Proton therapy shows promise in early-stage lung cancer patients with IPF: SMC study

Proton beam therapy could offer a new treatment option for lung cancer patients with idiopathic pulmonary fibrosis (IPF), a group that has often been unable to receive conventional radiation therapy due to the high risk of severe lung toxicity, a new study has found.

IPF is a chronic disease of unknown cause in which lung tissue progressively becomes scarred and stiff.

Patients with IPF face a higher risk of developing lung cancer than the general population, but treating their cancer is particularly challenging.

Their already damaged lungs are vulnerable to radiation, raising the risk of severe pulmonary toxicity and rapid deterioration. As previous studies have reported severe lung toxicity in 20 to 50 percent of such patients treated with conventional X-ray radiation therapy, many have forgone treatment altogether.

From left, Professors Pyo Hong-ryull, Noh Jae-myoung, Yang Kyung-mi, and Shin Hyun-ju (Courtesy of SMC)

To address this limitation, a research team led by Professors Pyo Hong-ryull, Noh Jae-myoung, Yang Kyung-mi, and Shin Hyun-ju of the Department of Radiation Oncology at Samsung Medical Center (SMC) investigated proton beam therapy.

Proton therapy can target tumors while substantially reducing radiation exposure to surrounding healthy lung tissue.

The researchers prospectively evaluated the safety and treatment outcomes of proton beam therapy in patients with non-small cell lung cancer (NSCLC) accompanied by IPF.

The findings were recently **published**in Radiotherapy and Oncology, an international journal in the field of radiation oncology, in a study titled "Prospective study of proton beam therapy for non-small cell lung cancer patients with idiopathic pulmonary fibrosis."

The study analyzed 41 patients with NSCLC and IPF treated between June 2020 and August 2023.

The patients had a median age of 70 and were considered a high-risk group, with severely impaired lung function. Their diffusing capacity for carbon monoxide (DLCO) was about 45 percent of the predicted value.

Proton therapy was found to be relatively safe in patients with early-stage lung cancer. Among 32 such patients, only 9.4 percent experienced severe pulmonary toxicity of grade 3 or higher, compared with rates of 20 to 50 percent reported in previous studies of conventional X-ray radiation therapy.

Treatment outcomes were also favorable. For patients with early-stage disease, the one-year overall survival rate was 80.6 percent, while the one-year local tumor control rate for all patients was 93.2 percent.

A patient is prepared for proton beam therapy. (Courtesy of SMC)

The researchers attributed the results to the physical characteristics of proton therapy. Because of the so-called Bragg peak, protons can deliver radiation to tumors while sharply reducing exposure beyond the targeted area compared with X-rays.

The team explained that even low-dose radiation exposure is known to contribute to severe pulmonary toxicity, making this advantage particularly important for IPF patients whose lung function is already compromised.

"Lung cancer accompanied by idiopathic pulmonary fibrosis has long been an area with limited treatment options because treatment itself carries substantial risks," Professor Noh said. "This study provides evidence that proton therapy can offer a potentially curative treatment option with an acceptable safety profile for patients with early-stage disease."

Professor Pyo said radiation therapy has traditionally been a difficult decision for patients with IPF because of the risks involved.

"If treatment strategies are tailored by considering both the stage of lung cancer and the severity of idiopathic pulmonary fibrosis, more patients may be able to receive treatment," he added.

The researchers, however, stressed that proton therapy should still be approached cautiously in patients with stage 3 or more advanced lung cancer.

Among nine patients with stage 3 disease, four, or 44.4 percent, developed severe pulmonary toxicity. The rate rose to 57.1 percent among patients who had both stage 3 lung cancer and severe IPF, classified as GAP stage 2 or 3.

Pulmonary toxicity was also substantially more common among patients who received chemotherapy with radiation therapy, at 50 percent, compared with 6.5 percent among those treated with radiation alone.

For these high-risk patients, the researchers recommended multidisciplinary discussions to consider alternatives such as palliative radiation therapy or chemotherapy alone.

The team plans to enroll additional patients and conduct follow-up studies to further refine individualized treatment criteria that take into account both lung cancer stage and the severity of pulmonary fibrosis.