Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Study of the one dimensional and transient bioheat transfer equation: multi-layer solution development and applications.

In this work we derive an analytical solution given by Bessel series to the transient and one-dimensional (1D) bioheat transfer equation in a multi-layer region with spatially dependent heat sources. Each region represents an independent biological tissue characterized by temperature-invariant physiological parameters and a linearly temperature dependent metabolic heat generation. Moreover, 1D Cartesian, cylindrical or spherical coordinates are used to define the geometry and temperature boundary conditions of first, second and third kinds are assumed at the inner and outer surfaces. We present two examples of clinical applications for the developed solution. In the first one, we investigate two different heat source terms to simulate the heating in a tumor and its surrounding tissue, induced during a magnetic fluid hyperthermia technique used for cancer treatment. To obtain an accurate analytical solution, we determine the error associated with the truncated Bessel series that defines the transient solution. In the second application, we explore the potential of this model to study the effect of different environmental conditions in a multi-layered human head model (brain, bone and scalp). The convective heat transfer effect of a large blood vessel located inside the brain is also investigated. The results are further compared with a numerical solution obtained by the Finite Element Method and computed with COMSOL Multiphysics v4.1©.

Characterization of a digital microwave radiometry system for noninvasive thermometry using a temperature-controlled homogeneous test load.

Microwave radiometry has been proposed as a viable noninvasive thermometry approach for monitoring subsurface tissue temperatures and potentially controlling power levels of multielement heat applicators during clinical hyperthermia treatments. With the evolution of technology, several analog microwave radiometry devices have been developed for biomedical applications. In this paper, we describe a digital microwave radiometer with built-in electronics for signal processing and automatic self-calibration. The performance of the radiometer with an Archimedean spiral receive antenna is evaluated over a bandwidth of 3.7-4.2 GHz in homogeneous and layered water test loads. Controlled laboratory experiments over the range of 30-50 degrees C characterize measurement accuracy, stability, repeatability and penetration depth sensitivity. The ability to sense load temperature through an intervening water coupling bolus of 6 mm thickness is also investigated. To assess the clinical utility and sensitivity to electromagnetic interference (EMI), experiments are conducted inside standard clinical hyperthermia treatment rooms with no EM shielding. The digital radiometer provided repeatable measurements with 0.075 degrees C resolution and standard deviation of 0.217 degrees C for homogeneous and layered tissue loads at temperatures between 32-45 degrees C. Within the 3.7-4.2 GHz band, EM noise rejection was good other than some interference from overhead fluorescent lights in the same room as the radiometer. The system response obtained for ideal water loads suggests that this digital radiometer should be useful for estimating subcutaneous tissue temperatures under a 6 mm waterbolus used during clinical hyperthermia treatments. The accuracy and stability data obtained in water test loads of several configurations support our expectation that single band radiometry should be sufficient for sub-surface temperature monitoring and power control of large multielement array superficial hyperthermia applicators.

Performance evaluation of a conformal thermal monitoring sheet sensor array for measurement of surface temperature distributions during superficial hyperthermia treatments.

PURPOSE: This paper presents a novel conformal thermal monitoring sheet (TMS) sensor array with differential thermal sensitivity for measuring temperature distributions over large surface areas. Performance of the sensor array is evaluated in terms of thermal accuracy, mechanical stability and conformity to contoured surfaces, probe self-heating under irradiation from microwave and ultrasound hyperthermia sources, and electromagnetic field perturbation. MATERIALS AND METHODS: A prototype with 4 x 4 array of fiber-optic sensors embedded between two flexible and thermally conducting polyimide films was developed as an alternative to the standard 1-2 mm diameter plastic catheter-based probes used in clinical hyperthermia. Computed tomography images and bending tests were performed to evaluate the conformability and mechanical stability respectively. Irradiation and thermal barrier tests were conducted and thermal response of the prototype was compared with round cross-sectional clinical probes. RESULTS: Bending and conformity tests demonstrated higher flexibility, dimensional stability and close conformity to human torso. Minimal perturbation of microwave fields and low probe self-heating was observed when irradiated with 915 MHz microwave and 3.4 MHz ultrasound sources. The transient and steady state thermal responses of the TMS array were superior compared to the clinical probes. CONCLUSIONS: A conformal TMS sensor array with improved thermal sensitivity and dimensional stability was investigated for real-time skin temperature monitoring. This fixed-geometry, body-conforming array of thermal sensors allows fast and accurate characterization of two-dimensional temperature distributions over large surface areas. The prototype TMS demonstrates significant advantages over clinical probes for characterizing skin temperature distributions during hyperthermia treatments of superficial tissue disease.

Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes.

We have shown that sterically stabilized (Stealth) liposomes (SL), can accumulate in the extracellular space within tumors, and may improve pharmacokinetics and therapeutic efficacy of encapsulated doxorubicin (SL-DOX). When SL-DOX were incubated in vitro at different temperatures with 50% bovine serum, approximately 20% of the encapsulated DOX was released at 42 degrees C within 1 min, compared with less than 1% DOX released at 37 degrees C. In vivo, mice were implanted s.c. with C-26 colon carcinoma in both flanks to produce matched tumors 6-10 mm in diameter. Topical hyperthermia treatment consisting of 42 degrees C minimum tumor temperature for 30 min was applied with a microwave device to the tumor on one side only at 1 h after i.v. injection of SL-DOX or free DOX. Tumor DOX concentration in the group which was given injections of SL-DOX and sacrificed 2 h after drug injection was 1.5-fold higher compared with the nonheated tumor in mice given injections of SL-DOX. At 24 h after injection the thermal enhancement ratio for DOX accumulation in tumor remained at 1.5. In addition, there was a 15-fold higher concentration of DOX in tumor from the group given injections of SL-DOX compared to mice given injections of free doxorubicin. To assess therapeutic efficacy, we treated mice with hyperthermia for 15 min either at 1, or at 24 h or at both time points after injection of SL-DOX. We have found that the life span of the group of mice treated with SL-DOX and two 15-min hyperthermia treatments increased 51% compared with control groups receiving the same dosage of SL-DOX but without hyperthermia, and 59% compared to those receiving two hyperthermia treatments but with free DOX. A single hyperthermia treatment either at 1 or 24 h was less effective in increasing life span compared with two treatments, but all groups treated with SL-DOX and single hyperthermia were still superior to the control groups, showing a 27-38% increase in life span.

Dielectric properties measurements of brown and white adipose tissue in rats from 0.5 to 10 GHz.

Brown adipose tissue (BAT) plays an important role in whole body metabolism and with appropriate stimulus could potentially mediate weight gain and insulin sensitivity. Although imaging techniques are available to detect subsurface BAT, there are currently no viable methods for continuous acquisition of BAT energy expenditure. Microwave (MW) radiometry is an emerging technology that allows the quantification of tissue temperature variations at depths of several centimeters. Such temperature differentials may be correlated with variations in metabolic rate, thus providing a quantitative approach to monitor BAT metabolism. In order to optimize MW radiometry, numerical and experimental phantoms with accurate dielectric properties are required to develop and calibrate radiometric sensors. Thus, we present for the first time, the characterization of relative permittivity and electrical conductivity of brown (BAT) and white (WAT) adipose tissues in rats across the MW range 0.5-10GHz. Measurements were carried out in situ and post mortem in six female rats of approximately 200g. A Cole-Cole model was used to fit the experimental data into a parametric model that describes the variation of dielectric properties as a function of frequency. Measurements confirm that the dielectric properties of BAT (εr = 14.0-19.4, σ = 0.3-3.3S/m) are significantly higher than those of WAT (εr = 9.1-11.9, σ = 0.1-1.9S/m), in accordance with the higher water content of BAT.

Current state of the art of regional hyperthermia treatment planning: a review.

