Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer.

OBJECTIVE: To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). PATIENTS AND METHODS: During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P < 0.001) and Gleason score (P = 0.18). The patients' median age was 66 years; the median follow-up was 6.1 years for all patients, 7 years for RP + RT and 5 years for the RP-alone. RESULTS: The 5- and 10-year actuarial survival was 92% and 73%, respectively, for RP + RT patients, and nearly identical for those in the RP-alone group (P = 0.73). The 5- and 10-year disease-free survival (DFS; PSA < 0.05 ng/mL) was 69% and 51%, respectively, for the former, and 71% and 60%, respectively, for the latter group. There was no significant difference in DFS between the treatment groups by pathological stage and Gleason score (P = 0.77). Likewise, there was no significant difference in mean and median time to relapse. A preoperative PSA level of < 10 vs 10-25 vs > 25 ng/mL did not influence overall survival but a PSA of > 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P < 0.001), while pathological stage was predictive of clinical recurrence and DFS (P < 0.001). After controlling for pathological stage and Gleason score, RP + RT patients were predicted to recur at 92% of the rate of RP-alone patients (P = 0.65). In all, 43 (10%) patients developed a clinical recurrence in the RP + RT group, including 30 (7%) patients with distant metastases alone, 13 (3%) with local recurrence, with an additional 88 (21%) who had PSA recurrence (PSA > 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. CONCLUSION: We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.

An image fusion study of the geometric accuracy of magnetic resonance imaging with the Leksell stereotactic localization system.

A special acrylic phantom designed for both magnetic resonance imaging (MRI) and computed tomography (CT) was used to assess the geometric accuracy of MRI-based stereotactic localization with the Leksell stereotactic head frame and localizer system. The acrylic phantom was constructed in the shape of a cube, 164 mm in each dimension, with three perpendicular arrays of solid acrylic rods, 5 mm in diameter and spaced 30 mm apart within the phantom. Images from two MR scanners and a CT scanner were obtained with the same Leksell head frame placement. Using image fusion provided by the Leksell GammaPlan (LGP) software, the coordinates of the intraphantom rod positions from two MRI scanners were compared to that of CT imaging. The geometric accuracy of MR images from the Siemens scanner was greatly improved after the implementation of a special software patch provided by the manufacturer. In general, much better accuracy was achieved in the transverse plane where images were acquired. Most distortion was found around the periphery while least distortion was present in the middle and most other parts of the phantom. For most intracranial lesions undergoing stereotactic radiosurgery, accuracy of target localization can be achieved within size of a voxel, especially with the Siemens scanner. However, extra caution should be taken for imaging of peripheral lesions where the distortion is the greatest.

Microwave transurethral applicator with helix-loaded-dipole-antenna (HLDA) for prostate treatment.

Three designs of transurethral applicators have been analysed to find the one that is best able to selectively heat the desired volume of prostate. A helix-loaded-dipole-antenna (HLDA) inserted into a Foley type catheter was found to be the most promising design. A change in the heat deposition pattern of the antenna depending on prostate size is possible by moving the position of the antenna within a Foley catheter. A number of prototypes of HLDA were manufactured and tested to optimize their design. These tests were performed in solid and liquid phantoms and in laboratory animals. Intra-operative measurements of intra-prostatic temperature distribution were also performed. A comparison of the HLDA with other commercially available transurethral applicators and the published data showed that the present design has a higher linear homogeneity coefficient and a better heat deposition in the prostate.

Radiosurgical management of benign cavernous sinus tumors: dose profiles and acute complications.

