PubMed HealthSearch

Biomedical subjects

M A Astrahan

Publications and source records attributed to M A Astrahan.

At least 19 recordsLinked to original sources

Temperature steering in prostate by simultaneous transurethral and transrectal hyperthermia.

Localized hyperthermia (HT) is presently under investigation as a treatment for benign prostatic hyperplasia and carcinoma of the prostate (CaP). One popular approach employs a transrectal (TR) device, a directional microwave (MW) applicator inserted into the rectum and aimed at the prostate. Alternatively, in the transurethral (TU) technique, a symmetrically radiating MW antenna is placed directly within the prostatic urethra. Used individually, TR applicators are capable of effectively heating (> 42 degrees C) the prostate up to 2 cm from the rectum, whereas TU applicators selectively heat the periurethral tissue with effective radial penetration of about 0.6 cm. Neither technique is of much value in heating the anterior prostate. In general, the highest temperatures are produced in the tissue immediately adjacent to the surface of intracavitary microwave devices. However, when MW antennas are used in arrays, the resulting heating pattern can differ significantly from that of the individual antennas. Heating at depth can be selectively enhanced and "steered" by adjusting the phase relationship between the devices. Prostatic temperature profiles were measured in 6 patients treated with TR alone, TU alone, and simultaneous TR and TU heating. In the combined treatments different phase relationships between the antennas were applied. We found that a higher temperature could be produced in the center of the prostate than on the surface of either applicator for certain phase relationships, and that the temperature profiles could be changed by shifting phase. The results of these measurements are in agreement with those of a computer simulation. Based on the above data we feel the combined use of TU and TR hyperthermia may be justified in Phase I-II trials for patients with locally advanced CaP.

Aged

Episcleral plaque thermoradiotherapy in patients with choroidal melanoma.

From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma.

Adolescent

Episcleral plaque radiotherapy in the treatment of uveal melanomas.

During an 8-year period, 85 patients with uveal melanomas were treated with episcleral plaque radiotherapy (EPRT). The T-stage was: T1-3 (4%), T2-29 (34%) and T3-53 (62%). The mean tumor elevation was 6.1 mm. Radiation dose was prescribed at the tumor apex and at D5mm. The mean D5mm dose was 150.1 Gy (range 70.5-430 Gy) and the mean dose at the apex was 102.6 Gy (range 29.8-200 Gy). Useful vision (greater than 5/200) was maintained in 73% of patients. The 5-year actuarial survival was 88%. Metastatic disease developed in 9 (11%) patients, 6 of whom died of their disease. Basal tumor dimensions were important factors predicting metastatic disease, p = 0.002. A decrease in tumor evaluation was seen in 82%. There was a much lower incidence of decrease in tumor radial and circumferential dimensions, 47.5 and 46%, respectively, p less than 0.001. Treatment complications were common (56%), particularly in patients with large tumors (72%), p = 0.04. The incidence of complications was higher in patients treated prior to 1988 as compared to those who were treated more recently (67 vs 35%, p = 0.010). There were 13 (15%) patients who had enucleation. This included 12 treated before 1986 and 1 patient treated subsequently (46 vs 2%, p less than 0.001). In a univariate analysis, tumor height and radiation dose at D5mm were important factors predicting enucleation, p = 0.004. In a multivariate analysis, however, the most important factor predicting enucleation was treatment administration prior to 1986, p less than 0.001). A sharp decrease in the incidence of severe complications, including enucleation, as seen after 1985, is likely due to a major effort in treatment optimization.

Adult

Transurethral hyperthermia for benign prostatic hyperplasia patients with retention.

