(P 035) RISK FACTORS FOR BONY METASTASES IN PEDIATRIC OSTEOSARCOMA PATIENTS

Objective: Development of non-pulmonary metastases is a less common path of osteosarcoma progression than pulmonary metastases and risk factors to predict the development of bony metastatic disease are unclear. We explore clinical features of patients who experienced bony metastatic relapse in conventional osteosarcoma to better predict and treat such occurrence.

Methods: After Institutional IRB exemption was obtained, we conducted a retrospective chart review of patients with non-metastatic osteosarcoma at initial presentation, who later developed bony metastatic disease and were treated at a tertiary care center over a 20-year period. Inclusion criteria for this review included an initial diagnosis of non-metastatic osteosarcoma, age less than or equal to 18 years at the time of diagnosis, and the development of bony metastases at the time of first or subsequent recurrence.

We collected the following clinical data in a secured RedCap database: patient demographics, medical, surgical, and family history, clinical features of osteosarcoma and its treatment including radiological, pathology and genetic sequencing data when available. Our primary aim was to evaluate clinical patterns that were associated with the development of bony metastases. Our secondary aim was to describe survival outcomes, including time to development of metastases in addition to overall survival.

Results: We identified 167 patients with the diagnosis code for osteosarcoma within the past 20 years (2002 - 2022), of whom 9 patients met inclusion criteria, and 8 had complete records available for data analysis. This small subset of patients was found to be 50% female and 50% African American with average age at diagnosis of 9.9 years (range 7-14 years). All tumors were high-grade osteosarcoma of conventional subtype treated with standard MAP chemotherapy (cisplatin, doxorubicin, high-dose methotrexate) and surgical resection of the primary tumor. Average primary tumor size was 11.3cm and 6 out of 7 patients had a negative margin (R0) resection with a repeat excision for positive margins to gain R0 status. 1 patient pathology margin status was missing. Only 25% of patients were considered good responders (>/=90% tumor necrosis). Four patients required amputation.
Half of the patients developed isolated bony metastases as their first relapse; the other 50% developed concomitant bone and lung metastases at time of first relapse. The average time from diagnosis to development of bony metastasis was 352 days. Eventually, all patients developed metastatic disease to the lung . For treatment of bony metastases, 4 patients received surgery + radiation, 1 patient received surgery alone, 1 patient received radiation alone, and 2 patients continued with medical management.
Tumor genetics performed using Next Generation Sequencing were sporadic without unifying theme. Mutations present in multiple patients include MCL1 amplification, TP53, and MYC amplification. No genetic results were found in the medical record for the remaining 4 patients.
At the time of this study, 7 of 8 patients have died and 1 patient is currently alive with progressive disease on a clinical trial. Average overall survival was 656 days. Average survival after development of bony metastases was 295 days (See Table 1).

Conclusion: As anticipated, patients with bony recurrence with osteosarcoma had a dismal prognosis. This may influence patient and family considerations for treatment. Our data identify the rarity of bony metastatic disease at the time of first recurrence in non-metastatic osteosarcoma patients. We further highlight the rarity of bony metastases in patients with favorable tumor necrosis at time of definitive primary tumor surgery. Lastly, we emphasize the adverse outcome for this group of patients for whom effective therapy remains largely unavailable.

Table 1 CTOS Bone Mets.docx