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

Radiother Oncol. 2021 Dec:165:174-178. doi: 10.1016/j.radonc.2021.10.019. Epub 2021 Nov 7.


Purpose: To compare long-term outcomes of high-grade, primary soft-tissue-sarcoma (STS), using Ifosfamide-Doxorubicin vs local therapy alone, in histology-specific sarcomas.

Methods: Retrospective 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.

Results: Median 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.

Conclusion: Ifosfamide-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.

Keywords: Chemotherapy; Localized; Soft tissue sarcoma.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Doxorubicin / therapeutic use
  • Humans
  • Ifosfamide / therapeutic use
  • Retrospective Studies
  • Sarcoma* / drug therapy
  • Soft Tissue Neoplasms*
  • Treatment Outcome


  • Doxorubicin
  • Ifosfamide