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Medicine Science

Experimental Blood Test Detects Cancer Up To Four Years Before Symptoms Appear (scientificamerican.com) 80

An anonymous reader quotes a report from Scientific American: For years scientists have sought to create the ultimate cancer-screening test -- one that can reliably detect a malignancy early, before tumor cells spread and when treatments are more effective. A new method reported today in Nature Communications brings researchers a step closer to that goal. By using a blood test, the international team was able to diagnose cancer long before symptoms appeared in nearly all the people it tested who went on to develop cancer. [...] Kun Zhang, a bioengineer at the University of California, San Diego, and a co-author of the study, and his colleagues began collecting samples from people before they had any signs that they had cancer. In 2007 the researchers began recruiting more than 123,000 healthy individuals in Taizhou, China, to undergo annual health checks -- an effort that required building a specialized warehouse to store the more than 1.6 million samples they eventually accrued. Around 1,000 participants developed cancer over the next 10 years.

Zhang and his colleagues focused on developing a test for five of the most common types of cancer: stomach, esophageal, colorectal, lung and liver malignancies. The test they developed, called PanSeer, detects methylation patterns in which a chemical group is added to DNA to alter genetic activity. Past studies have shown that abnormal methylation can signal various types of cancer, including pancreatic and colon cancer. The PanSeer test works by isolating DNA from a blood sample and measuring DNA methylation at 500 locations previously identified as having the greatest chance of signaling the presence of cancer. A machine-learning algorithm compiles the findings into a single score that indicates a person's likelihood of having the disease. The researchers tested blood samples from 191 participants who eventually developed cancer, paired with the same number of matching healthy individuals. They were able to detect cancer up to four years before symptoms appeared with roughly 90 percent accuracy and a 5 percent false-positive rate.

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Experimental Blood Test Detects Cancer Up To Four Years Before Symptoms Appear

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  • Too sensative? (Score:3, Interesting)

    by Tony Isaac ( 1301187 ) on Wednesday July 22, 2020 @10:47PM (#60321467) Homepage

    Our bodies contain cancer cells at all times. Normally, our immune systems seek and destroy these cells. It's only when the cancer cells begin to overwhelm the body's immune system that they start to grow out of control, forming tumors. If a test is too sensitive, it might lead to unnecessary treatments, some of which could itself harm a person's health.

    • by Misagon ( 1135 )

      I would trust doctors to instead use the test only as an indication to see if further tests (such as expensive CT scans) are necessary.

      That is, if this blood test doesn't become unattainable in comparison.

      • Doctor here. Just to be safe I'm putting you on chemo right away.
    • It's like all the argument over the number of asymptomatic and / or un-detected Covid19 "cases" and the resulting wild differences in estimating the case fatality rate. Perhaps the presence of some of the virus in your system doesn't matter if it doesn't result in transmission, immunity, or illness.
      • And your evidence that it doesn't result in transmission or illness?

        Asymptomatic carriers are a well understood vector for disease - perhaps you've heard the name "Typhoid Mary" before? And from what I've heard, it's estimated that roughly 1/3rd of new COVID cases were infected by asymptomatic carriers.

        Such carriers don't get sick, but they also aren't immune - the disease doesn't make them sick, but their bodies don't kill off the infection either, so they can still spread it. And they can potentially rem

    • by raymorris ( 2726007 ) on Wednesday July 22, 2020 @11:26PM (#60321543) Journal

      Hopefully your doctor reads at least the Slashdot summary, where it says the false positive rate is 5%. Meaning if a person tests positive, 95% chance they're going to have full-blown cancer if something isn't done - BUT that treatment can be relatively mild at that stage, or a year later when the cancer is definitely there, but small.

      Presumably, given the cancer doc has read at least one paragraph about the test on which she is basing treatment, this would be followed by further testing and potentially appropriate treatment at the right time based on risk. In any event, 95% is pretty strong. If I got a positive test, I'd darn sure take a treatment that makes me feel really crappy for a week and knocks out the stage 0 cancer.

      • With a sample size of 191, which is smaller than the number of possible cancers, it's really hard to be confident in a 5% false positive rate.

        • Well, it's not gonna be 50%, if that's what you mean

          It is too small, yes, and 1,000-10,000 people would be more up my alley, but enough for me to choose doing it if I'd ever need it.
          And I figure it's not exactly easy to get both 10k potential cancer patients and the financing for it too.

