Two studies presented at the 2020 American Association for Cancer Research virtual annual meeting confirm the value of different liquid biopsies in the early detection of different types of cancer.
cfDNA Detects More Than 50 Cancer Types
The Circulating Cell-free Genome Atlas (CCGA) study is a multicenter, case-control, observational study of a cell-free (cf)DNA early-detection blood test with longitudinal follow-up of 15,254 participants suspected of cancer who did not yet have a confirmed diagnosis. The planned follow-up is 5 years.
A single blood sample is collected at the point of care. The test is designed to detect the presence or absence of multiple cancer types, including those without screening paradigms, as well as to predict appropriately the tissue of origin to direct the diagnostic workup.
The study was divided into 3 substudies, including discovery (substudy 1), assay refinement (substudy 2), and assay validation (substudy 3).
In CCGA substudy 1, a methylation-based assay was superior to targeted sequencing and whole-genome sequencing approaches and was therefore moved to further development.
Substudy 2 used the methylation assay in patients with confirmed pathologic diagnosis or a high suspicion of cancer. In this substudy, “more than 50 cancers were detected at a specificity of over 99%,” said lead investigator David D. Thiel, MD, Chair, Department of Urology, Mayo Clinic Florida, Jacksonville. “Tissue of origin was predicted in 96% of samples with cancer-like signal. Of those, the tissue of origin localization was accurate in 93% of the cases.”
The results were then evaluated in a subgroup of 303 patients with a high clinical suspicion of cancer. Cancer status was confirmed within 6 weeks after the study blood draw by evaluating a pathologic specimen. The patients with confirmed cancer included participants with multiple types of cancers across all disease stages.
In this subgroup, specificity of the blood test was 100%. “High specificity, although with small sample size, suggests that the false-positive rate was not elevated in individuals with high risk versus the enrolled population,” Dr Thiel said.
In the subgroup with high clinical suspicion, the sensitivity for all cancers was 40.2% in the training set and 46.7% in the validation set. The tissue of origin prediction accuracy in this subgroup was 85.5% in the training set and 97.1% in the validation set. The sensitivity and prediction of tissue of origin were comparable with the sensitivity and tissue of origin prediction in CCGA substudy 2.
“This test is intended to be used alongside guideline-recommended screening and not replace it,” noted Dr Thiel.
DNA and Protein Test Doubles Cancer Detection
In the first-of-its-kind prospective study of a multicancer liquid biopsy called DETECT-A, 10,006 women aged 65 to 75 years who had no history of cancer were evaluated for cancer. The DETECT-A test incorporates DNA and protein markers to detect cancer. In this study, all patients with blood tests positive for cancer underwent diagnostic PET-CT to detect and localize the putative cancer.
An interim analysis showed that DETECT-A could identify 10 different cancer types, and 65% of these cancers were classified as local or regional disease, reported Nickolas Papadopoulos, PhD, MS, Professor of Oncology and Pathology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. The positive predictive value of the blood test alone was 19%, which is higher than existing noninvasive screening tests for individual cancers. When combined with standard-of-care screening, the number of cancers detected was doubled.
Of the 10 different cancer types detected, 7 do not have standard-of-care screening, Dr Papadopoulos pointed out. Furthermore, performing the blood test did not incur a large number of futile invasive follow-up tests, because “close to 99% of individuals did not undergo any procedure.”
Dr Papadopoulos concluded that “It is feasible for a minimally invasive blood test to safely detect several types of cancers in patients not previously known to have cancer, enabling treatment with intent to cure in at least a subset of individuals.”