Background:Diffuse intrinsic pontine glioma (DIPG) is one of the most aggressive pediatric brain tumors, with a median overall survival of less than 12 months despite radiotherapy remaining the current standard of care. This study aimed to evaluate the clinical outcomes and toxicity of concurrent radiotherapy with temozolomide followed by adjuvant therapy in newly diagnosed pediatric DIPG. Methods:Retrospective analysis of 24 consecutive pediatric DIPG patients (2006-2020) treated with focal radiotherapy (45-59.4 Gy) plus concurrent temozolomide (75 mg/m2/day), followed by adjuvant temozolomide (200 mg/m2/day, days 1-5, every 28 days for ≤13 cycles) was conducted. Primary endpoints included overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Response assessment utilized standardized neuroimaging criteria at predetermined intervals. Results:Median age was 7 years (range, 3-16 years). H3K27M mutation was detected in 74% of biopsied cases (14/19). Post-radiotherapy imaging showed partial response in 12 patients (50%), stable disease in 9 (38%), and progression in 3 (12%). Median OS was 12.0 months [95% confidence interval (CI): 7.0-14.0]; median PFS was 9.0 months (95% CI: 7.0-12.0). One- and two-year OS rates were 54% and 8%, respectively. Grade 3-4 hematological toxicity occurred in 10 patients (42%): leucopenia (n=4), thrombocytopenia (n=6). No treatment-related deaths occurred. Conclusions:Concurrent chemoradiotherapy achieved encouraging response rates with manageable toxicity profile. However, survival outcomes remain limited, underscoring the need for novel therapeutic approaches targeting specific molecular pathways in this devastating malignancy.

Background: Pediatric cancer is a highly stressful and potentially traumatic condition affecting physical health, emotional well-being, developmental trajectories, and family functioning. Hospitalization and intensive treatments often exacerbate emotional distress and symptom burden, negatively impacting quality of life (QoL). Integrating psychosocial and expressive interventions into pediatric oncology care is increasingly recognized as essential. Clay therapy is a multisensory, hands-on creative intervention that may promote emotional regulation, coping, and a sense of agency in hospitalized children. Objectives: This prospective pilot study evaluated the effects of clay therapy on emotional and physical well-being in pediatric oncology patients and explored potential indirect effects on caregivers' emotional status. Methods: From December 2023 to December 2024, forty hospitalized children with onco-hematological diseases and one parent per patient were enrolled. Each child participated in a one-hour clay therapy workshop led by a professional ceramist. Emotional outcomes were assessed before (T0) and immediately after (T1) the intervention using the Visual Analog Scale (VAS) and the ArtsObs observational scale. Physical symptoms, including pain, fatigue, and nausea, were also evaluated. Results: Following clay therapy, children showed statistically significant improvements across all VAS emotional domains, independent of age and gender. ArtsObs assessments confirmed a significant increase in observed mood, with high levels of relaxation and engagement; female patients demonstrated greater mood improvement than males. Significant reductions in pain, fatigue, and nausea were also observed. Parents exhibited a significant improvement in mood following their child's participation. Conclusions: These findings suggest that clay therapy is feasible and could be an effective supportive intervention in pediatric oncology, benefiting both emotional and physical well-being. Its integration into multidisciplinary, family-centered care models may enhance QoL during hospitalization and provide holistic support for children with cancer and their families.

BACKGROUND:Immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in childhood. Although viral infections and some vaccinations are recognized triggers, data on the onset or exacerbation of ITP following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pediatric patients remain limited. OBJECTIVES:To evaluate the incidence and clinical characteristics of new-onset ITP and the safety of SARS-CoV-2 vaccination in children with preexisting or resolved ITP. METHODS:We evaluated the incidence and clinical characteristics of ITP occurring after SARS-CoV-2 vaccination, as well as the effects of vaccination in children with preexisting ITP. RESULTS:De novo ITP: five cases of new-onset ITP were identified nationwide, most of which occurred after the first vaccine dose (80%). Despite low median platelet counts at presentation, no major or fatal bleeding events were observed. Most patients responded favorably to first-line treatments (intravenous immunoglobulins and/or corticosteroids), and 80% achieved normal platelet counts at the last follow-up. Preexisting ITP: among 164 vaccinated patients with complete clinical data, only 8.5% (n = 14) experienced a transient platelet count decline or new bleeding manifestations. Notably, no relapses occurred among the 34 patients who were in clinical remission at the time of vaccination. CONCLUSIONS:ITP following SARS-CoV-2 vaccination in the pediatric population is exceedingly rare and generally mild. Moreover, SARS-CoV-2 vaccination appears safe in children with preexisting or resolved ITP.

