Background Radiation therapy is used increasingly as a component of multidisciplinary treatment for many solid tumors. One complication of such treatment is the development of radiation-associated sarcoma (RAS). Undifferentiated pleomorphic sarcoma (UPS), previously termed “malignant fibrous histiocytoma” (MFH) is the most common histologic subtype of RAS. This study investigated the clinical outcomes for patients with radiation-associated UPS (RA-UPS/MFH). Methods The study identified 1068 patients with UPS/MFH treated at the authors’ institution. Patient and tumor factors were collected and compared. Regression analysis was performed to identify independent predictors of survival. A matched-cohort survival and recurrence analysis was performed for radiation-associated and sporadic UPS/MFH. Results The findings showed that RA-UPS/MFH comprised 5.1 % of the UPS population. The median latency to the development of RA-UPS/MFH was 9.3 years. The 5-year disease-specific survival (DSS) was 52.2 % for patients identified with RA-UPS/MFH (n = 55) compared with 76.4 % for patients with unmatched sporadic UPS/MFH (n = 1,013; p < 0.001). A matched-cohort analysis also demonstrated that the 5-year DSS was significantly worse for RA-UPS/MFH (52.2 vs 73.4 %; p = 0.002). Furthermore, higher local recurrence rates were observed for patients with RA-UPS/MFH than for patients with sporadic lesions (54.5 vs 23.5 %; p < 0.001). Radiation-associated status and incomplete resection were identified as independent predictors of local recurrence. Conclusion This study demonstrated worse clinical outcomes for patients with RA-UPS/MFH than for patients with sporadic UPS/MFH. Local recurrence was significantly higher for patients with RA-UPS/MFH, suggesting a unique tumor biology for this challenging disease.

Background Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The aim of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes. Methods A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA and outcome. Results At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63%. Clinical variables associated with improved DSS included age < 61 years, tumor size < 10 cm, margin-negative resection and sporadic-tumor status. At the protein level, loss of cyclin D1 (p=0.06), pEGFR (p=0.023), pIGF-1R (p=0.022), and PTEN (p<0.001) and overexpression of AXL (p=0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS) while RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R. Discussion Cyclin D1, AXL and PTEN are associated with cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and could also explain the aggressive phenotype seen in RA-UPS when compared to the sporadic lesions.