Paradoxical Association Between Relative Cerebral Blood Volume Dynamics Following Chemoradiation and Increased Progression-Free Survival in Newly Diagnosed IDH Wild-Type MGMT Promoter Methylated Glioblastoma With Measurable Disease

Jodi Goldman; Akifumi Hagiwara; Jingwen Yao; Catalina Raymond; Christian Ong; Rojin Bakhti; Elizabeth Kwon; Maguy Farhat; Carlo Torres; Lily G Erickson; Brandon J Curl; Maggie Lee; Whitney B Pope; Noriko Salamon; Phioanh L Nghiemphu; Matthew Ji; Blaine S Eldred; Linda M Liau; Albert Lai; Timothy F Cloughesy; Caroline Chung; Benjamin M Ellingson

doi:10.3389/fonc.2022.849993

Paradoxical Association Between Relative Cerebral Blood Volume Dynamics Following Chemoradiation and Increased Progression-Free Survival in Newly Diagnosed IDH Wild-Type MGMT Promoter Methylated Glioblastoma With Measurable Disease

Front Oncol. 2022 Mar 8:12:849993. doi: 10.3389/fonc.2022.849993. eCollection 2022.

Authors

Jodi Goldman^{1

2}, Akifumi Hagiwara^{1

2}, Jingwen Yao^{1

2}, Catalina Raymond^{1

2}, Christian Ong^{1

2}, Rojin Bakhti^{1

2}, Elizabeth Kwon^{1

2}, Maguy Farhat³, Carlo Torres³, Lily G Erickson³, Brandon J Curl³, Maggie Lee³, Whitney B Pope², Noriko Salamon², Phioanh L Nghiemphu⁴, Matthew Ji⁴, Blaine S Eldred⁴, Linda M Liau⁵, Albert Lai⁴, Timothy F Cloughesy⁴, Caroline Chung³, Benjamin M Ellingson^{1

2

6}

Affiliations

¹ UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
² Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
³ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
⁴ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁵ Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Background and purpose: While relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions.

Methods: 1,153 newly diagnosed IDH wild-type GBM patients were screened and 53 patients (4.6%) had measurable post-surgical tumor (>1mL). rCBV was measured before and after patients underwent chemoradiation. Patients with a decrease in rCBV >10% were considered rCBV Responders, while patients with an increase or a decrease in rCBV <10% were considered rCBV Non-Responders. The association between change in enhancing tumor volume, change in rCBV, MGMT promotor methylation status, and PFS or OS were explored.

Results: A decrease in tumor volume following chemoradiation trended towards longer OS (p=0.12; median OS=26.8 vs. 16.3 months). Paradoxically, rCBV Non-Responders had a significantly improved PFS compared to Responders (p=0.047; median PFS=9.6 vs. 7.2 months). MGMT methylated rCBV Non-Responders exhibited a significantly longer PFS compared to MGMT unmethylated rCBV Non-Responders (p<0.001; median PFS=0.5 vs. 7.1 months), and MGMT methylated rCBV Non-Responders trended towards longer PFS compared to methylated rCBV Responders (p=0.089; median PFS=20.5 vs. 13.8 months).

Conclusions: This preliminary report demonstrates that in newly diagnosed IDH wild-type GBM with measurable enhancing disease after surgery (5% of patients), an enigmatic non-response in rCBV was associated with longer PFS, particularly in MGMT methylated patients.

Keywords: MGMT methylation; chemoradiation; dynamic susceptibility contrast perfusion MRI; glioblastoma; rCBV.

Grants and funding

P50 CA211015/CA/NCI NIH HHS/United States