Central Nervous System

PD 03 - CNS 1 - Poster Discussion - Toxicity and Quality of Life

1020 - Early Diffusion Imaging Biomarkers of Prefrontal Lobe White Matter Microstructural Damage are Associated With Executive Dysfunction Following Radiation Therapy in Patients With Primary Brain Tumors: A Prospective, Longitudinal Study

Sunday, October 21
4:57 PM - 5:03 PM
Location: Room 217 A/B

Early Diffusion Imaging Biomarkers of Prefrontal Lobe White Matter Microstructural Damage are Associated With Executive Dysfunction Following Radiation Therapy in Patients With Primary Brain Tumors: A Prospective, Longitudinal Study
K. R. Tringale1, T. Nguyen1, N. Bahrami2, D. C. Marshall1, K. Leyden1, R. Karunamuni1, T. M. Seibert1, M. K. Gorman3, M. Connor1, J. Burkeen1, D. Piccioni4, N. Farid1, C. McDonald1, and J. A. Hattangadi-Gluth1; 1University of California, San Diego, La Jolla, CA, 2University of California, San Diego, CA, 3UC San Diego, La Jolla, CA, 4UC San Diego, San Diego, CA

Purpose/Objective(s): White matter in the prefrontal area, namely the anterior cingulate (AC), is critical to executive functioning (EF): a cognitive domain important for occupational status and quality of life in patients with brain tumors. Using advanced imaging and serial cognitive testing, we evaluated the longitudinal effects of radiation therapy (RT) on prefrontal white matter microstructure and executive function (EF) in a prospective, longitudinal trial of patients with primary brain tumors.

Materials/Methods: 22 patients with primary brain tumors were treated with brain RT on trial (median dose 54Gy, range 50.4-60Gy; 64% gliomas). Half the cohort was female and median age was 48 years. Diffusion tensor imaging to measure superficial white matter microstructure was obtained prior to RT, and at 3- and 6-months post-RT. Diffusion metrics included: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). The AC white matter was divided into the rostral AC (RAC) and caudal AC (CAC) given differential roles in cognitive processing. Cognitive EF testing included: Wisconsin Card Sorting Test perseverative errors (WCST-PE), Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency (LF) and Category Switching Accuracy (CSA). Reliable change indexes (RCIs) were calculated to determine significant baseline to 6 month changes in EF accounting for practice effects. Regression analyses were used to examine the relationship between early changes in white matter microstructure and later changes in EF, controlling for age and gender.

Results: From pre-RT to 3 months post-RT, FA decreased in the right CAC [t (19) = 2.38, p = .029], whereas MD increased in both the right [t (19) = -2.43, p = .026] and left [t (19) = -2.24, p = .038] CAC, reflecting white matter damage. Increases in MD were driven by increased RD in the right [t (19) = -2.84, p = .01] and left [t (19) = -2.42, p = .028] CAC, with no significant changes in AD during this time period. Group means revealed that the patients were largely intact in executive functioning at baseline, with a minimal number of patients impaired. At 6-month follow-up, there was a significant decline in performance on the WCST-PE at the group level [t (20) = -3.19, p = .005]. Decreases in FA (r = -.57, p = .034) and increases in MD (r = .56, p = .035) and RD (r = .70, p = .005) of the left CAC at 3 months were associated with 6-month decreases in D-KEFS-CSA performance. In addition, early increase in MD of the right CAC was associated with poorer performance on the WCST-PE (r = .56, p = .035) at 6 months.

Conclusion: Superficial white matter underlying the AC in the prefrontal area may be particularly vulnerable to radiation effects in brain tumor patients. Early microstructural damage in this area represents an important imaging biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation.

Author Disclosure: K.R. Tringale: None. T. Nguyen: None. N. Bahrami: None. T.M. Seibert: None. D. Piccioni: None. N. Farid: None. J.A. Hattangadi-Gluth: Research Grant; Varian Medical Systems.

Kathryn Tringale, MD, MS

UCSD School of Medicine

Disclosure:
No relationships to disclose.

Biography:
Dr. Tringale is currently in preliminary internal medicine internship at Kaiser Permanente in Los Angeles and will start her radiation oncology residency at Memorial Sloan Kettering Cancer Center in 2019. She received her biomedical engineering degree (BS) from Brown University in 2012, after which she conducted clinical research in brain computer interfaces at Massachusetts General Hospital. Throughout medical school at UC San Diego, Dr. Tringale was involved in a variety of research endeavors including outcomes research, clinical trials, and medical ethics, receiving a master's degree in Clinical Research in 2017. She recently received her MD from UC San Diego in 2018, where she was awarded the Igor Grant, MD Endowed Award for Academic Excellence and Biomedical Research, the Jean & Elliot Marvell Award in Radiation Oncology, and the Altman Clinical and Translational Research Institute Award.

Her primary CNS tumor research interest is the use of advanced imaging techniques to predict neurocognitive performance after radiation therapy. Her other research interests have included conflicts of interests introduced by industry payments to physicians, cost-effectiveness of immunotherapy, nature of malpractice claims in radiation oncology, and marijuana and opioid use in cancer patients.

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1020 - Early Diffusion Imaging Biomarkers of Prefrontal Lobe White Matter Microstructural Damage are Associated With Executive Dysfunction Following Radiation Therapy in Patients With Primary Brain Tumors: A Prospective, Longitudinal Study



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