Akifumi Hagiwara1,2,3, Talia C Oughourlian1,2,4, Nicholas S Cho1,2,5,6, Jacob Schlossman1,2, Chencai Wang1,2, Jingwen Yao1,2, Catalina Raymond1,2, Richard Everson7, Kunal Patel7, Sergey Mareninov8, Fausto J Rodriguez8, Noriko Salamon2, Whitney B Pope2, Phioanh L Nghiemphu9, Linda M Liau7, Robert M Prins7, Timothy F Cloughesy9,10, Benjamin M Ellingson1,2,5,9,11. 1. UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California, Los Angeles, Los Angeles, California, USA. 2. Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 3. Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan. 4. Neuroscience Interdepartmental PhD Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 5. Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, California, USA. 6. Medical Scientist Training Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 7. Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 8. Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 9. UCLA Neuro-Oncology Program, University of California, Los Angeles, Los Angeles, California, USA. 10. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 11. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Abstract
BACKGROUND: Diffusion MRI estimates of the apparent diffusion coefficient (ADC) have been shown to be useful in predicting treatment response in patients with glioblastoma (GBM), with ADC elevations indicating tumor cell death. We aimed to investigate whether the ADC values measured before and after treatment with immune checkpoint inhibitors (ICIs) and the changes in these ADC values could predict overall survival (OS) in patients with recurrent IDH wild-type GBM. METHODS: Forty-four patients who met the following inclusion criteria were included in this retrospective study: (i) diagnosed with recurrent IDH wild-type GBM and treated with either pembrolizumab or nivolumab and (ii) availability of diffusion data on pre- and post-ICI MRI. Tumor volume and the median relative ADC (rADC) with respect to the normal-appearing white matter within the enhancing tumor were calculated. RESULTS: Median OS among all patients was 8.1 months (range, 1.0-22.5 months). Log-rank test revealed that higher post-treatment rADC was associated with a significantly longer OS (median, 10.3 months for rADC ≥ 1.63 versus 6.1 months for rADC < 1.63; P = .02), whereas tumor volume, pretreatment rADC, and changes in rADC after treatment were not significantly associated with OS. Cox regression analysis revealed that post-treatment rADC significantly influenced OS (P = .02, univariate analysis), even after controlling for age and sex (P =.01, multivariate analysis), and additionally controlling for surgery after ICI treatment (P = .045, multivariate analysis). CONCLUSIONS: Elevated post-treatment rADC may be an early imaging biomarker for OS benefits in GBM patients receiving ICI treatment.
BACKGROUND: Diffusion MRI estimates of the apparent diffusion coefficient (ADC) have been shown to be useful in predicting treatment response in patients with glioblastoma (GBM), with ADC elevations indicating tumor cell death. We aimed to investigate whether the ADC values measured before and after treatment with immune checkpoint inhibitors (ICIs) and the changes in these ADC values could predict overall survival (OS) in patients with recurrent IDH wild-type GBM. METHODS: Forty-four patients who met the following inclusion criteria were included in this retrospective study: (i) diagnosed with recurrent IDH wild-type GBM and treated with either pembrolizumab or nivolumab and (ii) availability of diffusion data on pre- and post-ICI MRI. Tumor volume and the median relative ADC (rADC) with respect to the normal-appearing white matter within the enhancing tumor were calculated. RESULTS: Median OS among all patients was 8.1 months (range, 1.0-22.5 months). Log-rank test revealed that higher post-treatment rADC was associated with a significantly longer OS (median, 10.3 months for rADC ≥ 1.63 versus 6.1 months for rADC < 1.63; P = .02), whereas tumor volume, pretreatment rADC, and changes in rADC after treatment were not significantly associated with OS. Cox regression analysis revealed that post-treatment rADC significantly influenced OS (P = .02, univariate analysis), even after controlling for age and sex (P =.01, multivariate analysis), and additionally controlling for surgery after ICI treatment (P = .045, multivariate analysis). CONCLUSIONS: Elevated post-treatment rADC may be an early imaging biomarker for OS benefits in GBM patients receiving ICI treatment.
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Authors: Nicholas S Cho; Akifumi Hagiwara; Blaine S C Eldred; Catalina Raymond; Chencai Wang; Francesco Sanvito; Albert Lai; Phioanh Nghiemphu; Noriko Salamon; Lori Steelman; Islam Hassan; Timothy F Cloughesy; Benjamin M Ellingson Journal: Neurooncol Adv Date: 2022-08-04