1. Goodwin, Peter

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In initial research, men with prostate cancer assessed by standard clinical factors as "intermediate risk" are able to have their risk more accurately assessed as either high or low by use of a new test looking at a 100-locus DNA signature to measure genomic instability along with an index of tumor hypoxia. The research was reported at the European Society for Radiotherapy and Oncology Congress (Abstract O-0139).

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Robert G. Bristow, PhD, MD, a clinician-scientist at Princess Margaret Cancer Center and Professor at the University of Toronto, presented findings showing that among patients who went on to have image-guided radiotherapy, 93 percent of men with low levels of genetic alterations and low hypoxia in their tumor biopsy samples survived five years without recurrence as compared with only 49 percent of men with high levels of both.


As background, he explained that because 30 to 50 percent of prostate cancer patients have disease relapse within two years and have the highest risk of dying from their disease, a different test has been needed to identify them since existing clinical assessments at first diagnosis are not able to do so. "These men can then be offered additional treatments, such as chemotherapy and hormone therapy, that will combat the prostate cancer throughout their body, rather than therapies solely focused on the prostate, in order to improve their chances of survival," he said at an ESTRO news conference.


Array Comparative Genomic Hybridization

For the study, the genomic test used array comparative genomic hybridization (aCGH) to identify genome alterations in the DNA in pre-treatment biopsies from 126 men who had been risk-assessed by having a Gleason score 6 or 7; T1-T2, and PSA level below 20 mg/ml. Patients then had image-guided radiotherapy (IGRT) and were followed for a at a median of 7.8 years. Alterations in copy numbers of specific genes and at so-called fragile sites were detected, and tumors were scored for generalized genomic instability by measuring the percentage of genome altered.


Similar genomic assays were also completed for a comparator cohort of 150 clinically staged patients who went on to have radical prostatectomy.


The researchers measured tumor hypoxia in each patient treated with IGRT by using an Eppendorf pO2 probe and assessed the effect each patient's hypoxia had on 220 genes involved with genomic stability and the translation of DNA repair.


"This is the first report of a test using information derived from biopsy samples that can predict with close to 80 percent accuracy which men are at high or low risk of their prostate cancer recurring," Bristow said.


Asked for his opinion for this article, Adam P. Dicker, MD, PhD, Professor and Chair of the Department of Radiation Oncology at Thomas Jefferson University, said that what makes this test different is that it looks at the tumor microenvironment. Although it has been known for years that tumors are hypoxic and that this is related to genetic instability, which in turn is associated with the aggressiveness of a cancer, it has been difficult for companies to harness this process and market it commercially because hypoxia had to be assessed in vivo.


The next step is to attempt to validate the test over the next two to three years in different and larger groups of patients.


In a news release from the conference, ESTRO Immediate Past President Vincenzo Valentini, MD, a radiation oncologist at Policlinico Universitario A. Gemelli in Rome, said, "This is exciting research, because an accurate and quick test that can predict which men are most likely to need extra treatment to reduce the risk of a recurrence of their cancer is urgently needed. If the utility of this genetic signature is confirmed in further research over the next few years, it could become an important tool for helping us to better target appropriate treatment according to the genetic makeup of each man's tumor."