Many of these studies used liquid biopsy powered by the ddPCR platform to measure circulating tumor DNA (ctDNA) and evaluate ctDNA’s potential as a biomarker for guiding cancer treatment decisions and predicting efficacy.
Detecting and analyzing ctDNA in liquid biopsy samples is gaining recognition as a less invasive method of monitoring disease progression. Researchers are not only testing known mutations in various cancers but are also discovering new mutations that may become important biomarkers. However, wider clinical adoption requires that these ctDNA biomarkers be tested in various cancers and clinical conditions. The studies below highlight efforts to evaluate ctDNA as a potential biomarker vehicle to monitor treatment efficacy, tumor progression, or tumor recurrence.
Mutant BRAF ctDNA is a potential biomarker for advanced melanoma treatment efficacy
There are currently no validated blood-based biomarkers for monitoring treatment efficacy in patients with advanced melanoma. David Polsky, MD, PhD, of NYU Langone Medical Center, and his colleagues are one of the teams that are studying the potential of ctDNA as a biomarker for treatment efficacy in this disease.
The researchers examined ctDNA containing a mutated gene known as BRAF, which is commonly associated with melanoma, in 345 patients undergoing therapy. Using ddPCR technology, Polsky’s team was able to determine that baseline concentration of ctDNA with this mutation negatively correlated with patient survival. Additionally, Polsky found that patients survived longer when their levels of mutated BRAF ctDNA dropped to undetectable levels after four weeks of treatment.
“The reason we could conduct this quantitative analysis was because the ddPCR platform delivers highly accurate and precise measurements of the amount of mutated DNA in a sample,” said Polsky.
ctDNA may not reliably predict progression of melanoma metastases in the brain
Jenny Lee, MD, of Macquarie University in Sydney and the Melanoma Institute Australia, and her colleagues discovered the limitations of using ctDNA to analyze the progression of advanced melanoma when the cancer has metastasized specifically to the brain.
Following up on an earlier study, Lee and her colleagues used ddPCR technology to analyze ctDNA levels in 48 patients with advanced melanoma and brain metastases. All the patients were receiving immune checkpoint therapy. Eight had metastases in their brains but nowhere else. The researchers found that an absence of detectable tumor ctDNA at the start or at an early stage of treatment was a good sign. Specifically, it was associated with superior progression-free survival and overall survival, though this did not apply to responses observed in brain metastases.
As to why that might be the case, Lee noted that the metastases in the brain may have been smaller than those in other parts of the body and that the blood brain barrier could have filtered out ctDNA before it reached the blood.
The team concluded that though ctDNA could be useful for monitoring treatment efficacy in metastatic melanoma, it may not be helpful in detecting brain metastasis or monitoring whether the brain tumors respond to immune checkpoint therapy. This study has potentially important implications because up to half of melanoma patients exhibit brain metastases at some point in their treatment.
Chimeric cell-free DNA can track tumor recurrence in hepatocellular carcinoma
One third of patients with hepatocellular carcinoma (HCC) experience tumor recurrence within the first year following surgery. Detecting and tracking recurrent tumors is essential for physicians to implement therapeutic trials at the right time.
Most patients with HCC have been infected with hepatitis B virus (HBV) and harbor virus host (vh)-chimera DNA, the result of viral DNA integrating into HCC chromosomes. To determine whether vh-chimera DNA could serve as a more sensitive biomarker of HCC progression than currently available tests, Ya-Chun Wang, PhD, of TCM Biotech International Corporation, and his colleagues used ddPCR technology to quantify vh-chimera DNA in plasma samples in patients with HBV-related HCC before and after tumor removal surgery. The researchers detected and quantified vh-chimera DNA before surgery in 44 of 50 patients.
Of the patients whose plasma samples still contained vh-chimera DNA two months after surgery, 82 percent had a tumor recur in the following year. Furthermore, in all but two patients, the vh-chimera DNA matched that of the original clone, indicating that the majority of recurrences come from original HCC cells.
The authors note that the findings support vh-chimera DNA as a biomarker to complement existing ones in detecting the existence of HBV-HCC and in tracking tumor recurrence based on vh-chimera clonalities.
“The ddPCR assay provides an advantage for sensitive quantification of chimera DNA,” Wang said. “In our current practice, the target chimera DNA in blood can be detected as low as one to two copies per reaction.”
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