Radiosensitivity biomarker may aid in RT decisions for breast cancer

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Researchers have developed a radiosensitivity predictive assay and validated a molecular signature that could lead to improved radiation therapy (RT) decision-making in the treatment of breast cancer patients, according to an article published in Clinical Cancer Research.

The radiosensitivity molecular signature (RSI) used in the study had previously been validated for rectal, esophageal and head and neck cancers, but the current study focused solely on the benefits of the approach in the treatment of breast cancer, according to study authors Javier F. Torres-Roca, MD, of Moffitt Cancer Center in Tampa, Fla., and colleagues.

“The clinical impact of a successful assay would be broad and significant since [RT] is the single most common therapeutic agent in clinical oncology,” wrote the authors. “Approximately 60 percent of all cancer patients receive RT at some point during their treatment.”

Based on gene expressions for 10 specific genes and a linear regression algorithm, the RSI was developed in 48 cancer cell lines using a systems-biology strategy focused on identifying biomarkers for cellular radiosensitivity.

To validate the RSI’s benefit, Torres-Roca and colleagues tested it in 503 RT-treated patients at two facilities: Karolinska University Hospital in Stockholm, and Erasmus Medical Center in Rotterdam, Netherlands.

Results from the Karolinska dataset showed that patients predicted to be radiosensitive had improved five year relapse-free survival compare with radioresistant patients, with survival rates of 95 percent and 75 percent, respectively. Likewise, RT-treated patients in the Erasmus dataset who were radiosensitive also had improved five year distant-metastasis-free survival when compared with radioresistant patients. In both datasets, no difference was observed in patients treated without RT.

Multivariable analysis demonstrated that RSI is the strongest variable in RT-treated patients.

When factoring in previous research, the RSI becomes the “most extensively validated molecular signature in radiation oncology,” according to the authors. The technology has now been shown to have been successfully transitioned from cell lines to patients in multiple disease sites, a fact that Torres-Roca and colleagues said suggests the biological basis of cellular radiosensitivity is conserved between cell lines and patients, and also across epithelial tumors.

"Developing a radiosensitivity predictive assay has been a goal of radiation biology for decades," Torres-Roca, MD, said in a release. "This effort supports the emphasis on personalized medicine, where the goal is to use molecular signatures to guide therapeutic decisions."