Zapping cancer cells

In a bunker the size of a football field, a Houston research center will blast tumors with a colossal proton generator.

By Philip Siekman, Fortune

(Fortune Magazine) -- It's called a gantry, and it's downright eerie. An assemblage of steel and cables mounted some 16 feet above the floor of a concrete chamber, it's more than 30 feet in length and width, with ends bracketed by 17-foot steel wheels resting on double rollers. The gantry weighs 190 tons, about as much as a diesel locomotive, but when it begins to revolve there is neither creak nor hum. As it rolls counterclockwise a bit past the halfway point, stops, returns to center, and then rotates the other way, it could be a "Star Wars" battle cruiser maneuvering soundlessly in space.

Yes, we're in Houston - not at NASA, but at the University of Texas's M.D. Anderson Cancer Center. An equipment test is underway at its new proton radiation therapy center. And though the huge gantry is not a warship, it carries a weapon. While more new wonder drugs like Gleevec are still in the pipeline, proton therapy is a proven fighter in the war against cancer.

Oncologists have long known that substituting proton radiation for the X-rays now used to treat about half of all cancer patients would do less harm to normal tissues and organs and more damage to malignant growths. That, says Dr. James Cox, M.D. Anderson's chairman of radiation oncology and medical director of the proton center, would mean more cures.

The problem has long been cost. Both the equipment needed to generate a proton beam and the building in which to house it are extraordinarily expensive. Indeed, by the time the first patient arrives next January, the cost for the new Anderson Center will have mounted to some $130 million, making it probably the most expensive single-treatment medical facility ever built. But in a radical departure from customary practice, it is being paid for not by taxpayers or philanthropists but by private investors.

The science of protont herapy

In case you slept through high school physics, protons exist in the nuclei of atoms and have electrons orbiting them. For radiation therapy, physicists separate positively charged protons from hydrogen atoms by stripping off the negatively charged electrons. Powerful magnets bend the proton stream into a circular path and then control it as the stream is accelerated to near light speed inside either a cyclotron or, as at Anderson, its higher-energy cousin, a synchrotron. The speed of the resulting beam - and thus its energy - is measured in electron volts. The higher the electron voltage, the heavier the punch when the beam hits a tumor in the patient's body. Anderson's system will generate up to 250 million electron volts, enough to reach tumors in all but the most obese patients.

When protons strike a tumor, they have about the same impact on the cancer cells as X-rays. To greatly simplify a complex biophysical action, the energy from both disrupts bonds of molecules in the cell, leading to breaks in its DNA strands. If the cell cannot repair itself, it dies, or at least loses its ability to replicate.

The difference in the effectiveness of protons and X-rays lies in what takes place before and after radiation reaches the tumor. X-rays release much of their energy quickly after penetrating the skin, disrupting the molecules of healthy tissue and organs.

Protons can be managed so that they release most of their energy only when they get to their target. Also, unlike X-rays, which pass completely through the body - in one side, out the other - protons go no farther than the tumor, sparing everything behind it. More energy reaches the cancerous cells, so more damage is wrought by each burst of radiation. Side effects caused by the irradiation of normal tissue in front of and behind the tumor are, while not eliminated, greatly reduced.

Proton therapy is most effective when directed at single, well-defined tumors, especially ones close to sensitive nerves and organs, such as those growing in the lungs or prostate. Anderson estimates that the therapy can be used on 75 percent of those suffering from prostate cancer and that it will greatly reduce, and possibly eliminate, the incontinence and impotence that frequently follow other forms of treatment. (If a cancer has metastasized, the protection that proton therapy offers healthy cells is muted. When a large area must be radiated, such as in treating breast cancer, or when the whole body is radiated, as in leukemia and most cases of lymphoma, X-rays remain the preferred treatment.)

The high cost of fighting cancer

For decades U.S. and foreign universities have occasionally used their research cyclotrons and synchrotrons to treat cancer patients with protons. Harvard, for example, treated 9,116 patients before it shut down its aging equipment in 2002.

Because their equipment is limited in power and flexibility, universities use it mostly to irradiate shallow tumors near the spine or brain, such as melanomas behind the eye, or to treat cancer in children, where there is always a risk that radiation damage to healthy cells will inhibit growth or lead to radiation-induced tumors decades later.

