BARCELONA-The accuracy of radiation targeting using image-guided radiotherapy (IGRT) was significantly associated with overall survival in a study of a large cohort of patients treated with IGRT for their lung and esophageal cancers, reported at the 2018 European Society for Radiotherapy and Oncology (ESTRO 37) annual conference (Abstract OC-0322).
Cardiotoxicity
The key hazard was found to be unintended irradiation of the heart. "We found that patients who have a residual set-up error which moves their heart closer to the high-dose region have a significantly worse overall survival compared to those who have a residual shift away," said first author Corinne Johnson MSc, a physics PhD student at Christie NHS Foundation Trust, University of Manchester and Manchester Cancer Research Centre in the U.K.
Small Movements
The study investigated the relationship between errors in patient positioning (residual shifts) and overall survival in 780 patients with non-small cell lung cancer (NSCLC) and 177 patients with esophageal cancer who were being treated with IGRT under a protocol that routinely corrected positioning errors greater than 5 mm by defining this an "action threshold" to trigger adjustment of patients' positions to bring them back on target. Johnson noted that this threshold had still failed to prevent clinically significant exposure of patients' hearts.
Overall Survival
Residual shifts were strongly associated with overall survival with shifts toward the heart significantly associated with worse survival. The effect was independently confirmed in cohorts of patients with lung and esophageal cancer.
Using the standard protocol, each patient had an image taken before treatment to confirm radiation was being targeted within the accuracy margin of 5 mm. The study then used fine detail of the data from these images to assess how positioning shifts smaller than 5 mm had affected exposure patterns over the course of treatment and whether the beam had shifted slightly closer or slightly further away from each patient's heart.
Patients who had small shifts of the beam toward their hearts were more likely to die than those with similar-sized shifts away from their hearts. Patients with lung cancer who had significant residual shifts towards the heart were around 30 percent more likely to die: a hazard ratio (HR) for overall survival of 1.310. In patients with esophageal cancer, the mortality was greater: around 50 percent (HR=1.531).
"It basically means that with an increased shift [of the beam] towards the heart you have an increased risk of death," Johnson said. "When we studied the 'vector shift' to the heart (the residual shift toward or away from the heart from any direction), we found a hazard ratio of 1.091 for risk of death per millimeter shift towards the heart," said Johnson.
Threshold
At the time of the report, the Manchester clinicians had already reduced the action threshold, she said. "Now for patients [with lung cancer], they perform daily imaging and use a 2 mm action threshold. So they're looking for changes that are greater than 2 mm. We're currently looking at patients treated with this new protocol to see if [a] difference [in survival] still exists or not," Johnson said.
"By imaging patients more frequently and by reducing the threshold on the accuracy of their position, we can help lower the dose of radiation that reaches the heart and avoid unnecessary damage," she noted.
President of ESTRO, Yolande Lievens, MD, Head of the Department of Radiation Oncology at Ghent University Hospital, Belgium, commented that the study had thrown important light on the power of modern radiotherapy methods. "By improving our technical capabilities, we can now see better where we have to irradiate and, therefore, better spare the critical organs and better evaluate what we can do."
But Lievens emphasized that the skills of radiotherapy staff were paramount. "The second thing that is very important is showing that a human factor-where we position the patient-is extremely important for outcome. So it's focusing not only on the technology but on a well-educated group of people who can make a difference for the patient," she said.
"For me it means that, although radiotherapy is often perceived as a very technological discipline, it remains something where the human aspect is extremely important for getting the best for our patients."
The study authors noted that the analysis provided direct evidence in a large patient cohort of the importance of ensuring correct patient positioning when using IGRT and that it highlighted the dose sensitivity of the heart in thoracic radiotherapy with early effects on survival.
Peter M. Goodwin is a contributing writer.
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