Impact of chemotherapy on disseminated low‐grade glioma in children and adolescents: Report from the HIT‐LGG 1996 trial

BACKGROUND: We describe demographic data of disseminated childhood low-grade glioma (DLGG) prospectively recruited in the HIT-LGG 1996 study and evaluate the impact of primary chemotherapy (CT) on the outcome of these tumors, which have previously only been described in small and retrospective series. PATIENTS AND METHODS: The multicenter study HIT-LGG 1996 accrued 1181 children and adolescents with low-grade glioma. 61 patients (5.2%) had tumor dissemination, with 2.8% being present at diagnosis. Frequencies of dissemination for different subgroups were calculated. Efficiency of first-line CT with vincristine/carboplatin was defined in 24 children with dissemination prior to first-line non-surgical-treatment. RESULTS: Incidence of dissemination was high among infants (16%) with hypothalamic-chiasmatic-glioma (HCG) and diencephalic syndrome. A relevant percentage of HCG showed isolated spinal dissemination. CT achieved objective and overall response rates of 25% and 79% of the primary tumor and a similar response of disseminated lesions. Clinical stabilization or improvement could be achieved in the majority of patients during treatment. However, 20 of 24 patients experienced further progression and 5-year PFS was 6%. Dissemination prior to CT was a negative prognostic factor for PFS within the study (P = 0.005). Overall-survival of primary DLGG was inferior compared to LGG without dissemination at diagnosis (P < 0.001). CONCLUSION: Complete MRI scan should be a standard diagnostic procedure in young children with hypothalamic-chiasmatic tumors especially if presenting with diencephalic syndrome. Dissemination in childhood LGG relates to impaired PFS. CT delays progression for responders. Multicenter studies have to evaluate the efficacy of extended treatment strategies in DLGG to improve outcome.