GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma.

BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. METHODS: In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01). RESULTS: A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×106 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×106 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively. CONCLUSIONS: The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT03373097.).

Pediatric BCOR-Altered Tumors From Soft Tissue/Kidney Display Specific DNA Methylation Profiles.

In the pediatric population, BCL6-correpresor gene (BCOR)-upregulated tumors include primitive myxoid mesenchymal tumors/undifferentiated sarcomas (PMMTI/UND), clear cell sarcomas of the kidney (CCSK), and high-grade neuroepithelial tumors (HG-NET). We investigated DNA methylation (DNAm) and copy number variation (CNV) profiling in these tumors (N = 34) using an Illumina EPIC BeadChip to better define the potential use of these tools to confirm diagnosis and predict outcomes. Twenty-seven tumors from 25 patients (age range, 0-10 years), showed molecular confirmation of genetic abnormalities as follows: BCOR internal tandem duplication in 14 PMMTI/UND, 8 CCSK, and 3 HG-NET and YWHAE fusions in 2 PMMTI/UND. The remaining 7 cases lacking informative molecular data were analyzed by immunophenotyping and were included in the study as a training cohort, clearly separated from the main study group. These were 4 PMMTI, 1 HG-NET, and 1 CCSK in which poor RNA preservation precluded the confirmation of BCOR rearrangements and 1 CCSK in which no rearrangements were found. DNAm data were compared with those of brain tumor and/or sarcoma classifier. Differentially methylated regions (DMRs) were analyzed in the 3 groups. Twenty-two cases of the 24 molecularly confirmed PMMTI/UND and CCSK and 3 of 6 of those with only immunophenotyping were classified within the methylation class "BCOR-altered sarcoma family" with optimal calibrated scores. PMMTI/UND and CCSK showed similar methylation profiles, whereas thousands of DMRs and significantly enriched pathways were evident between soft tissue/kidney tumors and HG-NET. The CNV analysis showed an overall flat profile in 19 of the 31 evaluable tumors (8/10 CCSK; 9/18 PMMTI/UND; 2/4 HG-NET). The most frequent CNVs were 1q gain and 9p and 10q loss. Follow-up time data were available for 20 patients: ≥2 CNV significantly correlated with a worse overall survival rate. In conclusion, soft tissue and kidney BCOR sarcomas matched with BCOR-altered sarcoma methylation class, whereas those from the brain matched with the central nervous system tumor classifier HG-NET BCOR, supporting the notion that DNAm profiling is an informative diagnostic tool. CNV alterations were associated with a more aggressive clinical behavior.

Factors possibly affecting prognosis in children with Wilms' tumor diagnosed before 24 months of age: A report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) Wilms Tumor Working Group.

BACKGROUND: Children with Wilms' tumor (WT) aged under 24 months (infants) have a better prognosis than older patients. Our aim was to study the epidemiology of this age group, with focus on the modality of diagnosis, tumor size, and association with malformations/syndromes, seeking to understand if any of these factors might be related to prognosis. PATIENTS AND METHODS: Infants diagnosed with WT between 2003 and February 2010 were evaluated. A query form was used to collect data on the modality of WT diagnosis (symptomatic or incidental), tumor volume, maximum diameter, site, and stage. RESULTS: Data were collected for 117 of 124 WT infants registered. Twenty-four cases had an incidental diagnosis (ID) of renal mass, usually arising from an abdominal ultrasound performed for other reasons, and 93 had been diagnosed based on clinical signs/symptoms. The incidental cohort displayed unifocal disease, mean tumor diameter 5.52 cm, mean tumor volume 84.30 ml, and 14 patients showed associated malformations. Symptomatic patients had mean maximum tumor diameter of 10.18 cm, mean tumor volume of 451.18 ml, and six had associated malformations. CONCLUSIONS: Our study showed that 20% of the infants had an ID of WT; they had a relatively smaller nonmetastatic tumor and a higher rate of malformations than infants of the symptomatically diagnosed group, but we did not detect any difference in age at diagnosis between the two groups. Conversely, we found a significant difference in the 5-year event-free survival rate (P = 0.018) between infants under 1 year (96%), more frequently associated with congenital malformations, and infants 1-2 years (80%).

NRAS(Q61K) mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications.

BACKGROUND: Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. CASE PRESENTATION: A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF(V600E), GNAQ(Q209) and GNA11(Q209) mutations but the presence of a NRAS(Q61K) mutation. CONCLUSIONS: Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS(Q61K) mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study molecular profile. Further molecular profiling and preclinical models will be pivotal in testing combination of target therapy to treat this challenging disease.

