Survival of patients treated with radiation therapy for anaplastic astrocytoma

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Abstract

Background

Anaplastic astrocytoma (AA) represents 7% of primary brain tumors in adults. Patient-, tumor-, and treatment-related factors are thought to be predictive of survival. We retrospectively assessed the association of patient-, tumor-, and treatment-related factors with survival in AA treated with radiotherapy (RT) at our institution.

Patients and methods.

Medical records of patients with AA treated with RT between 1987 and 2007 were reviewed. Patient-, tumor-, and treatment-related variables were recorded and used to assign patients to a Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification. First use of chemotherapy was recorded. Log-rank tests and Cox regression models were used to assess for an association of patient-, tumor- and treatment-related factors with survival.

Results

One-hundred twenty-six patients were eligible for study. Median age, Karnofsky performance status, and duration of symptoms were 43 years, 90, and 8 weeks. Median radiation dose was 59.4 Gy; 61% of patients underwent tumor resection, and 17% and 41% of patients received temozolomide during and after RT. Median survival was 31 months, and 2-year survival was 58%. RTOG RPA class was associated with survival (p < 0.001), but use of temozolomide during or after RT was not (p > 0.05).

Conclusions

In this retrospective study with inherent limitations, RTOG RPA classification was associated with survival. Further studies are necessary to confirm or refute this finding.

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Most cited references 16

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Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.

E Bräuer-Krisch, Christopher P. Nelson, Rod Scott … (1993)

Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma. This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials. We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients. This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis. The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials.

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

G. Owens, Mhairi Alexander, J Ransohoff … (1978)

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.

J Bruner, V. Levin, S Zaknoen … (1999)

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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Author and article information

Journal

Journal ID (nlm-ta): Radiol Oncol

Journal ID (iso-abbrev): Radiol Oncol

Journal ID (publisher-id): RADO

Title: Radiology and Oncology

Publisher: Versita, Warsaw

ISSN (Print): 1318-2099

ISSN (Electronic): 1581-3207

Publication date Collection: December 2014

Publication date (Electronic): 5 November 2014

Volume: 48

Issue: 4

Pages: 381-386

Affiliations

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Author notes

Correspondence to: Christopher A. Barker, M.D., Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 22, New York, New York 10065, USA. Phone: 212 639 8168; Fax: 212 717 3104; E-mail: barkerc@ 123456mskcc.org

Disclosure: No potential conflicts of interest were disclosed.

Article

Publisher ID: rado-48-04-381

DOI: 10.2478/raon-2014-0019

PMC ID: 4230558

SO-VID: c27142dc-d367-44ae-a1d2-8a4b299a1c77

License:

This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

Survival of patients treated with radiation therapy for anaplastic astrocytoma

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Abstract

Background

Patients and methods.

Results

Conclusions

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Karger: Oncology

Most cited references 16

Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.

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

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.

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