Ovarian cancer cells. Researchers hope the tests for cancer cells will become part of a ‘universal screening’ tool. Photograph: Media for Medical/UIG via Getty Images
A blood test for 10 different types of cancers could one day help doctors screen for the disease before patients show symptoms, researchers at the world’s largest gathering of oncologists have said.
The test, called a liquid biopsy, screens for cancer by detecting tiny bits of DNA released by cancer cells into blood. The test had particularly good results for ovarian and pancreatic cancers, though the number of cancers detected was small.
Researchers hope the test will become part of a “universal screening” tool that doctors can use to detect cancer in patients.
“This is potentially the holy grail of cancer research, to find cancers that are currently hard to cure at an earlier stage when they are easier to cure,” said Dr Eric Klein, lead author of the research from Cleveland Clinic’s Taussig Cancer Institute. “We hope this test could save many lives.”
The study, by a research team that also included scientists from Stanford University, was presented at the annual conference of the American Society of Clinical Oncologists in Chicago.
Simon Stevens, the chief executive of NHS England, said “new techniques” such as cancer blood tests could “unlock enormous survival gains, as well as dramatic productivity benefits in the practice of medicine”.
“Now, as the NHS marks its 70th anniversary, we stand on the cusp of a new era of personalised medicine that will dramatically transform care for cancer and for inherited and rare diseases,” said Stevens.
The research scrutinised the cases of more than 1,600 people, 749 of whom were cancer-free at the time of the study, with no diagnosis, and 878 of whom had been newly diagnosed with a disease.
The test was most accurate for diagnosing pancreatic, ovarian, liver and gallbladder cancers, correctly finding the diseases in at least four out of five patients.
The blood test found lymphoma and myeloma with slightly less accuracy, at 77% and 73%, and bowel cancer in two out of three patients. Lung cancerwas detected in 59% of patients. Head and neck cancer was detected in 56% of patients.
Researchers said their results showed promise in the approach of blood screenings for cancer, but noted further “clinical development” was needed.
The number of patients in whom cancers were detected was small. For example, although the test detected ovarian cancer with 90% accuracy, only 10 ovarian cancers in total were detected.
Nevertheless, researchers aim to develop a tool that could be used by for all people regardless of their family history. “Potentially this test could be used for everybody,” said Klein.
Prof Nicholas Turner from the Institute of Cancer Research in London described the findings as really exciting and as a possible universal screening tool. “Far too many cancers are picked up too late, when it is no longer possible to operate and the chances of survival are slim,” he said. “The goal is to develop a blood test, such as this one, that can accurately identify cancers in their earliest stages.”
Klein added: “It is several steps away and more research is needed, but it could be given to healthy adults of a certain age, such as those over 40, to see if they have early signs of cancer.”
A simple-to-take test that tells if you have a tumor lurking, and even where it is in your body, is a lot closer to reality—and may cost only $500.
The new test, developed at Johns Hopkins University, looks for signs of eight common types of cancer. It requires only a blood sample and may prove inexpensive enough for doctors to give during a routine physical.
“The idea is this test would make its way into the public and we could set up screening centers,” says Nickolas Papadopoulos, one of the Johns Hopkins researchers behind the test. “That’s why it has to be cheap and noninvasive.”
Although the test isn’t commercially available yet, it will be used to screen 50,000 retirement-age women with no history of cancer as part of a $50 million, five-year study with the Geisinger Health System in Pennsylvania, a spokesperson with the insurer said.
That’s useful because early-stage cancer that hasn’t spread can often be cured.
Companies have been pouring money into developing liquid biopsies. One startup, Grail Bio, has raised over $1 billion in pursuit of a single blood test for many cancers.
For their test, Hopkins researchers looked at blood from 1,005 people with previously diagnosed ovarian, liver, stomach, pancreatic, esophageal, colorectal, lung, or breast cancer.
Their test searches for a combination of eight cancer proteins as well as 16 cancer-related genetic mutations.
The test was best at finding ovarian cancer, which it detected up to 98 percent of the time. It correctly identified a third of breast cancer cases and about 70 percent of people with pancreatic cancer, which has a particularly grim outlook.
The chance of a false alarm was low: only seven of 812 apparently healthy people turned up positive on the test.
The researchers also trained a machine-learning algorithm to determine the location of a person’s tumor from the blood clues. The algorithm guessed right 83 percent of the time.
“I think we will eventually get to a point where we can detect cancer before it’s otherwise visible,” says Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.
