The role of Ifosfamide–doxorubicin chemotherapy in histology-specific, high grade, locally advanced soft tissue sarcoma, a 14-year experience

Abstract

PurposeTo compare long-term outcomes of high-grade, primary soft-tissue-sarcoma (STS), using Ifosfamide–Doxorubicin vs local therapy alone, in histology-specific sarcomas. MethodsRetrospective analysis was performed on 127 patients from 2005 to 2018, with high-grade STS of extremity or trunk, >5 cm, that were either Synovial-Cell, Dedifferentiated-Liposarcoma (DDL), Myxofibrosarcoma, Round-Cell-Liposarcoma (RCLS), Undifferentiated-Pleomorphic-Sarcoma (UPS), or Undifferentiated-Sarcoma-not-otherwise-specified (US-NOS), with central pathology review. Ifosfamide–Doxorubicin was generally given neoadjuvant over 5 cycles, followed by radiation and wide excision, with chemotherapy given in 38 patients, while 89 received local therapy alone. Multi-variable-analysis (MVA) of prognostic factors was performed, and local-recurrence-free-survival (LRFS), distant-metastases-free-survival (DMFS), disease-specific-survival (DSS), and overall-survival (OS) were estimated using Kaplan–Meier, and adjusted using propensity-score matching. ResultsMedian follow-up was 4.5 years. Younger age (p < 0.0001) and Synovial histology (p = 0.0002) were more likely to undergo chemotherapy. Ifosfamide–Doxorubicin improved 5-year DMFS (p = 0.02), DSS (p = 0.01), and OS (p = 0.01), by univariate comparisons, as well as sub-analysis of non-synovial histology, but significance was lost after propensity-score matching for DMFS (p = 0.10), DSS (p = 0.09), and OS (p = 0.07). Size >10 cm, trunk location, and lack of chemotherapy significantly lowered DMFS, DSS, and OS on MVA, while DDL had more favorable survival; although size, trunk location, and DDL histology were not significantly different between treatment groups. Ifosfamide–Doxorubicin independently improved DMFS (p = 0.001), DSS (p = 0.01), and OS (p = 0.001) on MVA. ConclusionIfosfamide–Doxorubicin may be more beneficial in younger patients with >5 cm, high-grade, STS of the trunk or extremity in Synovial-Cell, DDL, Myxofibrosarcoma, RCLS, UPS, and US-NOS.