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Advances may enable on-the-spot prostate cancer treatment

Radioactive seeds used to treat prostate cancer

Douglass Henderson, professor of engineering physics, and Bruce Thomadsen, professor of medical physics, have developed a trio of technologies that may enable physicians to deliver more effective prostate cancer treatment. Central to their innovations are radioactive “seeds” (shown here). Just a few millimeters in diameter, they deliver cancer-killing radiation when physicians implant them strategically within diseased tissue. Photo: Bruce Fritz. (large image)

Prof. Douglass Henderson and Prof. Bruce Thomadsen

Professor Douglass Henderson and Associate Professor Bruce Thomadsen (large image)

A trio of innovations may enable physicians to plan prostate cancer patients' treatment in real time and to implant cancer-killing radiation "seeds" more accurately and efficiently.

Engineering Physics and Biomedical Engineering Professor Douglass Henderson, Medical Physics, Engineering Physics and Biomedical Engineering Associate Professor Bruce Thomadsen, and Mechanical Engineering Professor Nicola Ferrier developed directionally emitting radioactive sources, a device for placing needles and seeds, and a super-fast treatment-planning method. Together, this suite of inventions could mean on-the-spot treatment reoptimization — the holy grail of prostate cancer seed placement.

To eradicate diseased tissue, physicians implant up to 100 radioactive seeds in the prostate. Like a tiny grain of rice, each seed is cylindrically shaped and emits radiation in all directions — increasing its likelihood of zapping healthy tissue, too.

So, borrowing a concept from nuclear materials handling, Henderson, Thomadsen and graduate student Liyong Lin designed directional seeds — sources with vertical shielding along one side. “I think nobody's done it before because they look at these sources, which are only eight-tenths of a millimeter in outer diameter, and they say there isn't enough space to put shielding,” says Thomadsen. “We found you can compress things and you can do it.”

As a result, they can implant seeds, particularly at the boundaries between healthy and diseased tissue, that steer radiation where it's needed most.

The three investigators developed prototypes and conducted successful radiation simulations. Now they are working with a leading brachytherapy products company to develop experimental prototypes. To keep the seeds from rotating once they're implanted, the group also hopes to modify their design to incorporate a wedge-shaped anchor along one vertical side. “It only has to hold the source about three days, and after that time, tissues start sticking to it,” says Thomadsen.

Implanting the seeds accurately is no small feat. With a hole-studded grid mounted over the patient as a guide, physicians use a hollow needle to insert the seeds manually. They rely on real-time ultrasound images of the prostate to ensure proper seed location and depth.

But both the confines of the grid and the ultrasound itself limit the process, meaning that the radioactive seeds may not make it to the correct locations, says Thomadsen. “Because the needles are constrained to only be in those half-centimeter-by-half-centimeter holes and only parallel to the ultrasound probe, when you do the treatment plan, you can see very obviously that you don't get a real optimal plan — you'd want to put seeds where you can't because there are no holes,” he says. “And sometimes when you're doing the implant, you can't get the needles where you want to go because the pelvic bones are in the way,” he says.

So he, Professor Ferrier and his graduate student Michael Meltsner abandoned the grid and built a robot that could deliver seeds more precisely than a physician could by hand. “There's an additional impetus that came along when we started working on the directional sources,” says Thomadsen. “In order to get sources in the patient in the right orientation, it would be very hard for a physician to get the angles precisely.”

Meltsner built a prototype robot and has perfected it by programming it to implant seeds into oranges. “It's a really basic prototype, and he's at the point where we have to test to make sure that, in the simple form we have, it's going to perform exactly how we want,” says Thomadsen.

By next year, when the system is complete, it will provide countless angles for inserting seeds and will enable physicians to properly orient seeds that contain shielding.

To plan the seed placement for maximum effectiveness, physicians currently map an ultrasound view of the prostate on a 3-D grid, use optimization software to calculate several sets of possible seed locations, and determine which configuration will work best. But current optimization methods are iterative methods — that is, they calculate a solution, make a change, and so on.

Inspired by a reactor physics technique called adjoint, or "backward" transport, Henderson, Thomadsen and their graduate students developed a method that could reduce the time of this treatment-planning step from as long as 40 minutes to just a few seconds and graduate student Vibha Chaswal is adapting the method for the directional seeds. "The adjoint function plays a big role in the selection of the seed position," says Henderson.

Considering how both tissue and tumor in the region of interest will react to radiation delivered by one seed, a “greedy” algorithm optimization software chooses the best location for the first seed. Based on that choice, the software evaluates the best location for the second seed, then the third, and so on. In addition, the technique can combine more than one type of radioactive isotope and will specify seed angle and position based on whether it contains shielding.

Together, the suite of advances could represent the holy grail of seed implants: live-time reoptimization, says Thomadsen. “A plan would tell you where to put the seeds,” he says. “And each time you put in a seed, it would recalculate where to put the next seed based on where you actually put the first one.”

For patients, he says, that level of interactivity means less hassle and more peace of mind. "The patient wouldn't have to come in days early for a pre-scan," he says. "They could just come in for the procedure. Everything could happen right then, in live time."

The group received funding for its projects from the Department of Energy Nuclear Engineering Education Research program, the UW-Madison Graduate School, and the Wisconsin Alumni Research Foundation (WARF). Thomadsen, Henderson and colleagues are patenting the innovations through WARF.