FAQ - Frequently Asked Questions

General Hyperthermia | BSD-500 | BSD-2000 | BSD-2000 3D/MR

MECHANISM OF ACTION

Laboratory and clinical studies have documented multiple mechanisms of action for hyperthermia. Hyperthermia kills cells in solid tumors, without damaging normal tissues, because higher temperatures selectively destroy cells that are hypoxic and have low pH, a condition of tumor cells and not a condition of normal cells. The low pH and hypoxic condition of tumor cells also makes them radiation resistant, which makes hyperthermia and radiation complementary treatments. In addition, the elevated temperatures that would not be fatal to normal cells can destroy cancerous tissue, which lacks the normal vascular supply that dissipates heat and supplies oxygen.ii,v,vi,vii Recent physiological data show that hyperthermia substantially increases perfusion in solid tumors, by 50-100%, and moderately increases perfusion in surrounding normal tissue, leading to higher oxygen concentration.vi These effects on blood flow and tumor oxygenation make the cancer cells more susceptible to radiation therapy.viii Hyperthermia has also been shown to inhibit cellular repair mechanisms, induce heat-shock proteins, denature proteins, induce apoptosis, and inhibit angiogenesis.i,ii,iii,vi

HYPERTHERMIA AND RADIOTHERAPY

The complementary interaction of hyperthermia combined with radiation is due to the independent cytotoxic effects of hyperthermia combined with its radiosensitizing effects. Laboratory studies have shown that hyperthermia potentiates radiotherapy.ii Hyperthermia and radiation therapy kill cancer cells at different stages of growth. Hyperthermia increases blood flow, resulting in improved tissue oxygenation and thus increased radiosensitivity.ix Hyperthermia also interferes with cellular repair of the DNA damage caused by radiation.i The basis for the additive effect of hyperthermia on radiotherapy comes from the ability of hyperthermia to kill cells that are hypoxic, have a low pH, and are in the S-phase of division, which are all conditions that make cells radioresistant.viii Randomized studies have not shown an increase in either acute or late toxicity of radiotherapy from the addition of hyperthermia.ii

i  Dahl O, Dalene R, Schem BC, Mella O. Status of clinical hyperthermia. Acta Oncol. 1999;38(7):863-73.

ii  Van der Zee J. Heating the patient: a promising approach? Annals of Oncology 2002;13:1173-1184.

iii  Falk MH and Issels RD. Hyperthermia in oncology. Int J Hyperthermia 2001;17 (1):1-18.

iv  Kapp DS. Hyperthermia: rationale and clinical applications. Syllabus: Refresher Course 310, Presented at 38th Annual ASTRO Meeting. Los Angeles, CA. October 29, 1996.

v  Jones EL, Oleson JR, Posnitz LR, et al. A randomized trial of hyperthermia and radiation for superficial tumors. J of Clin Oncol 2005;23(13): 3079-85.

vi  Wust P, Hildebrandt B, Sreenivasa G, Rau B, et al. Hyperthermia in combined treatment of cancer. Lancet 2002;3:487-497.

vii  Hehr T, Wust P, Bamberg M, Budach W. Current and potential role of thermoradiotherapy for solid tumours. Oncologie 2003;26:295-302.

viii  Raaphorst GP. Fundamental aspects of hyperthermic biology. In Field SB, Hand JW (EDS): An Introduction to the Practical Aspects of Clinical Hyperthermia. London: Taylor and Francis 1990; 10-54.

ix  Song CWM, Shakil A, Griffin RF, Okajima K. Improvement of tumor oxygenation status by mild temperature hyperthermia alone or in combination with carbogen. Semin Oncol 1997; 24: 626-632.

BSD-500 Superficial / Interstitial System Questions

Questions specifically related to the BSD-500 Superficial/Interstitial Hyperthermia System

Are there any side effects or complications for head and neck cancer treatment by BSD-500? (Ex: blood vessel rupture, stoke, …)

No there have not been any complications that you have described. If the ear is involved with a tumor, there could be damage to the ear if the tumor is highly involved with the ear. The eye is a sensitive area which has low bloodflow, so you should avoid treating very close to the eye. If there are more specific concerns I can try to respond further. If there is scar area from prior surgeries in the area to be treated, the scar tissue will have less bloodflow and may get to higher temperatures than the normal

When we are setting and adjusting the MA-151 applicator, how to make sure that the tumor location is right?