Colorectal cancer (CRC) is extremely rare in paediatrics with aggressive histopathology and advanced presentation. Whilst pembrolizumab has shown efficacy in adult microsatellite instability-high or mismatch repair deficiency CRC, paediatric data remain scarce. A 12-year- old boy with Lynch syndrome-associated CRC developed severe cardiac toxicity after initial chemotherapy. Treatment was switched to off-label pembrolizumab, resulting in a complete response after 24 cycles. Despite good tolerability, the patient developed a delayed bowel stricture at the tumour site. After surgery, there was no pathological evidence of residual adenocarcinoma. This case demonstrates the potential of pembrolizumab in paediatric CRC, highlighting the importance of molecular-guided rather than age-restricted therapy selection.

Background/Objectives: Diencephalic syndrome (DS) is an uncommon pediatric disorder presenting with severe failure to thrive despite adequate caloric intake and preserved linear growth. First characterized by Russell, this condition predominantly affects infants under 12 months and remains diagnostically challenging. Methods: We performed a comprehensive literature review examining clinical presentation, underlying pathophysiology, associated pathology, diagnostic approaches, and long-term outcomes of DS. Results: DS typically manifests in the first year of life with profound cachexia, normal or increased appetite, preserved height velocity, and characteristic features including hyperactivity, euphorism, and visual pathway involvement. Low-grade gliomas of the hypothalamic–chiasmatic region, particularly pilocytic astrocytomas, represent the predominant underlying pathology. The pathophysiological mechanisms remain incompletely understood but likely involve complex dysregulation of hypothalamic energy homeostasis. While overall survival exceeds 90% at five years, most patients experience significant long-term morbidity including visual impairment, multiple endocrine deficiencies, and hypothalamic obesity. Diagnostic delays averaging 11 months contribute to irreversible complications. Conclusions: Early recognition of DS is essential to prevent permanent visual loss and optimize outcomes. Multidisciplinary management incorporating chemotherapy as first-line treatment for underlying gliomas has improved survival while reducing radiation-associated toxicities. However, survivors face substantial lifelong sequelae requiring comprehensive monitoring and intervention. Future research should focus on elucidating precise pathophysiological mechanisms, developing targeted molecular therapies, and improving management of hypothalamic obesity and other late effects.

Background/Objectives: Scoliosis is a prevalent comorbidity in Rett syndrome (RTT), often necessitating surgical intervention. This study investigated the impact of a 10-month individualized home exercise program (HEP) on scoliosis progression and gross motor function in girls aged six to 16 years with RTT. Methods: A multiple-baseline single-case design (AABA) was employed with 20 participants. A remotely supervised HEP, based on established principles focused on posture and physical activity, was implemented daily for at least one hour. The primary outcome was the rate of scoliosis progression assessed through the Cobb angle change measured via spinal radiographs at baseline, pre-intervention, and post-intervention. The secondary outcome was the gross motor function. Results: The HEP did not significantly reduce the rate of scoliosis progression. However, individual responses varied, with three participants showing scoliosis reduction. Significant improvements were observed in gross motor function, particularly in standing, walking, and stair-climbing abilities. Conclusions: The HEP did not significantly impact overall scoliosis progression, but a significant improvement was found in gross motor function. Further research into larger sample sizes is needed to confirm the effectiveness of exercise interventions in people with RTT.

Medulloblastoma represents a rare yet complex embryonal tumor of the posterior cranial fossa that, while predominantly affecting pediatric populations, occurs with increasing recognition among adolescents and young adults (AYAs, 15–39 years). The scarcity of medulloblastoma within this demographic creates substantial obstacles in diagnosis, treatment selection, and psychosocial management that differ markedly from established pediatric approaches. Emerging data reveal that AYA patients exhibit distinctive tumor biology, including altered molecular subgroup patterns, variable therapeutic responses, and unique survival trajectories when compared to younger patients. Current investigations examining autologous stem cell transplantation following intensive chemotherapy protocols in metastatic cases demonstrate encouraging preliminary results. Evidence increasingly supports adapting pediatric treatment paradigms for adult application, potentially improving therapeutic outcomes while reducing treatment burden. These cross-disciplinary approaches between pediatric and adult oncology demonstrate considerable promise for enhancing clinical results and minimizing therapy-associated morbidity, emphasizing the critical need for collaborative care models in managing this challenging malignancy across diverse age groups.

Traditionally, cancer treatment relied on the maximum tolerated dose (MTD) approach, in which chemotherapeutic agents are given at the highest dose that patients can tolerate, with scheduled breaks to allow for recovery. However, this method has notable drawbacks, including significant toxicity, tumor regrowth during drug-free intervals, and the development of resistance. Metronomic chemotherapy offers an innovative alternative, characterized by continuous low-dose administration without treatment interruptions. This approach primarily targets the tumor microenvironment, including tumor vasculature and cancer stem cells, while also affecting the immune system. By maintaining a steady level of drug exposure, metronomic therapy prevents the recovery of tumor endothelial cells and enhances immune surveillance, leading to prolonged disease stabilization and potentially improved long-term outcomes. Due to its reduced toxicity, cost-effectiveness, and suitability for oral administration, metronomic chemotherapy is especially beneficial for long-term maintenance therapy for the elderly, or frail patients. This review explores the mechanisms, clinical advantages, and challenges of metronomic chemotherapy, as well as its potential for integration with other treatment modalities to improve patient outcomes. Additional research is needed to optimize drug dosing, identify biomarkers for treatment response, and conduct large-scale clinical trials comparing metronomic approaches with standard chemotherapy regimens.

Background:Adult medulloblastoma (MB) represents less than 1% of central nervous system malignancies, lacking standardized therapeutic approaches due to its rarity. This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols. Methods:Eighteen patients (≥18 years) with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (January 1997-January 2024) were analyzed. All received craniospinal radiotherapy with posterior fossa boost, followed by adjuvant chemotherapy utilizing pediatric regimens (PNET3, PNET4, PNET5, or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue). Primary outcomes included overall survival (OS) and progression-free survival (PFS). Secondary analyses focused on comprehensive toxicity assessment. Results:The cohort included 11 males and 7 females (median age: 23 years). Metastatic disease was present in 6 patients (33%) at diagnosis. Histopathological distribution showed classic MB (55.5%), desmoplastic/nodular (39%), and large cell/anaplastic variants (5.5%). Molecular subgrouping (available in 6 patients) identified SHH subgroup in four cases and WNT subgroup in two. Three-year and five-year overall survival rates reached 94.5% and 88.8%, respectively. Treatment-related adverse events included grade 3-4 hematologic toxicities, clinically significant weight loss, and grade ≥3 neurological and ototoxic complications. These toxicities necessitated treatment modifications including dose adjustments, cycle delays, and occasional early discontinuation. Conclusions:Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-term survival outcomes, comparable to or surpassing historical data. Despite frequent toxicity requiring treatment modifications, these regimens proved feasible with acceptable risk-benefit profiles. These results support implementing modified pediatric protocols for adult MB management. Future multicenter investigations with larger cohorts are essential for refining risk stratification, optimizing treatment intensity, and evaluating long-term outcomes in this rare malignancy.

Solid pseudopapillary neoplasms (SPNs) represent a tumor of the exocrine pancreas, belonging to the group of pancreatic cystic neoplasms. It is exceedingly uncommon for SPNs to manifest in extrapancreatic locations, such as the mesocolon, greater omentum, jejunum, and ovary. SPNs are considered very rare, constituting about 0.17%-2.5% of all pancreatic neoplasms and 6% of cystic pancreatic neoplasms. We present two pediatric cases of SPNs: one involving a 16-year-old female patient and the other a 14-year-old girl, both diagnosed and treated in our center with surgical resection. The experience of our center confirms that wide margin surgery, with associated metastasectomy if necessary, represents the therapy of choice for SPNs, ensuring effective control of the disease.

Platinum-induced ototoxicity constitutes a significant adverse effect in pediatric oncology, frequently resulting in permanent hearing impairment with profound implications for quality of life, language acquisition, and scholastic performance. This comprehensive review critically evaluates contemporary ototoxicity monitoring practices across various pediatric oncology settings, analyzes current guideline recommendations, and formulates strategies for implementing standardized surveillance protocols. Through examination of recent literature—encompassing retrospective cohort investigations, international consensus recommendations, and functional outcome assessments—we present an integrated analysis of challenges and opportunities in managing chemotherapy-associated hearing loss among childhood cancer survivors. Our findings demonstrate marked heterogeneity in monitoring methodologies, substantial implementation obstacles, and considerable impact on survivors’ functional status across multiple domains. Particularly concerning is the persistent absence of an evidence-based consensus regarding the appropriate duration of audiological surveillance for this vulnerable population. We propose a structured framework for comprehensive ototoxicity management emphasizing prompt detection, standardized assessment techniques, and integrated long-term follow-up care to minimize the developmental consequences of platinum-induced hearing impairment. This approach addresses critical gaps in current practice while acknowledging resource limitations across diverse healthcare environments.

