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

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.

Efficacy of first-line doxorubicin and ifosfamide in myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLS) is a soft tissue sarcoma with adipocytic differentiation characterized by a unique chromosome rearrangement, t(12;16)(q13;p11). The exact efficacy of chemotherapy in MLS has not been clearly established. PATIENTS AND METHODS: We retrospectively analyzed the records of 37 histologically confirmed MLS patients who were treated at the University of Texas MD Anderson Cancer Center from January 2000 to December 2009 with doxorubicin 75-90 mg/m2 over 72 hours combined with ifosfamide 10 gm/m2 in the first-line setting. Response was assessed using RECIST and Choi criteria. The Kaplan-Meier method and log-rank test was used to estimate clinical outcomes. RESULTS: The median follow-up period was 50.1 months. The overall response rates were 43.2% using RECIST and 86.5% using the Choi criteria. The 5-year disease-free survival rate was 90% for patients with resectable tumors. Median time to progression and overall survival time for the advanced-disease group were 23 and 31.1 months, respectively. CONCLUSION: Our study demonstrates that doxorubicin-ifosfamide combination therapy has a role in the treatment of MLS. The Choi criteria may be more sensitive in evaluating response to chemotherapy in MLS.

Detection of MDM2 gene amplification or protein expression distinguishes sclerosing mesenteritis and retroperitoneal fibrosis from inflammatory well-differentiated liposarcoma.

Inflammatory liposarcoma is a variant of well-differentiated liposarcoma/atypical lipomatous tumor that consists of a mixture of lymphocytes, histiocytes, scattered atypical stromal cells, mature adipocytes, and rarely lipoblasts. When the inflammatory infiltrate predominates, the morphological features overlap with various fibroinflammatory disorders including sclerosing mesenteritis and retroperitoneal fibrosis, making the diagnosis difficult. Well-differentiated liposarcoma/atypical lipomatous tumor and dedifferentiated liposarcoma have characteristic molecular markers in the form of giant marker and ring chromosomes consisting of amplicons of 12q13-15, which includes MDM2. MDM2 immunohistochemistry (IHC) (Zymed; clone IF2) and dual color fluorescence in situ hybridization utilizing MDM2 (12q15) and chromosome 12 centromeric probes were performed on formalin-fixed and paraffin-embedded specimens from inflammatory well-differentiated liposarcoma (17 cases), sclerosing mesenteritis (14 cases), and idiopathic retroperitoneal fibrosis (10 cases). MDM2 expression as detected by IHC is a very sensitive tool in recognizing inflammatory well-differentiated liposarcoma (17 of 17); however, 21% (3 of 14) and 10% (1 of 10) of sclerosing mesenteritis and retroperitoneal fibrosis, respectively, displayed weak MDM2 immunoexpression. The MDM2 fluorescence in situ hybridization assay was very specific for inflammatory well-differentiated liposarcoma as 15 of 17 (88%) cases showed MDM2 amplification, whereas none of the cases of sclerosing mesenteritis or idiopathic retroperitoneal fibrosis showed amplification. Five cases of retroperitoneal fibrosis were noncontributory secondary to autofluorescence, potentially limiting the usefulness of the assay in certain situations such as inappropriate fixation. Increased MDM2 expression and/or MDM2 amplification can be employed to aid discrimination of inflammatory well-differentiated liposarcoma from fibroinflammatory mimics. MDM2 fluorescence in situ hybridization is a very specific method (100%), but less sensitive (88%), whereas MDM2 expression by IHC is very sensitive (100%), but less specific (83%). Therefore, a positive screen of difficult cases with MDM2 IHC would require confirmation by the fluorescence in situ hybridization. However, lack of MDM2 immunoexpression would rule out the possibility of inflammatory well-differentiated liposarcoma.