OBJECTIVE: Radiosurgery has emerged as an alternative treatment modality for cranial base tumors in patients deemed not suited for primary surgical extirpation, patients with recurrent or residual tumor after open surgery, or patients who refuse surgical treatment. We review our short-term experience with radiosurgical management of cavernous sinus region tumors with the Leksell gamma knife. METHODS: From August 1994 to February 1999, 69 patients with cavernous sinus lesions were treated in 72 separate treatment sessions. The tumor type distribution was 29 pituitary adenomas, 35 meningiomas, 4 schwannomas, and 1 paraganglioma. The median follow-up was 122 weeks. Lesions were stratified according to a five-level surgical grade. The grade distribution of the tumors was as follows: Grade I, 13; Grade II, 21; Grade III, 19; Grade IV, 12; Grade V, 4. Median tumor volume was 4.7 cm3. The median radiation dose was 15 Gy to the 50% isodose line. Median maximal radiation dose was 30 Gy. RESULTS: Analysis of tumor characteristics and radiation dose to optic nerve and pontine structures revealed a significant correlation between distance and dose. Much lower correlation coefficients were found between tumor volume and dose. One lesion in this series had evidence of transient progression and later regression on follow-up radiographic studies. No other lesions in this series were demonstrated to have exhibited progression. Complications after radiosurgical treatment were uncommon. Two patients had cranial nerve deficits after treatment. One patient with a surgical Grade III pituitary adenoma had VIth cranial nerve palsy 25 months after radiosurgical treatment that spontaneously resolved 10 months later. A patient with a bilateral pituitary adenoma experienced bilateral VIth cranial nerve palsy 3 months after treatment that had not resolved at 35 months after treatment. Six patients with preoperative cranial nerve deficits experienced resolution or improvement of their deficits after treatment. One patient with a prolactin-secreting adenoma experienced normalization of endocrine function with return of menses. CONCLUSION: Radiosurgical treatment represents an important advance in the management of cavernous sinus tumors, with low risk of neurological deficit in comparison with open surgical treatment, even in patients with high surgical grades.

A phantom study of the geometric accuracy of computed tomographic and magnetic resonance imaging stereotactic localization with the Leksell stereotactic system.

OBJECTIVE: To assess the spatial accuracy of magnetic resonance imaging (MRI) and computed tomographic stereotactic localization with the Leksell stereotactic system. METHODS: The phantom was constructed in the shape of a box, 164 mm in each dimension, with three perpendicular arrays of solid acrylic rod, 5 mm in diameter and spaced 30 mm apart within the phantom. In this study, images from two different MRI scanners and a computed tomographic scanner were obtained using the same Leksell (Elekta Instruments, Stockholm, Sweden) head frame placement. The coordinates of the rod images in the three principal planes were measured by using a tool provided with Leksell GammaPlan software (Elekta Instruments, Norcross, GA) and were compared with the physical phantom measurements. RESULTS: The greatest distortion was found around the periphery, and the least distortion (<1.5 mm) was present in the middle and most other areas of the phantom. In the phantom study using computed tomography, the mean values of the maximum errors for the x, y, and z axes were 1.0 mm (range, 0.2-1.3 mm), 0.4 mm (range, 0.1-0.8 mm), and 3.8 mm (range, 1.9-5.1 mm), respectively. The mean values of the maximum errors when using the Philips MRI scanner (Philips Medical Systems, Shelton, CT) were 0.9 mm (range, 0.4-1.7 mm), 0.2 mm (range, 0.0-0.7 mm), and 1.9 mm (range, 1.3-2.3 mm), respectively. Using the Siemens MRI scanner (Siemens Medical Systems, New York, NY), these values were 0.4 mm (range, 0.0-0.7 mm), 0.6 mm (range, 0.0-1.0 mm), and 1.6 mm (range, 0.8-2.0 mm), respectively. The geometric accuracy of the MRI scans when using the Siemens scanner was greatly improved after the implementation of a new software patch provided by the manufacturer. The accuracy also varied with the direction of phase encoding. CONCLUSION: The accuracy of target localization for most intracranial lesions during stereotactic radiosurgery can be achieved within the size of a voxel, especially by using the Siemens MRI scanner at current specifications and with a new software patch. However, caution is warranted when imaging peripheral lesions, where the distortion is greatest.

Radiotherapy for carcinoma of the bladder: a review.

Carcinoma of the bladder (CaB) is a common and important tumor in North America and Western Europe. There has been a steady increase in the incidence of CaB during the past 25 years in both of these regions with a simultaneous decrease in the mortality rates. The decrease in mortality is primarily due to an earlier diagnosis and the availability of more effective therapeutic interventions resulting from major advances in surgery and a wide use of multimodality bladder preservation therapy.The use of radiotherapy in the management of muscle-invasive CaB has undergone a major evolution. External beam radiotherapy alone is used infrequently in carefully selected patients. The same applies to the use of preoperative irradiation. Brachytherapy alone or combined with external beam radiotherapy has been used successfully in Europe but is used infrequently in North America. External beam radiotherapy is an essential component of a multimodality therapy consisting of cytoreductive surgery via transurethral resection of a bladder tumor followed by a planned combination of radiotherapy and chemotherapy. The outcomes of this bladder preservation therapy are similar to those reported in a like patient population treated with radical cystectomy. The main benefit of conservatively treated patients is functioning bladder in about 50% of those receiving conservative therapy. Radiotherapy alone or in a combination with chemotherapy remains an important and effective palliative therapy for patients with recurrent and/or metastatic CaB. Current research efforts are directed toward a better identification of important pretreatment risk factors predicting failure thus helping in a more optimal selection of patients who would benefit most from radical cystectomy or from the application of bladder preservation therapy.

