Hyperthermia-induced morphological changes in cerebral tissue of the rat.

The sensitivity of cerebral tissue to hyperthermia, its immediate effect, manifested by histological changes and the role of local blood flow, blood rheological properties, and the possible role of free radicals in development of mentioned changes have been studied. Through the cranial window local area of cerebral surface was irrigated by artificial CSF heated up to 41, 43 or 45 degrees C. Serial brain coronal sections 50 microm thick were analyzed under light microscope.

Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.

A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung).

TRIPAS: a triapplicator system with relocatable 'hot spot' at tissue depth.

Solving the problem of heat focusing and standardization of the clinical application of hyperthermia requires a mathematical prediction model. The model should include the medium constitutive parameter, and be able to predict positioning of the microwave applicators to optimize treatment planning and provide for reproducible treatment set-up. We present a configuration of 3 applicators subtended by an equilateral triangle in order to target and relocate a 'hot spot' for improved treatment of deep tumors.

A computer simulation of simultaneous heat and oxygen transport during heterogeneous three dimensional tumor hyperthermia.

Hyperthermia is a developing modelity for the treatment of cancer. This therapy is occasionally used by itself, however, usually it is used as an adjuvate with chemo or radiation therapy. The mechanism for this treatment is based on the fact that cancer cells are heated preferentially by heat application due to lower vascularity in the tumor tissue as compared with the surrounding normal tissue and that, when used with radiation therapy or chemo therapy, higher oxygen partial pressure in the tumor results in increased tumor cell damage.

Microwave hyperthermia as an adjunct to radiation therapy: summary experience of 256 multifraction treatment cases.

Results in 256 cases of malignant disease treated by multifraction combination hyperthermia-radiation therapy under the supervision of one physician are presented. The overall response rate was 94% including a 62% complete response. Complications specifically ascribed to hyperthermia were minor, and most side effects of combined treatment were radiation dose related.

Changes in tumor tissue oxygenation during microwave hyperthermia: clinical relevance.

As previously described (Bicher 1981) TpO2 and blood flow increase in tumor as temperature increases until 41 degrees C and decrease thereafter (microcirculation "breaking point"). In the present clinical study using O2 microelectrodes this response was reproduced in over 54 treatment sessions. However, it was found that as treatment progresses (patients are treated for one hour 10 times, twice weekly, and concomitantly receive 4000 rads of ionizing radiation) the initial increase of blood flow and TpO2 is reduced and there is immediate decrease in tissue oxygenation.

Loss of vascular fibrinolytic activity following irradiation of the liver--an aspect of late radiation damage.

The vascular fibrinolytic activity, known to originate from the endothelium, was studied histochemically by fibrinolysis autography in liver samples from beagles exposed to radiation treatment. Eighteen to thirty months prior to sacrifice, six dogs received X irradiation (4600 rad in 5 weeks) and three dogs received X irradiation plus aspirin (1 g/kg). Two dogs served as untreated controls.

Changes in tissue oxygenation and acidity induced by localized microwave hyperthermia and hematoporphyrin phototherapy, an update.

Changes in tumor tissue oxygenation and acidity were determined using ultramicroelectrodes, and presented in histogram fashion. The effect of Hyperthermia and Hpd photo-therapy were tested. It was found that both modalities affect tumor microcirculation, causing a marked drop in oxygen availability.

Impact of microcirculation and physiologic considerations on clinical hyperthermia.

Changes in tumor tissue oxygenation and acidity were determined using ultramicroelectrodes, and presented in histogram fashion. The effect of Hyperthermia and HpD phototherapy were tested. It was found that both modalities affect tumor microcirculation, causing a marked drop in oxygen availability.

Computer modeling of tumor hyperthermia (a dynamic lumped parameter model).

The thermal behavior of normal and neoplastic tissue is modeled by a set of coupled ordinary differential equations. The equations lump the tissue and tumor into individual compartments, so that the equations are time dependent. These equations represent an initial step in the development of a comprehensive model which may be used in studying the dynamics and control of the system under normo- and hyperthermic conditions.

Identification of viable regions in "in vitro" spheroidal tumors: a mathematical investigation.

In the treatment of solid tumors by hyperthermia, a major question is how to obtain an a priori knowledge of which tumors can be effectively treated with this modality. The key question is; given a solid tumor, what parameters in the various regions of the tumor, need to be measured so that a tumor-tissue model can provide a meaningful real time simulation of the hyperthermic treatment. This paper addresses the former question as a mathematical investigation, and the latter as a consequence of the former.

Results of a phase I/II clinical trial of fractionated hyperthermia in combination with low dose ionizing radiation.

This paper addresses, in part, the current status of hyperthermia as a new clinical modality and reports the results of a large, prospective clinical trial employing microwave hyperthermia in combination with low doses of ionizing radiation. In the protocol employed, each treated area received 8 hyperthermia treatments of 1.5 hour combined with 1600 rad over a total period of 5 weeks.

Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma.

Severe disturbances in microcirculation during advanced phases of tumor growth lead to restrictions of convective and diffusive transport. In addition, an inhomogeneous distribution of transport conditions develops, resulting in insufficient and heterogeneous substrate supply and an inadequate drainage of wastes. Polarographic measurements of the local tissue oxygen tension (PO2) using gold microelectrodes reveal that very low PO2 values are prevalent in C3H mouse mammary carcinomas.

A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids.

We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled.

Radiation sensitivity modification by chemotherapeutic agents.

Three chemotherapeutic agents, chlorambucil, mustargen, and BCNU-409962, being investigated for their possible clinical use in conjunction with radiation therapy have been shown in vitro to dramatically affect the characteristics of standard radiation survival curves (in V79 cells and spheroids). The agent mustargen, at a concentration of 0.25 microgram/ml administered 1 hour prior to 9-MeV-electron exposure, had a significant effect in reducing D0.

Effects of hyperthermia on normal and tumor microenvironment.

The effects of hyperthermia on pH, local blood flow (LBF) and tissue oxygen tension (TpO2) in several normal and tumor tissues were studied. It was found that TpO2, local blood flow and pH are inhomogeneous in tumor tissue. TpO2 is very low in certain areas which also seem deprived of blood flow and are at very low pH.

The physiological effects of hyperthermia.

In the application of hyperthermia to control cancer, physiological factors such as pH, pO2, and blood flow must be documented in vivo at normal and elevated temperatures for both the tumor and its normal host tissue. The present symposium was arranged to gather recent research done in this area and to expose the problems inherent in these efforts.