Preoperative regional therapy for extremity sarcoma. A tricenter update

Preoperative radiation with sensitizing doxorubicin has been popularized in the treatment of high grade sarcoma of the extremity. A multiinstitutional experience with this protocol that was initiated by the Southeastern Cancer Study Group in 1984 and maintained in three institutions was updated by the authors.

Patients with biopsied sarcoma had intraarterial infusion with doxorubicin hydrochloride (Adriamycin) 30 mg/24 hrs x 3 days and were allocated by the institution to receive radiation 30-35 Gy in 10 fractions or 46 Gy in 23-25 fractions followed by resection. Surgery was performed within 10 days or 30 days depending on the radiation dose. Postoperative chemotherapy was administered to 31 patients.

Of 66 patients, 32 were female and 34 were male. The median age was 46 years (range, 14-77 years); 73% had lower and 27% had upper extremity tumors. There were 55 soft-tissue and 9 malignant bone tumors. Common types were malignant fibrous histiocytoma 20%; liposarcoma, 17%; synovial sarcoma 18%; and 14% were osteosarcoma. American Joint Committee on Cancer stages were: I, IIB (17%), IIIA/B (59%), and IIIC/4A (24%). Limb salvage surgery was performed on 60 patients including radical resection in 21 with extensive tumors, wide local excision in 30, and limited excision in 2 patients. Primary amputation was performed on four patients and delayed amputation in two because of wound complications. Three patients had pulmonary metastasectomy in conjunction with primary surgery (2 are long term survivors > 5 years). There were no postoperative deaths, but wound complications occurred in 41% of the patients. Overall survival and disease free survival at 5 years was 59 and 49%. One patient (1.5%) had local recurrence 9 years after resection of an extensive synovial sarcoma of the shoulder. This was resected with limb salvage techniques. Among 23 patients who failed primarily in the lung, the median survival was 7 months with 4 surviving more than 5 years, after demonstration of the pulmonary metastases. Multivariant analysis of prognostic factors showed that extent of disease and stage correlated with disease free survival, whereas only extent of surgical resection correlated with overall surgical survival.

Combined therapy for extremity sarcoma in a multicenter setting using preoperative radiation with sensitizing chemotherapy and adequate resection was associated with an excellent local control rate (98.5%) and reasonable long term tumor control, although distant metastases continued to be a major challenge.