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Cancer Screening

“Liquid Biopsy” May Help to Personalize Treatment for Patients with Cancer

Liquid biopsy is a noninvasive blood test that can help identify cancerous cells or biomarkers, such as gene mutations that may respond to targeted therapies.
May 2018 Cancer Biomarkers and Molecular Testing
Caroline Helwick

A blood sample known as “liquid biopsy” is a new type of blood test that could soon be all it takes for patients to receive truly personalized cancer treatment. Liquid biopsies are non-invasive testing that can help to identify cancerous cells or biomarkers, such as gene mutations (changes), that may respond to targeted therapies.

Liquid biopsies avoid the invasive, risky, and costly tissue biopsies that currently virtually all patients with cancer undergo to diagnose cancer. Liquid biopsies involve analyzing a simple blood draw to identify tumor information in the blood, including biomarkers or gene mutations associated with specific tumors.

“Detection of tumor-specific mutations in a blood draw is an attractive alternative, especially when tissue biopsies are not feasible,” said Philip C. Mack, PhD, Director of Molecular Pharmacology, University of California Davis Comprehensive Cancer Center, at the 2016 meeting of the American Society of Clinical Oncology. “It is easy to do in any clinic, and avoids biopsy-treated complications,” he said.

Individualized Treatment

Different liquid biopsy tests analyze different kinds of tumor material, such as DNA, RNA, proteins, tiny vesicles called exosomes, and tumor cells. These tests detect such molecules or cells in blood, urine, cerebrospinal fluid, and saliva, which, when found, can reveal much of the same information as tissue biopsies.

“When we think of personalized cancer treatment, we think about individualizing therapy largely based on the characterization of the tumor. The emerging question is whether we can do this non-invasively,” said Ash A. Alizadeh, MD, PhD, Associate Professor of Medicine/Oncology, Stanford Cancer Institute in California, during the 2018 Gastrointestinal Cancers Symposium. Liquid biopsies may be the way to analyze the specific characteristics of a tumor in a non-invasive way, he said.

“There are two types of liquid biopsy that can allow us to look into tumors: circulating tumor cells, which is about cell number, and circulating tumor DNA, which is about the number of mutated molecules,” said Dr. Alizadeh.

Circulating Tumor Cells Tests

The first type of this technology, which has been approved by the FDA for several years now, is the CellSearch Circulating Tumor Cell Test, which identifies circulating tumor cells in the blood of patients with metastatic breast, colorectal, or prostate cancer. Having these cells has been associated with worse outcomes for patients compared with outcomes in patients without these cells. This test can also evaluate the patient’s response to treatment and determine if another treatment is needed.

More recently, circulating tumors cells have been studied for their ability to identify very early colon cancer and even polyps, which can develop into cancer. In a recent study in Taiwan using the CellMax circulating tumor cell assay, the test was 88% accurate in detecting colon cancer and 84% accurate in identifying polyps that could develop into cancer.

“The study demonstrated high accuracy for the detection of colorectal cancer using a novel circulating tumor cell assay that can pick up as little as 1 circulating tumor cell in 1 billion blood cells,” Wen-Sy Tsai, MD, PhD, Assistant Professor, Department of Colon and Rectal Surgery, Linkou Chang Gung Memorial Hospital, in Taipei, Taiwan, said during the 2018 Gastrointestinal Cancers Symposium.

If approved by the FDA, the CellMax test could replace colonoscopy for people unwilling to have this invasive procedure, Dr. Tsai said.

Circulating Tumor DNA

Newer tests are analyzing the blood for circulating tumor DNA, which are fragments of the genetic material of the tumor. The results are used to identify targetable mutations, or biomarkers, and any cancer cells that remain behind after treatment. With a fairly quick turnaround time, this test reveals genetic mutations that can be treated by “targeted therapies.”

Examples of targeted therapies are those developed to target EGFR mutations in the most common type of lung cancer, non–small-cell lung cancer (NSCLC), including Erbitux (cetuximab), Vectibix (panitumumab), Tarceva (erlotinib), or Tagrisso (osimertinib); or those therapies that target BRAF mutations in melanoma, such as Zelboraf (vemurafenib) and Tafinlar (dabrafenib).

