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QOL-10. Treatment-induced leukoencephalopathy in pediatric medulloblastoma survivors and its impact on long-term neurocognitive functioning

2022; Oxford University Press; Volume: 24; Issue: Supplement_1 Linguagem: Inglês

10.1093/neuonc/noac079.493

1523-5866

Lukas Wägner, Brigitte Bison, Anne Neumann‐Holbeck, T. Tischler, Anika Guiard, Denise Obrecht, Holger Ottensmeier, Rolf‐Dieter Kortmann, Katja von Hoff, Paul‐Gerhardt Schlegel, Marc Remke, Antje Redlich, Ursula Holzer, Claudia Blattmann, Gudrun Fleischhack, Annette Sander, Norbert Jorch, Martina Becker, Michael Karremann, Michael C. Frühwald, Miriam van Buiren, Nina Struve, Monika Warmuth‐Metz, Stefan Rutkowski, Martin Mynarek,

Cancer-related cognitive impairment studies

Abstract OBJECTIVES: Leukoencephalopathy (LEP, i.e. white matter T2-/FLAIR-hyperintensities on MRI) and impaired neuropsychological outcome are side effects of multimodal therapy of medulloblastoma. We identified risk factors for LEP and correlated LEP with neurocognitive functioning. PATIENTS AND METHODS: Severity of LEP either at the end of therapy (n=118), two years (n=126), or five years after surgery (n=139) was evaluated according to an adapted Fazekas classification for 162 survivors of medulloblastoma (median age: 7.4 years [range:0.67-19.8 years]). Severity of LEP two or five years after surgery was correlated with treatment and neurocognitive functioning ≥ five years after diagnosis using univariate analyses and multivariate generalized mixed linear models. RESULTS: Two and five years after surgery, incidences of mild/moderate/severe LEP were 21.4%/17.5%/9.5%, and 24.5%/23.7%/8.6%, respectively. Data on severity of LEP both at the end of therapy and five years after surgery was available for 103 patients: LEP grades increased for 1/2 degrees in 18/4 patients and decreased in 13/1 patients, respectively. Both treatment approaches - HIT-SKK chemotherapy including intraventricular methotrexate (SKK) and craniospinal irradiation (CSI) - were associated with increased severity of LEP (CSI+SKK > SKK only > CSI only; p<0.001). Severe LEP only occurred in patients treated with both CSI and SKK. In total 19% of all patients treated with this combination developed severe LEP. Severe LEP correlated with impaired fluid (p=0.013) and crystalline (p=0.012) intelligence and short-term memory (p=0.024) on both univariate level and in multivariate mixed linear models. Among patients treated with CSI doses >30Gy, severe LEP, but not SKK including intraventricular MTX, correlated with impaired neurocognitive functioning. CONCLUSION: After therapy strong changes in LEP rarely occurred. Severe LEP was associated both with the combination of SKK and CSI, and impaired neurocognitive functioning. Further research will be needed to weigh potential benefits of SKK including intraventricular methotrexate with CSI against its neurotoxicity.