Episcleral plaque thermoradiotherapy of posterior uveal melanomas.

Episcleral plaque radiotherapy is a widely applied treatment for selected patients with uveal melanomas. This treatment is well tolerated but may produce severe late radiation complications resulting in decreased visual acuity that reduces the attractiveness of conservative therapy. The purpose of this study was to access if the addition of episcleral hyperthermia decreases late radiation complications through radiation dose reduction while maintaining high incidence of local tumor control. In a 3-year period, episcleral plaque thermoradiotherapy was given to 25 patients with uveal melanoma in a Phase I study. The mean tumor height was 6.2 mm and the mean tumor basal area was 173 mm(2). The mean radiation dose given to the tumor apex was 72.2 Gy and the mean hyperthermia temperature, given once for 45 min, was 43.5 degrees C. Of the 25 patients treated, 22 (88%) showed tumor height reduction, 2 (8%) showed no change, and 1 (4%) had an increase in tumor height. At the last follow-up (range, 20-68 months; mean, 31.2 months), a 43% mean tumor height reduction was recorded (p = 0.0002). Of the 22 patients initially showing tumor regression, 2 (9%) had subsequent tumor progression. At least ambulatory vision (>5/200) was maintained by 20 (80%) patients. Severe complications, including hemorrhagic retinal detachment and a large vitreous hemorrhage, were seen in 2 (8%) patients early in this Phase I study. The treatment program was well tolerated by the study patients. Severe late treatment toxicity was sharply reduced by limiting the mean scleral temperature to < or equal to 44 degrees C. This study employing 30% lower radiation doses, showed tumor regression in the majority of patients. Longer follow-up is needed to assess long-term treatment efficacy and late treatment complications.

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.

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.

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.

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.

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.