Pazopanib Combined With Vincristine and Irinotecan in Relapsed Wilms Tumor: Encouraging Outcomes in a Heavily Pretreated Pediatric Cohort

ABSTRACT Background While Wilms tumor (WT) typically has a favorable prognosis, relapsed cases—especially those with high‐risk histology—remain therapeutically challenging after intensive frontline therapy. The combination of vincristine and irinotecan has demonstrated activity in pediatric solid tumors, and pazopanib, a multi‐targeted tyrosine kinase inhibitor, might enhance treatment efficacy through antiangiogenic mechanisms. Methods This report included six children with relapsed WT treated between 2015 and 2022 at Bambino Gesù Children's Hospital, Rome. All patients had received prior multimodal therapy, including six chemotherapeutic agents. The VIPaz regimen (vincristine, irinotecan, pazopanib) was administered as second‐ or third‐line therapy in combination with surgery and/or radiotherapy. Treatment response and toxicity were evaluated. Results Five out of six patients (83%) responded to the treatment. Three (50%) achieved complete remission and remained disease‐free at 27, 74, and 76 months post‐treatment. VIPaz was generally well‐tolerated. No Grade >3 toxicities were observed. Conclusion VIPaz in combination with surgery and/or radiotherapy demonstrated an acceptable safety profile and durable responses in 50% of heavily pretreated patients with relapsed high‐risk WT. Although limited by small sample size and retrospective design, these findings support further prospective evaluation of pazopanib‐based regimens and biomarker‐driven approaches in this population.

Association of MMP‐2 and MMP‐9 Polymorphisms and the Pathogenesis of Childhood Burkitt's Lymphoma

ABSTRACT Introduction Burkitt lymphoma (BL) is a highly aggressive and invasive non‐Hodgkin lymphoma derived from germinal center B cells and represents one of the most common childhood malignancies. Matrix metalloproteinases (MMPs) play a critical role in cancer progression by remodeling the extracellular matrix and modulating the tumor microenvironment. In advanced stages, MMPs facilitate tumor invasion and metastasis through the degradation of extracellular matrix components. This study aimed to investigate the association between MMP‐2 and MMP‐9 gene polymorphisms and the pathogenesis of childhood BL. Methods This study was conducted at the Pediatric Oncohematology Center of the University of Pernambuco between 2021 and 2023 and included patients of both sexes aged 1 to 18 years diagnosed with BL between 1993 and 2023. Genomic DNA was extracted from peripheral blood samples using the salting‐out method. Polymorphisms were identified by real‐time polymerase chain reaction (PCR) using the TaqMan system. Results A total of 56 patients diagnosed with BL were analyzed; most were male, with a mean age of 7.1 years. The overall survival rate was 92.6%. A protective effect of the mutant TT genotype was observed compared to the wild‐type CC genotype (OR = 0.0562; 95% CI: 0.0068–0.4644; p = 0.0016) for the MMP‐2 polymorphism. Furthermore, individuals carrying the mutant G allele showed a positive association with BL compared to the wild‐type A allele (G vs. A: OR = 1.9920; 95% CI: 1.1812–3.3594; p = 0.0130). Conclusion These findings contribute to a better understanding of the genetic factors influencing BL susceptibility and support the need for further functional and large‐scale studies to elucidate the mechanistic role of MMP‐2 and MMP‐9 polymorphisms in BL pathogenesis.

Incidence and Outcome of Infants With Cancer in Canada: A Report From Cancer in Young People in Canada Database

ABSTRACT Purpose Infants with cancer are rare and face unique challenges. Our study aims to describe the incidence of infantile cancers in Canada and to compare treatment‐related mortality (TRM) and their outcomes with those of older children. Methods We conducted a retrospective cohort study using the Cancer in Young People in Canada database, including all infants (0 to <1 year old) with newly diagnosed cancer from 2001 to 2020. Population‐based data were used to estimate annual cancer incidence. Cox proportional hazards models were used to compare TRM, event‐free survival (EFS) and overall survival (OS) between (1) neonates (<30 days old) and older infants (≥30 days to <1 year old, (2) younger (<6 months) and older infants (≥ 6 months), and (3) all infants with older children (≥1 to ≤10 years old). Results A total of 2256 infants were included. The incidence was 30.8 per 100,000 infant‐years, and this incidence increased with an annual percent change of 1.6%, p  < 0.001. Neonates had significantly higher TRM (6.1 vs. 3.6%, HR 2.76, p  < 0.001) as well as infants younger than 6 months (5.2 vs. 2.7%, HR 2.05, p  < 0.001). Compared with older children, infants experienced higher risk of TRM (4.1 vs. 2.1%, HR 2.45, p  < 0.001) and had inferior 5‐year EFS (66.2 vs. 68.6%, HR 1.27, p  < 0.001) and OS (77.5 vs. 78.6%, HR 1.22, p  < 0.001). Conclusion The annual incidence of infantile cancers in Canada has increased and their outcomes are significantly worse than those of older children, as they face a higher risk of TRM, particularly in younger infants. Précis The incidence of cancer in infants has increased significantly in Canada between 2001 and 2020 and their outcomes are significantly lower than those of older children, being at greater risk of TRM.

Congenital Myelodysplastic Syndrome in a Newborn With Germline JAK2 Variant Treated With Liposomal Cytarabine–Daunorubicin and Allogeneic Hematopoietic Stem Cell Transplant

Preoperative Cytopenia in Patients Affected by High‐Risk Neuroblastoma: Just a Matter of Platelets?

ABSTRACT Background and Aims In patients affected by high‐risk neuroblastoma (HR‐NB), complete macroscopic resection (CMR) is associated with better outcomes. These patients are often cytopenic due to intensive induction regimens. The aim of the present study is to assess the impact of preoperative cytopenia on surgical outcome in patients with HR‐NB. Methods A chart review of patients with HR‐NB operated on after neoadjuvant chemotherapy between January 2013 and July 2024 was conducted. Cytopenia was defined by full blood count values in the 24 h before surgery. Two primary outcomes were analyzed: the rate of CMR and the incidence of postoperative complications. Secondary outcomes were postoperative length of stay (LOS) and red blood cell transfusion requirement. Results Sixty‐eight patients underwent surgical removal of the primary tumor after induction chemotherapy. Thirty‐seven patients (54%) were cytopenic immediately before surgery; 17 patients had anemia (25%), 20 had thrombocytopenia (29%; 16 patients with platelets between 100 × 10 3 /µL and 50 × 10 3 /µL, four patients with platelets less than 50 × 10 3 /µL), and six had neutropenia (9%). Patients with platelets less than 50 × 10 3 /µL had a significantly higher postoperative complications rate (75% vs. 22%, p = 0.046) and increased median LOS [12.5 days (7–31) vs. 7 days (3–43), p = 0.040], but comparable CMR rate and perioperative RBC transfusion volumes. Anemia, neutropenia, and platelets between 100 × 10 3 /µL and 50 × 10 3 /µL had no impact on outcomes. Conclusions Anemia, neutropenia, and platelets between 100 × 10 3 /µL and 50 × 10 3 /µL are not contraindications to elective major surgery in patients with HR‐NB. The risk of surgical complications in patients with platelets less than 50 × 10 3 /µL has to be balanced against the risk of long delay in surgical treatment.

Anesthesia in Pediatric Radiotherapy: A Systematic Literature Review by the SIOP Europe Working Group on Pediatric Anesthesia in Radiation Therapy

ABSTRACT Radiotherapy (RT) is essential in pediatric cancer treatment and often requires complete immobility. In younger or noncompliant children, this is typically achieved through sedation or general anesthesia (GA), which raises concerns about acute complications and potential long‐term neurodevelopmental effects. Despite widespread use, standardized anesthesia protocols for pediatric RT are lacking. To support the development of practice recommendations, the SIOPE Working Group on Pediatric Anesthesia in Radiation Therapy conducted a systematic literature review. Studies from Medline and Embase were reviewed (March–September 2024) according to PRISMA guidelines, focusing on sedation and GA in pediatric RT. Thirty‐nine studies were included, mostly retrospective and of low to moderate quality. Considerable heterogeneity was observed in anesthetic techniques, staffing, and monitoring. Propofol‐based sedation was most frequently reported, with favorable safety when delivered by experienced pediatric anesthetists. Complication rates varied widely and were often poorly defined. Additional concerns included long‐term neurocognitive impact, vascular access, and procedural burden, especially in resource‐limited settings. Evidence supports the safe use of sedation/GA in pediatric RT, but current literature is limited and inconsistent. Standardized protocols and prospective studies are urgently needed to better define safety, long‐term outcomes, and staffing requirements.

The Evolving Spectrum of Paediatric Ovarian Malignancies From Childhood to Adulthood: A Multicentre Experience

ABSTRACT Background/Objectives Ovarian malignancies in children and young women exhibit distinct clinical characteristics and may be managed by either paediatric surgeons or gynaecologists, depending on patient age and institutional protocols. This multicentre retrospective study aims to evaluate similarities and differences in the management and outcomes of ovarian malignancies treated by different surgical teams. Design/Methods A multicentre retrospective review was conducted, including patients who underwent surgery for ovarian malignancies from 2013 to the present. Data were collected from two paediatric surgical departments and one adult gynaecological department. Patients were categorized into two groups according to the surgical team: Group A (paediatric surgeons) and Group B (gynaecologists). Clinical, diagnostic, surgical and oncological data were analysed. Results A total of 52 patients were included: 29 in Group A (median age 10 years, range 3–15) and 23 in Group B (median age 31 years, range 23–39). The most common tumour types were immature teratomas in Group A (45%) and borderline tumours in Group B (43.5%). Group A commonly underwent transabdominal ultrasound (87%) and MRI (31%), whereas Group B received transvaginal ultrasound (100%) and CT scans (78.2%). In Group A, 62% of girls underwent laparotomy, whereas 83.4% of women (Group B) underwent laparoscopy ( p  < 0.01). Oophorectomy was performed in 90% of cases across both groups. Patients in Group A presented more frequently with early‐stage disease (93% vs. 30%, p  < 0.05). During follow‐up, relapse occurred in three paediatric and four adult patients, and two patients (one from each group) died due to disease progression. Conclusions Despite variations in preoperative assessment and surgical approaches, postoperative oncological treatment and long‐term outcomes, including disease‐free and overall survival, were comparable between the groups. Integrating the strengths of both paediatric and gynaecological approaches may further optimize the management of ovarian malignancies in young patients.

Liver‐Related Late Effects in Long‐Term Survivors of High‐Risk Neuroblastoma: Insights From a Comprehensive Prospective Follow‐Up Study

ABSTRACT Background Therapeutic advances in pediatric oncology have significantly improved overall survival, with a higher incidence of long‐term adverse effects and sequelae. Among pediatric cancer survivors, the highest incidence of hepatic lesions has been observed in those previously treated for high‐risk neuroblastoma (HRNB). While hepatic nodules in these patients historically raised concern for tumor locations, recent attention has shifted toward non‐tumoral, late‐onset hepatic sequelae. Methods In this study, we retrospectively reviewed long‐term liver outcomes from an institutional perspective follow‐up protocol, including long‐term HRNB survivors (>5 years from diagnosis) treated between 1996 and 2018 at a tertiary pediatric center. Results A total of 47 patients were included, with a median follow‐up of 11.1 years. Liver parenchyma was normal in 11 (23%) patients throughout the whole follow‐up period. Diffuse parenchymal inhomogeneity was observed in 36 patients out of 47 (76%). Out of 36 patients, 16 showed a stable, diffuse, non‐nodular alteration of the liver during the whole follow‐up period, while in seven patients, the liver involvement completely regressed after a median of 2.8 years. Moreover, 13 out of 36 patients (36%) with diffuse parenchymal inhomogeneity developed nodular lesions after a median of 7.7 years from diagnosis and 1.7 years from the onset of parenchymal alterations. Alpha‐fetoprotein levels were normal in all patients. Conclusions A structured, integrated, multidisciplinary follow‐up program revealed an unexpectedly high prevalence of hepatic abnormalities on imaging. Further studies are needed to define the long‐term risk of developing liver complications, both in terms of malignancy and functional impairment.

