Giulio J. D'Angio

Non‐Hodgkin's lymphoma in children. A comparative study of two modalities of therapy

Eighty‐six children with non‐Hodgkins lymphoma were studied from 1964 to January 31, 1975. Seventy‐six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaports diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy‐six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty‐one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1–2 months from onset of therapy.

Disease‐free survival in children with Ewing's sarcoma treated with radiation therapy and adjuvant four‐drug sequential chemotherapy

Adjuvant chemotherapy was added to local radiation therapy for patients with Ewings 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.

Multidisciplinary treatment of embryonal rhabdomyosarcoma in children

Twenty‐nine children under 15 years of age with embryonal rhabdomyosarcoma were treated according to a multidisciplinary protocol (T‐2). The protocol consisted of surgical removal of the tumor if possible, followed by chemotherapy, and also with radiation therapy in patients with gross or microscopic residual disease. Radiation therapy was given in the 4500–7000 rads range. The chemotherapy consisted of cycles of sequential administration of dactinomycin, Adriamycin, vincristine, and cyclophosphamide, with obligatory periods of rest. The drug therapy was continued for 2 years. Following surgery, clinicopathologic staging of the disease revealed 10 patients with no residual disease (I‐A), 5 with microscopic residual disease (I‐B), 5 with unresectable tumors (II), 6 with unresectable tumors plus regional lymph node involvement (III), and 3 with disseminated tumors (IV). Twenty‐four (82%) of the patients (20 Stages I‐II, 4 Stage III) are alive with no evidence of disease for 4+ to 42+ months. These results are superior to those achieved between 1960–1970 among 108 children treated at Memorial Sloan‐Kettering Cancer Center.

Acute and late effects on normal tissues following combined chemo- and radiotherapy for childhood rhabdomyosarcoma and Ewing's sarcoma.

Twenty‐three patients with rhabdomyosarcoma and 15 patients with Ewings 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.

Combination therapy of urogenital embryonal rhabdomyosarcoma in children

Twenty‐seven children with embryonal rhabdomyosarcoma of the urogenital tract were treated between 1960‐1971. A review of their courses reveals that early stage of the disease at the time of diagnosis and multidisciplinary therapy —surgery, radiotherapy, and multiple drug therapy—offer the best chance for prolonged survival and cure. Seventeen (63%) of the 27 children are living and have been free of the tumor for 18 months‐10 years.

The changing management of childhood Hodgkin's disease.

Between 1929 and September 1974,211 children under 15 years of age with biopsy‐proven Hodgkins disease were treated at Memorial Sloan‐Kettering Cancer Center. For analysis these patients were placed into three historical groups which displayed the most marked changes in diagnostic workup and therapy. They are as follows: Pre‐1959—80 patients with “clinical” staging, local field radiation therapy, palliative chemotherapy; 1960–1969—86 patients with lymphangiographic staging, extended field radiation therapy, palliative chemotherapy; 1970‐September 1974—45 patients with “contemporary” staging, including laparotomy, involved field radiation therapy, and/or multiple drug chemotherapy. Twenty‐seven children with Stage IV disease at diagnosis or those with recurrent disease received this multiple drug regimen. This consisted of Adriamycin, followed by combined prednisone, procarbazine, and vincristine, then cyclophosphamide. Drug cycles were repeated every 3–4 months for a period of about 24 months. Twenty‐five achieved remission, 20 complete and 5 partial. The median duration of complete remission was 18+ months. This multidisciplinary management of Hodgkins disease has shown early, encouraging results. Longer followup is needed to determine that this improvement in survival will persist into adulthood.

Weekly total-skin electron-beam irradiation for mycosis fungoides.

Twenty-one patients with mycosis fungoides were given total-body irradiation with 2.5 and 3.5 MeV electrons, using four to six doses of 400 rads each. Prompt symptomatic relief and good long-term control of both ulcerated and nonulcerated lesions were obtained. Regression of lesions between fractions made subsequent treatments more efficient. No untoward immediate or late effects were noted in the irradiated bone marrow or normal skin. A severity scoring system used to evaluate radiation response is described.