Corrigendum: Comparison of 3DCRT and IMRT out-of-field doses in pediatric patients using Monte Carlo simulations with treatment planning system calculations and measurements.

[This corrects the article DOI: 10.3389/fonc.2022.879167.].

Single cell spatial biology over developmental time can decipher pediatric brain pathologies.

Pediatric low grade brain tumors and neurodevelopmental disorders share proteins, signaling pathways, and networks. They also share germline mutations and an impaired prenatal differentiation origin. They may differ in the timing of the events and proliferation. We suggest that their pivotal distinct, albeit partially overlapping, outcomes relate to the cell states, which depend on their spatial location, and timing of gene expression during brain development. These attributes are crucial as the brain develops sequentially, and single-cell spatial organization influences cell state, thus function. Our underlying premise is that the root cause in neurodevelopmental disorders and pediatric tumors is impaired prenatal differentiation. Data related to pediatric brain tumors, neurodevelopmental disorders, brain cell (sub)types, locations, and timing of expression in the developing brain are scant. However, emerging single cell technologies, including transcriptomic, spatial biology, spatial high-resolution imaging performed over the brain developmental time, could be transformational in deciphering brain pathologies thereby pharmacology.

Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide.

The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.

Brachial plexus peripheral nerve sheath tumors (PNSTs): clinical and surgical management in the pediatric population.

PURPOSE: Peripheral nerve sheath tumors (PNSTs) are rare in pediatric patients, especially in the brachial plexus. Research on PNSTs is lacking. This article presents a retrospective cohort study of pediatric patients diagnosed and treated with PNSTs, specifically brachial plexus tumors. METHODS: All pediatric patients intervened in a single center between 2007 and 2023 with brachial plexus tumors were systemically analyzed. RESULTS: Eleven pediatric patients with 14 brachial plexus PNSTs were studied. The gender distribution was 64% female and 36% male, with an average age of 10.7 years. Ninety-one percent had a previous NF-1 diagnosis. Right brachial plexus presented a higher prevalence (64%). Pain, Tinel's sign, and stiffness masses were common during diagnosis. Motor deficits were noted in 43% of the patients. Surgery was indicated for symptoms, particularly pain and rapid growth, increasing malignancy risk. Due to suspected malignancy, an en bloc resection with safety margins was performed. Among the patients, 57% received a histopathological diagnosis of MPNST (malignant peripheral nerve sheath tumor). Treatment included radiotherapy and chemotherapy. Clinical follow-up was conducted for all cases, involving clinical and oncological evaluations for all MPNSTs. CONCLUSIONS: This article present a series of pediatric brachial plexus tumors, especially in NF-1, and emphasizes the importance of thorough evaluation for this group. Swift diagnosis is crucial in pediatrics, enabling successful surgery for small lesions with limited neurological symptoms, improving long-term outcomes. Prompt referral to specialized services is urged for suspected masses, irrespective of neurological symptoms. Benign tumor postsurgical progression shows better outcomes than MPNSTs, with complete resection as the primary goal. Needle-guided biopsy is not recommended.

Briefing on Investigational Chimeric Antigen Receptor T-Cell Immunotherapies in Pediatric Neoplasms.

The promising results seen in the treatment of refractory hematologic malignancies with tisagenlecleucel (Kymriah), the pioneering Chimeric Antigen Receptor (CAR) T-cell immunotherapy, has stimulated a fast growth in research and clinical testing of novel CAR-T constructs, targets, and various generations of CAR T-cells. Pharmacists may receive inquiries about active clinical trials or may be contributing to the care of patients participating in these studies. This briefing discusses the on-going clinical trials that explore novel CAR T-cell immunotherapies in pediatric refractory malignancies of hematologic and solid organ origins. It can be valuable in assisting practitioners in navigating the rapidly evolving field of CAR T-cell immunotherapies.

Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age.

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009-2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5-21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months-20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or "round cell" features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1-119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Female Fertility Cryopreservation Outcomes in Childhood Cancer: A Systematic Review.

