Some thoughts on this as someone working on circulating-tumor DNA for the last decade or so:
- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.
- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.
- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).
This sort of thing is exactly like preventative whole body MRI scans. It's very noisy, very overwhelming data that is only statistically useful in cases we're not even sure about yet. To use it in a treatment program is witchcraft at this moment, probably doing more harm than good.
It COULD be used to craft a pipeline that dramatically improved everyone's health. It would take probably a decade or two of testing (an annual MRI, an annual sequencing effort, an annual very wide blood panel) in a longitudinal study with >10^6 people to start to show significant reductions in overall cancer mortality and improvements in diagnostics of serious illnesses. The diagnostic merit is almost certainly hiding in the data at high N.
The odds are that most of the useful things we would find from this are serendipitous - we wouldn't even know what we were looking at right now, first we need tons of training data thrown into a machine learning algorithm. We need to watch somebody who's going to be diagnosed with cancer 14 years from now, and see what their markers and imaging are like right now, and form a predictive model that differentiates between them and other people who don't end up with cancer 14 years from now. We [now] have the technology for picking through complex multidimensional data looking for signals exactly like this.
In the meantime, though, you have to deal with the fact that the system is set up exclusively for profitable care of well-progressed illnesses. It would be very expensive to run such a trial, over a long period of time, and the administrators would feel ethically bound to unblind and then report on every tiny incidentaloma, which completely fucks the training process.
This US is institutionally unable to run this study. The UK or China might, though.
> It would be very expensive to run such a trial, over a long period of time, and the administrators would feel ethically bound to unblind and then report on every tiny incidentaloma, which completely fucks the training process.
I wonder if our current research product is only considered the gold standard because doing things in a probabilistic way is the only way we can manage the complexity of the human body to date.
It’s like me running an application many, many times with many different configurations and datasets, while scanning some memory addresses at runtime before and after the test runs, to figure out whether a specific bug exists in a specific feature.
Wouldn’t it be a lot easier if I could look at the relevant function in the source code and understand its implementation to determine whether it was logically possible based on the implementation?
We currently don’t have the ability to decompile the human body, or understand the way it’s “implemented”, but that is something that tech is rapidly developing tools that could be used for such a thing. Either a way to corroborate enough information aggregated about the human body “in mind” than any person can in one lifetime and reason about it, or a way to simulate it with enough granularity to be meaningful.
Alternatively, the double-blindedness of a study might not be as necessary if you can continually objectively quantify the agreement of the results with the hypothesis.
Ie if your AI model is reporting low agreement while the researchers are reporting high agreement, that could be a signal that external investigation is warranted, or prompt the researchers to question their own biases where they would’ve previously succumbed to confidence bias.
All of this is fuzzy anyway - we likely will not ever understand everything at 100% or have perfect outcomes, but if you can cut the overhead of each study down by an order of magnitude, you can run more studies to fine-tune the results.
Alternatively, you can have an AI passively running studies to verify reproducibility and flag cases where it fails, whereas now the way the system values contributions makes it far less useful for a human author to invest the time, effort, and money. Ie improve recovery from a bad study a lot quicker rather than improve the accuracy.
EDIT: These are probably all ideas other people have had before, so sorry to anyone who reaches the end of my brainstorming and didn’t come out with anything new. :)
> This sort of thing is exactly like preventative whole body MRI scans. It's very noisy, very overwhelming data that is only statistically useful in cases we're not even sure about yet. To use it in a treatment program is witchcraft at this moment, probably doing more harm than good.
The child of a friend of mine has PTEN-Hamartom-Tumor-Syndrom, a tendency to develop tumors throughout life due to a mutation in the PTEN gene. The poor child gets whole body MRIs and other check-ups every half year. As someone in biological data science, I always tell the parents how difficult it will be to prevent false positives, because we don't have a lot of data on routine full body check-ups on healty people. We just know the huge spectrum on how healthy/ok tissue looks like.
>CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow...
I guess the problem is a mismatch between detection capability and treatment capability? We seem to be getting increasingly good at detecting precancerous states but we don't have corresponding precancer treatments, just the regular cancer treatments like chemo or surgery which are a big hit to quality of life, expensive, harmful etc.
Like if we had some kind of prophylactic cancer treatment that was easy/cheap/safe enough to recommend to people even on mild suspicion of cancer with false positives, we could offer it to positive tests. Maybe even just lifestyle interventions if those are proven to work. That's probably very difficult though, just dreaming out loud.
>I guess the problem is a mismatch between detection capability and treatment capability?
the problem is you do the test for 7 billion people, say, 30 times over their life... 210000000000 tests. imagine how many false negatives and false positives, the cost of follow up testing only to find... false positive. the cost of telling someone they have cancer when they don't. the anger of telling someone they are free of cancer, only to find out they had it all along
this tech isn't that good, nowhere near it, more like a 1 in 100 or 10 in 100 rate of "being wrong". those numbers can get cheesed towards more false positives or false negatives.
as for grail, they tried to achieve this and printed OK numbers... ... .. but their test set was their training set. so the performance metrics went to shit when they rolled it out to production
I think chemo in general kills rapidly dividing cells, which is a characteristic of cancer cells and, unfortunately, many types of regular cells as well, hence many of the side effects, like hair loss. If it is precancerous, then probably it’s not yet dividing in that way, so probably wouldn’t make much of a difference, unless you’d actually catch the moment when the switch to full fledged malignant happens.
Would you say ctDNA tools are sensitive and specific enough now to be able to make a decision about post op adjuvant therapies? “Now that I’ve had surgery, did the R0 resection get it all, or do I need to do chemo and challenging medication like mitotane?”
I’ve seen it most commonly thought of as using ctDNA to detect relapse earlier.
So, more like — did the tumor come back? And if that does happen, with ctDNA, can you detect that there is a relapse before you would otherwise find it with standard imaging. Most studies I’ve seen have shown that this happens and ctDNA is a good biomarker for early detection of relapse.
The case for proactively looking for circulating tumor DNA without an initial diagnosis or underlying genetic condition is a bit dicier IMHO. For example, what if really like to know (I haven’t read this article, but I’m pretty familiar with the field) is how many people had a detectable cancer in their plasma (ctDNA), but didn’t receive a cancer diagnosis. It’s been known for a while that you can detect precancerous lesions well before a formal cancer diagnosis. But, what’s still an open question AFAIK, is how many people have precancerous lesions or positive ctDNA hits that don’t form a tumor?
This seems like yet another place where the base rate is going to fuck us: intuitively (and you've actually thought about this problem and I haven't) I'd expect that even with remarkably good tests, most people who come up positive will not go on to develop related disease.
Ideally, you'd want a test (or two sequential ones) that's both very sensitive (rule candidates in) and specific (rule healthy peeps out). But that's only the first step, because there's no point knowing you're sick (from the populational and economic pov) if you can't do something useful about it. So you also have to include downstream tests and treatments in your assessment and all this suddenly becomes a very intricate probability network needing lots of data and thinking before decisions are made. And then, there's politics...
You might be able to target and preemptively treat some aggressive cancers!
I lost my wife to melanoma that metastasized to her brain after cancerous mole and margin was removed 4 years earlier. They did due diligence and by all signs there was no evidence of recurrence, until there was. They think that the tumor appeared 2-3 months before symptoms (headaches) appeared, so it was unlikely that you’d discover it otherwise.
With something like this, maybe you could get lower dose immunotherapy that would help your body eradicate the cancer?
Literally anything that reduces cancer deaths is a win. I'm certainly not campaigning against early detection tests like this! Just talking about a challenge that comes up operationalizing them.
How about tracking deltas between blood draws starting ant youngish age when things are on average presumed to be in a good state? When a new feature turns up in a subsequent blood draw, could it then be something more concerning?
The sensitivity challenge is compounded by the signal-to-noise ratio problem at ultra-low allelic fractions (<0.1%), where technical artifacts from library preparation and sequencing can mask true variants.
It’s when bone marrow cells acquire mutations and expand to take up a noticeable proportion of all your bone marrow cells, but they’re not fully malignant, expanding out of control.
Long term the goal should be to find a treatment that is safe enough and with so small side effects that it can be used for any suspicious mutations even though it may be decades away from killing you.
Yes.. as I read the OP post I was thinking about how many weak natural poisons (ie bloodroot) have been shown to be effective at dispersing through the body and how they might be a good treatment ie 1-2 month course of pills.
