Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy.

Background: Preoperative chemotherapy has been advocated for the treatment of soft tissue sarcomas, yet there is little information about how these tumors respond pathologically to therapy or whether tumor response can be predicted from a pretreatment biopsy.

Methods: Biopsy was done of 25 intermediate- or high-grade soft tissue sarcomas before they were treated with three cycles of doxorubicin and cisplatin and resected. The authors compared the pathologic features of the treated tumors with clinical and radiologic evidence of response to identify the pathologic features that best reflected chemotherapeutic effect. They analyzed the pretreatment biopsy specimens by light microscopic study and flow cytometry to identify parameters that predict short-term response to chemotherapy.

Results: In the treated tumors, the clearest indicator of early chemotherapeutic effect was the percentage of the resected mass composed of viable neoplasm. Eleven of 25 resection specimens contained less than 15% viable neoplasm (patients with pathologic response); 9 of these had 5% or less. Flow cytometric estimates of the proliferative rate in the initial biopsy specimen predicted early chemotherapeutic effect; 7 of 10 tumors with S-phase fractions (SPF) greater than 6% responded pathologically, whereas only 3 of 12 tumors with lower SPF responded (P = 0.041). Initial tumor grade, cell type, percent tumor necrosis, mitotic rate, cellularity, and ploidy did not predict chemotherapy response.

Conclusion: These results indicate that soft tissue sarcomas often respond dramatically to chemotherapy, that the amount of residual viable sarcoma is an indicator of short-term effect, and that flow cytometric estimates of cell proliferation predict early response to chemotherapy.