          • You're right, it's not going to be 50% overall. But the percentage is not likely to be evenly distributed. Some cancers may have a much higher false positive rate than others. In other words, it's the kind of thing that would lend itself to edge cases.

            It's also still being promoted by the original researcher / company. Others have yet to duplicate this kind of success.

        • With a sample size of 191, which is smaller than the number of possible cancers, it's really hard to be confident in a 5% false positive rate.

          Summaries, how do they work?

          Zhang and his colleagues focused on developing a test for five of the most common types of cancer: stomach, esophageal, colorectal, lung and liver malignancies.

      • by uncqual ( 836337 ) on Thursday July 23, 2020 @12:37AM (#60321637)

        They were able to detect cancer up to four years before symptoms appeared with roughly 90 percent accuracy and a 5 percent false-positive rate.

        Consider if 10,000 people are tested and 100 (1%) actually have one of the detected cancers.

        An "accuracy rate" of 90% is a "sensitivity" of 90% and means that 90 (90%) of the 100 with cancer would get a positive result and the remaining 10 would incorrectly get a negative result.

        A "false-positive rate" of 5% is a "specificity" of 95% and means that 495 of those 9,900 without cancer would incorrectly get a positive result.

        Therefore out of 504 positive tests, only 1.8% (9 of 504) of those with positive tests actually have one of these cancers. Presumably, each of those tests would need to be followed up on -- possibly with a procedure that is invasive (such as a biopsy), damaging to the patient (such as PET/CT), and/or expensive. If no follow up is done, there is no reason to do the test on that person in the first place. Since these would generally be detecting very early stage cancer, the followup may not be very accurate either.

        So, it would make little medical or economic sense to do this test every year on all adults (where perhaps 1% of that population may have one of these cancers in a given year).

        For high risk groups (age, family history, lifestyle) it might make sense as the percent of that population would have a much higher rate of one of those cancers in a given year.

        • Consider if 10,000 people are tested and 100 (1%) actually have one of the detected cancers.

          Given that both lung and colorectal are included here the actual cancers should be higher than 1%, significantly so.

          An "accuracy rate" of 90% is a "sensitivity" of 90% and means that 90 (90%) of the 100 with cancer would get a positive result and the remaining 10 would incorrectly get a negative result.

          A "false-positive rate" of 5% is a "specificity" of 95% and means that 495 of those 9,900 without cancer would incorrectly get a positive result.

          Therefore out of 504 positive tests, only 1.8% (9 of 504) of those with positive tests actually have one of these cancers. Presumably, each of those tests would need to be followed up on -- possibly with a procedure that is invasive (such as a biopsy), damaging to the patient (such as PET/CT), and/or expensive.

          In the civilized world where healthcare is not paid by the individual, cancers are quite expensive. That's why we have things like screening; the cost of screening an entire population is lower than treating the cancer cases that otherwise could be prevented. Picking up 9 cancer cases (the actual number would be higher than your example when screening at-risk sub-populations) out of 504 is a d

          • There's a difference between "not paid for by the individual" and "paid for by government, complete with price controls."

            The latter slows development, leading to net more deaths as the decades crawl by and invention of cures is slowed.

            Proof: Let's do price controls on new iPhones and see how development rates stay the same instead of falling off a cliff!

          • by uncqual ( 836337 )

            Given that both lung and colorectal are included here the actual cancers should be higher than 1%, significantly so.

            In any given year, across the entire population, 1% of the population first contracting (i.e., being detectable) one of these cancers is probably in the ballpark.

            Oh, and PET/CT/MR scans are not damaging.

            MR scans are not (ignoring occasional issues such as someone who has a metal fragment in their eye from an injury long ago and are unaware of it and get an MRI anyway) which is why I didn't inc

        • by AmiMoJo ( 196126 ) on Thursday July 23, 2020 @06:17AM (#60322085) Homepage Journal

          Depends why the false positives happen. If it's because of some temporary condition then you can just repeat the test again in a month or two and see if it goes away. You might even be able to test for whatever is known to cause false positives, say some hormone or something, and correct it.

          If this can detect cancer years in advance of where it normally gets detected then time is on our side.

          • by uncqual ( 836337 )

            True. The origins of the false positives would have to be better understood and perhaps they could be mediated. If they could be mediated, the false positive rate would effectively be much lower.