He cautions that screening tests can sometimes harm rather than help. That can happen if they set off too many false alarms or if doctors end up treating slow-growing cancers that are not likely to do much harm.
'Liquid biopsy' detects tumour DNA and can track alterations in 13 different genes
Women with advanced stages of breast cancer could receive potentially life-extending personalised treatment after taking a new blood test that detects tumour DNA.
The test, known as a “liquid biopsy”, can detect and track alterations in 13 different genes, including some of the most important drivers of the disease.
A doctor examines a mammograph of a breast cancer patient Rex Features
Breast cancer is the most common type of cancer in the UK, with around 150 new cases diagnosed every day.
For patients whose cancer has spread beyond the breast and nearby glands – the most deadly stage of the disease – the new test could be used to improve and individualise their treatment as the disease progresses, researchers have said.
Around 10 per cent of women have metastatic, or stage four, breast cancer at the time of their diagnosis, according to cancer support charity Macmillan. The average survival rate is around two years.
This is the first time scientists have been able to analyse two kinds of acquired DNA mutation in a single blood test.
The study, published in the journal Clinical Chemistry, described how the researchers first looked at cells grown in a laboratory before analysing DNA in blood donated by 42 women with advanced breast cancer.
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Cancer-specific genetic changes were detected in half the women. In the case of one in five patients, information from the tumour DNA could have been used to alter treatment.
None of the mutations were found in the blood of nine healthy women that was also tested.
One gene that can be examined for changes using the new blood test is called HER2. It usually makes proteins that control the growth of healthy breast cells, but also plays a role in the development of around 15 to 25 per cent of breast cancer cases.
These “HER2 positive” breast cancers can be targeted with the drug Herceptin.
In addition, the test can spot mutations in the oestrogen receptor gene ESR1, linked to resistance to anti-hormone therapies such as aromatase inhibitors.
Once a patient is known to have these mutations, she can be offered other forms of treatment such as chemotherapy.
“By analysing blood plasma to measure for cancer-specific changes to key breast cancer genes – including the HER2 and oestrogen receptor genes – we hope this test could help doctors and patients choose the best treatment at the best time,” said Dr David Guttery, from the University of Leicester.
Somatic “point” mutations occur when DNA molecules are shuffled in the wrong order. Copy number alterations (CNA) are another type of mutation involving extra copies of genes that produce too much protein.
“We have developed a novel blood test that can simultaneously detect somatic mutations and copy number alterations that are integral in driving the growth of breast cancer,” said Dr Guttery.
“This study represents proof of concept, and further validation is now needed to confirm the clinical usefulness of this test before any test could be rolled out.”
The study was funded by two charities, Breast Cancer Now and Cancer Research UK.
Baroness Delyth Morgan, chief executive of Breast Cancer Now, said: “If validated by further research, this blood test could help tell us how a patient's secondary breast cancer is evolving.
“Analysing the genetic make-up of tumours could enable us to identify women who might benefit from changing their treatment, ensuring that breast cancer patients receive the most personalised therapy possible.“
Dr Justine Alford, senior science information officer at Cancer Research UK, said: “While survival for women with early breast cancer has greatly improved, the outlook for patients with advanced disease is still poor, something we urgently need to change. This early research could help achieve this.
“The researchers may have developed a way to track breast cancer as it grows, allowing doctors to act swiftly and give patients the treatments that are right for them as early as possible. On top of that, such a tailored approach could spare patients receiving drugs, and the side effects that go with them, that aren't likely to work.”
For many people with cancer, the needle biopsy — an invasive procedure that isolates tumor tissue for analysis — is an uncomfortable part of diagnosis and treatment. Recent research reveals that the information obtained from this biopsy might be less accurate than previously thought. By Jim Stallard
on Monday, August 11, 2014
Experimental pathologist Jorge Reis-Filho says “liquid biopsies” could provide more comprehensive ways to assess tumors.
Summary
Experimental pathologist Jorge Reis-Filho explains how tumor DNA obtained from the blood could lead to noninvasive — yet highly sensitive — ways of detecting and monitoring cancer in the body.
For many people with cancer, the needle biopsy — an invasive procedure that isolates tumor tissue for analysis — is an uncomfortable part of diagnosis and treatment. Recent research reveals that the information obtained from this biopsy might be less accurate than previously thought.