From 1989 to 1990, 32 poor surgical risk patients with urinary retention were treated with transurethral microwave hyperthermia at the department of urology, University of Leuven in Belgium. Mean patient age was 73 years (range 58 to 90 years) and mean duration of retention was 4 weeks (range 3 to 12 weeks). Followup ranged from 13 to 82 weeks, with a mean of 31 weeks. Bilobar or trilobar hyperplasia was diagnosed in 25 patients (78%), while 7 (22%) had median lobe or median bar hypertrophy. The mean prostatic volume was 52 cc (range 25 to 150 cc). Transurethral microwave hyperthermia was given with a helical antenna at 915 MHz. once or twice per week. The mean number of transurethral microwave hyperthermia sessions was 8.9 (range 5 to 10). Each session consisted of a 60-minute treatment at a mean maximum temperature of 45.4C (range 43.7 to 47.2C), average temperature 43.9C (range 42.7 to 45.5C) and minimum temperature 42.0C (range 40.2 to 43.0C). The temperature was continuously monitored, including thermal mapping in all patients. Of the 25 patients who presented with bilobar or trilobar hyperplasia 18 (72%) were catheter-free for the duration of followup. Of the 7 median lobe or median bar patients 1 (14%) showed sufficient improvement to warrant catheter removal. This patient, however, had recurrent retention 4 months after transurethral microwave hyperthermia. In patients with bilobar and trilobar hyperplasia a strong correlation was observed among maximum temperature (p = 0.0006), average temperature (p = 0.0033) and treatment response. As expected, no such correlation existed between minimum temperature and response to treatment (p = 0.56). Our study has again demonstrated therapeutic activity in patients with benign prostatic hyperplasia treated with transurethral microwave hyperthermia. A new finding was a strong correlation between temperature and response.

Aged

Interstitial temperature measurements during transurethral microwave hyperthermia.

Microwave hyperthermia is presently being investigated as a treatment for alleviating the symptoms of urinary outlet obstruction associated with benign prostatic hyperplasia. Two clinical techniques using intracavitary microwave applicators are being evaluated for safety and efficacy at various institutions. The transrectal technique uses a directional microwave radiator that is inserted into the rectum adjacent to the prostate. The transurethral approach uses a symmetrically radiating applicator located within the prostatic urethra. Transrectal prostatic heating techniques require surface cooling to prevent hazardous temperatures in the intervening rectal mucosa. Since transurethral applicators radiate from within the prostatic urethra, heating is confined to the obstructive tissue immediately surrounding the applicator. Concern has been expressed regarding the possibility of thermal injury to the prostate and adjacent rectum during transurethral hyperthermia treatment. In this report we present interstitial temperature measurements of prostatic and rectal temperatures in 5 patients. Temperature was observed to decrease at a rate of about 6C/cm. outward from the applicator. No clinically significant temperature increase was observed beyond 1 cm, outside the prostatic capsule or in the rectal mucosa.

Aged

An interactive treatment planning system for ophthalmic plaque radiotherapy.

Brachytherapy using removable episcleral plaques containing sealed radioisotope sources is being studied as an alternative to enucleation in the treatment of choroidal melanoma and other tumors of the eye. Encouraging early results have been reported, but late complications which lead to loss of vision continue to be a problem. A randomized national study, the Collaborative Ocular Melanoma Study (COMS) is currently in progress to evaluate the procedure. The COMS specified isotope is 125I. Precise dosimetric calculations near the plaque may correlate strongly with complications and could also be used to optimize isotope loading patterns in the plaques. A microcomputer based treatment planning system has been developed for ophthalmic plaque brachytherapy. The program incorporates an interactive, 3-dimensional, solid-surface, color-graphic interface. The program currently supports 125I and 192Ir seeds which are treated as anisotropic line sources. Collimation effects related to plaque structure are accounted for, permitting detailed study of shielding effectiveness near the lip of a plaque. A dose distribution matrix may be calculated in any subregion of a transverse, sagittal, or coronal planar cross section of the eye, in any plane transecting the plaque and crossing the eye diametrically, or on a spherical surface within or surrounding the eye. Spherical surfaces may be displayed as 3-dimensional perspective projections or as funduscopic diagrams. Isodose contours are interpolated from the dose matrix. A pointer is also available to explicitly calculate and display dose at any location on the dosimetry surface. An interactive editing capability allows new plaque designs to be rapidly added to the system.

Brachytherapy

Measurement of dose rate from exposure-calibrated 125I seeds.

