SPCR-02 NEUROCOGNITIVE FUNCTION IN PATIENTS WITH LEPTOMENINGEAL METASTASIS TREATED WITH PROTON CRANIOSPINAL IRRADIATION

Abstract

BACKGROUNDProton craniospinal irradiation (pCSI) as a potential treatment for patients with solid tumor leptomeningeal metastasis (LM) is being assessed in a phase II randomized study comparing it with photon involved-field radiotherapy (RT). We report the preliminary results of prospective neurocognitive function in a subset of patients treated with pCSI. METHODSPatients with LM and without evidence of CNS disease progression completed standardized neurocognitive tests of attention and working memory, executive function, and verbal memory at baseline (pre-pCSI), and 3 and 6 months post-pCSI. All patients received chemotherapy (baseline and follow up) and memantine (follow up). Means across the three timepoints were estimated for each neurocognitive test score using a linear mixed model (LMM) predicting the score by timepoint. Mean changes between pairs of timepoints were similarly estimated from the LMMs and tested for statistical significance using model-based contrasts. RESULTSBaseline, 3-month and 6-month neurocognitive data were available for 12, 11, and 8 patients, respectively. Linear mixed model analyses showed a significant decline in graphomotor speed (Trails A, p=0.03), verbal learning (HVLT-R Total Learning, p<0.001), and verbal recognition memory (HVLT-R Discrimination, p=0.03) from baseline to 3 months post-pCSI, with scores remaining stable at 6 months post-pCSI. There was a significant decline in timed set-shifting (Trails B, p=0.04) from baseline to 6 months post-pCSI. There were no significant changes in attention and working memory over the follow-up period. CONCLUSIONPreliminary results in a subset of patients showed a decline in graphomotor speed and verbal memory at 3 months and executive function at 6 months post-pCSI, possibly related to the early adverse effects of RT. These results are overall consistent with findings in other populations treated with whole-brain RT. However, there was no change in attention and working memory and most cognitive domains remained stable at six months with pCSI.