Biomedical subjects
Publications and source records attributed to N Jaffe.
Intra-arterial Cis-diammine dichloroplatinum (II) administered to five patients produced systemic and sustained hypertension in four of them. This finding persisted for six months despite discontinuation of the drug. This complication has not been observed in patients receiving the drug by the intravenous route. Possible etiologic factors are discussed.
The records of 455 children were reviewed to investigate the relationship of nutritional status at time of first referral to various measurements of disease and survival. Initial symptoms of weight loss, anorexia, fatigue, and early satiety were all directly correlated. Serum albumin level and nutritional status were not directly correlated. Likewise, there was no direct relationship between performance status and nutritional status. However, higher values of serum albumin were associated with better performance status. Nutritional status was directly related to freedom from relapse among children with solid tumors whether they had localized or non-localized disease. In addition, improved survival was related to good nutritional status for children with localized disease, whereas those with advanced disease had a poorer survival regardless of their nutritional status. Nutritional status appears to have prognostic implications among children with cancer.
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The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field (p < 10(-4)). The odds for ovarian failure in patients with both ovaries in the field are 19.7 higher than those for other irradiated patients (95% confidence interval, 5.3 to 72.8). Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure.
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The effect of low dose irradiation on subsequent compensatory renal enlargement in a group of children operated upon with unilateral nephrectomy for Wilms' tumor is reported. Comparison groups were children whose remaining kidney received either no direct irradiation or irradiation to only the upper portion of the kidney. The rate of growth of the kidney in the irradiated group was slightly less but this was not statistically significant. Thus, radiation therapy in children with Wilms' tumor, so crucial to optimum survival, does not seem to cause significant renal toxicity.
This communication provides a description and update of the three adjuvant regimens utilized at the Sidney Farber Cancer Institute. The disease-free survivals are: Study I--42% at 4 years; Study II--58% at 3 years; and Study III--currently 78%. In the limb salvage experience, among the evaluable patients, 6 of 12 treated with preoperative chemotherapy are disease free (median 32 months) and 12 of 14 (86%) treated without preoperative chemotherapy are disease free (median 13 months).
From 1972 to 1979, high-dose methotrexate (HDMTX) and 3 adjuvant regimens were used at the Sidney Farber Cancer Institute and Children's Hospital Medical Center. In the first regiment, HDMTX was used alone; the second, HDMTX and adriamycin, and the third, weekly courses of HDMTX and combination. Actuarial disease-free survival achieved with these regimens in patient with local control of the primary lesion varied from 42 to 75% at 3 years. This compared favorably with historical control patients, of whom 50% were free of disease at 6 months and only 20% at 12 months. Among 41 patients with established pulmonary metastases, 14 were alive and free of disease from more than 4 to over 60 months. The most efficacious method of administering HDMTX was a weekly schedule which produced an overall response rate of 48% in the treatment of pulmonary metastases and primary tumor in patients previously not exposed to HDMTX. Urinary alkalinization was not a standard procedure, and investigations failed to demonstrate any significant effect of alkalinization on HDMTX pharmacokinetics.
Of seventy-four children who were treated at a mean age of seventeen months for neuroblastoma and survived more than five years, fifty-six (76 per cent) had spinal deformity due either to the disease or to the treatment after a mean follow-up of 12.9 years. Of these fifty-six, 50 per cent had post-radiation scoliosis (mean, 18 degrees; range, 5 to 79 degrees), and 16 per cent had post-radiation kyphosis, most frequently at the thoracolumbar junction (mean, 39 degrees; range, 13 to 61 degrees), at the time of follow-up. Two kyphotic thoracolumbar curve patterns were identified: (1) an angular kyphosis with a short radius of curvature and its apex at the twelfth thoracic and first lumbar vertebrae, and (2) a thoracic kyphosis with a long radius of curvature that extended into the lumbar spine. The post-radiation deformity--both the scoliosis and the kyphosis--progressed with growth, the scoliosis at a rate of 1 degree per year and the kyphosis at a rate of 3 degrees per year. Epidural spread of the neuroblastoma was associated with most of the cases of severe scoliosis and kyphosis. The deformity was due either to the laminectomy or to the paraplegia acting in conjunction with the radiation. Eighteen per cent of 419 children with this malignant disease survived more than five years, and of the survivors, 20 per cent had spinal deformity severe enough to warrant treatment. The factors associated with the development of spinal deformity in patient treated for neuroblastoma were: (1) orthovoltage radiation exceeding 3000 rads, (2) asymmetrical radiation of the spine, (3) thoracolumbar kyphosis, and (4) epidural spread of the tumor.
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Fifty-six patients with osteosarcoma were studied to determine the onset of pulmonary and bone metastases. While pulmonary metastases were always detected prior to bone metastases in the era before adjuvant chemotherapy, in this study of patients on adjuvant therapy 16% of patients with metastases showed osseous metastases prior to or without pulmonary metastases.
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Total parenteral nutrition TPN has been used to treat or prevent malnutrition in 65 children with a variety of solid tumors and leukemia in the past 7 years. TPN was used in 58 patients with gastrointestinal complications of surgery, chemotherapy, or radiation; in 2 patients for preoperative correction of malnutrition; and in 8 who were entered into a prospective study. During TPN, general nutrition and appearance improved in all patients. Weight gain was noted in most. Despite gastrointestinal complications, which usually require the interruption of chemotherapy and radiation, treatment could be continued at full dose in 31 children with nutritional support by TPN. TPN was discontinued in 6 patients when blood cultures became positive. Sepsis was treated successfully by removal of the central venous catheter in all 6 and administration of antibiotics in 3. TPN appears to be safe and effective means of combating malnutrition which may occur with cancer and its therapy.
The records of one hundred seventy-six patients with Wilm's tumor treated with transabdominal nephrectomy only or transabdominal nephrectomy, post-operative radiation therapy and several chemotherapy programs were reviewed. Three conclusions were reached: 1) The addition of postoperative radiation therapy and adjuvant chemotherapy has not improved the excellent, disease-free survival of patients with Stage I disease who were less than twenty-four months of age at diagnosis; 2) The addition of postoperative radiation therapy and adjuvant single agent chemotherapy has not improved the disease-free survival of patients with Stage II disease who were over twelve months of age at diagnosis; and 3) The use of combination chemotherapy with vincristine and actinomycin D has improved the disease-free survival of patients who present with Stage II disease.
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Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalies or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments.