Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas?

Abstract

PURPOSE To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). PATIENTS AND METHODS One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation-associated and sporadic malignant fibrous histiocytoma (MFH). Results Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH-the most common RAS type-the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001). CONCLUSION Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type.

Fig 1.

Histology of primary radiation-associated sarcomas (n = 130). MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve sheath tumor.

Fig 2.

(A) Disease-specific survival (DSS) for resected primary radiation-associated sarcomas (RASs) and (B) subtype-specific DSS for resected primary RASs (P = .004). LMS, leiomyosarcoma; AS, angiosarcoma; MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve sheath tumor; FS/MYXF, fibrosarcoma or myxofibrosarcoma.

Fig 3.

Disease-specific survival (DSS) for radiation-associated sarcomas (RASs) compared with sporadic soft tissue sarcomas. (A) Patients with RAS malignant fibrous histiocytoma (MFH) have inferior DSS compared with sporadic MFH patients; case mix with a 1:2 ratio (P = .070). (B) DSS for high-grade RAS malignant peripheral nerve sheath tumor (MPNST) patients is inferior to that for primary sporadic MPNST patients (P = .001).

Fig A1.

Latency of resected primary radiation-associated sarcomas varies with histologic type. Boxplots represent distribution of latency where the median is represented by a solid line. LMS, leiomyosarcoma; AS, angiosarcoma; MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve sheath tumor; FS/MYXF, fibrosarcoma or myxofibrosarcoma.