Phase II study of bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy for newly diagnosed glioblastoma Journal Article
| Authors: | Omuro, A.; Beal, K.; Gutin, P.; Karimi, S.; Correa, D. D.; Kaley, T. J.; Deangelis, L. M.; Chan, T. A.; Gavrilovic, I. T.; Nolan, C.; Hormigo, A.; Lassman, A. B.; Mellinghoff, I.; Grommes, C.; Reiner, A. S.; Panageas, K. S.; Baser, R. E.; Tabar, V.; Pentsova, E.; Sanchez, J.; Barradas Panchal, R.; Zhang, J.; Faivre, G.; Brennan, C. W.; Abrey, L. E.; Huse, J. T. |
| Article Title: | Phase II study of bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy for newly diagnosed glioblastoma |
| Abstract: | Purpose: Bevacizumab is associated with decreased vascular permeability that allows for more aggressive radiotherapy schedules. We conducted a phase II trial in newly diagnosed glioblastoma utilizing a novel hypofractionated stereotactic radiotherapy (HFSRT) schedule combined with temozolomide and bevacizumab. Experimental Design: Patients with tumor volume ≤60 cc were treated with HFSRT (6 x 6 Gy to contrast enhancement and 6 x 4 Gy to FLAIR hyperintensity with dose painting) combined with concomitant/adjuvant temozolomide and bevacizumab at standard doses. Primary endpoint was 1-year overall survival (OS): promising = 70%; nonpromising = 50%; α = 0.1; β = 0.1. Results: Forty patients were enrolled (median age: 55 years; methylated MGMT promoter: 23%; unmethylated: 70%). The 1-year OS was 93% [95% confidence interval (CI), 84-100] and median OS was 19 months. The median PFS was 10 months, with no pseudo-progression observed. The objective response rate (ORR) was 57%. Analysis of The Cancer Genome Atlas glioblastoma transcriptional subclasses (Nanostring assay) suggested patients with a proneural phenotype (26%) fared worse (ORR = 14%, vs. 77% for other subclasses; P = 0.009). Dynamic susceptibility-contrast perfusion MRI showed marked decreases in relative cerebral blood volume over time (P < 0.0001) but had no prognostic value, whereas higher baseline apparent diffusion coefficient (ADC) ratios and persistent hypermetabolism at the 6-month FDG-PET predicted poor OS (P = 0.05 and 0.0001, respectively). Quality-of-life (FACT-BR-4) and neuropsychological test scores were stable over time, although some domains displayed transient decreases following HFSRT. Conclusions: This aggressive radiotherapy schedule was safe and more convenient for patients, achieving an OS that is comparable with historical controls. Analysis of advanced neuroimaging parameters suggests ADC and FDG-PET as potentially useful biomarkers, whereas tissue correlatives uncovered the poor prognosis associated with the proneural signature in non-IDH-1-mutated glioblastoma. |
| Keywords: | adolescent; adult; cancer survival; clinical article; treatment outcome; aged; overall survival; bevacizumab; drug withdrawal; cancer radiotherapy; temozolomide; nuclear magnetic resonance imaging; progression free survival; quality of life; multiple cycle treatment; tumor volume; kidney failure; lung embolism; glioblastoma; patient safety; neuropsychological test; clinical effectiveness; stereotactic treatment; brain ischemia; brain blood volume; thrombotic thrombocytopenic purpura; hypofractionated stereotactic radiotherapy; diffusion coefficient; chemoradiotherapy; human; male; female; article |
| Journal Title: | Clinical Cancer Research |
| Volume: | 20 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2014-10-01 |
| Start Page: | 5023 |
| End Page: | 5031 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-14-0822 |
| PROVIDER: | scopus |
| PUBMED: | 25107913 |
| PMCID: | PMC4523080 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
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