(P 71) CHEMOTHERAPY AND PROGNOSTIC SIGNIFICANCE OF EXTENT OF DEDIFFERENTIATION IN DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA

Objective: Dedifferentiated parosteal osteosarcoma (DDPOS) is a rare variant of osteosarcoma representing high-grade transformation of conventional low-grade parosteal osteosarcoma (CPOS). DDPOS is often treated similarly to other high-grade osteosarcomas; however, the impact of extent of dedifferentiation, the presence of chondroblastic heterologous differentiation, and the pathologic response to neoadjuvant chemotherapy on survival outcomes is not well-defined. We sought to evaluate the prognostic significance of the percentage and morphology of the dedifferentiated component as well as the tumor necrosis as it relates to chemotherapy benefit and clinical outcomes.

Methods: Patients diagnosed with CPOS and DDPOS between 1985-2021 were identified by retrospective review of the institutional pathology database. Clinical and treatment data were collected. Percent, morphology of dedifferentiation, and chondroblastic heterologous differentiation was assessed in resection specimens based on review of available H&E slides by a bone and soft tissue pathologist. The Kaplan-Meier method was used to estimate rates of both overall survival (OS) and relapse-free survival (RFS). Log-rank tests were used to assess for significance of differences between groups.

Results: 71 patients with POS were identified including CPOS (n=31) and DDPOS (n=40). For DDPOS, median age at diagnosis was 36.5 years (range, 18-79). Tumors most commonly involved the femur (n=26). The majority (n=35, 88%) presented with localized disease at diagnosis. 17 patients underwent up-front resection with DDPOS identified at time of resection. Tumor size ranged from 2.4-25cm and contained varying extent of dedifferentiated component (range 5-95%). 29 of 35 patients with localized disease received chemotherapy for DDPOS. The most common neoadjuvant regimen was doxorubicin/cisplatin. Pathologic tumor necrosis was variable (range 0-95%); 3 of 23 patients exhibited >90% necrosis. DDPOS was associated with increased risk of relapse (HR 2.8 (95% CI: 1.1, 7.2), p=0.033) and of death (HR 5.1 (95% CI: 1.2, 23.0), p=0.032) as compared to CPOS. Within DDPOS, patients with metastasis at diagnosis had inferior OS (mOS 3.4 years v not reached, p=0.01). The risk of relapse/death amongst patients with DDPOS who did not receive either neoadjuvant or adjuvant chemotherapy was significantly greater than those who received chemotherapy as part of their initial treatment (HR 3.6, p=0.046). There was no difference in RFS or OS between patients stratified by % of dedifferentiation nor by exhibiting a chondroblastic component. There was no correlation between pathologic treatment response and survival outcomes in DDPOS.

Conclusion: Presence of dedifferentiation, regardless of extent, is associated with worse survival outcomes in patients with parosteal osteosarcoma. Histological response was variable and not prognostic in our limited data set. Chemotherapy should be considered as standard treatment for all patients with DDPOS.