Here's what may seem like an unrelated question in response: how can we get 10^7+ bits of information out of the human body every day?
There are a lot of companies right now trying to apply AI to health, but what they are ignoring is that there are orders of magnitude less health data per person than there are cat pictures. (My phone probably contains 10^10 bits of cat pictures and my health record probably 10^3 bits, if that). But it's not wrong to try to apply AI, because we know that all processes leak information, including biological ones; and ML is a generic tool for extracting signal from noise, given sufficient data.
But our health information gathering systems are engineered to deal with individual very specific hypotheses generated by experts, which require high quality measurements of specific individual metrics that some expert, such as yourself, have figured may be relevant. So we get high quality data, in very small quantities -a few bits per measurement.
Suppose you invent a new cheap sensor for extracting large (10^7+ bits/day) quantities of information about human biochemistry, perhaps from excretions, or blood. You run a longitudinal study collecting this information from a cohort and start training a model to predict every health outcome.
What are the properties of the bits collected by such a sensor, that would make such a process likely to work out? The bits need to be "sufficiently heterogeneous" (but not necessarily independent) and their indexes need to be sufficiently stable (in some sense). What is not required if for specific individual data items to be measured with high quality. Because some information about the original that we're interested in (even though we don't know exactly what it is) will leak into the other measurements.
I predict that designs for such sensors, which cheaply perform large numbers of low quality measurements are would result in breakthroughs what in detection and treatment, by allowing ML to be applied to the problem effectively.
Or perhaps even routine bloodwork could incorporate some form of sequencing and longitudinal data banking. Deep sequencing, which may still be too expensive, generates tons of data that can be useful for things that we don't even know to look for today, capturing this data could let us retroactively identify meaningful biomarkers or early signals when we have better techniques. That way, each time models/methods improve, prior data becomes newly valuable. Perhaps the same could be said of raw data/readings from instruments running standard tests as well (as opposed to just the final results).
I'd be really curious to see how longitudinal results of sequencing + data banking, plus other routine bloodwork, could lead to early detection and better health outcomes.
Last time someone tried to inject chips into the bloodstream, public opinion didn't handle it too well. It's the same as we would learn a lot by being more cruel to research animals. But most people have other priorities. Good or bad ? Who knows ? Research meets social constructs.
Apart from the likely technical infeasibility of your idea in today's society, this would require a humongous and diversified population sample to be meaningful (your 'heterogeneous bits'). This follows directly from the complexity of metabolic pathways you wish to analyze. Socially, you'll only be able to achieve that by not asking your sample for consent. Otherwise you'll have a highly biased sample, which could still be useful but for severely restricted research questions.
There are some pretty big longitudinal studies with consent ( "45 and up" are a quarter of a million people, for example - that's big enough that working predictions within the cohort would be a worthwhile health outcome).
There are nevertheless privacy issues, which I did not address as my first comment was already very long, especially for a tangent. Most obviously, people would be consenting to the collection of data whose significance they cannot reasonably forsee.
I do agree that most current AI companies are unlikely to be a good steward of such data, and the current rush to give away health records needs to stop. In a way it's a good thing that health records are currently so limited, since the costs will so obviously outweigh the benefits.
Someone should add a sensor to all those diabetes sensors people have in their arms all day and collect general info. It would obviously bias towards diabetics but that's like half the US population anyways so maybe it wouldn't matter that much.
I think it's a very interesting approach and I highly support such an initiative. The easiest way to get a lot of data out of the body is probably to tap the body's own monitoring system - the sensory nerves.
A chemosensor also sounds like a useful thing it should give concentration by time. Minimally invasive option would be to monitor breath, better signal in blood.
Sadly health insurance in the US is unlikely to pay for most preventative care because the followup costs of false-positives and that they are betting that down the line someone else will pick up the tab when you get sick decades later (like the government).
It's kind of why I'm favor of universal option to align financial incentives. Like given how sick the US population is, it probably makes sense to put a lot more people of GPL-1s and invest in improving their efficacy and permanence. Like nationalize-the-patent COVID-operational-warp-speed level urgency. There are over 100M Americans that are pre-diabetic, the cost of treating a diabetic is about 20k/yr. So $4 trillion in new costs, on top of the misery and human suffering.
I have a friend nearing mid-60s. Retired military so now covered by Medicare, then Tri-Care. Having prostate issues. PSA went from 12 to 19. Desperate to get a PET scan to determine his is benign BPH, or cancer. Cannot get his scan approved since both insurances will not approve a PET as an early diagnostic tool (scan is about $7500). Cannot imagine what will happen if everyone getting a cancer DNA signal of this type tries to get clarification via additional tests. USA health care really does not work that way. HTH, RF
A PSA of 12 is pretty far past the threshold for an MRI (don’t know about a PET scan) and an MRI would be pretty determinative about whether or not a biopsy is warranted. A biopsy would be pretty good at identifying cancer.
Sounds like either there are complicating factors or an absence of standard protocol adherence.
US health insurance is a mess, but that doesn’t sound like the entire story. I suspect urologists see a fair amount of friction for routine procedures related to prostrate health.
He had the MRI. Not conclusive. The PSA jump (alredy very high) is biggest concern. PET would -- according to him -- be most conclusive. Yet he cannot get it approved, so lives in a cruel medical purgatory.
He had a biopsy a while ago. It was negative (and very painful he said). He has been working closely with his urologist who has recommended the PET. Given the PSA jump he is really worried, and cannot get what I presume is his urologist's next recommendation. He has taken all the right steps, just to be denied re: PET. (To be honest I do not know if PET is that effective, but he says it would be definitive.) He was told, though, that should he get cancer the PET would be approved to enhance the diagnosis. My heart goes out to him. RF.
They care about prevention but only if it's very cheap. I get emails all the time from my insurance company about joining their program that is supposed to help you live a healthier lifestyle.
I started getting emails from Cigna about Omada after switching over to them last year. They pitch it as something you can sign up for to get health coaching. They (or their AI, soon if not already) provide that by sending you some "free" sensors (scale, pedometer, etc) and collecting lots of health information.
Searching the web shows that Cigna forces some patients to use this program in order to receive coverage for certain conditions. They're likely saving all the info collected through it in order to use it to deny you coverage if they can at all make an argument that something was caused by your lifestyle, was pre-existing for a certain amount of time, etc-- at least, that's the vibe I got from researching it.
How do you convince those pre-diabetic people to use a GLP-1? There was quite a bit of backlash about the one-time injection COVID vaccine when it was mandated.
You don’t need to mandate it, heaps of people who are obese or overweight are eager to take it, because they are sick of being this way, worried about the long-term health risks, feel the societal sigma, etc. For many such people who currently don’t, the big reason is not that they don’t want to, it is that their insurance doesn’t cover it and they can’t afford the $$$ of paying for it uninsured-but as patents expire the price is going to come down. Other people don’t like injecting themselves, but oral formulations are becoming available
COVID was different because being a transmissible disease, there was a strong motivation to try to maximise the percent of the population immunised. With GLP-1 agonists, if you made them freely available, likely over >50% of eligible patients would take them voluntarily, which would result in massive long-term cost savings from lifestyle diseases, even considering the continued costs from the other 50% who will refuse. And insurers may even give discounts to those who take GLP-1s (if permitted by regulators)
GLP-1s are probably going to have the unintended side effect of increasing weight stigma - already obesity skews poor, once most of the well-off obese people cure their obesity with GLP-1s it is going to skew even more poor. I can foresee a cycle in which GLP-1s increase weight stigma which pushes more people into taking them which then increases weight stigma even more, which could drive up their adoption even further
Any bureaucratic system is going to be inefficient. You see it in countries with universal healthcare. In Canada, some provinces now have wait times of over a year from referral to treatment. Many European countries face similar access issues, though France and the Netherlands perform somewhat better.
The U.S. is a different kind of mess. It’s a patchwork of heavy government restrictions, large public programs like Medicare, and for-profit corporations, all thrown together without a coherent design. It’s no surprise it’s expensive. In 2023, healthcare spending was nearly 18% of GDP. Another factor could simply be wealth: higher per capita GDP tends to correlate with higher healthcare spending. To be fair to the U.S. healthcare system, it is highly capitalized, with much higher concentrations of diagnostic equipment like MRI machines than other OECD countries, and it does have some of the highest five-year survival rates for cancer and heart disease.
