Radiation and concomitant chemotherapy for patients with glioblastoma multiforme

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Abstract

Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy (hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.

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Most cited references 35

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Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.

L. Stewart (2002)

Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. We undertook a systematic review and meta-analysis to assess the effects of such treatment on survival and recurrence. We did a systematic review and meta-analysis using updated data on individual patients from all available randomised trials that compared radiotherapy alone with radiotherapy plus chemotherapy. Data for 3004 patients from 12 randomised controlled trials were included (11 published and one unpublished). Overall, the results showed significant prolongation of survival associated with chemotherapy, with a hazard ratio of 0.85 (95% CI 0.78-0.91, p<0.0001) or a 15% relative decrease in the risk of death. This effect is equivalent to an absolute increase in 1-year survival of 6% (95% CI 3-9) from 40% to 46% and a 2-month increase in median survival time (1-3). There was no evidence that the effect of chemotherapy differed in any group of patients defined by age, sex, histology, performance status, or extent of resection. This small but clear improvement in survival from chemotherapy encourages further study of drug treatment of these tumours.

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Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

P. Tai, C Hao, Marjorie A. Chan … (2004)

To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

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Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial.

Rolf Kortmann, Salvador Villà, René-Olivier Mirimanoff … (2006)

The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

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Author and article information

Journal

Journal ID (nlm-ta): Chin J Cancer

Journal ID (iso-abbrev): Chin J Cancer

Journal ID (publisher-id): CJC

Title: Chinese Journal of Cancer

Publisher: Sun Yat-sen University Cancer Center

ISSN (Print): 1000-467X

ISSN (Electronic): 1944-446X

Publication date (Print): January 2014

Volume: 33

Issue: 1

Pages: 25-31

Affiliations

[1 ]Radiation Oncology,

[2 ]Medical Oncology, Catalan Institute of Oncology, HU Germans Trias, Badalona 08916, Catalonia, Spain.

Author notes

Corresponding Author: Salvador Villà, Radiation Oncology, Catalan Institute of Oncology, HU Germans Trias, Badalona 08916, Catalonia, Spain. Tel: +34-934978805; Email: svilla@ 123456iconcologia.net .

Article

Publisher ID: cjc-33-01-025

DOI: 10.5732/cjc.013.10216

PMC ID: 3905087

PubMed ID: 24325790

SO-VID: 359acdaf-0168-490b-9a55-d873ffa9e160

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

Radiation and concomitant chemotherapy for patients with glioblastoma multiforme

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Karger: Oncology

Most cited references 35

Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial.

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