Li-Fraumeni associated osteosarcomas: the French experience.
Abstract
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.