New study shows lung cancer proton therapy may reduce risk of heart disease

Research suggests proton therapy for lung cancer lowers risk of heart disease


When treating lung cancer with radiation therapy, there is a significant concern that the treatment dose will expose the heart to excess radiation. One way to avoid this unnecessary radiation is by using proton therapy, a more precise form of radiation therapy compared to traditional radiation therapy (x-rays/photons).

Researchers now say there is a link between lung cancer proton therapy and a reduced risk of certain heart diseases, including mini-strokes and heart attacks.


The findings of the study from Penn Medicine were first presented at the American Society for Radiation Oncology’s (ASTRO) annual meeting in October 2020 by Timothy Kegelman, MD, PhD, chief resident in the department of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania.

Kegelman and his team of researchers followed more than 200 patients who underwent either proton therapy or traditional radiation therapy for locally advanced non-small cell lung cancer. The retrospective trial specifically looked at the percentage of patients who experienced cardiac side effects, including transient ischemic attacks (mini-strokes), myocardial infarctions (heart attacks), atrial fibrillation, coronary artery disease, heart failure, and stroke.


With a median follow up period of just under two a half years, the study found a significant difference in the incidence of mini-strokes. Just 1.1 percent of patients treated with proton therapy experienced a mini-stroke, compared to 8.2 percent of patients treated with traditional radiation therapy.

“This shows us another potential benefit of proton therapy for lung cancer patients,” Kegelman said. “We know proton has the ability to minimize radiation doses to surrounding organs like the heart. And these latest findings suggest that sparing correlates with fewer cardiac problems compared to conventional therapy.”

The authors of the study also pointed out a reduction in the incidence of heart attacks for proton therapy patients; although they were careful to note it’s not a statistically significant difference. Nine percent of traditional radiation therapy patients experienced heart attacks during the follow up period, compared to just 2.3 percent for the proton therapy group.

Researchers say there was no difference in the number of cases of atrial fibrillation, coronary artery disease, heart failure, or stroke.


The Penn Medicine study is the first of its kind to suggest proton therapy is more beneficial than intensity modulated radiotherapy (IMRT), a widely-used form of traditional x-ray radiation therapy, when it comes to reducing the effects of radiation to the heart.

It provides a promising starting point on which researchers can build. Kegelman and his team  continue to compare the effects of protons and photons on cardiac events by looking more closely at the severity of heart-related side effects, as well as the radiation dose to specific parts of the heart.

“While these findings are promising and add to growing evidence, more research will help us better determine and understand how treating with protons may reduce cardiac event risk,” noted Kegelman.

Much of that research is expected to come from a specific prospective trial. A large, international phase III clinical trial comparing proton therapy to photon therapy for lung cancer patients began in 2014. The authors of the Penn Medicine study expect this trial to show that protons reduce heart-related disease and death, which will translate into a higher cure rate.

Ultimately, the findings of this study, along with other research such as the phase III trial, will allow radiation oncologists to better understand how to maximize radiation doses to lung cancer cells, while minimizing the risk of exposing the heart to unnecessary radiation.


In addition to the heart-related benefits found in the Penn Medicine study, there are several other advantages for lung cancer proton therapy over traditional radiation therapy. Patients often experience fewer, if not none, of the common side effects associated with radiation therapy for lung cancer, including nausea, shortness of breath, fatigue, and weight loss.

Not only are these patient-reported outcomes more desirable, studies also show significant clinical benefits including:

  • 35% relative increase in overall survival for Stage II & III lung cancer.1
  • 56% relative reduction in incidences of serious (grade 3) pain with swallowing (esophagitis).2
  • Up to 4-week reduction in treatment time for select cases.3

Research shows that this reduction in side effects is accompanied by similar levels of efficacy. In other words, compared to traditional radiation therapy, lung cancer proton therapy is just as effective at destroying cancer cells, but provides patients with considerably more benefits that can improve their quality of life.


Sources & Studies

  1. Higgins KA, O’Connell K, Liu Y, et al. National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017;97(1):128-137. doi:10.1016/j.ijrobp.2016.10.001
  2. Chang JY, Verma V, Li M, et al. Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study [published correction appears in JAMA Oncol. 2017 Sep 1;3(9):1286] [published correction appears in JAMA Oncol. 2017 Dec 1;3(12):1742]. JAMA Oncol. 2017;3(8):e172032. doi:10.1001/jamaoncol.2017.2032
  3. Bush DA, Cheek G, Zaheer S, et al. High-dose hypofractionated proton beam radiation therapy is safe and effective for central and peripheral early-stage non-small cell lung cancer: results of a 12-year experience at Loma Linda University Medical Center. Int J Radiat Oncol Biol Phys. 2013;86(5):964-968. doi:10.1016/j.ijrobp.2013.05.002