(P 50) ANALYSIS OF CLINICAL FEATURES AND OUTCOMES FOR PATIENTS WITH MULTIFOCAL OSTEOSARCOMA: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP

Objective: Patients with metastatic osteosarcoma have inferior survival rates ranging from 20-30% with standard multimodal therapy. Those presenting with multifocal osteosarcoma (one or more extrapulmonary metastases) are thought to have an especially poor prognosis secondary to disease burden and challenges to achieving complete surgical remission but detailed outcome data are limited. We aimed to better understand event free survival (EFS) and overall survival (OS) to facilitate clinical trials in this patient population. Further understanding of clinical behavior and outcomes of this population is needed to create benchmark knowledge required to inform risk stratification and historical comparison populations for patients enrolled on contemporary clinical trials.

Methods: Patients with newly diagnosed high grade multifocal osteosarcoma [with presence of ≥ 1 extrapulmonary (bone or soft tissue) metastasis] enrolled on four historical Children Oncology Group clinical trials: CCG-7943, INT-0133, AOST0121, and AOST06P1 were included in this study. Chemotherapy varied among trials but all utilized common agents active in osteosarcoma; CCG-7943 included an upfront topotecan window. Skip metastases within the same bone as the primary tumor were excluded from this analysis. Data ascertained from trial case report forms included demographics, clinical characteristics (primary tumor site, axial vs. extremity, site of metastases), and outcomes. EFS and OS estimates were obtained using the Kaplan-Meier estimator and tests for equality of survival curves were conducted using the logrank test.

Results: : Across the four studies, 84 patients met the definition of multifocal osteosarcoma and had outcome data available for analysis. 10% of patients had axial primary tumors. Metastatic sites included bone (n=79, 94%) and soft tissue (n=9,11%). 89% of patients had pulmonary metastases in addition to extrapulmonary sites. A number of patients experienced events while on active primary therapy. Aggregating across studies, estimated EFS at 6 months and 12 months for patients with multifocal osteosarcoma was 60% (95% CI 51-72) and 43% (95% CI 34-55); estimated OS at 6 and 12 months was 88% (85% 81-95) and 70% (95% CI 60-80). No significant difference in risk of EFS-event among trials was observed (p=0.59), and there was no observed difference in risk of death among studies (p=0.33).

Conclusion: Patients with multifocal osteosarcoma demonstrate aggressive clinical patterns of behavior. An estimated 40% of patients experience an event during the first 6 months after enrollment while on therapy, and death occurs in an estimated 30% of patients within the first year after enrollment. Given the poor outcomes after standard osteosarcoma chemotherapy agents, this patient population should be considered for trials of novel approaches. Trial designs in this patient population should consider the occurrence of progression on therapy.