This small applicator has a heating pattern that is about 2.5cm in diameter and is centered on the applicator. It is generally possible to place the center of the bolus at the center of the tumor.

If the tumor > 3cm, the MA-151 Applicator can’t cover the tumor. Could we exchange the MA-151 to MA-100?

Or what should we do? You will find that a 3cm tumor will still respond well with the MA-151 treatment. You may find that moving the applicator position after 30 minutes at temperature to another position for the last 30 minutes could cover the tumor with heat better. When the treatment is along with radiation therapy, there will normally 5 to 10 heat treatments which allows for different applicator positions as the tumor may be decreasing in volume during the treatment series. The MA-100 can also be used to treat smaller 3cm tumors and the contact with the water bolus. The MA-100 bolus could be placed to have the water bolus only contact a smaller diameter of the surface tissue to confine the heating to a smaller heating zone. Typically for superficial tumors the water temperature is set between 40 to 42degC.

When patients treat with hyperthermia for an hour, they may feel uncomfortable or move. How to make sure that the bolus is attached to the skin surface and the target tumor site?

It is best to place the patient in a comfortable position so that the patient movement is avoided. The operator should be with the patient and observe if there is movement so that the applicator position can be adjusted. Remember that the treatment is heating tissue to a high fever temperature of about 42 to 43degC which would not cause harm to normal tissues.

Could you please give us the protocol and treatment guide for head and neck cancer treatment by BSD-500?

There is no specific protocol that is any different that treatment in other superficial areas of the body. The rate of heating is best limited to between 1 to 2 degrees per minute to maintain patient comfort. Most often the water bolus for tumors involved near the surface is between 40 to 42degC, but can be lower if there is a deeper tumor. If possible temperature sensors can be placed into the tumor using plastic needle/catheters and should be placed along the surface.

HT treatment is preferred to be within 1 hour of the radiation therapy treatment.” How about the chemotherapy combine with hyperthermia? (like Neoadjuvant).

I have attached article #3185 as a current reference for such treatments for educational purposes to respond to your question. If chemotherapy is combined with hyperthermia it is common that the chemotherapy is being circulated in the patient during the heat treatment when the doctor wants to enhance the effect of the chemotherapy by the target tissue being elevated in temperature.

If the patients have fungating wounds or surgical wounds on their breast, could they still treat hyperthermia? How could we dress the wound part when the patients treat hyperthermia?

In such cases where the surface is moist, a thin plastic film layer can be placed on the skin surface. This will allow the attachment of the temperature sensor probes to the plastic film being secured by tape (the edge of the tape is best folded back to form a tab when it is time to remove the probe from the plastic). Surgical wounds on the breast will be scar tissue that will have less bloodflow. This will cause the scar tissue to retain the MW heating and could reach higher temperatures than other tissues. Place temperature sensors at the scar tissue to avoid temperatures over 43degC. This can help to avoid causing thermal blisters in the scar tissue.

The cancer treatment in Wanfang Hospital is combined treatment(radiotherapy + chemotherapy + hyperthermia). But they combine those treatments in one day, patients may feel exhausted. At the same time, the departments need to communicate and catch the time point of treatment. Could you give us some advice how to arrange interval time for combined treatment? Or we could rearrange the treatment plan to one day radiotherapy + hyperthermia and another day chemotherapy + hyperthermia?

It is common to do only 1 or 2 hyperthermia treatments per week when used along with radiation therapy. This is because the boost to the radiation dose has been shown to extend for more than 24 hours after the heat treatment to enhance the radiation treatment of the next day. So if the hyperthermia was given only on a Tuesday and a Thursday, the radiation therapy treatments would be enhanced for Tuesday, Wednesday, Thursday, and Friday. The article 3185 shows a protocol where there was only one heat treatment per week. This would be better to be done on a day of radiation, but also before a day of another radiation treatment. Clinical evidence shows the early work showing an effect of hyperthermia 24 hours later to boost radiation therapy.