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed.

Treatment planning for ferromagnetic seed heating.

Computer simulations of ferromagnetic seed heating have been performed for the case of a single constant-temperature ferromagnetic seed. Results obtained from both 2-dimensional and 3-dimensional thermal models are compared to determine the appropriate use and limitations of the 2-dimensional model for the case of array implants. It has been determined that the 2-dimensional model that assumes infinite extent of the ferromagnetic seed(s) is applicable for calculating the thermal distribution in any plane perpendicular to the axes of the implant(s) up to 1 cm from the ends of the seed(s). The feasibility of spatially interspersed ferromagnetic and radioactive seeds for concurrent hyperthermia and brachytherapy has also been studied. The steady-state temperature distribution within an array of ferromagnetic seed implant has been examined as a function of implant spacing and blood perfusion rate. The results have been quantified in generalized histograms that are readily applicable to pre-treatment planning.

Thermal distribution studies of helical coil microwave antennas for interstitial hyperthermia.

An implantable 915 MHz helical coil antenna was developed for improved localization and control of interstitial microwave hyperthermia. The radiating element consisted of a fine wire coil wound back over the inner conductor of a miniature semi-rigid coaxial cable in place of the terminal portion of outer conductor. The power deposition profiles from single helical coil antennas were studied both in homogeneous phantom and in muscle tissue in vivo and compared to those of single half-wavelength linear dipole antennas. The effects of variable coil length, turn density, and antenna insertion depth in tissue were characterized. The helical coil antennas produced a well-localized heating pattern with a sharp falloff of temperature in both directions axially from the coil element. One of the best heating patterns was obtained with a 35 turn, 35 mm long helical coil element which was separated from the antenna feedline outer conductor by a 1 mm gap (HCS-35(1)/36). This antenna showed a marked shift of the effectively heated volume toward the antenna tip and essentially no dependence of the heating pattern on insertion depth. In contrast, the axial power deposition profiles of dipole antennas were strongly affected by insertion depth and exhibited an inadequately heated area at the antenna tip even with 1/2-3/4 wavelength insertion. Thermal distribution studies showed that the single helical coil microwave antenna provided more predictable, well-localized heating of deep-seated tissues, with minimal requirement for over-implanting of the treatment volume.

Interstitial microwave hyperthermia in a canine brain model.

A dual frequency microwave system was constructed for interstitial heating of brain tissue. Single-junction dipole antennas were tested in a phantom model and in normal dog brain to determine how variations in physical factors affected temperature distributions. Non-survival studies were performed at both 915 and 2450 MHz to determine heating patterns that could be achieved within normal brain using this system. Chronic survival studies were performed using a single dipole antenna inserted laterally into one hemisphere of brain and driven at 2450 MHz. Temperatures of 43 or 44 degrees C for 30 min at a reference point 0.5 cm from the antenna junction were used to induce a thermal lesion of approximately 1 cm diameter in the right cerebral hemisphere of dogs. Neurologic and physical changes in dogs were monitored daily for up to 16 weeks after induction of cerebral lesions. The extent and development of thermal lesions was monitored with weekly computed tomographic (CT) examinations and, after death, at histopathologic examination. Results of the phantom studies showed that the longitudinal heating pattern was bell-shaped at both frequencies used and that there was some variation in heating length that depended on insertion depth. Acute studies in dog brain showed that 915 MHz antennas implanted less than 6.5 cm deep produced erratic heating patterns that usually included excessive heating of the surface of the brain. Conversely, 2 cm-long antennas driven at 2450 MHz gave reproducible temperature distributions both longitudinally along and radially away from the antenna. The steepest gradients--about 1 degree C/mm--occurred in the radial direction away from the antenna junction. A single 30 min heat treatment produced a large focal lesion that consisted of central coagulation necrosis surrounded by a sharply demarcated hypervascular zone. Edematous changes were minimal and were observed only during the first week after treatment. As assessed by serial CT scans, thermal lesions reached a maximum size by the first week after treatment and were essentially resolved by 16 weeks after treatment.

