Clinical outcomes and MRI-based neurotoxicity assessment of elderly primary CNS lymphoma
Hiroaki Nagashima1, Kazuhiro Tanaka1, Shunsuke Yamanishi1
1Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Background:
The optimal management of primary central nervous system lymphoma (PCNSL) in elderly patients remains challenging, as whole-brain radiotherapy (WBRT) is associated with substantial delayed neurotoxicity.
Methods:
We retrospectively analyzed 65 patients aged ≥ 65 years diagnosed with PCNSL between 2008 and 2024 who received either high-dose methotrexate (HD-MTX) followed by WBRT (n = 29) or R-MPV with or without WBRT (n = 36). Clinical characteristics, cerebrospinal fluid (CSF) biomarkers, treatment outcomes, and MRI-based ventricular volume-used as a surrogate for treatment-related neurotoxicity-were evaluated. White matter changes were additionally assessed using the Fazekas scale.
Results:
The median age was 72 years. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 32.8 and 38.2 months, respectively. WBRT was independently associated with inferior PFS and OS. Patients treated with R-MPV without WBRT achieved longer PFS (53.2 vs. 27.2 months) and superior OS (not reached vs. 35.9 months) compared with those receiving HD-MTX plus WBRT. MRI analysis demonstrated significantly greater ventricular enlargement in the WBRT group (14.6% vs. 2.9% per year; p < 0.001). Among WBRT-treated patients, elevated CSF IL-10 (>100 pg/mL) correlated with accelerated ventricular enlargement. Progression of white matter changes assessed by the Fazekas scale was also significantly greater in the WBRT group.
Conclusions:
In elderly PCNSL patients, R-MPV without routine WBRT provides effective disease control while being associated with less structural brain change. CSF IL-10 may represent a potential biomarker of susceptibility to treatment-related brain structural alterations.
