William Cham

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 chemotherapy and radiation therapy in the treatment of metastatic osteogenic sarcoma

Fourteen patients with 16 metastatic osteogenic 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.

Malignant ovarian tumors in childhood. Prognosis in relation to initial therapy

Twenty‐two children with malignant ovarian tumors (12 malignant teratomas, six endodermal sinus tumors, and four embryonal carcinomas) were studied from 1960 through March 1975. Comparison is made between different modalities of therapy, such as surgery alone or surgery in combination with either radiation or chemotherapy. Because of the poor results obtained with the aforementioned treatment methods, a new approach, consisting of more aggressive initial surgery followed immediately by radiation therapy and an intensive chemotherapeutic regimen called the T2 protocol, was begun in 1971 with encouraging results. To date six of ten patients are alive and free of disease with a median observation period of 22+ months. A new grouping defining the extent of disease is also provided. Of the ten patients on the T2 protocol, only one was a Group I; eight were Group III and one was Group IV at the time treatment was initiated. An analysis of the mode of spread, as well as a discussion of the results obtained with previous modalities of therapy in relation to initial grouping and pathology, constitute the background for the proposed treatment.

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.

Radiotherapy of Ewing's Sarcoma: Local Control with and without Intensive Chemotherapy

Primary tumor control rates were studied in two groups of patients with Ewings 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.

Endodermal Sinus Tumors of the Ovary in Children

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 authors 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.

Patterns of extension as a guide to radiation therapy in the management of ovarian neoplasms in children

Sixteen cases of childhood malignant ovarian neoplasms of varied histology and stages were reviewed with special reference to the patterns of disease extension within the pelvis and abdomen. All patients had initial surgery elsewhere before referral to Memorial Hospital. Two patients had distant metastases (bone and lung). None of the other 14 girls had disease restricted to the pelvis. The first extension in 11 was to sites within the abdominal cavity as well as to the pelvis and in three to the abdomen without pelvic involvement. Total abdominal irradiation would have been required to encompass all known disease‐bearing areas in these 14 girls.

Involved field radiation therapy for early stage Hodgkin's disease in children. Preliminary results

Twenty Stage I and II children with Hodgkins disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were: nodular sclerosis (seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse‐free survival and survival rates at 3 years are 57 and 89%, respectively.