Aldrink, Jennifer H.

11535 Background: Twenty-five percent of patients with Ewing Sarcoma (EWS) have metastatic disease at diagnosis, most commonly in the lungs. Our objectives were to compare overall (OS) and pulmonary disease-free survival (PDFS) between patients with metastatic EWS at diagnosis who achieve rapid complete response (RCR), defined as radiographic resolution of all pulmonary nodules at the end of induction chemotherapy, and those with residual pulmonary nodules after induction chemotherapy (non-RCR). Methods: This multi-center, retrospective cohort study included children under 20 years of age with metastatic EWS treated from 2007-2020 at 19 institutions participating in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups, and p < 0.05 was considered significant. Kaplan-Meier curves were generated for OS and PDFS. Cox regression was performed for OS, controlling for whole lung irradiation (WLI), extrapulmonary metastases, and age. Results: Among 153 patients with metastatic EWS at diagnosis, 61 (40%) achieved RCR, and 87 (57%) did not (5 unknown). The median number of pulmonary nodules was 3.5 in the RCR vs 5 in the non-RCR groups (p = 0.02), while bilateral disease was present in 44 (72%) RCR vs 75 (86%) non-RCR patients (p = 0.03). Pulmonary relapse occurred in 58 (38%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = 0.14). Factors associated with pulmonary relapse in the univariate analysis include median age [15 years (IQR: 12-17) with pulmonary relapse vs 12 years (IQR: 9-16) without (p = 0.03)] and extrapulmonary metastases at diagnosis [24 (41%) patients with pulmonary relapse vs 26 (27%) patients without pulmonary relapse (p = 0.05)]. WLI was performed in 100 patients and was not associated with a reduction in pulmonary relapse (p = 0.93). Complete surgical clearance of pulmonary disease was attempted in 29 (19%) patients, including 17 of the patients who met the criteria for RCR. On Kaplan-Meier analyses, 5-year PDFS did not significantly differ based on RCR (67%) vs. non-RCR (53%, p = 0.13), or WLI (61%) vs. no WLI (54%, p = 0.32). However, 5-year OS did vary significantly between patients with RCR and WLI (85%), RCR without WLI (55%), non-RCR with WLI (60%), and non-RCR without WLI (25%; p < 0.01). In Cox regression analysis, RCR was associated with improved OS after controlling for WLI, extrapulmonary metastases, and patient age (HR 0.51, p = 0.03). Conclusions: Patients with EWS who had pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse. Further research is needed to determine whether clearance of pulmonary disease achieved through surgical metastasectomy provides a comparable survival benefit and if any subsets of patients have a reduced risk of pulmonary relapse after resection.

Objective: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. Background: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. Methods: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. Results: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P=0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P=0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P=0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. Conclusions: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

AbstractWilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi‐institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event‐free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage‐specific treatment regimens.