Faculty Bibliography

PURPOSE: To investigate how the performance characteristics of ultrasound tissue typing (UTT) affect the design of a population-based prostate dose-painting protocol. METHODS AND MATERIALS: The performance of UTT is evaluated using the receiver operating characteristic curve. As the imager's sensitivity increases, more tumors are detected, but the specificity worsens, causing more false-positive results. The UTT tumor map, obtained with a specific sensitivity and specificity setup, was used with the patient's CT image to guide intensity-modulated radiotherapy (IMRT) planning. The optimal escalation dose to the UTT positive region, as well as the safe dose to the negative background, was obtained by maximizing the uncomplicated control (i.e., a combination of tumor control probability and weighted normal tissue complication probability). For high- and low-risk tumors, IMRT plans guided by conventional ultrasound or UTT with a one-dimensional or two-dimensional spectrum analysis technique were compared with an IMRT plan in which the whole prostate was dose escalated. RESULTS: For all imaging modalities, the specificity of 0.9 was chosen to reduce complications resulting from high false-positive results. If the primary tumors were low risk, the IMRT plans guided by all imaging modalities achieved high tumor control probability and reduced the normal tissue complication probability significantly compared with the plan with whole gland dose escalation. However, if the primary tumors were high risk, the accuracy of the imaging modality was critical to maintain the tumor control probability and normal tissue complication probability at acceptable levels. CONCLUSION: The performance characteristics of an imager have important implications in dose painting and should be considered in the design of dose-painting protocols

PURPOSE: To evaluate the toxicity and efficacy of individualized neoadjuvant androgen deprivation (AD) to maximal response followed by external beam radiotherapy (RT) with continued AD for a total of 9 months in a prospective phase II trial. PATIENTS AND METHODS: One hundred twenty-three patients received a total of 9 months of flutamide and luprolide combined with RT. RT initiation was individualized to begin after maximum response to AD as assessed by monthly digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant phase was restricted to no more than 6 months. RESULTS: Median time to initiation of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes were biochemical disease-free survival, (DFS) 63% +/- 7%; clinical DFS, 75% +/- 5%; cancer-specific survival, 99% +/- 1%; and overall survival, 89% +/- 3%. Patients initiating RT after 6 months of AD had significantly lower biochemical and clinical DFS. Those patients whose testosterone recovered to normal after completion of AD had a significantly superior survival rate. Of those patients potent before treatment, 65% remained so at last follow-up. CONCLUSION: The combination of 9 months of AD and RT, with initiation of RT individualized on the basis of maximum response to AD, achieves disease control rates comparable with past studies, while preserving potency in many patients. Further studies are warranted to determine the optimal combination of AD and RT in this patient population

PURPOSE: Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous 'margin' is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. METHODS AND MATERIALS: The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. RESULTS: Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of > or =3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer using intensity-modulated radiotherapy with 5-mm margin coverage from the clinical target volume (prostate gland) was performed. With a posterior shift of 10 mm for the prostate, the dose coverage dropped from 95-107% to 71-100% coverage. CONCLUSION: We have described a technique that corrects for the daily prostate motion, allowing for extremely precise prostate cancer treatment. This technique has significant implications for dose escalation and for decreasing rectal complications in the treatment of prostate cancer

Our research is intended to develop ultrasonic methods for characterizing cancerous prostate tissue and thereby to improve the effectiveness of biopsy guidance, therapy targeting, and treatment monitoring. We acquired radio frequency (RF) echo-signal data and clinical variables, e.g., PSA, during biopsy examinations. We computed spectra of the RF signals in each biopsied region, and trained neural network classifiers with over 3,000 sets of data using biopsy data as the gold standard. For imaging, a lookup table returned scores for cancer likelihood on a pixel-by-pixel basis from spectral-parameter and PSA values. Using ROC analyses, we compared classification performance of artificial neural networks (ANNs) to conventional classification with a leave-one-patient-out approach intended to minimize the chance of bias. Tissue-type images (TTIs) were compared to prostatectomy histology to further assess classification performance. ROC-curve areas were greater for ANNs than for the B-mode-based classification by more than 20%, e.g., 0.75 +/- 0.03 for neural-networks vs. 0.64 +/- 0.03 for B-mode LOSs. ANN sensitivity was 17% better than the sensitivity range of ultrasound-guided biopsies. TTIs showed tumors that were entirely unrecognized in conventional images and undetected during surgery. We are investigating TTIs for guiding prostate biopsies, and for planning radiation dose-escalation and tissue-sparing options, and monitoring prostate cancer