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms.

PURPOSE: The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. METHODS AND MATERIALS: Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3-151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. RESULTS: The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7 degrees C, 38.7 degrees C, and 41.0 degrees C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. CONCLUSION: These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.

Thermoradiotherapy of recurrent malignant brain tumors.

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.

Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.

PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.

Microwave hyperthermia for choroidal melanoma in rabbits.

Radiation has provided excellent local control rates in choroidal melanoma, but significant impairment in visual acuity has occurred in 30-60% of patients due in part to the development of radiation vasculopathy in the fovea and optic disc. Hyperthermia has been shown to have a synergistic effect when added to radiation therapy in human malignancies. The use of hyperthermia in ocular melanoma may allow a reduction in the total radiation dose necessary to achieve local control. A 2450-MHz microwave plaque applicator with integral surface cooling was used to deliver hyperthermia treatments to rabbit eyes containing choroidal melanomas. Extensive thermal mapping was done in acute eyes. In 18 survival animals, a single 23-G needle thermocouple probe with three sensors was inserted into the tumor. Target temperatures of 41.0-46.0 degrees C were maintained for 1 hour. All tumor-bearing eyes were followed for 1 month after treatment, or until tumor growth was noted, with serial ultrasound measurements and visual examinations. A 92% response rate was obtained in tumors treated at temperatures greater than 43.0 degrees C for 1 hour with no significant toxicity. Heat alone has significant tumoricidal properties in this animal model.

31P magnetic resonance spectroscopy of animal uveal melanoma.

Scleral surface coils were used to obtain in vivo magnetic resonance spectra (MRS) of Greene melanoma implanted in the rabbit uvea. Well-localized tumor spectra (4.7 Tesla) with good signal-to-noise ratios (S/N) were obtained from the tumor with a "single-pulse" sequence in less than 1 hour. Tumor localization was confirmed with one-dimensional spectroscopic imaging studies. Serial 31P spectra were obtained during tumor growth and after both optimal and suboptimal hyperthermia. Early 31P MRS change is correlated with tumor treatment response and preceded histologic evidence of cell destruction. Twenty-four to 48 hours after successful treatment, the inorganic phosphate/nucleoside triphosphate (NTP), and phosphomonoester/NTP ratios were significantly increased from 1.2 +/- 0.1 to 1.7 +/- 0.1 and 1.3 +/- 0.1 to 1.8 +/- 0.2, respectively. In contrast, untreated or ineffectively treated tumors showed little change. Interpretation of 31P MRS data in this animal uveal melanoma model after the first week was complicated by decreased S/N, increased contamination from contiguous tissues, ingrowth of fibroblasts, macrophages, and intratumor hemorrhage.

An improved bolus configuration for commercial multielement ultrasound and microwave hyperthermia systems.

A simple modification is presented for two commercially available hyperthermia applicators which dramatically improves the regulation and dynamic control of the temperature at the bolus/tissue interface. This alteration requires the addition of a variable speed pump, bubble trap, simple heat exchanger, and a few minor changes to the existing system. With this modified design, the water within the bolus is directly circulated and temperature controlled. The convective nature of the circulating system ensures uniform temperature throughout the extended bolus and increases the thermal energy transfer at the bolus/tissue interface. This modification also provides significantly improved flexibility in controlling the treatment temperature distributions since the bolus/tissue interface temperature can now be dynamically varied during a treatment, in addition to adjusting the applicator power output and frequency.

Thermal and SAR characterization of multielement dual concentric conductor microwave applicators for hyperthermia, a theoretical investigation.

