Inverse relation between prostate-specific antigen and insulin-like growth factor-binding protein 3 in bone metastases and serum of patients with prostate cancer.

The usual osteoblastic phenotype of metastatic prostate cancer is unexplained. Here we show that tissue and serum concentrations of prostate-specific antigen (PSA)-vary inversely with a substrate protein that binds a growth factor known to activate osteoblasts. These findings suggest that PSA may contribute to the osteoblastic phenotype, and could thus represent a new drug target devoid of antiandrogenic toxicity.

Active minimisation of radiation scatter during breast radiotherapy: management implications for young patients with good-prognosis primary neoplasms.

BACKGROUND AND PURPOSE: Radiotherapy is used to reverse or prevent local tumour growth but is also a carcinogen in its own right. A recent audit of post-radiotherapy second malignancies in this institution revealed a striking preponderance of tumours originating near the outside edge of the treatment field. Since this finding suggests the existence of a critical subtherapeutic dose range predisposing to tumourigenesis, we attempted to define and reduce this radiation scatter dose. MATERIALS AND METHODS: We undertook a dosimetric review of 6 MV scatter from a linear accelerator in sites matching the putative tumourigenic region, and then extended this analysis to patients and tissue phantoms. RESULTS: A wide range of radiation scatter doses was confirmed-for example, doses 3 cm from the field edge varied from 1.7 to 22% of the therapeutic dose depending upon the field parameters. Scatter doses were then assessed in a sample of eight patients undergoing standard breast radiotherapy. Contralateral breast sites 4-12 cm from the midline received 4-10% of the therapeutic dose, or 200-500 cGy for a 50 Gy treatment, approximating historical estimates of the tumourigenic range. The deep component of this scatter dose from medial field breast irradiation was reduced 19% simply by replacing the 15 degrees medial tangential field wedge with a 30 degrees lateral wedge. Other manoeuvres which reduced contralateral breast dose by up to 46% included making the posterior field edges co-planar and shielding the breast during medial field irradiation. CONCLUSIONS: These results suggest that the risk of radiogenic second malignancies could be significantly decreased by careful attention to the treatment details. Greater awareness of these measures may prove particularly relevant to the conservative management of young patients with good-prognosis breast neoplasms such as ductal carcinoma in situ.

Hormonal factors associated with weight loss in patients with advanced breast cancer.

Fasting blood samples were collected from 83 patients with histologically proven breast cancer and analysed for plasma glucagon, serum immunoreactive tumour necrosis factor (TNF alpha), insulin, glucose, growth hormone, cortisol and TSH. Samples from patients with known diabetes mellitus or thyroid disease, and those on parenteral nutrition or with evidence of infection were excluded as were patients who had a history of weight loss through dieting or who were anorexic. Fasting plasma glucagon, serum cortisol and immunoreactive TNF alpha concentrations in patients with stage IV breast cancer who had developed weight loss were significantly higher than those in patients with stage IV disease who had not developed weight loss. There were no significant differences in the fasting serum concentrations of insulin, glucose, growth hormone and TSH between the two patient groups. The association between weight loss in stage IV breast cancer and increased concentrations of plasma glucagon, serum cortisol and TNF alpha suggests a possible role for these hormonal factors in the development of cancer cachexia.

The serum levels of some trace and bulk elements in cancer patients.

The levels of copper, zinc, calcium, manganese and magnesium have been monitored in the sera of patients suffering from various types of cancer. Only serum copper appeared to be of any diagnostic significance, its levels being above the normal reported range in the breast cancer, leukaemia and Hodgkin's lymphoma patients. In the case of breast cancer, serum copper is progressively elevated according to the stage of the disease. Serum calcium levels were also significantly lower in patients with tumours of the breast, gastrointestinal tract and cervix. The results suggest that serum copper levels could be of prognostic significance in breast cancer patients receiving radiotherapy.

Serum galactosyl transferase levels in patients with advanced cancer.

Serum galactosyl transferase was significantly higher in patients with various types of cancer than in age-matched controls. The highest serum enzyme levels were observed in the breast and respiratory cancer, followed by ovarian and gastrointestinal tumours; whereas the enzyme activity in prostatic cancer patients was not significantly higher than in the control subjects. In the cancer patients the serum levels of this enzyme were not significantly higher in the presence of metastases. In terminally ill patients, the serum enzyme activity decreased proportionately in accordance with the progression of their disease.

Results of 27 cases with hepatic metastases treated by combination chemotherapy.

The results of using a standard combination of cytotoxic agents in 27 cases of secondary liver cancer are reported. A brief review of the methods available for treating hepatic metastases from solid tumours, as opposed to lymphomata, is included. The response rate depends on the site of the primary lesion. It is suggested that in patients with mammary or colorectal primary tumours, combination chemotherapy represents an advance in treatment with an objective response rate of 73% and 66% respectively in the 2 groups. The method requires no specialized equipment as neither grossly deranged liver enzymes nor jaundice are contra-indications to treatment, and toxicity is easily monitored and readily controlled.

Seventy-five cases of solid tumours treated by a modified quadruple chemotherapy regime.

Seventy-five cases of malignant solid tumours treated by a quadruple chemotherapy regime are described. These tumours originated in the breast, head and neck, bronchus, genital tract, cutaneous melanoma, soft tissue and gastro-intestinal tract. All 14 patients with breast carcinoma underwent remission and in 6 this was complete. Significant remissions were seen in gastro-intestinal and head and neck malignancies, and also in the soft tissue group. A short response was noted in 6 of 14 cases of bronchial carcinoma. Malignant melanoma, testicular, ovarian and cervical carcinomata failed to respond.In all, 40 of 75 patients underwent objective remission.

Preliminary clinical assessment of I.C.R.F. 159 in acute leukaemia and lymphosarcoma.

I.C.R.F. 159, a new antitumour agent, has been assessed in six patients with acute leukaemia and three with lymphosarcoma. In all but two there was a considerable fall in circulating primitive cells, and in one there was bone-marrow evidence of a partial remission. Severe toxic effects were seen in only one case; they consisted of alopecia and gastroenteritis. It is suggested that I.C.R.F. 159 is worth further examination in all forms of acute leukaemia and lymphosarcoma.