Schoettler, Peter

ABSTRACT Background and Objectives Non‐rhabdomyosarcoma soft tissue sarcomas (NRSTS) account for less than 4% of pediatric cancers. Treatment and outcomes have been described in adults, but pediatric data are lacking. The purpose of this study is to review our institution's outcomes of extremity NRSTS in pediatric patients. Methods Ninety‐eight (56 male: 42 female) pediatric patients with NRSTS of the extremity at our institution were reviewed. Mean age at diagnosis was 11 ± 5 years, and mean follow‐up was 12 ± 10 years. The most common diagnosis was synovial sarcoma (27%), and 60% were high‐grade. Results Treatment included surgical resection in all patients, with 33% receiving radiation and 37% receiving systemic therapy. 20‐year local recurrence‐ (LRFS) and metastatic disease‐free survival (MDFS) were 91% and 91%, respectively, with 92% disease specific survival (DSS). High grade tumors were associated with lower LRFS ( p = 0.02) and DSS ( p = 0.03). Tumor size < 5 cm demonstrated improved MDFS ( p = 0.03), and stage 3 tumors showed worse MDFS ( p < 0.01). Conclusions Treatment of pediatric NRSTS was variable, with large, deep, high‐grade tumors more likely to receive neoadjuvant and adjuvant treatments. Multidisciplinary treatment was associated with high rates of local control and durable survival. This study provides an extended follow‐up of pediatric patients to identify late complications.

ABSTRACTBackgroundThe Pediatric Oncology Group P9262 Phase 2 study of single‐agent paclitaxel demonstrated one complete response (CR), one partial response (PR), and four with stable disease (SD) among 15 patients with recurrent Wilms tumor (WT). Based on this activity, paclitaxel‐containing regimens have been used as salvage therapy for treatment‐refractory WT. We conducted a multi‐institutional retrospective study to further characterize the clinical activity of paclitaxel‐containing regimens in recurrent WT.MethodsTwelve institutions submitted anonymized data from patients with relapsed WT treated with paclitaxel. Response after one or two cycles of a paclitaxel‐containing regimen was reported according to Response Evaluation Criteria in Solid Tumors.ResultsTwenty‐eight patients with a median age at diagnosis of 5.5 years (range: 3 months to 31.9 years) were reported. Twenty had non‐anaplastic WT; eight had diffuse anaplasia (DA). Stage at diagnosis was I (n = 1), II (n = 1), III (n = 11), IV (n = 14), and V (n = 1). Patients received a mean of 8.5 anticancer drugs (range: 6–12) before paclitaxel, including eight who received high‐dose therapy/stem cell transplant. Paclitaxel (n = 13) or nab‐paclitaxel (n = 15) were predominantly administered in combination with other agents, most commonly doxorubicin and/or gemcitabine. Eleven of 26 patients with measurable disease had a partial response (7 = non‐anaplastic; 4 = DA), four had stable disease, and 11 had progressive disease. Two patients without measurable disease maintained a complete response for 12 and 16 months. The mean duration without progression was 7.6 months (range: 1–35 months).ConclusionsPaclitaxel‐containing regimens appear to be active against heavily pretreated WT with either non‐anaplastic or DA histology. Prospective studies are warranted to formally evaluate the efficacy of paclitaxel‐based therapies.

Abstract Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available. Experimental Design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study. Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli–Leydig cell tumor at a median age of 14 years (range: 11 months–66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli–Leydig cell tumors were diagnosed before 4 years of age. Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

Abstract Background Anaplastic sarcoma of the kidney (ASK) is a DICER1 ‐related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1 ‐related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. Methods Individuals with known or suspected DICER1 ‐related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. Results Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two‐year event‐free survival (EFS) for stage I–II ASK was 81.8% (95% confidence interval [CI]: 67.2%–99.6%), compared with 46.6% EFS (95% CI: 24.7%–87.8%) for stage III–IV ( p = .07). Two‐year overall survival (OS) for stage I–II ASK was 88.9% (95% CI: 75.5%–100.0%), compared with 70.0% (95% CI: 46.7%–100.0%) for stage III–IV ( p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02–0.31) and 0.08 (95% CI: 0.02–0.42), respectively. Conclusion ASK is a rare DICER1 ‐related renal neoplasm. In the current report, we identify clinical and treatment‐related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.