In 1990, California's Loma Linda University, an affiliate of the Seventh-day Adventist Church, opened the first hospital-based proton treatment center in the U.S. with funding from the church and the National Cancer Institute and a synchrotron built by the Fermi National Accelerator Laboratory. Many radiologists and oncologists initially questioned the therapy's cost and efficacy. During the 1990s, however, Loma Linda increased the number of patients it could treat and began reporting good results with reduced side effects.

Almost as important, it convinced Medicare and other insurers that they should cover the treatments. Currently Medicare reimburses clinics or patients $850 for the most complex proton radiation session, vs. $308 for the most expensive X-ray session. But the extra cost is offset because fewer expenses are incurred treating side effects, and the number of treatment sessions can be reduced. Anderson's Jim Cox estimates that the bill for proton treatment of a lung- or colon-cancer patient will be in the $60,000 to $75,000 range - about the same as conventional treatments.

By the late '90s many radiation oncologists had begun to recognize proton therapy's benefits. Massachusetts General, the teaching hospital for Harvard's medical school, decided to go ahead with the second U.S. hospital-based proton-treatment facility. The University of Indiana said it would build its own center using an existing cyclotron. (Both are now in operation.)

Oncologists at Anderson had also concluded that proton radiation would be a useful tool. However, Anderson was in the midst of a $700 million expansion of research and patient facilities; despite the advances, Dr. John Mendelsohn, Anderson's president, knew that the Texas University regents weren't about to dig up another $100 million or so for a single new therapy.

After the collapse of an agreement with Tenet Healthcare (Charts), the New York Stock Exchange-listed hospital operator, Mendelsohn went looking for another partner and found two: Styles & Co., a family-owned hospital manager, and Sanders Morris Harris, an investment bank. Working together, the two Houston firms put together a $30 million limited partnership that includes a group of individuals and two pension funds.

General Electric (Charts) is also an investor, but the big player is Hitachi (Charts), which is providing, installing, and from here on out maintaining all the proton equipment. Eager to get into what looks like an expanding global market that has been dominated by a Belgian firm, Ion Beam Applications, the Japanese are financing their entire share of the project.

Besides expensive equipment, machinery and computer systems, there's the building itself. From the street it looks like a handsome if modest-sized one-story structure. That's just the conning tower. The synchrotron and treatment cells are underground, where they occupy a concrete bunker the size of a football field. To shield people inside and out from a spray of neutrons that can be released when protons collide with anything, the exterior walls are three feet thick, and those around the treatment cells are a solid eight feet. Enough concrete was poured at the facility to build a 20-story office building.

Seed money

When treatments begin at Anderson in 2006, its synchrotron will create a proton beam that will, as needed, be magnetically diverted from a main transport line into one of four patient-treatment rooms or a fifth area used for research. In one patient area, reserved for such cancers as ocular tumors, the patient will sit in a special chair with his head held in a frame.

Each of three other treatment cells will contain one of those huge gantries, hidden from the view of anxious patients. Each gantry bears a nozzle that will shape the beam of protons aimed into the patient lying within its arc and constrained by a foam mattress molded to his shape.

During treatment sessions, technicians working remotely from behind thick walls will maneuver the supine patient into position by minutely adjusting the bed in six directions. That maneuverability, coupled with precise computer control of the gantry and beam, will enable them to home in on a tumor with an accuracy of better than plus or minus one spherical millimeter - about the diameter of a pencil dot.

While getting everything in place and the patient positioned could take up to half an hour, the actual blast of protons will last only 30 to 60 seconds. Anderson should have all its treatment areas operating by mid-2006, but it will be several years until the center has refined all the processes and can move enough patients through what will be 16-hour days to reach its full capacity of 3,500 a year.

Proton therapy is gaining more and more support from oncologists. Soon after Anderson gets operating, the University of Florida will open its proton facility, which was financed with public money and philanthropic contributions. Still more centers would be started if money could be found.

There is always the risk that the volume of patients planned for won't materialize or that researchers might discover a pill that cures cancer or develop a less expensive radiation treatment. But the Houston partners, who say their investors will have their money back and then some by about 2011, aren't concerned. They point out that cancer is not one disease but dozens or hundreds, making a single cure or treatment unlikely.

Dr. Cox believes that as cancer patients and their physicians begin to understand the benefits of proton radiation, he might have more people who want to come to his center than he will be able to treat. He says, "The investors worry about not having enough patients. I worry about having too many."  Top of page

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