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Peter Attia MD213 ‒ Liquid biopsies and cancer detection | Max Diehn, M.D. Ph.D.
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At a glance
WHAT IT’S REALLY ABOUT
Max Diehn Explains Liquid Biopsies, ctDNA, and Cancer Screening Challenges
- Diehn traces his path from a Stanford MD-PhD in Pat Brown's microarray lab to radiation oncology, and says his liquid biopsy work began with the clinical frustration of not knowing which treated early-stage lung cancer patients would relapse.
- He and Attia explain why imaging is blind below roughly a billion cells, and why protein biomarkers and circulating tumor cells fell short on specificity or sensitivity before cell-free DNA became his focus.
- Detecting tumor-derived DNA with next-generation sequencing, by tracking many known tumor mutations at once, makes minimal residual disease testing very sensitive, down to about one part in a million with his newest method.
- Diehn and Attia argue that sensitivity and specificity must be read alongside disease prevalence, and that current multi-cancer screening tests have very low stage I sensitivity and would give many false positives in low-risk people.
- Diehn says near-term uses are guiding adjuvant therapy and avoiding overtreatment in cancers like lung, colorectal and breast, while true screening will probably need combined mutation, methylation and fragment-size features and randomized trials proving survival benefit.
IDEAS WORTH REMEMBERING
5 ideasLiquid biopsy research started from a clinical need, not a technology.
Diehn says he was frustrated that after radiating early-stage lung cancer he could not tell who would recur, and he runs his lab by starting from clinical problems.
Imaging is effectively blind until a tumor reaches about a billion cells.
Diehn says tumors much smaller than about 1 cm are hard to see, and micrometastatic deposits spread through the body can add up to billions of cells while remaining undetectable.
Protein markers and circulating tumor cells each had a critical flaw.
Proteins like PSA, CEA, and CA 19-9 lack specificity, while circulating tumor cells were scarce, needed rapid processing, and could be mimicked by normal epithelial cells.
Tracking many known tumor mutations at once makes ctDNA detection highly sensitive.
Rather than hunting for one mutation, Diehn's group sequences a patient's tumor and looks in plasma for any of dozens of its mutations, since seeing one is enough to indicate residual cancer.
A test that sounds good can still mislead in a low-risk population.
Attia showed that 50% sensitivity and about 99% specificity with 1% pretest probability gives a positive predictive value near 40%, and Diehn agreed, adding that sensitivity should be reported by granular stage.
WORDS WORTH SAVING
5 quotesthe way I and, you know, and all of us, you know, in this, in these areas think about it is, is it worth, uh, doing?
— Max Diehn
I think one of the, uh, keys to being a successful scientist, whether you're a physician scientist or a, a laboratory, purely laboratory-based scientist, is following the data, following the data that you generate, um, uh, to where it leads you as opposed to fo- you know, saying, "I have to work in one area."
— Max Diehn
Even though they're exciting technologies and, uh, we're, we're very hopeful that they will, we shouldn't just give them a pass because they're high tech and not do the right clinical science.
— Max Diehn
The surgeon can cure what he can see or she can see, right? What, what they can cut out.
— Max Diehn
I want people to just anchor to this idea that from zero to a billion cells, we're pretty much flying blind.
— Peter Attia
High quality AI-generated summary created from speaker-labeled transcript.
