Researchers in Hong Kong report that testing patient blood for DNA from Epstein-Barr virus (EBV) during treatment for nasopharyngeal carcinoma effectively predicts clinical outcome. A biomarker test like this, when perfected, could identify patients whose treatment could be intensified after a month or so of standard therapy as well as those who might benefit from lighter treatment.
The study, presented at the American Association for Cancer Research Molecular Diagnostics in Cancer Therapeutic Development meeting held here September 22-25, highlights the strong link between the virus and this cancer, which is common in Southern China and also develops in Chinese immigrants It further suggests that genetic levels of EBV should be assessed before and during treatment, not just after therapy, as it is now.
"We found that patients with undetectable EBV DNA mid-course through treatment had a greatly reduced risk of developing cancer recurrence two years after treatment, compared with patients with detectable EBV DNA," said the study's senior investigator, Anthony Chan, M.D., director of the Cancer Center at the Chinese University of Hong Kong.
Although EBV is associated with nasopharynx cancer, which develops in the upper area of the throat, a causal relationship hasn't been established, Chan says. Still, cancer cells contain EBV genetic material, which leaks into the bloodstream and can be detected using DNA tests. "That means a larger number of nasopharynx cancer cells in the body would give rise to a larger amount of EBV genetic material in the blood circulation, and so the EBV DNA level is a marker of the extent of cancer."
Researchers know that the amount of EBV DNA found after treatment is a recognized prognostic marker of survival because residual detectable EBV DNA "implies incomplete killing of cancer and thus a poor prognosis," Chan said. The question the researchers investigated is whether there is a way to identify patients with such a viral load before treatment is finished so that more aggressive therapy might be instituted.
"We need to know what to do for those patients with residual EBV. These patients usually do not have clinical evidence of cancer at that point and the residual cancer burden is at a microscopic level. Any extra treatment would be for undetectable cancer, and we need to prove that such treatment has an impact on improving survival," Chan said.
In this study, researchers tested 108 patients with advanced stage cancer for EBV DNA before the start of treatment, after a month of therapy, and then within three months after completion of treatment, and matched these levels to outcomes two-years later. They found that 94 percent of patients had detectable EBV DNA before therapy, but that it became undetectable in 54 percent of patients midway through treatment. The 42 percent of patients who had both low pretreatment and undetectable four-week viral levels constituted a "good risk group" because their recurrence rate was only nine percent.
Conversely, they found that levels detected after four weeks of treatment correlated with detectable post-treatment amounts, with an almost threefold greater risk of cancer recurrence and threefold higher risk of distant metastasis at two years.
"It is possible to test for EBV DNA levels at any time point, so based on further validation studies, we may be able to use biomarker levels at several time points to guide clinical therapy," Chan said.
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