Biologic, genetic markers predict radiation toxicity in oncology patients
medwireNews: A combination of biologic and genetic markers may be useful to predict which patients will experience toxicity following radiotherapy, suggest data presented at the ESTRO 38 conference in Milan, Italy.
Chris Talbot (University of Leicester, UK), told the ESTRO 38 conference that the findings could help doctors to assess which patients were most sensitive to radiation and either change the radiotherapy dose or plan other ways to avoid the side effects.
The international REQUITE study included 4441 patients with breast (n=2071), prostate (n=1810), or lung (n=560) cancer who were screened for radiation-induced lymphocyte apoptosis (RILA), as well as genome-wide and cancer-specific single-nucleotide polymorphisms (SNPs) prior to receiving radiotherapy.
Talbot and colleagues explain that the RILA assay assesses the percentage of radiation-induced apoptosis in lymphocytes, detected by flow cytometry 48 hours after ex-vivo irradiation of whole blood.
In a press statement, Talbot said: “A low percentage of radiation-induced cell death is associated with worse side effects, although we don’t know why this is. It may show that the state of the immune system on the day of radiotherapy is important.”
Indeed, the researchers found that the degree of RILA was significantly lower among patients with breast fibrosis at 2 years relative to those without fibrosis, at a mean of 12% versus 20%.
In addition, RILA was significantly inversely associated with urinary toxicity at 1 year among the patients with prostate cancer, and with acute breast pain among the breast cancer patients.
By contrast, there were no associations between RILA and other acute toxicities, which the researchers say was expected and “suggests that acute breast pain may be caused by different biological mechanisms than other radiation-induced side effects.”
Talbot and team also further investigated previous findings of a circadian rhythm effect on radiation response, reporting results that have also been published in Clinical Oncology.
They found that, overall, breast patients given radiotherapy in the morning were 60% more likely to experience late toxicity than those treated in the afternoon but genotyping for SNPs in the period circadian regulator 3 (PER3; n=361) and Nocturnin (NOCT) genes suggested the effect was not universal.
Specifically, the 46% of individuals who carried the PER3 4/4 variable number tandem repeat (VNTR) had a 4.8-fold increased risk for toxicity when treated in the morning versus later in the day, whereas no such increase was seen among carriers of the 4/5 or 5/5 VNTRs.
In addition, the 68% of patients with a NOCT A/A variant had a 2.7-fold increased risk for toxicity when treated in the morning, whereas those with the A/G variant had no increased risk.
Conversely, the analysis showed that variants in these genes were associated with a significant 3.5-fold increase in the likelihood for acute diarrhoea among prostate cancer patients treated in the afternoon versus morning.
Talbot said: “This is the largest study to date to assess the use of biomarkers to predict radiotherapy-related toxicity.”
He added: “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. We are currently working on the biological mechanisms involved, but in breast cancer patients we believe it is due to the timing of the division of skin cells.”
Commenting on the data in the press release, the chair of the ESTRO Young Committee Dr Pierfrancesco Franco, from the University of Turin in Italy, said: “This study is an elegant demonstration of how translational research potentially can help oncologists during the clinical decision-making process in order to offer patients a personalised approach that balances the need to control the tumour with the need to minimise the side effects on normal tissues, optimising radiotherapy treatment.”
By Laura Cowen
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