Due to rarity and variability in pediatric tumors presentation, robotic oncologic surgery remains a challenging field. This study analyses clinical features that can impact outcomes of robotic excision of neuroblastic tumors (pNBTs) in children. Retrospective cohort of children who underwent robotic resection of pNBTs between 2020 and 2025. Exclusion criteria: biopsy only, follow-up ≤ 6 months. Forty-four children included, 24 girls (54.5

We report a case of hepatosplenic candidiasis (HSC) in a neutropenic child with ovarian teratoma. Using high-frequency ultrasonography, we detected subtle hypoechoic pseudonodules in the spleen during profound neutropenia (ANC 30/μL), challenging the dogma that lesions only appear after immune recovery. These precursors evolved into classic ''bull's-eye'' lesions. Candida tropicalis was confirmed via splenectomy. This case highlights high-frequency ultrasound's role in early HSC diagnosis before neutrophil recovery.

Congenital sacrococcygeal teratomas (SCTs) are rare tumors with highly variable prognosis, influenced by associated abnormalities and marked histological heterogeneity. SCTs may exhibit somatic renal differentiation, encompassing a wide spectrum of cytological and architectural features, for which accepted diagnostic criteria are lacking. This renders the distinction between immature nephrogenic tissue and true nephroblastoma particularly challenging. We report an illustrative neonatal case of SCT containing a minor nephroblastomatous component and conducted a systematic review to evaluate management and outcomes in newborns (≤28 days old) with renal tissue identified within SCTs. A comprehensive search of PubMed, Scopus, and Web of Science yielded 532 records, of which 16 studies met inclusion criteria. Including the present case, 19 newborns were analyzed. Renal tissue was described as immature or ectopic nephrogenic tissue in 15 cases (79%) and as overtly malignant, consistent with Wilms tumor, in 4 cases (21%). All patients underwent surgical resection, while chemotherapy (n = 5; 26.3%) and radiotherapy (n = 2; 10.5%) were less frequently administered. Median follow-up was 29.5 months (range: 4-154), with no cancer-related mortality. In the absence of standardized diagnostic criteria, renal differentiation within SCTs represents a diagnostic and therapeutic dilemma, supporting a cautious, multidisciplinary management approach.

Neuroblastoma is the most common extracranial solid tumour in childhood. Although minimally invasive surgery (MIS) is increasingly used in selected patients with neuroblastic tumours, comparative data between robot-assisted and conventional MIS are lacking. A single-centre retrospective study was conducted on 84 patients who underwent minimally invasive resection of neuroblastic tumours between 2008 and 2025. Patients were divided into conventional MIS and robot-assisted surgery groups. Demographic data, tumour characteristics and surgical and oncological outcomes were compared. The robot-assisted group included a higher number of patients with Image-Defined Risk Factor (IDRF) ≥ 1 (57

Abstract Background: PREME (PeRsonalizEdMEdicine) program is an Italian, multicentric, prospective study focused on research of possible molecular therapeutic targets for early and relapsed/refractory neuroblastoma (NB). Methods: From 2019 to 2024, 86 patients were enrolled out of 106 eligible. Molecular alterations (MA) were detected by whole-exome-sequencing (WES) and by Cancer Gene Panel (CGP) sequencing. Somatic Point Mutations (SPM) were classified as either Very-High-Priority (VHP) or High-Priority (HP). Results: MA, including somatic, germline or copy-number-variations (CNVs): 9 were detected at first diagnosis and 43 at relapse. Specifically, SPM were detected in 94% of patients (n=49), 9 at disease-onset and 40 at relapse. Around 35% (n=17) had VHP alterations, 43% (n=21) HP and 22% (n=11) both. Samples from 11 patients were analyzed at different times during the course of disease: first diagnosis and relapse (n=3), primary and further relapses (n=8); in 9 of those, assessment of molecular tumor changes were detected. An actionable target emerged in 75.5% of patients with SPM (n= 37). A molecular target-therapy was proposed by the study-expert-board, which was implemented in 21 patients. ALK was the most frequent mutated gene (43%), but other potentially actionable alterations were detected, both in tumor at first diagnosis and at relapse. Among tumor samples at relapse, from WES analysis emerged alterations in gene encoding for mitogen-activated protein kinase (MAPK; 12% of cases), ATM mutation (4%), in gene encoding for proteasome subunit member proteins (PSMC/B; 6%) and other less common SPMs, such as CULA4, TP53, TNKS, PIK3R1, mTOR, and ATR mutations in 6 corresponding patients. Targeted-therapy was implemented in 11 patients with ALK mutations, in 2 patients with MAPK alterations, in one patient with PSMC/B mutation, in one patient with ATM mutation and in those 6 patients harboring the less common SPMs. Generally, among all patients treated, a complete remission was obtained in 3 patients, a partial response in 13, and stable disease as best response in 2 cases. A progression disease and subsequent death occurred in 3 patients. Somatic CNVs were detected in 31 patients (59.61%); among them, 3 patients showed no SPM and a targeted-therapy potentially actionable somatic CNVs was proposed for one of those harboring TSC2-deletion. Germline alterations were found in 19.2% of patients (n=10). Conclusions: PREME program is a useful tool to improve the prognosis of refractory/relapsing NB. Citation Format: Francesca Parisi, Eleonora Ciampi, Veronica Bensa, Federica Serafino, Matilde Tirelli, Laura De Rosa, Vito A. Lasorsa, Mario Capasso, Chiara Brignole, Loredana Amoroso, Massimo Conte, Mirco Ponzoni, Fabio Pastorino. Clinical impact of the personalized medicine for neuroblastoma patients: Six years of experience of the PREME program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2520.

