Researchers propose genomically-based model for radiotherapy

por John R. Fischer, Senior Reporter | August 26, 2019
Rad Oncology
Researchers have proposed a
genomically-based model for personalizing
radiation doses delivered to cancer patients
Researchers at the Moffitt Cancer Center have proposed the development of what they claim would be the first genomically-based model for personalizing radiation oncology treatment for individual patients.

Naming their approach GARD (genomically-adjusted radiation dose), the team has tested it in the treatment of a number of tumors and are currently working to set up a clinical trial to evaluate the ability of the model to determine radiation dose amounts for breast cancer patients.

"Genomically personalized radiation oncology is critical to improve treatment outcomes as well as spare normal tissues from radiation therapy," Dr. Kamran Ahmed, an assistant member of the department of radiation oncology at Moffitt Cancer Center, told HCB News. "The results that we've found with GARD indicate that a genomic approach to radiation dose personalization is feasible. Although, there is still work to be done in testing the work in prospective trials our current results across tumor types are encouraging."

While personalized approaches have been developed over the last few decades for targeted drugs that treat particular tumor types with specific mutations or patterns, little has been done to personalize the radiation oncology front, which still commonly relies on a one-size-fits-all approach. The use of GARD has shown lower values for tumors that are resistant to radiation and higher ones for those sensitive to it.

Using a radiation sensitivity index (RSI) they built to predict the radiation sensitivity of tumors based on the patterns of 10 genes, the team combined it with a model used to determine the effect of radiation dose on tumor and normal tissues. The aim was to enable the RSI to more accurately determine the appropriate radiation dose for individual patients.

They then tested the model on two separate groups of 58 and 55 triple-negative breast cancer patients who either underwent radiation therapy in Europe, or the Total Cancer Care program at Moffitt, respectively. The outcomes were associated with the risk of locally recurring breast cancer.

They also calculated individualized radiation dose for each breast cancer patient in the group at Moffitt, coming back with a range of 30 to 76 Gy as the range for biological radiation dose in triple negative breast cancer. The finding demonstrates that the current standard of delivering 60 Gy to all patients could be an overdose in a significant number.

The team hopes the clinical trial at Moffitt will open up more research opportunities, with the model personalizing radiation therapy for patients, while minimizing the risks of additional radiation exposure.

"Breast cancer affects one in eight women and is one of the most common cancer types treated with adjuvant radiotherapy," said Ahmed, lead author of the study. "We have previously published our experience utilizing GARD in lung, pancreatic, and glioblastoma tumor types. There are currently plans to test the GARD metric prospectively in a number of tumor types."

The study was funded by the Morton Plant Mease Foundation.

The findings were published in EBioMedicine.

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