Nonrandomized comparison of surgery with and without adjuvant pelvic irradiation for patients with pT3N0 adenocarcinoma of the prostate.

The purpose of this study was to evaluate the outcome of radical prostatectomy alone and compare it with that of surgery followed by planned adjuvant radiotherapy in patients with pT3N0 prostate cancer (CaP). A total of 402 patients with CaP were treated with prostatectomy, including 311 (77%) who received a planned course of adjuvant radiotherapy (RT) (surgery [S] + RT) to the prostatic fossa (median dose: 48 Gy) and 91 (23%) who had surgery alone. Patients in the former group had worse risk factors than those in the latter group, such as a higher clinical and pathologic stage (p = 0.001), higher Gleason score (p = 0.09), and higher preoperative prostate-specific antigen (PSA) level (p = 0.0001). PSA failure was defined as more than 0.05 ng/ml. Median follow-up was 59 months. The 5- and 10-year overall survival for the 311 S+RT patients was 91% and 81%, respectively, and it was similar for those 91 in the surgery-alone group, p = 0.59. The 5- and 10-year probability of freedom from PSA and/or clinical failure for the former group was 70% and 53%, respectively, whereas it was 66% and 46%, respectively, for the latter group, p = 0.72. Any recurrence developed in a total of 96 (31%) patients in the S+RT group as compared with 23 (25%) in the surgery-alone group. Local recurrence was noted in 10 (3.2%) S+RT and in 6 (6.6%) surgery-alone patients (N.S.). The time to clinical or chemical recurrence was also similar for both treatment groups (median time: 3.0 versus 3.8 years). Patients with pT3b tumors had relatively poor 5- and 10-year disease-free survival (53% and 32%, respectively, for S+RT and 38% and 0%, respectively, for surgery alone, p = 0.82). In multivariate analyses, pathologic stage and Gleason score were independent predictors of recurrence, each with p < 0.001 after controlling for the other. The worst prognostic category included patients with pT3bN0, Gleason score 7-10 disease who had 5.0 times the risk of recurrence as compared with pT3aN0, Gleason score 2-6 patients. No significant difference in disease-free survival by the treatment group was seen in Cox regression analysis controlling for pathologic stage (p = 0.59), Gleason score (p = 0.99), and PSA (p = 0.28). S+RT patients were predicted to have disease recurrence at 83% the rate of surgery-alone patients, p = 0.42. Preoperative PSA (>25 ng/ml) was predictive of recurrence (2.0 x risk) in univariate analysis, but it was not a significant predictor in multivariate analysis. It appears that moderate-dose, localized fields postoperative irradiation reduced the incidence of local recurrence in patients who were at a higher risk of recurrence as compared with those treated with surgery alone. New treatment strategies need to be developed to manage pT3bN0, Gleason score 7-10 patients whose 10-year disease-free survival was poor.

Radioactive plaque therapy for metastatic choroidal carcinoma.

PURPOSE: To describe the outcome of radioactive episcleral plaque therapy for treatment of metastatic carcinoma to the choroid. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Five patients (six eyes) with carcinoma metastatic to the choroid. METHODS: Retrospective review of the clinical records of five patients (six eyes) who underwent radioactive episcleral plaque therapy for choroidal metastases. MAIN OUTCOME MEASURES: Tumor height, visual acuity, radiation optic neuropathy, and radiation retinopathy. RESULTS: Radioactive episcleral plaque therapy resulted in shrinkage of the treated tumors and resolution of subretinal fluid in all eyes. After plaque treatment, best-corrected visual acuity was maintained within two lines of initial visual acuity for two eyes, decreased more than two lines for one eye, and improved more than two lines in three eyes. The treatment was well tolerated and there was no acute toxicity. Late complications included optic nerve atrophy (at 2 years) with proliferative radiation retinopathy (at 3 years) in one eye and optic atrophy (at 6 months) in another eye that had received prior external beam therapy. CONCLUSIONS: In carefully selected cases, radioactive episcleral plaque therapy appears to be an effective and reasonable treatment for carcinoma metastatic to the choroid.

