Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach

BACKGROUND: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. METHODS: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. RESULTS: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). CONCLUSIONS: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.

Solitary Primary Leptomeningeal Glioma: Case Report

We report a case of solitary primary leptomeningeal glioma. The mass was totally removed under awake surgery. Intraoperatively, no parenchymal involvement was noted. Histopathological study revealed a predominant anaplastic oligodendroglioma component and a focal anaplastic astrocytoma component, which was consistent with an anaplastic oligoastrocytoma. Adjuvant tomotherapy was followed and the tumor has not recurred until 12 months after surgery. A focal type of primary leptomeningeal glioma is extremely rare. We report a rare case of solitary primary leptomeningeal anaplastic oligoastrocytoma.

Clinical Outcome of the Mixed Glioma: Preliminary Analysis

The authors analyzed preliminary outcome of 10 patients with mixed glioma(3 patients with low-grade oligoastrocytoma and 7 patients with anaplastic oligoastrocytoma) who underwent surgical resection and were treated or are in treatment with or without adjuvant therapy at our institute since May 1993. In the low-grade oligoastrocytoma group, gross total tumor resection was done in all three cases and postoperative radiation therapy was performed in 2 cases. In the anaplastic oligoastrocytoma group, all seven cases were divided as to the amount of tumor removal(gross total resection; 4 cases, subtotal resection; 1 case, partial resection; 2 cases) and clinical course and prognosis were analyzed as to performing postoperative radiation therapy with or without chemotherapy. In the low-grade oligoastrocytoma group, one patient who didn't undergo postoperative radiation therapy suffered from tumor recurrence that showed histopathologically malignant transformation. In the anaplastic oligoastrocytoma group, 2 patients who underwent subtotal tumor resection and partial tumor resection with postoperative radiation therapy showed tumor progression and histopathologically more malignant transformation. The authors propose that gross total tumor resection with postoperative radiation therapy in low-grade oligoastrocytoma and adding chemotherapy(especially with procarbazine, lomustine, vincristine; PCV regimen) in anaplastic oligoastrocytoma appear to be associated with more prolongation of patient's survival.