This is a retrospective study conducted on patients with OPG, aged less than 19 years, treated with bevacizumab as a single agent, since 2010 at IHOPe (Institute of Pediatric Hematology and Oncology). Efficacy of the treatment was evaluated on the tumor response rate on MRI with a centralized review basing upon RAPNO criteria and with visual assessment basing upon a 0.2 log change in the logMAR scale. Thirty-one patients with OPG have been included. From a radiological point of view, best anytime responses were: 1 major response, 6 partial responses, 7 minor responses and 14 stable diseases; achieving disease control in 28 (96%) out of 29 patients. Ophthalmological response was evaluated in 25 patients and disease control was achieved in 22 (88%) out of 25, with 14 steady states and 8 significant improvements. Among patients treated with chemotherapy after the bevacizumab course, nine relapsed and have been retreated with objective responses. Bevacizumab used as single agent seems effective in children and adolescents with OPG. Our work paves the way for a phase II study in which bevacizumab alone could be used as frontline therapy.

Cytomegalovirus (CMV) infection is a common complication in newborns with severe combined immunodeficiency (SCID). Prolonged antiviral treatment in immunocompromised patients increases the risk of the emergence of drug resistance. We analyzed drug resistance in a newborn with SCID who developed neonatal CMV infection. Sequencing of viral DNA polymerase (DP; UL54), protein kinase (UL97), and terminase (UL51, UL56, UL89) genes identified ganciclovir (GCV) and foscarnet (PFA) resistance mutations in blood, but not cerebrospinal fluid. After treatment was shifted to cidofovir and letermovir (LMV), a LMV resistance mutation rapidly emerged in UL56 (C325F). Eventually, a multidrug-resistant genotype was established (DP-V781I and UL56-C325F). Whole-genome sequencing of CMV in clinical blood samples showed an otherwise stable genotype. This case describes a CMV infection complicated by compartmentalization and the emergence of resistance to GCV, PFA, and LMV. It highlights the need for further investigation into alternative antiviral strategies for the prevention and treatment of CMV.

Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized by oncogenic fusions rather than multiple mutated genes. CNS pediatric tumors associated with oncogenic fusions represent a complex landscape of tumors with wide radiological, morphological and clinical heterogeneity. In the fifth CNS WHO classification, there are few pediatric CNS tumors for which diagnosis is based on a single oncogenic fusion. This work aims to provide an overview of the impact of rare oncogenic fusions (NTRK, ROS, ALK, MET, FGFR, RAF, MN1, BCOR and CIC genes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated with NTRK (n = 2), ROS (n = 1) and FGFR3 (n = 1) oncogenic fusion genes as a proof of concept. Cases presentation and literature review: The literature review and the cohort that we described here underline that most of these rare oncogenic fusions are not specific to a single morpho-molecular entity. Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. Conclusions: These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.

Background and Aims: During the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic, we developed a teleconsultation model and conducted a survey-based study with the aim to evaluate satisfaction and emotions of health workers (HWs), to assess the feasibility of teleconsultations, and to evaluate technical issues. Materials and Methods: This is a prospective monocentric exploratory study based on synchronous, video consultations between HWs and pediatric patients treated for blood or solid malignancies or blood benign diseases. Every HW completed an online survey which covered technical aspects, data concerning satisfaction, quality of the interaction with the patient, and emotions felt after the teleconsultation. A score was calculated for each aspect. Results: Eleven specialists participated in the study, and we selected 84 questionnaires. With a satisfaction rate of 74%, HWs felt mostly calm (80%), relaxed (70%), stress-free (69%), and relieved (65%). We calculated the following median scores: an overall satisfaction score of 6.67 (0 to 10), a global feeling score of 8.79 (3.33 to 10.00), and a quality score of 7.34 (2.50 to 10.00). A strong correlation between the quality of teleconsultation and the satisfaction of the HWs has been highlighted (r=0.588). Conclusion: Our series is an encouragingly positive experience from the perspective of the HWs, their feelings, and perceptions.

Background: Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare pediatric central nervous system tumors, first recognized in the 2016 WHO classification. Their clinical course is highly heterogeneous, and no international consensus treatment guidelines are currently available. This study aims to describe clinical characteristics, disease evolution, and management strategies for pediatric DLGNT patients, with a focus on aggressive forms. Methods: This retrospective, multicenter, international study (Belgium and France) included pediatric patients diagnosed with DLGNT between 1 February 2016 and 31 December 2024. Clinical, radiological, histopathological, molecular, and therapeutic data were collected. Findings were analyzed and contextualized through an extensive literature review. Results: Eleven patients were enrolled (median age: 8.2 years; median follow-up: 52 months). The median delay between the first MRI and definitive diagnosis was 6.5 months. Symptoms of intracranially elevated pressure were present in 55% of patients. Two-thirds of the patients presented with leptomeningeal dissemination at diagnosis. The primary tumor site could not be identified in two patients. A KIAA1549::BRAF transcript fusion was detected in 82% of cases, and chromosome 1q gain in 38%. All patients underwent surgery at diagnosis. The median number of therapeutic lines was four: 82% received chemotherapy (weekly vinblastine in 55%, vincristine/carboplatin regimen in 45%), 64% received MAPK pathway-targeted therapy, and 18% underwent radiotherapy. Five-year overall survival (OS) was 68.5%, and median progression-free survival (PFS) was 5.3 months after first-line therapy and 16.5 months after the second line. At the end of follow-up, only one patient achieved complete remission, and 78% of survivors presented with persistent neurological deficits. Conclusions: This study underscores the significant diagnostic delay, clinical heterogeneity, and absence of standardized therapeutic approaches in pediatric DLGNT patients. Conventional low-grade glioma chemotherapy constitutes the current treatment backbone, while MAPK pathway-targeted therapies show promising potential. Further studies and the establishment of an international registry are crucial to better characterize aggressive subtypes and optimize management strategies.