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      Prognostic factors and outcomes in anaplastic gliomas: An institutional experience

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          Abstract

          Background:

          There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients.

          Materials and Methods:

          Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software.

          Results:

          A total of 100 patients were included in the study. The median age was 35 years (range 6–68 years). Eighty-four patients had follow-up details and were included for survival analysis. The 5-year overall survival (OS) was 58%. Age, presentation with seizures, and focal neurological deficit were not found to significantly influence survival. The 5-year survival for oligodendroglioma and astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance Score (KPS) of ≥70 had a significantly better 5-year OS (65%) as compared to those with KPS <70 (33%) ( P = 0.000). The use of adjuvant temozolomide (TMZ) showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive adjuvant chemotherapy ( P = 0.018). Patients receiving both concurrent and adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two patients had recurrence with average time to recurrence being 37 months. Fourteen patients underwent salvage surgery and two patients received reirradiation.

          Conclusions:

          OS significantly correlated with KPS and receipt of concurrent and adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and adjuvant TMZ should be the standard of care for AGs.

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          Most cited references 17

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          Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

          A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.
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            Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.

            To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
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              Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas.

              High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial. Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH). Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH. Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.
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                Author and article information

                Journal
                South Asian J Cancer
                South Asian J Cancer
                SAJC
                South Asian Journal of Cancer
                Medknow Publications & Media Pvt Ltd (India )
                2278-330X
                2278-4306
                Jan-Mar 2018
                : 7
                : 1
                : 1-4
                Affiliations
                Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
                Author notes
                Correspondence to: Dr. Monica Malik, E-mail: dr_monica11@ 123456yahoo.com
                Article
                SAJC-7-1
                10.4103/sajc.sajc_55_17
                5865085
                Copyright: © 2018 The South Asian Journal of Cancer

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                Categories
                ORIGINAL ARTICLE: Brain Tumors

                anaplastic gliomas, chemoradiation, survival, temozolomide

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