Carcinoma of the kidney, testis, and rare urologic malignancies.

The purpose of this symposium was to provide a forum for discussion on current information on the etiology and diagnosis of, and therapy for, tumors of the kidney, testis, and several uncommon malignancies of the genitourinary tract. The most recent contributions in epidemiology and molecular genetics were discussed with specific reference to their importance for clinical practice. Contemporary treatment approaches with the emphasis on multidisciplinary patient management of tumors commonly seen in the clinic as well as those that are only rarely diagnosed by urooncologists were presented. Major stress was given to the management optimization as it pertains to short- and long-term quality of life issues of patients treated for these tumors. Methods to reduce treatment toxicity including carcinogenic potential of chemotherapy, radiotherapy, or their combination were found to be of nearly equal importance to patient survival. Symposium participants reached consensus on a number of important points: 1) The management of patients with several malignancies discussed requires the presence of a multidisciplinary team of specialist who are interested in diagnosis and treatment of genitourinary tumors; 2) Patients managed in such an environment are expected to have optimal survival and the best possible quality of life; 3) Real advances in the management of patients can be best obtained through well-designed prospective clinical trials; and 4) There is a need for timely introduction of relevant advances in epidemiology and molecular genetics to clinics.

Update on impact of moderate dose of adjuvant radiation on urinary continence and sexual potency in prostate cancer patients treated with nerve-sparing prostatectomy.

OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to 54 Gy achieves results comparable to higher doses. We studied the effect of moderate doses of postoperative radiation therapy on urinary continence and sexual potency in prostate cancer patients who had undergone nerve-sparing prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate cancer patients were selected to undergo nerve-sparing prostatectomy. A total of 94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy to the prostatic bed, based on microscopic positive margins, seminal vesicle involvement, and/or Gleason score. Subjective patient reports regarding the potency and urinary continence status were recorded during a semistructured telephone interview at 3 or more years after treatment. The findings in irradiated and nonirradiated patients were compared and correlated to those obtained from the same patients preoperatively and 1 year postoperatively. RESULTS: At 3 or more years of follow-up no significant difference among irradiated and nonirradiated patients was detected. Most patients described optimal urinary continence and approximately one third had maintained potency after bilateral nerve-sparing prostatectomy. None of the patients who had undergone unilateral nerve-sparing surgery remained potent. Using a multivariable analysis, the significant predictors for maintaining potency were the status at 1 year postoperatively and bilateral versus unilateral nerve-sparing procedure. CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy) did not affect the long-term pattern of maintenance of either function.

Stereotactic radiosurgery in the treatment of metastatic disease to the brain.

OBJECTIVE: In recent years, stereotactic radiosurgery has been growing in popularity as a treatment modality for metastatic disease to the brain. The technique has advantages of reduced cost and low morbidity compared with open surgical treatment. Furthermore, it avoids the potential cognitive side effects of fractionated whole-brain radiotherapy. We undertook this study to determine the usefulness of adjuvant radiation therapy and to determine prognostic factors in patients treated with stereotactic radiosurgery. METHODS: We reviewed our series of patients with metastatic tumors treated using gamma knife stereotactic radiosurgery from August 1994 to February 1999. Nonparametric methods were used to compare treatment subgroups by demographic features including age, Karnofsky Performance Scale score, diagnosis, and systemic disease status. Univariate and multivariate analyses of survival and freedom from progression were performed using Kaplan-Meier and Cox proportional hazards regression techniques. RESULTS: This study included 190 patients harboring 431 lesions who were treated in 263 treatment sessions. The median follow-up after radiosurgery was 36 weeks for all patients. The median actuarial survival from the time of radiosurgery in all patients was 34 weeks. When patients were stratified according to tumor histology, those without melanoma had a median survival of 39 weeks, and those with melanoma had a median survival of 28 weeks. The cause of death could be determined in 122 (92%) of the patients known to have died during the data capture period. For patients harboring melanoma, death was attributable to systemic disease in 31 (47%), to central nervous system-related processes in 29 (44%), and to unknown causes in 6 (9%). For non-melanoma patients, death was attributable to systemic disease in 45 (68%), to central nervous system-related processes in 17 (26%), and to unknown causes in 4 (6%). Significantly improved survival (P = 0.002) was observed in patients with controlled systemic disease. No significant difference in survival could be ascertained for patients presenting with up to four lesions, although patients with a total tumor volume greater than 9 cc had shortened survival. No survival benefit could be demonstrated for whole-brain radiotherapy administered either concomitantly or after radiosurgery. CONCLUSION: Factors correlated with significantly improved survival included controlled systemic disease and non-melanoma histology. We found no significant survival benefit that could be discerned from adjuvant whole-brain radiotherapy in this patient group.

