Nils D Arvold1, Shyam K Tanguturi2, Ayal A Aizer1, Patrick Y Wen3, David A Reardon3, Eudocia Q Lee3, Lakshmi Nayak3, Laura W Christianson1, Margaret C Horvath1, Ian F Dunn4, Alexandra J Golby4, Mark D Johnson4, Elizabeth B Claus5, E Antonio Chiocca4, Keith L Ligon6, Brian M Alexander7. 1. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. 2. Harvard Radiation Oncology Program, Boston, Massachusetts. 3. Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. 4. Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. 5. Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts; School of Public Health, Yale University, New Haven, Connecticut. 6. Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. 7. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. Electronic address: bmalexander@lroc.harvard.edu.
Abstract
PURPOSE: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). METHODS AND MATERIALS: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. RESULTS: Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). CONCLUSIONS: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly.
PURPOSE: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). METHODS AND MATERIALS: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. RESULTS:Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). CONCLUSIONS: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly.
Authors: Rifaquat Rahman; Paul J Catalano; David A Reardon; Andrew D Norden; Patrick Y Wen; Eudocia Q Lee; Lakshmi Nayak; Rameen Beroukhim; Ian F Dunn; Alexandra J Golby; Mark D Johnson; E Antonio Chiocca; Elizabeth B Claus; Brian M Alexander; Nils D Arvold Journal: J Neurooncol Date: 2015-06-02 Impact factor: 4.130
Authors: Scott M Glaser; Michael J Dohopolski; Goundappa K Balasubramani; John C Flickinger; Sushil Beriwal Journal: J Neurooncol Date: 2017-05-19 Impact factor: 4.130