The Effectiveness of Daily Hyperthermia Treatments
and Thermotolerance

Optimal Number And Frequency Of Treatments In Clinical Hyperthermia

Although the effectiveness of Hyperthermia is now well established, the optimal fractionation (number and frequency of treatments) is yet to be determined. In the past, most pioneering efforts (including our own) were done using a schedule of 2 or 3 treatments a week. The 48hour gap between treatments was considered necessary because of the phenomenon of thermo tolerance, an investigational finding described early in the development of this cancer treatment modality. Thermo tolerance has been established in the laboratory by in vitro and in vivo experiments. Both normal and cancer cells and tissue have been found to resist a second heat insult for over a month following initial heating. It is far from clear, however, what affect thermo tolerance has a long with the many other factors that affect tumor response to hyperthermia in clinical practice, as no definite evidence has yet been presented of the presence of thermo tolerance in human tumors.

With this paradox in mind we have treated patients with daily hyperthermia treatments, 5 days per week and have found significantly better tumor response using daily treatment. The number of superficial and deep tumors that failed to regress was 32/105 (31%) with 2 treatments a week as compared to only 13/109 (12%) following five hyperthermia treatments a week.

These gratifying results provide further demonstration that thermo tolerance is much less important in clinical hyperthermia practice than other factors. Tumor heating is never homogeneous, and it is likely that the in homogeneities vary from one hyperthermia treatment to another; thus inhomogeneous heating may actually be advantageous by heating cells that have not developed thermo tolerance.

Other groups have used daily hyperthermia treatment successfully. Moffat et al (1985) and Falk et al (1986a) reported 178 patients with unresectable hepatic neoplasm given “1 to 25 treatment courses (median 6 courses) --- of 1 – 5 consecutive daily sessions of 75-120 min thermotherapy ---“ Horn back et al (1986) treated stage IIIB cancer of the cervix with irradiation given 150 to 200 cGy per day to 40 Gy and “ each patient was exposed to 40 to 45 minutes of heat after each external radiation treatment”. Corry et al (1982) gave one to three courses of hyperthermia for superficial tumors, that” consisted of one hour treatment on three successive days of each week”. Falk et al (1986b) treated pancreatic cancer with “two to three consecutive daily sessions “. Horn back et al (1979) treated a hemangiosarcoma of the scalp with “3000 rad at 200 rad/ day, each treatment followed immediately by 20 minutes of heat “ Earlier they (Horn back, 1977) reported on 21 patients given 3 – 6000 rads at 100 –200 rads/day with “ 20 minutes of microwave radiation to the local tumor area immediately prior to the prescribed dose of ionizing radiation”.

Arcangeli and Nervi (1984) gave weekly or twice weekly hyperthermia to separate tumors in the same patients for 5 weeks. When comparing equal RT fractionation schedules, they found better results without added toxicity with the increased number of fractions. They concluded that: “Our data does not seem to evident ate any thermo tolerance induction in human tumors, at least by using clinical treatment schedules like those employed in this study”. Our data supports their conclusion.

REFERENCE:

Arcangeli G, Nervi C: The lack if clinical evidence of tumor thermo tolerance after some schedules of combined heat (HT) and radiation (RT) In Overgaard J. (ed): Hypethermic
Oncology 1984 1: Taylor & Francis, London and Philadelphia, 1984 pp 231-234.

Corry PM, Barlogie B, Tilchen EJ, et al: Ultrasound induced hyperthermia for the treatment of human superficial tumors. Int J Radiat Oncol Biol Phys 8: 1225-1229, 1982.

Falk RE, Newhook L, Moffat FL, et al: Thermo chemotherapy for unresectable hepatic cancer. Recent Results Cancer Res. 100: 315-320, 1986.

Falk RE, Moffat FL, Lawler M, et al: Combination therapy for resectable and unresectable adenocarcinoma of the pancreas. Cancer 57: 685-688, 1986.

Hornback NB, Shupe RE, Shidnia H, et al: Preliminary clinical results of combined 433 megahertz microwave therapy and radiation therapy on patients with advanced cancer. Cancer 40: 2854-2863, 1977.

Hornback NB, Shupe RE, Shidnia H, et al: Radiation and microwave therapy in the treatment of advanced cancer. Radiology 130: 459-464, 1979.

Hornback NB, Shupe RE, Shidnia H, et al: Advanced stage III B cancer of the cervix treatment by hyperthermia and radiation. Gyn oncol 23: 160-167, 1986

Moffat FL, Gilas T, Calhoun K, et al : Further experience with regional radio frequency hyperthermia and cytoxic chemotherapy for unresectable hepatic neoplasia. Cancer 55: 1291-1295, 1985