Transient global ventricular dysfunction in an adolescent affected by pancreatic adenocarcinoma.

BACKGROUND: Takotsubo cardiomyopathy (TC) is characterized by a transient decrease in ejection fraction and a reversible left ventricular dysfunction. The pathophysiology of TC is not completely understood. Heterogeneous and multifactorial mechanisms are involved: drugs, emotional and physical stress, genetic and hormonal factors. CASE PRESENTATION: A 17 year-old male with metastatic pancreatic adenocarcinoma, under chemotherapy containing 5-fluorouracil, presented severe left ventricular dysfunction requiring mechanical ventilation and inotropes administration. He completely recovered in 2 weeks. CONCLUSION: To our knowledge this is the first report of transient form of ventricular dysfunction, mimicking TC, in an adolescent. We believe that children and adolescents receiving 5-fluorouracil should be closely monitored and referred for investigation if they develop cardiac symptoms.

Widening the spectrum of players affected by genetic changes in Wilms tumor relapse.

Few studies investigated the genetics of relapsed Wilms tumor (WT), suggesting the SIX1 gene, the microRNA processing genes, and the MYCN network as possibly involved in a relevant percentage of relapses. We investigated 28 relapsing WT patients (10 new cases and 18 cases in which the involvement of SIX and miRNAPG had been excluded) with a panel of ∼5000 genes. We identified variants affecting genes involved in DNA damage prevention and repair in 12/28 relapsing patients (42.9%), and affecting genes involved in chromatin modification and regulation in 6/28 relapsing patients (21.4%), widening the spectrum of anomalies detected in relapsed tumors. The disclosure of molecular pathways possibly underlying tumor progression might allow to use molecularly targeted therapies at relapse. Surprisingly, germline anomalies, mostly affecting DNA damage prevention and repair genes, were identified in 13/28 patients (46.4%), raising the issue of performing a genetic testing to all children presenting with a WT.

The coexistence of a BRCA2 germline and a DICER1 somatic variant in two first-degree cousins suggests their potential synergic effect.

Cancer predisposition syndromes are recognized in about 10% of pediatric malignancies with several genes specifically involved in a subset of pediatric tumors such as DICER1, in pleuropulmonary blastoma, cystic nephroma, and brain sarcomas. By contrast, the role of BRCA1/2 in pediatric cancer predisposition is still under investigation. We present two cases of young first-degree cousins, both carrying a germline BRCA2 variant and developing tumors characterized by somatic DICER1 mutations. Patient 1 presented with a cystic nephroma harboring a somatic DICER1 variant (p.Asp1810Tyr), while patient 2 had a primary intracranial DICER1-mutated sarcoma showing a distinct somatic DICER1 variant (p.Asp1709Glu) as well as biallelic inactivation of TP53 (p.Val173Leu, VAF 91%) and APC (p.Ile1307Lys, VAF 95%) and a pathogenic variant in KRAS (p.Gln61His). Both patients carried the same germline BRCA2 variant (p.Arg2842Cys) of unknown significance. The same variant was found in the mother of patient 2 and in the father of patient 1, who are siblings. A homologous recombination deficiency signature was not identified in any of the two tumors, possibly suggesting a reduction of BRCA2 activity. The association of BRCA2 and DICER1 variants in our cases hints at a potential cooperative role in cancer pathogenesis. Further studies are warranted to elucidate the interplay between BRCA1/2 and DICER1 variants and their implications for cancer predisposition and treatment in pediatric patients.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

INTRODUCTION: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. METHODS: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. RESULTS: Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. CONCLUSION: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Synchronous bilateral Wilms tumor: a report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND: The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades. METHODS: This analysis concerns patients with synchronous BWT registered at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers between 1990 and 2011; details on their treatment and outcome are presented and discussed. RESULTS: Ninety BWTs were registered in the AIEOP Wilms tumor database. Preoperative chemotherapy was given for a median 12 weeks before definitive tumor resection was attempted. Forty-eight percent of the patients had preservation of bilateral renal parenchyma. The proportion of bilateral nephron-sparing surgeries was not higher in the 37 patients initially given doxorubicin/vincristine/actinomycin D (32%) than in the 43 children receiving vincristine/actinomycin D alone (58%). The 4-year disease-free survival rate was 66.5% ± 5% and overall survival was 80% ± 5% for the cohort as a whole. The 4-year disease-free survival (overall survival) for 18 children with diffuse anaplasia or postchemotherapy blastemal-type tumors was 51% ± 13% (62% ± 13%), as opposed to 72% ± 3% (88% ± 4%) for 68 children with a favorable histology (log-rank P = .04 [P = .007]). CONCLUSIONS: These results provide further evidence that the optimal duration and choice of drugs for preoperative chemotherapy remain an open question. Outcome remained significantly worse for BWT than for unilateral Wilms tumor. To enable the conservative treatment of as many affected kidneys as possible, only centers with experience in BWT should manage such cases.

