Long-term cognitive deficits in pediatric low-grade glioma (LGG) survivors reflect pretreatment conditions-report from the German LGG studies

Thomas Traunwieser; Daniela Kandels; Franz Pauls; Torsten Pietsch; Monika Warmuth-Metz; Brigitte Bison; Juergen Krauss; Rolf-Dieter Kortmann; Beate Timmermann; Ulrich-Wilhelm Thomale; Peggy Luettich; Anne Neumann-Holbeck; Tanja Tischler; Pablo Hernáiz Driever; Olaf Witt; Astrid K Gnekow

doi:10.1093/noajnl/vdaa094

Long-term cognitive deficits in pediatric low-grade glioma (LGG) survivors reflect pretreatment conditions-report from the German LGG studies

Neurooncol Adv. 2020 Aug 8;2(1):vdaa094. doi: 10.1093/noajnl/vdaa094. eCollection 2020 Jan-Dec.

Authors

Thomas Traunwieser¹, Daniela Kandels¹, Franz Pauls², Torsten Pietsch³, Monika Warmuth-Metz⁴, Brigitte Bison⁴, Juergen Krauss⁵, Rolf-Dieter Kortmann⁶, Beate Timmermann⁷, Ulrich-Wilhelm Thomale⁸, Peggy Luettich⁹, Anne Neumann-Holbeck¹⁰, Tanja Tischler¹⁰, Pablo Hernáiz Driever¹¹, Olaf Witt⁹, Astrid K Gnekow¹

Affiliations

¹ Paediatrics and Adolescent Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.
² Department of Clinical Psychology, Helmut Schmidt University, Hamburg, Germany.
³ Institute of Neuropathology, DGNN Brain Tumor Reference Center, University Bonn, Bonn, Germany.
⁴ Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany.
⁵ Section of Pediatric Neurosurgery, University Hospital Wuerzburg, Wuerzburg, Germany.
⁶ Department of Radio-Oncology, University Leipzig, Leipzig, Germany.
⁷ Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), German Cancer Consortium (DKTK), Essen, Germany.
⁸ Pediatric Neurosurgery, Charité Universitaetsmedizin Berlin, Berlin, Germany.
⁹ Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) and Heidelberg University Hospital, Heidelberg, Germany.
¹⁰ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Pediatric Oncology/Hematology, Charité-Universitaetsmedizin Berlin, Corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Abstract

Background: Disease and treatment contribute to cognitive late effects following pediatric low-grade glioma (LGG). We analyzed prospectively collected neuropsychological data of German pediatric LGG survivors and focused on the impact of hydrocephalus at diagnosis, neurofibromatosis type 1 (NF1) status, and extent of surgery.

Methods: We used the Neuropsychological Basic Diagnostic screening tool based on the Cattell-Horn-Carroll model for intelligence and the concept of cross-battery assessment at 2 and 5 years from diagnosis for 316 patients from the German pediatric LGG study and LGG registry (7.1 years median age; 45 NF1; cerebral hemispheres 16%, supratentorial midline 39%, infratentorial 45%). Hydrocephalus was classified radiologically in 137 non-NF1 patients with infratentorial tumors (95/137 complete/subtotal resection).

Results: Patients with NF1 versus non-NF1 exhibited inferior verbal short-term memory and visual processing (P < .001-.021). In non-NF1 patients, infratentorial tumor site and complete/subtotal resection were associated with sequelae in visual processing, psychomotor speed, and processing speed (P < .001-.008). Non-NF1 patients without surgical tumor reduction and/or nonsurgical treatment experienced similar deficits. Degree of hydrocephalus at diagnosis had no further impact. Psychomotor and processing speed were impaired comparably following chemo-/radiotherapy (P < .001-.021). Pretreatment factors such as NF1 or tumor site were relevant at multivariate analysis.

Conclusions: All pediatric LGG survivors are at risk to experience long-term cognitive impairments in various domains. Even surgical only management of cerebellar LGG or no treatment at all, that is, biopsy only/radiological diagnosis did not protect cognitive function. Since pattern and extent of deficits are crucial to tailor rehabilitation, neuropsychological and quality of survival assessments should be mandatory in future LGG trials.

Keywords: hydrocephalus; neurofibromatosis; neuropsychology; pediatric low-grade glioma; resection.