As researchers identify genetic changes that trigger cancer and promote its growth, there is a growing awareness that effective treatments could be undermined by tumor heterogeneity — the variation among cancer cells both within the primary tumor and within distinct tumors formed by a cancer’s spread, or metastasis, to distant sites. For example, genetic mutations present in one biopsy sample might be absent from another biopsy taken from a different part of the tumor. This type of discrepancy complicates clinical decisions and confounds research efforts.
Now scientists are looking for less invasive and more comprehensive ways to examine tumors. One approach might be to rely on “liquid biopsies,” which analyze tumor cells or tumor cell DNA that has entered the bloodstream simply by drawing a blood sample from the patient.
Memorial Sloan Kettering experimental pathologist Jorge Reis-Filho, who studies the genetic alterations that drive the malignant behavior of breast cancer cells, discussed with us the potential of analyzing circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) in a blood sample and explained ways that ctDNA might provide insights for treatments that go beyond current conventional clinical tests.
What are the differences between CTCs and ctDNA and what can they reveal about a tumor?
CTCs have been recognized over the last decade as clinically useful cancer biomarkers in certain cases, but researchers have recently begun to focus on ctDNA as a potentially superior source of genetic information.
One limitation of CTCs is that they require elaborate methods for detection and retrieval. First, they need to be isolated from other blood material, which is difficult because they are very rare. Then extracting the DNA to study the genetic makeup of the cells is itself a cumbersome process. In addition, it is unclear what causes cells to break off from a tumor. We don’t know whether CTCs represent the entire makeup of cancer cells in the tumor or only a subpopulation, so it has yet to be defined how many CTCs need to be analyzed with molecular methods in each patient.
ctDNA, on the other hand, is much easier to isolate. When cells die, including cancer cells, some of the DNA they shed ends up in the [blood] plasma. This DNA in the circulation can be extracted from plasma and used for the characterization of the genetic makeup of tumor cells. In patients with advanced disease, tumor DNA can be collected even from a single vial of blood. As this is minimally invasive, multiple vials can be collected and the DNA extracted can provide important insights into the biology of the tumor.
More important, ctDNA may actually provide a more global — and therefore more accurate — picture of the cancer in the body. We have shown that at least in some patients, sequencing the ctDNA can capture all genetic alterations found in cancer cells in different parts of the body, because the cells dying and releasing DNA would come from all parts of the primary tumor and metastases.
What has made the study of ctDNA such a focus of interest recently?
The big change has been the introduction of next-generation sequencing, a new technology that allows us to sequence entire genomes of tumor cells to detect mutations with great accuracy. For example, we have a test here called MSK-IMPACT™, which can look for hundreds of cancer-related mutations at once with very high sensitivity. We have used this test to detect every clinically relevant mutation present in ctDNA from cells all over the body. Just a few years ago, this type of analysis would have pertained to the realm of science fiction.
Being able to detect the entire range of mutations could be of great help in planning therapy. If ctDNA sequencing can detect all mutations present in the different cancer cells from a patient, we have a better chance to select the optimal drug or combination of drugs for that particular patient.
How could analysis of ctDNA be used to monitor disease progression and treatment?
As with CTCs, there have been studies showing that disease progression can be tracked by monitoring ctDNA levels, particularly by how concentrated the ctDNA is in the blood. As cancer progresses, the levels go up. In addition, in the last two years, research here at MSK and elsewhere has shown that next-generation sequencing of ctDNA from the plasma of breast cancer patients could identify genetic alterations that arise at different stages of the disease and potentially tell us whether a tumor will recur.
When it comes to treatment, we are beginning to see that genomic analysis of ctDNA over time makes it possible to track how cancer cells evolve in response to therapy. We recently published a study demonstrating this approach in a single patient with advanced breast cancer that had spread to the liver and bone. Genetic analysis from the primary tumor had revealed a mutation in a gene called AKT, so the patient was enrolled in a clinical trial testing a targeted therapy. We also sequenced DNA from the liver metastasis and from plasma samples collected both before the patient started the trial and at multiple points after receiving the drug.
We saw that the mutations in the cancer cells changed as the patient first responded to the drug and then relapsed. The changes in genetic composition mirrored the response to the drug as indicated by PET scans of the tumor and metastases. Significantly, however, we detected increases in the amount of ctDNA in plasma that preceded the detection of disease progression by imaging analysis or biochemical tests.
Although this analysis was done in a single patient, it does establish an important proof of principle that we might use this technique to track new mutations as they arise in response to targeted therapy. Analyzing ctDNA could give us a fuller picture of disease progression and drug resistance.