Bridging the Gap: Regional Disparities in Access to Pediatric Hematopoietic Stem Cell Transplantation (HSCT) in the Andean Subregion

ABSTRACT Background Pediatric hematopoietic stem cell transplantation (HSCT) is a life‐saving therapy for malignant and non‐malignant hematologic diseases. However, access to this high‐complexity treatment remains limited and uneven across the Andean subregion. This study aimed to evaluate the current status, capacity, and equity of pediatric HSCT programs in six Andean countries (Bolivia, Chile, Colombia, Ecuador, Peru, and Venezuela) within the framework of WHO Global Initiative of Childhood Cancer. Methods A mixed‐methods, cross‐sectional situational assessment was conducted between November 2024 and January 2025 under the coordination of the Andean Health Organization (ORAS‐CONHU) and the Pan American Health Organization (PAHO). Standardized national and center‐level surveys (34 and 150 items, respectively) were applied to Ministries of Health and HSCT centers to collect data on infrastructure, workforce, financing, quality management, and barriers to access. Quantitative data were analyzed descriptively and validated by national committees, complemented by qualitative interviews with key stakeholders. Results Twenty‐seven HSCT centers were identified across the subregion, revealing major disparities in access and capacity. Chile reached 100% coverage of estimated transplant needs, whereas Colombia, Peru, and Venezuela achieved 80%, 29%, and 42.5%, respectively. Bolivia and Ecuador had the lowest coverage (1.6% and 24%). Only 28% of units were pediatric‐exclusive, and less than two‐thirds met full quality and training standards. High‐cost medicines, limited infrastructure, and shortages of specialized personnel were identified as critical barriers, whereas regional collaboration and national policies emerged as key facilitators. Conclusion The study highlights significant inequities in pediatric HSCT access and capacity across the Andean subregion. Strengthening infrastructure, workforce training, financing mechanisms, and data systems, supported by sustained regional cooperation, is essential to achieve equitable, high‐quality transplant care for all children.

Creation of Blinatumomab Administration Standards: A Single Institution's Experience

ABSTRACT Background Blinatumomab has transformed the treatment of pediatric B‐acute lymphoblastic leukemia (B‐ALL). However, it presents distinct operational challenges for administration given it is delivered as a continuous infusion and has unique toxicities. The objective of this project was to develop, implement, and evaluate a standardized institutional protocol for blinatumomab administration to optimize safety, efficiency, and patient experience. Procedure This quality improvement (QI) initiative was conducted at The Hospital for Sick Children, Toronto, Canada. A multidisciplinary Blinatumomab Working Group developed harmonized standards across five domains: (1) caregiver education, (2) fever management, (3) nursing‐led assessments, (4) infusion interruption management, and (5) use of 7‐day infusion bags. Patients receiving blinatumomab for upfront therapy or for relapsed disease between July 2024 and August 2025 were included. Demographic and clinical data were extracted from the institutional data warehouse. Outcomes included rates of caregiver education completion, antibiotic use during blinatumomab initiation, and completion of nursing‐led assessments. Results Fifty‐three patients received standard of care blinatumomab. All eligible caregivers (100%) completed standardized education. The rate of empiric antibiotic use during blinatumomab initiation decreased from 68% to 22% following adoption of selective antibiotic initiation without increased readmission, or prolonged stay. Nursing assessment completion was 95% for inpatients and 81% for outpatients. Infusion interruptions were managed using a standardized, risk‐based algorithm without observed safety events. Conclusion Implementation of multidisciplinary, standardized blinatumomab administration protocols was feasible and safe. These processes improved antibiotic stewardship, empowered nursing‐led care, and reduced practice variability. This framework may inform best practices for the safe and efficient delivery of blinatumomab in other pediatric oncology centers.