Optimizing Radiation Delivery and Dissecting the Response to Radiation for Patients with Localized Prostate Cancer
Abstract
Prostate cancer is the most common non-cutaneous malignancy among men in the United States, with over 190,000 new cases diagnosed annually. For many men, the chance of cure is high, and therefore the predominant factor in their decision-making regarding treatment is the quality of life after treatment. The risk of experiencing urinary toxicity after radiotherapy increases slowly over time, meaning that long-term survivors have a real risk of experiencing urinary toxicity years after their radiation has been completed. One of the main challenges in preventing these toxicities is the difficulty in accurately controlling how radiation dose is delivered to the prostatic urethra and a portion of the bladder called the trigone. Both structures can exhibit significant variations in size, shape, and position during and between treatments. A second challenge is that some men unfortunately experience recurrences after prostate cancer (radio-recurrent disease). While some recurrences are slow-growing, others are highly aggressive, and we do not understand much about how prostate cancer becomes radio-recurrent. As a result, we struggle to determine the best strategies for patients with recurrences after radiation and do not use this biology to improve initial management by identifying which men may need either an alternative treatment modality or an intensified radiotherapy-based treatment as their initial treatment. In the current proposal, we describe a two-pronged approach in which we will optimize radiation delivery to minimize urinary toxicity and dissect the response to radiation by evaluating post-radiation biopsies. These projects will take place in parallel and will leverage data available through independently proceeding clinical trials of radiation for prostate cancer. To optimize radiation delivery, we will develop technologies that will allow the radiation oncologist and medical physicist to account for day-to-day changes in urethra and trigone anatomy with unprecedented accuracy when calculating and planning dose delivery. To understand the response to radiation, we will perform whole genome sequencing and other relevant testing on cancers that are either persistent or recurrent after radiation. There is no risk to patients from the proposed research, as patients are already enrolled on the relevant clinical trials are not undergoing extra procedures simply for the purposes of this research. We anticipate that, overall, this project will require 4 years of work. The technology to optimize radiation delivery will be made readily available to all patients undergoing radiotherapy for prostate cancer. The insights into biology of radio-recurrence will need to be further investigated in early-phase clinical trials before broader applicability would be feasible. Dr. Amar Kishan, the Principal Investigator, is an Assistant Professor in Radiation Oncology at the University of California, Los Angeles. His career goal is to discover, validate, and deploy interventions that will either prolong life or improve the quality of life for patients with prostate cancer. As a radiation oncologist, he wishes to be at the forefront of technological and scientific innovations that will allow him to achieve these goals. The proposed research project perfectly allows him to gain the requisite knowledge and experience that will be necessary to become an independent physician-scientist, as it contains both a medical physics focus and a basic biology focus. By directly working with a team of physicists to develop and trouble-shoot a novel form of radiation therapy delivery, he will gain a sophisticated level of insight into technological innovation in radiation oncology that is typically not accessible to clinicians. Dr. Ke Sheng, the mentor for that portion of the project, is a world authority on technological development in radiation oncology, and the two have already designed a thorough mentorship plan. Similarly, Dr. Kish
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210044
Entities
People
- Amar Kishan
Organizations
- United States Army
- University of California, Los Angeles