Chemotherapy-induced cavitating Wilms' tumor pulmonary metastasis: Active disease or scarring? A case report and literature review.

The second most common abdominal tumor in children is Wilms' tumor, and the lung is where it most often metastasizes. The typical metastases are multiple, peripherally located, round, and variable-sized nodules. Atypical patterns are also possible and may create diagnostic challenges, especially in patients treated with chemotherapy. Among these, cavitating metastases are an anecdotal type of atypical secondary lung lesions. Here, we report a case of a chemotherapy-induced cavitating Wilms' tumor pulmonary metastasis discovered during the follow-up for an anaplastic nephroblastoma in a 6-year-old girl. Furthermore, we conducted a review of the existing literature on this exceedingly rare radiological pattern to establish its best management.

Intrathoracic synovial sarcoma with BRAF V600E mutation.

We report a case of 15-year-old boy with intrathoracic synovial sarcoma who relapsed after standard chemotherapy, surgery and radiotherapy. The molecular analysis of the tumour identified a BRAF V600E mutation at time of progression of relapsed disease under third line systemic treatment. This mutation is commonly seen in melanomas and papillary thyroid cancers, but less prevalent (typically <5%) across a variety of other cancer types. The patient underwent selective BRAF inhibitor Vemurafenib treatment achieving partial response (PR) with a progression free survival (PFS) ratio of 1.6 months and an overall survival of 19 months, alive in continuous PR. This case highlights the role of routinely next generation sequencing (NGS) used to drive treatment choice and to investigate extensively synovial sarcoma tumour for BRAF mutation.

A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications.

A nationwide questionnaire-based survey was designed to evaluate the management and prophylaxis of febrile neutropenia in pediatric patients admitted to hematology-oncology and hematopoietic stem cell transplant units. Of the 34 participating centers, 40 and 63%, respectively, continue to prescribe antibacterial and antimycotic prophylaxis in low-risk subjects and 78 and 94% in transplant patients. Approximately half of the centers prescribe a combination antibiotic regimen as first-line therapy in low-risk patients and up to 81% in high-risk patients. When initial empirical therapy fails after seven days, 63% of the centers add empirical antimycotic therapy in low-and 81% in high-risk patients. Overall management varies significantly across centers. Preventive nursing procedures are in accordance with international guidelines. This survey is the first to focus on prescribing practices in children with cancer and could help to implement practice guidelines.

Tandem high-dose 131I-MIBG therapy supported by dosimetry in pediatric patients with relapsed-refractory high-risk neuroblastoma: the Bambino Gesu' Children's Hospital experience.

OBJECTIVE: 131I-meta-iodobenzylguanidine (131I-MIBG) combined with myeloablative chemotherapy represents an effective treatment in children affected by relapsed/refractory neuroblastoma (NBL) for disease palliation and in improving progression-free survival. The aim of our study is to evaluate the feasibility, safety and efficacy of tandem 131I-MIBG followed by high-dose chemotherapy with Melphalan. METHODS: Thirteen patients (age range: 3-17 years) affected by relapsed/refractory NB, previously treated according to standard procedures, were included in the study. Each treatment cycle included two administrations of 131I-MIBG (with a dosimetric approach) followed by a single dose of Melphalan with peripheral blood stem cell rescue. RESULTS: At the end of the treatment, ten patients experienced grade 4 neutropenia, two grade 3 and one patient grade 2, three patients presented febrile neutropenia and all needed RBC and platelets transfusions; one patient presented grade 4 mucositis, four grade 3 and one patient grade 2 mucositis. One patient showed progressive disease, eight patients showed stable disease and four patients showed partial response. CONCLUSION: High-dose 131I-MIBG therapy combined with chemotherapy represent a well-tolerated and effective modality of treatment in heavily pretreated patients affected by relapsed/refractory NBL. However, further studies, including a wider cohort of patients, are needed.

The Fight Just Born-Neonatal Cancer: Rare Occurrence with a Favorable Outcome but Challenging Management.

