Childhood cancer comprises a heterogeneous group of diseases, with disproportionately higher mortality in low- and middle-income countries (LMICs) due to limited access to molecular diagnostics. Pediatric germ cell tumors (GCTs) are rare and represent 3

BACKGROUND:Bilateral ovarian tumors in pediatric patients present a surgical challenge requiring complete tumor removal while preserving sufficient ovarian tissue for endocrine function and future fertility. In bilateral disease, preservation is often feasible only on the ovary that retains salvageable parenchyma. Exoscope systems provide high-definition magnified visualization of the operative field. To our knowledge, this is one of the first reports of exoscope-assisted ovarian-sparing surgery in pediatric patients. This study describes the technical feasibility of the technique and the completeness of tumor removal with preservation of ovarian parenchyma. METHODS:We conducted a retrospective case series of four patients with bilateral ovarian tumors who underwent exoscope-assisted ovarian-sparing surgery between 2020 and 2024 at a Brazilian pediatric cancer center. Eligible patients had imaging consistent with benign lesions and normal serum tumor markers. Surgical technique combined exoscopic magnification with intraoperative ultrasonography in open procedures. RESULTS:All patients had mature teratomas confirmed on final pathology. No intraoperative capsular ruptures occurred across the four preservation procedures. Mean follow-up was 31.0 months (range 20-39). Two patients maintained regular spontaneous menses without hormonal supplementation. One patient developed clinical hypogonadism 8 months after surgery and received hormone replacement therapy, after which regular cycles resumed. One patient was not assessable for spontaneous menstrual recovery because continuous combined hormonal contraception was started after surgery at her request. No tumor recurrence occurred during follow-up. CONCLUSIONS:Exoscope-assisted ovarian-sparing surgery was technically feasible for the contralateral or remaining ovary in adolescents with bilateral mature teratomas. Spontaneous menstrual function was preserved in two of four patients, one required hormone replacement therapy, and one was not assessable. Controlled studies that include objective ovarian reserve markers and extended follow-up are required before the added value of the exoscope can be established.

Adrenocortical carcinoma (ACC) in children is a rare and aggressive malignancy. Despite representing a small fraction of pediatric adrenal tumors, ACC poses distinct challenges due to its heterogeneous biological behavior, frequent hormone secretion, and the limited availability of standardized, pediatric-specific treatment protocols. Complete surgical resection remains the cornerstone of curative intent therapy, and complete adrenalectomy offers the best chance for long-term survival. Given the aggressiveness of ACC, particularly in advanced disease, adjuvant therapies are often considered to improve outcomes. The aim of this consensus meeting was to bring together international experts to develop international guidance based on the best available evidence and collective clinical experience to harmonize long-term management. A modified 3-step Delphi consensus method was used to finalize the statements from an international panel of pediatric ACC experts from 4 continents (Europe, the Americas, and Asia, and Oceania). An electronic survey was developed by the steering committee (ENSAT Kids) and distributed to the panel. Agreement and disagreement were rated using a 6-point Likert scale with the opportunity to provide structured feedback. Consensus was defined a priori as ≥75% agreement. This Delphi process yielded consensus statements for therapy guidance, comprising 12 surgical statements and 68 medical treatment statements, organized by strategy and disease stage. These statements are intended to support clinicians in delivering more consistent and standardized therapeutic strategies for pediatric ACC. Future efforts should prioritize the design and conduct of high-quality, collaborative research studies in order to provide more evidence and therapy improvements.

IntroductionGerm cell tumors (GCTs) are rare neoplasms affecting approximately 3.5% of all pediatric patients, with diverse histological subtypes. Despite their clinical and biological heterogeneity, pediatric GCTs generally exhibit a low mutational burden. Compared to adult GCTs, however, the molecular characterization of pediatric cases remains limited, hindering the development of targeted therapeutic strategies. Therefore, we aimed to elucidate the genomic landscape of pediatric GCT patients via whole exome sequencing (WES).MethodsWES was performed in 16 pediatric GCTs and respective matched normal samples, including ten ovarian, five testicular, and one mediastinal tumor. The somatic alterations found were described and compared with the clinicopathological characteristics, as well as related to molecular databases.ResultsThe somatic mutations found resemble those observed in adult GCTs and recent pediatric GCTs studies. Genes with predicted oncogenic variants were found in seven samples (43.75%) out of 16 and included KIT (12.5%), KRAS (6.25%), MTOR (12.5%), PIK3CA (6.25%), AKT2 (6.25%), LARP4B (6.25%), and ACSL6 (6.25%). Copy number alterations were identified on chromosomes 4, 7, 8, 10, 12, 21, and 22, with amplification of CDKN1B, KRAS, CCND2, ETV6, and KDM5A genes, and deletions of KIT and PTEN genes. Clinically significant mutations (KIT: Asp816Val, Ala829Pro; and KRAS: Gln61Leu) suggest potential therapeutic targets for GCT, while MTOR, PIK3CA, and AKT2 emerge as candidates for targeted therapy.DiscussionThese findings provide insights into the genomic alterations of pediatric GCTs and emphasize the potential for targeted therapies.