Background: Neuroblastoma is the most common embryonal cancer. Since several population-based studies in Europe have revealed differences in 5-year survival across countries and regions. Objectives: We principally investigated the impact of stage at diagnosis on survival in Italy. Methods: Data were obtained from 26 population-based cancer registries (PBCRs), covering 319 cases (ages 0-14) diagnosed between 2013 and 2017, representing about 80% of the national population. Stage was classified according to the Toronto guidelines. Information on treatment and treating hospitals was also collected. Stage at diagnosis was further refined using probabilistic linkage with the Italian Neuroblastoma Registry (RINB). Results: Overall survival (OS), defined as all-cause mortality, was estimated using the Kaplan-Meier method. Most patients presented with stage M disease (37%), while a small proportion remained unclassified (2%). Three-year survival analysis showed significant differences between stages, ranging from >95% in localised (stage I) and MS stages to 78% in stage M (stage IV). No significant disparity across the Italian regions was observed in stage distribution or survival. Surgery and radiotherapy treatments of neuroblastoma were mostly centralized in the Centre and North of Italy. However, the cross-regional health migration from the South was limited to, and interpreted as appropriate for, high-volume centres. Conclusions: This population-based study highlights the high quality of care provided to children with neuroblastoma by an effective national clinical network. Compared with previous studies, we observed very limited variation across regions. A national childhood cancer registry remains essential to obtain a comprehensive picture of the country.

Background/Objectives: Despite overall excellent outcomes for Wilms tumour, regional variations in stage at diagnosis and care pathways remain a concern across Europe. We evaluated stage distribution, three-year survival, and treatment patterns in Italy, considering hospital care as a proxy for healthcare capacity and migration. Methods: Data were obtained from 26 population-based cancer registries (PBCRs), covering 148 patients (ages 0-14) diagnosed between 2013 and 2017, representing about 80% of the Italian population. Stage was classified according to the Toronto guidelines. Information on treatment and diagnosed/treating hospitals was collected. Stage at diagnosis was further refined using probabilistic linkage with the clinical registry 1.01 Model. Overall survival, defined as all-cause mortality, was estimated using the Kaplan-Meier method. Results: Most patients presented with localized disease (77%), 32% Stage I, while 19% were Stage IV. Three-year survival analysis showed significant differences between stages, ranging from 98% in patients with Stage I to 78% in the ones with Stage IV. No significant disparity across the Italian regions was observed in stage distribution or survival. Diagnoses and treatments were mostly (>90%) centralized in the same region for patients residing in the Centre or North of Italy. However, the cross-regional health migration from the South was of about 30% for diagnosis and larger for treatments. Conclusions: This study shows that standardized staging improves data comparability and highlights challenges in managing metastatic cases and regional care pathways. The results support the use of clinical and PBCR information to interpret survival patterns and guide improvements in paediatric oncology care.

[This corrects the article DOI: 10.1016/j.mmcr.2026.100777.].

