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DNA mutations in blood predict response to immunotherapy

A liquid biopsy is a diagnostic tool based on the idea that genetic information about the state of disease can be found in blood or other bodily fluids.

By Amy Wallace

Oct. 2 (UPI) -- Researchers at the University of California San Diego School of Medicine found in a new study that a blood sample containing DNA mutations can predict a cancer patient's response to immunotherapy.

The use of checkpoint inhibitor immunotherapy, which has grown in recent years, is meant to reactivate the immune system to recognize cancer cells. A cancer cell with more mutations stands out compared to normal tissue making it easier for the immune system to recognize and target a tumor.

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A blood sample, or other form of liquid biopsy, is a diagnostic tool based on the idea that genetic information about the state of disease can be found in tumor DNA circulating in the blood.

In the new study, researchers found that patients with a higher number of alterations had longer progression free survival with patients who responded to immunotherapy at two months and had higher numbers of genomic alterations in the blood had an average response lasting nearly two years.

"Checkpoint inhibitor immunotherapy is exciting, but it is currently given to patients with all types of cancer, and most of the time it is not known if it will result in a response," Dr. Razelle Kurzrock, director of the Center for Personalized Cancer Therapy at UC San Diego Moores Cancer Center, said. "Indeed, more than 80 percent of patients with cancer fail to respond to checkpoint inhibitor immunotherapy."

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For the study, published in the October edition of Clinical Cancer Research, researchers analyzed blood-derived DNA from 69 patients with different types of cancer who were treated with checkpoint inhibitors using Guardant360, a liquid biopsy that evaluated up to 70 genes for genomic alterations.

Among participants, 45 percent of patients with more than three genomic alterations in circulating tumor DNA, or ctDNA, found in biopsies responded to checkpoint inhibitor-based immunotherapy.

Patients with fewer alterations had a 15 percent response to checkpoint inhibitor-based immunotherapy.

"Tumors that have the most mutations, and used to be considered the worst tumors, are now considered the best cancers in that they are the most amenable to treatment with immunotherapy," said Kurzrock.

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