Neoadjuvant chemotherapy for primary high grade extremity soft tissue sarcoma: A matched case control study

Reviewer: Neha Vapiwala, MD
Last Modified: June 1, 2003

Presenter: S. R. Grobmyer
Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center and Dana-Farber Cancer Institute
Type of Session: Scientific


    The investigation of high grade (HG) extremity soft tissue sarcomas (STS) is often challenging secondary to the relative rarity of these tumors. Furthermore, acquiring broad treatment data is difficult given the substantial heterogeneity of tumor subtypes. A meta-analysis of 14 randomized controlled high-risk sarcoma trials demonstrated a statitically significant improvement in recurrence-free survival with the use of preoperative doxorubicin-based chemotherapy compared to control pts undergoing surgery and postoperative radiation therapy when indicated. No overall survival difference was seen in the whole group, although subgroup analysis of extremity lesions did demonstrate a 10-yr survival advantage of ~7%. Three small prospective randomized trials evaluated doxorubicin/ifosfamide therapy in primary STS, although only one of these showed a survival difference with adjuvant combination chemotherapy. The goal of this study was to characterize survival predictors in patients with large, HG STS as well as the association of neoadjuvant chemotherapy with survival and recurrence.

Materials and Methods

  • Case-control study using pts with HG STS of size > 5 cm identified from MSKCC and Dana-Farber databases from 1978 to 2001
  • Control pts (n=411) = no chemotherapy but were treated with surgery and, in most cases, postoperative radiation
  • Case pts (n=76) = neoadjuvant AIM chemotherapy (adriamycin/ifosfamide/mesna) prior to surgery
  • Median follow-up for controls = 50 mos
  • Median follow-up for cases = 38 mos
  • First, multivariate analysis performed to determine factors associated with disease specific survival in control group
  • These factors were then used to match controls to treated cases
  • After matching, controls and cases were randomly grouped in a 5:1 ratio when possible
  • Sarcoma-specific, local relapse-free and distant relapse-free survivals were evaluated


  • No significant difference in 4-yr sarcoma- specific survival between two groups
  • However, 2-yr sarcoma-specific survival showed benefit of 11% in chemotherapy group
  • No significant difference in local and distant relapse-free survivals
  • Four factors found to be significant survival predictors on multivariate analysis: 1) age > 60 yrs old 2) histologic subtype 3) size > 10 cm 4) positive margins
  • No significant difference in disease-specific survival between histologic subtypes in the chemotherapy group
  • Leiomyosarcoma and malignant peripheral nerve sheath subtypes associated with decreased survival in multivariate analysis of control group

Author's Conclusions

  • Size of primary lesion, histologic subtype, age of pt, and positive margins all factors significantly associated with disease specific survival
  • Neoadjuvant chemotherapy with AIM gives a 2-yr sarcoma-specific survival benefit.
  • This benefit is not seen on longer follow-up.
  • 2-yr and 4-yr distant recurrence-free survival rates did not differ between the case and control arms.

Clinical/Scientific Implications

    Established predictors of survival in large, high-grade sarcomas include patient age, histologic subtype, tumor size and margin status. The addition of neoadjuvant doxorubicin-based combination chemotherapy to the treatment algorithm of pts with high risk soft tissue sarcomas appears to have a short-term benefit in sarcoma-specific survival. However, 4-yr data do not show a continued benefit to adding chemotherapy, as compared to control pts treated with surgery +/- postoperative radiation only. In light of this observation, the authors suggest that new neoadjuvant regimens might be developed for future trials to better delineate the role of chemotherapy in optimizing outcome for high risk patients. Currently there is no role for neoadjuvant chemotherapy in the treatment of STS outside of a clinical trial.

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