Introduction:Pediatric germ cell tumors (GCTs) are rare malignancies, comprising only about 3% of childhood cancers. Despite surgery and platinum-based chemotherapy being mainstays of treatment, their effectiveness varies by tumor subtype, and long-term toxicities remain a concern. We therefore explored the immune landscape of pediatric GCTs to uncover subtype-specific immunological features and identify potential immunotherapeutic targets. Methods:This retrospective study investigated the immune landscape of pediatric GCTs, utilizing a cohort of 17 patients, including 14 extracranial GCTs (11 ovarian, 3 testicular), three central nervous system (CNS) mixed tumors and four non-neoplastic tissues (controls). Results:Immune profiling revealed distinct immune microenvironments across the GCT subtypes. Dysgerminomas exhibited an immune-active profile with elevated levels of T cells, CD8+ T cells, and cytotoxic cells, alongside upregulation of immune checkpoints CTLA4, TIGIT, and IDO1, suggesting potential responsiveness to checkpoint inhibitors. In contrast, yolk sac tumors displayed an immunosuppressive environment with high CD24 and PVR expression, indicative of unique immune evasion mechanisms. Embryonal carcinomas also showed high CD24 expression. An in silico analysis of adult GCTs highlighted similarities and differences with pediatric cases; IDO1 and CD24 were consistently upregulated across age groups, while CTLA4 and PVR showed variation. Conclusion:Overall, this study provides new insights into pediatric GCT immunology, supporting the potential for tailored immunotherapeutic strategies targeting the distinct immune profiles of pediatric GCT histologies.

INTRODUCTION:In Brazil, inequalities in access to treatment and survival of childhood cancer are observed across different geographic regions. In 2014, under the coordination of Hospital de Câncer Infantojuvenil de Barretos (Fundação Pio XII), six hospitals met weekly for case discussion. In 2019, the AMARTE (Apoio Maior Aumentando Recursos e Treinamentos Especializados) Alliance officially began with the aim to improve the quality of pediatric oncology care in Brazil and became a collaborative network of innovation, research, and learning with 31 member institutions in 2024. METHODS:AMARTE follows four strategic pillars: (1) equalize diagnostics, (2) homogenize treatment, (3) epidemiological and survival studies, and (4) scientific development and innovation. Fundação Pio XII and St. Jude Children's Research Hospital provide infrastructure and human resources. Implementation resources are supported mainly by the member institution. The first strategic goal was to maintain sustainable member engagement. A semestral assessment (SCORE) monitors the progress and engagement level, based on defined indicators. RESULTS:Three engagement reports have been published, with an increase in members' scores: 17 hospitals increased their SCORE, 7 decreased, and 1 hospital did not change. Key achievements include a common data registry, diagnostic and treatment protocols, regular technical-scientific meetings, and the formation of a fundraising group to achieve financial sustainability. CONCLUSION:The first decade of the AMARTE Alliance highlights the relevance of collaboration in pediatric oncology. Challenges refer to the sustainable participation of specialists and heterogeneous governance structure across members, requiring flexibility in the implementation of shared initiatives. Outcome indicators are being developed to assess long-term impact.

Multiple logistic regression T-ALL

BACKGROUND:This study aimed to assess five pediatric hematology/oncology fellowship programs in Latin America by analyzing the profile of trainees and graduates, and their integration into the workforce. METHODS:To train pediatric hematologists/oncologists, the St. Jude Global Academy collaborates with five institutions in Latin America: Unidad Nacional de Oncología Pediátrica (Guatemala), Hospital Civil de Guadalajara (Mexico), Hospital Pereira Rossell (Uruguay), Hospital Oncológico de Barretos (Brazil), and GRAACC (Brazil). Data on the origin of graduates, current job roles, and responsibilities were assessed. RESULTS:Between 2003 and 2024, 110 physicians from 14 countries in Latin America started training in the five programs. Sixty-eight (61.8%) physicians completed training, while 36 (32.7%) are still currently in training. Six trainees (5.5%) withdrew from training prior to completion. Of 59 survey respondents, 47 (79.7%) currently work at a pediatric cancer unit. Thirty-seven (62.7%) graduates started working in pediatric oncology immediately after finishing training. The mean time for the 47 graduates working in pediatric cancer units to find a position was 0.18 years. After entering the pediatric oncology workforce, the mean time dedicated to pediatric oncology was 52.0%, with 15.5% spent on benign hematology, 12.8% on other clinical areas, 9.2% on administrative tasks, 6.9% on teaching, and 4.2% on research. Twenty-six (44%) graduates currently have a leadership role at their institutions. CONCLUSION:The five programs have trained Latin American specialists to care for children with cancer, with high integration into the pediatric oncology workforce. Graduates now contribute across the region, though further analyses are needed to define a comprehensive regional workforce strategy.

Simulation derived logistic regression models

Germ cell tumors (GCTs) are rare, heterogeneous neoplasms derived from primordial germ cells. Although they typically develop in the gonads, they may also arise in extragonadal locations along the midline of the body. Approximately 90% of patients respond well to cisplatin‑based chemotherapy; however, ~30% exhibit treatment resistance. Epithelial‑mesenchymal plasticity (EMP), a recognized hallmark of cancer, has been implicated in promoting metastasis and chemoresistance. Nonetheless, studies investigating the specific role of EMP in GCT treatment resistance remain limited. The present review compiles key studies on GCTs, EMP markers and cisplatin resistance using both in vitro and in vivo models; it highlights the roles of associated genes, transcription factors and proteins, identifying potential therapeutic targets. Advancing our understanding of EMP and identifying novel therapeutic targets may support the development of treatment strategies that complement or replace cisplatin. This, in turn, could improve survival outcomes and create new avenues for molecular research and clinical applications.

Vaginal malignant germ cell tumors (MGCTs), predominantly yolk sac tumors, are extremely rare, with no established consensus on optimal management. This study evaluated whether post-chemotherapy surgery is necessary for vaginal MGCTs. A retrospective analysis was conducted on patients diagnosed with vaginal MGCTs from 1996 to 2023. Progression-free survival (PFS), overall survival (OS), the impact of surgical intervention, and the presence of post-chemotherapy residual mass (RM) were assessed. Seventy-five patients (median age:11 months) were included. Six underwent initial tumor resection, and all received platinum-based chemotherapy. RM was detected post-chemotherapy in 57