Radiosurgical salvage therapy for patients presenting with recurrence of metastatic disease to the brain.

OBJECTIVE: Radiosurgery has emerged as an important modality in the management of metastatic disease to the brain. A number of groups have published results suggesting that high local control rates can be achieved, with improvements in overall survival that rival the results of open surgical treatment. Typically, however, whole-brain radiotherapy has been used in the salvage therapy of patients who have undergone previous craniotomy or radiosurgery. We describe our experience with radiosurgical salvage in this group of patients. METHODS: From August 1994 to February 1999, 190 patients with brain metastasis were treated with gamma unit radiosurgery at our institution. A subset of 45 patients, who underwent radiosurgical salvage for new tumors in a region remote from an initially treated tumor, form the population base for this study. The usual criteria for repeat treatment were recurrence with five or fewer discrete lesions outside of the previously treated radiosurgical volume and Karnofsky Performance Scale score of at least 70. Survival and freedom from progression were measured from the time of radiosurgical treatment and were computed by the Kaplan-Meier product-limit method. Two or more curves were compared using the log-rank method. RESULTS: In this subgroup of patients, a total of 176 tumors were treated. The median time from first radiosurgical procedure to first salvage was 17.4 weeks. Median survival from the second radiosurgical intervention was 28 weeks. Of the 45 study patients, 34 patients underwent a single salvage procedure, 10 patients underwent two salvage procedures, and 1 patient had three salvage procedures. The actuarial freedom from progression for treated tumors at 52 weeks was 92.4%. Patients undergoing upfront whole-brain irradiation were less likely to require salvage therapy (P = 0.008). There were 33 deaths after salvage radiosurgery during the reporting period. Central nervous system causes accounted for 13 deaths, whereas 19 deaths resulted from systemic disease. The cause of death in one patient could not be determined. No statistically significant advantage in overall survival could be demonstrated in patients treated with whole-brain irradiation. CONCLUSION: Radiosurgical salvage represents a valuable means of treatment for central nervous system recurrence for patients who have undergone previous treatment for metastatic disease to the brain. Whole-brain irradiation may reduce the need for salvage therapy, but no advantage in overall survival could be demonstrated in this subgroup.

Comparison of preoperative embolization followed by radical nephrectomy with radical nephrectomy alone for renal cell carcinoma.

A series of 474 patients with renal cell carcinoma (RCC), who had radical nephrectomy during a period of 15 years, was studied to assess the prognostic significance of various pathologic parameters (tumor stage [pT], lymph node status, metastasis, tumor grade, venous involvement) and value of preoperative embolization of renal artery. There were: 20 (4%) pT1, 204 (43%) pT2, 245 (52%) pT3, and 5 (1%) pT4 patients. All 474 patients underwent nephrectomy including a group of 118 (25%) patients (24 pT2, 90 pT3, and 4 pT4) who underwent preoperative embolization of the renal artery. To compare treatment outcomes in embolized patients with RCC, a group of 116 (24%) nonembolized patients with RCC was selected. This group was matched for sex, age, stage, tumor size, and tumor grade, with the embolized patients (p<0.01). All important prognostic factors were studied as to their influence on survival by the treatment group. The overall 5- and 10-year survival was 62% and 47%, respectively. The 5- and 10-year survival rates were significantly better (p<0.01) for patients with pT2 than for those with pT3 tumors (79% vs. 50% and 59% vs. 35%, respectively). Involvement of regional lymph nodes (N+) was an important prognostic factor for survival in patients with pT3 tumors. The 5-year survival for pT3 N+ was 39%, compared with 66% in those with pT3N0 (p<0.01). Preoperative embolization was also an important factor influencing survival. The overall 5- and 10-year survival for 118 patients embolized before nephrectomy was 62% and 47%, respectively, and it was 35% and 23%, respectively, for the matched group of 116 patients treated with surgery alone (p = 0.01). The most important finding of this study was an apparent importance of preoperative embolization in improving patients' survival. This finding needs to be interpreted with caution and confirmed in a prospective randomized trial.

