Conductive interstitial hyperthermia in the treatment of intracranial metastatic disease.

BACKGROUND: Intracranial metastases commonly complicate oncologic care affecting 140,000 patients per year in the United States. Treatment of these tumors is difficult and often unsuccessful. Hyperthermia is a treatment alternative that has shown promise in treating cancer in other areas. Therefore it was employed in an attempt to provide increased tumor control in CNS metastases. METHODS: This Phase I and Phase II clinical trial of interstitial hyperthermia with recurrent or progressive intracranial metastatic disease was undertaken to evaluate complications, delivery of heat and patient outcome. RESULTS: Feared complications of clinically significant bleeding, increased mass, or infection from the interstitial implant and treatment did not occur. The seizures which occurred in 4 patients were controlled with additional anticonvulsants. Three venous thromboembolic events were treated medically and with percutaneously placed inferior vena cava filters. The KPS of the majority of patients declined slightly with treatment but rebounded to near baseline within several months. CT scans demonstrated decrease or stabilization of tumor volumes in 7 of the 13 patients. In 4 of these patients, regression or stabilization persisted until death from nonCNS disease. CONCLUSIONS: Interstitial hyperthermia therapy for intracranial metastases is technically feasible and may provide increased tumor control. In this small series, it did not cause unreasonable complications. This therapy has some positive effect, but requires study of more patients before its role is definitively known. Combining hyperthermia with brachytherapy and/or chemotherapy is being evaluated.

Continuous monitoring of cerebral perfusion by thermal clearance.

Currently, no commercially available system exists to continuously monitor the effective tissue perfusion within the parenchyma of the brain. While several methods exist for accurately measuring cerebral perfusion; among them: 133xeonon clearance, hydrogen clearance and radiolabeled microsphere injection; none of these methods provides continuous monitoring. The Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System (Bloomington, IN, USA) was initially developed to treat brain tumours by maintaining constant, moderate hyperthermia within a defined tissue volume over an extended duration. The system continuously adjusts the power applied to heating elements in order to maintain a constant temperature within the treatment volume. Because tissue perfusion is a primary factor responsible for removing heat from tissue, monitoring the amount of power applied to the heating elements allows one to continuously estimate tissue perfusion in the vicinity of the heating elements. In the current study, regional blood flow in the vicinity of heater/sensor catheters implanted in the brain parenchyma of three dogs was estimated by the VH8500 tissue perfusion algorithm and directly measured with radioactive labeled microspheres. The accuracy of the perfusion estimate (Thermal Perfusion Index) was evaluated by comparing these values. A range of blood flow was achieved in each animal by infusing nitroprusside. It was found that with the perfusion estimation algorithm of the Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System as it is currently implemented, the Thermal Perfusion Index tended to underestimate regional perfusion as measured with radioactive microspheres, but the relationship was nearly linear. Thus, the system currently tracks changes in regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Droop: a rapidly computable descriptor of local minimum tissue temperature during conductive interstitial hyperthermia.

Although the goal of local hyperthermia therapy for cancer is to elevate the temperature of a tumour to cytotoxic levels, without the presence of 'cold spots', varying blood flow has made the achievement of consistent, therapeutic temperature distributions extraordinarily difficult. The paper presents a novel approach to estimating local minimum tumour temperatures during conductive interstitial hyperthermia which facilitates identification and elimination of cold spots. Conductive interstitial hyperthermia is modelled mathematically for a parallel array of implanted, electrically heated catheters which warms the treated tissue by thermal conduction and blood perfusion. Computer simulations employing the bioheat transfer equation reveal a predictive relationship between implanted catheter temperature, catheter power, implantation geometry and local minimum tumour temperature. Formulation of this relationship in terms of a parameter named 'droop' allows estimation of local minimum intratumoural temperatures from individual catheter temperature and power. Computer simulations are also performed to determine the sensitivity of the droop-based estimator to variations in properties of the tissue and catheters. Generally, variations in geometry or thermal properties of about 10 per cent cause estimation errors of less than 1 degree C in magnitude. These results suggest that online estimates of thermal 'droop' may provide a practical route to more consistent control of intratumoural minimum temperature during conductive interstitial heat therapy.

Effective estimation and computer control of minimum tumour temperature during conductive interstitial hyperthermia.

The goal of heat therapy in the treatment of malignant disease is to raise the temperature of all neoplastic tissue to a cytotoxic temperature for a predetermined period of time. This seemingly simple task has proved difficult in vivo in part because of non-uniform power absorption and in part because of non-homogeneous and time-varying tumour blood flow. We have addressed this difficulty first by utilizing the conceptually simple technique of conductive interstitial hyperthermia, in which the tumour is warmed by multiple, electrically heated catheters, and second by implementing on-line control of minimum tumour temperatures near each catheter, estimated on the basis of the steady-state ratio of catheter power to catheter temperature rise. This report presents an analysis of the accuracy, precision, and stability of the on-line minimum temperature estimation/control technique for 22 patients who received 31 separate courses of conductive interstitial hyperthermia for the treatment of malignant brain tumours, and in whom temperature was monitored independently by 12-16 independent sensors per patient. In all patients the technique was found to accurately and precisely estimate and control the local minimum temperatures. Comparison of measured and estimated temperatures revealed a mean difference of 0.0 +/- 0.4 degrees C for those sensors within 1.0 mm of the expected location for minimum temperatures. This technique therefore offers an attractive method for controlling hyperthermia therapy-even in the presence of time varying local blood flow.

Design and evaluation of closed-loop feedback control of minimum temperatures in human intracranial tumours treated with interstitial hyperthermia.

The dynamic nature of blood flow during hyperthermia therapy has made the control of minimum tumour temperature a difficult task. The paper presents initial studies of a novel approach to closed-loop control of local minimum tissue temperatures utilising a newly developed estimation algorithm for use with conductive interstitial heating systems. The local minimum tumour temperature is explicitly estimated from the power required to maintain each member of an array of electrically heated catheters at a known temperature, in conjunction with a new bioheat equation-based algorithm to predict the 'droop' or fractional decline in tissue temperature between heated catheters. A closed loop controller utilises the estimated minimum temperature near each catheter as a feedback parameter, which reflects variations in local blood flow. In response the controller alters delivered power to each catheter to compensate for changes in blood flow. The validity and stability of this estimation/control scheme were tested in computer simulations and in closed-loop control of nine patient treatments. The average estimation error from patient data analysis of 21 sites at which temperature was independently measured (three per patient) was 0.0 degree C, with a standard deviation of 0.8 degree C. These results suggest that estimation of local minimum temperature and feedback control of power delivery can be employed effectively during conductive interstitial heat therapy of intracranial tumours in man.

Computer-aided design and evaluation of novel catheters for conductive interstitial hyperthermia.

Conductive interstitial heating is a modality in which heating elements are implanted directly into the treated tissue. One implementation of such therapy employs electrically heated catheters that are implanted in staggered, parallel rows. To explore strategies for maximising the uniformity of tissue temperature distributions achieved with heated catheters, a two-dimensional computer model with cylindrical co-ordinates was used to evaluate radially and longitudinally the temperature distributions produced by a typical interior catheter surrounded by other similar catheters. Insights from the computer model led to new designs for catheters containing multiple heating elements that produced more uniform thermal distributions, eliminating previous 'cold spots' within the treatment volume located near the ends of the catheter. The new catheter designs also include compartments for the optional placement of radioactive seeds for simultaneous thermoradiotherapy.