Healthcare professionals in pediatric oncology are at a high risk of burnout. Art therapy is being increasingly recognized as a potential tool for reducing stress and improving emotional well-being. The Art-Out pilot project aimed at nursing staff was initiated in a pediatric oncology unit. The staff members participating in the project were guided in a team-building course integrated with art and clay therapy, aiming to reduce burnout levels, improve emotional climate, and strengthen resilience. Methods: Burnout levels were assessed through the Maslach Burnout Inventory (MBI), alexithymia was measured with the Toronto Alexithymia Scale (TAS-20), and emotional regulation difficulties were evaluated through the Difficulties in Emotion Regulation Scale (DERS); these tests were assessed before (T0) and after (T1) the team-building course (Art-Out project). Results: Data analysis showed a significant reduction in burnout, alexithymia, and emotional dysregulation, highlighting the positive impact of this approach in improving team dynamics and emotional management. Conclusions: Our study confirms the high risk of burnout, alexithymia, and emotional dysregulation among pediatric oncology healthcare workers, underscoring the need for targeted interventions to prevent and mitigate these risks.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical during platinum-based therapy, playing key roles in the early detection of hearing loss. Interdisciplinary collaboration amongst paediatric oncologists, audiologists and otolaryngologists is essential for optimal management and to minimize the long-term consequences of hearing loss. This narrative review concludes that, whilst platinum-based chemotherapeutic agents demonstrate significant therapeutic efficacy in paediatric malignancies, platinum-induced ototoxicity remains a substantial clinical challenge. Continued research into prevention, monitoring and treatment strategies is essential for preserving hearing and improving the overall quality of life for survivors of childhood cancer.

Background:Pediatric central nervous system (CNS) tumors are the second most common malignancy in children and are associated with significant long-term morbidity despite advancements in therapy. Endocrine dysfunction is one of the most frequent and impactful late sequelae, requiring timely detection and management. This study aimed to investigate the timing and risk factors associated with endocrine dysfunction in pediatric brain tumor survivors and to propose optimized follow-up protocols. Methods:A cohort of 33 pediatric patients with brain tumors, excluding craniopharyngiomas, pituitary adenomas, and germ cell tumors, treated at the Pediatric Oncology Unit of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS in Rome (2005-2015), was retrospectively analyzed. Endocrine dysfunction was assessed through clinical and laboratory evaluations, with a median follow-up of 114.1 months. Results:Endocrine dysfunction was identified in a high percentage of patients, with hypothyroidism and panhypopituitarism being the most common. Age at diagnosis and treatment influenced the appearance and the timing of dysfunction. Hypothalamic and suprasellar tumors were associated with early onset, while tumors in posterior cranial fossa exhibited delayed onset. Conclusions:Tumor location and patient age are critical determinants of the timing of endocrine dysfunction in pediatric brain tumor survivors. We propose a stratified follow-up based on tumor location, with immediate evaluation for hypothalamic and supratentorial tumors and periodic assessments for other regions. These tailored recommendations aim to ensure timely detection and management of endocrine complications, improving outcomes and quality of life. Future research with larger cohorts is needed to validate and refine these findings.

Purpose To assess the prevalence of alterations in anthropometric parameters predictive of metabolic syndrome and cardiovascular risk among childhood brain tumor survivors. Methods Anthropometric parameters predictive of metabolic syndrome and cardiovascular risk were analyzed [height, weight, BMI, waist circumference, hip circumference, waist-height ratio (WHtR), waist-hip ratio (WHR, blood pressure] of 25 patients who survived childhood brain tumors. Results 21 patients (84%) showed alteration of at least one predictive anthropometric parameter. 11 patients (44%) showed a BMI > 75th percentile and 19 patients (76%) showed a pathological WHR value. A pathological WHtR (> 0.5), was identified in 17 patients (68%); the average WHtR observed was 0.53. 9 patients (36%) showed an alteration of all three anthropometric parameters considered. Comparing this subpopulation with the subpopulation with less than three altered parameters, a greater prevalence of the combined alteration was observed in the female sex compared to the male sex (67% vs. 26%). No significant differences were observed regarding the age of diagnosis and end of treatment nor the treatments carried out (chemotherapy, radiotherapy, steroid therapy) between the two groups. Conclusion These results suggest that this population is at high risk of presenting pathological values of BMI, WHR and WHtR with consequent high risk of developing metabolic syndrome and cardiovascular diseases.