What applications do you see for this technology in the near future?
The use of ctDNA from plasma is still in its infancy. We can’t lose sight of all that we don’t yet know. With circulating tumor cells, a lot of initial hopes have not yet been fully realized; however, the experience accrued with the analysis of CTCs may prove instrumental for the use of ctDNA in clinical practice. The lessons we have learned over the last decade about the development of molecular tests for treatment decision-making, coupled with technological developments, are cause for optimism that this type of liquid biopsy will lead to noninvasive — yet highly sensitive — ways of detecting and monitoring cancer in the body.
Liquid biopsies are non-invasive blood tests that detect circulating tumour cells (CTCs) and fragments of tumour DNA that are shed into the blood from the primary tumour and from metastatic sites
Date: 29 Sep 2014
Author: Giuseppe Curigliano
Affiliation: European Institute of Oncology, Milan, Italy
Article extracted from the ESMO 2014 onsite newspaper.
This technology has enormous diagnostic and treatment implications for oncology and I believe it is poised to transform clinical practice. As an integral part of precision medicine, the importance of liquid biopsies was highlighted in a Special Session on Saturday, at which experts from around the world discussed its potential and limitations.
Guiseppe Curigliano, Congress Daily, Guest Associate Editor, European Institute of Oncology, Milan, Italy
So, what’s all the fuss about? Tumour genome sequencing to inform treatment decisions is already central to the management of many patients with cancer and I have witnessed this change the hallmark of cancer care. Tailored therapy relies on the identification of the correct molecular tumour target. Currently, tumour biopsy tissue, generally from the primary tumour, is used to determine molecular targets at a single time point, before treatment commences. These biopsies carry some risks for patients, they are painful, they are costly and, importantly, the process takes time. Also, given the complexities of tumour heterogeneity, both within a tumour and between a primary tumour and metastases, a tissue sample may not be a true representation of the molecular profile. A liquid biopsy, on the other hand, may capture the entire heterogeneity of the disease. What is more, tumour genotypes are notoriously unstable and prone to changes under selection pressure. In this regard, liquid biopsies offer what tissue biopsies cannot, due to risks to the patients and cost; the opportunity to take serial samples in order to monitor tumour genomic changes in real time. This will allow clinicians to ensure that the therapy they have selected, based on a particular molecular target, remains relevant and observe the emergence of any resistance. Instead of waiting for information from scans, we may be able to identify at an earlier stage if a treatment is not working and to spare the patient the unnecessary toxicity of a drug that no longer provides any benefit. At the same time, we may be able to observe if any new molecular targets appear that could be suitable for treatment. All this could help to provide patients with the right treatment for the right target without delay.
Liquid biopsies also present us with a unique opportunity to move forward with our understanding of metastatic disease development and they may help to identify signalling pathways involved in cell invasiveness and metastatic competence. Ultimately, at some point in the not too distant future, these tests will be used in the diagnosis of cancer. This will revolutionise cancer care, providing clinicians with rapid access to information on a molecular level at diagnosis, thereby optimising treatment choices.
In terms of samples, CTCs have been the most studied. While these cells are relatively rare and require sensitive collection and enrichment technology, they provide information at both the genetic and cellular level. However, cell-free tumour DNA (cfDNA) is emerging as an effective alternative to CTCs, with the benefits of easier collection and analysis. Today, a Poster Discussion Session on Trials and Tribulations in Oncology: Future Approaches (13.00 – 14.00, Pamplona) will feature two abstracts on cfDNA liquid biopsies: one on the use of serial next generation sequencing of cfDNA to monitor response and progression during administration of drugs in the phase I setting (Abstract LBA6) and another on the de novo detection of cfDNA in patients with refractory cancer (Abstract 1571PD). These studies should help us to build on our understanding of the type of information cfDNA-based liquid biopsies can give us.
We do know that standardisation will be a key factor in ensuring consistency between centres and in determining its clinical success. It is crucial that we standardise the assays used to evaluate cfDNA and also define the optimum sampling specimen (i.e. serum or plasma). In fact standardisation across the board would be ideal: blood collection, processing, storage, and DNA extraction, quantification, analysis and reporting of data. Future development of liquid biopsies will need to provide a cost-effective analysis, mainly identifying the genes known to be recurrently mutated in each tumour. Therefore, developing standardised methodologies for cfDNA analysis and validation in large prospective clinical studies is mandatory for the implementation of the liquid biopsy approach in the clinical management of cancer patients.