Even so, all of these healthcare systems are heavily dysfunctional in many ways.
In contrast to all of this, cosmetic surgery and laser eye surgery are the only fields of medicine where prices have actually fallen in inflation-adjusted terms, which is extraordinary, as prices in healthcare in general have increased much faster than inflation. The superior performance of these fields is because of basic market dynamics. People pay out of pocket, so they’re price conscious, and providers compete. There are also fewer regulatory restrictions since these fields aren’t tied up in government programs like Medicare.
Innovation is the only thing that reliably drives prices down. But in most of healthcare, it moves slowly. Devices often take 10-30 years to cycle out. Compare that to consumer electronics, where turnover happens every 1-2 years.
If it were up to me, I’d make restrictions on medical providers much lighter. Anyone could offer medical procedures as long as they disclose they’re uncertified and include a government-mandated warning. That kind of freedom is necessary to solve hard problems. You can’t regiment innovation and industry development. Gatekeeping in the name of consumer safety is the worst thing that can be done to any industry, and unfortunately, there is heavy gatekeeping in healthcare.
That is not to say that I am opposed to government intervention in general. I think it can play a critical role in advancing healthcare. Where government intervention creates the most value is in funding research for the public domain: drug designs, medical procedures, and open datasets. These investments have enormous returns and are best handled by governments. If the private sector focused on delivery and innovation, with governments making strategic contributions in foundational research, healthcare would see revolutionary improvements generation after generation.
US private healthcare insurance is required to pay for “medically necessary” treatments and generally does pay for medicine where they are unlikely to see the benefits (see statins).
The big secret is that they could detect cancer very early in most people, but the health care companies don't want to pay for the screening. You can pay out of pocket for these procedures. I was told this by a cancer researcher
EDIT:
Adding these caveats:
1. There is a ton of nuance in the diagnosis, since most people have a small amount of cancer in their blood at all times
2. The screenings are 5-10k + follow up appointments to actually see if its real cancer
3. All in cost then could be much higher per person
4. These tests arent something that are currently produced to be used at mass scale
The not so big secret is that we can detect cancer early in a lot of people, but we also would detect a lot of not-cancer. We don't currently know the cost/benefit of that tradeoff for all these new types of screening, and therefore insurers and health systems are reluctant to pay the cost of the both screening and the subsequent workup. This is not just a financial consideration, though the financial part is a big part -- the workup for those that end up as not-cancer has non-negligible risks for the patients as well (I have had patients of mine suffer severe injury and even die from otherwise routine biopsies), and on top of that, some actual cancers may not really benefit from early discovery in the first place.
This is not to downplay the potential benefit of early cancer detection... which is huge. And in the US/UK anyway, there are ongoing large trials to try to figure some of this stuff out in the space of blood-based cancer screening, as part of the path to convincing regulatory bodies and eventual reimbursement for certain tests. As mentioned, you can currently at least get the Galleri test out of pocket (<$1k, not cheap, but not exorbitant either), as well as whole body MRIs (a bit more expensive, ~$2-5k).
Many prostate cancers, for instance, are slow growing and won't kill you before something else does. If you try to take that kind of cancer out surgically or zap it with radiation or chemo the side effects could be severe.
Treatments for prostate cancer are consistently improving. And what makes sense when you are 55 might be different than what does at 75…like all health care issues.
Yeah, after a detection there is alot of work to determine if what they detected should be worried about. But this doesnt take away from the fact that cancer can be detected very early, and these screenings could easily save your life
There's not a lot of evidence that full body MRIs are beneficial. A lot of people have pre-cancerous growths that may or may not become cancer in the future, so you may just be giving them unnecessary surgery, and surgeries are not risk-free. If you don't operate, they might develop an anxiety disorder.
We do a lot of CT imaging in the emergency department and it sucks if we incidentally find an abnormal growth in a young patient's CT head. These are usually benign and often not worth performing brain surgery to get a biopsy.
Why not just rescan them every few months to see if it's still growing? After all, you wouldn't have to rescan the full body, just the section where the growth is.
No, the potential harm comes from follow-up tests. That's why screening strategies are designed by professionals. It's a pretty complex field, and all the people here fielding their opinions on how we should proceed about tests don't have a single idea about the implications of their theories.
What a ridiculous statement to make. No wonder the US is in the state it is in. Lets let the ignorant and uninformed decide on policy rather than the scientific community and experts. What could possibly go wrong?
Honestly, you don't have access to the necessary data to make rational decisions. That's not gatekeeping, it's logic. I don't have access to it either, although I'm indeed a healthcare pro. Screening strategies are a hyperspecialized domain and only experts somewhat understand what they're doing. It's just like making theories about what the CERN guys should be doing while not having passed physics 101 with no access to experimental data. That's why I'm just saying: you're certainly allowed to question, but you certainly can't make up assertions either.
Get treated for the cancer you will now survive because you just caught early. The answer is so obvious I think I may have misunderstood what you mean here.
The fact that this answer is so obvious to you means you have to read up on diagnostic test performance and how screening works, because it's in fact not obvious at all. I mean that in the nicest way possible. Those companies offering expensive screening are not what they seem. Whether their offering is useful or whether they're just swindling you is a question that needs lots of time, money and sweat to answer.
Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up. The only people who would benefit from these screenings are already unhealthy and cancer might be just one of many potential conditions they could experience—the goal of healthcare is not to dedicate an inordinate amount of resources for procedures that may amount to not much of any long term benefit.
People talk about the “immune system” but they are really referring to a number of systems the body uses to regulate itself, more or less successfully, around environmental pressures. The body is a system under tension, sometimes extreme tension leads to extreme success (success here being growth of power), sometimes it breaks the body, and sometimes the systems have been slowly failing for a while, and most treatments will not help. Medicine is only useful in the specific case where the power of the body would be promoted if not for one thing, that the body would be healthy, at least manageably so, without that issue.
> Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up
Incorrect.
There are tons of cancers that hide and mask with symptoms common to other symptoms. Kidney cancer, for example, presents pretty similarly to both kidney stones and UTIs. Even blood in the urine isn't proof positive that anything is wrong beyond either of those conditions. And, by the time blood is in the urine, it's often too late.
Liver cancer is even worse. The first symptoms you get can be thought of as a simple pulled muscle, just a little ache in the back. By the time you have appreciable problems, like turning yellow, it's quite advanced and too late to really do much.
There are common cancers like colon, skin, breast, and prostate that more fit your description of being mostly harmless so long as you get regular screenings and eat healthy. But, for every part of the body, a cancer can form and the symptoms are very often invisible.
I'm unfortunately all too familiar with how cancer looks. My wife currently has stage 4 cancer that started as kidney cancer. She does not drink or smoke, gets enough rest, and is very active.
No I mean that people who are healthy in general are less likely (or completely unlikely) to “get cancer” in the first place because cancer is something that has more to do with an immune system failure, which happens due to unhealthy lifestyles or genetic problems in general which are unavoidable. Cancer only affects people who generally already have other problems (old, sick, unhealthy lifestyles etc.) and young people because they are growing very quickly.
Thus, in young people cancer presents rapidly as they develop, these screenings are expensive and unnecessary. For old/sick/unhealthy people, or people who are predisposed to certain cancers, they will probably get something else anyway, so its an expensive workup to help treat a disease that won’t actually benefit much in the long term.
I’m not against treating cancer, however let’s recognize that cancer treatment is already an expensive and resource/labor intensive process. And 10yr survival rates are not great for most cancers, we’re only slowing the burn, not stopping it. Sometimes you get lucky and die of something else before the cancer can come back, but nobody is ever “cured,” they are all just delaying the inevitable. Which, as we have seen, can sometimes be worth it (who wouldn’t want another 10 years with a loved one?), but that doesn’t mean our goal should be to find a way to “cure” cancer, it should be to find a way to better manage it, and these screenings don’t seem like they really are, or at least the use-cases for them are minimal.
IDK TBH. My wife had all the general recommended screenings. The only thing that showed potential problems was slightly elevated WBC. It was ultimately what they thought was a UTI that stayed a little too long that got us to get a CT and ultimately the diagnosis.
I do wonder if a 5 year whole body MRI or CT would be generally beneficial for the population. I don't think it needs to be Annual to have benefits.
The problem is it really isn't uncommon for your body to create random puss fill sacks all over the place. It's one thing our cancer doctor warned us about. My wife is now on a 6 month CT regimen and ultimately, they'll just ignore new lumps.
