Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: A report from the Children's Oncology Group

Background: Previous studies of the prognostic importance of FOXO1 fusion status in patients with rhabdomyosarcoma (RMS) have had conflicting results. We re�examined risk stratification by adding FOXO1 status to traditional clinical prognostic factors in children with localized or metastatic RMS. Methods: Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531; two studies each for low�, intermediate� and high�risk patients) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1727 evaluable patients. Survival tree regression for event�free survival (EFS) was conducted to recursively select prognostic factors for branching and split. Factors included were age, FOXO1, clinical group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Definition and outcome of the proposed risk groups were compared to existing systems and cross�validated results. Results: The 5�year EFS and overall survival (OS) for evaluable patients were 69% and 79%, respectively. Extent of disease (localized versus metastatic) was the first split (EFS 73% vs 30%; OS 84% vs. 42%). FOXO1 status (positive vs negative) was significant in the second split both for localized (EFS 52% vs 78%; OS 65% vs 88%) and metastatic disease (EFS 6% vs 46%; OS 19% vs 58%). Conclusions: After metastatic status, FOXO1 status is the most important prognostic factor in patients with RMS and improves risk stratification of patients with localized RMS. Our findings support incorporation of FOXO1 status in risk stratified clinical trials

Alveolar Rhabdomyosarcoma with Regional Nodal Involvement: Results of a Combined Analysis from Two Cooperative Groups

BACKGROUND: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). METHODS: We retrospectively identified patients with ARMS-N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. RESULTS: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49%(95%CI=39–59) and 44%(95%CI=30–58), and overall survival (OS), 51%(95%CI=41–61) and 53.6%(95%CI=40–68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. CONCLUSIONS: The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients

Prevalence and Perceptions of Team Training Programs for Pediatric Surgeons and Anesthesiologists.

BACKGROUND: Team training programs adapt crew resource management principles from aviation to foster communication and prevent medical errors. Although multiple studies have demonstrated that team training programs such as TeamSTEPPS improve patient outcomes and safety across medical disciplines, limited data exist about their application to pediatric surgical teams. The purpose of this study was to investigate usage and perceptions of team training programs by pediatric surgeons and anesthesiologists. We hypothesized that team training programs are not widely available to pediatric surgical teams. MATERIALS AND METHODS: We performed an online survey of Pediatric Surgery (General, Plastic, Urologic, Orthopedic, Otolaryngologic, and Ophthalmologic) and Anesthesiology members of the American Academy of Pediatrics. The survey inquired about completion and perceptions regarding efficacy of team training programs. Simple descriptive statistics and a Student t-test were used to evaluate the data. RESULTS: One hundred fifty-two pediatric surgeons and 12 anesthesiologists completed the survey with a 10% response rate. Over half of the respondents were general pediatric surgeons. Home institutions offered TeamSTEPPS or another crew resource management style team training program for 39% of respondents. Of those with a program, 77% of respondents had completed training. Although most (76%) who participated in team training programs did so by requirement, 90% found it helpful. Of the 61% of surgeons who said their institution did not offer team training programs, 60% said they would participate if one were offered and an additional 32% said they might participate. The biggest barriers to participation were not enough free time or that the team training program was not offered to their department. CONCLUSIONS: Team training programs are considered beneficial among pediatric surgeons and anesthesiologists who have completed them. Unfortunately, despite substantial evidence showing training for team work improves team functioning and patient outcomes, many pediatric surgical teams do not have team training programs at their institutions. Further expansion of team training programs may be valuable to improving a culture of safety in children\u27s hospitals