Scientists said their findings, published in the journal Annals of Oncology, show that the test accurately detects cancer often before any signs or symptoms appear, while having a very low false positive rate.
The test, developed by US-based company Grail, looks for chemical changes in fragments of genetic code – cell-free DNA (cfDNA) – that leak from tumours into the bloodstream.
The Guardian first reported on the test last year and how it had been developed using a machine learning algorithm – a type of artificial intelligence. It works by examining the DNA that is shed by tumours and found circulating in the blood. More specifically, it focuses on chemical changes to this DNA, known as methylation patterns.
Now the latest study has revealed the test has an impressively high level of accuracy. Scientists analysed the performance of the test in 2,823 people with the disease and 1,254 people without.
It correctly identified when cancer was present in 51.5% of cases, across all stages of the disease, and wrongly detected cancer in only 0.5% of cases.
In solid tumours that do not have any screening options – such as oesophageal, liver and pancreatic cancers – the ability to generate a positive test result was twice as high (65.6%) as that for solid tumours that do have screening options such as breast, bowel, cervical and prostate cancers.
Meanwhile, the overall ability to generate a positive test result in cancers of the blood, such as lymphoma and myeloma, was 55.1%.
The test correctly also identified the tissue in which the cancer was located in the body in 88.7% of cases.
Dr Eric Klein, chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic in the US and first author on the research, said: “Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer.
“These data suggest that, if used alongside existing screening tests, the multi-cancer detection test could have a profound impact on how cancer is detected and, ultimately, on public health.”
Dr Marco Gerlinger, from the Institute of Cancer Research in London and consultant medical oncologist at the Royal Marsden NHS foundation trust, said: “This new study shows impressive results for a simple blood test that can detect multiple cancer types.
“False positives are low which is important as this will avoid misdiagnoses. For some of the most common tumour types such as bowel or lung cancer, the test even picked up cancers that were very small, at a stage where many of them could potentially be cured.
“The study was done in patients whose cancer was already diagnosed based on other tests and this screening technology still needs to be tested in actual screening trials before routine use.
“But it already allows a glance at early cancer detection in the future which will almost certainly be built around liquid biopsy tests, which detect cancer DNA in the bloodstream.”
Meanwhile, the results of the NHS pilot of the test, which will include 140,000 participants, are expected by 2023.
Prof Peter Johnson, national NHS clinical director for cancer, said: “This latest study provides further evidence that blood tests like this could help the NHS meet its ambitious target of finding three-quarters of cancers at an early stage, when they have the highest chance of cure.
“The data is encouraging and we are working with Grail on studies to see how this test will perform in clinics across the NHS, which will be starting very soon.”
Cancer is the second most common cause of death. It's more curable when detected earlier.
Although some cancers develop completely without symptoms, some do have signs you are likely to ignore.
1. Unexplained Weight Loss
Weight loss for no known reason, not through exercise or changes in diet is a common sign of cancers related to lung, stomach or pancreas.
2. Fever
Fever may be a sign of early cancer in the blood like leukemia and lymphoma. Fever may also reveal kidney and colon cancer at an early stage.
3. Fatigue
Extreme fatigue that cannot get better after rest can be a symptom of several cancer types such as leukemia, colon cancer, and stomach cancer.
4. Pain
Sometimes bone cancer or testicular cancer can cause pain. A headache that doesn't get better after a long-time treatment may be a symptom of a brain tumor. Back pain may be a sign of cancer in the ovary or colon.
5. Unusual Bleeding
Coughing up blood may be a sign of lung cancer. Blood in the stool or urine can forecast colon cancer or kidney or bladder cancer. A bloody discharge from the nipple can indicate breast cancer.
6. Lump
A lump that is usually hard, not painful, irregularly shaped or firmly attached deep in the soft tissue or under the skin is often caused by cancer.
7. Nagging Cough
More than half of people who have a cough that just wouldn't go away are diagnosed with lung cancer. Excessive coughing is also common signs of laryngeal and thyroid cancer.
