Blood tests that detect somatic mutations (“liquid biopsies”) offer the promise of exquisite specificity because they are based on driver gene mutations that are expected to be found only in abnormal clonal proliferations of cells, such as cancers. To date, the vast majority of cancer patients evaluated with mutation-based liquid biopsies have advanced-stage disease. In addition, no studies have examined a large number of healthy control individuals, which is essential for evaluation of the specificity of such tests. Diagnostic sensitivity is also an issue for liquid biopsies. Available evidence indicates that patients with early-stage cancers can harbor less than one mutant template molecule per milliliter of plasma, which is often beyond the limit of detection of previously reported technologies that assess multiple mutations simultaneously. The diagnosis of neoplasia through blood analysis has never been exploited in preventative terms. This is because the appearance of the known disease markers was thought to appear only when the tumor had reached such a size as to make the term of “early diagnosis” vain. Each type of tumor has its markers that can be dosed mostly in order to control the course of the disease, the aggressiveness of the tumor and the phases of remission. Abbreviations such as PSA (specific prostatic antigen), CA15-3 or CA-125 and CA19-9 (antigens of reproductive and colon carcinomas) are known and associated with the concept of monitoring the growth or silence activity of cancer.
What if instead there was a method to simultaneously search for traces of the markers of the eight most common tumors? This is the new frontier opened by the researchers of the John Hopkins University of Baltimore, led by Dr. Joshua Cohen. The examination is able to recognize the 8 most common forms of cancer by combining the analysis of DNA and tumor proteins and has a reliability that varies from 69 to 98% of cases depending on the type of cancer. The method, tested on a sample of 1005 patients, was called CancerSEEK. The group was able to evaluate the mutations of 16 tumor genes, along with the levels of 10 proteins circulating in the blood, for breast, liver, ovarian, lung, stomach, pancreas, esophagus and of the right colon. The research team tested it on patients diagnosed with tumors of varying severity, and on 850 healthy volunteers. The method allowed to find the DNA of tumor cells circulating in the blood along with the levels of some proteins, which may be indicative of the development of cancer. It is therefore a more complete test that can allow greater customization of the therapy, suitable for patients who have certain genetic characteristics.To make the test even more reliable is the very low probability that it can give false positives: the study has highlighted only 7 of 1005.
One of the most important attributes of a screening test is the ability to detect cancers at relatively early stages. The median sensitivity of CancerSEEK was 73% for the most common stage evaluated (stage II), similar (78%) for stage III cancers, and lower (43%) for stage I cancers. The sensitivity for the earliest-stage cancers (stage I) was highest for liver cancer (100%) and lowest for esophageal cancer (20%).In some cases the test was able to give information about the origin of the diseased tissue, what turned out always difficult in the past. In the study the diagnosis was made to people with a tumor with no sign of metastasis, based only on the symptoms. The next goal will be to diagnose the tumor before they appear. The researchers estimate that the cost of this blood test can be around 400 euros, more or less the cost of individual screening tests for a single tumor, such as a colonoscopy. Their research has other implications, apart from the precocity and the personalization of the therapy. One of these is the streamlining of the diagnostic costs of which oncology is overloaded, in the face of the immense cohort of patients who every year fall ill with cancer. On the other hand, waiting times, for the execution of examinations in hospital or private facilities, which could be greatly reduced.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Cohen JD et al. Science 2018 Feb 23; 359(6378):926-930.
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