Blood-based test to detect cancers stirs up debate

Promoters of a new cancer screening blood test bet on the ‘disruptive’ technology, but not all clinicians are convinced

Blood-based test to detect cancers stirs up debate

Datar Cancer Genetics launched a cancer screening profile in the form of ‘Easycheck360’, a blood test for the detection of 16 types of cancers. 

Announcing the launch, Rajan Datar, MD, Datar Cancer Genetics, said the test is based on the discovery of circulating tumour cells and their clusters (C-ETACs).

“Our technology is very sensitive and specific to detect circulating tumour cell clusters in the blood, which is by far the most powerful evidence of malignant activity in the body,” he stated, claiming that the breakthrough test is capable of detecting most solid organ cancers such as those of the breast, the ovaries, lung cancer, colon and liver cancers.

Not backed by strong evidence

However, Dr C.S. Pramesh, Director, Tata Memorial Hospital and Professor and Head of Thoracic Surgery, Tata Memorial Centre, Mumbai says screening tests that are not backed by strong evidence can cause increased anxiety and guilt and that such tests exploit the innocent public.

 In the study carried out by Datar Cancer Genetics and published in the International Journal of Cancer under the title — ‘Circulating ensembles of tumour-associated cells: A redoubtable new systemic hallmark of cancer’, Dr Dadasaheb Akolkar, Research Director, Datar Genetics, said it was the first study of its kind to investigate the prevalence of circulating tumour emboli or C-ETACs (Circulating Ensembles of Tumor Associated Cells), in a population size cohort of over 16,000 participants to establish a definitive new systemic hallmark of cancer. “The technique we have used is breakthrough innovation. When clusters of cells break off from an early-stage tumour and enter the bloodstream, we can efficiently and accurately isolate a few hundred malignant cells from more than 100 million cells from just 10 ml of blood. While almost all the cancer samples had these cell clusters, they were seen in very few of the samples which were apparently without cancer,” he said in a press release.

The study involved 16,134 participants, including 5,509 patients with cancer (TrueBlood study) and 10,625 individuals with no symptoms (RESOLUTE study). The test had shown an accuracy of more than 94%. The C-ETACs were seen in 89.8% of cancer cases and in only 3% of apparently healthy, asymptomatic individuals who had no abnormal findings in presently used screening tests. The study was the largest of its kind in the world.

Dr Velumani, CEO, Thyrocare, a co-marketer of the test,  who tweeted a pamphlet announcing the test as a disruptive cancer diagnosis, commented; “I strongly believe that Datar has a cancer diagnostic test. He has scientific publications as evidence for it. It could have, like many other tests used for diagnosis of cancer, false negative and false positive. But one would know only after using it. Use it and if it does not give any diagnostic advantage it can be stopped always.” It is unfortunate if some professional ego or politics prevents the use of a technology, he rued.

Dr Preetam Jain, Medical Oncologist at Bhatia Hospital, Mumbai said: “These screening packages are not recommended in clinical practice at present as these tests are still in the research stage. Tests for screening cancers require strong evidence with randomised clinical trials to prove the benefits.”

He further added that data is not strong enough to support benefits in high-risk normal individuals who have not developed cancers. The 16 tumours mentioned in the test have different risk factors, biology and epidemiology. Hence many cancers are not ideal for screening as the tests lack survival benefit. They also increase the cost burden and strong marketing of these screening packages can promote biased commercial aspects without any clinical benefit. Personally, he would not recommend such screening packages to his patients, he said. 

Non-invasive biopsy

Commenting on the subject, Dr Vishwanath S, Medical Oncologist, Apollo Hospitals, Bangalore, said “Circulating ensembles of tumour-associated cells (C-ETACs), comprising tumour emboli, immune cells and fibroblasts is one of the hallmarks of cancer. These are shed into the vasculature from primary tumours and are postulated to contain a subpopulation of cells with the potential to spread and initiate distant metastases. The advantage is that the test is simple and non-invasive and may turn out to be a substitute for an invasive biopsy in certain cases where invasive biopsies are technically challenging. Dr Akolkar and colleagues have to be commended on their recent publication.”

According to him, the study specifically addresses the methodology of enrichment and detection of clusters of viable apoptosis-resistant circulating tumour-associated (C-TACs) and their assemblages (circulating ensembles of tumour-associated cells (C-ETACs) from peripheral blood rather than detecting single CTCs. The results state that C-ETACs were detected in 4,944 (89.8%, 95% CI: 89.0-90.7%) out of 5,509 cases of cancer. C-ETACs were detected in 255 (3%, 95% CI: 2.7-3.4%) of the 8,493 individuals with no abnormal findings in screening. C-ETACs were detected in 137 (6.4%, 95%CI: 5.4-7.4%) of the 2,132 asymptomatic individuals with abnormal results in one or more screening tests.

He further added that the era of personalised medicine enables us to customise treatments based on the patient’s molecular profiling. The use of circulating tumour cells (CTCs) is one step in this direction and its role is also significantly evolving in disease stratification and decision making, real-time monitoring for response and detection of resistance, disease progression, tumour heterogeneity analysis and the development of newer targeted therapies. Its current role in screening asymptomatic individuals is rather limited at the current time. Larger global studies have to be undertaken to validate the current results before it is commercially used for screening asymptomatic high-risk individuals as a companion test along with other screening tests. Moreover, the word ‘cancer’ is associated with a lot of fear and anxiety and pre-test and post genetic counselling should also be mandatory should it become commercially available in the future following regulatory authorities’ approval, he said.

‘Liquid phase’ of solid tumours

Commenting on the same, Dr Mallika Tewari, Senior Consultant, and Programme Lead Surgical Oncology, Dept of Surgical Oncology, Wockhardt Hospitals, Mumbai Central, said: “Solid tumours can release a surprisingly high number of cells everyday into the circulation. These cells are called circulating tumour cells (CTCs). CTCs are a rare and have the potential to function as a seed for metastases. Cancer cells metastasise through the bloodstream either as single migratory CTCs or as CTC clusters, which consist of aggregates of two or more cells. CTCs preserve primary tumour heterogeneity and mimic tumour properties. CTCs and circulating tumour DNA (ctDNA) give an insight into the “liquid phase” of solid tumours and are being studied extensively.”

Although CTCs originating from primary tumours are considered transitional in the search for a new home, most of these cells are fated to die in circulation owing to mechanical and environmental trauma such as sheer force, oxidative stress and attacks by the immune system. Only a small fraction of CTCs are capable of surviving, seeding distant organs, and eventually giving rise to overt metastatic disease. Most CTCs have a short half-life of less than 2.5 hours in circulation and are apoptotic. CTC clusters are encountered more rarely in circulation. However, these cell groupings are associated with high metastatic potential. These are detected by special techniques which are complex yet evolving, and not 100% accurate in capturing the cells in transit.

The study of CTCs offers broad pathways to develop new biomarkers for tumour patient diagnosis, prognosis, and response to therapy, as well as translational models accelerating oncologic drug development. Its clinical utility for the diagnosis of early cancer is an area of intense research and is the best stated investigational at the moment. However, several studies have supported its use as a prognostic tool. Given the value of prognosis prediction of CTCs, the US Food and Drug Administration (FDA) has approved their clinical use in metastatic breast, colorectal and prostate cancers.

In the future, we may see liquid biopsies replacing invasive biopsies in solid tumours but as of now, it will remain complementary to the standard cancer diagnostic tests available. 

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