Neoadjuvant chemotherapy for Ewing's sarcoma of bone in patients older than thirty-nine years.

The aim of this study was to determine whether the behaviour of Ewing's sarcoma of bone in adult patients is the same as that observed in children and adolescents. We reviewed the clinical features and outcomes of 23 patients over the age of 39 (17 males, 6 females) who had been treated with neoadjuvant chemotherapy between 1983 and 1995 at our institution. The most common primary sites of tumor were the extremities (16 cases); tumor volume was more than 100 ml in 17 patients, and elevated serum LDH levels were found in 6 cases. The local treatment was surgery in 8 cases, surgery plus radiotherapy in 8, and radiotherapy alone in 7 cases. Chemotherapy comprised a 4-drug regimen in 10 patients, while the other 13 patients received 6 drugs. At a follow-up of 8.8 years (3.5-15) 13 patients remained continuously free of disease and 10 relapsed. The 5-year disease-free survival and overall survival rates were 53% and 59%, respectively. Clinical features, dose intensity, and toxicity of chemotherapy, as well as the outcome of these 23 patients were found to be exactly comparable to the findings observed in 327 patients younger than 40 years treated at our institution in the same period, with the same therapy. We conclude that Ewing's sarcoma of bone in adults is no different from that occurring in children, and we therefore recommend the inclusion of all adult patients in multidisciplinary treatment trials of this tumor.

Prognostic significance of serum LDH in Ewing's sarcoma of bone.

The pretreatment serum lactic dehydrogenase (SLDH) levels of 618 patients with Ewing's sarcoma of the extremities (136 metastatic at presentation and 482 localized) were analyzed to evaluate whether the enzyme level had a clinical value in predicting the course of the disease. The percentage of patients with increased SLDH was significantly higher in the metastatic group than in the group of patients with localized disease (68% vs 32%; P<0.0001). In the latter group treated with neoadjuvant chemotherapy the 5-year disease-free survival rate was significantly higher in patients with normal pretreatment SLDH than in those with high levels (65% vs 41%; P<0.0001). The time to relapse was significantly shorter for patients with elevated SLDH than in patients with normal values of the enzyme. The site of the tumor was significantly related with the stage of the disease, and for patients with localized disease, with the disease survival rate, at the multivariate analyses site of the tumor and SLDH levels were independently related with the stage of disease and with prognosis. These data demonstrate that in Ewing's sarcoma of bone pretreatment SLDH have a prognostic value and should be considered in the comparison of the results achieved with different therapies and in planning new randomized clinical therapeutic trials.

Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities.

Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.

Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients.

28 patients with telangiectatic osteogenic sarcoma of the extremities were treated between March 1983 and March 1990 with neoadjuvant chemotherapy according to two different protocols activated successively. With the first protocol, patients preoperatively received high dose methotrexate (HDMTX)-cisplatinum (CDP) and postoperatively, depending on the histological response, either HDMTX-CDP-doxorubicin (ADM) or ADM-"BCD". With the second protocol patients were preoperatively treated with HDMTX-CDP-ADM and postoperatively either with the same drugs or with the same drugs plus ifosfamide and VP-16. Preoperatively, CDP was delivered intraarterially. A good histological response (tumour necrosis > 90%) was observed in 25 patients (89%) and at a mean follow-up of 5 years (2-9 years) 23 patients (82%) remained continuously disease-free and 5 developed lung metastases. These results are better than those obtained in 272 contemporary cases of conventional osteosarcoma of the extremities treated with the same protocols (62% good histological responses and 61% continuously disease-free survival).