Endodermal sinus tumor of the ovary in children has been characterized by its general resistance to therapy and its almost uniform fatality. The multidisciplinary treatment of 5 such cases is described. The author's experience suggests that these tumors are responsive to irradiation. The rationale for a combined approach is discussed, and radiation treatment volumes and doses are suggested.

Twenty-three patients with rhabdomyosarcoma and 15 patients with Ewing's sarcoma, treated with radiation therapy to the local site and systemic multiagent chemotherapy are described. Acute reactions from combination chemotherapy and radiation therapy were noted in both groups of patients. These reactions often appeared after low doses of irradiation, required unplanned interruptions of treatments, and in some patients, led to discontinuation of radiation therapy. The chronic effects on normal tissues in both groups of patients have been severe in several cases.

Primary tumor control rates were studied in two groups of patients with Ewing's tumor. They received high doses of radiation combined with a standard chemotherapy regimen incorporating multiple agents. Another 17 had either less chemotherapy or none at all. The data suggest that treatment dose and control are correlated and that intensive chemotherapy contributes to destruction of the primary tumor.

Fourteen patients with 16 metastatic ostogenic sarcoma lesions were treated with high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and pulse high-dose cyclophosphamide combined with radiation therapy. Thirteen of 16 lesions responded. Responses consisted of relief of pain (6/6 patients) in bone lesions, roentgenographic and clinical evidence of decrease in the size of the bone lesions (6/7 patients), and a decrease in the size of pulmonary metastases (2/4 patients). The 2 patients whose pulmonary metastases responded to combined therapy developed pulmonary fibrosis and pneumonitis in the treated areas 3 months after radiation therapy (RT) (1400 and 1600 rads respectively). Of two bulky primary tumors that appeared to respond, both were ultimately found to contain viable tumor; a third less bulky primary tumor appeared to respond more completely. Three smaller metastatic bone lesions that were ultimately biopsied showed no evidence of active tumor. It is concluded that: 1) combination therapy (particularly HDMTX and RT) has an additive effect in controlling osteogenic sarcoma bone lesions, but bulky primary tumors cannot be completely eradicated; 2) although synergistic in treating osteogenic sarcoma, combination therapy can produce enhanced toxicity in surrounding normal lung tissue; and 3) combination therapy is of value in the palliative treatment of metastatic lesions other than that of lung, and in the treatment of small primary bone lesions. However, experience to date does not justify the delay in surgical ablation of a primary lesion in a child who presents without metastatic disease.

Adjuvant chemotherapy was added to local radiation therapy for patients with Ewing's sarcoma to treat widespread microfoci of disease presumed to be present at the time of diagnosis. Since June 1970, 12 children have been treated with radiation therapy and sequential adjuvant chemotherapy: dactinomycin, adriamycin, vincristine, and cyclophosphamide, continued for 2 years. Two children developed reversible congestive heart failure after cumulative adriamycin doses of 905 mg/m2 in one patient and 720 mg/m2 in another patient who had mediastinal irradiation. Adriamycin is now generally limited to cumulative doses of 720 mg/m2 but is further limited to 500 mg/m2 in children who receive mediastinal or pulmonary irradiation. Of 12 children entered into this study and followed for from 10 to 37 months, all continue in disease-free remission without evidence of recurrent tumor, metastatic tumor, or central nervous system disease.