ESTRO 38: REQUITE Project Finds Predictive Biomarkers for Late Radiotherapy Toxicity
The latest results from the REQUITE project, which aimed to discover what makes patients more likely to experience adverse effects after radiotherapy, have shown that a combination of biologic markers and certain genetic changes can predict radiation sensitivity. In addition, the international team of researchers in the project found further evidence to support an earlier finding (in a smaller group of patients with breast cancer) that the time of day when radiotherapy is given can affect whether patients with particular gene variants suffer from adverse side effects. These findings were presented by Talbot et al at ESTRO 38, the annual congress of the European Society for Radiotherapy & Oncology (ESTRO) (Abstract OC-0647).
First author Chris Talbot, PhD, senior lecturer at the University of Leicester, told conference attendees that findings could help doctors to assess which patients were most likely to suffer from side effects of radiotherapy and tailor treatment methods to minimize them.
“We know that patients vary in the way they respond to radiation treatment. Approximately 5% are sensitive to [radiotherapy] and at risk of suffering side effects, but we don’t have a reliable way of identifying these patients…. So radiation doses for all patients are currently limited by the risk of side effects in the most sensitive patients. This is the largest study to date to assess the use of biomarkers to predict radiotherapy-related toxicity,” he said.
REQUITE Project Details
A total of 4,438 patients at 26 hospitals in 8 countries enrolled in the REQUITE project, which began in 2014 and was completed in September 2018. The patients had breast cancer (n = 2,069), lung cancer (n = 561), or prostate cancer (n = 1,808).
Before receiving radiotherapy, patients completed a short questionnaire and provided a blood sample, which was analyzed for approximately 250,000 single-nucleotide polymorphisms (SNPs) in the complete genetic material of each patient (genome-wide), as well as a similar number of SNPs that are known to be associated with cancer. The researchers also tested for other biomarkers that might predict sensitivity to radiation treatment.
Researchers followed up with the patients until September 2018 to see who suffered short- or long-term adverse side effects. Events included urinary problems or rectal bleeding for patients with prostate cancer, and pain or scar tissue in patients with breast cancer.
Findings
Interim results after 1 year of follow-up had shown that radiation-induced lymphocyte apoptosis (RILA) could predict longer-term side effects, such as urinary problems in men with prostate cancer and worse scar tissue in patients with breast cancer. However, as the researchers expected, the most recent analysis, which was a 2-year follow-up, showed that RILA could not predict which patients would suffer acute adverse side effects—those that occur during or just after radiotherapy—such as the skin burn that occurs in some patients with breast cancer.
The exception was acute breast pain; low RILA predicted which patients would be affected by this in the short term. “This suggests that acute breast pain may be caused by different biologic mechanisms than other radiation-induced side effects,” said Dr. Talbot.
The team also found that people who smoked had lower RILA and, therefore, were likely to be at higher risk of side effects.
Earlier Analysis
Earlier analysis published by Johnson et al in Clinical Oncology of 343 patients with breast cancer from the REQUITE study and 535 patients from another study had found that side effects from radiotherapy were affected by whether patients had a natural preference for the morning or the evening. Patients with variations in the PER3 or NOCT genes, which are associated with having an evening preference, had worse side effects if they received radiotherapy in the morning. The latest analysis of all the REQUITE patients has found that variations in these genes also have the same effect for acute diarrhea in patients with prostate cancer.
“If these findings are confirmed, we could avoid side effects in patients simply by testing for these genes and then advising on the best time of day to be treated,” said Dr. Talbot. “We are currently working on the biologic mechanisms involved, but in patients [with breast cancer], we believe it is due to the timing of the division of skin cells.”
He concluded, “Before these finding can be implemented in the clinic, we need to carry out further research in larger groups of patients and in more countries. Then, we need to do a clinical trial to investigate timing of treatment and to show that this does, indeed, reduce the occurrence of adverse side effects.”
Disclosure: For full disclosures of the study authors, visit estro.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
