Papers by Giada Del Baldo
Cancers
Central nervous system (CNS) metastatic spread in neuroblastoma (NB) is rare and occurs more ofte... more Central nervous system (CNS) metastatic spread in neuroblastoma (NB) is rare and occurs more often at relapse/progression. We report on CNS involvement in high risk (HR) NB over 25 years. For this retrospective study, we reviewed the CNS imaging of all the patients treated at Bambino Gesù Children Hospital from 1 July 1996 to 30 June 2022. A total of 128 patients with HR NB were diagnosed over 26 years. Out of 128 patients, CNS metastatic spread occurred in 6 patients: 3 patients presented a metastatic spread at diagnosis, while in 3 patients, CNS was involved at relapse. Overall, the rate of occurrence of CNS spread is 4.7% with the same distribution at diagnosis and at relapse, namely 2.3%. Interestingly, CNS spread at diagnosis was observed only before 2012, whereas CNS was observed at relapse only after 2012, in the immunotherapy era. CNS metastases presented similar imaging features at diagnosis and at relapse, with a peculiar hemorrhagic aspect and mainly hemispheric localizat...
New England Journal of Medicine
Frontiers in Immunology
Childhood malignant brain tumors remain a significant cause of death in the pediatric population,... more Childhood malignant brain tumors remain a significant cause of death in the pediatric population, despite the use of aggressive multimodal treatments. New therapeutic approaches are urgently needed for these patients in order to improve prognosis, while reducing side effects and long-term sequelae of the treatment. Immunotherapy is an attractive option and, in particular, the use of gene-modified T cells expressing a chimeric antigen receptor (CAR-T cells) represents a promising approach. Major hurdles in the clinical application of this approach in neuro-oncology, however, exist. The peculiar location of brain tumors leads to both a difficulty of access to the tumor mass, shielded by the blood-brain barrier (BBB), and to an increased risk of potentially life-threatening neurotoxicity, due to the primary location of the disease in the CNS and the low intracranial volume reserve. There are no unequivocal data on the best way of CAR-T cell administration. Multiple trials exploring the...
Frontiers in Cell and Developmental Biology
Development of the cerebellum is characterized by rapid proliferation of cerebellar granule cell ... more Development of the cerebellum is characterized by rapid proliferation of cerebellar granule cell precursors (GCPs) induced by paracrine stimulation of Sonic hedgehog (Shh) signaling from Purkinje cells, in the external granular layer (EGL). Then, granule cell precursors differentiate and migrate into the inner granular layer (IGL) of the cerebellum to form a terminally differentiated cell compartment. Aberrant activation of Sonic hedgehog signaling leads to granule cell precursors hyperproliferation and the onset of Sonic hedgehog medulloblastoma (MB), the most common embryonal brain tumor. β-arrestin1 (ARRB1) protein plays an important role downstream of Smoothened, a component of the Sonic hedgehog pathway. In the medulloblastoma context, β-arrestin1 is involved in a regulatory axis in association with the acetyltransferase P300, leading to the acetylated form of the transcription factor E2F1 (E2F1-ac) and redirecting its activity toward pro-apoptotic gene targets. This axis in th...
Neuropathology and Applied Neurobiology
Diagnostics, Nov 9, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Diagnostics
Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood.... more 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.
International Journal of Environmental Research and Public Health
Background: Cancer is very disruptive in adolescence and hospitalizations interfere with this dev... more Background: Cancer is very disruptive in adolescence and hospitalizations interfere with this development stage in becoming independent, developing social relationships, and making plans for the future. A major challenge in the care of adolescents with cancer is being able to enhance their quality of life. The aim of this project is to increase our understanding of how adventure therapy influenced quality of life for adolescents with cancer. Methods: Bambino Gesù Children’s Hospital, in collaboration with the Tender to Nave Italia Foundation (TTNI), has been conducting a unique project, located on a beautiful brigantine of the Italian Navy. Adventure therapy is a form of experiential therapy that consists of various types of adventure, in particular outdoor and sailing activities. Ninety teenagers have been the protagonists of this project to date and filled out two questionnaires about quality of life and self-esteem, before and after the sailing experience. Results: The adventure ...
Frontiers in Cell and Developmental Biology
Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childho... more Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24 h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the...
Medicina
In the last two decades, thanks to the data that have been obtained from the Human Genome Project... more In the last two decades, thanks to the data that have been obtained from the Human Genome Project and the development of next-generation sequencing (NGS) technologies, research in oncology has produced extremely important results in understanding the genomic landscape of pediatric cancers, which are the main cause of death during childhood. NGS has provided significant advances in medicine by detecting germline and somatic driver variants that determine the development and progression of many types of cancers, allowing a distinction between hereditary and non-hereditary cancers, characterizing resistance mechanisms that are also related to alterations of the epigenetic apparatus, and quantifying the mutational burden of tumor cells. A combined approach of next-generation technologies allows us to investigate the numerous molecular features of the cancer cell and the effects of the environment on it, discovering and following the path of personalized therapy to defeat an “ancient” di...
Frontiers in Immunology
High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS)... more High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical t...
Journal of Medical Genetics
BackgroundLittle is known about risks associated with germlineSUFUpathogenic variants (PVs) known... more BackgroundLittle is known about risks associated with germlineSUFUpathogenic variants (PVs) known as a cancer predisposition syndrome.MethodsTo study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germlineSUFUPV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives withSUFUPV (89 patients) using the Nelson-Aalen estimator.ResultsOverall, 117/172 (68%)SUFUPV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4...