In the field of oncology, we see so many innovations come and go, without lasting impact. Will the promise of liquid biopsies be a clinical reality? It is hard for me to not to be excited about the benefits they can offer to patients and I believe that they will be invaluable to cancer research and treatment.
I would like to thank the Congress Daily Editorial Team of Evandro de Azambuja (Editor-in-Chief), Markus Joerger and Floriana Morgillo (Associate Editors) for giving me the opportunity to write this editorial.
Company Bets on Catching Cancer With 'Liquid Biopsy'
JAN 10 2016,
byMAGGIE FOX
Gene sequencing company Illumina is betting it can diagnose cancer in people long before they have any symptoms at all with a blood test called a liquid biopsy.
The San Diego-based firm launched a spinoff company Sunday named Grail, with obvious references to the "Holy Grail."
"The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage," said Dr. Richard Klausner, a former director of the National Cancer Institute who's a member of the new company's board of directors.
The plan is to use Illumina's super-fast genetic sequencing technology to look for genetic material from tumor cells in peoples' blood long before they have any evidence of cancer. The test would check for genetic mutations known to be found in tumors.
Something similar is already done sometimes in people who already have cancer. The liquid biopsies are used to see how well cancer treatment is working.
Blood Test May Detect Pancreatic Cancer in Early Stages1:34
Some big names in investing and cancer researcher are signing on for the enterprise.
They include Amazon founder Jeff Bezo's Bezos Expeditions, Microsoft co-founder Bill Gates and Sutter Hill Ventures. Klausner; Dr. Jose Baselga, physician in chief at Memorial Sloan Kettering Cancer Center and president of the American Association for Cancer Research; and Dr. Brian Druker, director of the Oregon Health & Science University, have signed on to the advisory board.
"We hope today is a turning point in the war on cancer," said Jay Flatley, Illumina's chief executive and chairman of Grail.
"By enabling the early detection of cancer in asymptomatic individuals through a simple blood screen, we aim to massively decrease cancer mortality by detecting the disease at a curable stage."
It will be years before any such test could be designed, and it would have to be tested in thousands of people before regulators could consider approving it. Right now one of Illumina's whole-genome tests costs about $1,000, so it would be a pricey cancer screening test unless that cost can be brought down.
And while tumors are known to drop bits of genetic material into the blood, cancer experts caution that some early cancers may not secrete DNA fragments and require other types of detection.
Cancer is the No. 2 killer overall in the United States, but it's neck and neck with heart diseases.
Last week, the American Cancer Society projected that cancer would be diagnosed in close to 1.7 million Americans this year and that it would kill nearly 600,000. Most deaths are of people whose cancer had already spread before it was treated.
In September, the FDA slapped Pathway Genomics over its "liquid biopsy" testthat claims to do what Grail proposes.
The FDA said the company had not shown the $699 test worked, warned that it "may harm the public health" and said the company hadn't applied for proper regulatory approval.
What tests are involved when someone has liver problems?
Liver disease is one of the leading causes of early death in England as one in ten people who die in their forties die of liver diseasePhoto: Alamy
5:00AM GMT 27 Nov 2014
Alcohol-related liver disease is often first suspected when tests for other medical conditions show that the liver has been damaged.
This is because the condition causes few obvious symptoms in the early stages.
Nationally deaths from liver disease, which can be caused by excessive drinking, obesity and infection with hepatitis, have risen from 7,841 in 2001 to 10,948 in 2012.
It is the only major killer disease which is still rising in England. Across the rest of Europe it is decreasing.
There are a number of tests that can be carried out to determine your diagnosis.
Blood tests
Blood tests used to assess the liver are known as liver function tests. They can detect enzymes in your blood that are normally only present if your liver has been damaged.
Imaging tests / scans
An ultrasound scan,CT scan or MRI scan may also be carried. These scans can produce detailed images of your liver. Some scans may also measure the stiffness of the liver, which is a good indication of whether your liver is scarred.
Liver biopsy
During a liver biopsy, a fine needle is inserted into your body. A small sample of liver cells is taken and sent to a laboratory to be examined under a microscope. The biopsy is usually carried out under local anaesthetic.
The sample can be used to determine the degree of scarring in the liver and the cause of the damage.
Endoscopy
An endoscope is a flexible tube with a light and a video camera at one end. During an endoscopy, the instrument is passed down your oesophagus and into your stomach.
Pictures of your oesophagus and stomach are transmitted to an external screen.
