Debate over effectiveness of proton therapy versus IMRT therapy continues

One more reason to hope

Lillian Guevara-Castro, Gainesville Sun,
Staff writer
Published: Sunday September 9, 2012 at 6:01 a.m.

University of Florida Proton Therapy Institute
University of Florida Proton Therapy Institute in Jacksonville.
(Courtesy of the UFCollege of Medicine)

Two years ago, Don Denton was having regular blood work done for high blood pressure when the lab measured his PSA (prostate-specific antigen), a protein that is often found in increased amounts in the blood of patients with prostate cancer.

It was trending upward. After a biopsy confirmed he had prostate cancer, he was referred to a urologist who told him that, with surgery, he would have a 65 percent survival rate of more than 10 years and would have quality-of-life issues, including permanent incontinenance and impotence.

"When you're first disagnosed, it's devastating, especially when you don't know much about [prostate cancer]," said Denton, a retired engineer in the mountain hamlet of Townsend, Tenn.

Then Denton heard about the University of Florida's Proton Therapy Institute in Jacksonville, where among the treatments for various forms of cancer is the use of proton therapy, a relatively new form of radiation therapy that uses beams of protons to deliver more targeted, precise doses of radiation to the cancer.

"Proton therapy is the best-kept secret," said Denton, 64. "There are no side effects, and it gets rid of the cancer. They're trying to lower the treatment cost, and the good news is more centers are being developed.

"It will be the treatment option of the future," he said.

UF's Proton Therapy Institute opened in 2006 in Jacksonville. Its medical director, Dr. Nancy Mendenhall, had been a UF College of Medicine faculty member since 1985, and the chair of the Department of Radiation Oncology at UF since 1993, when she decided to step down to help get the Proton Therapy Institute off the ground.

"One of my jobs [as Department of Radiation Oncology chair] was to look ahead and see the future of radiation oncology and determine where best to focus the university's research efforts," Mendenhall said.

Radiation energy causes changes in the cells that injure or destroy them. That's true for both normal cells and cancer cells. The difference between X-rays and protons is that proton therapy deposits much less radiation in the normal tissues that are not being targeted.

As illustration, Mendenhall compares X-rays to a bullet that passes through a person leaving a track of damage. With X-rays, there is an entrance dose, a target dose and an exit dose. As an X-ray passes through the patient, it does most of the damage right under the skin's surface, and by the time it exits, there is less dose. Complications come from radiation that is inadvertently desposited in the normal tissue.

Because doctors can better control where proton therapy releases its highest concentration of energy, proton therapy is believed to affect less healthy tissue and have fewer side effects than traditional radiation therapy.

"With X-rays, Cyberknife, IMRT, or radialtherapy, it's always the case that the majority of the dose is outside the target," Mendenhall said. "With proton therapy, most of the radiation is deposted inside the cancer — the target.

"The key in oncology is getting the radiation dose in the tumor and keeping it out of the normal tissues. Proton therapy takes us a huge step forward in improving that basic dose distribution. It helps us put most of the radition energy in the tumor instead of the normal tissues. We can leverage that damage."

With less toxicity in the normal tissues, doctors can increase the radiation dose to the tumor, which results in higher cure rates.

But the National Cancer Institutes said in an article published in 2009 that "there is concern among members of the medical and research communities that enthusiasm for this promising therapy may be getting ahead of the research."

"Theoretically, proton beams are much more exact than X-rays," Dr. Norman Coleman, associate director of the Radiation Research Program at the National Cancer Institutes, said in the 2009 article. "On the computer screen, the calculations look great, and the enthusiasm is understandable. But is that what's really happening in the patient?"

There is no published evidence to indicate that proton therapy is detrimental to patients, Dr. Coleman said, but "when you have something that is so precise with such sharp edges, you need to make sure that it's also accurate. This requires being certain that the target is hit as planned on the computer, including accounting for the uncertainties in diagnostic imaging, reproducibility in patient setup, and internal organ motion."


Proton therapy costs more than radiation therapy. The equipment is more expensive, and the steps taken to get the patient ready for treatment are also more complicated.

"If we have a smart bullet that will go exactly where we tell it to, we have to be sure we send it to the right place," said Mendenhall. "That means we have a little more work to do to make sure the equipment is accurate. And that translates into a higher cost for proton therapy." Medicare reimbursement rates, based on actual costs, are about one-third more for proton therapy than they are for IMRT (Intensity-Modulated Radiation Therapy).

But the overall cost to patients actually might be reduced if one takes into account the lower to no side effects and higher cure rates, Mendenhall said.

"It may have cost us more for the initial treatment, but it may end up costing less in the long run for that patient, because we have reduced the number of patients with recurrance, and reduced the number of patients with toxicity," she said.

Over the past 20 years, as more patients survive cancer, what has emerged is increasing evidence that even very low doses of radiation cause damage to the brain, heart and lungs and might also cause second cancers, Mendenhall said.

"There was a time when we didn't think that low doses of radiation to normal tissues were too much of a problem, not that we could do anything about it," she said. "And in children, we know from very elegant studies that there is no threshhold for causing injury with low-dose radiation to children's brains. It will cause damage."

From February to April 2011, Denton received proton therapy treatments five times a week, for a total of 39 treatments. After markers were placed in the prostate to indicate where the cancer was located, the actual radiation treatments each lasted about a minute.

Denton said his insurance company initially denied coverage, claiming proton therapy is an experimental treatment. But after the Protone Therapy Institute made a call on his behalf, the insurance company accepted the claim.

Denton's bill for the approximately $152,000 treatment was a deductible of $8,000.

"I think the cost was lower. I don't know what the insurance company actually paid," he said.

Looking at the issue of cost is complicated, Mendenhall said. "You have to look at the course of the disease and the potential for shortening the overall treatment that comes with proton therapy. It has tremendous promise."

Mendenhall said treatments are protracted in an effort to expose normal tissues to as small a daily dose of radiation as possible, and consequently reduce the damage. In 2006, the nine-week course of radiation treatment was reduced to an eight-week course after as-yet unpublished evidence of a reduction in exposure to normal tissue.

"After treating a large number of patients, we had seen such a low complication rate that we made another redution. Now our most popular regiment is 5 1/2 weeks, just a little more than half of the regular IMRT course," Mendenhall said.

Since opening in 2006, the UF Proton Therapy Institute has treated more than 3,000 prostate cancer patients from 49 of the 50 states, and five different continents, Mendenhall said.

"We're getting ready to record our five-year results, and 98 percent of low- to intermediate-risk patients have had no recurrance," she said. "It looks like it's extremely effective."

Like Don Denton, the patients are self-referred.

"They call it a radiation vacation," said Denton, who lived in Jacksonville with his wife, Susie, for two months while he was being treated. There were temporary minor side effects and some initial discomfort, but overall Denton can't say enough about the process. "Our experience was wonderful."

His last treatment was in April 2011 and, after driving the 598 miles home to Tennessee, Denton said he went hiking in the mountains the next morning.

"Just 3 to 5 miles. That's the kind of benefits you get from proton therapy," Denton said. "I was very fortunate."

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