Moffitt Researchers Develop First Genomics-Driven Model for Personalized Radiation Therapy

December 19, 2016

TAMPA, Fla.  – Cancer therapeutics is currently in the era of precision medicine – personalized medicine for individual patients based on their tumor biology. Precision medicine is generally drug-based and little emphasis is placed on radiation therapy that is often assumed to be a “one-size-fits-all” treatment. Moffitt Cancer Center researchers have been instrumental is changing this assumption.  Their study published today in The Lancet Oncology describes a novel genomics model that allows a personalized approach to radiation therapy.

Cancer is a highly heterogeneous disease, and it is now understood that patients can achieve better outcomes if their treatments are tailored to the specific biology of their tumors. However, despite the growth of precision medicine, little progress has been made in personalizing radiation therapy. It is generally assumed that all patients have the same potential to benefit from it.  Moffitt researchers believe that precision medicine also has a role in radiation therapy and that it could be used to improve patient outcomes and reduce toxicities.

Previously, a team of Moffitt researchers, led by Javier F. Torres-Roca, M.D., developed a gene-expresssion based radiosensitivity index (RSI) that predicts tumor sensitivity to radiation therapy based on the expression of 10 specific genes. The RSI accurately predicts clinical outcomes in many different cancer patients treated with radiation, including breast, head and neck, glioblastoma, pancreas, and metastatic colorectal cancer patients.

The researchers used the RSI to develop a genomics model called the genomic-adjusted radiation dose (GARD) that predicts the therapeutic effect for radiotherapy and could guide radiation dosing to match an individual’s tumor radiosensitivity. They demonstrate that GARD values were consistent with the clinical heterogeneity of radiotherapy therapeutic benefit. For example, gliomas and sarcomas are known to be resistant to radiation and had the lowest GARD values, while cervical and head and neck cancers which are known to be sensitive and radiocurable had the highest GARD values.

“There is a high degree of variability among the GARD values for different patients within a single tumor type,” said Torres-Roca. “This suggests that different patients with the same type of tumor have different sensitivities to radiation therapy, further suggesting that the ‘one-size-fits-all’ approach to radiation therapy dose can be further optimized and personalized using tumor genomics

The study confirmed that the GARD model could predict the clinical outcomes of 263 breast cancer patients who were treated with radiation therapy and surgery.  It could also predict the outcomes of additional sets of patients, including glioblastoma, lung, and pancreatic cancer patients.  

This study demonstrates that it is possible to differentiate those patients who may benefit from radiation therapy through genomics approaches. GARD could be used to customize a patient’s radiation dose so that they are receiving the optimum dose to achieve the greatest benefit with the least amount of toxicity. Additionally, GARD could be used in clinical trials to stratify patients based on their radiation sensitivity.

“With multi-disciplinary care becoming standard for the majority of cancer patients, it is critical that precision medicine is expanded beyond drug therapy,” said Louis B. Harrison, M.D, FASTRO, chair of Moffitt’s Radiation Oncology Department. “The GARD model provides the first opportunity to genomically-inform radiation dose and is a safe and feasible approach to precision radiation oncology.”

The was supported by grant funds from the National Institutes of Health (R21CA101355/R21CA135620), U.S. Army Medical Research and Materiel Command, National Functional Genomics Center (170220051), Bankhead-Coley Foundation (09BB-22), the DeBartolo Personalized Medicine Institute and the Merck-Moffitt Research Partnership.

 

About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 47 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, clinical trials, prevention and cancer control. Moffitt is the No. 6 cancer hospital in the nation and has been listed in U.S. News & World Report as one of the “Best Hospitals” for cancer care since 1999. Moffitt devotes more than 2.5 million square feet to research and patient care. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 5,200 team members, Moffitt has an economic impact in the state of $2.1 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter and YouTube

 

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