Quality assurance of beam accuracy for Leksell Gamma Unit.

For the acceptance test and annual quality assurance of the Leksell Gamma Unit, measurement of the beam accuracy, defined as a distance between mechanical and radiological isocenters, poses a challenge to medical physicists. The specification for the beam accuracy is within 0.5 mm for the 4-mm collimator helmet. In this report, we introduce a simple technique to analyze the beam accuracy by using a conventional film densitometer plus mathematical modeling. A small piece of film was placed inside the film cassette containing a sharp needle. The needle is located such that its tip is exactly positioned at the mechanical isocenter. Before exposure, the film was pierced by the needle. Density profile was measured by using a densitometer with a spatial resolution of 0.8 mm. The profile was then fitted to a model of the two Gaussian functions. One is for the radiation field profile, the other for a dip caused by the narrow hole. The difference between the centers of the two Gaussian functions defines the deviation of the beam accuracy from the mechanical center of the unit. The deviations for x, y, and z directions from one of our annual measurements are 0.032, 0.054, and 0.195 mm, respectively. The combined deviation is 0.20 mm, which is well within the specification and in excellent agreement with the results from the manufacture's laser measurement. This technique provides a simple, accurate and practical tool for measurement of the beam accuracy in the acceptance test and annual quality assurance of the Leksell Gamma Unit.

Localized current field hyperthermia in carcinoma of the cervix: 3-D computer simulation of SAR distribution.

Software was developed for the 3D simulation of SAR distribution for a 500 kHz localized current field hyperthermia system to be used in patients with carcinoma of the cervix. This hyperthermia system was specifically designed for use with a modified Fletcher-Suit intracavitary applicator. It consists of software modules for data input, tetrahedral grid generation and a numerical calculation of SAR distribution using an adaptive, multilevel finite element code. The AVS (Advanced Visual System, Inc.) system was used for the visual presentation of the results. A quasi-static approach was employed for the determination of SAR distribution. Results of the performed numerical tests were presented and they showed an important, clinically relevant ability to obtain a selective power deposition. This selective power deposition depended on the applicator geometry, i.e. the distance between the components of a Fletcher-Suit applicator and their relative position and the use of different modes of excitation.

Dosimetric comparison of three photon radiosurgery techniques for an elongated ellipsoid target.

PURPOSE: To examine the dosimetric differences among three radiosurgery techniques: gamma knife, linac multiple arcs, and conformally-shaped static fields. METHODS AND MATERIALS: A simulated target was taken to be a prolate ellipsoid, 25 mm in diameter, 35 mm in length, centrally located in a three-dimensional (3D) model of a patient head taken from MR images. Single isocenter linac treatment plans were developed, 9 portals for the static shaped field technique, and a 7-arc plan for the multiple arc method. A total of 13 isocenters with 3 different collimators were used in the gamma knife plan. RESULTS: At dose levels from 25% to 50% of the reference dose, multiple arc and shaped-field plans treated a greater volume than the gamma knife plan. The linac plans, however, delivered the dose more homogeneously across the target volume as compared to the gamma knife plan. For the dose levels between 50-100%, the shaped fields and gamma knife plan have a similar dose distribution, and treated slightly less volume than the multiple arc plan. CONCLUSION: For a target of limited volume and essentially any shape, one can obtain closely conformal dosimetry with the gamma knife. For a regular-shaped target, the single isocenter multiple arc technique gives a more homogenous dose distribution within the target. Static shaped fields offer an alternative radiosurgery technique, with dosimetry similar to the multiple arc method, applicable to targets of any shape.

Comparison of outcomes of radical prostatectomy with and without adjuvant pelvic irradiation in patients with pathologic stage C (T3N0) adenocarcinoma of the prostate.