Guardant360 is a circulating tumor DNA biopsy assay that is approved in 30 countries and is now under FDA review for approval. In more than 15,000 patients, this test detected gene mutations (or biomarkers) in 85% of patients with breast, lung, or colorectal cancer; and these biomarkers all had an approved therapy that specifically targets those mutations.1The Guardant360 liquid biopsy identified a potential treatment option for 63.6% of the patients in the study.1 To show that these tests can improve cancer outcomes, researchers in Taiwan tracked the treatment outcomes of 193 patients with advanced cancer whose therapy was selected based entirely on the findings from the Guardant360 biopsy.2 The patients who were identified with an “actionable” mutation (mutation that can be treated with an available therapy) responded well to treatment that was matched with their biomarker. In 88% of patients with lung cancer, and in 60% of patients with stomach cancer, those therapies were able to shrink the tumor.2 In 2016, the FDA approved another test—the “cobas EGFR Mutation Test v2—to identify patients with NSCLC linked to a specific type of EGFR mutation, such as exon 19 deletion or exon 21 substitution, who would benefit from the targeted therapy Tarceva, or those with the EGFR T790M mutation, who would benefit from treatment with Tagrisso.

Predicting disease Recurrence

Because liquid biopsies are fairly simple and can be easily repeated, they are already proving useful in detecting tumor changes over time and monitoring patients’ responses to therapy. Tracking a patient’s response to treatment may allow oncologists to adjust treatment for each patient, as needed.

For example, a study of patients with lymphoma, supported by the National Cancer Institute, showed that reductions in circulating tumor DNA levels correlated with good responses to chemotherapy; by contrast, increases in circulating tumor DNA levels were associated with cancer recurrence (returning), even months before the cancer was visible on CT scan.3 Mark J. Roschewski, MD, PhD, one of the study researchers, said, “In our study, the liquid biopsy test was much more sensitive than imaging techniques.”3

Some resistance (lack of response) to treatment can be caused by new mutations that develop over time in some patients with cancer. For example, although most patients with NSCLC initially respond to treatment with a class of drugs called tyrosine kinase inhibitors, in most cases, these drugs eventually stop working. Circulating tumor DNA showed that most patients eventually have the EGFR mutation T70M that causes resistance to treatment, and can now be treated with Tagrisso, which targets that biomarker.

Detecting Minimal Residual Disease

Circulating tumor DNA tests have been used to identify cancer cells that remain in the body after treatment for breast, colon, and lung cancer, in patients who have no other signs of cancer. The test may help to identify patients who need further treatment.

Dr. Alizadeh and his team collected blood from patients with lung cancer, and then examined it 4 months after surgery, radiotherapy, and/or chemotherapy.4 “What struck us was that patients with detectable disease almost invariably recurred and most died, but we saw only 1 recurrence among patients without detectable circulating tumor DNA,” he said.

Dr. Alizadeh said this test could help identify patients who, after their initial treatment, still have what doctors call “minimal residual disease,” which is hard to detect, and those patients may benefit from additional treatment. By contrast, the test could also identify other patients who should avoid treatment.

They saw something similar in patients with stage II or III colon cancer who had surgery but did not have chemotherapy. In blood samples taken 10 days after surgery, disease recurrence and death from cancer were “highly predicted” by the circulating tumor DNA findings. Patients with detectable circulating tumor DNA found on such a blood test had a 12 times increase in cancer recurrence over about 4 years.

“We think that’s remarkable. Outcome is highly predicted by a single assay done 10 days after surgery,” he commented. “Circulating tumor DNA can really be informative.”

The Future?

Although a new report from the American Society of Clinical Oncology and the College of American Pathologists indicates that the evidence is not yet sufficient to use liquid biopsies as a routine screening test, this report projects that given the rapid pace of research focused on liquid biopsies in cancer, we can expect to have this type of biomarker testing available soon for cancer screening in general practice.5

References

1. Zill OA, Mortimer S, Banks KC, et al. Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA. Journal of Clinical Oncology. 2016; 34(15 suppl):Abstract LBA11501.
2. Lee J, Kim ST, Kim KM, et al. Cell-free DNA sequencing-guided therapy in a prospective clinical trial: NEXT-2 trial—a feasibility analysis. Journal of Clinical Oncology. 2016;34(15 suppl):11534.
3. National Cancer Institute. Liquid biopsy: using DNA in blood to detect, track, and treat cancer. Cancer Currents blog. November 8, 2017. www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer.
4. Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discovery. 2017;7(12):1394-1403.
5. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. Journal of Clinical Oncology. 2018 Mar 5. Epub ahead of print.

Key Points

  • Liquid biopsy is a simple blood test that can avoid invasive and costly tissue biopsies
  • Liquid biopsies may be the way to personalized care for patients with cancer
  • These tests can help track a patient’s response to treatment
  • Experts suggest that this new technique may soon be available for general screening to detect cancer
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Last modified: June 26, 2018

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