Reduction in Whole Brain Volume is Associated with Decline in Verbal Memory Following Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer

Abstract

Whole brain radiation therapy (WBRT) is associated with both radiographic reduction in brain volume and clinical decline in neurocognitive function, but the relationship between these findings is unknown. This study evaluated an association between whole brain volume loss and neurocognitive decline following prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC). This was a secondary analysis of a prospective clinical trial that accrued patients at a single institution from 2013 to 2016. Patients with limited-stage SCLC and complete response to standard thoracic chemo-radiation received PCI to a total of 25 Gy in 10 fractions, with mean hippocampal dose limited to less than 8 Gy. The primary objective was to determine whether changes in whole brain volume were associated with changes in verbal memory, assessed with the Hopkins Verbal Learning Test-Revised (HVLT-R). Whole brain volumes were measured on MR imaging obtained before and at 6, 12, 18, and 24 months after PCI. Volumes were evaluated as the absolute change (mL) and proportional change (%) compared to baseline. Verbal memory was assessed before and at 6 and 12 months after PCI. Univariate and multivariate linear regression evaluated associations between changes in whole brain volume and verbal memory. Twenty-two patients enrolled. The median whole brain volume before PCI was 1301 mL (range 1056 – 1578). Whole brain volumes progressively decreased following PCI, reaching the greatest extent of reduction at 18 months after PCI (median change -23 mL, range -142 – 20, p = 0.009). On univariate linear regression, decline in the Delayed Recall component of the HVLT-R was significantly associated with absolute and proportional reduction in whole brain volume at 6 months after PCI (β = 0.041/mL, p = 0.02; β = 0.57/%, p = 0.03). On multivariate linear regression, reduction in whole brain volume was associated with decline in the Delayed Recall and Percent Retained components of the HVLT-R, independent of global cognitive function prior to PCI or years of education (Table 1). This is the first study to quantitatively correlate reduction in whole brain volume and decline in neurocognitive function following WBRT. This suggests that loss of brain volume after WBRT may be clinically significant and subsequently impact cognition and quality of life. Formal comparative studies are needed to confirm these findings.Abstract 22; Table 1Multivariate linear regression correlating changes in verbal memory, evaluated by the HVLT-R, and changes in whole brain volume (WBV) after PCI. Covariates in each model included global cognitive function (Mini-Mental State Examination) prior to PCI and years of education.OutcomePredictorβpR2Change in HVLT-R Delayed RecallAbsolute change in WBV (mL)0.074/mL0.0160.35Proportional change in WBV (%)0.99/%0.0150.36Change in HVLT-R Percent RetainedAbsolute change in WBV (mL)0.95/mL0.00420.46Proportional change in WBV (%)12.9/%0.00300.48 Open table in a new tab