ASTRO: Unstable chromosomes linked to poor response

Detailed evaluation of a prostate cancer tumor biopsy may predict treatment outcomes for image-guided radiation therapy (IGRT) or surgery for prostate cancer.

That conclusion comes from a study presented on Wednesday at the American Society for Radiation Oncology (ASTRO) annual meeting in Atlanta.

Researchers found that patients who have abnormal levels of breaks at common fragile sites -- areas within chromosomes that are sensitive to DNA damage -- are more likely to have their cancer return, indicating a failure of treatment.

Lead author Dr. Robert Bristow, PhD, from the University of Toronto, and colleagues assessed the outcomes of 280 prostate cancer patients. The group reviewed the DNA characteristics of each patient's tumor using the initial diagnostic core biopsy to determine if gene copy number alterations, or breaks in the common fragile sites, were related to treatment failure.

The subjects were organized into two groups: 126 localized intermediate-risk prostate cancer patients who had received IGRT, and 154 localized intermediate- and high-risk patients who had undergone radical prostatectomy. The researchers discovered a pattern in which the patients who failed treatment had abnormal levels of gene copy number alterations at the common fragile sites. In the IGRT group, those alterations occurred frequently, with 80 patients (64%) having a gene copy number alteration in one or more sites.

The breaks are a sign that the cancer cell has numerous genetic changes, indicating that the cancer is more aggressive and can spread early and outside the prostate gland, Bristow said in an ASTRO statement.

The data suggest that patients are failing treatment due to early metastatic disease, he said. If the results can be validated in larger groups of patients, researchers may be able to develop a test for common fragile site breaks, which could help determine the most appropriate treatment for each patient.

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