BACKGROUND AND AIMS: As survival rates in childhood cancer progress significantly, health outcomes in adulthood are pivotal to quality of life (QoL). Female patients undergoing chemotherapy and radiation for childhood cancer may experience adverse effects such as gonadotoxicity-related ovarian insufficiency. Ovarian tissue cryopreservation (OTC) is well studied in adults, but has only recently started to be explored in an effort to preserve fertility in young patients with childhood cancer. This systematic review aims to critically highlight contemporary outcomes of cryopreservation in female pediatric cancer patients. METHODS: A systematic search was conducted in PubMed, Embase, and Web of Science databases to identify English-language full text articles and abstracts published between 2004 and 2022 describing cryopreservation among female children (0-21 years old) with cancer. Abstracts and full-text articles were screened for inclusion. Subsequently, data from eligible studies was extracted and analyzed. Descriptive statistics were utilized to estimate overall outcomes of cryopreservation. RESULTS: Of 104 abstracts and 34 full-text articles, 12 studies were included. Data was collected from 7 world countries and involved some 612 pediatric and adolescent patients with malignant disease. Most common cancers included hematological malignant disease (81%), CNS nervous system malignant tumors (56%), and sarcomas (39%). Of the 6 studies with full reporting, OTC was undertaken in 501 patients, and 5.9% (30/501) of these patients underwent ovarian tissue transplantation (OTT). After OTT, 27 patients desired pregnancy and 33% (9/27) became pregnant. Six of these 9 patients (67%) had live births. CONCLUSIONS: Preliminary analysis showed that OTC has been successfully performed but not yet studied thoroughly in pediatric cancer patients in a longitudinal manner. This study has further shown that cryopreservation outcomes are mainly reported among adult patients living in high income countries, demonstrating a crucial need for long-term outcome studies focused on pediatric and prepuberal OTC, subsequent OTT, and potential pregnancy. This work is considered critical to aid standardize recommendations of fertility preservation in childhood cancer patients and to better inform the efficacy of these procedures to benefit patients in world nations of all fiscal income levels. LEVEL OF EVIDENCE: Level III.

Image-guided biopsy of intracranial lesions in children, with a small robotic device: a case series.

BACKGROUND AND OBJECTIVES: Robot-assisted biopsies have gained popularity in the last years. Most robotic procedures are performed with a floor-based robotic arm. Recently, Medtronic Stealth Autoguide, a miniaturized robotic arm that work together with an optical neuronavigation system, was launched. Its application in pediatric cases is relatively unexplored. In this study, we retrospectively report our experience using the Stealth Autoguide, for frameless stereotactic biopsies in pediatric patients. METHODS: Pediatric patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to May 2023 were included in this study. Clinical, neuroradiological, surgical, and histological data were collected and analyzed. RESULTS: Nineteen patients underwent 20 procedures (mean age was 9-year-old, range 1-17). In four patients, biopsy was part of a more complex surgical procedure (laser interstitial thermal therapy - LITT). The most common indication was diffuse intrinsic brain stem tumor, followed by diffuse supratentorial tumor. Nine procedures were performed in prone position, eight in supine position, and three in lateral position. Facial surface registration was adopted in six procedures, skull-fixed fiducials in 14. The biopsy diagnostic tissue acquisition rate was 100% in the patients who underwent only biopsy, while in the biopsy/LITT group, one case was not diagnostic. No patients developed clinically relevant postoperative complications. CONCLUSION: The Stealth Autoguide system has proven to be safe, diagnostic, and highly accurate in performing stereotactic biopsies for both supratentorial and infratentorial lesions in the pediatric population.

An atypical location of pineoblastoma RB1 subgroup without pineal or retinal tumor.

PURPOSE: To describe the clinical and imaging features of a sellar-suprasellar pineoblastoma RB1 subgroup without pineal or retinal involvement. CASE REPORT: An 11-month-old girl presented to the emergency department with fever, rhinorrhea, vomiting, altered level of consciousness, and one seizure. Head CT and brain MRI demonstrated a large lobulated mass with calcifications and heterogeneous enhancement in the suprasellar region causing mass effect to the ventricular system and hydrocephalus. Histology revealed a CNS embryonal tumor not otherwise specified (NOS) with small round nuclei with mitotic activity and necrosis. DNA methylation analysis classified the tumor in the pineoblastoma RB1 subgroup. CONCLUSION: Pineoblastoma RB1 subgroup should be considered in the differential diagnosis of large sellar-suprasellar masses with calcifications and heterogeneous enhancement in children younger than 18 months even in cases of absent pineal or retinal involvement. Molecular analysis with DNA methylation profiling is critical for diagnosis and management.

Fine needle aspiration cytology in pediatric tumors: a low-cost, high-accuracy diagnostic tool for resource-limited settings.

