Bryan J. Dicken

Background: In many pediatric malignant germ cell tumor (MGCT) protocols, patients who do not achieve a complete response (CR; normal tumor markers, no radiological/histological residual) after three cisplatin–etoposide–bleomycin (PEb) cycles receive two to three “consolidation” cycles of the same regimen. Evidence for this practice is limited, and historical outcomes for non‑CR patients remain poor. Methods: We retrospectively reviewed patients diagnosed with intermediate‐risk MGCT, enrolled in AGCT0132, between 2003 and 2011. All patients received three cycles of PEb and underwent response assessment at the end of induction. Patients not in CR were prescribed three additional cycles of PEb as consolidation. We compared event‐free survival (EFS) and overall survival (OS) for patients who did and did not receive consolidation. Results: Among 210 patients enrolled, two patients were excluded from analyses: one without complete information, and one had rapid progressive disease (PD) and did not complete induction therapy. Out of 208 patients, 193 had a CR after three cycles of induction chemotherapy, and their post‐induction 4‐year EFS and OS were 93% and 99%. Fifteen patients were not in CR at the end of the first three cycles. Twelve received consolidated chemotherapy as mandated per protocol, and their 4‐year EFS and OS were 61% and 65%, respectively. Three patients were deemed to have progressive disease at the end of induction and received second‐line therapy. Conclusion: Children with MGCTs who did not achieve CR after the first three cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. We conclude that consolidation is of unclear benefit. We suggest that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy may receive a salvage regimen with different agents rather than consolidation with more of the same chemotherapy.

Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment‐related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard‐risk disease, and intensify therapy for patients with poor‐risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker‐negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology‐driven, biomarker‐defined, histology‐specific, risk‐stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.

Purpose Typically, preoperative imaging is viewed in two dimensions (2D) only, but three-dimensional (3D) virtual models may improve viewers’ anatomical perspective by permitting them to interact with the imaging through manipulating it in space. Research into the utility of these models in most surgical specialties is growing rapidly. This study investigates the utility of 3D virtual models of complex pediatric abdominal tumors for clinical decision making, particularly the decision to proceed with surgical resection or not. Methods 3D virtual models of tumors and adjacent anatomy were created from CT images of pediatric patients scanned for Wilms tumor, neuroblastoma or hepatoblastoma. Pediatric surgeons individually assessed the resectability of the tumors. First, they assessed resectability using the standard protocol of viewing imaging on conventional screens and then reassessed resectability after being presented with the 3D virtual models. Inter-physician agreement on resectability for each patient was analyzed using Krippendorff’s alpha. Inter-physician agreement was used as a surrogate for correct interpretation. Participants were also surveyed afterward on the utility and practicality of the 3D virtual models for clinical decision making. Results Inter-physician agreement when using CT imaging alone was “fair” (Krippendorff’s alpha α = 0.399), while inter-physician agreement when using 3D virtual models increased to “moderate” (Krippendorff’s alpha α = 0.532). When surveyed about model utility, all 5 participants considered them helpful. Two participants felt the models would be practical for clinical use in most cases, while 3 felt they would be practical for select cases only. Conclusion This study demonstrates the subjective utility of 3D virtual models of pediatric abdominal tumors for clinical decision making. The models are an adjunct that can be particularly useful in complicated tumors that efface or displace critical structures that may impact resectability. Statistical analysis demonstrates the improved inter-rater agreement with the 3D stereoscopic display over the 2D display. The use of 3D displays of medical images will increase over time, and evaluation of their potential usefulness in various clinical settings is necessary.

Liver neoplasms are quite rare in childhood. They often involve 6.7 cases per 10 million children aged 18 years or younger. Hepatoblastoma (HB) is the most frequent tumor, but this neoplasm’s rarity points essentially to the difficulty of performing biologic studies and large-scale therapeutic trials. On the pathological ground, HB is separated into an entirely epithelial neoplasm or a mixed neoplasm with epithelial and mesenchymal components. This last category has been further subdivided into harboring teratoid features or not. The ‘teratoid’ HB includes a mixture of components with heterologous origin. The heterologous components include neuroectoderm, endoderm, or melanin-holding cells with or without mesenchymal components. The most important criterium for the teratoid component is neuroepithelium, melanin, and, more recently, a yolk-sac-like component and neuroendocrine components. The mesenchymal components include muscle, osteoid, and cartilage, which are most often observed mainly in ‘teratoid’ neoplasms. The teratoid component or mesenchymal components are diagnosed with biopsies. They appear more prominent after chemotherapy due to the response and shrinkage of epithelial elements and non- or low-responsive components of mixed HB. This review focuses on the clinical, radiological, and pathological findings of HB with teratoid features.

Purpose: In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development.Patients and methods: Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies—yolk sac tumor, embryonal carcinoma, or choriocarcinoma—were included. Patients were compared with respect to event‐free survival (EFS) and overall survival (OS).Results: Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non‐GD patients (mean age, 12.1 years). The estimated 3‐year EFS for patients with GD was 66.7% (95% CI 28.2–87.8%) and for non‐GD patients was 88.8% (95% CI 80.2–93.8%). The estimated 3‐year OS for patients with GD was 87.5% (95% CI 38.7–98.1%) and for non‐GD patients was 97.6% (95% CI of 90.6–99.4%).Conclusion: Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high‐risk group that requires a more aggressive chemotherapy regimen.