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Original Investigation |

Combined-Modality Therapy With Radiation and Chemotherapy for Elderly Patients With Glioblastoma in the Temozolomide Era A National Cancer Database Analysis

Chad G. Rusthoven, MD1; Matthew Koshy, MD2,3; David J. Sher, MD4; Douglas E. Ney, MD5; Laurie E. Gaspar, MD1; Bernard L. Jones, PhD1; Sana D. Karam, MD, PhD1; Arya Amini, MD1; D. Ryan Ormond, MD6; A. Samy Youssef, MD, PhD6; Brian D. Kavanagh, MD1
[+] Author Affiliations
1Department of Radiation Oncology, University of Colorado School of Medicine, Aurora
2Department of Radiation Oncology, University of Illinois at Chicago School of Medicine, Chicago
3Department of Radiation and Cellular Oncology, University of Chicago School of Medicine, Chicago, Illinois
4Department of Radiation Oncology, University of Texas Southwestern, Dallas
5Division of Neuro-Oncology, Department of Neurology, University of Colorado School of Medicine, Aurora
6Department of Neurosurgery, University of Colorado School of Medicine, Aurora
JAMA Neurol. 2016;73(7):821-828. doi:10.1001/jamaneurol.2016.0839.
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Importance  The optimal management for elderly patients with glioblastoma (GBM) is controversial. Following maximal safe resection or biopsy, accepted treatment paradigms for elderly patients with GBM include combined-modality therapy (CMT) with both radiotherapy (RT) and chemotherapy (CT), RT alone, and CT alone.

Objective  To evaluate the overall survival (OS) outcomes associated with RT, CT, and CMT for elderly patients with GBM in the modern temozolomide era.

Design, Setting, and Participants  In this retrospective cohort study of a prospectively maintained, multi-institutional national cancer registry, the National Cancer Database was queried for elderly patients (≥65 years) with newly diagnosed GBM from January 1, 2005, through December 31, 2011, with complete data sets for RT, CT, tumor resection, Charlson-Deyo comorbidity scores, age, sex, and year of diagnosis. Data analysis was performed from October 2015 through December 2015.

Interventions  Combined-modality therapy, RT, CT.

Main Outcomes and Measures  Survival by treatment cohort was estimated using the Kaplan-Meier method and analyzed using the log rank test, univariate and multivariate Cox models, and propensity score–matched analyses.

Results  A total of 16 717 patients (median [range] age, 73 [65-≥90 y]; 8870 [53%] male) were identified. The median OS by treatment was 9.0 (95% CI, 8.8-9.3) months with CMT (8435 patients), 4.7 (95% CI, 4.5-5.0) months with RT alone (1693 patients), 4.3 (95% CI, 4.0-4.7) months with CT alone (1018 patients), and 2.8 (95% CI, 2.8-2.9) months with no therapy (5571 patients) (P < .001). On multivariate analysis, CMT was superior to both CT alone (hazard ratio, 1.50 [95% CI, 1.40-1.60]; P < .001) and RT alone (hazard ratio, 1.47 [95% CI, 1.39-1.55]; P < .001), whereas no differences were observed between CT alone vs RT alone (P = .60). Propensity score–matched analyses redemonstrated improved OS with CMT over CT alone (P = .002) and RT alone (P < .001); no differences were observed between CT alone vs RT alone (P = .44). On subgroup analyses, a consistent OS advantage was observed with CMT over both CT alone and RT alone across each age stratification (65-69, 70-74, 75-79, and ≥80 years) and among patients treated with or without tumor resection (all P < .001).

Conclusions and Relevance  In this analysis of multimodality therapy for elderly patients with GBM, OS was superior with CMT compared with CT alone and RT alone. Survival was similar between CT alone and RT alone, and both CT alone and RT alone were superior to no therapy. This analysis supports the use of CMT for suitable elderly candidates.

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Figure 1.
Treatment Patterns by Year of Diagnosis for Patients at Least 65 Years Old in the National Cancer Database

CT indicates chemotherapy, and RT, radiation therapy. Corresponding percentages for treatment groups by year are displayed in eTable 1 in the Supplement.

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Figure 2.
Overall Survival (OS) by Treatment Group

CT indicates chemotherapy, and RT, radiation therapy.

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Figure 3.
Overall Survival (OS) by Treatment Group Stratified by Age

CT indicates chemotherapy, and RT, radiation therapy.

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Submit a Comment
Benefit when biopsy only
Posted on May 24, 2016
Alain RAUSS
ARCOSA
Conflict of Interest: None Declared
The study presented answers to a very important issue as randomized clinical trials excludes generally elderly patients. If the benefit is statistically significant, the difference in the median of overall survival is small and we have no idea of the real benefit for the patients in quality of life at this time of the life. The benefit for patients with biopsy only is a very important question because of a shorter overall survival. In the publication we don't have the median overall survival for that kind of patient while we know that if there is biopsy only it is because resection is not possible taking into account the size of the tumor or the place of it and because we think it could be a glioblastoma. That's why the real benefit is so important for that kind of patients. With the publication, a quick conclusion should be when the Karnofsky status is good to select the combined-modality therapy even if the real benefit is very very small and for a very bad quality of life for the end of life. Even if the statistically significant is fundamental, in balance, the quality of life should be presented and discussed for patients with biopsy only.
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