Risk Factors For Early Cognitive Deterioration After Whole-Brain Radiation Therapy For Brain Metastasis

To clarify clinical factors associated with early cognitive deterioration after WBRT for brain metastasis. We administered a set of neurocognitive functioning tests (NFTs) to patients undergoing WBRT for brain metastasis in April 2012–March 2017. A total WBRT dose of 35 Gy/14 fractions, 30 Gy/10 fractions, or 25 Gy/10 fractions was delivered. Patient eligibility criteria: a Karnofsky Performance Status ≥60 and absence of severe neurological deficits that could interfere with the NFTs. The NFT set was: the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall (TR), delayed recall (DR), and delayed recognition (DRecog) subdomains; the Trail Making Test (TMT) -A and -B subdomains; and the Controlled Oral Word Association (COWA). The NFTs were administered before WBRT (baseline) and at 4 and 8 months post-WBRT. We calculated each NFT's Z-score and compared the NFT's 4-month Z-score median to that at baseline. We divided the patients into two groups by relevant factors: age (<65 vs. ≥65 yrs), Graded Prognostic Assessment (GPA) pre-WBRT ( worse-GPA 0–1.5 vs. good GPA 2.0–4.0), intracranial tumor control at 4 months (intracranial progressive disease [PD] vs. non-PD), and the number of NFTs (8-month-complete group: the patients who completed the three planned examinations vs. 4-month-dropout group: those who underwent two examinations and then dropped out). The association between the deterioration of the 4-month Z-scores and the clinical factors was analyzed with the Wilcoxon signed-rank test. P-values <0.05 were considered significant. Consecutive 41 patients underwent the NFTs.Thirteen patients underwent the NFTs at 4 months but not at 8 months, due to death from primary cancer (n=8) or worsened general condition (n=5). In all 41 patients, there were significant declines in two items, TR (p=0.01) and DRecog (p=0.01). In the ≥65 yr-old group, there were significant declines in TR (p=0.01) and DRecog (p=0.02). The worse-GPA group showed significant declines in TR (p=0.02) and DRecog (p=0.04). In the intracranial PD group, four items demonstrated significant declines: TR (p<0.01), DR (p=0.02), DRecog (p<0.05), and COWA (p=0.04). The 4-month-dropout group showed significant declines in TR (p=0.02), DR (p=0.04), and DRecog (p=0.02). There were no significant 4-month declines in each corresponding counterpart. The early cognitive deterioration after WBRT is related to age, estimated survival, intracranial tumor control, and the ability to continue undergoing NFTs.