The Impact of Chemotherapy on the Survival of Patients With High-grade Primary Extremity Liposarcoma

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Abstract
To determine if chemotherapy offers a survival benefit to patients with large, high-grade, primary extremity liposarcoma. The impact of chemotherapy on the survival of patients with primary extremity soft tissue sarcoma is controversial and its effect on individual histologic subtypes is not defined. Two prospectively collected sarcoma databases were used to identify all patients with >5 cm, high-grade, primary extremity liposarcoma that underwent surgical treatment of cure from 1975 to 2003 (n = 245). Clinical, pathologic and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS). Sixty-three (26%) patients were treated with ifosfamide based chemotherapy (IF), 83 (34%) with doxorubicin based chemotherapy (DOX) and 99 (40%) received no chemotherapy (NoC). To assess the impact of DOX, a contemporary cohort analysis of patients treated from 1975 to 1990 was performed. The 5 year DSS of the DOX treated patients was 64% (53%–74%) compared with 56% (51%–79%) for the NoC patients (log-rank P value = 0.28). To assess the impact of IF, a contemporary cohort analysis of patients treated from 1990 to 2003 was performed. The 5 year DSS of the IF treated patients was 92% (84%–100%) compared with 65% (51%–79%) for the NoC patients (log-rank P value = 0.0003). Independent prognostic factors for improved DSS were smaller size (HR = 0.7, P = 0.01), myxoid/round cell histologic subtype (HR = 0.3, P = 0.03) and treatment with IF (HR = 0.3, P = 0.01). The five-year DRFS of the IF treated patients was 81% (70%–92%) compared with 63% (50%–76%) for the NoC patients (log-rank P value = 0.02). The 5 year LRFS of the IF treated patients was 86% (76%–96%) compared with 87% (77%–97%) for the NoC patients (log-rank P value = 0.99). In patients with large, high-grade, primary extremity liposarcoma; DOX is not associated with improved DSS and IF is associated with an improved DSS. Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma.