Purpose : Describe clinical characteristics and outcome of Li-Fraumeni-associated osteosarcomas. Methods : TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from the SEER (National Cancer Institute’s Surveillance, Epidemiology, and End Results) for patients of the same age group. Results : Median age at first osteosarcoma diagnosis was 13.7 years (range:5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients <10 years (23% versus 9%) and, when compared with osteosarcomas in patients <25 years were characterized by an excess of axial (16% versus 10%) and jaw sites (15% versus 3%) and histology with predominant chondroblastic component (35% versus 16%) and periosteal subtypes (17% versus 1%). Metastases incidence (25%) was as expected in unselected osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%[95%CI:42.6−71.1]) were as expected in unselected series of osteosarcomas whereas the 5-year event-free survival was 36.5%[95%CI: 25.3−52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 55.3%[95%CI:34.3-69.5]. Conclusion : In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Purpose: To identify national consensus criteria for the management of children with chemotherapy-induced febrile neutropenia (FN) and for evidence-based step-down treatment approaches for patients classified as having a low risk of severe infection. Methods: In August 2018, a five-section, 38-item survey was e-mailed to all pediatric hematology and oncology units in France. The five sections contained statements on possible consensus criteria for (i) the definition of FN, (ii) the initial management of children with FN, (iii) the conditions required for initiating step-down therapy in low-risk patients, (iv) the management strategy for low-risk patients, and (v) antibiotic treatment on discharge. Consensus was defined as 75% of “somewhat agree” + “strongly agree” answers. Results: Sixty-five physicians, all specialists in pediatric onco-hematology, from 18 centers completed the survey questionnaire (participation rate: 58%). A consensus was reached on 22 of the 38 statements, including the definition of FN, the criteria for step-down therapy in children at low risk of severe infection, and the initial care of patients with FN. There was no consensus on the type and duration of antibiotic therapy on discharge for patients at low risk of severe infection. Conclusion: A consensus has been reached on the criteria for initiating evidence-based step-down treatment of children with FN and a low risk of severe infection. The lack of consensus on the step-down antimicrobial regimen means that the post-discharge antibiotic treatment can be defined according to local preferences.