My NP would tell me "nothing to worry about" whether she knows what's going on or not, but that's beside the point.
GP wasn't asking what they should personally do. They were asking how the doctor would screen for it. (The truth is, the doctor can't/won't-- an annual MRI on every otherwise healthy person, for example, would be prohibitively expensive with how MRIs are currently set up-- and as another commenter pointed out, findings from those can be just as easily ignored or put off until it's too late.)
Yeah but then you'd go through life having biopsies all the time. If all people did a full body MRI almost everyone would have weird lumps that doctors would have to biopsy to be really sure, and then what do you do? Do you biopsy yourself every time some weird tissue appears? Most of those will be nothing and you'll be going through the complications of surgeries and anesthesia all the time just to always make sure.
Assuming some future MRI technology which was very cheap, wouldn't you have MRIs at fairly regular intervals, to first see if the lump was growing or changing shape? And if this was being done at population scale, you'd train up an AI on the known outcomes, to have it flag up problems for a human to review.
Assuming MRIs weren't exorbitantly expensive, then the answer would probably be to simply rescan a month or 2 later and biopsy the lumps that don't go away.
Doing this could be actively worse for you and society based on the false positive rate. Testing and accidental unneeded treatment carry very real risks that could lead to net suffering and more death or damage if enough people are tested.
Public healthcare policy is absolutely not something personal.
It involves costs of healthcare for all people involved, workload on health professionals, hospital occupancy, etc and so forth.
If the rate of false positives in these tests are too high, people that need treatment for their actual illnesses might be on a waiting list because too many are doing follow-up screening and biopsies for non-issues.
And to address your silly "collectivist" fear-mongering, your hyper-individualist mentality is a societal disease. We could do with some more collectivism, in the sense that people have a better understanding of the constraints and conditions of the society they are inserted in.
That's just wrong. Taking a test doesn't do anything to the data-generating process, your chance of death is 100%. The test merely informs your posterior about the timing of the event.
The timing is pretty important to most people, and is actually the whole point of taking the test in the first place so the generating process and the test are not independent. See ?! What you said is just wrong too ! ;-)
The usual story is that you’re just better off not knowing because you’ll end up doing more harm than good chasing every little suspicious diagnosis. Cancer happens all the time, but many times doesn’t lead to anything.
I actually know a little about this through my work. Cell-free DNA (CfDNA) Has been known about for a few decades, but has become more of a focus in recent years because of the advent of immunotherapies, which are often highly targeted drugs. CfDNA has also been used in "liquid biopsies" i.e, a simple blood draw, because it can help you profile the tumor and location of the cancer.
In my field, we all think that CfDNA testing will eventually become a standard thing that will go along with your annual physical's blood test, because it has predictive/preventative abilities.
how actionable is the result? let's say you do detect trace amounts of tumoral DNA in your blood, what can you do? can you prevent it from developing into a full-on tumor if you don't even know where it is?
Seems this newfound ability to detect cancers earlier than we thought possible could be used to develop better treatments to boost the body's innate ability to eliminate cancerous cells before they turn malign: 1) identify thousands of people with traces of cancerous DNA that are too weak to merit immediate action and who are willing to participate in a trial. 2) Divide them into two groups, one group gets for one month a daiiy dose of auricularia auricula fungus extract or whatever that is believed to possibly prevent cancers from developing, the other group gets a placebo. 3) Run the early-detection test again at the end of the month to see whether or not there is a difference in cancerous DNA signal strength between the two groups.
A relative had this or a similar test come back positive. This sounds like a helpful signal on paper, but in reality it's not always actionable.
They assumed their previous cancer had survived and metastasized. Doctors couldn't find the source. It turned into a waiting game, where they lived with a sword of Damocles over their head. They were retested every few months and monitored. Then after a year the tests the levels dropped off. And the end result was nothing came of it so far.
It's normal to have some amount of pre-cancerous cells get naturally removed by your immune system. And this catches those too.
How to use such test results? I propose your GP knows your test results but you don't. You see the GP about a mole or something and the GP (not you) gets to decide on further tests / treatment, or sends you home saying don't worry about it.
Quite interesting to me and first time I am hearing about this.
Question for you, what do you do when it shows you may have cancer? Do you speak to your physician? Surely, this will change your life even if it doesn't need treatment for next 6 years? Does the treatment change? Can the treatment be done based on those results?
So many questions.
I'm hoping we find more stuff for Alzheimer's. My aunt and now mother have it. I fear that I am next and I am too scared of doing the DNA test to check for genes.
You immediately bring the results to your doctor ASAP. They'll recommend follow-up testing since they want verification of third-party results and, well, are doctors and will know better about what to test for. If you do indeed have cancer, they will refer you to an oncologist who sub-specializes in that type of cancer.
I have heard rumors of a universal healthcare system in this mythical far off "eee ewe" land, where people don't pay out of pocket for ordinary procedures, and medical bankruptcy isn't a thing. Perhaps that is related to their query.
Some life insurance companies offered it for free as part of a service to existing clients. Mine claimed they would not know the results. I hope its true because I did take them up on the offer. Results were statistically favorable for me so I appreciate the test for what it is.
Curious to see how these hold up over the long term.
Have you seen function health? It’s now a unicorn.
As far as I can tell, they did a wholesale deal with quest diagnostics, and run your results through ChatGPT and give you supplement / diet recs via a pretty web portal 2x a year for $499.
Claim is it’s 100 biomarkers and would cost avg person $15k retail.
Full text is paywalled, and no mention in abstract of false positive rate in control group. Has this test actually been independently verified? No mention of that important fact in the press release.
Some thoughts on this as someone working on circulating-tumor DNA for the last decade or so:
- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.
- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.
- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).
This sort of thing is exactly like preventative whole body MRI scans. It's very noisy, very overwhelming data that is only statistically useful in cases we're not even sure about yet. To use it in a treatment program is witchcraft at this moment, probably doing more harm than good.
It COULD be used to craft a pipeline that dramatically improved everyone's health. It would take probably a decade or two of testing (an annual MRI, an annual sequencing effort, an annual very wide blood panel) in a longitudinal study with >10^6 people to start to show significant reductions in overall cancer mortality and improvements in diagnostics of serious illnesses. The diagnostic merit is almost certainly hiding in the data at high N.
The odds are that most of the useful things we would find from this are serendipitous - we wouldn't even know what we were looking at right now, first we need tons of training data thrown into a machine learning algorithm. We need to watch somebody who's going to be diagnosed with cancer 14 years from now, and see what their markers and imaging are like right now, and form a predictive model that differentiates between them and other people who don't end up with cancer 14 years from now. We [now] have the technology for picking through complex multidimensional data looking for signals exactly like this.
In the meantime, though, you have to deal with the fact that the system is set up exclusively for profitable care of well-progressed illnesses. It would be very expensive to run such a trial, over a long period of time, and the administrators would feel ethically bound to unblind and then report on every tiny incidentaloma, which completely fucks the training process.
This US is institutionally unable to run this study. The UK or China might, though.
> It would be very expensive to run such a trial, over a long period of time, and the administrators would feel ethically bound to unblind and then report on every tiny incidentaloma, which completely fucks the training process.
I wonder if our current research product is only considered the gold standard because doing things in a probabilistic way is the only way we can manage the complexity of the human body to date.
It’s like me running an application many, many times with many different configurations and datasets, while scanning some memory addresses at runtime before and after the test runs, to figure out whether a specific bug exists in a specific feature.
Wouldn’t it be a lot easier if I could look at the relevant function in the source code and understand its implementation to determine whether it was logically possible based on the implementation?
We currently don’t have the ability to decompile the human body, or understand the way it’s “implemented”, but that is something that tech is rapidly developing tools that could be used for such a thing. Either a way to corroborate enough information aggregated about the human body “in mind” than any person can in one lifetime and reason about it, or a way to simulate it with enough granularity to be meaningful.
Alternatively, the double-blindedness of a study might not be as necessary if you can continually objectively quantify the agreement of the results with the hypothesis.
Ie if your AI model is reporting low agreement while the researchers are reporting high agreement, that could be a signal that external investigation is warranted, or prompt the researchers to question their own biases where they would’ve previously succumbed to confidence bias.
All of this is fuzzy anyway - we likely will not ever understand everything at 100% or have perfect outcomes, but if you can cut the overhead of each study down by an order of magnitude, you can run more studies to fine-tune the results.
