Radiation-Associated Undifferentiated Pleomorphic Sarcoma is Associated with Worse Clinical Outcomes than Sporadic Lesions

Abstract

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.

Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma

“…Sixty-five (31%) patients were treated with systemic chemotherapy and 118 (57%) received radiation therapy. As we have previously reported differences in clinical outcomes among patients with sporadic versus RA-UPS 4 , we also analyzed the current data within the context of disease setting (Table 1). …”

“…Although RA-UPS is associated with poorer survival outcomes than sporadic UPS 4 , currently no molecular distinctions between the two disease settings have been identified. Therefore, we examined protein and miRNA expression patterns separately.…”

“…Despite aggressive surgery, local recurrences occur in 13–42% of patients and nearly 31–35% will develop metastatic disease. 2–4 Although the addition of chemotherapy has shown some benefit in meta-analyses, these responses are marginal at best, highlighting the need for improved therapeutic options for UPS patients. 5,6 The use of radiation therapy is associated with reduced local recurrences in high grade sarcomas; however, approximately 3–5% of UPS arise in a prior site of therapeutic radiation for an unrelated malignancy and are termed radiation-associated UPS (RA-UPS), making radiation therapy controversial in this subset of the patients due to the comorbidities of re-irradiation 7,8 .…”

“…4 While recent studies have described genomic rearrangements and gene expression profiles of UPS tumors, the expression patterns and prognostic potential of specific proteins and microRNAs (miRNAs) have not yet been extensively investigated. 9–12 Previously, Tomita et al 13 found that high levels of activated (phosphorylated) AKT (pAKT), a key step in the phosphatidylinositiol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, correlated with poorer overall (OS) and disease-specific survival (DSS) outcomes.…”

Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral Retinoblastoma

“…UPS is considered aggressive and is characterized by rapid growth, local recurrence, and metastasis, most commonly to lung (90%) followed by bone (8%), and liver (1%). UPS associated with radiation has a worse overall survival and a higher rate of local recurrence than sporadic UPS [15]. …”