            For example if a retest of positives two months later results in 99% of the false positives now coming back negative, the test protocol perhaps could be defined as "One test negative => negative. Two positive tests separated by two months => positive". This would effectively increase the specificity of the tes

        • You make a good point.

          When testing for something that is extremely rare a priori, the false positives can be higher than the true positives, even though the false positive *rate* is low.

          On the other hand, cancer is not extremely rare. 38% of Americans get cancer at some point. If you didn't pay attention to high-risk groups and tested people at random every five years, something like 10% would be on their way to developing cancer. If you test people over 40 years old, the rate is higher.

          You also used the r

          • by uncqual ( 836337 )

            Of course I didn't RTFA and am relying in the summary and title. The title indicates that this test can detect cancer up to four years before symptoms appear.

            Assume, for the sake of argument, that on the average it will detect cancer two years before symptoms appear. In this case, screening every four years would result in (roughly) half the people testing negative (ignoring false positives and negatives) and showing symptoms before (or at) the time of their next test. In that scenario, the test would have

            • I note that after looking for methylation at 500 DNA locations, the program classified them into two groups a) expect cancer in the next few years or b) methylation is low, probably no cancer soon.

              Obviously there will be patients that are borderline, who have moderate methylation so they are close to the line between "cancer is very likely" and "cancer is noy likely". If I were the doctor, I would Re-test the borderline people 6 or 12 months later.

        • You make a very interesting point but I think you may have a slight problem with your math. In your example, you state that there are 504 positive results: 495 from false-positives and 9 from correct positives, but above that you had mentioned 100 people actually had cancer and the test reported positive for 90 (not 9) of those people. Unless I'm missing something, that would mean that 90 / (495 + 90) which comes out to 15.38% of the people who tested positive actually have cancer. And that presupposes t
          • by uncqual ( 836337 )

            Good catch. I started the analysis with a smaller sample size and ended up with a fractional person with cancer (or a person with a fractional cancer?). I therefore increased the sample size by a factor of ten to eliminate the fraction but failed to propagate that change everywhere :(

            This

            Therefore out of 504 positive tests, only 1.8% (9 of 504) of those with positive tests actually have one of these cancers.

            should read

            Therefore out of 585 positive tests, only 15.38% (90 of 585) of those with positive tests

      • "Hopefully your doctor reads at least the Slashdot summary,"

        You must be new here, nobody does, not even doctors.

      • by burgundy ( 53979 )

        You need to know more than the false positive rate alone. Rolling a D20 would give you a false positive rate of 5% too.

      • Hopefully your doctor reads at least the Slashdot summary, where it says the false positive rate is 5%. Meaning if a person tests positive, 95% chance they're going to have full-blown cancer if something isn't done

        NO! It does not mean that at all! This is a very common misinterpretation of false positive and false negative rates. What it means is that if a group of 100 people were all cancer free then about 5 of them would test positive under this test. In order to determine the probability of actually having cancer if you test positive, you need to fold in the a priori probability of having cancer and apply Bayes' Theorem [wikipedia.org].

    • Sounds like a good business model.

  • Elizabeth Holmes

    • Elizabeth Holmes deflected scientific scrutiny of her claims and convinced a bunch of VCs with unicorn fever that they should value Theranos at billions of dollars. This team has published a peer-reviewed article in Nature. What's the connection?
  • by ghoul ( 157158 ) on Wednesday July 22, 2020 @11:09PM (#60321511)

    The US medical system is about profit not health. Hospitals dont make much money if preventive measures are used to prevent cancer. They do make a lot of money from cancer surgery , chemo , radiation etc

    If this test works and cancer rates actually fall most hospital corporations will no longer be able to afford to pay multi million dollar CEO salaries.

    • Re: (Score:2, Insightful)

      by Krishnoid ( 984597 )

      Insurance companies can pay those salaries, why can't HMOs? They just have to sell the fear of cancer and insurance, not the cancer itself.

    • by khchung ( 462899 ) on Thursday July 23, 2020 @02:05AM (#60321757) Journal

      Out of 123K individuals, 1K developed cancer.

      Which one is more profitable? Yearly testing of 123K people + early treatment of 1K people, or only later stage cancer treatment of 1K people?

      With many business hoping to move to subscription model, it seems to me that yearly testing would be much more profitable, easier to streamline/increase efficiency and generally make more business sense.

