285 - WF-1801: Cognitive Outcomes of a Single Arm Pilot Study of Ramipril for Prevention of Radiation-Induced Cognitive Decline in Glioblastoma Patients Receiving Chemoradiotherapy
Presenter(s)
A. Goetz1, S. Smith2, E. Dressler3, B. R. Page4, J. S. Wefel5, S. R. Rapp6, E. Ip3, M. Gilbert7, S. Pugh8, A. L. Sumrall9, K. E. Weaver10, G. J. Lesser11, M. D. Chan12, C. K. Cramer12, R. Strowd13, Z. K. Vaslow14, and G. Volas Redd15; 1Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 2Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston Salem, NC, 3Atrium Health Wake Forest Baptist, Winston Salem, NC, 4Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 5The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 7NCI Center for Cancer Research, Bethesda, MD, 8The American College of Radiology, Philadelphia, PA, 9Levine Cancer Institute, Atrium Health, Charlotte, NC, 10Department of Social Sciences and Health Policy, Winston Salem, NC, 11Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC, 12Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 13Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC, 14Cone Health, Greensboro, NC, 15Georgia Cancer Specialists, Atlanta, GA
Purpose/Objective(s): Patients with glioblastoma (GBM) experience cognitive decline after chemoradiation (CRT). The control arm of the RTOG 0825 trial represents an excellent historical control population of patients treated with temozolomide and modern radiation doses and volumes. A trial with matched inclusion criteria and treatment protocol to RTOG 0825 was conducted where patients were also treated ramipril in an attempt to mitigate radiation- induced cognitive decline. Cognitive outcomes were then compared between the trials.
Materials/Methods: This was a prospective, single-arm study (NCI-2018-01807) coordinated by the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base. Ramipril was administered as a cytoprotective agent meant to prevent treatment-induced cognitive decline in patients with GBM. Patients were treated with daily ramipril during CRT, and for 3 months after completion of CRT. Ramipril was escalated from 1.25 mg qD to a maximum dose of 5 mg per day. The same neurocognitive battery as the one used in RTOG 0825 was administered at baseline, end of RT, and 1 and 4 months after RT. This Consisted of Hopkins Verbal Learning Test-Revised (HVLT-R) , Trail Making Test (TMT), and Controlled Oral Word Association Test (COWA). Time to cognitive failure (a decrease of 1 standard deviation, SD) was ascertained for a composite score for the neurocognitive test and for each individual neurocognitive test. Time to failure of each test was compared to the corresponding outcomes from the standard arm of the RTOG 0825 study.
Results: 75 participants were enrolled between 3/25/2019 and 11/14/23. 61% of patients completed >=75% of doses of ramipril; 57% completed all cognitive assessments. The median (range) change in cognitive composite score at 1 month after RT completion was 0.01 (-82.6, 13.0) versus RTOG-0825 median of 0.10 (-48.2, 8.6); p=0.49. 10.6% of RTOG 0825 patients and 44.2% of WF-1801 patients experienced a 1 SD improvement 1 month post-RT in TMT Part B (p<0.01). 12.8% of RTOG 0825 patients and 51.1% of WF-1801 patients experienced a 1 SD improvement 1 month post-RT in COWA (p<0.01). There were no statistical differences at 1 month between RTOG 0825 and WF-1801 patients in percentage of patients with a 1 SD drop in HVLT-R Total Recall (19.5% vs 12%), HVLT-R Delayed Recall (23.2 vs 10.6%), HVLT-R Recognition Memory (19.4 vs 23.5%), or TMT Part A (3.9 vs 15.6%).
Conclusion: Ramipril did not improve cognition or mitigate the cognitive decline following CRT in GBM patients when compared to RTOG 0825 in the majority of individual cognitive tests. There was also not a signi?cant difference in the deterioration or change in the composite neurocognitive battery score.
Funding Information This project was supported by grants UG1CA189824 (Wake Forest NCORP Research Base) U10CA180868 (NRG Oncology Operations), and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).