Prostate cancer remains a worldwide public health issue and cause of mortality, with annual diagnosis and mortality rates exceeding 1.1 billion and 307 million patients, respectively.1 Brachytherapy is widely accepted and utilized in the management of prostate cancer. Due to recent evidence showing improved disease control in patients with potentially lethal cancers using approaches incorporating brachytherapy, its utilization is expected to increase. Successful brachytherapy hinges on adequately dosing prostate while avoiding excessive radiation to adjacent tissues. Well-recognized contributors to poor dosimetry are source positioning errors, poor source visualization and edema, which in aggregate lead to regions of excessive as well as inadequate dose. In response to the recognized need for dynamic visualization of sources and intraoperative dose analysis during the procedure, our work has led to the development of a system of intraoperative ultrasound and fluoroscopy (iRUF) dynamic dose calculation using fluoroscopy-based seed reconstruction and fusion with intraprocedure ultrasound imaging. Following our pilot feasibility trial, we developed an FDA-approved dedicated brachytherapy platform, and have confirmed this technique in a Phase II trial, with outstanding dosimetry on a consistent basis.2,3 Currently, whole-gland treatment is standard in prostate cancer therapy. The need for whole-gland treatment stems from the uncertainty and difficulty in precisely identifying tumor foci within. Unfortunately, such approaches inevitably result in radiation exposure of adjacent critical structures, with potential toxicity and permanent quality of life effects. As long as whole gland therapy is delivered, the ability to limit normal tissue doses remains constrained by their proximity. New advances in PET imaging targeting Prostate Specific Membrane Antigen (PSMA) and second-generation PSMA-binding agents now allow highly specific and sensitive identification of extraprostatic and intraprostatic tumors.4,5,6 Focal therapy using PSMA PET/CT-and dynamic dosimetry-guided seed placement promises to further improve the standard of care in brachytherapy, allowing the physician to precisely tailor the dose to the individual?s tumor. This requires precise tumor imaging combined with dynamic intra-operative localization of the implant in relation to the target volume, as well as surrounding uninvolved prostate and normal anatomy.7,8,9,10 Combining iRUF and PSMA PET/CT would break new ground through addition of precise targeting via purely computational methods.
We aim to develop a clinically feasible image-guidance platform for dynamic, quantitative evaluation of partial-gland, focal dosimetry during brachytherapy. The system would allow personalized brachytherapy, achieving excellent cancer control while avoiding unnecessary toxicity for prostate cancer survivors.

Public Health Relevance

Despite changes in PSA screening, prostate cancer remains the most common cancer afflicting men and a leading cause of cancer-related death. Brachytherapy (implantation of radioactive seeds into the prostate) is widely used in the treatment of prostate cancer, and recent randomized evidence has shown it to be superior to dose-escalated beam radiation for patients with potentially lethal prostate cancer, but its use in this manner is tempered by concerns regarding toxicity from dose to nearby critical tissue structures, or insufficient dose to the cancerous regions. We plan to develop a system which allows physicians to use image-guided brachytherapy while also visualizing involved and uninvolved regions of prostate as identified on PET, thus allowing maximal sparing of normal tissues while maintaining or enhancing tumoricidal effect.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA151395-05
Application #
9382210
Study Section
Biomedical Imaging Technology B Study Section (BMIT-B)
Program Officer
Capala, Jacek
Project Start
2010-06-09
Project End
2022-05-31
Budget Start
2017-06-13
Budget End
2018-05-31
Support Year
5
Fiscal Year
2017
Total Cost
$532,313
Indirect Cost
$133,226
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Lee, Junghoon; Mian, Omar Y; Le, Yi et al. (2017) Intraoperative Registered Ultrasound and Fluoroscopy (iRUF) for dose calculation during prostate brachytherapy: Improved accuracy compared to standard ultrasound-based dosimetry. Radiother Oncol 124:61-67
Dehghan, Ehsan; Le, Yi; Lee, Junghoon et al. (2016) CT AND MRI FUSION FOR POSTIMPLANT PROSTATE BRACHYTHERAPY EVALUATION. Proc IEEE Int Symp Biomed Imaging 2016:625-628
Kuo, Nathanael; Dehghan, Ehsan; Deguet, Anton et al. (2014) An image-guidance system for dynamic dose calculation in prostate brachytherapy using ultrasound and fluoroscopy. Med Phys 41:091712
Kuo, Nathanael; Dehghan, Ehsan; Deguet, Anton et al. (2013) A Dynamic Dosimetry System for Prostate Brachytherapy. Proc SPIE Int Soc Opt Eng 8671:
Dehghan, Ehsan; Lee, Junghoon; Fallavollita, Pascal et al. (2012) Ultrasound-fluoroscopy registration for prostate brachytherapy dosimetry. Med Image Anal 16:1347-58
Kuo, Nathanael; Deguet, Anton; Song, Danny Y et al. (2012) Automatic segmentation of radiographic fiducial and seeds from X-ray images in prostate brachytherapy. Med Eng Phys 34:64-77
Lee, Junghoon; Kuo, Nathanael; Deguet, Anton et al. (2011) Intraoperative 3D reconstruction of prostate brachytherapy implants with automatic pose correction. Phys Med Biol 56:5011-27
Lee, Junghoon; Labat, Christian; Jain, Ameet K et al. (2011) REDMAPS: reduced-dimensionality matching for prostate brachytherapy seed reconstruction. IEEE Trans Med Imaging 30:38-51
Dehghan, Ehsan; Lee, Junghoon; Fallavollita, Pascal et al. (2011) Point-to-volume registration of prostate implants to ultrasound. Med Image Comput Comput Assist Interv 14:615-22