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M A Astrahan

Publications and source records attributed to M A Astrahan.

15 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

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

Microwave applicator for transurethral hyperthermia of benign prostatic hyperplasia.

An applicator for heating the prostate gland using a transurethral approach is described. This technique uses three microwave antennas and a thermometry sensor attached to the outer surface of a balloon (Foley) type urological catheter. Each microwave antenna also includes a built-in thermistor to control temperature and balance power. The balloon catheter assures rapid and reproducible localization of the antennas in the prostatic urethra. The two-dimensional SAR and steady-state temperature distributions surrounding the applicator in tissue equivalent phantom are reported. Longitudinal temperature distributions measured in situ at the applicator-urethral interface and the longitudinal and radial temperature distributions measured in normal canine prostate are presented and discussed. The technique appears to be capable of elevating temperature to greater than 42 degrees C in a cylindrically symmetrical volume up to 5 cm length and 0.5 cm radial penetration surrounding the applicator.

Hot Temperature

Adjuvant pelvic hyperthermia in advanced cervical carcinoma. I. Feasibility, thermometry and device comparison.

From 1981 to 1989, a total of 26 women with locally or regionally advanced carcinoma of the uterine cervix were treated with radiotherapy (RT) and pelvic regional hyperthermia (HT), in the Divisions of Radiation Oncology at the University of Utah Medical Center (UU) and the Kenneth Norris Jr Cancer Hospital of the University of Southern California (USC). HT was produced by the BSD-1000 HT system and the annular phased array (AA) applicator usually driven at 60-65 MHz, or the BSD-2000 HT system and the Sigma-60 (S60) applicator usually driven at 70-85 MHz. During the HT sessions acute toxicity was common, particularly because of pain within or outside the applicator, which was power-limiting in 43% of the patients overall. Pain was more easily manipulated, but more commonly power-limiting with the S60. Systemic stress was power-limiting in 22% of patients treated with the AA, but in no patients with the S60. Detailed thermal mapping and temperature analysis were performed on 26 patients. The mean overall average intratumour temperature achieved was 41 +/- 1.1 degrees C for 30 min; 5% and 35% of the monitored intratumour loci exceeded 43 degrees C and 42 degrees C, respectively. Temperatures recorded in the cervical os and proximal vagina appeared lower relative to the monitored normal structures in the region. Subacute treatment related toxicities occurred in five patients and included protracted pain (three) and superficial second degree burns (one), all of which resolved with supportive non-surgical therapy.

Adenocarcinoma