Ewing's sarcoma: a trial of adjuvant chemotherapy and sequential half-body irradiation.

The results of a pilot study using adjuvant chemotherapy and sequential half-body irradiation (HBI) for nonmetastatic Ewing's sarcoma are presented. Seventeen patients received Cyclophosphamide, Vincristine, and Adriamycin (8 cycles), followed by sequential radiation treatment of the upper (500 cGy) and lower (600 cGy) half body. Survival at 3 years was 49%. These results are contrasted with those for 18 concurrently treated patients who received standard adjuvant therapy. Overall 5-year survival and relapse-free survival for these 35 consecutive patients was 61 and 53%. The pilot protocol was given on an out-patient basis with limited and acceptable acute toxicology. Further study is necessary to determine the value of the pilot protocol.

Primary and secondary tumors of childhood involving the heart, pericardium, and great vessels. A report of 75 cases and review of the literature.

Between 1919 and 1981, 16 children with primary cardiac tumors (8 rhabdomyomas, 5 fibromas, 2 myxomas, and 1 rhabdomyosarcoma) and 59 children with secondary tumors of the cardiovascular system were seen at The Hospital for Sick Children in Toronto. Distant metastases in 45 children of the latter group, in descending order of frequency, were from non-Hodgkin's lymphoma, neuroblastoma, soft tissue and bone sarcoma, Wilms' tumor, and hepatoma, and involved the myocardium and pericardium. In the remaining 14 children, tumor thrombi from Wilms' tumor (9 cases), adrenal (2 cases) and hepatocellular carcinoma (2 cases), and endodermal sinus tumor (1 case) extended directly into the great veins and/or cardiac chambers. Children with primary and secondary tumors often present with nonspecific clinical, plain radiographic, electrocardiographic, and M-mode echocardiographic findings. Early recognition, utilizing special diagnostic procedures such as two-dimensional echocardiography, computerized axial tomography, angiocardiography, and inferior venocavography, followed by elective surgical resection of tumor under cardiopulmonary bypass and/or radiation and chemotherapy, offers patients with cardiovascular tumors the best chance of cure.

Neuroblastoma: influence of age at diagnosis, stage, tumor site, and sex on prognosis.

A study of a consecutive series of 99 children with neuroblastoma seen at two major Toronto hospitals between 1951 and 1971 is reported. The children who were aged 24 months or less at diagnosis showed an overall two-year survival rate of 59 percent. Analysis, including fitting of a log-linear model, showed that increased probability of survival was associated with younger age at onset, nonadrenal site, and lower staging and the each of these factors acted independently. The sex of the child had no prognostic effect. This study thus extends earlier work by demonstrating the independent prognostic influence of site of tumor. The implications for treatment policy are discussed.

Echocardiography in adriamycin cardiotoxicity.

Twenty-six patients receiving adriamycin for osteogenic sarcoma had serial echocardiographic assessments of their left ventricular function. A statistically significant deterioration of function was noted throughout the course. Ventricular function tended to normalize in the period following cessation of adriamycin. The velocity of circumferential fibre shortening (Vcf) and ejection fraction (EF) were the best parameters. Sudden declines in these values resulted in us withholding therapy until the parameters again improved. Fatal congestive heart failure was seen in only one patient. Echocardiography thus provides the clinician with a valuable tool enabling one to improve the therapeutic usefulness of adriamycin by removing much of the uncertainty over the development of cardiotoxicity.

Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyclophosphamide, and oncovin (PATCO) combination chemotherapy.

One hundred-sixty-three children with acute nonlymphocytic leukemia (ANLL) were treated with a multiple-drug induction program (PATCO) consisting of prednisone (PDN), cytosine arabinoside ((Ara-C), 6-thioguanine (6-TG), cyclophosphamide (CPM), and Oncovin (VCR). Ninety-six, 59%, obtained a remission. Remission was maintained with daily 6-TG and four-day pulses of Ara-C and CPM with a single dose of VCR every 28 days. The median duration of remission was 11.5 months. Certain prognostic factors affected induction rate and remission duration. Initial white blood count (WBC) was a significant factor in achieving a remission, whereas age, sex, and type of ANLL had no effect. Initial WBC, age, and sex had a significant effect on remission duration, but type of ANLL had no effect. Relapsing patients were treated with daunomycin and 5-azacytidine. The reinduction rate was 53% with a median second remission duration of 190 days. Overall survival for the 163 patients is 55.4% at 12 months, 31.5% at 24 months, 21.4% at 36 months, and 19% at 48 months.

Wilms' tumour: adjuvant treatment with actinomycin D and vincristine.

In an unselected series of 49 children with Wilms' tumour treated in 1969-74 the 5-year relapse-free survival and survival rates were 78% and 81%, respectively, whereas in the series of children treated in 1963-68 the corresponding rates were 49% and 70%. The significant improvement in the relapse-free survival rate was a result of adjuvant treatment with actinomycin D and vincristine (AMD + VCR), which, in some patients, eradicated occult metastatic disease. In the treatment of lung metastases the combination of whole-lung irradiation and maintained chemotherapy with AMD + VCR proved excessively toxic: in 5 of 11 patients acute diffuse pneumonitis developed, and it was fatal in 3. Adjuvant AMD + VCR therapy is advocated in all patients with Wilms' tumour except children less than 12 months old with a tumour of moderate size, limited to the kidney and completely resectable.

Hodgkin's disease in children. A retrospective analysis: 1958-73.

One hundred nine children with Hodgkin's disease consecutively treated at The Princess Margaret Hospital, Toronto, during 1958-1973 are reviewed. Crude 5-year survival rates, regardless of stage, were 1958-64--50%; 1965-68--73%; and 1969-73--95%. The corresponding 5-year relapse-free rates were 19%, 20%, and 57%. This progressive improvement in results was associated with the sequential introduction of lymphography and laparotomy with splenectomy, the change from involved field to extended field irradiation, and the introduction of multiple agent chemotherapy, at first for generalized relapse and recently as elective initial therapy, combined with extended field irradiation for children in advanced stages.

Wilms' tumour: treatment of 113 patients from 1960 to 1971.

The crude 5-year survival rate among children with Wilms' tumour increased from 54% for those diagnosed from 1960 to 1965 to 81% for the period 1966 to 1971. This resulted from an increased ability to cure metastatic disease and, to a lesser extent, to an increased ability to prevent relapse. It is proposed that, after resection and postoperative irradiation, maintained combination chemotherapy with actinomycin D and vincristine should be used electively to prevent relapse, but that this use should also be selective in order that overall morbidity be minimized. Of urgent priority, therefore, is improved delineation of present-day prognostic factors in children with Wilms' tumour.

Dermatophyphics in childhood leukemia.

The dermatoglyphics of 54 leukemic children do not differ significantly from those of 25 mothers and 592 unrelated controls with respect to frequency of digital pattern types, position of axial triradius, or type of palmar flexion creases. These findings do not support the hypothesis that children with leukemia have an increased frequency of unusual dermal patterns, but suggest that the dermatoglyphics of leukemic children are not distinctive and therefore have no practical value in the diagnosis of childhood leukemia. Whatever factors are responsible for the development of leukemia in children, these factors do not appear regularly to affect the differentiation of the dermal ridges.