Alternatively, you can have an AI passively running studies to verify reproducibility and flag cases where it fails, whereas now the way the system values contributions makes it far less useful for a human author to invest the time, effort, and money. Ie improve recovery from a bad study a lot quicker rather than improve the accuracy.
EDIT: These are probably all ideas other people have had before, so sorry to anyone who reaches the end of my brainstorming and didn’t come out with anything new. :)
> This sort of thing is exactly like preventative whole body MRI scans. It's very noisy, very overwhelming data that is only statistically useful in cases we're not even sure about yet. To use it in a treatment program is witchcraft at this moment, probably doing more harm than good.
The child of a friend of mine has PTEN-Hamartom-Tumor-Syndrom, a tendency to develop tumors throughout life due to a mutation in the PTEN gene. The poor child gets whole body MRIs and other check-ups every half year. As someone in biological data science, I always tell the parents how difficult it will be to prevent false positives, because we don't have a lot of data on routine full body check-ups on healty people. We just know the huge spectrum on how healthy/ok tissue looks like.
Hopefully gene therapy can fix this sort of problem.
is it even possible for gene therapy to just rewrite all the existing DNA in a body? can't you only do that to cells that are dividing or whatever?
They've managed to treat sickle cell.
>CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow...
https://www.fda.gov/news-events/press-announcements/fda-appr...
I guess the problem is a mismatch between detection capability and treatment capability? We seem to be getting increasingly good at detecting precancerous states but we don't have corresponding precancer treatments, just the regular cancer treatments like chemo or surgery which are a big hit to quality of life, expensive, harmful etc.
Like if we had some kind of prophylactic cancer treatment that was easy/cheap/safe enough to recommend to people even on mild suspicion of cancer with false positives, we could offer it to positive tests. Maybe even just lifestyle interventions if those are proven to work. That's probably very difficult though, just dreaming out loud.
People are routinely notified they are pre-diabetes.
It gives people the agency to alter their lifestyle trajectory.
I personally suspect that people get and cure cancer all the time.
I wonder if cancer is just damage to your body - either a lot of direct damage or interfering with the body's ability to manage/heal itself.
if someone was pre-cancer, would it help to exercise, cut out sugar, use the sauna, stop overeating? I'll bet it might make a difference
>I guess the problem is a mismatch between detection capability and treatment capability?
the problem is you do the test for 7 billion people, say, 30 times over their life... 210000000000 tests. imagine how many false negatives and false positives, the cost of follow up testing only to find... false positive. the cost of telling someone they have cancer when they don't. the anger of telling someone they are free of cancer, only to find out they had it all along
this tech isn't that good, nowhere near it, more like a 1 in 100 or 10 in 100 rate of "being wrong". those numbers can get cheesed towards more false positives or false negatives.
as for grail, they tried to achieve this and printed OK numbers... ... .. but their test set was their training set. so the performance metrics went to shit when they rolled it out to production
do the chemo medications not do anything useful at low(er) doses in these precancerous situations?
I think chemo in general kills rapidly dividing cells, which is a characteristic of cancer cells and, unfortunately, many types of regular cells as well, hence many of the side effects, like hair loss. If it is precancerous, then probably it’s not yet dividing in that way, so probably wouldn’t make much of a difference, unless you’d actually catch the moment when the switch to full fledged malignant happens.
Weren't the mRNA vaccines created exactly for that?
Would you say ctDNA tools are sensitive and specific enough now to be able to make a decision about post op adjuvant therapies? “Now that I’ve had surgery, did the R0 resection get it all, or do I need to do chemo and challenging medication like mitotane?”
I’ve seen it most commonly thought of as using ctDNA to detect relapse earlier.
So, more like — did the tumor come back? And if that does happen, with ctDNA, can you detect that there is a relapse before you would otherwise find it with standard imaging. Most studies I’ve seen have shown that this happens and ctDNA is a good biomarker for early detection of relapse.
The case for proactively looking for circulating tumor DNA without an initial diagnosis or underlying genetic condition is a bit dicier IMHO. For example, what if really like to know (I haven’t read this article, but I’m pretty familiar with the field) is how many people had a detectable cancer in their plasma (ctDNA), but didn’t receive a cancer diagnosis. It’s been known for a while that you can detect precancerous lesions well before a formal cancer diagnosis. But, what’s still an open question AFAIK, is how many people have precancerous lesions or positive ctDNA hits that don’t form a tumor?
(I’ve done a little work in this area)
It seems like adjuvant treatment is rather routine at this point?
And the question would be “do I believe the test when it tells me the cancer is gone?” When you know it’s not 100% accurate?
Or do you always do the adjuvant treatment considering the very small chance the test is wrong has a very high cost (death)?
This seems like yet another place where the base rate is going to fuck us: intuitively (and you've actually thought about this problem and I haven't) I'd expect that even with remarkably good tests, most people who come up positive will not go on to develop related disease.
Ideally, you'd want a test (or two sequential ones) that's both very sensitive (rule candidates in) and specific (rule healthy peeps out). But that's only the first step, because there's no point knowing you're sick (from the populational and economic pov) if you can't do something useful about it. So you also have to include downstream tests and treatments in your assessment and all this suddenly becomes a very intricate probability network needing lots of data and thinking before decisions are made. And then, there's politics...
You might be able to target and preemptively treat some aggressive cancers!
I lost my wife to melanoma that metastasized to her brain after cancerous mole and margin was removed 4 years earlier. They did due diligence and by all signs there was no evidence of recurrence, until there was. They think that the tumor appeared 2-3 months before symptoms (headaches) appeared, so it was unlikely that you’d discover it otherwise.
With something like this, maybe you could get lower dose immunotherapy that would help your body eradicate the cancer?
I'm so sorry about your wife.
Literally anything that reduces cancer deaths is a win. I'm certainly not campaigning against early detection tests like this! Just talking about a challenge that comes up operationalizing them.
How about tracking deltas between blood draws starting ant youngish age when things are on average presumed to be in a good state? When a new feature turns up in a subsequent blood draw, could it then be something more concerning?
The sensitivity challenge is compounded by the signal-to-noise ratio problem at ultra-low allelic fractions (<0.1%), where technical artifacts from library preparation and sequencing can mask true variants.
> due to CHIP
What is CHIP?
Clonal hematopoiesis of indeterminate potential.
It’s when bone marrow cells acquire mutations and expand to take up a noticeable proportion of all your bone marrow cells, but they’re not fully malignant, expanding out of control.
https://en.wikipedia.org/wiki/Clonal_hematopoiesis
Long term the goal should be to find a treatment that is safe enough and with so small side effects that it can be used for any suspicious mutations even though it may be decades away from killing you.
Yes.. as I read the OP post I was thinking about how many weak natural poisons (ie bloodroot) have been shown to be effective at dispersing through the body and how they might be a good treatment ie 1-2 month course of pills.
It could motivate to shift to plant based diet; start meditating; stop drinking; begin regular 5-7 day fasts; etc.
Here's what may seem like an unrelated question in response: how can we get 10^7+ bits of information out of the human body every day?
There are a lot of companies right now trying to apply AI to health, but what they are ignoring is that there are orders of magnitude less health data per person than there are cat pictures. (My phone probably contains 10^10 bits of cat pictures and my health record probably 10^3 bits, if that). But it's not wrong to try to apply AI, because we know that all processes leak information, including biological ones; and ML is a generic tool for extracting signal from noise, given sufficient data.
But our health information gathering systems are engineered to deal with individual very specific hypotheses generated by experts, which require high quality measurements of specific individual metrics that some expert, such as yourself, have figured may be relevant. So we get high quality data, in very small quantities -a few bits per measurement.
Suppose you invent a new cheap sensor for extracting large (10^7+ bits/day) quantities of information about human biochemistry, perhaps from excretions, or blood. You run a longitudinal study collecting this information from a cohort and start training a model to predict every health outcome.
What are the properties of the bits collected by such a sensor, that would make such a process likely to work out? The bits need to be "sufficiently heterogeneous" (but not necessarily independent) and their indexes need to be sufficiently stable (in some sense). What is not required if for specific individual data items to be measured with high quality. Because some information about the original that we're interested in (even though we don't know exactly what it is) will leak into the other measurements.
I predict that designs for such sensors, which cheaply perform large numbers of low quality measurements are would result in breakthroughs what in detection and treatment, by allowing ML to be applied to the problem effectively.
