Cancer patients treated with proton therapy suffer fewer side effects than those treated with conventional X-ray radiation therapy, according to a recent study published in JAMA Oncology (2020;6(2):237-246). The study-titled "Comparative effectiveness of proton therapy versus photon therapy as part of concurrent chemo-radiotherapy for locally advanced cancer"-included more than 1,500 patients from a database of several cancer types, including brain, lung, and head cancer. None of the patients in the study had metastatic cancer.

Patients treated with a combination of proton therapy and chemotherapy had far fewer emergency room visits and a lower rate of hospitalizations than those who were treated with X-ray radiation and chemotherapy, the study found. There was minimal difference in survival between the proton and conventional groups. After 1 year, survival for the proton group was 83 percent versus 81 percent for the X-ray radiation group.

But there was a massive difference in patient side effects. In the X-ray group, 27.6 percent of patients experienced a severe side effect, compared with 11.5 percent of the proton therapy group. The proton therapy group also suffered fewer side effects despite being older, on average, and having more medical problems than those in conventional group. When the researchers controlled for these factors, they found that the group being treated with proton therapy had their risk of side effects reduced by two-thirds of over the first 90 days of treatment compared to the group receiving X-ray therapy.

Brian Baumann, MD,-the study's first author, Assistant Professor of Radiation Oncology at Washington University, and Adjunct Assistant Professor of Radiation Oncology at University of Pennsylvania-believes that this is the best and largest dataset on proton therapy to date.

"One of the things that stood out to us is the large magnitude of the benefit in favor of proton therapy," he noted. "We expected that there would be a benefit. But the fact that there was a two-thirds reduction in grade 3 toxicities, which are severe toxicities associated with hospitalizations, was more than what we had anticipated."

Proton therapy may reduce side effects because of the way it enters the body. Baumann said that traditional X-ray radiation enters the body through one side and leaves the body through the other, going beyond the target of the therapy and hitting other organs. But proton therapy is more exact, he stated, hitting only the target within the body and allowing minimal radiation to touch other parts of the body.

"I could treat a big tumor in your lung, right in front of your heart, and have the radiation stop just before it hits your heart," Baumann said of proton therapy. "Your heart might get a little or no radiation dose. Whereas if I'm treating that same tumor with X-ray radiation, I'm going to expose much more of the heart to radiation, which could lead to the long-term side effects."

But there's a money problem: proton therapy is expensive and isn't often covered by private insurance companies. Baumann stated that Medicare typically covers proton therapy, but the majority of cancer patients don't have financial access to this treatment. By reducing side effects-and therefore hospital stays-Baumann believes that the cost of proton therapy could be largely offset when compared to the costs associated with traditional X-ray radiation. He hopes that insurance companies will take note that they've demonstrated that proton therapy is just as effective, if not more effective, than conventional radiation and consider covering proton therapy for more cancer patients.

"I don't think the protons are the answer for all patients, even combined chemotherapy and radiation," Baumann stated. "I think these results are very exciting for the future of proton therapy, but research is needed to further elucidate what the role for proton therapy should be. But I think these results are really impressive."

Baumann also hopes that physicians who read this study will develop clinical trials that test higher doses of proton therapy to see if that may improve cure rates. "The results of this research show that that proton therapy can reduce the severe side effects and it often opens up the opportunity for intensifying treatments or giving higher dose radiation than we could have safely given with conventional radiation," he said.

The results of this study may also allow researchers to experiment with combining proton radiation with novel systemic drugs or higher doses of existing systemic drugs to improve the cure rate, Baumann explained.

"The fact that proton therapy is associated with less toxicity means we could intensify treatments and study that in the future. And that's where proton therapy might show itself to be a game changer."

Hal Conick is a contributing writer.