Faculty Bibliography

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

Angioplasty balloons inflated with a solution of the beta-emitter Re-188 have been used for intravascular brachytherapy to prevent restenosis. Coronary stents are in extensive clinical use for the treatment of de novo atherosclerotic stenoses. In this study, the effect of an interposed stent on the dose distribution has been measured for Re-188 balloon sources using the proprietary BANG polymer gel dosimeters and He-Ne laser-beam optical CT scanner. In polymer gels, after ionizing radiation is absorbed, free-radical chain-polymerization of soluble acrylic monomers occurs to form an insoluble polymer. The BANG polymer gel dosimeters used in these measurements allow high resolution, precise, and accurate three-dimensional determination of dosimetry from a given source. Re-188 liquid balloons, with or without an interposed metallic stent, were positioned inside thin walled tubes placed in such a polymer dosimeter to deliver a prescribed dose (e.g., 15 Gy at 0.5 mm). After removing the balloon source, each irradiated sample was mounted in the optical scanner for scanning, utilizing a single compressed He-Ne laser beam and a single photodiode. In the absence of a stent, doses at points along the balloon axis, at radial distance 0.5 mm from the balloon surface and at least 2.5 mm from the balloon ends, are within 90% of the maximum dose. This uniformity of axial dose is independent of the balloon diameter and length. Dose rate and dose uniformity for intravascular brachytherapy with Re-188 balloon are altered by the presence of stent. The dose reduction by the stent is rather constant (13%-15%) at different radial distances. However, dose inhomogeneity caused by the stent decreases rapidly with radial distance

Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204-223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts from a range of federal agencies, academia and industry. This workshop, Education and Training for Radiation Scientists, addressed the need to establish a sustainable pool of expertise and talent for a wide range of activities and careers related to radiation biology, oncology and epidemiology. Although fundamental radiation chemistry and physics are also critical to radiation sciences, this workshop did not address workforce needs in these areas. The recommendations include: (1) Establish a National Council of Radiation Sciences to develop a strategy for increasing the number of radiation scientists. The strategy includes NIH training grants, interagency cooperation, interinstitutional collaboration among universities, and active involvement of all stakeholders. (2) Create new and expanded training programs with sustained funding. These may take the form of regional Centers of Excellence for Radiation Sciences. (3) Continue and broaden educational efforts of the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Association for Cancer Research (AACR), the Radiological Society of North America (RSNA), and the Radiation Research Society (RRS). (4) Foster education and training in the radiation sciences for the range of career opportunities including radiation oncology, radiation biology, radiation epidemiology, radiation safety, health/government policy, and industrial research. (5) Educate other scientists and the general public on the quantitative, basic, molecular, translational and applied aspects of radiation sciences

OBJECTIVES: To study prospectively the prognostic significance of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay for patients with prostate cancer treated definitively with external beam radiotherapy. The RT-PCR assay for prostate-specific antigen (PSA) has been used to detect circulating prostate cancer cells in the serum of patients with prostate cancer. METHODS: In prospective fashion, serum RT-PCR testing was performed before and/or after definitive therapy, with the results scored as positive or negative. The results were analyzed for 161 patients, and the RT-PCR result was correlated with the treatment outcome. RESULTS: The median follow-up was 29 months. The pretreatment RT-PCR result was not predictive of biochemical relapse-free survival (bRFS) or clinical disease-free survival (DFS). Of 25 patients with T3-T4 tumors, those with a negative pretreatment RT-PCR result had better bRFS and a trend was noted toward better DFS compared with those with a positive result. Among patients with Gleason score 8 to 10 tumor who underwent pretreatment testing (n = 19), those with a negative RT-PCR result had better bRFS and DFS compared with those with a positive result. A trend toward better bRFS was seen for patients with negative versus positive post-treatment RT-PCR results. The DFS was better for patients with negative versus positive post-treatment RT-PCR results. CONCLUSIONS: RT-PCR, when obtained before radiotherapy, may be predictive of outcome for patients with more advanced stages or higher Gleason scores. Post-treatment testing predicted for clinical relapse. Additional study is needed before RT-PCR is used regularly in clinical practice

One of the major concerns with multileaf collimators (MLC) is the jagged field edge that produces a larger penumbra compared with that produced by a Cerrobend block. The dosimetric undulation of the MLC can be minimized by replacing an existing MLC with a mini-MLC, an expensive replacement, or by software implementation, which essentially converts a regular MLC into a virtual mini-MLC. In this study, the dosimetry in the penumbra region of a virtual mini-MLC replacing the Cerrobend block is investigated for clinical applications. HD270, a software program implemented by Siemens (Concord, CA), combines the use of an MLC and a table translation perpendicular to the leaf plane to produce a smooth field edge, thus reducing isodose undulation. Three different step resolutions are available: 5 mm, 3 mm, and 2 mm. Using film dosimetry, the penumbra regions are studied at two different depths for clinical blocks and corresponding MLC setup, as well as HD270 with different resolutions for both 6-MV and 15-MV x-ray beams. The dose delivery time for HD270 on auto-sequencing mode is compared with the use of Cerrobend blocks. The clinical applications of HD270 in head-and-neck (head and neck) and prostate treatments are investigated. For single-field irradiation, the 80-20% penumbra widths for both the 45 degrees block and the circular block are reduced with HD270 compared with MLC for both 6 and 15 MV at different depths. At 2-mm resolution, the scalloping isodose lines (IDLs) with MLC completely disappear, although the penumbra is still larger than the Cerrobend block. On the other hand, the difference in dose undulations between 2-mm and 3-mm resolution is small. In the head and neck irradiation, the 80-20% widths with HD270 are 1 to 2 mm less than MLC, but they are still 2 mm wider than with a Cerrobend block. The 50% IDL is reduced by 2 mm with HD270 compared with MLC, which provides safety near spinal cord. Dose-volume histogram (DVH) calculations for the different shielding techniques indicate that the HD270 improves the spinal cord dose distribution significantly compared with MLC. A similar improvement in dose undulation is observed for the prostate case. In the dose region, >60% of the prescribed dose, there is approximately 10% less irradiated volume for the rectum when HD270 (3 mm resolution) is employed compared with MLC. The treatment time was compared with that from the Cerrobend block, and it was found that even at 3-mm resolution, there is a 20% reduction in treatment time in a head and neck treatment; with a 2-mm resolution, there is a 15% increase in time. The isodose undulation due to MLC can be significantly reduced with the HD270. Clinical application with HD270 for head and neck and prostate irradiation provides a smaller penumbra region compared with MLC, although it still gives a larger one compared with the Cerrobend block. In the clinical cases presented in this study, the 3-mm resolution is the most effective in improving the penumbra and delivery time. The HD270 implementation is a versatile and cost-effective solution for reducing MLC undulation