Or perhaps even routine bloodwork could incorporate some form of sequencing and longitudinal data banking. Deep sequencing, which may still be too expensive, generates tons of data that can be useful for things that we don't even know to look for today, capturing this data could let us retroactively identify meaningful biomarkers or early signals when we have better techniques. That way, each time models/methods improve, prior data becomes newly valuable. Perhaps the same could be said of raw data/readings from instruments running standard tests as well (as opposed to just the final results).
I'd be really curious to see how longitudinal results of sequencing + data banking, plus other routine bloodwork, could lead to early detection and better health outcomes.
Last time someone tried to inject chips into the bloodstream, public opinion didn't handle it too well. It's the same as we would learn a lot by being more cruel to research animals. But most people have other priorities. Good or bad ? Who knows ? Research meets social constructs.
I am not proposing injecting chips.
Apart from the likely technical infeasibility of your idea in today's society, this would require a humongous and diversified population sample to be meaningful (your 'heterogeneous bits'). This follows directly from the complexity of metabolic pathways you wish to analyze. Socially, you'll only be able to achieve that by not asking your sample for consent. Otherwise you'll have a highly biased sample, which could still be useful but for severely restricted research questions.
There are some pretty big longitudinal studies with consent ( "45 and up" are a quarter of a million people, for example - that's big enough that working predictions within the cohort would be a worthwhile health outcome).
There are nevertheless privacy issues, which I did not address as my first comment was already very long, especially for a tangent. Most obviously, people would be consenting to the collection of data whose significance they cannot reasonably forsee.
I do agree that most current AI companies are unlikely to be a good steward of such data, and the current rush to give away health records needs to stop. In a way it's a good thing that health records are currently so limited, since the costs will so obviously outweigh the benefits.
Someone should add a sensor to all those diabetes sensors people have in their arms all day and collect general info. It would obviously bias towards diabetics but that's like half the US population anyways so maybe it wouldn't matter that much.
If you can let the detector be so cheap, doctor will love you!
I think it's a very interesting approach and I highly support such an initiative. The easiest way to get a lot of data out of the body is probably to tap the body's own monitoring system - the sensory nerves.
A chemosensor also sounds like a useful thing it should give concentration by time. Minimally invasive option would be to monitor breath, better signal in blood.
Sadly health insurance in the US is unlikely to pay for most preventative care because the followup costs of false-positives and that they are betting that down the line someone else will pick up the tab when you get sick decades later (like the government).
It's kind of why I'm favor of universal option to align financial incentives. Like given how sick the US population is, it probably makes sense to put a lot more people of GPL-1s and invest in improving their efficacy and permanence. Like nationalize-the-patent COVID-operational-warp-speed level urgency. There are over 100M Americans that are pre-diabetic, the cost of treating a diabetic is about 20k/yr. So $4 trillion in new costs, on top of the misery and human suffering.
I have a friend nearing mid-60s. Retired military so now covered by Medicare, then Tri-Care. Having prostate issues. PSA went from 12 to 19. Desperate to get a PET scan to determine his is benign BPH, or cancer. Cannot get his scan approved since both insurances will not approve a PET as an early diagnostic tool (scan is about $7500). Cannot imagine what will happen if everyone getting a cancer DNA signal of this type tries to get clarification via additional tests. USA health care really does not work that way. HTH, RF
A PSA of 12 is pretty far past the threshold for an MRI (don’t know about a PET scan) and an MRI would be pretty determinative about whether or not a biopsy is warranted. A biopsy would be pretty good at identifying cancer.
Sounds like either there are complicating factors or an absence of standard protocol adherence.
US health insurance is a mess, but that doesn’t sound like the entire story. I suspect urologists see a fair amount of friction for routine procedures related to prostrate health.
He had the MRI. Not conclusive. The PSA jump (alredy very high) is biggest concern. PET would -- according to him -- be most conclusive. Yet he cannot get it approved, so lives in a cruel medical purgatory.
Prostate biopsy is an out-patient procedure and is a standard protocol for determining the presence of cancer.
Like I said, there is more to this story.
He had a biopsy a while ago. It was negative (and very painful he said). He has been working closely with his urologist who has recommended the PET. Given the PSA jump he is really worried, and cannot get what I presume is his urologist's next recommendation. He has taken all the right steps, just to be denied re: PET. (To be honest I do not know if PET is that effective, but he says it would be definitive.) He was told, though, that should he get cancer the PET would be approved to enhance the diagnosis. My heart goes out to him. RF.
It is sad that prevention is not something the US considers very important.
They care about prevention but only if it's very cheap. I get emails all the time from my insurance company about joining their program that is supposed to help you live a healthier lifestyle.
Any details on this program?
I started getting emails from Cigna about Omada after switching over to them last year. They pitch it as something you can sign up for to get health coaching. They (or their AI, soon if not already) provide that by sending you some "free" sensors (scale, pedometer, etc) and collecting lots of health information.
Searching the web shows that Cigna forces some patients to use this program in order to receive coverage for certain conditions. They're likely saving all the info collected through it in order to use it to deny you coverage if they can at all make an argument that something was caused by your lifestyle, was pre-existing for a certain amount of time, etc-- at least, that's the vibe I got from researching it.
> They're likely saving all the info collected through it in order to use it to deny you coverage
Oh God, that is so sad and infuriating. :(
How do you convince those pre-diabetic people to use a GLP-1? There was quite a bit of backlash about the one-time injection COVID vaccine when it was mandated.
You don’t need to mandate it, heaps of people who are obese or overweight are eager to take it, because they are sick of being this way, worried about the long-term health risks, feel the societal sigma, etc. For many such people who currently don’t, the big reason is not that they don’t want to, it is that their insurance doesn’t cover it and they can’t afford the $$$ of paying for it uninsured-but as patents expire the price is going to come down. Other people don’t like injecting themselves, but oral formulations are becoming available
COVID was different because being a transmissible disease, there was a strong motivation to try to maximise the percent of the population immunised. With GLP-1 agonists, if you made them freely available, likely over >50% of eligible patients would take them voluntarily, which would result in massive long-term cost savings from lifestyle diseases, even considering the continued costs from the other 50% who will refuse. And insurers may even give discounts to those who take GLP-1s (if permitted by regulators)
GLP-1s are probably going to have the unintended side effect of increasing weight stigma - already obesity skews poor, once most of the well-off obese people cure their obesity with GLP-1s it is going to skew even more poor. I can foresee a cycle in which GLP-1s increase weight stigma which pushes more people into taking them which then increases weight stigma even more, which could drive up their adoption even further
Are you expecting the government to mandate GLP-1 agonists the same way they tried to mandate the covid shot?
Any bureaucratic system is going to be inefficient. You see it in countries with universal healthcare. In Canada, some provinces now have wait times of over a year from referral to treatment. Many European countries face similar access issues, though France and the Netherlands perform somewhat better.
The U.S. is a different kind of mess. It’s a patchwork of heavy government restrictions, large public programs like Medicare, and for-profit corporations, all thrown together without a coherent design. It’s no surprise it’s expensive. In 2023, healthcare spending was nearly 18% of GDP. Another factor could simply be wealth: higher per capita GDP tends to correlate with higher healthcare spending. To be fair to the U.S. healthcare system, it is highly capitalized, with much higher concentrations of diagnostic equipment like MRI machines than other OECD countries, and it does have some of the highest five-year survival rates for cancer and heart disease.
Even so, all of these healthcare systems are heavily dysfunctional in many ways.
In contrast to all of this, cosmetic surgery and laser eye surgery are the only fields of medicine where prices have actually fallen in inflation-adjusted terms, which is extraordinary, as prices in healthcare in general have increased much faster than inflation. The superior performance of these fields is because of basic market dynamics. People pay out of pocket, so they’re price conscious, and providers compete. There are also fewer regulatory restrictions since these fields aren’t tied up in government programs like Medicare.
Innovation is the only thing that reliably drives prices down. But in most of healthcare, it moves slowly. Devices often take 10-30 years to cycle out. Compare that to consumer electronics, where turnover happens every 1-2 years.
If it were up to me, I’d make restrictions on medical providers much lighter. Anyone could offer medical procedures as long as they disclose they’re uncertified and include a government-mandated warning. That kind of freedom is necessary to solve hard problems. You can’t regiment innovation and industry development. Gatekeeping in the name of consumer safety is the worst thing that can be done to any industry, and unfortunately, there is heavy gatekeeping in healthcare.
