Abstract BACKGROUND Pediatric diffuse midline gliomas (DMGs), H3 K27-altered, represent the 5-10% of all pediatric brain tumors. The preferential location is the brainstem (diffuse intrinsic pontine glioma, DIPG). Median overall survival is 11 months. In this study, we report about treatment and survival on one of the largest known single-institution cohort of DMGs. MATERIAL AND METHODS The study included patients between 3 and 22 years, affected with DMGs. Primary endpoint was the comparison of median progression-free survival (PFS) and overall survival (OS) in different front line treatment: group A (intravenous nimotuzumab- vinorelbine scheme) and group B (oral temozolomide) in combination with external beam radiotherapy (RT). The secondary endpoint was to assess the impact of reirradiation at first progression in the two cohorts. Nimotuzumab was administered at 150 mg/m2 weekly for 12 weeks and then every two weeks; vinorelbine was administered 20 mg/m2 weekly and then 25 mg/m2 every two weeks. Temozolomide was administered 75 mg/m2 during RT and then 150-200 mg/m2/day, 5 days/month in 28- day cycles. Focal radiotherapy was delivered at total dose of 54 Gy in first line and at 19 Gy at first progression. Response was evaluated based on radiological findings according to RAPNO criteria. Adverse events (AE) were evaluated in both groups according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 5.0 (CTC-AE5). RESULTS one hundred five patients (median age 9 years) were treated for DMG H3K27 altered in our institution between 2009 and 2024. First-line treatment, in the entire cohort (105 patients, 100%), involved focal radiotherapy; 86 patients (82%), group A, received concomitant first-line medical treatment with nimotuzumab vinorelbine, and the remaining 19 patients (18%), group B, were treated with temozolomide. Median OS and PFS were superposable between the two groups, specifying that 24 patients in group A were excluded from the analysis because enrolled in the ongoing trial. OS in group A was 14.6 months (range 4.8-57.8 months) vs 14.4 months in group B (range 1.9-115.6 months). The median PFS was 8 months (range 2.5-19.6 months) in group A and 8.2 months (range 1.9-93 months) in group B. An increase in the median OS was observed in group A versus group B (respectively 17.38 vs 10.9 months, p = 0.0004) in the reirradiation at first progression. Most common drug-related AEs were hematological with 10 events grade 4 in group B, while mostly of hematological toxicities were mild (grade 1-2) and no severe toxicity grade 4 was reported in group A. CONCLUSIONS Nimotuzumab-Vinorelbine scheme in an outdoor setting was well tolerated and had comparable efficacy in terms of median PFS and OS respect to the use of oral temozolomide in DMGs.
Cacchione et al. (Wed,) studied this question.