Central Nervous System

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

1024 - Dosimetric Predictors of Cognitive Decline in Attention and Processing Speed After Fractionated Brain Radiation Therapy

Sunday, October 21
5:21 PM - 5:27 PM
Location: Room 217 A/B

Dosimetric Predictors of Cognitive Decline in Attention and Processing Speed After Fractionated Brain Radiation Therapy
M. P. Huynh-Le1, K. R. Tringale1, R. Karunamuni1, D. C. Marshall1, J. Burkeen2, T. M. Seibert1, T. Nguyen1, V. Moiseenko1, C. McDonald1, and J. A. Hattangadi-Gluth1; 1University of California, San Diego, La Jolla, CA, 2University of California San Diego, La Jolla, CA

Purpose/Objective(s): Neurocognitive decline, including changes in attention/processing speed, can be an unfortunate consequence of brain radiation therapy (RT). The corpus callosum (CC) and right-sided subcortical white matter (WM) are known to subserve this cognitive function. We aimed to determine dosimetric predictors of attention/processing decline at 6 months after fractionated RT in patients with primary brain tumors.

Materials/Methods: Twenty-three patients with primary brain tumors were enrolled on a prospective cohort study. Patients had neurocognitive assessments and high resolution diffusion and volumetric MRI imaging pre-RT and 6 months post RT. Subjects were tested on Delis-Kaplan Executive Function System trail making number and letter sequencing. Reliable change indices accounting for practice effects (RCI-PE) scores were calculated as a normalized measure of cognition change from pre- to post-RT. Practice effects accounts for expected improvements in tasks with repetition. Binary variables decline and substantial decline were defined as RCI-PE <0 and <-1, respectively. Brain WM regions were segmented using a validated probabilistic diffusion tensor WM atlas. Regions of interest (ROIs) were CC and total right-sided subcortical WM with and without CC. Tumor and edema were censored from ROIs. Data including Vx (structure volume receiving ≥ x Gy) in 5 Gy intervals, minimum, maximum, and mean doses to each ROI were extracted from RT plans. A general linear model on dosimetric/volumetric data was created to identify predictors of decline (significance defined as p<0.05).

Results: Most patients (n=15, 62%) had benign or low-grade tumors. Median age at RT was 51 years (range 20-75) and 48% of patients were male. 15 patients (65%) underwent resection pre-RT and 9 (39%) patients received concurrent chemotherapy. Between 60-69% of patients experienced a decline; substantial number and letter sequencing decline was seen in 5 (22%) and 2 (9%) patients, respectively. Minimum dose to CC predicted for substantial letter sequencing decline (p<0.001), but there were no significant predictors of number sequencing. In right sided subcortical WM excluding CC, V30 predicted for substantial number sequencing decline (p<0.001) while minimum dose (p<0.001) and V30-V40 (all p<0.001) predicted for substantial letter sequencing decline. Within right-sided subcortical WM including CC, V30 predicted for substantial number sequencing decline (p<0.001) while V30-V35 (p<0.001) predicted for substantial letter sequencing decline.

Conclusion: In this prospective cohort study, increasing volume receiving 30-40Gy within the right-sided total subcortical WM predicted for decreased attention/processing speed at 6 months after RT. Minimum dose to CC also predicted for decline. This suggests that dose-dependent subcortical WM effects contribute to cognitive decline. Further complex modeling is needed to generate normal tissue parameters for WM structures to guide cognitive sparing brain RT.

Author Disclosure: M. Huynh-Le: None. K.R. Tringale: None. J. Burkeen: None. T.M. Seibert: None. T. Nguyen: None. J.A. Hattangadi-Gluth: Research Grant; Varian Medical Systems.

Minh-Phuong Huynh-Le, MD

University of California, San Diego

Disclosure:
No relationships to disclose.

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