That is not to say that I am opposed to government intervention in general. I think it can play a critical role in advancing healthcare. Where government intervention creates the most value is in funding research for the public domain: drug designs, medical procedures, and open datasets. These investments have enormous returns and are best handled by governments. If the private sector focused on delivery and innovation, with governments making strategic contributions in foundational research, healthcare would see revolutionary improvements generation after generation.
> though France and the Netherlands perform somewhat better.
It's all private in the Netherlands, just with non-discriminatory mandatory private insurance, so that makes sense.
US private healthcare insurance is required to pay for “medically necessary” treatments and generally does pay for medicine where they are unlikely to see the benefits (see statins).
I wonder how much of that is directly tied to corn subsidies.
The big secret is that they could detect cancer very early in most people, but the health care companies don't want to pay for the screening. You can pay out of pocket for these procedures. I was told this by a cancer researcher
EDIT:
Adding these caveats:
1. There is a ton of nuance in the diagnosis, since most people have a small amount of cancer in their blood at all times
2. The screenings are 5-10k + follow up appointments to actually see if its real cancer
3. All in cost then could be much higher per person
4. These tests arent something that are currently produced to be used at mass scale
The not so big secret is that we can detect cancer early in a lot of people, but we also would detect a lot of not-cancer. We don't currently know the cost/benefit of that tradeoff for all these new types of screening, and therefore insurers and health systems are reluctant to pay the cost of the both screening and the subsequent workup. This is not just a financial consideration, though the financial part is a big part -- the workup for those that end up as not-cancer has non-negligible risks for the patients as well (I have had patients of mine suffer severe injury and even die from otherwise routine biopsies), and on top of that, some actual cancers may not really benefit from early discovery in the first place.
This is not to downplay the potential benefit of early cancer detection... which is huge. And in the US/UK anyway, there are ongoing large trials to try to figure some of this stuff out in the space of blood-based cancer screening, as part of the path to convincing regulatory bodies and eventual reimbursement for certain tests. As mentioned, you can currently at least get the Galleri test out of pocket (<$1k, not cheap, but not exorbitant either), as well as whole body MRIs (a bit more expensive, ~$2-5k).
Or cancers that aren't clinically relevant.
Many prostate cancers, for instance, are slow growing and won't kill you before something else does. If you try to take that kind of cancer out surgically or zap it with radiation or chemo the side effects could be severe.
Treatments for prostate cancer are consistently improving. And what makes sense when you are 55 might be different than what does at 75…like all health care issues.
Yeah, after a detection there is alot of work to determine if what they detected should be worried about. But this doesnt take away from the fact that cancer can be detected very early, and these screenings could easily save your life
There's not a lot of evidence that full body MRIs are beneficial. A lot of people have pre-cancerous growths that may or may not become cancer in the future, so you may just be giving them unnecessary surgery, and surgeries are not risk-free. If you don't operate, they might develop an anxiety disorder.
We do a lot of CT imaging in the emergency department and it sucks if we incidentally find an abnormal growth in a young patient's CT head. These are usually benign and often not worth performing brain surgery to get a biopsy.
I had one at detected at 5mm close to the amigdala and they just scanned again in 3-6 months on MRI to prove it wasn't growing. That was a decade ago.
Why not just rescan them every few months to see if it's still growing? After all, you wouldn't have to rescan the full body, just the section where the growth is.
... or could do you harm, which is an important point.
To clarify is the harm that many healthy people would stress while it was confirmed the detection was not cancer?
No, the potential harm comes from follow-up tests. That's why screening strategies are designed by professionals. It's a pretty complex field, and all the people here fielding their opinions on how we should proceed about tests don't have a single idea about the implications of their theories.
this is medical gate keeping ("only the holy priests can practice medicine"), please take this attitude elsewhere
"my ignorance is as valid as your knowledge"
The internet is a powerful tool of communication, but turns out some people don't have anything worthwhile to communicate.
What a ridiculous statement to make. No wonder the US is in the state it is in. Lets let the ignorant and uninformed decide on policy rather than the scientific community and experts. What could possibly go wrong?
Honestly, you don't have access to the necessary data to make rational decisions. That's not gatekeeping, it's logic. I don't have access to it either, although I'm indeed a healthcare pro. Screening strategies are a hyperspecialized domain and only experts somewhat understand what they're doing. It's just like making theories about what the CERN guys should be doing while not having passed physics 101 with no access to experimental data. That's why I'm just saying: you're certainly allowed to question, but you certainly can't make up assertions either.
[flagged]
How could the screening do you harm? (other than financial)
What are you gonna do if the screening test comes back positive?
Get treated for the cancer you will now survive because you just caught early. The answer is so obvious I think I may have misunderstood what you mean here.
The fact that this answer is so obvious to you means you have to read up on diagnostic test performance and how screening works, because it's in fact not obvious at all. I mean that in the nicest way possible. Those companies offering expensive screening are not what they seem. Whether their offering is useful or whether they're just swindling you is a question that needs lots of time, money and sweat to answer.
What if it's just some lump that would not have developed into cancer? The surgery to get it removed isn't risk free.
Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up. The only people who would benefit from these screenings are already unhealthy and cancer might be just one of many potential conditions they could experience—the goal of healthcare is not to dedicate an inordinate amount of resources for procedures that may amount to not much of any long term benefit.
People talk about the “immune system” but they are really referring to a number of systems the body uses to regulate itself, more or less successfully, around environmental pressures. The body is a system under tension, sometimes extreme tension leads to extreme success (success here being growth of power), sometimes it breaks the body, and sometimes the systems have been slowly failing for a while, and most treatments will not help. Medicine is only useful in the specific case where the power of the body would be promoted if not for one thing, that the body would be healthy, at least manageably so, without that issue.
> Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up
Incorrect.
There are tons of cancers that hide and mask with symptoms common to other symptoms. Kidney cancer, for example, presents pretty similarly to both kidney stones and UTIs. Even blood in the urine isn't proof positive that anything is wrong beyond either of those conditions. And, by the time blood is in the urine, it's often too late.
Liver cancer is even worse. The first symptoms you get can be thought of as a simple pulled muscle, just a little ache in the back. By the time you have appreciable problems, like turning yellow, it's quite advanced and too late to really do much.
There are common cancers like colon, skin, breast, and prostate that more fit your description of being mostly harmless so long as you get regular screenings and eat healthy. But, for every part of the body, a cancer can form and the symptoms are very often invisible.
I'm unfortunately all too familiar with how cancer looks. My wife currently has stage 4 cancer that started as kidney cancer. She does not drink or smoke, gets enough rest, and is very active.
No I mean that people who are healthy in general are less likely (or completely unlikely) to “get cancer” in the first place because cancer is something that has more to do with an immune system failure, which happens due to unhealthy lifestyles or genetic problems in general which are unavoidable. Cancer only affects people who generally already have other problems (old, sick, unhealthy lifestyles etc.) and young people because they are growing very quickly.
Thus, in young people cancer presents rapidly as they develop, these screenings are expensive and unnecessary. For old/sick/unhealthy people, or people who are predisposed to certain cancers, they will probably get something else anyway, so its an expensive workup to help treat a disease that won’t actually benefit much in the long term.
I’m not against treating cancer, however let’s recognize that cancer treatment is already an expensive and resource/labor intensive process. And 10yr survival rates are not great for most cancers, we’re only slowing the burn, not stopping it. Sometimes you get lucky and die of something else before the cancer can come back, but nobody is ever “cured,” they are all just delaying the inevitable. Which, as we have seen, can sometimes be worth it (who wouldn’t want another 10 years with a loved one?), but that doesn’t mean our goal should be to find a way to “cure” cancer, it should be to find a way to better manage it, and these screenings don’t seem like they really are, or at least the use-cases for them are minimal.
What's a good way for an otherwise healthy person to screen for kidney cancer, in terms of trade-offs?
Annual MRI?
IDK TBH. My wife had all the general recommended screenings. The only thing that showed potential problems was slightly elevated WBC. It was ultimately what they thought was a UTI that stayed a little too long that got us to get a CT and ultimately the diagnosis.
I do wonder if a 5 year whole body MRI or CT would be generally beneficial for the population. I don't think it needs to be Annual to have benefits.
The problem is it really isn't uncommon for your body to create random puss fill sacks all over the place. It's one thing our cancer doctor warned us about. My wife is now on a 6 month CT regimen and ultimately, they'll just ignore new lumps.