The occurrence of cancer in newborns within the first 28 days of life is uncommon, with different clinical presentation from other age groups. Prenatal diagnosis is reported in about half of patients, while a genetic predisposition condition is supposed. The management of a newborn with cancer can be challenging and needs to be tailored according to the histology and the primary tumor site; surgery represents the main strategy, while chemotherapy should be considered with caution because of the higher toxicity and mortality due to different pharmacokinetics in neonates compared to older children. We describe the first Italian series over a 15-year period of patients affected by both benign and malignant neoplastic diseases diagnosed within the first 28 days of life; 74 newborns were diagnosed with neonatal tumors, representing 1.5% of the cancer population in the same period, and a prevalence of germ cell tumors (55%) and neuroblastoma (16%) was observed. Surgery was performed on 80% of patients, while chemotherapy was necessary for about 20% of patients. The 5-year overall survival (OS) exceeded 90%; treatment-related deaths are a major concern, representing 80% of overall deaths. A genetic/syndromic condition was detected in 16% of the population; additionally, a cancer predisposition syndrome (CPS) was identified in about 10% of patients. According to our experience, all newborns affected by cancer should warrant genetic counselling and a screening test for CPS.

Vascular Access in Pediatric Oncology and Hematology: State of the Art.

Management and successful use of vascular access are critical issues in pediatric patients affected by malignancies. Prolonged course of disease, complex and various treatment protocols require long-lasting vascular access providing adequate tools to administrate those therapies and to collect routine blood sampling without painful and repeated venipuncture. For these reasons, central venous catheters are currently an important component in pediatric onco-hematological care, with a direct influence on outcome. Indeed, there are peculiar issues (techniques of insertion, management, complications etc.) which must be well-known in order to improve the outcome and the quality of life of children with cancer.

Personalized dosimetry for a deeper understanding of metastatic response to high activity 131I-mIBG therapy in high risk relapsed refractory neuroblastoma.

BACKGROUND: Dosimetry in molecular radiotherapy for personalized treatment is assuming a central role in clinical management of aggressive/relapsed tumors. Relapsed/refractory metastatic high-risk neuroblastoma (rrmHR-NBL) has a poor prognosis and high-activity 131I-mIBG therapy could represent a promising strategy. The primary aim of this case series study was to report the absorbed doses to whole-body (DWB ), red marrow (DRM ) and lesions (DLesion ). A secondary aim was to correlate DLesion values to clinical outcome. METHODS: Fourteen patients affected by rrmHR-NBL were treated with high-activity 131I-mIBG therapy (two administrations separated by 15 days). The first administration was weight-based whereas the second one was dosimetry-based (achieving DWB equals to 4 Gy). In all patients DWB and DRM was assessed; 9/14 patients were selected for DLesion evaluation using planar dosimetric approach (13 lesions evaluated). Treatment response was classified as progressive and stable disease (PD and SD), partial and complete response (PR and CR) according to the International Neuroblastoma Response Criteria. Patients were divided into two groups: Responder (CR, PR, SD) and Non-Responder (PD), correlating treatment response to DLesion value. RESULTS: The cumulative DWB , DRM and DLesion ranged from (1.5; 4.5), (1.0; 2.6) and (44.2; 585.8) Gy. A linear correlation between DWB and DRM and a power law correlation between the absorbed dose to WB normalized for administered activity and the mass of the patient were observed. After treatment 3, 2, 4 and 5 patients showed CR, PR, SD and PD respectively, showing a correlation between DLesion and the two response group. CONCLUSIONS: Our experience demonstrated feasibility of high activity therapy of 131I-mIBG in rrmHR-NBL children as two administration intensive strategy. Dosimetric approach allowed a tailored high dose treatment maximizing the benefits of radionuclide therapy for pediatric patients while maintaining a safety profile. The assesment of DLesion contributed to have a deeper understaning of metabolic treatment effects.

The Pitfall of Ganglioneuroblastoma-Nodular Diagnosis: Clinical and Imaging Considerations over a Rare Bifocal Sporadic Case.

Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed. Herein, we describe a case of multifocal NT (thoracic and abdominal localization) occurring in a 4-year-old male. Different histological subtypes, namely GNBI and GNBN, were revealed in the two lesions. We focus on the difficulties of proper diagnosis and risk stratification, underlining the usefulness of several diagnostic tools for appropriate management and therapeutic choices.

Hemorrhage During Induction Chemotherapy in Neuroblastoma: Additional Risk Factors in High-Risk Patients.

