Hyperthermia in the treatment of cancer.

There is now considerable evidence that heat can be used to destroy tumours. The metabolism of many types of cancer cell is selectively damaged at temperatures of 42-43 degrees C, and deficient tumour blood-flow at raised temperature represents a further exploitable Achilles heel. A striking feature of tumour heating is that metastases may regress with cure of the host; this has occurred with recurrent melanoma and sarcomas of the limbs. Heat acts synergistically with X-rays and some cytotoxic drugs to increase the therapeutic ratio for local tumour control. Guidelines for tumour heating are now being formulated against a strong experimental background in animal systems. The association of a wide variety of disciplines from oncology to electronics has already resulted in techniques for selectively treating human tumours at 50 degrees C and in internal heat applicators for insertion via natural passages. It is predicted that heat will achieve a place, most likely as an adjuvant, in cancer therapy. Work on animals and in vitro is of limited value in helping to define this place. The complexity of the tumour/host response to heat and the deficiencies in our knowledge of the biophysics of heating militate against early routine application of hyperthermia in the clinic.

Effect of hyperthermia on the immune response of normal rabbits.

Sequential skin responses to dinitrochlorobenzene challenge and repeat assays of serum antibody titer after two injections of bovine serum albumin were used as functional indices of cellular and humoral immunocompetence following hyperthermia in normal adult New Zealand White rabbits. The animals were subjected to different degrees of local hyperthermia by watercuff or radio-frequency heating of the normal thigh muscles maintained at 42 degrees for 1 hr on 3 consecutive days or 47--50 degrees for 30 min, respectively, or to total body hyperthermia (42 degrees for 1 hr on three occasions) in a humidified incubator. No alteration occurred in the response of heated rabbits to dinitrochlorobenzene challenge over a 3-month period. The humoral immune response to bovine serum albumin was significantly depressed (p less than 0.02) in the treated animals, and the reduction was independent of method and degree of heating. The results suggest that the B-lymphocytes are more susceptible to hyperthermic damage than is the T-cell population.

Milk bolus obstruction in the neonate.

Seventeen cases of neonatal intestinal obstruction due to inspissated milk curds were seen at this hospital in the 9 years 1964-1972. The obstruction started on the 2nd to 10th day of life. Half the babies passed blood from the rectum and in most the x-rays were diagnostic. All survived, 14 after operation and 3 after medical treatment with a Gastrografin enema. Incomplete absorption of solids, particularly the fat from cows' milk feeds, is suggested as the cause.

The influence of tumor volume and the degree of heating on the response of the solid Yoshida sarcoma to hyperthermia (40-42 degrees).

The solid Yoshida sarcoma implanted on the feet of rats was subjected to local hyperthermia by water bath immersion. Tumor response was governed by the temperature and duration of heating (i.e., the degree of heating) and by tumor volume. With small tumors (1.0- to 1.5-ml volume) an intratumor temperature of 42 degrees maintained for 1 hr led to tumor regression in 11 to 13 days, and the tumor volume was halved every 2.6 days. Following 2 hr hyperthermia (42 degrees) the tumors disappeared in 6 to 7 days, and tumor volume was halved every 1.2 days. Tumors of 2 to 3-mol volume had left the exponential phase of the growth curve and required 2 hr at 42 degrees for cure. Following heating at 40 degrees for 1 hr, there was a 50% increase in O2 uptake and anaerobic CO2 production by the tumor, accompanied by enhanced dissemination by lymphatic, vascular, and direct routes, and tumor was found in organs not usually the site of metastases (e.g., testis and stomach). With large tumors (3.0 to 4.5 ml), the survival time of the rats was significantly reduced. These results occurred in the absence of a rise in body temperature of the animals. It is concluded that in this animal-tumor system, hyperthermia at a temperature inadequate for tumor destruction (40 degrees) can result in changes in the tumor that represent a hazard to the host.

Hyperthermia (42 degrees C) as an adjuvant to radiotherapy and chemotherapy in the treatment of the allogeneic VX2 carcinoma in the rabbit.

As assessed by decrease in tumour volume and inhibition of tumour cell respiration and glycolysis, hyperthermia (intra-tumour temperature 42°C for one hour) potentiated the destructive effect of radiotherapy (1000 rad) on the allogeneic VX2 carcinoma in the hind limb of rabbits, and chemotherapy (methotrexate) produced a similar potentiation of irradiation. The resulting regression of the primary tumour in each case after dual therapy was comparable to that occurring after 3 applications of local hyperthermia, which has been shown to cure 50% of animals with this carcinoma. Combination therapy did not increase the survival time of the rabbits, however, all of which had lung and lymph node metastases at autopsy. The results focus attention on the relationship between a primary tumour and its metastases. The histological picture and the animal survival data suggest that the mechanism of tumour cell death and resorption of necrotic material following treatment may be important in enabling the host to deal with metastatic cells. After combination therapy, many metabolically and mitotically active cancer cells remained in the tumour mass, and the incomplete destruction of the primary tumour may have left the host with a burden of tumour cells too large to be destroyed by the immune system.