      Not to mention the potential business opportunity of "up-selling" to 123x more regular customer.

      The problem with US business is the extreme short-sightedness of only looking at the next quarter, instead of looking at the next decade.

      • The problem with US business is the extreme short-sightedness of only looking at the next quarter, instead of looking at the next decade.

        That "US" problem, drives every damn stock market in the entire world.

        The problem with analyzing Greed, is we often try and color it, which is stupid. Humans suffer from the Disease of Greed, and that's been raging for thousands of years.

        • by khchung ( 462899 )

          The problem with US business is the extreme short-sightedness of only looking at the next quarter, instead of looking at the next decade.

          That "US" problem, drives every damn stock market in the entire world.

          Which is why most of the rest of the sane world do NOT let private for-profit companies takeover the health care of its citizens, and have some form of nationalized health care.

          Letting profit dictate health care makes this a US specific problem.

          • by ghoul ( 157158 )

            Its not only the US. India has the same problem too. However in India once in a while the mob lynches a few doctors and hospital administrators which keeps the greed and fear in balance

      • by dgatwood ( 11270 )

        Which one is more profitable? Yearly testing of 123K people + early treatment of 1K people, or only later stage cancer treatment of 1K people?

        Or continuous treatment of cancer as a chronic disease. If they do it right, they can come up with a treatment that just keeps it at bay, that you have to take once a month for the rest of your life....

        (Yeah, that's better than dying, but at some point, profit seeking leads to clearly worse outcomes.)

    • by AmiMoJo ( 196126 )

      I'm really glad we have universal healthcare that is motivated to keep you healthy and detect problems early.

    • The US medical system is about profit not health.

      A cancer test sounds like a great way to deny people insurance.

  • Not sure (Score:5, Interesting)

    by backslashdot ( 95548 ) on Wednesday July 22, 2020 @11:50PM (#60321575)

    Always wait for a second lab to independently confirm. These journals don't verify what you're saying is true or false, they only validate that what you REPORT is scientifically sound. As in, you have to report that you did all the proper verifications and controls properly. It could be 100% fabricated/made up data. In fact that's happened to me before numerous times .. we often waste months trying to replicate stuff idiots publish. The worst example so far (there are many) was when I wasted a bunch of hours one summer because some fool reported that an Argonaute protein (NgAgo) can be used for DNA editing. Believe me I'm still fucking bitter about that. Not only because it was false but because stupidly it made intuitive sense to me at the time so I wanted to believe it was true and kept trying to repeat the experiment without being more stringent.

  • They claim very high specificity; but looking at the graphs it sure seemed like there were more false positives than one would like. I'd hope this tool - if it pans out in further testing - is mainly used for "let's monitor you more frequently" rather than "yup, you should get your affairs in order now".

  • by Moof123 ( 1292134 ) on Thursday July 23, 2020 @12:22AM (#60321619)

    So a 5% false positive rate, and a 0.8% actual occurrence rate? So a positive test tells you you have a 1 in 7 chance of actually getting cancer? I see value in maybe identifying folks needing more frequent follow up checking, but 6 out of 7 positive results will not pan out but leave those folks freaking the hell out assuming their is a dagger over their heads constantly.

    • That is actually not bad numbers. Often it is far worse than one out 7.
      The main issue is how the doctors present it to the patient. They should not be saying "you tested positive for cancer". Instead they need to say something like "You have an indicator of cancer, we should do a test to be absolutely sure."

  • by BAReFO0t ( 6240524 ) on Thursday July 23, 2020 @01:46AM (#60321721)

    Why does that sound like exactly the ones caused directly by pollution and crap in our food and air?

  • by Djoulihen ( 1805868 ) on Thursday July 23, 2020 @02:38AM (#60321811)

    I was wondering why they chose these types of cancer (stomach, esophageal, colorectal, lung and liver) but did not include breast and prostate cancer, which are very common. It seems that they targeted the most deadly forms of cancer rather than the most common. Some numbers from WHO [who.int]:

    The most common cancers are:

            Lung (2.09 million cases)
            Breast (2.09 million cases)
            Colorectal (1.80 million cases)
            Prostate (1.28 million cases)
            Skin cancer (non-melanoma) (1.04 million cases)
            Stomach (1.03 million cases)

    The most common causes of cancer death are cancers of:

            Lung (1.76 million deaths)
            Colorectal (862 000 deaths)
            Stomach (783 000 deaths)
            Liver (782 000 deaths)
            Breast (627 000 deaths)

    Or breast and prostate cancer are just harder to spot ?

