1. Goodwin, Peter M.

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TURIN, Italy-Curative radiotherapy for early stage lung cancer can increase non-cancer deaths according to research from the Netherlands reported at ESTRO 2016-the annual meeting of the European Society for Radiotherapy and Oncology. In a new study, stereotactic body radiation therapy (SBRT) was found to be associated with a small but increased risk of death from causes other than cancer, which the authors attribute to radiation toxicity in upper regions of the heart.

European Society for... - Click to enlarge in new windowEuropean Society for Radiotherapy and Oncology. 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 non-cancer death for patients with early stage lung cancer, and they indicate which regions of the heart possibly play a role," said Barbara Stam, PhD, a postdoctoral fellow in Radiation Oncology, at the Netherlands Cancer Institute and the Antoni van Leeuwenhoek Hospital in Amsterdam, lead author of the investigation of radiation dose to heart substructures and non-cancer death after stereotactic radiotherapy in patients with stage 1 non-small cell lung cancer (NSCLC) (Abstract OC-0399).


Stam said that, since radiation dose to the lungs needs to be maximized to cure early lung cancer, the study data should help clinicians plan this in a more informed way so as to spare upper regions of the heart where collateral irradiation seems to increase mortality the most.


She told Oncology Times that the rationale for the work came from the knowledge that in the very long-term patients treated with radiation for breast cancer or for Hodgkin's disease are at risk for dying early because of heart disease. "So we were wondering if such a relationship also occurs in the short-term," she said.


Because it was not possible to look into heart disease specifically, the investigators decided to look at the relationship between radiation dose and the risk of non-cancer death.


The study analyzed data from 565 patients diagnosed with early NSCLC who were treated with SBRT between 2006-2013 in five institutions in Europe and North America.


To work out how much radiation was delivered to the various heart sub-structures, the researchers created a "template" image of the heart on to which they could map the patient's anatomy. The actual dose for each patient was then added to the template to assess the impact of radiation in different parts of the heart.


The study found non-cancer death and was associated with maximum dose to the left atrium and the superior vena cava and concluded that heart-sparing radiotherapy could potentially improve outcomes.


"Finding if there is a relationship between dose to sub-structures and non-cancer death is only relevant if this still exists when other factors-that are known to be related to non-cancer death-are also taken into account. Therefore, we performed a second statistical analysis, including factors such as age, lung function and performance status," said Stam.


After a median follow-up of 28 months, 58 percent of patients were alive. "We found that dose to all sub-structures of the heart was associated with non-cancer death for this group of patients. Two sub-structures had the strongest association: the maximum dose on the left atrium and the dose to a small area of the superior vena cava. Patients with low doses on the left atrium combined with low doses on the superior vena cava had a higher chance of survival than patients with high doses on the left atrium combined with high doses on the superior vena cava. This association remained after adjustments for the factors included in the second analysis," she said.


The associations between higher radiation doses to the left atrium and the superior vena cava and deaths from causes other than cancer were small but significant: in the left atrium, for every 1Gy above the average dose of 7.9Gy the risk increased by 1.5 percent, while for other structures the risk increased by between 1 and 2 percent.


Fiona McDonald, MD, MA, Consultant Thoracic Clinical Oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in London-who was not involved in the study-told Oncology Times it was always very important to weigh up the safety of radiation against the benefits patients could get.


"No treatment for cancer is completely safe, whether that's systemic therapy or surgery or radiotherapy," she said, adding that, although stereotactic radiotherapy had been associated with low toxicity rates, clinicians were still learning about where it can be harmful. "Because we want to select patients better-maybe those with underlying cardiac disease-for which we need to adjust our risk benefits," she said.


However, McDonald regarded the new data as hypothesis-generating. "We are starting to get more concerned about toxicity to the heart, where maybe previously we focused more on toxicity to the lungs and the esophagus," she said. And she added that analysis of large data sets such as from this new study to make it possible to analyze dose to sub-structures of the heart was important to help design new clinical trials.


When asked about improving radiotherapy to spare the left atrium and superior vena cava-whilst perhaps even increasing dose to the lungs to improve cure rates-she agreed this was possible in theory. "But I don't think we've got enough data to start changing treatment on this at the moment," she said, adding that in this setting of early stage lung cancer and locally advanced disease there was a need to take cardiac doses more seriously.


Peter M. Goodwin is a contributing writer.