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Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 in recurrent glioblastoma

BACKGROUND: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical tr...

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Detalles Bibliográficos
Autores principales: Ellingson, Benjamin M, Patel, Kunal, Wang, Chencai, Raymond, Catalina, Brenner, Andrew, de Groot, John F, Butowski, Nicholas A, Zach, Leor, Campian, Jian L, Schlossman, Jacob, Rizvi, Shan, Cohen, Yael C, Lowenton-Spier, Noa, Minei, Tamar Rachmilewitz, Shmueli, Shifra Fain, Wen, Patrick Y, Cloughesy, Timothy F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350152/
https://www.ncbi.nlm.nih.gov/pubmed/34377989
http://dx.doi.org/10.1093/noajnl/vdab082
Descripción
Sumario:BACKGROUND: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial. METHODS: Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (>1.24 µm(2)/ms) or low (<1.24 µm(2)/ms) ADC(L), the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor. RESULTS: Baseline tumor volume (P = .3460) and ADC(L) (P = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADC(L) had a significant survival advantage in all patients (P = .0006), as well as BV (P = .0159) and BV+VB-111 individually (P = .0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume, and ADC(L) identified continuous measures of tumor volume (P < .0001; HR = 1.0212) and ADC(L) phenotypes (P = .0012; HR = 0.5574) as independent predictors of OS. CONCLUSION: Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111.