Abstract
Background: Radiation-associated osteosarcoma (RAO) is a rare, life-threatening complication from radiation. Many physicians presume RAO has a worse prognosis than sporadic osteosarcoma (SO), although limited objective data exist. We conducted a retrospective study comparing these entities.Methods: We identified adults treated at our institution with osteosarcoma (1990–2016) and categorized tumors as SO or RAO based on location within a prior radiation field. We extracted data on demographics, treatment and primary malignancy and examined available tumor samples for MTA-1 and ezrin using immunohistochemistry (IHC).Results: Of 159 identified patients, 28 had RAO, diagnosed at a median interval from radiation of 11.5 years (1.5–28 years). Median follow-up was 2.8 years (0.1–19.6 years). Median progression free survival (PFS) and overall survival (OS) were not significantly different in the small population of patients with metastases, SO (n = 20) vs. RAO (n = 6): PFS 10.3 months vs. 4.8 months (p = 0.45) and OS 15.6 months vs. 6.1 months (p = 0.96), respectively. For the larger group with localized disease, median relapse-free survival (RFS) and OS were significantly different, NR vs. 12.2 months (p < 0.001) and NR vs. 27.6 months (p = 0.001) in SO (n = 111) vs. RAO (n = 22), respectively. On IHC, there were significant differences in distribution of high, intermediate or low MTA-1 (p = 0.015) and ezrin (p = 0.002) between RAO and SO tumors.Conclusions: Patients with metastases at diagnosis fared poorly irrespective of prior radiation. RAO patients with localized disease had worse outcomes without detectable differences in therapy rendered or treatment effect in resected specimens. Higher expression of MTA-1 in RAO patients may suggest an underlying difference in tumor biology to explain differences in outcomes.
Highlights
Osteosarcoma is a rare, primary bone tumor that has a bimodal distribution of incidence with a peak in children and adolescents and a second, smaller peak in the elderly
We identified 159 patients with osteosarcoma, of which 28 had radiation-associated osteosarcoma (RAO) (Table 1)
There were no differences in the location of metastases between the two groups
Summary
Osteosarcoma is a rare, primary bone tumor that has a bimodal distribution of incidence with a peak in children and adolescents and a second, smaller peak in the elderly. As the use of radiation therapy for the management of cancer has increased, so have reports of radiation-associated osteosarcoma (RAO). RAO has been thought to carry a poor prognosis based on retrospective analyses, with a reported disease free survival as low as 17% (2). McHugh et al reported on the difference between primary vs radiation-associated craniofacial osteosarcoma (5). Craniofacial osteosarcoma carries an overall favorable prognosis compared to its appendicular counterpart. In this series, 47% of de-novo craniofacial OS were high-grade with 80% of patients alive without disease. Radiation-associated osteosarcoma (RAO) is a rare, life-threatening complication from radiation. Many physicians presume RAO has a worse prognosis than sporadic osteosarcoma (SO), limited objective data exist.
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