Background During the last decade, there has been a growing number of cases of children born from pregnancy-associated cancer (PAC), however there are currently insufficient data on the follow up to be observed in this category of newborns. Objective of the study was to evaluate the neonatal outcomes of infants born to mother with PAC, the potential adverse effect of chemotherapy during pregnancy and the risk of metastasis to the fetus. Methods Maternal clinical data and neonatal outcomes of child born to mothers diagnosed with PAC were collected; infants were divided into those were and were not exposed to chemotherapy during fetal life and their outcomes were compered. Results A total of 37 newborn infants from 36 women with PAC were analyzed. Preterm delivery occurred in 83.8% of the cases. No significant differences in neonatal outcomes were found between infants who were and were not exposed to chemotherapy during pregnancy. The median follow-up period was 12 months. Conclusions PAC treatment during the second or third trimester does not seem to be dangerous for the fetus, however infants born from PAC must be carefully evaluated for to rule out the consequences of chemotherapy and exclude the presence of metastasis. Long-term follow-up, especially in children exposed to chemotherapy, should be encouraged to obtain relevant data on long-term toxicity.

Background/Objectives: Appendiceal neuroendocrine neoplasms (ANENs) are usually found incidentally during histology examination after appendectomy for appendicitis. Due to their rarity in pediatric populations, there is no consensus on treatment or follow-up. The analysis of patients with ANENs of our and other studies will increase the understanding of this tumor. Methods: Pediatric patients with ANENs were uniformly managed at our center between 1998 and 2023. Patients’ presenting symptoms, surgery, tumor histology, post-surgical work-up, follow-up and outcome were analyzed. Results: Our report describes 17 patients with a diagnosis of ANEN after appendectomy. The median age was 14 years (range of 4–17 years). Tumors were located at the tip of the appendix in 58.8% of cases and only one had a diameter >1 cm. All were well-differentiated tumors with free resection margins. The submucosa was invaded in five cases, muscularis propria in eight and subserosa in four. Post-appendectomy work-up included tumor marker measurement, abdominal ultrasound and computed tomography or magnetic resonance imaging, chest X-ray and octreotide scintigraphy. No residual tumors or metastases were detected. Additional surgery was not necessary. Follow-up was carried out for a median duration of 6 years (range of 1–10 years). Only one patient was lost to follow-up and all other patients are alive without tumor recurrence. Conclusions: The tumor characteristics of our patients confirmed data from the literature. With the lack of a sufficient number of large prospective trials, it is important to add more information to confirm the benign nature and excellent outcome of this tumor, even without additional surgery. Consensus guidelines are needed for ANENs in pediatric populations.

Individuals with intellectual and developmental disabilities (IDD) present multiple co-morbidities within the medical, physiological, and mental areas, thereby putting them at an increased risk for a variety of illnesses. Moreover, many of them are living a life of inactivity, thereby worsening their health condition. Many researchers have identified a clear relationship between physical fitness and wellness. This chapter will describe the poor physical condition of individuals with IDD and will suggest some intervention possibilities, focusing on motivational factors and integration into the person’s daily living routines. While some physical activity possibilities are free and can be found online, other more advanced tools for promoting an active lifestyle can be implemented with this group of people. The present chapter will suggest research-based effective strategies to enhance the physical activity of people with IDD through remote activity intervention programs, virtual reality training, and personally adapted simple training applications.

Background: Physical therapy plays a crucial role in addressing the physical challenges faced by individuals with autism spectrum disorder (ASD). Amidst the COVID-19 pandemic lockdown, physical therapists (PTs) working in special education centers for ASD children were tasked with deploying remote telehealth interventions (RTIs), an uncommon approach in physical therapy until then. The present article aims to describe and discuss the PTs’ perspective of using RTI with children with ASD during the national Israeli COVID-19 lockdown. Methods: Reports from 13 experienced PTs who treated and supported 244 children with ASD using RTIs over six weeks were analyzed. The study employed quantitative research methods, including freely written reports and discussions addressing the question “what were your experiences as a PT treating ASD children remotely during the nationwide COVID-19 lockdown?” Results: the reports were categorized into four main themes: (a) the implications of RTIs on the children; (b) the implications of RTIs on the PTs; (c) modifications for applying RTI; and (d) PTs’ family rapport as a necessary basis for RTI. Noteworthy findings include the unaffected implementation of RTIs by ASD severity level and the dependence of RTI’s success on parental availability and the ability of parents to tailor activities for their child. Conclusions: The findings of the current research suggest that PT services through RTIs are well-suited for individuals with ASD and their families.