Abstract
PURPOSE: Radiation-associated sarcomas (RAS) are rare but aggressive malignancies. We sought to characterize the histology-specific presentation and behavior of soft tissue RAS to improve individualized prognostication. METHODS: A single-institutional prospectively maintained database was queried for all patients with primary, nonmetastatic RAS treated with surgical resection from 1982 to 2019. Patients presenting with the five most common RAS histologies were propensity-matched to those with sporadic tumors of the same histology. Incidence of disease-specific death (DSD) was modeled using cumulative incidence analyses. RESULTS: Among 259 patients with RAS, the five most common histologies were malignant peripheral nerve sheath tumor (MPNST; n = 19), myxofibrosarcoma (n = 20), leiomyosarcoma (n = 24), undifferentiated pleomorphic sarcoma (UPS; n = 55), and angiosarcoma (AS; n = 62). DSD varied significantly by histology (P = .002), with RAS MPNST and UPS having the highest DSD. In unadjusted analysis, RAS MPNST was associated with increased DSD compared with sporadic MPNST (75% v 38% 5-year DSD, P = .002), as was RAS UPS compared with sporadic UPS (49% v 28% 5-year DSD, P = .004). Unadjusted DSD was similar among patients with RAS AS, leiomyosarcoma, or myxofibrosarcoma and sporadic sarcoma of the same histology. After matching RAS to sporadic patients within each histology, DSD only differed between RAS and sporadic MPNST (83% v 46% 5-year DSD, P = .013). Patients with RAS AS presented in such a distinct manner to those with sporadic AS that a successful match was not possible. CONCLUSION: The aggressive presentation of RAS is histology-specific, and DSD is driven by RAS MPNST and UPS histologies. Despite the aggressive presentation, standard prognostic factors can be used to estimate risk of DSD among most RAS. In MPNST, radiation association should be considered to independently associate with markedly higher risk of DSD.