Combined Modality Therapy Superior in Glioblastoma

Multiple modalities were found to be superior to single modality therapies in elderly patients with glioblastoma.

Multiple modalities are superior to single modality therapies in the treatment of gliobastoma (GBM) and are suitable for elderly patients, according to a study published in JAMA Neurology. The study1 by Chad G. Rusthoven, MD, of the University of Colorado School of Medicine, and colleagues was the first to compare outcomes to standard therapeutic strategies among older patients, confirming a survival benefit for the use of combined modality therapy (CMT) for the treatment of GBM in a base of 16 717 patients over age 65.

Patients between age 65 and 90 with newly-diagnosed GBM between 2005 and 2011 were selected from the National Cancer Database. Just over half (53%) were male, and the median age was 73. Among the cohort, 8435 (50%) received CMT treatment of both radiotherapy (RT) and chemotherapy (CT), 1693 (10%) were given RT alone, and 1018 (6%) were given CT alone. One-third of patients diagnosed (5571 [33%]) received no treatment at all.

Patient selection for the analysis was specifically limited to those diagnosed after 2005, when the results of the highly significant EORTC-NCIC trial2 reported that the addition of temozolomide to RT significantly improved survival in GBM, and was thereafter considered a standard of care. Despite this, based on patterns of care, it was estimated that at least 3% of patients in the current study may have been given different chemotherapeutic treatment.

Comparisons between single modalities — RT vs CT — showed little difference in median overall survival (OS) of 4.7 (95% CI, 4.5-5.0) months and 4.3 months (95% CI, 4.0-4.7), respectively. Survival in patients who received no treatment was significantly lower at 2.8 months (95% CI, 2.8-2.9). Treatment with CMT was far superior to all other modalities: 9.0 months (95% CI, 8.8-9.3) (P<.001).

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Differences in patterns of treatment emerged during the later years studied, where the frequency of CMT following surgical resection increased specifically among patients who were younger, male, white, and had lower comorbidity scores according to the Charlson-Deyo comorbidity index.

In the accompanying editorial3, Stephen W. Clark, MD, PhD, of Vanderbilt University Medical School and Vanderbilt-Ingram Cancer Center, both in Nashville, Tenn., pointed out the significance of expanding more aggressive treatment to the elderly population, a group that by the year 2035 may comprise as much as 70% of patients with cancer. He further suggested that age as a comparative factor is a limitation to such studies, and that global DNA methylation is a better comparative marker of therapy.

For decades, RT has been the standard of care for elderly patients with GBM, based on the results of studies from the 1970s and 1980s4,5, and despite evidence from the more recent EORTC-NCIC trial2 showing survival benefits to CTM among patients younger than 65. Evidence from the current study supports the use of CTM for older GBM patients who once were candidates mainly for single modality treatment.


  1. Rusthoven CG, Koshy M, Sher DJ, et al. Combined-Modality Therapy With Radiation and Chemotherapy for Elderly Patients With Glioblastoma in the Temozolomide Era: A National Cancer Database Analysis. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.0839.
  2. Minniti G, De Sanctis V, Muni R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol. 2008;88:97-103.
  3. Clark SW. The Age Factor in the Treatment of Glioblastoma. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.1331.
  4. Kristiansen K, Hagen S, Kollevold T, et al. Combined modality therapy of operated astrocytomas grade III and IV. confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer. 1981;47:649-652.
  5. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: a cooperative clinical trial. J Neurosurg. 1978;49:333-343.