Preoperative radiochemotherapy in soft tissue sarcomas for improving localtumor control and postoperative functional outcome

Background: Adequate local control rates > 90% and acceptable functional re sults are the paramount goals in the treatment of soft-tissue sarcoma. Purp ose of this paper is to evaluate response, long-term control, functional ou tcome and toxicity following neoadjuvant radiochemotherapy (RCT) in advance d and recurrent soft tissue sarcoma. Patients and Methods: Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible enter ed the study. Sixteen patients had primary and 7 patients recurrent sarcoma . The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-c ourse radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of I week after 30 Gy) with concomitant chemotherapy usi ng adriamycin (50 mg/m(2)/d on days 2 and 30) and ifosfamide (1.5 g/m(2)/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 mo nths). Results: Twenty-two patients underwent surgery with a curative (R0) resecti on being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-down staging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 pa tient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED- and distant-metastases-free survival ra tes were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dyin g of septicemia. The functional results were good to excellent in 18/22 (82 %) patients. Conclusion: Accelerated split-course radiation with 60 to 64 Gy and concurr ent chemotherapy using adriamycin/ifosfamide is a safe and effective treatm ent for soft tissue sarcoma. This regimen may be considered in all cases wi th recurrent and advanced disease not amenable to primary curative or limb sparing surgery.