Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy

Abstract

High-dose chemotherapy and whole brain radiotherapy (WBRT) can prolong survival in primary CNS lymphoma (PCNSL) patients, but is often associated with clinically significant cognitive decline. In this study we assessed neuropsychological functioning prospectively in newly diagnosed PCNSL patients treated with induction chemotherapy followed by reduced-dose WBRT. Twelve patients underwent neuropsychological evaluations at diagnosis, after induction chemotherapy, and 6 and 12 months after WBRT. Nine patients completed additional cognitive evaluations 18 and 24 months post-treatment. At diagnosis, patients had impairments in Executive Functions, Verbal Memory, and Motor Speed. There was a significant improvement in Executive Functions (P < 0.01) and Verbal Memory (P < 0.05) following induction chemotherapy, and scores remained relatively stable up to 12 months post-treatment. Among the nine patients who completed a 2-year follow-up, there was a significant improvement in the Executive domain (P < 0.05) and a trend toward a decline in the Verbal Memory domain. Executive and Verbal Memory functions improved following induction chemotherapy, likely due to decreased tumor burden and discontinuation of corticosteroid and anticonvulsant medications. There was no significant cognitive decline up to 24 months post-chemotherapy and reduced-dose WBRT in this group of PCNSL patients, however, difficulties in Verbal Memory and Motor speed persisted over the follow-up period.

Fig. 1

Executive, Verbal Memory, and Motor Domain Scores at Baseline and Follow-up. T1 = Pre-Treatment (n = 12); T2 = post-induction chemotherapy (n = 12); T3 = 6 months Post-RT ± ARA-C (n = 12), T4 = 12 months Post-RT ± ARA-C (n = 12), T5 = 18 months Post-RT ± ARA-C (n = 9), T6 = 24 months Post-RT ± ARA-C (n = 9). Mean z score ± SEM. ** Time 1-Time 2 and Time 3-Time 6 (Executive), P < 0.01.* Time 1-Time 2 (Memory), P < 0.05

Fig. 2

Cognitive Test Performance by White Matter Grade for patients who completed all follow-ups (n = 9). (0–1) = no/minima white matter change; (2–3) = white matter confluence. T1 = baseline; T2 = post-induction chemotherapy; T3 = 6 months Post-RT ± ARA-C; T4 = 12 months Post-RT ± ARA-C; T5 = 18 l months Post-RT ± ARA-C, T6 = 24 months Post-RT ± ARA-C.Values plotted represent mean z score ± SEM