Thomas Perwein1, Martin Benesch1, Daniela Kandels2, Torsten Pietsch3, René Schmidt4, Franz Quehenberger5, Brigitte Bison6, Monika Warmuth-Metz6, Beate Timmermann7, Jürgen Krauss8, Ulrich-Wilhelm Thomale9, Rolf-Dieter Kortmann10, Pablo Hernáiz Driever11, Astrid Katharina Gnekow2. 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.
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.
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