Several problems are associated with the standard biopsies required to treat two of the biggest causes of human mortality: cancer and sepsis. Could these be solved by switching to flow biopsies? We'll be posting several blogs over the coming weeks highlighting these problems.
Prior to receiving a diagnosis for a particular disease, it is often necessary for a clinician to perform a biopsy. This could be in the form of a tissue biopsy, in which diseased tissue is removed from the patient and analysed, or a liquid biopsy, in which a blood sample is acquired and analysed. These samples are analysed for specific biomarkers (e.g., a protein or a gene) to determine the presence or extent of a disease, to help aid in treatment selection and monitoring.
Biopsies are routinely performed to diagnose cancer. However, several other diseases also require different types of biopsies. These may include, but are not limited to, autoimmune diseases, heart disease, kidney disease, infectious diseases, and endometriosis.
Idris Oncology are developing another type of biopsy, the flow biopsy. This involves the introduction of a wire, via an already placed catheter, into the bloodstream of patients. This wire is coated with proprietary technology enabling it to capture specific bio-analytes (cells, proteins, or bacteria) as they flow past in the bloodstream. Almost like using a fishing rod to catch a fish in a flowing river. These can then be taken from the blood and analysed in a similar fashion to tissue and liquid biopsies.
Unfortunately, there are several limitations associated with traditional tissue and liquid biopsies. Below outlines some of the problems clinicians face when dealing with two of the world’s most deadly killers, cancer and sepsis, and how flow biopsies may solve them:
1. THE PROBLEM: Many types of tissue biopsies are too invasive and dangerous.
The rise in popularity of liquid biopsies to aid in cancer diagnosis and treatment selection is partly due to the invasiveness and risks involved with certain tissue biopsies. Lung cancer biopsies are associated with $1.5 billion in complication costs per year, in the US alone. Only 10% of patients will suffer from complications but they are so severe that they make up more than three-quarters of the total lung biopsy costs in the US. This is only one type of cancer; complication costs are associated with many other types of cancer tissue biopsies.
2. THE PROBLEM: There is often not enough detectable bio-analyte (what you want to measure) in a standard liquid biopsy blood sample.
A standard blood sample will be in the range of 7 to 10ml for adults. This Is often too little blood to detect circulating bio-analytes. A cancer patient’s sample may contain, if any, 1 to 1.5 circulating tumor cells (these break off from a tumor and circulate in the bloodstream) per ml (1). This would be significantly lower in early-stage cancer patients whose cancers aren't yet metastatic. It is simply impossible to capture the hundreds of the CTCs required for analysis using a single blood sample (2).
Other liquid biopsy-based bioanalytes detected from cancer patients include circulating tumor DNA (ctDNA). These again exist in such low numbers in a standard blood sample. Furthermore, their detection is hindered by the complex make up of other cells and material in the blood sample. Identifying ctDNA often requires complex next generation sequencing followed by machine learning algorithms which isn't always reliable. This results in many false negatives (when ctDNA isn’t detected despite it being present) requiring invasive tissue biopsies as a follow up.
Blood samples to detect bacterial infection, the leading cause of sepsis, will not contain enough bacteria for analysis, particularly during the initial stages of infection. For this reason, the blood sample needs to be cultured (to grow the bacteria) for up to several days to ensure that enough bacterial colonies form before their analysis and the prescription of antibiotics. The likelihood of mortality due to systemic bacterial infection increases by 8% every hour the patient is left untreated. A timely diagnosis is crucial.