Background: Neuroblastoma is the most common solid extracranial tumor in children. Patients affected by neuroblastoma are stratified into low, intermediate, and high risk in terms of event-free and overall survival. Some high-risk patients have an additional risk of acute hemorrhagic complications during induction chemotherapy. Aim: To find easily and rapidly assessed parameters that help clinicians identify those patients affected by high-risk neuroblastoma who have an additional risk of hemorrhagic complications. Methods: The clinical notes of patients diagnosed with high-risk neuroblastoma from January 2013 until February 2021 were retrospectively reviewed. Clinical, demographic and laboratory data, biological characteristics of the tumor, and information about treatment and hospital stay were identified. Results: In the examined period, 44 patients were diagnosed with high-risk neuroblastoma. Four of these patients had hemorrhagic complications within 2-7 days after the initiation of induction chemotherapy; two patients had hemothorax, one patient had hemoperitoneum and one patient had hemothorax and hemoperitoneum. The patient with isolated hemoperitoneum was treated with blood components transfusions, clotting factors and colloids infusions; the three patients with hemothorax underwent thoracostomy tube placement and respiratory support. At initial presentation, patients who suffered from hemorrhagic complications had a higher degree of hypertension (stage 2, p = 0.0003), higher levels of LDH (median 3,745 U/L, p = 0.009) and lower levels of hemoglobin (mean 7.6 gr/dl, p = 0.0007) compared to other high-risk patients. Conclusions: A subgroup of "additional" high-risk patients can be identified within the high-risk neuroblastoma patients based on mean arterial pressure, LDH levels and hemoglobin levels at presentation. Further studies to define cut-off values and optimal management strategies for these patients are needed.

Rhabdoid Tumor Predisposition Syndrome: From Clinical Suspicion to General Management.

Rhabdoid tumors are rare aggressive malignancies in infants and young children with a poor prognosis. The most common anatomic localizations are the central nervous system, the kidneys, and other soft tissues. Rhabdoid tumors share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, members of the SWI/SNF chromatin-remodeling complex. Rhabdoid tumor predisposition syndrome (RTPS) is a condition characterized by a high risk of developing rhabdoid tumors, among other features. RTPS1 is characterized by pathogenic variants in the SMARCB1 gene, while RTPS2 has variants in SMARCA4. Interestingly, germline variants of SMARCB1 and SMARCA4 have been identified also in patients with Coffin-Siris syndrome. Children with RTPS typically present with tumors before 1 year of age and in a high percentage of cases develop synchronous or multifocal tumors with aggressive clinical features. The diagnosis of RTPS should be considered in patients with rhabdoid tumors, especially if they have multiple primary tumors and/or in individuals with a family history. Because germline mutations result in an increased risk of carriers developing rhabdoid tumors, genetic counseling, and surveillance for all family members with this condition is recommended.

The Multidimensional Assessment for Pediatric Patients in Radiotherapy (M.A.P.-RT) Tool for Customized Treatment Preparation: RADAR Project.

Aims: Pediatric patients may experience considerable distress during radiotherapy. Combining psychological interventions with standard therapies can reduce the need for sedation. The RADAR Project aims to use a systematic method of recording data that can reveal patients' difficulties and fragility during treatment. In this context, the aim of our study was to investigate the ability of a multidimensional assessment tool (M.A.P.-RT schedule) to predict the need for sedation during radiotherapy. The schedule, which is administered during the first evaluation, was created to collect information on patients and their families in a standardized way. Materials and Methods: The study enrolled pediatric patients (aged 0-18 years or 18-21 with cognitive impairment). Data were collected by means of the M.A.P.-RT module; this explores various thematic areas, and is completed by the radiation oncologist, psychologist and nurse during their first evaluation. Features were selected by means of the Boruta method (random forest classifier), and the totals of the significant partial scores on each subsection of the module were inserted into a logistic model in order to test for their correlation with the use of anesthesia and with the frequency of psychological support. The results of logistic regression (LR) were used to identify the best predictors. The AUC was used to identify the best threshold for the scores in the evaluation. Results: A total of 99 patients were considered for this analysis. The feature that best predicted both the need for anesthesia and the frequency of psychological support was the total score (TS), the AUC of the ROC being 0.9875 for anesthesia and 0.8866 for psychological support. Conclusion: During the first evaluation, the M.A.P.-RT form can predict the need for anesthesia in pediatric patients, and is a potential tool for personalizing therapeutic and management procedures.