Dose rate in water 1 cm transverse to an 125I seed calibrated for air kerma strength is not well established; 125I dosimetry calculations are, however, based on this constant. The specific dose constant was obtained from a series of dose rate measurements using thermoluminescent dosimetry (TLD) in a rigid geometry, full scatter acrylic phantom for individual model 6711 seeds. With a statistical precision of approximately +/- .5%, the dose rate to an infinitesimal mass of water located in acrylic at a perpendicular distance of 1 cm from the seed was found to be 0.977 cGy/h per microGy-m2/h of air kerma strength. Dose rate in a water phantom was calculated using a model that takes into account differences in both attenuation and scatter between water and acrylic. The specific dose constant in water was determined to be 0.932 (1.184 cGy-cm2/mCi-h, for the conventional exposure rate constant of 1.45 R cm2/mCi-h). This value is 7.5% less than dose rate in water from an unattenuated point source, and 9.7% less than the value commonly used for dosimetry calculations. The results suggest that most clinical 125I dosimetry estimates to date should be reconsidered for a possible reduction by about 10%. Relative scatter attenuation factors at 3 and 5 mm are also presented.

Calibration

Transurethral hyperthermia for benign prostatic hyperplasia: preliminary clinical results.

A total of 21 patients with biopsy proved benign prostatic hyperplasia underwent treatment on a pilot protocol involving intracavitary transurethral radiating microwave (630 or 915 MHz.) antenna hyperthermia. Acute and subacute toxicity was mild and consisted primarily of bladder spasm (26% of the patients), hematuria (23%) and dysuria (9%), none of which significantly limited the achievement of desired temperatures during the treatment sessions. No chronic treatment-related morbidity or mortality was observed. Detailed thermal mapping, performed along the course of the prostatic urethra, recorded temperatures of 43C or more at greater than 75% of the loci. Highly significant increases in urine flow rate, decrease in post-void residual urine capacity and decrease in frequency of nocturia were observed. A marginally significant decrease in prostate volume was noted and, with a median followup of 12.5 months, only 3 patients have required subsequent prostatic resection. Transurethral hyperthermia represents a safe and promising outpatient approach to treatment of benign prostatic hyperplasia, particularly for patients who are not candidates for conventional surgical approaches because of medical or personal reasons. Further studies with the goal of optimizing the technique appear to be warranted, although long-term results would be best evaluated with prospective phase 3 trials.

Aged

Episcleral radioactive plaque therapy: initial clinical experience with 56 patients.

Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.

Adult

Dosimetric calculations and measurements of gold plaque ophthalmic irradiators using iridium-192 and iodine-125 seeds.

The dosimetry of ophthalmic plaques designed to hold iridium-192 or iodine-125 seeds is investigated experimentally and by means of a computer model. A phantom for thermoluminescent dosimetry (TLD) which permits measurements to within 2 mm of the plaque surface is described. TLD data are compared with model calculations that take into account the active length of the seeds, anisotropy of dose distribution from single seeds, and scatter within the phantom. An isotropic point source calculational model is accurate for clinical calculations, particularly at depths greater than 5 mm. Relative central axis dose measurements for 125I in a gold plaque are also in agreement with the model. Comparisons of 192Ir, 125I and 60Co plaques are presented. The relative advantages of using these isotopes in eye plaques are discussed.

Brachytherapy

Characteristics of the high-energy photon beam of a 25-MeV accelerator.

The CGR Saturne 25 is an isocentrically mounted standing wave medical linear accelerator that produces dual-energy photon beams and a scanned electron beam with six selectable energies between 4 and 25 MeV. The highest energy photon beam is nominally referred to as 23 MV. For this beam the mean energy of the accelerated electron beam on the 1.3 radiation length (4 mm) tungsten x-ray target is found to be approximately 21 MeV, with the energy acceptance stated to be +/- 5%. The electron beam traverses a 270 degrees bending magnet upstream of the x-ray production target. The resulting bremsstrahlung beam passes through a combination steel and lead flattening filter, 4-cm maximum thickness. Dosimetric data for the 23-MV beam are presented with respect to rectangular field output factor, depth of maximum dose as a function of field size, surface and buildup dose, central axis percent depth dose, tissue-phantom ratios, beam profile, applicability of inverse square, and block transmission. Some data are also presented on the effect of different flattening filter designs on apparent beam energy.

Electrons

Backscatter measurements from a single seed of 125I for ophthalmic plaque dosimetry.