BACKGROUND:Severe infections are a leading cause of morbidity and mortality in pediatric oncology, especially among children receiving high-dose chemotherapy. High-risk neuroblastoma (HR-NB) provides a paradigmatic model of prolonged multimodal treatment, yet recent data describing the burden and timing of severe infections during its therapeutic course are limited. PROCEDURE:We retrospectively reviewed 184 consecutive HR-NB patients diagnosed and treated at the IRCCS Istituto Giannina Gaslini (Genoa, Italy) according to the SIOPEN/HR-NBL1 protocol between 2002 and 2021. Severe infectious events were defined as bloodstream infections (BSI) and invasive fungal diseases (IFDs) according to international criteria. Incidence rates per 100 patient-days at risk (pdr) and phase-specific distributions (induction, consolidation, maintenance) were analyzed. RESULTS:Over 80,202 patient-days at risk, 104 severe infections were recorded (cumulative incidence 56.5%). BSI represented 93.3% of events, predominantly Gram-positive (55.8%) and Gram-negative (37.5%) pathogens; 6.7% were IFDs. The induction phase accounted for the highest incidence, while consolidation (hematopoietic stem cell transplantation) showed the highest infection rate per pdr. Approximately 70% of BSI occurred in non-neutropenic patients and were central venous catheter (CVC) related; in neutropenic cases (30%), half were CVC associated. Infection-related mortality was 1.1% (two out of 184). CONCLUSIONS:Severe infections remain frequent and clinically significant complications in HR-NB therapy, though infection-related mortality was low. The low incidence of IFDs despite the absence of systematic prophylaxis suggests potential optimization of preventive strategies. These data provide an epidemiologic benchmark for infection risk in the era of immunotherapy and CAR-T approaches for solid tumors.

A previously healthy three-year-old girl presented with persistent diarrhoea, progressive abdominal distension and weight loss. After negative infectious and anatomical workup, abdominal imaging (ultrasound, MRI and CT) revealed a retroperitoneal mass consistent with neuroblastoma (NB), confirmed by image-guided biopsy. Urinary catecholamines were markedly elevated. Following initial chemotherapy, worsening symptoms and refractory diarrhoea prompted surgical resection of the tumour. The diarrhoea was attributed to vasoactive intestinal peptide (VIP) secretion, a rare presentation in NB. Postoperative recovery was uneventful, with clinical and radiologic remission at six months. This case highlights the need to consider NB in chronic paediatric diarrhoea and supports surgery as the treatment of choice in VIP-secreting tumours.

PURPOSE:Patients with high-risk neuroblastoma (HR NB) frequently present with metastases in the bone marrow and bone. Approximately 15% of these patients are refractory to induction therapy, and 50% relapse. Dinutuximab beta is an anti-GD2 monoclonal antibody approved in Europe for maintenance therapy of pediatric patients with HR NB. Immunotherapy with anti-GD2 antibodies improves the survival of children with HR NB and relapsed or refractory disease. It is associated with adverse events, such as pain, fever, allergic reactions, capillary leak syndrome, and diarrhea. This manuscript aims to propose a practical guide in support and prevention treatment of adverse events. METHODS:MEDLINE was searched using the terms "GD2," "ch14.18/CHO," "anti-GD2 antibody," "dinutuximab beta," and "neuroblastoma." The experts reappraised available evidence discussing different clinical Italian experiences. RESULTS:Neuropathic pain is the main toxicity associated with dinutuximab beta and can be prevented with analgesics, including intravenous opioids and gabapentin by mouth. The intensity of the supportive treatment decreases from course to course. CONCLUSION:In the experience of the authors, adverse events associated with dinutuximab beta may be prevented and managed in experienced centers. The supportive therapy may be reduced after the first cycle to improve the quality of life.

