Neoadjuvant Chemotherapy and Radiotherapy for Large Extremity Soft Tissue Sarcomas

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 7, 2001

Presenter: T.F. DeLaney
Presenter's Affiliation: Massachusetts General Hospital, Boston, MA
Type of Session: Scientific

Background
The management of extremity soft tissue sarcomas has evolved from amputation to limb sparing surgery with radiation therapy. While local control rates are generally quite high, the development of distant metastases remains a significant problem. This current study was undertaken to determine if the addition of chemotherapy reduces the incidence of metastases and increases overall survival

Materials and Methods

48 patients with large (>8cm) high grade extremity soft tissue sarcomas were enrolled.

Patients received 3 cycles of pre-operative chemotherapy consisting of Mesna, Adriamycin, Ifosfamide, and Dacarbazine (MAID)interdigitated with radiotherapy (44 Gy).

Following completion of this therapy patients had a three week break, followed by resection.

If surgical margins were positive an additional 16 Gy was administered

All patients were scheduled to receive 3 more cycles of MAID post-operatively.

Results

Median age was 50 years

Median tumor size was 14 cm.

Median follow-up was 4 years.

83% of patients got all 6 cycles of MAID.

Freedom from distant metastases was 75%, which was significantly higher than 44% for matched historical controls.

Disease free survival(DFS) was 70% versus 42% for the historical controls.

2 year DFS was 90% for the experimental group.

Overall survival was also significantly higher, 87% versus 58%.

25% of patients had at least one episode of febrile neutropenia.

30% had moist skin desquamation, and 30% had delayed wound healing.

Author's Conclusions
Treatment with neoadjuvant MAID chemotherapy interdigitated with preoperative radiotherapy, surgery, and postoperative MAID chemotherapy +/- postoperative boost radiotherapy appears to be effective in reducing distant metastases and increasing disease free survival and overall survival in this population, as compared to historic controls who mostly had surgery and radiation therapy.

Clinical/Scientific Implications

The results of this study are consistant with findings from a recent RTOG study.

This suggests that pre-operative chemotherapy should be considered in patients with large, high grade extremity soft tissue sarcomas.

However, comparisons to historical controls can be fraught with problems because of multiple confounding variables and differences in follow-up time between the groups.

Additional prospective studies are needed to evaluate this approach

Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology and Pharmacia Oncology.