INTRODUCTION: Fine needle aspiration cytology (FNAC) is gaining popularity in diagnosing pediatric tumors because of ease of performance, easy reproducibility, and low morbidity. However, literature on its efficacy in resource-limited settings is lacking. Hence, the present study evaluated the diagnostic accuracy of FNAC in pediatric tumors in a North Indian center where ancillary diagnostic techniques are unavailable. MATERIALS AND METHODS: This was a four-year retrospective and 1-year prospective study. Both direct and radiology-guided FNAs were performed in children under 14 years. Cytomorphologic diagnoses were compared with the corresponding histopathologic diagnoses, wherever available, and the concordance rates determined. The diagnostic accuracy of FNAC for pediatric tumors was assessed using sensitivity, specificity, and positive and negative predictive values. RESULTS: The present study included 125 cases of pediatric tumors, of which 65 were benign and 60 were malignant. The most common site of involvement was the head and neck. The most common benign pediatric tumor was pleomorphic adenoma, while the most common malignant tumor was non-Hodgkin lymphoma. The overall cytologic-histopathologic concordance was high (96.3%), with an overall sensitivity and specificity of 95.65% and 96.88%, respectively. CONCLUSIONS: FNAC is a highly sensitive and specific technique for diagnosing pediatric tumors, with a high histopathologic concordance, even in resource-limited setups where advanced ancillary techniques are unavailable. Nevertheless, additional ancillary techniques can complement FNAC to improve this diagnostic accuracy further.

Radiomics for Differentiation of Pediatric Posterior Fossa Tumors: A Meta-Analysis and Systematic Review of the Literature.

PURPOSE: To better define the overall performance of the current radiomics-based models for the discrimination of pediatric posterior fossa tumors. METHODS: A comprehensive literature search of the databases PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus was designed and conducted by an experienced librarian. We estimated overall sensitivity (SEN) and specificity (SPE). Event rates were pooled across studies using a random-effects meta-analysis, and the χ2 test was performed to assess the heterogeneity. RESULTS: Overall SEN and SPE for differentiation between MB, PA, and EP were found to be promising, with SEN values of 93% (95% CI = 0.88-0.96), 83% (95% CI = 0.66-0.93), and 85% (95% CI = 0.71-0.93), and corresponding SPE values of 87% (95% CI = 0.82-0.90), 95% (95% CI = 0.90-0.98) and 90% (95% CI = 0.84-0.94), respectively. For MB, there is a better trend for LR classifiers, while textural features are the most used and the best performing (ACC 96%). As for PA and EP, a synergistic employment of LR and NN classifiers, accompanied by geometrical or morphological features, demonstrated superior performance (ACC 94% and 96%, respectively). CONCLUSIONS: The diagnostic performance is high, making radiomics a helpful method to discriminate these tumor types. In the forthcoming years, we expect even more precise models.

Targeted therapy for pediatric central nervous system tumors harboring mutagenic tropomyosin receptor kinases.

The family of the neurotrophic tyrosine kinase receptor (NTRK) gene encodes for members of the tropomyosin receptor kinase (TRK) family. Rearrangements involving NTRK1/2/3 are rare oncogenic factors reported with variable frequencies in an extensive range of cancers in pediatrics and adult populations, although they are more common in the former than in the latter. The alterations in these genes are causative of the constitutive activation of TRKs that drive carcinogenesis. In 2017, first-generation TRK inhibitor (TRKi) larotrectinib was granted accelerated approval from the FDA, having demonstrated histologic-agnostic activity against NTRKs fusions tumors. Since this new era has begun, resistance to first-generation TRKi has been described and has opened the development of second-generation molecules, such as selitrectinib and repotrectinib. In this review, we provide a brief overview of the studies on NTRK alterations found in pediatric central nervous system tumors and first and second-generation TRKi useful in clinical practice.

Clear cell sarcoma of kidney: A mimicker of Wilms' tumor.

The differential diagnosis for an abdominal mass in a 2-year-old child is broad and includes lesions of renal, hepatic, gastrointestinal, adrenal, and lymphatic origins. Of these, Wilms' tumor and neuroblastoma are the most common tumors, where Wilms' tumor represents about 92% of renal masses in children. Non-Wilms' renal tumors, rhabdoid tumors, and clear cell sarcoma of the kidney (CCSK) are uncommon. CCSK constitutes approximately 3% of all malignant renal tumors in childhood. In this report, we present a child presenting with a huge renal mass consistent with Wilms' tumor on computed tomography and initial biopsy. However, the final pathologic diagnosis after resection revealed CCSK.

Corrigendum: Comparison of 3DCRT and IMRT out-of-field doses in pediatric patients using Monte Carlo simulations with treatment planning system calculations and measurements.

[This corrects the article DOI: 10.3389/fonc.2022.879167.].

Analysis of microsatellite instability (MSI) in pediatric gonadal and extra-gonadal germ cell tumors.

Gonadal and extragonadal pediatric germ cell tumors (GCTs) are rare neoplasms with different clinical behavior. Although surgery and cisplatin-based chemotherapy are resolutive in most cases, some patients do not respond to chemotherapy and have a worse outcome. Microsatellite instability (MSI) was correlated to resistance to chemotherapy and sensitivity to immunotherapy in different neoplasms. A series of 21 pediatric GCTs were tested by immuno-histochemistry and PCR to evaluate MSI status. Next generation sequencing was applied to further evaluate cases with discordant results between immunohistochemistry and PCR. Twenty-one cases of pediatric GCT were included in the series. The mean age ranged between 1 and 10 years. Nine cases were gonadal GCTs and the remaining 12 were extra-gonadal GCTs. By immunohistochemistry, one case showed a deficit of Mismatch repair (MMR) proteins. This case was a 1-year-old children affected by gonadal yolk sac tumor. However, all cases resulted microsatellite stable (MSS) by PCR and NGS. MSI was not detected in our series of pediatric GCTs, as well as the data present in literature about adult patients with GCTs. Molecular techniques could have a role to confirm the MSI status in case of dMMR by immunohistochemistry.

Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody.

Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets. PRL3-zumab, a first-in-class humanized antibody, was administered in a dose escalation schedule in a first-in-child clinical trial to study toxicity, pharmacokinetics, and clinical outcomes. Among 64 pediatric tumors, PRL3 was most frequently expressed in neuroblastoma (100%), rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcomas (71%), and renal sarcomas (60%) but absent in paired normal tissues. PRL3 was expressed in 75% of relapsed tumors and associated with shorter median event-free survival. Microarray profiling of PRL3-positive tumors showed elevation of angiogenin, TIMP1 and TIMP2, and GPCR-MAPK signaling proteins that commonly interacted with PRL3. The first use of PRL3-zumab in a pediatric patient saw no adverse events. A 28.6% reduction in maximum target lesion diameter was achieved when PRL3-zumab was administered concurrently with hypofractionated radiation. These findings support wider exploration of PRL3 expression in embryonal and mesenchymal tumors and further clinical application of PRL3-zumab in pediatric patients.

Oncolytic virotherapies for pediatric tumors.

INTRODUCTION: Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients. AREAS COVERED: We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies. EXPERT OPINION: Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

Pediatric Laryngeal Granular Cell Tumor: Case Report and Literature Review.

Granular cell tumors (GCTs) are rare benign tumors that can occur in any part of the body. They are most commonly found in the head and neck region, especially the tongue. Laryngeal GCTs are rare, accounting for only 3% to 10% of all GCTs. This case report describes a 4-year-old boy with a laryngeal GCT. The patient presented with a history of hoarseness for 2 years. Stroboscopy revealed a large mass occupying the entire length of the left vocal cord. The mass was successfully removed by microlaryngeal surgery with laser ablation. The patient's symptoms resolved after surgery, and he had an uneventful recovery. This case highlights the importance of considering GCTs in the differential diagnosis of patients with hoarseness. Early diagnosis and treatment can lead to excellent outcomes.

Cryoablation for Bone and Soft Tissue Lesions in Pediatric Patients: Complications and Preventive Measures.

PURPOSE: To evaluate complications associated with cryoablation in a pediatric population and review preventive measures to mitigate these complications. MATERIAL AND METHODS: Retrospective study including all the image guided cryoablations performed on pediatric population. Immediate and delayed complications were analyzed, and we identified the different protective measures used and the clinical outcomes from follow-up. Point estimates for the percentage of complications were calculated by maximum likelihood, and 95% confidence intervals for the true percentages were calculated using the Clopper-Pearson exact method. RESULTS: Eighty-seven ablations were performed on 68 patients (age range of 2-18 years, mean 12.4 years) for non-neoplastic (70%) and neoplastic (30%) lesions. The percentage of ablations resulting in complications was 18% (95% confidence interval (CI) 11% to 28%). Of these, 5% (95% CI 1% to 11%) were grade 3 complications, and 14% (95% CI 7% to 23%) were grade 2 complications. Thermal protection was performed in 27.6% of ablations (n = 24). The mean clinical follow-up duration was 348 days. CONCLUSION: Cryoablation in pediatric patients is relatively safe, with a major complication rate per ablation of 5%. Thermal protective measures can be considered to mitigate these complications.