UFPTI explores hypofractionation

Proton therapy clinicians are exploring the benefits and risks of treating slow-growing cancers with higher individual proton doses over a more accelerated time frame, cutting the total treatment period by a third or more.

“If the same tumor control goal can be accomplished safely in a shorter time with fewer proton fractions, it could have a huge benefit on health outcomes,” says Nancy Mendenhall, M.D., Clinical Director of the University of Florida Proton Therapy Institute. “And it could reduce the cost of treating some of the common cancers.”

Practitioners at the Jacksonville, Florida facility are in the midst of their second clinical trial evaluating the use of fewer, larger-sized fractions of the total proton dose, called hypofractionated proton therapy, to treat prostate cancer. UF Proton Therapy Institute is also conducting a clinical trial to assess hypofractionated proton treatments for lung tumors.

For some cancers, hypofractionation may allow clinicians to more fully optimize the power of protons, Mendenhall says. “It’s possible that certain types of cancers will be better controlled with hypofractionated proton therapy as compared with standard fractionated proton therapy,” says Mendenhall.

Other clinical trials of hypofractionated proton therapy are under way at ProCure Proton Therapy Centers in Oklahoma City, Oklahoma, and in Warrenville, Illinois. Those trials, overseen by the nonprofit Proton Collaborative Group, target prostate cancer.

And the Roberts Proton Therapy Center at the University of Pennsylvania’s Abramson Cancer Center in Philadelphia, Pennsylvania, is conducting a clinical trial to evaluate breast cancer treatments using hypofractionated proton doses.

Under conventional proton protocols, radiation oncologists may use a total proton dose of 70 to 80 gray-equivalents to treat certain cancers, Mendenhall explains. That total dose is divided into individual treatment doses, called fractions, of 1.8 to 2.0 gray-equivalents apiece. And each fraction is delivered to the patient regularly over an eight- to nine-week period of outpatient care.

“Historically, the whole reason for protracted radiation courses was to minimize the daily dosage to normal tissue and allow for repair of some sub-lethal damage,” says Mendenhall. But higher dose treatments using intensity-modulated radiation therapy demonstrated that hypofractionated photon treatments could be done fairly safely and effectively.

“If hypofractionation can be accomplished safely with x-rays, hypofractionation should be possible with protons — and possibly with less toxicity to healthy tissue since protons, unlike x-rays, have no exit dose and less entrance dose,” she adds.

Clinical application of hypofractionated proton beam therapy for common cancers was first delivered in the 1990s at Loma Linda University Medical Center in Loma Linda, California for early stage lung cancer, Mendenhall recalls.  “Results were excellent,” she says. “Since then, hypofractionated photon therapy has been used in lung, breast, and prostate cancer.  So far, hypofractionated proton therapy has been limited to clinical trials, particularly in prostate cancer.”

Two approaches to hypofractionated proton treatments are currently being pursued, mirroring ongoing photon studies.  The first is “moderate” hypofractionation, which reduces the total treatment period to about four to five-and-a-half weeks, Mendenhall continues, by increasing the fraction size to approximately 2.4 to 3.1 gray-equivalents.  The second is “extreme” hypofractionation, which dials each proton fraction up to a range of 4.7 to 8.0 gray-equivalents, reducing the treatment time to as few as two to two-and-a-half weeks.

Each approach has its advocates, says Mendenhall, and data ultimately will drive clinical application. “There’s a fair amount of emerging data that we’re watching involving extreme hypofractionation that may inform our next steps,” Mendenhall says, pointing to the ProCure clinical trials. And clinicians will need to be alert for unanticipated late-term effects of moderate and extreme hypofractionation, which may not appear for several years after treatment.

Researchers currently speculate that the best tumor candidates for hypofractionated proton treatments are small volume early-stage breast, prostate, and lung cancers.