Diffusion MRI is an early biomarker of overall survival benefit in IDH wild-type recurrent glioblastoma treated with immune checkpoint inhibitors

Akifumi Hagiwara; Talia C Oughourlian; Nicholas S Cho; Jacob Schlossman; Chencai Wang; Jingwen Yao; Catalina Raymond; Richard Everson; Kunal Patel; Sergey Mareninov; Fausto J Rodriguez; Noriko Salamon; Whitney B Pope; Phioanh L Nghiemphu; Linda M Liau; Robert M Prins; Timothy F Cloughesy; Benjamin M Ellingson

doi:10.1093/neuonc/noab276

Diffusion MRI is an early biomarker of overall survival benefit in IDH wild-type recurrent glioblastoma treated with immune checkpoint inhibitors

Neuro Oncol. 2022 Jun 1;24(6):1020-1028. doi: 10.1093/neuonc/noab276.

Authors

Akifumi Hagiwara^{1

2

3}, Talia C Oughourlian^{1

2

4}, Nicholas S Cho^{1

2

5

6}, Jacob Schlossman^{1

2}, Chencai Wang^{1

2}, Jingwen Yao^{1

2}, Catalina Raymond^{1

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 Cloughesy^{9

10}, Benjamin M Ellingson^{1

2

5

9

11}

Affiliations

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.

Keywords: ADC; ICI; IDH wild type; MRI; recurrent glioblastoma.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Biomarkers
Brain Neoplasms* / diagnostic imaging
Brain Neoplasms* / drug therapy
Diffusion Magnetic Resonance Imaging
Glioblastoma* / diagnostic imaging
Glioblastoma* / drug therapy
Humans
Immune Checkpoint Inhibitors / therapeutic use
Retrospective Studies

Substances

Biomarkers
Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding