An experimental model for the study of thermochemotherapy in vivo.

Human melanomas serially passaged in nude mice as xenotransplants were used as models for the study of the effects of thermochemotherapy of human malignant tumours in vivo. Three such melanomas, one (BRO) fast-growing, one (SCH) slow-growing, and one (BEL) of intermediate growth rate, were chosen. One group was left untreated as a control, one received chemotherapy (cyclophosphamide), one received hyperthermia, and one a combination of both treatments. In all three tumours, the best results were obtained associating chemotherapy with hyperthermia. The fastest growing tumor responded more than the slower, which responded better than the slowest. This model should prove useful in testing the effectiveness of anticancer agents used in association with hyperthermia.

Heterotransplantation of human breast carcinomas in nude mice. Correlation between successful heterotransplants, poor prognosis and amplification of the HER-2/neu oncogene.

Four hundred and thirty-three human breast carcinomas and 23 cell lines derived from human breast carcinomas were heterotransplanted in nude mice. Twenty-eight tumors and 13 cell lines took and could be serially transplanted. Their human origin was established by isozyme analysis performed on successive passages. Sixteen primary infiltrating duct-cell carcinomas (PIDC) took, from a total of 262 transplanted (6.1%). This is in striking contrast to the greater than 50% rate of takes of most major cancers of epithelial origin. All 16 PIDC growing in nude mice were highly cellular and lacked desmoplastic hyperplasia. The clinical prognosis of the PIDC patients whose tumors were successfully transplanted was poor. Ten of 16 (63%) died of their disease within 3 years, compared to only 49 (20%) of the 246 PIDC patients whose tumors did not take in nude mice. This could not be attributed to later stage disease of the tumors that took, because only 15% of these patients had 4 or more positive axillary lymph nodes as opposed to 28% of the patients whose tumors did not take. Sixty-four percent of the breast carcinomas growing in nude mice exhibited amplification of the HER-2/neu oncogene which is also correlated with poor prognosis in human breast cancer. It is possible that the nude mouse is more susceptible to a population of highly invasive and lethal breast carcinomas.

Treatment of cancer of the liver. Twenty years' experience with infusion and resection in 414 patients.

The factors influencing survival for patients with cancer of the liver were studied by reviewing the records of 414 patients operated on in a private oncology practice. Approximately half (47%) had colorectal metastasis; 17% had metastatic breast carcinoma, 14% had malignant hepatoma, 5% had metastatic melanoma, and the remainder had a variety of primary cancers. Eighty-two per cent of all patients had advanced liver disease when first diagnosed. One quarter of the patients had some type of resection; the remainder had abdominal exploration plus insertion of an infusion catheter into the hepatic artery. The postoperative mortality rate after liver resection for 108 patients was 6.5%. After resection, the most important prognostic factor influencing survival was the presence or absence of extrahepatic metastases. When possible, resection was by far the best treatment available, and the best results were seen in patients who had resection of a solitary lesion. For advanced disease, when resection was not possible, intra-arterial chemotherapy, primarily with 5-fluorouracil (5-FU), was associated with response rates of 36% for colorectal cancer, 45% for breast cancer, 13% for hepatocellular cancer, 12% for melanoma, and 14% for metastases from other primary sites. The patients who responded to infusion lived longer than those who did not respond. For example, at 18 months, 26% of the responders with colorectal cancer were alive, as were 50% of the responders with breast cancer and 40% of the responders with hepatocellular cancer. In contrast, at 18 months, there were no survivors among the nonresponders with colorectal, breast, or hepatocellular cancer. For those patients treated solely by infusion chemotherapy, the extent of disease in the liver was the most reliable factor in predicting the length of survival. However, very few patients treated in this manner lived longer than 3 years.

A ten year study of partial mastectomy for carcinoma of the breast.

Since 1970, 334 patients have undergone partial mastectomy, axillary dissection and irradiation for treatment of invasive carcinoma of the breast. The average follow-up period is 59 months. Survival curves were calculated for the entire study group and for patients classified by tumor size, nodal status and stage of disease. The five year over-all survival rate for 334 patients is approximately 87 per cent; the ten year survival rate is approximately 64 per cent. Of the 334 patients, 247 (74 per cent) have been observed for at least two years. Fourteen of these patients (5.7 per cent) have had a recurrence of carcinoma develop within the treated breast.