Search

BACKGROUND: Data regarding the role of systemic therapy in patients with advanced well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) are limited. METHODS: From 2000 to 2010, 208 patients with advanced WDLPS/DDLPS received chemotherapy in 11 participating institutions. Clinical and pathological data were collected by reviewing medical records. RESULTS: Median age was 63 years (range 32-84). Combination chemotherapy was delivered in 85 cases (41%) and single agent in 123 cases (59%), respectively. One hundred and seventy-one patients (82%) received an anthracycline-containing regimen. Using RECIST, objective response was observed in 21 patients (12%), all treated with anthracyclines. Median progression-free survival (PFS) was 4.6 months [95% confidence interval (CI) 3.3-5.9]. On multivariate analysis, age and performance status (PS) were the sole factors significantly associated with poor PFS. Median overall survival (OS) was 15.2 months (95% CI 11.8 -18.7). On multivariate analysis, grade and PS were the sole factors significantly associated with OS. CONCLUSIONS: Chemotherapy was associated with clinical benefit in 46% of patients with advanced WDLPS/DDLPS. OS remains poor, even though visceral metastatic disease is less frequent than in other sarcomas.

Background: The purpose of this study was to retrospectively analyze the relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with high-grade extremity sarcomas. Patients and methods: Inclusion criteria were high-grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between 1990 and 2001 were treated with surgery only (n = 282) or NAC containing doxorubicin/ifosfamide/mesna (AIM) (n = 74). The stratified Cox proportional hazards model was used to test the effect of NAC on disease-specific survival and recurrence while adjusting for known prognostic factors. Results: NAC was associated with improved disease-specific survival for this cohort of patients (P = 0.02). This overall improvement appears to be driven by the benefit of NAC on disease-specific survival for patient with tumors >10 cm. The 3-year disease-specific survival for tumors >10 cm was 0.62 (95% CI: 0.53 ‐ 0.71) for patients not receiving NAC and 0.83 (95% CI: 0.72 ‐ 0.95) for patients receiving NAC. Conclusion: NAC with AIM was associated with a significant improvement in disease-specific survival in patients with high-grade extremity soft tissue sarcomas >10 cm. These data emphasize the need for further prospective clinical studies of neo-adjuvant or adjuvant chemotherapy for patients

Background: Data regarding the role of systemic therapy in patients with advanced pleomorphic liposarcomas (PLPS) are very limited.

Introduction Data related to management and outcome of BM of sarcoma are scarce. Methods From 1991 to 2010, from over 4500 sarcoma pts treated at MSKCC, 107 developed BM. Results Highest relative frequency came from ASPS (26%,7/27 pts), with an absolute number highest for LMS(37%). BM metachronous in 96 cases (90%). Median time between diagnosis of metastatic sarcoma and the diagnosis of BM was 9 months (range 5.5–12.5). Locoregional treatment (surgery ± RT) in 83 pts (78%). Systemic CT in 18 pts (17%) after diagnosis of BM. One PR (EWS) in 15 evaluable pts. One hundred-one pts died (94%), 6 still alive. Two living pts with follow-up >24 months had complete surgery of BM. Deaths related to BM progression were 54 (54%), related exclusively to systemic PD were 47 (46%). Median OS was 3.6 months (95% CI: 2.9-4.3). One-year OS rate was 16% (95% CI 9–23). On univariate analysis, histology, delay between the diagnosis of sarcoma and BM relapse, number of lesions, disease status and PS were significantly associated with OS. Surgery was significantly related to improved OS while RT was not. On multivariate analysis, time between diagnosis of sarcoma and BM relapse and disease status were pre-therapeutic prognostic factors associated with OS. Conclusions SARCOMA pts with BM have poor outcome. RT was not associated with improved survival. Long-term survival is achieved in small proportion of pts managed by surgery. CT had little activity after BM, consistent with the advanced nature of the pts' sarcomas. Disclosure All authors have declared no conflicts of interest.

It is been known for many years that the insulin-like growth factor (IGF) signalling pathway is important in human cancer. The IGF-1 receptor (IGF-1R) is upregulated in colorectal, breast, prostate and lung cancers. It was also known to be a potential target in Ewing's sarcoma. The advent of specific monoclonal antibodies and small molecule tyrosine kinase inhibitors of IGF-1R led to many clinical trials. A combination of figitumumab with platinum doublet chemotherapy resulted in a higher response rate and improved progression-free survival (PFS) in phase II, but a phase III trial was negative. In Ewing's sarcoma activity was seen with R-1507, figitumumab and other agents. However, response rates in phase II studies were generally low, 14.2% with figitumumab, and duration generally short, e.g. with figitumumab median PFS 1.9 months, median survival 8.9 months. Occasionally, durable responses have been seen lasting for several years. Could better selection by the use of circulating biomarkers, e.g. IGF-1, or IGF binding proteins, be useful or does the answer lie with combinations? Laboratory studies suggest that combining IGF-1R inhibitors with inhibitors of AKT/mTOR, EGFR or MEK, could help to overcome resistance. Given the dearth of new agents for Ewing's sarcoma it is to be hoped that continued access to these agents will enable further work on mechanisms of resistance and appropriate combination phase I/II studies to be performed. The book is not yet closed on IGF-1R as a target. Disclosure The author has declared no conflicts of interest.