    • by Solandri ( 704621 ) on Thursday July 23, 2020 @04:38AM (#60321971)
      There's a lot of variation in cancer rates between countries. Cancer in the digestive tract is much more common in Asia than in the West. I've heard it speculated that it's because salting and refrigeration were the primary means of food preservation in the West, while fermenting is common in the East. Dunno if there's anything to that. Meanwhile, prostate cancer is relatively rare in China (breast cancer is a bit less common). Here are cancer incidence rates for China and the U.S. [nih.gov]

      Male
      • Lung - China 21.7%, U.S. 15.4%
      • Prostate - China 2.1%, U.S. 25.0%
      • Skin - China 0.1%, U.S. 4.7%
      • Liver - China 18.1%, U.S. 2.0%
      • Stomach - China 19.5%, U.S. 1.8%
      • Esophageal - China 10.8%, U.S. 1.7%
      • Colorectal - China 7.7%, U.S. 10.6%

      Female

      • Lung - China 14.3%, U.S. 14.5%
      • Breast - China 14.2%, U.S. 26.4%
      • Skin - China 0.1%, U.S. 4.0%
      • Liver - China 9.1%, U.S. 0.9%
      • Stomach - China 12.4%, U.S. 1.2%
      • Esophageal - China 7.0%, U.S. 0.5%
      • Colorectal - China 8.0%, U.S. 10.8%
      • This is really interesting information, with some obvious hypothesis from the data (though they may be wrong.

        Lung China> USA for men but not women: Air pollution and working in a factory vs home, or is it the far greater rate of smoking - do men in china smoke > women?

        Prostate may simply be food, and breast cancer may simply be a combination of Ashkenazi jews (genetic predisposition) plus the older pollution that America filled itself with before the 60's regulated it.

        Skin cancer may simply be due to

        • Maybe the higher use of squat toilets? We know there's a connection to sitting toilets and hemorrhoids. Perhaps there are other perks to using them we haven't really realized. Or perhaps it's related to a slight difference in life expectancy - data appears to be in the US' favor by a couple years.

          Would be interesting to see how other places in the work line up as it might make for interesting research.

      • Interesting data. I`ve read promising studies [nih.gov] of frequent green tea drinking slowing any potential prostate progression. As chinese generally take this with almost every meal, this data may support these theories.

  • Let's say the test is accurate enough. An individual gets diagnosed 4 years before symptoms appear. Then what happens? Immediate preventative chemo? Change of lifestyle?

    Or more likely: "We'll keep an eye on this for the next few years and then we'll be able to start addressing it. Maybe you'll be fortunate and nothing will come of it."

  • Aaaaand 95% of the posts: "Big Pharma is just going to use this to overcharge us!"
    5% of the posts: "This is so good we'll never hear of it again!"

    Whenever one of our universities or foundations makes a significant discovery with practical applications, perhaps we would all be making use of it sooner if we just gave it away to China and let them run with it.

  • The researchers tested blood samples from 191 participants who eventually developed cancer, paired with the same number of matching healthy individuals

    I see no reason to use the same number of people in the non-cancer group. Ideally you's use the whole 132,000 to build a statistically solid sample. Using 191 healthy people to compare to buys you nothing over a larger amount. There is no magic in that number, or their equality.

    Cost, maybe, but not statistical accuracy.

  • So they have 1.6M tests, but 1000 people developed cancer. Of those, about 20% developed cancer that was relevant to the test, so we'll assume the relevant healthy population was 320000 people.

    Of those 5% will get a "false positive" test: 16000 people. Of the 200 that will develop one of the tested-for cancers 180 will get a positive test like the 16000 people who won't. And 20 will be negative like the 304000 people who won't get cancer in the relevant period.

    Anyway, so now we're stuck with 16180 people wi

  • Okay; so you got tested and there is a 90 percent chance you'll have cancer in 4 years.
    Now what? Which cancer? How do I (pre-?)treat?
    Now I get to spend the next 4 years anxious over my impending disease, with no idea how it will manifest!

    I can make predictions, too. I predict that you will die sometime in the future (presuming you are live now).

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