Proton Radiotherapy in Patients with LA-NSCLC May Aid in Reducing Risk of Heart Disease


This study found that found that mini-strokes and heart attacks were significantly less common among patients with locally advanced non-small cell lung cancer who underwent proton therapy versus conventional photon-based radiation therapy.

A retrospective analysis of definitive treatment of locally advanced non-small cell lung cancer (LA-NSCLC) presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting found that mini-strokes were significantly less common among patients who underwent proton therapy versus conventional photon-based radiation therapy.1

Additionally, patients treated with proton therapy in the study also experienced fewer heart attacks.

“This shows us another potential benefit of proton therapy for lung cancer patients,” Timothy Kegelman, MD, PhD, chief resident in the department of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania, said in a press release.2 “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.”

Between December 2008 and November 2016, researchers identified 202 consecutive patients with LA-NSCLC who were treated definitively with chemotherapy and either proton beam radiotherapy or photon radiotherapy. Overall, 98 patients (48.5%) received proton radiotherapy and 104 (51.5%) received photon radiotherapy.

Median follow-up was 29 months (IQR, 16-64 months). Those included in the proton beam radiotherapy cohort were significantly older, with a median age of 69.4 years (IQR 65.3-74.7) compared to 63.0 years (IQR, 56.3-70.4) (P < .001) and had a more extensive smoking history (mean 38.8 vs 30.5 pack-years; P = .021). The median radiotherapy dose received in both groups was 66.6 Gy (range 50.2-74.0 Gy).

Overall, mean heart dose was found to be significantly lower in the proton beam radiotherapy group (mean 6.7 Gy vs 15.2 Gy; P < .001) as were heart V5Gy (22.9% vs 46.1%), V30Gy (12.3% vs 21.6%), and V40Gy (9.1% vs 15.3%) (all P < .001).

Prior to the start of radiotherapy, cardiovascular events were identified in 46.9% of the proton group (87 events in 46 patients) and 31.7% of the photon group (57 events in 33 patients). After radiotherapy, cardiovascular events were recorded in 53.1% of the proton group (108 events in 52 patients) and 47.1% of the photon group (116 events in 49 patients). Of note, the type of radiotherapy received did not correlate with the development of most recorded cardiovascular events.

Post-treatment transient ischemic attack was shown to be less common in those receiving proton beam radiation therapy (1.1 % vs 8.2%; P = .037). Moreover, myocardial infarction was less common in the proton beam radiation therapy cohort (2.3% vs 9.0%), though this was not found to be significant (P = .06). Overall survival at three years was also not significantly different between the groups (38.8% in proton group, 42.1% in photon group; P = .99).

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

Notably, a large prospective, international phase 3 clinical trial is currently investigating the difference between proton therapy and photon therapy in patients with lung cancer and has been underway since 2014. The study investigators anticipate that the study will reveal that protons can reduce cardiac-related morbidity and mortality, which will also translate into a higher cure rate. The trial is expected to complete patient accrual in 2022.


1. Kegelman TP, Jain V, Feigenberg SJ, et al. Cardiac Events Following Radiotherapy for Locally Advanced Non-Small Cell Lung Carcinoma: A Comparison between Photon and Proton Beam Radiotherapy. Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. Abstract #: 1046.

2. Proton Therapy for Lung Cancer May Help Reduce Risk of Heart Diseases [news release]. Philadelphia. Published October 22, 2020. Accessed November 5, 2020.

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