External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma.

BACKGROUND: The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. METHODS: Twenty-six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6-104 ng/mL). All patients received external beam radiation therapy using a four-field technique. The median radiation dose was 6,800 centigrays (cGy) given in 200-cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 degrees C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan-Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow-up for all patients was 71 months. RESULTS: The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%, respectively, and the median and 5-year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06). CONCLUSIONS: The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted.

LINAC-based spinal stereotactic radiosurgery.

The authors' report on the use of a prototype spinal stereotactic radiosurgery frame which was employed for the treatment of 9 patients who presented with recurrent neoplastic involvement of the spinal column. All patients had failed standard therapy consisting of surgery, external fractionated radiation therapy, and/or chemotherapy. Eight of the lesions represented metastatic tumors in the vertebral column, one of the lesions was a primary osteosarcoma involving multiple vertebral bodies. The lesions were found at multiple levels, from the cervical through the sacral region. Six out of the 9 patients presented with epidural compression: 4 of the 9 patients with evidence of myelopathy: 2 of the 9 patients with radicular symptoms secondary to compression from the tumor, and 1 patient was free of any compressive symptoms. All patients had pain requiring narcotics. Patients were treated with a median radiosurgical dose of 800 cGy (range 800-1.000) with a median of 1 isocenter (range 1-7 isocenters) and median normalization of 80% to the isodose contour (range 80-160). Median dose delivered to the already prior irradiated spinal cord was 179 cGy (range 52-320 cGy) with a median spinal cord dose of 34 (range 4-68). To date, there have been three minor complications: one radiation-induced esophagitis which was treated medically: one wound infection, and 1 patient requiring an additional 24 h of hospitalization stay. There have been no major complications. To date, 5 of the 9 patients have died, all from causes unrelated to the spinal radiosurgery. Three out of the 9 patients have been followed for more than 1 year. In all 3, there was radiographic regression of the tumor and epidural compression. In 2 patients, there was histologic confirmation of absence of tumor in the treated site: in 1 patient. no tumor was found at postmortem. 12 months after treatment, when the patient died of unrelated causes. Although the number of patients followed is limited, the phase I study clearly shows the technical feasibility of spinal radiosurgery for the control of metastatic involvement of the vertebral column even in the face of epidural compression.

Preliminary clinical experience with linear accelerator-based spinal stereotactic radiosurgery.

A prototype device called an extracranial stereotactic radiosurgery frame was used to deliver stereotactic radiosurgery, with a modified linear accelerator, to metastatic neoplasms in the cervical, thoracic, and lumbar regions in five patients. In all patients, the neoplasms had failed to respond to spinal cord tolerance doses delivered by standard external fractionated radiation therapy to a median dose of 45 Gy (range, 33-65 Gy/11-30 fractions). The tumors were treated with single-fraction stereotactic radiosurgery with the spinal stereotactic frame for immobilization, localization, and treatment. The median number of isocenters was one (range, one to five) with a median single fraction dose of 10 Gy (range, 8-10 Gy) with median normalization to 80% isodose contour (range, 80-160%). There has been a single complication of esophagitis to date from radiosurgery of a tumor involving the C6-T1 segments; the esophagitis resolved with medical therapy. Median follow-up in this group of patients has been 6 months (range, 1-12 mo). To date, there has been no radiographic or clinical progression of the treated tumor in any patient. Two patients have died from systemic metastatic disease. In the three surviving patients, there has been computed tomographic- or magnetic resonance-documented regression of the treated tumor with a decrease of thecal sac compression with a median follow-up of 6 months (range, 3-14 mo). These five patients represent the first clinical application of stereotactic radiosurgery in the spine. The results suggest that extracranial radiosurgery may be suitable for the treatment of paraspinal neoplasms after external fractionated radiation therapy, even in the face of spinal cord compression.

Tolerances in setup and dosimetric errors in the radiation treatment of breast cancer.