8. Shortness of Breath
Cancer in or near the lungs may cause a blockage of the tubes that carry air. Breathlessness is also common with breast cancer tumors, ovarian or liver cancer.
9. Difficulty Swallowing
Mouth or throat cancers can make the swallowing difficult. It's also a common sign of various head and neck cancers such as esophageal, oropharyngeal cancer, thyroid, and laryngeal cancers.
10. Heartburn
Heartburn that doesn't go away or gets worse could mean cancer of the throat, stomach, or ovaries. Excessive food, alcohol, or stress can cause serious heartburn.
11. Belly Pain and Depression
It rarely happens, but belly pain plus depression can be a sign of pancreatic cancer. But you don’t need to worry unless this disease runs deep in your family.
12. Skin Changes
Any freckle, mole or wart that changes color, shape, or size should be examined for skin cancer. Besides, darker looking skin, reddened skin, itching, yellowish eyes, and skin may also be linked to cancers.
13. Change in Bowel or Bladder Habits
Long-term diarrhea, constipation or a change in the size of the stool can be a symptom of rectal or colon cancer. Pain when passing or blood in urine can be related to bladder or prostate cancer.
14. White Patches Inside the Mouth
White patches inside the mouth can be leukoplakia, which is pre-cancerous and can become mouth cancer if it's not treated early.
15. Continued Itching
Precancerous conditions of the genital or anal areas can cause persistent itching. If the itching continues with over-the-counter topical medications, consult your doctor.
16. Non-healing Sores
Common sores usually heal quickly. If you have persistent sores in areas like your mouth, you may have cancer and should raise concerns and see a doctor.
Artificial intelligence capable of spotting deadly diseases like cancer is to receive a £50 million funding boost in a bid to speed up diagnosis times.
Jamie Harris, PA Science Technology Reporter
The extra cash is being awarded to three specialist centres based in Coventry, Leeds and London, delivering digital upgrades to pathology and imaging services across an additional 38 NHS trusts, the Department of Health and Social Care (DoH) said.
It is hoped the technology will improve outcomes for millions of patients, providing a more accurate diagnosis and freeing up NHS staff time, as part of a Government commitment to detect three quarters of cancers at an early stage by 2028.
Health Secretary Matt Hancock said: “Technology is a force for good in our fight against the deadliest diseases – it can transform and save lives through faster diagnosis, free up clinicians to spend time with their patients and make every pound in the NHS go further.
Health Secretary Matt Hancock said the investment will ‘make every pound in the NHS go further’ (Jonathan Brady/PA)
“I am determined we do all we can to save lives by spotting cancer sooner.
“Bringing the benefits of artificial intelligence to the front line of our health service with this funding is another step in that mission.
“We can support doctors to improve the care we provide and make Britain a world-leader in this field.
“The NHS is open and I urge anyone who suspects they have symptoms to book an appointment with their GP as soon as possible to benefit from our excellent diagnostics and treatments.”
The Government said the investment will support its long-term response to Covid-19, allowing centres to work with British businesses and thereby support the economic recovery.
The DoH said that since the beginning of the coronavirus pandemic, more than 92% of urgent cancer referrals have been investigated within two weeks and 85,000 people have started treatment.
Darren Treanor, a consultant pathologist at Leeds Teaching Hospitals NHS Trust and director of one of the three centres, said: “This investment will allow us to use digital pathology to diagnose cancer at 21 NHS trusts in the North, serving a population of six million people.
“We will also build a national network spanning another 25 hospitals in England, allowing doctors to get expert second opinions in rare cancers, such as childhood tumours, more rapidly.”
A Tokyo-based bio-venture company has developed a simple and effective test for cancer screening that requires just a drop of the subject's urine and a bunch of roundworms known as nematodes.
By SHINGO FUKUSHIMA/ Staff Writer
October 3, 2019 at 16:30 JST
Nematodes used for cancer screening (Provided by Hirotsu Bio Science)
Hirotsu Bio Science, a venture concern with roots in Kyushu University, announced plans Oct. 1 to start trial tests this month using a urine test kit called N-Nose in conjunction with local governments in Fukuoka Prefecture.
