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

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 non-surgical 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 non-surgical 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.