Radioactive seeds gain position

Anthony D’Amico faced a tricky problem. How to place 100 radioactive seeds, each smaller than a rice grain, into tumors inside a walnut-size prostate gland. Properly placed, the seeds destroy cancer cells.

Implanting the seeds – called brachytherapy – offers a way to treat early stages of prostate cancer in a way that, for some patients, may be superior to the usual methods of surgical removal of the gland or seven weeks of external radiation. However, the technique is not free of problems: improper placement of the seeds can lead to such life-spoiling complications as impotence, incontinence, rectal bleeding, and other side effects.

For proper placement, doctors now rely on images of the prostate made by sending high-frequency sound waves through the gland. The sound travels through the prostate at different speeds than through its surrounding tissues, creating images that accurately locate the gland. But these two-dimensional images result in lower success rates and more complications than cancer specialists wanted.

D’Amico, an associate professor of radiation oncology at Harvard Medical School, works at Brigham and Women’s Hospital in Boston where he has extensive experience with magnetic resonance imaging (MRI). He is familiar with MRI machines being used to produce high-resolution pictures of the brain that his colleagues use to guide removal of brain tumors. Why not use such images for placing radioactive seeds into cancerous prostates, he thought.

D’Amico assembled a team of experts including radiologist Clare Tempany, urologist Sanjaya Kumar, and physicist Robert Cormack. Together they did their first MRI-guided seed placements in November 1997. Since then, the team has done more than 140 procedures without any failures or recurrence of cancer.

“Patients experience fewer side effects than with ultrasound placement,” D’Amico says. “That’s because we can place seeds more precisely, allowing delivery of more radiation to tumors while sparing healthy tissues.” Up to a point, the higher the radiation dose, the less the chance that residual cancer cells will survive.

Compared with surgery, the most common procedure, D’Amico’s group sees less impotence and incontinence caused by damage to normal tissues. “That’s what we’re trying to do – cure patients while preserving the quality of their lives,” he says.

Selecting patients

But D’Amico stops well short of bragging about his seed implanting technique as a revolutionary treatment. “It’s too early to make favorable comparisons with other methods,” he says flatly. “We’ll need to do many more patients, and follow them for about 10 years.”

The team now takes only those patients with the smallest, least aggressive tumors. These patients also boast excellent sexual and continence functions. “We want those who have the most to gain from preserving these abilities,” D’Amico notes. “Such selectivity gives us an advantage over those who treat patients no matter what stage of cancer they’re in, or how sick they are.”

With surgery, incidences of impotence and incontinence are higher than most surgeons like to admit. A study published earlier this year of 1,291 men found that 108 of them were incontinent 18 months or more after surgery. A startling 773 (almost 60 percent) were impotent.

With external radiation, rates of impotence are lower and those of incontinence are much lower, but rates of cancer recurrence are higher. Also, 2 to 3 percent of men who undergo external radiation suffer rectal bleeding for indefinite periods.

“For a selected group of patients, we would hope, in years to come, to eliminate incontinence, impotence, and rectal bleeding with the MRI seed method,” D’Amico says.

At present, the Harvard team operates the only MRI machine in the world used for this purpose. That should change soon. D’Amico notes that cancer centers in New York City, San Francisco, and Houston plan to purchase this equipment.

Patients are treated in the sub-basement of Brigham and Women’s Hospital. They lie horizontally inside the hole of what looks like a gigantic white doughnut, stood on its side and split vertically. The 6-foot-high doughnut halves hold magnets that polarize water molecules in the patient’s body. A combination of the magnetic field and timed radio pulses produce superb images of the watery soft tissue in the prostate. Spots of cancer show up as lighter areas in the computer image, and these are marked with red dots.

A plastic grid that is the same as the MRI image sits over the patient’s skin, and long needles are inserted through holes at the positions of the red dots. A computer screen shows the needle as a green line moving to each red dot, like an arrow approaching a bull’s-eye.

Each needle holds tiny titanium seeds full of radioactive iodine. The specialists position anywhere from 80 to 120 of these pellets in the prostate. The radiation destroys DNA in the cancer cells, and the titanium casings remain in the patient’s body for life.

One of the problems with the ultrasound technique involves seeds that get into blood vessels and end up in a lung. “Since we see blood vessels in the MRI image, we can avoid this problem,” D’Amico says.

Steady as a robot

If the needle handler strays from the red dots, an assistant watching real-time computer images of the prostate corrects his aim. However, the human hand is not always steady, so D’Amico and his colleagues plan to substitute a computer-guided robotic arm. “It would complement – not replace – the surgeon,” he notes. A prototype, already built, is being tested in human models. It could be ready for use with patients in the next two years.

Also in planning is a fiber-optic device that would map the prostate with a beam of infrared light. An ultra-thin catheter run over the surface of – or inserted into – the prostate would generate optical images that enable surgeons to see details as tiny as a single cell, a thousand times the resolution of MRI images.

“Optical imaging is the next step toward more precise location of cancers, particularly small ones,” D’Amico says. “MRI limits you to structures you can see by eye; optical imaging gives you the kind of detail you can see in a microscope.”

Working with colleagues at the Massachusetts Institute of Technology, where he earned a Ph.D. in physics before going on to get his M.D. degree, D’Amico is now identifying single cells in human prostate tissue removed by surgery. Next year, he wants to build an optical device that will enable his team to examine prostates still in place.

Even that kind of detail won’t satisfy D’Amico. He expects someday to view the molecules that make up cells; the actual DNA that contains instructions for what other molecules do in a cell. After that, he wants to see the genes themselves. How do genes in a cancer cell differ from those in a healthy cell? The answer is over the horizon now, but he thinks it may be visible in the future.

“The direction we’re going in prostate cancer is to find it at earlier stages,” D’Amico notes. “This has been made possible by measuring PSA (a protein secreted by prostate cancer cells and detectable with a blood test). PSA has revolutionized our ability to detect cancer in stages when it can be treated with less invasive methods like brachytherapy.” Presumably, earlier detection and more precise treatment will save the lives of many men who now die at the rate of about 40,000 a year from prostate cancer. And the goal is not only to save their lives but to give those lives a better quality.