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).
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.
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
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.
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.
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).
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.
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
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.
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.
https://archive.ph/uE18w
Blood testing sounds like a great opportunity for a startup…….
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.
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.