Rhabdomyosarcoma (RMS) is a well-described cancer in Li-Fraumeni Syndrome (LFS), resulting from germline TP53 pathogenic variants (PVs). RMS exhibiting anaplasia (anRMS) have been associated with a high rate of germline TP53 PVs. This study provides an updated estimate of the prevalence of TP53 germline PVs from a large cohort of patients (n=239) enrolled in five Children’s Oncology Group (COG) clinical trials. Although the prevalence of germline TP53 PVs in anRMS patients in this series is much lower than previously reported, this prevalence remains significantly elevated. Germline genetic evaluation for TP53 PVs should be strongly considered in patients with anRMS.

Background: ABVD, the standard-of-care in adult Hodgkin lymphoma (HL), has not been directly compared to ABVE-PC, a pediatric regimen designed to reduce late-effects. We aimed to compare the effectiveness and associated toxicities of these two regimens used in the same institution. Methods: This retrospective cohort study evaluated a total of 224 patients diagnosed with HL between 1999 and 2018 at Children’s Hospital Los Angeles (CHLA), of which 93 patients were eligible having received ABVD (n=46) or ABVE-PC (n=47) chemotherapy as their initial treatment. Descriptive analyses were performed using the Student’s t-test or Fisher’s exact test. Survival analysis used the Kaplan-Meier method. Events included: death, relapse, secondary malignancy, need for radiation therapy, pulmonary toxicity and cardiomyopathy determined by shortening fraction <29%. Analyses followed an intention-to-treat principle. Results: There was no difference in baseline characteristics between the patients receiving ABVE-PC or ABVD in regard for stage, risk group or prognostic variables, such as the presence or absence of “B” symptoms, bulky disease, and extra-nodal involvement. A greater proportion of patients treated with ABVE-PC received consolidating external beam radiation treatment (XRT) either by randomization or by response compared to ABVD (59.6% vs 32.6% respectively, p=0.01). While not statistically significant, response to therapy, assessed by PET/CT where available, mirrored the need for radiation (rapid response 58.3% vs 90.0%, n=34, p=0.11). There was no difference in event-free survival (p=0.63) or overall survival (p=0.37) with a median follow up length of 3.9 years. Conclusion: ABVD and ABVE-PC achieved similar survival outcomes in our single-institution cohort

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 using different schemas of chemotherapy. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that this subgroup may benefit from the EpSSG strategy which included maintenance chemotherapy.