Faculty Bibliography

Conventional B-mode ultrasound currently is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy to treat prostate cancer. Yet B-mode images do not adequately display cancerous lesions of the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of radiofrequency (rf) echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. This method of tissue-type imaging utilizes nonlinear classifiers, such as neural networks, to classify tissue based on values of spectral parameter and clinical variables. Two- and three-dimensional images based on these methods demonstrate potential for guiding prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional images are being generated in real time in ultrasound scanners used for real-time biopsy guidance and have been incorporated into commercial dosimetry software used for brachytherapy planning. Three-dimensional renderings show promise for depicting locations and volumes of cancer foci for disease evaluation to assist staging and treatment planning, and potentially for registration or fusion with CT images for targeting external-beam radiotherapy

Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning radiotherapy (i.e., brachytherapy and external-beam radiation) of prostate cancer (CaP). Yet B-mode images essentially do not allow visualization of cancerous lesions of the prostate. Ultrasonic tissue-typing imaging based on spectrum analysis of radiofrequency (RF) echo signals has shown promise for overcoming the limitations of B-mode imaging in distinguishing cancerous from common forms of non-cancerous prostate tissue. Such tissue typing utilizes non-linear methods, such as nearest-neighbor and neural-network techniques, to classify tissues based on spectral-parameter and clinical-variable values. Our research seeks to develop imaging techniques based on these methods for the purpose of improving the guidance of prostate biopsies and the targeting of brachytherapy and external-beam radiotherapy of prostate cancer. Images based on these methods have been imported into real-time instrumentation for biopsy guidance and into commercial dose-planning software for real-time brachytherapy. Three-dimensional renderings show locations and volumes of cancer foci. These methods offer exciting possibilities for effective low-cost depiction of prostate cancer in real-time and off-line images. Real-time imaging showing cancerous regions of the prostate can be of value in directing biopsies, determining whether biopsy is warranted, assisting in clinical staging, targeting brachytherapy, planning conformal external-beam radiation procedures, and monitoring treatment

PURPOSE: Although radionuclide bone scans are frequently recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. We hypothesized that Gleason score, prostate-specific antigen (PSA), and clinical stage could predict for a positive bone scan (BS), and that a low-risk group of patients could be identified in whom BS might be omitted. METHODS: All patients who had both pathologic review of their prostate cancer biopsies and radionuclide BS at our institution between 1/90 and 5/96 were studied. Gleason score, PSA, and clinical stage (AJCC, 4th edition) were evaluated by univariate and multivariate analyses for their ability to predict a positive BS. Groups analyzed were Gleason of 2-6 vs. 7 vs. 8-10; PSA of 0-15 vs. greater than 15-50 vs. greater than 50; and clinical stage of T1a-T2b vs. T2c-T4. Univariate analysis using chi(2) and multivariate analysis using logistic regression were performed. RESULTS: Of the 631 consecutive patients, 88 (14%) had positive BS. Multivariate analysis (64 excluded due to missing PSA and/or clinical stage) showed Gleason score, PSA, and clinical stage to be significant independent predictors for positive BS (p < 0.002, p < 0.001, p < 0.001, respectively). The odds ratios were 5.25 (confidence interval [CI], 3.43-8.04) for PSA > 50 vs. 0-15; 2.25 (CI, 1.43-3.54) for Gleason of 8-10 vs. 2-6; 2.15 (CI, 1.54-2.99) for clinical stage T2c-T4 vs. T2b or less. Three of 308 (1%) had a positive BS in patients with Gleason 2-7, PSA of 50 or less, and clinical stage of T2b or less. In the subset of the same risk group with PSA of 15 or less, all 237 had negative bone scans. In patients with PSA greater than 50, 49/99(49.5%) had positive BS. CONCLUSION: Gleason score, PSA, and clinical stage were independent predictors for a positive radionuclide BS in newly diagnosed prostate cancer patients. PSA is the major predictor for positive BS. About one-half of the patients analyzed were in the low-risk group (Gleason 2-7, PSA < or = 50, clinical stage < or = T2b) and elimination of BS in these patients would result in considerable economic savings

PURPOSE: The dosimetric merit of a permanent prostate implant relies on two factors: the quality of the plan itself, and the fidelity of its implementation. The former factor depends on source type and on source strength, while the latter is a combination of skill and experience. The purpose of this study is to offer criteria by which to select a source type ((125)I or (103)Pd) and activity. METHODS AND MATERIALS: Given a prescription dose and potential seed positions along needles, treatment plans were designed for a number of seed types and activities, specifically for (125)I with activities ranging from 0.3 to 0.7 mCi, and for (103)Pd with activities in the range of 0.8 to 1.6 mCi. To avoid human planner bias, an automated computerized planning system based on integer programming was used to obtain optimal seed configurations for each seed type and activity. To simulate the effect of seed-placement inaccuracies, random seed-displacement 'errors' were generated for all plans. The displacement errors were assumed to be uniformly distributed within a cube with side equal to 2sigma. The resulting treatment plans were assessed using two volumetric and two dosimetric indices. RESULTS: For (125)I implants a coverage index (CI) of 98.5% or higher can be achieved for all activities (CI is the fraction of the target volume receiving the prescribed or larger dose). The external volume index (EI) (i.e., the amount of healthy tissue, as percentage of the target volume, receiving the prescribed or larger dose) increases from 13.9% to 20% as the activity increases from 0.3 to 0.7 mCi. For implants using (103)Pd, the external volume index increases from 10. 2% to 13.9% whenever CI exceeds 98.5%. Volumetric and dosimetric indices (coverage index, external volume index, D90, and D80) are all sensitive to seed displacement, although the activity dependence of these indices is more pronounced for (125)I than for (103)Pd implants. CONCLUSIONS: For both isotopes, the lower activities studied systematically result in lower EIs. If seeds can be placed within approximately 0.5 cm of their intended position (103)Pd should be preferred because its EI is lower than that of (125)I. For all activities the coverage indices and D90 are within the required range. If seed placement uncertainties are larger than 0.5 cm, (125)I provides slightly better target coverage; however, in terms of external volume (healthy tissue) covered, (103)Pd is superior to (125)I

Because of the uncertainties regarding the efficacy of postoperative radiation therapy for early prostate cancer, treatment strategies following radical prostatectomy include: (1) observation alone in high-risk patients, (2) adjuvant radiation therapy (PSA undetectable) in high-risk patients, or (3) salvage radiation therapy for biochemical and clinical recurrence. Fifty-two patients treated with postoperative radiation therapy in either an adjuvant setting (13) or for salvage (39) were retrospectively reviewed. The actuarial biochemical disease-free survival (bNED) rates following radiation therapy were calculated using the life-table method. Univariate and multi variate analyses were used to define the clinical factors that predict biochemical failure following postoperative radiation therapy. In addition, the bNED survival rate for 36 high-risk surgery patients who were simply observed following prostatectomy was determined. The 3-year bNED survival rate for the adjuvant radiation group was 85% compared with 27% for salvage radiation and 43% for the observation group. These results are statistically significant. Factors that predict biochemical failure following postoperative radiation therapy include preoperative PSA level, pre-radiation therapy PSA level, and seminal vesicle involvement. At our institutions, adjuvant radiation therapy was a superior strategy compared with either observation alone or salvage radiation therapy for high-risk postoperative prostate cancer patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 29-36 (2000)