Interim results from CAR-Study B: An ongoing randomized trial on the effect of SRS or WBRT on cognitive performance in patients with 11-20 brain metastases

Wietske Schimmel*, Eline Verhaak, Patrick Hanssens, Xynthia Kavelaars, Joris Mulder, Maurits Kaptein, Margriet Sitskoorn, Karin Gehring

*Corresponding author for this work

Research output: Contribution to journalMeeting AbstractScientificpeer-review

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Both stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) have proven to be effective treatments for multiple brain metastases (BM) with similar overall survival. Cognition and Radiation (CAR) Study B is a randomized trial on the effect of Gamma Knife radiosurgery (GKRS) or WBRT on cognitive performance in patients with 11-20 BM. The primary and secondary aim of this interim analysis were to check whether Bayesian stopping rules for cognitive failure were met, and to compare cognitive changes after treatment respectively, for the first 45 patients enrolled.

Material and Methods
Patients with 11-20 newly diagnosed BM on a triple-dose contrast-enhanced MRI-scan, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70, were stratified by age, histology, total BM volume, systemic treatment, KPS, and baseline Hopkins Verbal Learning total recall (HVLT-R TR) score, and randomized 1:1 (minimization) to GKRS or WBRT. Neuropsychological tests were administered before (T0) treatment (n=21 vs n=20), and at 3 (T3; n=16 vs n=14) and 6 (T6; n=9 vs n=9) months thereafter. A decline of ≥5 points in HVLT-R TR score was considered a cognitive failure. The trial would be halted if the posterior probability for a higher cognitive failure rate in one group versus the other was >0·975 at T3 or T6 according to the employed beta (2.09,2.91) prior (prior mean of 42%), based on the average failure rates at 4 months reported by Chang et al. (2009). Between-group differences in changes of test performances over 6 months were analyzed using mixed ANOVAs. Proportions of cognitive changes (T0-T6) at the individual level based on reliable change indices correcting for practice effects, were determined.

HVLT-R TR failure rates in the GKRS versus WBRT group were 31% versus 29% at T3, and 0% versus 33% at T6. The observed failure rates after WBRT at T3 and T6 were lower than the average failure rates of Chang et al. (2009). Posterior probabilities were 0·451 at T3 and 0·918 at T6. Over 6 months, changes in performance on tests of immediate (p=·003) and delayed recall (p=·024), and information processing speed (p=·003) were significantly different between groups (large effect sizes), with significant declines after WBRT, but not after GKRS. Over 6 months, at the individual patient level, there were no declines in performances across all tests in the GKRS group (n=8) while performances declined in 4 out of 8 patients in the WBRT group.

The stopping rules were not met since the posterior probabilities did not cross the threshold. Other preliminary findings in this small sample suggest that cognitive decline, both at group and individual level, is more pronounced after WBRT compared to GKRS. Accrual is continued (NCT02953717; ZonMw 842003006).
Original languageEnglish
Pages (from-to)ii24-ii24
Issue numberSuppl 2
Publication statusPublished - 2022


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