To determine the dosimetric effect of a gold plaque applicator used in 125I ophthalmic irradiation, relative dose rates at points 2-18 mm transverse to the axis of a single seed of 125I were measured in an acrylic phantom under three different measurement conditions. The detectors were 1-mm diameter X 3-mm length LiF thermoluminescent dosimeters (TLD's). Conditions corresponded to the following: (i) full scatter, (ii) the presence of an ophthalmic gold plaque, and (iii) no scatter material on the side of the seed opposite to the TLD's. The dose rate with the gold plaque is less than that with full scatter phantom. There is no significant decrease in dose rate at 2.2 mm from the seed. Dose rate is significantly reduced at greater distances. The does rate decrease ranges from 4% at 5 mm to 10% at 18 mm. The 125I seed in the gold plaque gives 3%-5% higher dose rate than in the absence of backscatter material.

Brachytherapy

Output factor constituents of a high-energy photon beam.

Measurements designed to separate primary and various scatter components of central axis dose of the highest energy photon beam of the CGR Saturne 25 linear accelerator are described. This beam has an unusually large output variation with field size. The measurements are performed both in air and in a water phantom, with and without an aperture external to the collimator system. Results are presented in the form of relative output factors for different field sizes due to (i) flattening filter scatter, (ii) water phantom scatter, (iii) collimator backscatter into the monitor chamber, and (iv) collimator forward scatter onto the central axis. It is found that the flattening filter is the single largest scatter component, but that each of the other factors is significant in determining the output dose per monitor unit as a function of field size.

Humans

Optimization of 125I ophthalmic plaque brachytherapy.

Episcleral plaques containing 125I sources are often used in the treatment of ocular melanoma. Within four years post-treatment, however, the majority of patients experience some visual loss due to radiation retinopathy. The high incidence of late complications suggests that careful treatment optimization may lead to improved outcome. The goal of optimization would be to reduce the magnitude of vision-limiting complications without compromising tumor control. We have developed a three-dimensional computer model for ophthalmic plaque therapy which permits us to explore the potential of various optimization strategies. One simple strategy which shows promise is to maximize the ratio of dose to the tumor apex (T) compared to dose to the macula (M). By modifying the parameters of source location, activity distribution, source orientation, and shielding we find that the calculated T:M ratio can be varied by a factor of 2 for a common plaque design and posterior tumor location. Margins and dose to the tumor volume remain essentially unchanged.

Biophysical Phenomena

Algorithm for dosimetry of multiarc linear-accelerator stereotactic radiosurgery.

Treatment planning for multiarc radiosurgery is an inherently complex three-dimensional dosimetry problem. Characteristics of small-field x-ray beams suggest that major simplification of the dose computation algorithm is possible without significant loss of accuracy compared to calculations based on large-field algorithms. The simplification makes it practical to efficiently implement accurate multiplanar dosimetry calculations on a desktop computer. An algorithm is described that is based on data from fixed-beam tissue-maximum-ratio (TMR) and profile measurements at isocenter. The profile for each fixed beam is scaled geometrically according to distance from the x-ray source. Beam broadening due to scatter is taken into account by a simple formula that interpolates the full width at half maximum (FWHM) between profiles at isocenter at different depths in phantom. TMR and profile data for two representative small-field collimators (10- and 25-mm projected diameter) were obtained by TLD and film measurements in a phantom. The accuracy of the calculational method and the associated computer program were verified by TLD and film measurements of noncoplanar multiarc irradiations from these collimators on a 4-MV linear accelerator. Comparison of film measurements in two orthogonal planes showed close agreement with calculations in the shape of the dose distribution. Maximal separation of measured and calculated 90%, 80%, and 50% isodose curves was less than or equal to 0.5 mm for all planes and collimators. All TLD and film measurements of dose to isocenter agreed with calculations to within 2%.

Algorithms

The accuracy of temperature measurement from within an interstitial microwave antenna.

Temperature measurement from within microwave interstitial antennas is a promising new development for hyperthermia. These antennas could enable the development of multipoint temperature regulation, leading to improved control of temperature distributions and therefore more effective hyperthermia treatments. In the complex environment of an antenna within a plastic catheter, measured temperatures were found to differ from the estimated local tissue temperature by up to 8 degrees C. In the design evaluated in this report the primary source of this error appears to be self-heating distal to the antenna junction, particularly in the outer copper conductor. The magnitude of self-heating is directly proportional to applied microwave power. Catheter wall thickness, tissue perfusion, and longitudinal temperature gradient also influence the measured temperature.

Humans