High doses of stereotactic body radiation therapy (SBRT), particularly to the left atrium of the heart and the superior vena cava, are associated with a small but increased risk of death from noncancer causes in patients with early stage non-small cell lung cancer (NSCLC), according to a presentation at ESTRO 35, the 2016 annual meeting of the European Society for Radiotherapy and Oncology.

“Our results show that even within a few years a radiation dose to the heart is associated with an increased risk of noncancer death for early stage lung cancer patients, and they indicate which regions of the heart possibly play a role,” said Barbara Stam, PhD, from the Netherlands Cancer Institute, in Amsterdam.

“Validation and further investigations into the exact mechanisms and which heart structures are critical are warranted,” Stam said. But patients may benefit from heart-sparing radiotherapy. ”We still need to investigate if heart sparing is possible, what compromises need to be made, and whether it can increase survival. Further research and a wider discussion on heart sparing at the cost of possibly a higher average lung doses is required.”


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This study analyzed data from 565 patients with early stage NSCLC diagnosed between 2006 and 2013 at 5 institutions in Europe and North America who were treated with SBRT. SBRT administers focused radiation beams that minimize exposure to nearby organs.

The researchers calculated the amount of radiation delivered to the heart by creating a template image of the heart with its substructures and mapped the anatomy of each of the 565 patients. This process, called deformable image registration, enabled the researchers to determine minimum, average, and maximum doses for the various parts of the heart.

“Then we determined the association between these dose parameters and noncancer death for each substructure and for each dose parameter,” explained Stam. The relationship between dose to substructures and noncancer death is only relevant if it still exists when other factors related to noncancer death are also taken into account. Therefore, a second statistical analysis that included factors such as age, lung function, and performance status was performed.

After a median follow-up of 28 months, 58% of the patients were still alive. Dose to all substructures of the heart was associated with noncancer death for these patients with early stage NSCLC. The strongest association between noncancer death and SBRT was found with maximum dose to the left atrium and dose to a small area of the superior vena cava. In the left atrium, for every 1 Gy above the average dose of 7.9 Gy, the risk increased by 1.5%; the risk increase for other structures was 1% to 2%.

Heart problems are hypothesized to be responsible for the majority of the deaths in these patients; although, no autopsies were performed and the patients were elderly (average age, 73 years). However, research in breast cancer patients, who have a much longer life expectancy than patients with lung cancer, has shown that radiotherapy can have an adverse effect on the heart.

Stam stated that these findings led her team to begin investigations on how to deliver radiotherapy while sparing these crucial heart structures as much as possible.

Reference

1. Stam B, Peulen H, Guckenberger M, et al. Dose to heart substructures is associated with non-cancer death after SBRT in stage I NSCLC patients. Presentation at: ESTRO 35; April 29-May 3, 2016; Turin, Italy. Abstract OC-0399.