PURPOSE: Treatment failure in radiation therapy, as well as unexpected complications, can be associated with set up changes or variations that can cause deviations from the prescribed radiation dose distribution both inside and outside the target volume. The effect of various deviations from the planned setup on the delivery of the prescribed radiation dose to the desired treatment volume was studied. METHODS AND MATERIALS: Adding a second simulation was investigated as means of minimizing setup changes on treatment. The first simulation was used for planning the treatment and the second simulation was essentially a mock treatment. Dosimetric evaluations based on dose volume histograms were analyzed for each deviation in the setup. RESULTS: In 95% of the patients, the frequency of the changes in the setup parameters between the second simulation and the treatment setup were reduced significantly from the changes that occurred between the first simulation and the second simulation. The changes in isocenter coordinates up to +/- 1.0 cm have minimal effects (+/- 2%) on the dose distributions. Gantry angle variations up to +/- 4 degrees produce a change of less than +/- 5% in the dose distribution within the target volume. However, this angular variation resulted in additional tissue irradiation outside of the desired treatment field (about 10 cm3 for a large patient). A gantry angle variation of +/- 6 degrees can change the volume of tissue that receives the prescribed dose by at least +/- 10%. In addition, such a change can increase the volume of tissue outside the desired treatment field that is irradiated. CONCLUSION: It is concluded that individually, deviations in one of the parameters from the planned setup of +/- 1.0 cm in isocenter position and +/- 4 degrees in gantry angle do not produce significant deviations from the planned dose distribution. However, a significant change in dose distribution is observed if the setup parameters are concurrently changed. A second simulation may minimize the deviations of the treatment setup from the planned setup and maximize the precision in dose delivery to the target volume.

Feasibility and toxicity of transrectal ultrasound hyperthermia in the treatment of locally advanced adenocarcinoma of the prostate.

PURPOSE: This Phase I trial tests the ability of a new hyperthermia device, the transrectal ultrasound probe, to heat the prostate gland, and evaluates the toxicity of transrectal ultrasound hyperthermia (TRUSH) given with concurrent standard external beam irradiation in the treatment of locally-advanced adenocarcinoma of the prostate. METHODS AND MATERIALS: Between June, 1990 and August, 1991, 14 patients with American Urological Society Stage C2 or D1 adenocarcinoma of the prostate were treated with TRUSH concurrently with standard external beam radiotherapy to the prostate. Twenty-two heat treatments were delivered in 14 patients; 8 patients received two TRUSH procedures, each separated by 1 week. Patient age ranged between 53-86 (mean: 72) years. Three patients had well-, 6 patients had moderately-, and 5 patients had poorly-differentiated adenocarcinoma of the prostate. Karnofsky status ranged from 70-90. Standard radiotherapy to the prostate and periprostatic tissues was delivered using a four-field approach with 1.8-2 Gy daily fractions delivered 5 x/week to a total dose of 67-70 Gy calculated to the minimum tumor volume. TRUSH was delivered after transperineal placement of multipoint thermometry probes by a urologist, under transrectal ultrasound guidance. Two to three thermocouple probes containing seven sensors each were placed in the prostate in an attempt to sample temperatures throughout the gland. The sensor depth from the rectal wall ranged from 5-25 mm. RESULTS: Thirty-six percent of all sensors were heated above 42.5 degrees C averaged over 30 min; and all patients had at least some sensors within the prostate heated to temperatures > or = 42.5 degrees C. The average temperature of all sensors of all sensors (T(ave) +/- s.d.) over all treatments, however, was only 41.9 degrees C +/- 0.9 degrees C over 30 min. The maximum temperature for normal tissues outside the gland was 41.1 degrees C +/- 1.3 degrees C. Treatments have been well-tolerated with few complications. Tolerance has been "good" in 17/22, "fair" in 3/22, and "treatment limiting" in 2/22 treatments secondary to position intolerance and/or pain. There has been one episode of hypotension related to narcotic administration and three episodes of rapidly resolving pain during hyperthermia treatment. Mild hematuria has occurred in 5/22, and moderate hematuria has occurred in 2/22 transperineal thermometer catheter placements. CONCLUSION: In conclusion, TRUSH is well-tolerated and has great potential for consistently heating the prostate gland. We anticipate that further equipment modifications will improve our ability to heat the entire prostate to temperatures > 42.5 degrees C.