City authorities in Kurume and Ogori will provide urine samples from employees for testing by the company. Participants will be informed of the results.
Hirotsu Bio Science said it intends to put the cancer screening kit into practical use from January.
Nematodes, a type of worm that is about 1 millimeter long and lives in soil, is known to be strongly attracted to the odor of cancer cells.
The technology automatically analyzes the worms' movements after approaching urine.
The company's president, Takaaki Hirotsu, said that even a single drop of urine was enough to detect cancer.
Once a positive diagnosis is made, doctors can examine the cancerous cell to determine what type of cancer is involved.
Hirotsu said 15 kinds of cancers can be detected, including stomach cancer, lung cancer and breast cancer. He said even cancer in the early stages can be detected at a higher rate than conventional tests.
A single examination costs just 9,800 yen ($91) as nematodes are cheap to rear.
The company has conducted clinical research at 17 facilities across the nation since 2018.
In the trial test, 100 Kurume and 20 Ogori local officials will participate. The test results of cancer risks will be divided into several stages and shown to the participants.
The test also aims to examine how the results should be conveyed to participants.
Hirotsu Bio Science has contracted with other companies and local governments to receive up to 250,000 samples so it can start full-fledged operations next year.
“If low cost and highly accurate cancer screening is available, the rate of screening will surely increase,” Hirotsu said. “I want to get the message out to people by working with local governments.”
Kurume Mayor Tsutomu Okubo, a staunch supporter of the project, pledged to do his utmost to ensure the kit is put into practical application "as a world-class invention.”
Ogori Mayor Ryoko Kaji, another supporter, noted that if cancer screening can be achieved with just a drop of urine, "more people are bound to take the test as a first step to prevent cancer."
Takaaki Hirotsu is trying to harness the power of the nematode worm — a tiny, transparent roundworm that lives in soil or water — to detect all forms of cancer at their earliest stages.
The use of nematodes for superearly cancer detection — a project not being undertaken by anyone else at the moment — could dramatically change the way cancer is screened and treated, both in Japan and overseas.
The 45-year-old biologist stunned the world in March 2015 when, as a researcher at Kyushu University, he announced in a science journal his discovery of the nematode’s unique ability to detect the odors of cancerous cells. The research, published in Plos One, said the roundworm was found to be attracted to diluted urine samples of cancer patients and tended to quickly home in on them while moving away from the urine of healthy people.
The scent detection worked with about 95 percent accuracy, a remarkable result compared with other tumor-marker diagnostic tests using blood samples, according to the paper.
Now, 2½ years later, he runs his own venture, Hirotsu Bio Science, where he collaborates with more than 20 hospitals and cancer research institutions nationwide to conduct clinical trials for this novel cancer-screening method.
He aims to launch a diagnostic kit — N-Nose — by early 2020, with the goal of eventually making it the predominant first-stage screening tool in Japan and abroad.
Hirotsu’s interest in the nematode worm, which measures about 1 mm long, spans more than two decades, dating back to the late 1990s, when he was in a master’s program in biology at the University of Tokyo, commonly known as Todai. His primary research interest at the time was the mating behavior of the nematode worm — which is either male or hermaphrodite. A hermaphrodite nematode has both male and female reproductive organs and can self-reproduce.
“The nematode worm is mostly hermaphrodite and can create its clones,” he said. “To boost its survivability in the environment, it only occasionally mates with a male. When that happens, the male nematode circles around the hermaphrodite one, which is kind of like the mating dances of fish and other animals, though not as conspicuous. I found that interesting and wanted to find out why.”
But it was a secondary, side theme given by his Todai professor that really opened up his research opportunities: scent.
Using the worm, he established that a well-known cancer protein called Ras is activated by the scent stimuli — a discovery that was published in the journal Nature in 2000. For years after that, he continued to research smells, using the nematode as a model organism.