Patients with localized adenocarcinoma of the prostate gland (CaP) are frequently (approximately 50%) found at radical prostatectomy to have extracapsular disease or positive surgical margins. The management of these patients is a subject of controversy because some question the impact of this manifestation of CaP on patient survival or disease-free survival. Between 1976 and 1991, 241 patients with pathologic stage C (T3N0) were treated in this medical center. Of these 241 patients, 201 (83%) received a planned postoperative pelvic irradiation consisting of 48 Gy given to the prostatic fossa, whereas 40 (17%) patients were treated with radical prostatectomy alone. The two study urologists selected these patients not to receive postoperative irradiation based on intraoperative findings and important prognostic factors. Comparison of treatment outcomes in these two treatment groups is a subject of this report. The 201 patients treated with surgery-radiotherapy (S+RT) combination had a higher pathologic stage, greater incidence of seminal vesicle involvement, p = 0.002, and higher mean and median preoperative prostate-specific antigen level, p < 0.0001, than the 40 surgery (S) alone patients. There was no significant difference in the incidence of higher Gleason's score by the treatment group, p = 0.14. In univariate analysis, there was no significant difference in survival, disease-free survival, and time to failure between the two treatment groups. In multivariate analysis after controlling for pathologic stage and Gleason's score, the 201 adjuvant radiotherapy patients were predicted to have recurrence at 68% (95% confidence interval 39%-118%) the rate of the 40 surgery-alone patients. Local recurrence with or without metastatic disease was found in 10% of surgery-alone patients as compared to 5% in those also receiving postoperative irradiation. Treatment tolerance was very good with minor radiotherapy complications only. There was no significant difference in the incidence of incontinence between the two treatment arms. In summary: (a) The use of moderate-dose postoperative radiotherapy was of low toxicity and it did not increase the incidence of incontinence. (b) Local recurrence was 5% in S+RT and 10% in S-alone patients. (c) In multivariate analysis, S+RT patients had 68% rate of recurrence of S-alone patients. (d) Adjuvant RT probably reduces the risk of recurrence in patients with poor prognostic factors. (e) These data need to be interpreted with caution because of the nonrandomized nature of the study.

Adjuvant radiotherapy in patients with pathologic Stage C (pT3N0) adenocarcinoma of the prostate.

OBJECTIVES: This report is an update on the outcomes in the management of pathologic Stage C (T3N0) prostate cancer (CaP) with postoperative irradiation. METHODS: Between 1976 and 1994, 311 patients with pathologic Stage C CaP were treated with radical prostatectomy. Pathologic stage was as follows: C1, 60 patients (19%), C2, 146 patients (47%), and C3, 105 patients (34%). Gleason score was 2 to 4 in 10 patients (3.2%), 5 to 6 in 121 (39%), 7 in 101 (32%), and 8 to 10 in 76 (24%); median prostate-specific antigen (PSA) level was 11.9 ng/mL. Postoperative irradiation consisted of a median dose of 48 Gy. Follow-up was up to 18 years (median 5). RESULTS: The 10-year actuarial survival was 81% and 10-year disease-free survival was 51%. Pathologic stage and Gleason score were independently predictive of recurrence, each with P >0.001 after controlling for the other. Patients with pathologic Stage C3 and Gleason score 7 to 10 were in the worst prognostic category and had 5.4 times the risk of recurrence compared with patients with pathologic Stage C1-C2, Gleason score 2 to 6. Preoperative PSA was a good (P = 0.02) predictor of disease-free survival. Clinical recurrence was seen in 28 patients (9%), including 10 (3.2%) with local recurrence. PSA recurrence (PSA greater than 0.05 ng/mL) developed in 68 patients (22%). CONCLUSIONS: With the known limitations of a nonrandomized clinical trial, on the basis of the experience of this study we recommend the use of moderate dose, limited-field postoperative radiotherapy in patients with pathologic Stage C disease with Gleason score greater than 4.

Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complications.

OBJECTIVE: Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS: We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS: The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION: Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

Stereotactic radiosurgery in the treatment of metastatic disease to the brain.

We review 190 consecutive patients with 434 metastatic tumors treated by gamma knife stereotactic radiosurgery, from August 1994 to February 1999. Median actuarial survival for all patients was 34 weeks. Factors correlated with significantly improved survival included controlled systemic disease and nonmelanoma histology. We found that no significant survival benefit could be discerned from adjuvant whole brain radiotherapy in this patient group. Survival was not statistically different for patients initially presenting with 1-4 metastases at initial treatment.