Translational Genomics Research Institute (TGen), Mayo Clinic in Arizona, The Cancer Research UK, and Biodesign Institute at Arizona State University contributed to a study that suggests that the test called TARDIS, Targeted Digital Sequencing, is as much as 100 times more sensitive than other blood-based cancer monitoring tests.
The TARDIS, a “liquid biopsy” specifically identifies and quantified small fragments of cancer DNA circulating in the bloodstream of the patient, known as circulating tumor DNA (ctDNA). The study stated that TARDIS detected ctDNA in as low as 2 parts per 100,000 in the patient blood.
“By precisely measuring ctDNA, this test can detect the presence of residual cancer, and form physicians if cancer has been successfully eradicated by treatment,” said Muhammad Murtaza, M.B.B.S., Ph.D., Assistant Professor and Co-Director of TGen’s Center for Noninvasive Diagnostics.
“This has enormous implications for women with breast cancer. This test could help plan the timing and extent of surgical resection and radiation therapy after patients have received pre-operative therapy,” said Dr. Barbara A. Pockaj, M.D., a surgical oncologist who specializes in breast and melanoma cancer patients at Mayo Clinic in Arizona and is one of the senior authors in the study.
Liquid biopsies, unlike the traditional biopsies, use a simple blood draw, and so could safely be performed repeatedly, as often as needed, to detect a patient’s disease status.
“TARDIS is a game changer for response monitoring and residual disease detection in early breast cancer treated with curative intent. The sensitivity and specificity of patient-specific TARDIS panels will allow us to tell very early, probably after one cycle, whether neo-adjuvant (before surgery) therapy is working and will also enable detecting micro-metastatic disease and risk-adapted treatment after completing neo-adjuvant therapy,” said Dr. Caldas, a Senior Group Leader at the Cancer Research UK Cambridge Institute, and one of the contributing authors in the study.
After a number of trials, it may happen someday that TARDIS can be used routinely for monitoring patients during cancer treatment, and discovering when patients are essentially cured and cancer free.
“The results of these tests could be used to individualize cancer therapy avoiding overtreatment in some cases and under treatment in other,” Dr. Murtaza said. “The central premise of our research is whether we can develop a blood test that can tell patients who have been completely cured apart from patients who have residual disease. We wondered whether we can see clearance of ctDNA from blood in patients who respond well to pre-surgical treatment.”
“Fragments of ctDNA shed into blood by tumors carry the same cancer-specific mutations as the tumor cells, giving us a way to measure the tumor,” said Bradson McDonald, a computational scientist in Dr. Murtaza’s lab, and the first author of the study.
“The problem is that ctDNA levels can be so low in non-metastatic cancer patients, there are often just not enough fragments of ctDNA in a single blood sample to reliably detect any one mutation. This is especially true in the residual disease setting, when there is no obvious tumor left during or after treatment,” McDonald said. “So, instead of focussing on a single mutation from every patient, we decided to integrate the results of dozens of mutations from each patient.”
The results from the study suggested that personalized ctDNA analysis, using TARDIS, can be quite helpful in identifying patients with a curative response following pre-surgical drug therapy.
“Together with imaging and tissue-based predictive biomarkers, ctDNA is rapidly becoming a useful diagnostic test to determine individualised decisions about additional treatment,” Dr. Murtaza said.
Dr. Pockaj mentioned: “We are excited that TARDIS has the potential to really individualize clinical management of patients with non-metastatic cancer.”
Thomas Slavin, M.D., Assistant Clinical Professor at City of Hope National Medical Center, and a contributing author of the study, noted that “reliably identifying, often multiple, circulating tumor mutations in the plasma of patients with non-metastatic breast cancer also holds promise that ctDNA may one day be a great tool for every breast cancer detection.”
TGen is currently looking forward to work with the best partners in order to scale TARDIS and make it broadly available to benefit patients in need.
“This data represents an exciting strategy to improve the sensitivities of liquid biopsies, which have been challenging for breast cancer,” said Karen Anderson, M.D., Ph.D., a researcher at the Biodesign Institute, a medical oncologist at Mayo Clinic in Arizona, and one of the contributing authors in the study. “This work represents highly collaborative efforts across multiple institutions, and with the generosity and foresight of our patients who have contributed to this study.”
The samples from the patients for this study were collected at Mayo Clinic, at Addenbrookes Hospital at the University of Cambridge, and at City of Hope.
The National Cancer Institute, the V Foundation for Cancer Research, The Ben and Catherine Ivy Foundation, Cancer Research UK, Mayo Clinic Center for Individualized Medicine, Science Foundation Arizona, SmartPractice, TGen and City of Hope are some of the names that have funded the research.