“People’s like or dislike of the same smell changes depending on its concentration,” he said. “Indole, for example, is an aromatic substance that, when diluted, smells like jasmine. But when it’s in a concentrated form, it smells like feces. I found such things amazing, and did countless experiments on how the worm reacted to the same aromas differently as their concentration changed.”
It was only in 2013 when Hirotsu — who until then considered himself a basic research scientist — began studying whether the worm can be used to sniff out cancer. It was after a doctor who studied the use of dogs for cancer detection asked him whether it was possible.
Dogs have long been known for their ability to smell cancer, even in its early stages, though it is not known exactly why they are so good at it. One promising theory is that they can smell a mixture of gases discharged only by cancerous cells. But training such specialist dogs is an expensive undertaking, and there are currently not nearly enough canines capable of screening everyone in Japan.
“Since I was confident that I had done more tests, and was more skilled at fine-tuning them, on the worm’s reaction to smells than anybody else, I thought I would be the first one to find out whether it would work (for cancer detection),” he said.
And so he did. He says he is now convinced that nematodes are the best cancer screening tool. The worms are cheap and easy to keep, and are just as good as — if not better than — dogs in their sensitivity to smells, he said.
But why are nematodes attracted to cancerous cells? While the precise reason is unknown, they seem to hate humans in general, as they shy away from any sample type, be it urine, saliva or human tissue, he said.
One potential reason is that cancer cells produce certain odors that smell a lot like the food of nematodes, he said, adding that they feed on E. coli and other bacteria.
“It could be possible that the chemicals discharged by cancer cells smell like their food and they are carried through the bloodstream into the urine of cancer patients,” he said.
Hirotsu wants to make N-Nose the universal, first-stage screening tool for everyone submitting just a tiny urine sample. And for a reasonable price, too — less than ¥10,000. Keeping the price down is one reason he decided to set up his own venture and became its CEO in August 2016, instead of having others run the business. (He disbanded his previous venture, which he set up in late 2015 and asked someone else to head, after clashes over management policy.)
Currently, C. elegans, the nematode’s scientific name, can detect whether or not someone has cancer, but not the disease’s location. Hirotsu, though, is working on engineering nematodes that react to specific types of cancer.
“The way cancer smells is said to be different according to cancer types,” he said. “So it’s theoretically possible that, once someone is confirmed to have cancer using the wild-type C. elegans, we can find out what type, using genetically modified nematodes that react to particular cancer types.”
He said his research priority is creating a series that can single out pancreatic cancer because it is the hardest cancer to detect early on and is known for its poor prognosis.
One serious issue N-Nose could raise is that, because the worm’s ability is so exceptional, and because it can detect cancer at such an early stage, it may not be possible to confirm the results using conventional tests that are available now. This could result in a situation where someone tests positive in N-Nose but is left with no options to find out what type of cancer they have or to get it treated.
To address such concerns, Hirotsu is preparing to set up an academic group involving doctors, ethicists and psychologists to create guidelines on how to explain the test results to people.
“We need to decide beforehand what kind of explanations the doctors will give to patients, what kind of exams to take next, and what to do when the patients test negative in the follow-up exam,” he said.
But that does not discount the value of the nematode test itself, claimed Hirotsu, who also plans to roll out the diagnostic kit overseas by around 2020.
“As a nematode researcher, I want everyone’s cancer to be detected early, instead of late,” he said.
That, he believes, will change people’s perception of cancer — from the incurable to the curable.
“Right now, getting a cancer diagnosis is like a death sentence for many,” he said. “Many people cite the fear of a diagnosis as a reason to avoid screenings. But when our test becomes widely available, more people will have their cancers discovered and cured. The time will come when people will feel happy to get a cancer diagnosis. It would change the way people look at cancer. It would help enrich people’s lives.”
“Generational Change” is a series of interviews, profiling people in various fields who are taking a leading role in bringing about changes in society.
