Influence of sequence and interval on the biological response to combined hyperthermia and radiation

Experimental studies on the influence of sequence and interval between hyperthermia and radiation are reviewed. In general, experimental data in vitro and in tumor and normal tissues agree and indicate that maximal thermal enhancement occurs after simultaneous application of heat and radiation. However, such treatment is likely to enhance both tumor and normal tissue to the same degree and therefore does not increase the therapeutic effect. In normal tissue, sequential treatment with heat before radiation causes a higher and longer thermal enhancement than with the opposite sequence in which the thermal enhancement generally disappears with intervals greater than 4 hours. However, in most solid tumors, a moderate thermal enhancement exists with long intervals between the modalities independent of sequence and is probably a consequence of a direct hyperthermic destruction of the acidic and chronically hypoxic cells. Based on this biological conclusion, the clinical application of hyperthermia and radiation is discussed in the light of the technical problems related to the application of a homogeneous and selective local tumor heating.