Exploiting evolution to treat prostate cancer

December 21, 1999

Researchers are sending forth strings of binary digits to go forth and multiply-all in the name of human health.

Using strands of 0s and 1s to stock a digital community, complete with mating, offspring, and the occasional mutation, is nothing new to scientists who create genetic algorithms. These mathematical formulas are governed by Darwin's "survival of the fittest" mantra and rely on the principles of evolution to create solutions in a variety of applications, including financial analyses, computer-assisted scheduling, and target detection for the military.

Now scientists at the University of Rochester Medical Center are exploring use of the formulas to treat prostate cancer by improving how radiation is delivered. The formulas have been developed by medical physicist Yan Yu, Ph.D., a well-known expert on radiation treatment planning who heads a task force on the subject for the American Association of Physicists in Medicine. His algorithms are at the heart of a new start-up company aimed at improving a common prostate cancer procedure called brachytherapy, where tiny radioactive seeds are implanted into the prostate and destroy cancer cells in the organ over several weeks. It's an increasingly popular procedure for treating the nearly 200,000 men each year who are diagnosed with cancer of the prostate, which is an organ about the size of a small peach between the rectum and bladder that contributes fluids to semen.

Medical physicists like Yu, an associate professor of radiation oncology, play an often unseen role in cancer treatment, ultimately deciding how to deliver radiation to best eradicate cancerous tissue or organs without hurting healthy tissue. In cases of prostate cancer, the stakes are very high: the bladder, rectum, urethra, and nerves that control sexual function are all packed together near the organ, making it an especially challenging disease to treat. Brachytherapy is a little bit like baking a single muffin from the inside out, with physicists and physicians trying to ensure that every bit of the "muffin" is cooking at the exact same temperature while the other muffins nearby stay cool.

Choosing the right pattern for the seeds, which are radioactive particles about the size of a grain of rice, is daunting. Physicians commonly turn to commercial programs to help them decide how to place the particles. The recommended treatment plan is put in the hands of a surgeon, who actually inserts several dozen seeds into the prostate during a one- or two-hour surgical procedure.

Yu's work, dubbed PIPER for Prostate Implant Planning Engine for Radiotherapy, uses artificial-intelligence technology to recommend a radiation treatment plan. Based on an ultrasound scan of a patient's prostate and other pelvic organs, PIPER sets up a competition between the possible configurations. Yu and colleagues create a digital community with 64 "members" whose binary codes each represent a different radiation pattern. Community members compete to pass on their "genetic material"-bits of binary code-to the next generation. Each pattern's viability is determined by mathematical criteria which favor radiation plans that irradiate the prostate efficiently and knock out cancerous cells while sparing vital organs. In a game of virtual natural selection, binary code that embodies these qualities survives and multiplies, while poor code perishes.

Over the course of 200 generations the community evolves, with codes coming together randomly, combining their genetic material, and even mutating occasionally. In this way, the genetic algorithm creates a huge range of potential solutions that it constantly sifts to find the best candidate for a treatment plan. "A genetic algorithm can look at a much greater range of options than we otherwise could. There might be certain combinations that would never occur to a physicist to try," says Yu.

In just two minutes, PIPER presents to physicists and physicians the "winner"-the plan that the program decides is most likely to work best. The speed of PIPER, whose underlying technology has been patented by the University, may make it possible to do the radiation planning right in the operating room immediately before surgery, instead of several weeks beforehand as is now standard. That's a tremendous advantage, says surgeon Edward Messing, M.D., chair of the Department of Urology, who has performed scores of brachytherapy procedures at the University's Strong Memorial Hospital.

"The prostate you see in the operating room is never the same one you saw three weeks previously in your office," says Messing. "Hormone therapy before surgery can shrink the prostate, for instance, and even anesthesia can change the positioning of the pelvis the day of surgery. This oftentimes makes deviations from the now-dated plan necessary during surgery." Yu's goal is to make the process more precise. With a radiation treatment plan compiled just minutes before the operation, the plan is more likely to match what physicians actually confront in the operating room.

To commercialize the technology, the University has joined with Real Time Enterprises, a Rochester software engineering firm, to create a new company, RTek Medical Systems LLC. RTek will focus on the development of new radiation treatment planning systems based on Yu's algorithms. Any such system must be tested rigorously before any application for marketing approval will be submitted to the U.S. Food and Drug Administration, and the FDA must approve any product before it would become available.

At the University, the FDA has approved a clinical trial of the current system as an investigational device on about 30 patients. Messing, Yu and their colleagues will study the radiation treatment plans recommended by the system, along with the effects on tumor control, quality of life, and complications in patients who get the PIPER treatment compared to patients who receive a commercially available treatment. The clinical study will build on more than five years of basic research that has been funded by a variety of sources, including the National Cancer Institute and the Whitaker Foundation.

New product development and support is part of the expertise that Real Time Enterprises (RTE) brings to the partnership. The company specializes in software for medical equipment and devices like blood pressure monitors, vision screeners, and other diagnostic equipment used around the world.

"This line of research really is compelling," says RTE President Robert Ruppenthal. "People who treat cancer are visibly excited and impressed by the potential of this technology, because it's so different from what's out there today. Current treatment planning tools are trial and error: They will tell a physician what dose a given seed distribution will deliver, but they will not tell the doctor where to put the seeds."

RTek is the result of an accelerated effort by the University to commercialize technology developed in its laboratories. "There are many exciting technologies being developed in the Medical Center and across the entire University," says Jay Stein, M.D., senior vice president of the Medical Center and vice provost for health affairs. "This is one of the first of what we expect to be an ongoing series of technologies we plan to commercialize."
-end-


University of Rochester

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