Key events in Hirotsu’s life
1972 Born in Suo-Oshima, Yamaguchi Prefecture
1995 Graduates from the University of Tokyo, faculty of biology
1997 Completes a master’s degree program with a focus on biochemistry at the university
1997 Joins Suntory Inc.
1998 Leaves Suntory, starts a Ph.D. program at the University of Tokyo
2000 Publishes a paper on cancer protein Ras
2001 Receives a Ph.D. in science from the university
2004 Becomes a postdoctoral research fellow at Kyoto University
2005 Joins Kyushu University as an assistant professor
2016 Establishes Hirotsu Bio Science Inc. and becomes CEO
Venture behind worm cancer-screening method raises ¥30 million from Shinkin Capital
Takaaki Hirotsu, CEO of Hirotsu Bio Science (second from right), poses with Shinkin Capital President Kazuo Yamaguchi (far left) and heads of two regional Shinkin banks in Tokyo on Thursday. | TOMOKO OTAKE
Hirotsu Bio Science, a medical venture developing a cancer screening tool using nematodes, has secured ¥30 million in funding from Shinkin Capital Co. to accelerate growth in overseas markets, the firm announced Thursday.
The Tokyo-based venture run by Takaaki Hirotsu, formerly a biology researcher at Kyushu University, is creating a method to detect early-stage cancers with nematodes, which he discovered are attracted to the diluted urine of cancer patients.
The firm plans to introduce the urine test kit, named N-Nose, by January 2020. It is currently conducting clinical trials involving patients with about 10 different cancers at over 20 hospitals and cancer research institutes across Japan.
At a news conference held Thursday in Tokyo with Shinkin Capital, a subsidiary of the Shinkin Central Bank, Hirotsu said a roll-out of the product abroad will occur around the same time as the Japan launch.
Earlier this month, Hirotsu’s firm reached a joint research agreement with Queensland University of Technology in Australia, and is scheduled to start clinical trials there starting this winter. With results of the research in Australia, it hopes to market the screening kit in the U.S. and Europe.
“N-Nose is painless, quick and cheap. And it can detect cancers in super-early stages,” Shinkin Capital President Kazuo Yamaguchi said. “We find it to be a socially valuable investment.”
Takaaki HIROTSU has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
Abstract: The present invention provides a method for evaluating the taxic behavior of nematodes in response to an odor substance based on olfactory sense, and a dish and a behavior evaluation system to be used for the evaluation method. [Solution] Provided is a method for evaluating the taxic behavior of nematodes in response to odor of a test sample, the method including: a) providing a dish in which the test sample is arranged on the bottom surface, and nematodes are arranged in a region or a site of the bottom surface 1 cm to 3 cm away from the test sample; b) observing the arrangement of the nematodes on the bottom surface at 3 to 15 minutes after the later one of the test sample or the nematodes is arranged; and c) evaluating whether the nematodes show attraction behavior or avoidance behavior in response to the test sample, from the arrangement of the nematodes observed, and a dish or a taxic behavior evaluation system suitable for the method.
Abstract: A cancer detection method characterised in that a nematode is bred in the presence of bio-related material originating from a test subject, or a processed product of same, and cancer is detected using the chemotaxis due to the sense of smell of the nematode as an indicator.
Type: Application
Filed: December 10, 2014
Publication date: January 19, 2017
Applicant: KYUSHU UNIVERSITY, NATIONAL UNIVERSITY CORPORATION
As computers get better at spotting cancer, doctors will have more time to focus on treating patients. 15th March 2018 inHealth
In the US alone, tens of millions of mammograms are performed each year. Analyzing these images takes up a lot of doctors' time. The use of computer assistance to help read mammograms is becoming widespread, but doubts persist about whether the practice is helpful enough to justify its steep price tag. Lower-cost deep learning systems, which train themselves to recognize cancer, could help. Thanks to deep-learning methods like those more commonly used to spot everyday objects in photographs, a new system identified cancer’s precise location more than 90 percent of the time in tests. We spoke with the study’s author, Dezso Ribli of Hungary’s Eötvös Loránd University, to learn more.
ResearchGate: What role does computer assisted detection already play in breast cancer detection?
Dezso Ribli: Computer assisted detection (CAD) is supposed to help the doctors detect lesions that could have been overlooked. In the United States, where mammograms are evaluated by one radiologist, CAD usage is widespread. In Europe, where mammograms are reviewed by two radiologists, CAD is practically not used.
