Prospective Study in Lung Cancer Patients with IPF: Bragg Peak Spares Healthy Lung Tissue
Proton therapy may offer a new treatment option for lung cancer patients with idiopathic pulmonary fibrosis (IPF), a group that has long been difficult to treat, according to a new study.
IPF is a chronic disease of unknown cause in which the lungs progressively stiffen and scar. People with IPF are at higher risk of developing lung cancer than the general population, yet treating the cancer when it develops is far from simple. This is because their already-damaged lungs often cannot withstand radiation and may deteriorate rapidly, a complication known as severe pulmonary toxicity. With conventional X-ray radiation therapy, 20% to 50% of these patients have been reported to experience severe pulmonary toxicity, and many have forgone treatment altogether as a result.
To overcome these limitations, a research team led by Professors Hongryull Pyo, Jae Myoung Noh, Kyungmi Yang, and Hyun Ju Shin of the Department of Radiation Oncology at Samsung Medical Center turned to proton therapy.
Proton therapy can target the tumor while substantially reducing the radiation dose delivered to the surrounding healthy lung tissue. The team prospectively evaluated the safety and treatment outcomes of proton therapy in patients with non-small cell lung cancer (NSCLC) and IPF. The findings were recently published in Radiotherapy and Oncology (IF 5.3), the official journal of the European Society for Radiotherapy and Oncology (ESTRO).
The researchers analyzed 41 patients with NSCLC and IPF treated between June 2020 and August 2023. The patients' median age was 70. Their diffusing capacity of the lungs for carbon monoxide (DLCO) was only 45% of the normal level, placing them in a high-risk group with already severely impaired lung function. In patients with early-stage lung cancer, proton therapy was delivered safely. Of the 32 early-stage patients, only 9.4% experienced grade 3 or higher severe pulmonary toxicity. That is a marked reduction from the 20% to 50% rate reported with conventional X-ray therapy.
Treatment outcomes were also favorable. The 1-year overall survival rate among early-stage patients was 80.6%, and the 1-year local tumor control rate across all patients reached 93.2%. The researchers attributed these results to the physical properties of protons. Because of a characteristic known as the Bragg peak, protons expose areas outside the tumor to far less radiation than X-rays. Even low-dose radiation exposure is known to be a major cause of severe pulmonary toxicity. For that reason, the researchers explained, this difference can be decisive for IPF patients, whose lung function is already fragile.
"Lung cancer accompanied by idiopathic pulmonary fibrosis has been a blind spot in cancer care because it is so difficult to treat," said Professor Jae Myoung Noh. "This study is meaningful because it provides evidence that early-stage patients can safely pursue curative treatment with proton therapy. It also sets out criteria for which patients require a more cautious approach."
"For patients with IPF, radiation therapy has always been a decision that involved taking on risk," said Professor Hongryull Pyo. "If we develop personalized treatment strategies that consider both cancer stage and IPF severity, more patients will have the chance to receive treatment."
However, the research team emphasized that caution is still warranted for patients with stage III or more advanced lung cancer. Among the nine patients with stage III disease, four (44.4%) developed severe pulmonary toxicity. In patients who had both severe IPF (GAP stage II–III) and stage III lung cancer, the rate rose to 57.1%. Pulmonary toxicity was also more common among patients who received chemotherapy in combination with proton therapy (50%) than among those treated with radiation alone (6.5%). For these patients, the researchers recommend a multidisciplinary discussion to also consider other options, such as palliative radiation therapy or chemotherapy alone.
The team plans to enroll additional patients and conduct follow-up studies to refine personalized treatment criteria that take into account both cancer stage and the severity of pulmonary fibrosis.