Background: Risk assessment at diagnosis is crucial for neuroblastoma (NB) in order to address patients at highrisk to the most timely and appropriate treatments. 3-O-methyldopa (3-OMD), a direct metabolite of L-Dopa, is a promising biomarker of NB at diagnosis able to stratify high-risk patients. Methods: We show the development and validation of a method for measuring 3-OMD from dried plasma samples (DPS) and plasma using liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) on a Thermo Fisher Scientific Orbitrap Exploris 120. Results: The method was accurate and reproducible in the range 7.8-4000 ng/mL, from small amounts (50 mL) of plasma and DPS (obtained starting from 30 mL plasma). 3-OMD concentrations measured in plasma and DPS were highly correlated (R = 0.99 95 %CI 0.993-0.996). Differences of 3-OMD levels across stages L1 and M and L1 and L2 (p-value < 0.05) were statistically significant. Receiving Operator Curve (ROC) analysis showed that 3OMD was able to discriminate patients at high-risk with high sensitivity and specificity both from plasma or DPS (AUC = 0.8295 %CI 0.71-0.94, P < 0.0001). Conclusions: 3-OMD is confirmed as an interesting biomarker of high-risk NB. The described method is an added value for further prospective studies involving multiple sites. The stability of 3-OMD in DPS allows for easy shipment and storage at room temperature.

To outline the long-term neuropsychological profile of a pediatric cohort with Opsoclonus-Myoclonus-Ataxia Syndrome (OMAS), and evaluate whether volumetric brain abnormalities correlate with clinical findings years after onset. Twelve patients diagnosed with OMAS between 2008 and 2020 (6 males, mean age 9.6 years, median follow-up 5.4 years) underwent a videorecorded neurological examination and a standardized cognitive and neuropsychological assessment. Patients and 12 age-matched controls underwent advanced 3-Tesla brain MRI studies. Voxel-Based Morphometry (VBM) and targeted cerebellar evaluation using ACAPULCO and ENIGMA pipelines were performed. The results were correlated with neuropsychological scores. Nine subjects (75

Background GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.Methods Thirty microliters of peripheral blood (PB) plasma samples from 83 children with NB at diagnosis and 83 age-matched healthy controls were analyzed by LC-MS/MS. From stage M patients, 29 additional PB plasma samples were collected after induction therapy, 7 before and after immunotherapy, and 6 at relapse. For 22 stage M patients, bone marrow (BM) plasma samples were also collected at diagnosis.Results C18 and C20 GD2 concentrations were significantly higher in children with NB than in controls. Receiver operating characteristic (ROC) analysis showed a cut-point of 44.1 and 0.47 nM for C18 and C20, respectively, able to discriminate with high specificity and sensitivity in patients with NB from controls. Circulating C18 and C20 levels in PB strongly correlated with those in BM. At diagnosis, C18 and C20 GD2 concentrations were significantly higher in stage M, deceased patients, and in those bearing tumors with MYCN amplification. ROC analysis identified prognostic cut points for the whole population, whereas only C20 concentrations above the cut points were significantly associated with a worse event-free survival of patients with stage M disease or with MYCN-amplified tumors. C18 and C20 plasma concentrations strongly decreased during treatment but increased at relapse.Conclusions Measurement of circulating GD2 seems to have prognostic power in the subsets of patients with stage M disease and with MYCN-amplified tumors, and be able to early detect relapse, thus its ability to monitor disease should be prospectively evaluated in future studies.

Denosumab is a human monoclonal antibody approved by the Food and Drug Administration in 2013 for use in adults with inoperable giant cell tumor of bone (GCTB). In children, it is used as an off-label drug in some giant cell-rich tumors of bone (GCRTB) and giant cell granuloma (GCG). The aim of the study is to evaluate the efficacy and acute toxicity of denosumab in children. From February 2022 to December 2023, at the Istituto Giannina Gaslini, 5 patients were treated with denosumab, 2 females and 3 males. Age ranged from 8 to 17 years. Two had ABC (hemipelvis and D9), and 3 had GCG (sphenoid, jaw, and maxilla). An assay of calcium and vitamin D as well as a dental scan was performed before administering denosumab due to possible side effects such as hypocalcemia and jaw osteonecrosis. Therapy was given subcutaneously at the dose of 70 mg/m2 (weight < 50 kg) or 120 mg (weight > 50 kg) at days +1, +8, +15, +28, and then monthly for 3-5 months, followed by imaging evaluation. Overall, 21 doses were administered to Patient 1, 20 doses to Patient 2, 11 doses to Patient 3, 10 doses to Patient 4, and 9 doses to Patient 5. Calcium carbonate and vitamin D were given as supportive therapy. We observed lesion volume reduction in 4 patients and radiological stability in 1 patient. Surgery was possible in 1 case thanks to the significant reduction of lesion size. A longer administration over 22 months was safe and well tolerated. No disease progression or side effects were observed. This study confirms literature data about the use of denosumab in inoperable GCRTB. These results are preliminary; further studies are necessary on a larger series of cases, with a longer follow-up (3-5 years), with data collection even from other pediatric centers.

Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of children, responsible for 15% of childhood cancer deaths. Recently, cell surface Nucleolin (NCL) was suggested as a target for NB therapy and its expression at RNA level was validated as an independent (adjusting for age, INSS stage, and MYCN status) prognostic marker for NB. Extracellular vesicles (EVs) may express different surface proteins derived from the parental cells. Liquid biopsy-derived EVs from NB patients might reveal a possible diagnostic/prognostic role of NCL at the protein level. Here we evaluated the expression of small EVs (sEVs)-derived NCL in the peripheral bloods (PB) of low risk- (LR) and high risk- (HR) NB patients at onset and in relapse, and of aged-matched controls (CTRs). PB were firstly centrifuged at 400 g for 10 min at 4°C, then the supernatant was re-centrifuged at 1600 g for 10 min at 4°C to collect plasma. Isolation of EVs was performed from 500 μl of plasma through ultracentrifugation at 20.000 g to remove large EVs and secondly at 100.000 g to isolate sEVs. sEVs were characterized in term of size distribution by using Nano Traking Analysis (NTA). Twenty μg of sEVs-derived proteins were used in Western Blot analysis to evaluate the expression of the EVs markers as well as NCL. The isolated CD63- and CD9-expressing sEVs range in size between 81.6 and 138.7 nm. Interestingly, particles concentration results significantly higher in the PB derived from HR-NB, both at onset and at relapse, compared to that from both CTR and LR-NB patients. Furthermore, we have found a higher NCL protein expression on sEVs derived from the PB of all NB patients, compared to that derived from CTR. Noteworthy, NCL expression results significantly higher in the sEVs derived from HR-NB patients at onset, compared to that observed in LR-HR patients, suggesting a potential prognostic value of sEVs-derived NCL in clinic. The extracellular vesicles-derived protein nucleolin in the peripheral blood of patients may represent a prognostic factor for neuroblastoma. AIRC IG n. 24397 to PF Veronica Bensa, Danilo Marimpietri, Martina Morini, Martina Ardito, Eleonora Ciampi, Martina Fragola, Massimo Conte, Alberto Garaventa, Joao N. Moreira, Xhuliana Kajana, Alessandro Garbarino, Gino Tripodi, Roberto Bandettini, Giovanni Candiano, Mirco Ponzoni, Chiara Brignole, Fabio Pastorino. Extracellular vesicles-derived nucleolin as a novel biomarker in neuroblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6561.

BACKGROUND:Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor in childhood, causing 15 % of cancer mortality. We recently demonstrated that cell surface nucleolin (NCL) represents a novel cellular target for preclinical therapy against NB cell lines. METHODS:NB cells derived from i) infiltrated bone marrow (BM; 132 patients, 85 at onset, 47 relapsed/refractory); ii) NB tumor tissues from 11 relapsed/refractory NB patients; iii) murine generations of 9 patient-derived xenografts (PDX) were evaluated for cell surface NCL expression by flow cytometry and immunohistochemistry analyses. The antitumor efficacy of a liposomal formulation of doxorubicin (DXR) functionalized with the F3 peptide-recognizing NCL (F3-lipo[DXR]) was tested towards patient-derived multicellular tumor spheroids (MCTS) and PDX models of NB. RESULTS:About 60 % of BM-infiltrating NB cells and NB cells derived from tumor biopsies, and about 80 % of NB cells derived from PDX expressed cell surface NCL. In vitro, F3-lipo[DXR] resulted significantly more effective in terms of reducing cell viability of all the patient-derived MCTS models used, compared to the untargeted liposomal formulation (lipo[DXR]). In the in vivo PDX models, F3-lipo[DXR] significantly delayed tumor growth, induced tumor cells apoptosis and partly reduced the tumor vasculature. Furthermore, in a PDX model harboring the ALK mutation p.F1174L, the administration of the anti-ALK inhibitor crizotinib significantly increased the antitumor efficacy of F3-lipo[DXR]. CONCLUSION:Our results confirm that cell surface NCL is a biomarker and a potential target for NB, paving the way for further investigations aimed at the future clinical translation of innovative combination strategies against NB.