While initial studies showed promising increases in cancer detection rates with CAD, recently a large study by Lehman et al. found no positive impact of CAD usage on radiologist performance. The benefits of the current technology are therefore questionable, while more than $400 million is spent on it yearly in the US.
RG: How is your new system different?
Ribli: Routinely used CAD solutions are based on methods that predate the revolution of deep learning in computer vision. With deep learning, carefully designed neural networks with many, many layers are trained to recognize visual patterns. Unlike previous methodologies, these neural networks learn the meaningful patterns and representations only from the data itself. In a nutshell, deep learning models can recognize objects on images if you show them enough labeled examples, and they “learn” by refining the parameters of subsequent filtering steps.
In some visual tasks, deep learning has decreased error rates by tenfold compared to previous technologies. We think that the old methods in CAD could be replaced by deep learning, and the accuracy of CAD could be drastically increased. Our system applies one of the best deep learning frameworks for object detection to mammography analysis.
“In some visual tasks, deep learning has decreased error rates by tenfold compared to previous technologies.”
RG: How well did your system perform when you tested it?
Ribli: The system secured the 2nd place in The Digital Mammography DREAM Challenge, a prestigious data science competition with more than 1,200 registered participants. Our model was the only one of the best performing solutions able to accurately localize cancers, which is essential for a CAD system in order to be practically usable. Since then, the model's performance has been significantly improved. Details will be shared in another paper about the second phase of the challenge.
With the most recent public digital mammography dataset (INbreast) the model is able to detect more than 90 percent of the cancers with precise positions, while producing only 0.3 false positive detection per image.
RG: How does this model compare to standard mammography analysis methods?
Ribli: Unfortunately, direct comparison with currently used solutions is not possible, because those methods were never evaluated on the same datasets. But the results suggest that our model performs better than commercially available solutions.
RG: What were the limitations of your study?
Ribli: Publicly available mammogram datasets are rather small. Our model was mostly trained on around 2,000 scanned cancer images from the 1990s and a small number of additional cancers on digital images. To put that in context, deep learning models for recognizing everyday objects are usually trained on datasets containing hundreds of thousands or even millions of images.
We are sure that, with larger training datasets, the performance of deep learning CAD models will improve. Creating a huge training dataset is not an impossible task: In the US alone, tens of millions of screening mammography exams are performed annually.
RG: Could your approach be adapted to work with other kinds of imaging and other kinds of cancer?
Ribli: Yes, deep learning, and specifically object detection models, have the potential to help with any kind of cancer imaging or medical imaging.
“Doctors will be able to concentrate their power of the hardest and most complicated cases, which are more suitable for a human mind.”
RG: Do you think there will be a point in the future where AI takes over breast cancer detection altogether, or will there always be a role for human radiologists in analyzing mammograms?
Ribli: Breast cancer screening is performed on the scale of a hundred million exams a year. I think in the next few decades AI is going to assist radiologists, and progressively take over the easier tasks, which are monotonous and tiring for humans. Doctors will be able to concentrate their power of the hardest and most complicated cases, which are more suitable for a human mind, and less suitable for a machine. AI will also relieve the pressure on doctors caused by a lack of specialized radiologists.
But keep in mind that, in the end, the detected cancers have to be validated with a biopsy, and surgeries are often performed. I think these tasks will be performed by human doctors for a long time. The potential role of AI in screening mammography is to handle the millions of routine imaging exams, presenting the potential cancers to the doctors who perform follow-up procedures.
RG: What’s next for this research?
Ribli: Larger training and testing datasets need to be collected to enable further improvements. One interesting direction is breast tomosynthesis, an imaging technique proven to be superior to standard mammography. Tomosynthesis analysis takes even more time for a radiologist, and CAD has a potential role in that modality too. Another very important next step is to close the gap between research and practice. We would like to test the system in a clinical setup and eventually introduce it to routine care.
A demonstration version of the CAD model is available here.
