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
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.
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.
Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.
Sep 22, 2011 - Tumor necrosis factor-α and melphalan-based isolated limb perfusion therapy has a limb salvage rate of 81 percent in patients with locally advanced extremity soft tissue sarcomas who would have otherwise undergone amputation, according to a study published online Sept. 19 in the Journal of Clinical Oncology.