Patients with Wilms tumour have benefited from the results of decades of large collaborative clinical trials, leading to improved care. In the National Wilms Tumor Study Group and now Children’s Oncology Group (COG) trials, risk stratification evolved and expanded with each generation of studies and, therefore, ensuring that each patient receives the appropriate therapy has become increasingly complex. A new risk stratification system has been developed that forms the basis of the upcoming COG favourable-histology Wilms tumour (FHWT) study. Topics of diagnostic and prognostic uncertainty, such as the findings of tumour pulmonary emboli or extra-abdominal lymphadenopathy at diagnosis, will be integrated into the central review determination of staging of FHWT by committee consensus to facilitate clinical classification for therapeutic studies. Clear documentation of the elements of current risk stratification are of particular importance as refinement of the classification of patients with FHWT continues in an effort to optimize research, personalize treatment and provide an educational resource.

BackgroundOn the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT.MethodsFour-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy.ResultsEighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p = .28). When combining studies, the 4-year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic.ConclusionsPatients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365). The results of this study indicated that treatment of clear cell sarcoma of the kidney can be risk-adapted based on disease stage, radiotherapy should be omitted for patients with stage I disease if lymph nodes are sampled, and patients with stage IV disease appear to benefit from a carboplatin-containing regimen. With treatment according to the Children's Oncology Group AREN0321 study, most relapses occurred within 3 years, and the most common sites of recurrence were in the central nervous system.

Background: The Children's Oncology Group recommends upfront resection of Wilms tumor (WT), however, unique scenarios warrant neoadjuvant chemotherapy and delayed resection. We hypothesized that in the context of neoadjuvant chemotherapy, minimally invasive surgery (MIS) to resect WT achieves equivalent oncologic fidelity and better maintains therapy schedules. Methods: A retrospective analysis of WT treated between 2010-2021 at a free-standing children's hospital was performed. Patient and disease specific characteristics were collected, and pre-resection tumor volumes (TV) were calculated. Impact of MIS or open resection on oncologic fidelity and time to resume chemotherapy was analyzed. Results: For the study period, 62 patients were treated for 65 WT, and 14 patients (22.6%) received neoadjuvant chemotherapy to treat 17 WT (26.2%): 7 Stage I (all predisposition syndromes), 2 stage III, 7 stage IV, and 1 stage V (bilateral). MIS was utilized to resect 6 WT from 5 patients. For partial nephrectomy, pre-resection TV was 0.38 ml if MIS and 10.38 ml if open ( P = .025). For radical nephrectomy, pre-resection TV was 31.58 ml if MIS and 175.00 ml if open ( P = .101). No significant differences between surgical approach were detected regarding pathologic variables or survival. Epidural use was significantly greater with open procedures ( P = .001). Length of stay was 2.00 days after MIS compared to 6.00 for open resection ( P = .004). Time to resume chemotherapy was 7.00 days after MIS versus 27.00 for open ( P = .004). Conclusion: After neoadjuvant chemotherapy for WT, MIS partial and radical nephrectomies achieved equivalent oncologic fidelity, reduced epidural use and post-operative stays, and better maintained adjuvant therapy timelines when compared to open resections.

Infantile/congenital fibrosarcoma (IFS) is the most common soft tissue tumor in children less than one year of age. The most common anatomic site of IFS is in the extremities or trunk, and rarely in the abdomen or retroperitoneum. Approximately 70-90% of cases are characterized by a distinct t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. As such, TRK inhibitors are considered frontline therapy in TRK-fusion positive IFS. The ETV6-NTRK3 fusion is also detected in congenital mesoblastic nephroma (CMN) and less frequently in myeloid leukemias, secretory breast carcinoma, and mammary-type secretory carcinoma of the skin and salivary glands. Infrequently, cases of tumors with IFS-like morphology without the characteristic ETV6-NTRK3 gene fusion have been identified. Herein, an ETV6-NTRK3 fusion negative spindle cell sarcoma with IFS-like morphology subjected to genomic profiling revealed a PDE10A-BRAF fusion, a fusion event that has been detected previously in an isolated case of undifferentiated infantile sarcoma.