Biological basis for clinical treatment with combined hyperthermia and radiation: a proposal for an EORTC study

The biological rationale for the use of hyperthermia as an adjuvant to radiotherapy depends on the ability to achieve selective tumor heating. A simultaneous heat and radiation treatment utilizing hyperthermic radiosensitization gives the highest thermal enhancement, but to the same degree in tumor and normal tissue. Such a treatment is therefore only advantageous if selective tumor heating can be achieved. If both tumor and surrounding normal tissue are heated, a sequential treatment schedule (i.e., heat 4 hours after radiation) should be used. This is based on the almost selective hyperthermic cytotoxicity against acidic and chronically hypoxic radioresistant tumor cells. Such treatment yields a smaller thermal enhancement in the tumor, but does not increase the radiation response in normal tissue. A clinical study designed to explore this biological rationale is described