High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group

Thomas Perwein; Martin Benesch; Daniela Kandels; Torsten Pietsch; René Schmidt; Franz Quehenberger; Brigitte Bison; Monika Warmuth-Metz; Beate Timmermann; Jürgen Krauss; Ulrich-Wilhelm Thomale; Rolf-Dieter Kortmann; Pablo Hernáiz Driever; Astrid Katharina Gnekow

doi:10.1093/neuonc/noaa296

High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group

Neuro Oncol. 2021 Jul 1;23(7):1148-1162. doi: 10.1093/neuonc/noaa296.

Authors

Affiliations

¹ Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
² Swabian Children's Cancer Center, University Hospital Augsburg, Augsburg, Germany.
³ Institute of Neuropathology, Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), University of Bonn, Bonn, Germany.
⁴ Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
⁵ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
⁶ Institute of Diagnostic and Interventional Neuroradiology, University of Würzburg, Würzburg, Germany.
⁷ West German Proton Therapy Center Essen/Clinic for Particle Therapy, Essen University Hospital, Essen, Germany.
⁸ Section of Pediatric Neurosurgery, University Hospital Würzburg, Würzburg, Germany.
⁹ Pediatric Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Department of Radio-Oncology, University of Leipzig, Leipzig, Germany.
¹¹ Department of Pediatric Oncology/Hematology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Abstract

Background: Knowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.

Methods: We analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).

Results: Spinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.

Conclusions: The majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.

Keywords: children; low-grade gliomas; spinal cord glioma; surgery; therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / genetics
Brain Neoplasms* / therapy
Child
Disease Progression
Glioma* / genetics
Glioma* / therapy
Humans
Prospective Studies
Spinal Cord