Through the 1990s, production of accelerators for medical treatment went commercial. The Belgian company Ion Beam Applications entered the market with an off-the-shelf prototype at Mass General in 1994. It cost far more than Mass General’s $46 million tab, but IBA swallowed the expense, gaining a foothold in the market, credibility and, soon enough, rising share value.
The popularity and cost of protons blindsided the federal government. Medicare in 2000 allowed proton treatment, on a case-by-case basis, for “conditions of possible benefit” — usually prostate cancer — never suspecting the number of treatment centers would grow. From 2006 to 2009, the number of beneficiaries doubled, and Medicare’s annual tab reached $27 million. As of March 2013, more than 105,743 patients have been treated around the world with protons — 17,829 of them at Loma Linda alone, according to the Particle Therapy Cooperative Group, which tracks usage.
As patients and revenues improved, so did competing technology and data on how patients fared in the years after treatment. Conventional radiation with photons gave way to intensity-modulated radiation therapy, or IMRT, in which more precise beams of photons could be moved dozens or hundreds of times with varying intensities, attacking tumors in three dimensions with safer high doses.
As data on proton treatments continued to dribble in, it was hard for Zietman to accept the implications of his own studies, which tracked patients’ progress. Their quality of life had not improved. They had not escaped the gastrointestinal issues, rectal bleeding, incontinence and impotence associated with other forms of radiation such as IMRT. One case still haunts Zietman — a patient with bleeding that couldn’t be stopped, the complications cascading until the patient was dependent on transfusions. The realization that something was amiss had been in the background. “I had a creeping sense of concern and despair,” he says.
Eventually, “the data was staring me in the face: Protons weren’t any better. They were being sold as if they had zero side effects.”
But they did have side effects.
In June 2011, a study of radiation therapy for prostate cancer found that patients receiving conventional radiation experienced fewer gastrointestinal problems than a similar group exposed to proton beams. In 2012, a separate study of 1,600 patients from 2002 through 2007 found that men treated for prostate cancer with proton beam therapy experienced more bowel problems, such as bleeding and blockages, than those treated with the more common IMRT. “We did not find a significant benefit in patient outcomes,” its lead author, University of North Carolina radiation oncologist Ronald Chen, told Discover. “Our results call for additional comparative effectiveness research.”
Zietman realized an experiment was the only way to settle the matter. In 2011, he helped lead the first randomized trial comparing IMRT with equivalent doses of protons. The first results aren’t expected for several years.
The industry, its backers and some clinicians say the trial is a waste of time and money — and unethical. Goitein, the physicist who helped bring 3-D to proton therapy, challenges the wisdom of subjecting half of the study’s 400 test subjects to IMRT instead of what he is convinced is a better therapy.
“Most people who do proton therapy believe physician and biological arguments are compelling enough to make it impossible to say to a patient with a straight face, ‘I think it is a toss-up,’ ” Goitein says. “People who advocate trials are ignoring the physical evidence.”
Zietman counters that good intentions and business imperatives sometimes blind scientists to the truth about risks and effectiveness. “It’s amazing how many people drank the Kool-Aid,” he says. “When you are enthralled to an investment company or have opened a center at enormous expense and must treat hundreds of patients, you kind of have to believe. You become an evangelist for a cause.”