similar to previously published studies. Two of 25 grade II and III tumors, and 1 of 17 glioblastomas had IDH1 mutations on immunohistochemical testing. Nine cases had sufficient tissue for mutation profiling, 1 case had a BRAF V600E mutation and 2 had 2 PIK3CA mutations. CONCLUSIONS: Survival outcomes for adult WHO Grade II to IV brainstem gliomas were similar to supratentorial IDH1 wild-type tumors of similar grade and histology. Potentially actionable mutations can be identified from small biopsy samples in a subset of adult brainstem gliomas.

Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard?

Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation, timely diagnosis of which has been a challenge. Given that tissue sampling of the MRI changes would be expected to accurately distinguish psPD from true progression when MRI changes are first seen, we examined the utility of surgery in diagnosing psPD and influencing patient outcome. We retrospectively reviewed data from adults with GBM who had MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection. Three subsets-tumor, psPD or mixed-were identified based on histology and immunohistochemistry in the surgical group and by imaging characteristics in the nonsurgical group. A cohort of patients with stable disease post-chemoRT served as control. PFS and OS were determined using the Kaplan-Meier method and log rank analysis. Concordance for psPD between radiological interpretation and subsequent histological diagnosis was seen in only 32% of cases (11/34) 95%CI 19-49%. A large proportion of patients had a histologically "mixed" pattern with tumor and treatment effect. No significant differences in PFS or OS were seen among the three subtypes. Surgical sampling and histologic review of MRI changes after chemoRT may not serve as a gold standard to distinguish psPD from true progression in GBM patients. Refinement of the histological criteria, careful intraoperative selection of regions of interest and advanced imaging modalities are needed for early differentiation of PsPD from progression to guide clinical management.

Intracranial germinoma.

Pineal region tumors make up less than 1% of all intracranial neoplasms, with the majority being of germ cell origin. We describe the diagnostic evaluation and treatment of a patient presenting with neurological deficits who was found to have a germinoma of the pineal gland.