| Abstract: |
Primary therapy is predicated on surgical resection with an adequate margin of normal tissue. For high-risk patients, local control is improved with postoperative adjuvant radiation or intraoperative brachytherapy. Despite the most recent meta-analysis or encouraging phase II data for neoadjuvant chemotherapy, there is no dearly proven role for adjuvant or neoadjuvant chemotherapy in the treatment of locally advanced or recurrent sarcoma. Nevertheless, distinct subpopulations of sarcoma patients are appropriate for consideration of neoadjuvant/adjuvant chemotherapy due to their high risk of distant recurrence and potential for chemoresponsiveness. Patients with high-grade (≤10 cm) extremity sarcomas are at high risk for distant recurrence and are reasonable candidates for chemotherapy trials. Similarly, patients with high-risk intra-abdominal sarcomas may be reasonable candidates. If chemotherapy is considered, the patient should receive a combination chemotherapy including both ifosfamide and doxorubicin, as ifosfamide-lacking adjuvant regimens have little to no efficacy in the adjuvant setting. Future investigational trials will need to address in a randomized manner the adjuvant and/or neoadjuvant use of combinational chemotherapeutic regimens that contain both doxorubicin and ifosfamide. Also, these trials will need to be directed at high-grade, large (>10 cm) extremity soft tissue sarcomas or large, high-grade intra-abdominal tumors. These have a high risk of distant metastasis, and these patients are most likely to benefit from chemotherapy and demonstrate a therapeutic effect. Previous studies may have failed to demonstrate benefit to adjuvant chemotherapy specifically because the patient population was too broad, contained patients with good prognosis, or included tumors with extremely poor response rates to chemotherapy. Finally, better systemic therapeutic agents for sarcoma need to be sought out as our best chemotherapy regimens are only modestly effective with major response rates consistently less than 40%. |
