Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.
It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.
CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.
The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.
The sensitivity of the test ranged from 98% in ovarian cancer to 33% in breast cancer, but the specificity was greater than 99% with only 7 of 812 control participants having a positive result. “We could not be certain that the few ‘false positive’ individuals identified among the healthy cohort did not actually have an as-yet undetected cancer, but classifying them as false positives provided the most conservative approach to classification and interpretation of the data,” the authors wrote.
Based on cancer stage, sensitivity for stage I cancers was 43%, for stage II 73%, and for stage III 78%. Again, sensitivity varied depending on cancer type, with 100% sensitivity for stage I liver cancer and 20% sensitivity for stage I esophageal cancer.
When tumor tissue samples from 153 patients with statistically significant ctDNA levels were analyzed, identical mutations were found in the plasma and tumor in 90% (138) of all cases.
The protein markers in the CancerSEEK test might also be able to anatomically locate malignancies. Using machine learning to analyze patients testing positive with CancerSEEK, the results narrowed the source of the cancer to two possible anatomical sites in approximately 83% of patients and to one anatomical site in approximately 63% of patients. Accuracy was highest for colorectal cancer and lowest for lung cancer.
As the study included otherwise healthy patients with known malignancies, the results need to be confirmed with prospective studies of incidence cancer types in a large population. Patients in the screening setting may have less advanced disease and other comorbidities that could impact the sensitivity and specificity of the CancerSEEK test, the researchers wrote.
The study was funded by multiple sources including grants from the National Institutes of Health. The authors reported various disclosures involving diagnostics and pharmaceutical companies.
SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247 .