THE HISTOLOGICAL RESPONSE TO CHEMOTHERAPY AS A PREDICTOR OF THE ONCOLOGICAL OUTCOME OF OPERATIVE TREATMENT OF EWING SARCOMA

Seventy-four patients who had a Ewing sarcoma of bone were managed wit h preoperative and postoperative chemotherapy and operative resection, with or without postoperative irradiation. The primary objectives of the study were to determine the histological response to preoperative chemotherapy in terms of the percentage of turner necrosis and to asse ss the relationship between the histological response and the oncologi cal outcome. The minimum duration of follow-up of the surviving patien ts who were continuously free of disease was five years. Sections of e ach operative specimen mere examined, and the histological response to chemotherapy was graded semiquantitatively, Grade I indicated necrosi s of 50 per cent of the tumor or less; grade II, necrosis of more than 50 per cent but less than 90 per cent; grade III, necrosis of 90 to 9 9 per cent; and grade IV, necrosis of 100 per cent of the tumor. Of th e seventy-four tumors, forty-four (59 per cent) were exquisitely sensi tive to chemotherapy and had complete (grade-IV) or nearly complete (g radle-III) necrosis, In contrast, fourteen tumors (19 per cent) had li ttle or no response to chemotherapy (grade I) and sixteen (22 per cent ) had a moderate degree of necrosis (grade II). The histological respo nse to preoperative chemotherapy (p = 0.0001), followed by the size of the tumor (p = 0.001), were the most important predictors of event-fr ee survival. At five Sears, the rate of event-free survival was zero o f fourteen patients who had had a grade-I response, six of sixteen who had had a grade-II response, and thirty-seven (84 per cent) of forty- four who had had a grade-m or TV response. The risk of local recurrenc e was most strongly associated with the operative margins; there were only four local recurrences (6 per cent) after sixty-seven resections with negative margins. Local recurrence may also have been influenced by the histological response and the use of local radiation. There wer e no local recurrences after operative treatment of six tumors that ha d been associated with pathological fracture. The histological respons e to preoperative chemotherapy and the size of the primary tumor are t he most important clinical predictors of the outcome of operative trea tment of non-metastatic Ewing sarcoma, These indicators should be used to identify patients who are at high risk for metastasis as such pati ents may be candidates for more intensive or novel therapies.