Talking to your doctor is the simplest thing that might work.
My NP would tell me "nothing to worry about" whether she knows what's going on or not, but that's beside the point.
GP wasn't asking what they should personally do. They were asking how the doctor would screen for it. (The truth is, the doctor can't/won't-- an annual MRI on every otherwise healthy person, for example, would be prohibitively expensive with how MRIs are currently set up-- and as another commenter pointed out, findings from those can be just as easily ignored or put off until it's too late.)
but that's beside the point
Being beside that hypochondric point is statistically a much healthier place to be.
The current state of medicine is the current state of medicine in the actual world.
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Probably not true. It’s much cheaper to catch cancer early than to treat advanced cancer later
Yeah but then you'd go through life having biopsies all the time. If all people did a full body MRI almost everyone would have weird lumps that doctors would have to biopsy to be really sure, and then what do you do? Do you biopsy yourself every time some weird tissue appears? Most of those will be nothing and you'll be going through the complications of surgeries and anesthesia all the time just to always make sure.
Assuming some future MRI technology which was very cheap, wouldn't you have MRIs at fairly regular intervals, to first see if the lump was growing or changing shape? And if this was being done at population scale, you'd train up an AI on the known outcomes, to have it flag up problems for a human to review.
Assuming MRIs weren't exorbitantly expensive, then the answer would probably be to simply rescan a month or 2 later and biopsy the lumps that don't go away.
That's true in the case someone actually does have cancer, but what about paying for all the negative tests?
Nope, the cost is 5-10k maybe more, and there is alot of nuance and follow ups to those detections
Doing this could be actively worse for you and society based on the false positive rate. Testing and accidental unneeded treatment carry very real risks that could lead to net suffering and more death or damage if enough people are tested.
This is a collectivist opinion on something which is very personal
Public healthcare policy is absolutely not something personal.
It involves costs of healthcare for all people involved, workload on health professionals, hospital occupancy, etc and so forth.
If the rate of false positives in these tests are too high, people that need treatment for their actual illnesses might be on a waiting list because too many are doing follow-up screening and biopsies for non-issues.
And to address your silly "collectivist" fear-mongering, your hyper-individualist mentality is a societal disease. We could do with some more collectivism, in the sense that people have a better understanding of the constraints and conditions of the society they are inserted in.
Would you take a test if doing so statistically increases your probability of death?
Is it moral for a doctor to give a test they think is going to increase someone's chance of death.
That's just wrong. Taking a test doesn't do anything to the data-generating process, your chance of death is 100%. The test merely informs your posterior about the timing of the event.
The timing is pretty important to most people, and is actually the whole point of taking the test in the first place so the generating process and the test are not independent. See ?! What you said is just wrong too ! ;-)
It's not personal, it's perfectly rational statistics, i.e. epidemiology. Designing screening strategies is not an amateur's game.
> The big secret is that they could detect cancer very early in most people, but the health care companies don't want to pay for the screening.
thanks for adding the caveats; they suggest that there are good reasons why it isn't clear cut that health care companies should pay.
Wrong.
The usual story is that you’re just better off not knowing because you’ll end up doing more harm than good chasing every little suspicious diagnosis. Cancer happens all the time, but many times doesn’t lead to anything.
But what could we expect as fair price if mass scale production happens ?
Health insurers would absolutely pay for the screennig if the sum spent on screening everyone was cheaper than long term cancer care.
It's the same reason they pay for annual physicals in the first place.
Nah the tests can go up to 10k per person
>if the sum spent on screening everyone was cheaper than long term cancer care
I actually know a little about this through my work. Cell-free DNA (CfDNA) Has been known about for a few decades, but has become more of a focus in recent years because of the advent of immunotherapies, which are often highly targeted drugs. CfDNA has also been used in "liquid biopsies" i.e, a simple blood draw, because it can help you profile the tumor and location of the cancer.
In my field, we all think that CfDNA testing will eventually become a standard thing that will go along with your annual physical's blood test, because it has predictive/preventative abilities.
how actionable is the result? let's say you do detect trace amounts of tumoral DNA in your blood, what can you do? can you prevent it from developing into a full-on tumor if you don't even know where it is?
I imagine the signature isn't simply binary but with several dimensions of differentiation?
Seems this newfound ability to detect cancers earlier than we thought possible could be used to develop better treatments to boost the body's innate ability to eliminate cancerous cells before they turn malign: 1) identify thousands of people with traces of cancerous DNA that are too weak to merit immediate action and who are willing to participate in a trial. 2) Divide them into two groups, one group gets for one month a daiiy dose of auricularia auricula fungus extract or whatever that is believed to possibly prevent cancers from developing, the other group gets a placebo. 3) Run the early-detection test again at the end of the month to see whether or not there is a difference in cancerous DNA signal strength between the two groups.
That sort of thing would be awesome. I suspect it’d have to be community driven. Perhaps with some academics but who knows if IRBs would approve.
Doing this same idea but with inflammation monitoring would be enormously valuable as well.
A relative had this or a similar test come back positive. This sounds like a helpful signal on paper, but in reality it's not always actionable.
They assumed their previous cancer had survived and metastasized. Doctors couldn't find the source. It turned into a waiting game, where they lived with a sword of Damocles over their head. They were retested every few months and monitored. Then after a year the tests the levels dropped off. And the end result was nothing came of it so far.
It's normal to have some amount of pre-cancerous cells get naturally removed by your immune system. And this catches those too.
https://archive.ph/uE18w
How to use such test results? I propose your GP knows your test results but you don't. You see the GP about a mole or something and the GP (not you) gets to decide on further tests / treatment, or sends you home saying don't worry about it.
AgelessRx offers the Galleri Multi-Cancer Early Detection test: https://agelessrx.com/galleri-multi-cancer-early-detection-t...
Ageless also provides many other longevity therapies.
That test is cheaper directly from https://www.galleri.com/ ($799 vs $949).
I get it every year. So far, so good!
Quite interesting to me and first time I am hearing about this.
Question for you, what do you do when it shows you may have cancer? Do you speak to your physician? Surely, this will change your life even if it doesn't need treatment for next 6 years? Does the treatment change? Can the treatment be done based on those results?
So many questions.
I'm hoping we find more stuff for Alzheimer's. My aunt and now mother have it. I fear that I am next and I am too scared of doing the DNA test to check for genes.
You immediately bring the results to your doctor ASAP. They'll recommend follow-up testing since they want verification of third-party results and, well, are doctors and will know better about what to test for. If you do indeed have cancer, they will refer you to an oncologist who sub-specializes in that type of cancer.
Isn’t $799 expensive for average families?
what about Europe ?
> what about Europe ?
what about Europe?
I have heard rumors of a universal healthcare system in this mythical far off "eee ewe" land, where people don't pay out of pocket for ordinary procedures, and medical bankruptcy isn't a thing. Perhaps that is related to their query.
as far as tumors go, that one has become fairly benign in the last century.
Benign ? It metastisized through the ocean stream to develop aggressively a bit more to the west.
Some life insurance companies offered it for free as part of a service to existing clients. Mine claimed they would not know the results. I hope its true because I did take them up on the offer. Results were statistically favorable for me so I appreciate the test for what it is.
Curious to see how these hold up over the long term.
Blood testing sounds like a great opportunity for a startup…….
I wonder if they could work with very small amounts of blood …?
What if they took a small amount, but ran many different tests with it?
What if the testing unit was so small it could sit on your kitchen counter and send the results digitally to your doctor?
What if major venture capitalists rallied around a charismatic founder and gave the startup huge financial backing.
What if the founder had a really nice deep voice to convince everyone that they're legit?
Fake it till you make it.
that made me chuckle.
then i remembered a month or so ago seeing this, and not knowing what to make of it.
https://siphoxhealth.com/
Have you seen function health? It’s now a unicorn.
As far as I can tell, they did a wholesale deal with quest diagnostics, and run your results through ChatGPT and give you supplement / diet recs via a pretty web portal 2x a year for $499.
Claim is it’s 100 biomarkers and would cost avg person $15k retail.
I’m a member and love it.
Seems like it might be overhyped. Here is the study
https://aacrjournals.org/cancerdiscovery/article-abstract/do...
Full text is paywalled, and no mention in abstract of false positive rate in control group. Has this test actually been independently verified? No mention of that important fact in the press release.