Six aperture array dual concentric conductor (DCO) microwave hyperthermia applicators were studied using theoretical models to characterize power deposition (SAR) and steady state temperature distributions in perfused tissue. SAR patterns were calculated using the finite difference time domain (FDTD) numerical method, and were used as input to a finite difference thermal modeling program based on the Pennes Bio-Heat Equation in order to calculate corresponding temperature distributions. Numerous array configurations were investigated including the use of different size DCC apertures (2, 3, and 4 cm), different spacing between apertures (1.0-2.0 cm), and different water bolus thicknesses (5-15 mm). Thermal simulations were repeated using blood perfusion values ranging from 0.5 to 5 kg/m3 s. Results demonstrate the ability of DCC array applicators to effectively and uniformly heat tissue down to a depth of 7.5-10 mm below the skin surface for a large number of different combinations of DCC element size, spacing, and water bolus thickness. Results also reveal the close correlation between SAR patterns and corresponding temperature distributions, verifying that design studies of the applicator can be performed confidently by analysis of SAR, from which the thermal behavior can be estimated. These simulations are useful in the design optimization of large microwave DCC array applicators for superficial tissue heating and for identifying appropriate aperture spacing and bolus thickness parameters for different size DCC aperture arrays and tissue blood perfusion conditions.

Interstitial helical coil microwave antenna for experimental brain hyperthermia.

A helical coil 2450-MHz microwave antenna was used to induce interstitial hyperthermia in normal dog brain. The HCS-10(1)/11 antenna consisted of a miniature semirigid coaxial cable around which a fine wire coil with 10 turns per 1-cm length was wound. A single antenna and two or three temperature probes were implanted stereotactically, and the temperature distributions surrounding the antenna were measured and compared to those induced using a dipole antenna. The helical coil antenna produced well-localized temperature distributions at depths that were symmetrical around the coil and that extended to the antenna tip. There was minimal variation of the heating patterns with insertion depth using the HCS-10(1)/11 antenna and no excessive heating of extracerebral tissues. In contrast, 2450-MHz dipole antennas induced temperatures of 43 to 46 degrees C at the brain surface and extracerebral tissues (skull, muscle, and scalp), with a relatively uniform but lower temperature in the targeted brain volume. One week after hyperthermia treatment, the thermal lesions induced by the helical coil antenna were visualized using computed tomography. The heating patterns correlated well with the location of the heat lesions and were reproducible among animals. The results indicated that the helical coil antenna could be used to induce localized hyperthermia at specific depths in normal brain without inducing unacceptable heating of the brain surface or extracerebral tissues. Consequently, this antenna seems to be suitable for studying the response of normal brain after a heat insult and may be effective in the application of interstitial microwave brain hyperthermia for malignant brain tumors.

Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.

Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

Effect of complex bolus-tissue load configurations on SAR distributions from dual concentric conductor applicators. Specific absorption rate.

Power deposition [specific absorption rate (SAR)] distributions from a two-element array configuration of 4-cm-square 915-MHz dual concentric conductor (DCC) microwave antennas were characterized theoretically for several clinically realistic complex bolus-tissue load models using the finite difference time domain (FDTD) numerical method. The purpose of this effort was to determine the perturbing effects on SAR of three often unavoidable heterogeneities in the bolus-tissue load. The three cases studied in this work consist of bone (two ribs spaced 1 cm apart) embedded 5-mm or 1-cm deep in muscle or layered fat-muscle tissue, small air bubbles trapped between the coupling bolus and tissue surface, and variable thickness water bolus layer due to sharply contoured anatomy. Results of the FDTD simulations demonstrate rather small effects on SAR distribution for both rib-sized bones > or = 5-mm deep in muscle and small air pockets < or = 1-mm thick. Larger air bubbles > 1-cm diameter by 3-mm depth showed a distinct concentration of SAR near the lateral sides of the air bubbles, and a blocking effect under the bubbles when located directly under the center of a DCC aperture where there is a higher normal E-field component. Variation from 2.5- to 7.5-mm bolus thickness under the two aperture array produced only minor perturbation of the uniformity and penetration of SAR, along with minor reduction in SAR under the thicker bolus which should be accommodated sufficiently by changes in applied power to the array elements.