Cancers
Background: Ewing sarcoma (ES) is a rare and aggressive pediatric cancer. Numerous studies have a... more Background: Ewing sarcoma (ES) is a rare and aggressive pediatric cancer. Numerous studies have attempted to identify new prognostic biomarkers. The predictive value of serum LDH and CRP has not been clearly described, to date. Methods: The objective of our retrospective study was to investigate the prognostic value of LDH and CRP levels and their association with overall survival in a series of ES patients. Results: Between 2004 and 2019, 89 ES patients were included. In a univariable analysis, high levels of LDH and CRP were associated with the worst prognosis. In a multivariable analysis, only higher LDH values remained associated with a lower survival. The high-LDH-level group experienced all 21 deaths registered in our population (24%) and about 90% of disease progressions. The 5-year overall survival was 66.4% in the high-LDH-level group, while no deaths were observed in the low-LDH-level group. The 5-year progression-free survival was 57.9% in the high-LDH-level group versus ...
Frontiers in Surgery
BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clini... more BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. Approximately 15% of OPGs occur in patients affected by neurofibromatosis type 1 (NF1): the clinical course of these cases is more indolently than sporadic ones, and NF1 patients less frequently require treatment including surgery. Instead, over 90% of sporadic OPGs require one or more therapeutic approaches. The management of OPG is controversial. They are also characterized by a high risk of morbidity including hypothalamic damage, endocrine deficits, visual deficit and/or neurological impairment.Materials and MethodsIn this paper, we evaluated visual and endocrinological outcomes of a population of OPG followed at our center from 2013 to 2021, with a particular emphasis on the role of surgery.ResultsTwenty-six patients were included in this study (mean age of 40.7 months). Tumor location on imaging was described by the Dodge classification. Five cases had NF 1. Thirteen ca...
Emerging Microbes & Infections
AbstractDue to an increasing number of infections in adults, Lactococcus (L.) garvieae has gained... more AbstractDue to an increasing number of infections in adults, Lactococcus (L.) garvieae has gained recognition as an emerging human pathogen, causing bacteraemia and septicaemia.In September 2020, four paediatric onco-hematologic patients received a platelet concentrate from the same adult donor at Bambino Gesù Children's Hospital IRCCS, Rome. Three of four patients experienced L. garvieae sepsis one day after transfusion.The L. garvieae pediatric isolates and the donor's platelet concentrate were retrospectively collected for whole-genome sequencing and shot-gun metagenomics, respectively (Illumina HiSeq). By de novo assembly of the L. garvieae genomes, we found that all three pediatric isolates shared a 99.9% identity and were characterized by 440 common SNPs. Plasmid pUC11C (conferring virulence properties) and the temperate prophage Plg-Tb25 were detected in all three strains. Core SNP genome-based Maximum Likelihood and Bayesian trees confirmed their phylogenetic common origin and revealed their relationship with L. garvieae strains affecting cows and humans (bootstrap values >100 and posterior probabilities = 1.00). Bacterial reads obtained by the donor's platelet concentrate have been profiled with MetaPhlAn2 (v.2.7.5); among these, 29.9% belonged to Firmicutes, and 5.16% to Streptococcaceae (>97% identity with L. garvieae), confirming the presence of L. garvieae in the platelet concentrate transfusion.These data showed for the first time three episodes of sepsis due to a transfusion-associated transmission of L. garvieae in three pediatric hospitalized hematology patients. This highlights the importance to implement the screening of platelet components with new human defined pathogens for ensuring safety of blood supply, and, more broadly, for surveillance of emerging pathogens.
Neuro-Oncology
BACKGROUND: Incidence of iatrogenic pulmonary toxicity is around 20%. Apart from bleomycin fibros... more BACKGROUND: Incidence of iatrogenic pulmonary toxicity is around 20%. Apart from bleomycin fibrosis, the role of lomustine, HD-thiotepa, autologous stem-cells transplantation(APBSCT) and their synergy with craniospinal irradiation(CSI) are unclear. To elucidate their role in lung-function impairment, we retrospectively evaluated 39 medulloblastoma patients treated at INT-Milan and OPBG-Rome. METHODS: 39 patients (17 females, median RT age 8 years) treated for localized(29) or metastatic(10) medulloblastoma in 2000-2020 and with spirometric assessment, were considered. Treatment included: SIOP-like-PNET IV(19), high-risk protocol(19), infant protocol without RT(1). CSI doses were: 23.4Gy(20), 31.2Gy(8), 36Gy(6) and 39Gy(4); 4 received protons and 34 photons(9 VMAT, 25 3D), 11 hyperfractionated-accelerated-RT; 33 had 6 median CCNU cycles; 6 APBSCT. RESULTS: Median follow-up: 98 months. All patients performed at least one spirometry at median 5 years after RT. Eight (20.6%) had mildly ...
Cancers
The occurrence of cancer in newborns within the first 28 days of life is uncommon, with different... more 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...
Diagnostics, 2022
High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognos... more High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10–12% of pediatric HGGs (pHGG) occur in children younger than five years of age at diagnosis, specifically infants (iHGG), with an unexpected overall survival rate (OS) in 60–70% of cases. In the literature, iHGGs include a large variety of heterogeneous lesions with different molecular profiles that likely explain their different outcomes. We report our single-institution experience of iHGG including 11 children under five years of age with newly diagnosed HGG between 2011 and 2021. All patients received surgery and adjuvant chemotherapy; only two patients received radiotherapy because their age at diagnosis was more than four years-old. Molecular investigations, including next generation sequencing (NGS) and DNA methylation, detected three NTRK-fusions, one ROS1-fusions, one MN1-rearrangement, and two PATZ1-fusions. According...
Cancer Reports, 2022
Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In ... more Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In young patients, adenocarcinoma is the most frequent histotype and 3–7% expresses the rearrangement of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by the FDA.
Digestive and Liver Disease, 2017
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Papers by Giada Del Baldo