Cancer Detection Methods

Current blood-based cancer screening tests detect only ~20% of early-stage lung cancers due to low circulating tumor DNA levels. This study explored whether analyzing the immune system's response to cancer through TCR sequencing could provide a complementary detection method. Methods: Researchers analyzed blood samples from 463 lung cancer patients (86% stage I) and 587 controls. They: - Sequenced TCR β chains from blood buffy coats - Generated ~113,571 TCR clonotypes per sample - Clustered similar TCRs into "repertoire functional units" (RFUs) - Used machine learning to identify cancer-associated patterns - Compared performance with ctDNA and protein biomarkers Results: The study identified 327 cancer-associated RFUs and achieved: - 48% sensitivity for stage I lung cancer at 80% specificity - Similar performance across all cancer stages (unlike other biomarkers) - Up to 20 percentage point improvement when combined with ctDNA and proteins - Strong correlation with HLA types, suggesting antigen-driven responses - Tumor infiltrating lymphocyte analysis confirmed that cancer-associated TCRs recognize tumor antigens, including MAGE cancer antigens. Conclusions: TCR repertoire sequencing represents a promising orthogonal approach to cancer detection that leverages immune surveillance rather than tumor-shed materials. The method's consistent performance across cancer stages and complementary nature with existing biomarkers suggests significant potential for improving multi-cancer early detection tests. This approach could be readily integrated into existing liquid biopsy workflows using the buffy coat fraction typically discarded in current ctDNA assays. Paper and research by Yilong Li, Michelle N.  Roman Yelensky and larger team at Serum Detect, Inc.

Making sure you saw an important announcement from GRAIL that I’m quite excited about.   Early detection of cancer—before symptoms appear—is often the key to cure. Some cancers have recommended screening tests, like mammograms or colonoscopies. But many arrive unannounced, often too late for curative treatment, bringing profound grief and suffering for patients and families.    Imagine being able to detect dozens of cancers from a single blood test—before a person has symptoms.   That kind of leap would’ve seemed impossible a decade ago. But this week’s results from Grail suggest multi-cancer early detection, or #MCED, may be within reach.    #PATHFINDER2 is a longitudinal study of 35,000+ adults. The first 25,000 now have data mature enough for interpretation. Among those who remained cancer-free, the test achieved 99.5% specificity, meaning it accurately ruled out cancer in nearly everyone who didn’t have it. And 43% of positive results were confirmed to be cancer, a meaningful improvement over earlier versions.    What makes this test so promising is its scope: it screens for 50+ cancers, including many that lack routine screening. It analyzes cell-free #DNA (#cfDNA) in the blood using #nextgenerationsequencing and #AI to detect #cancer signals.   As cells die, fragments of DNA—including cancer-derived DNA—are released into the bloodstream. These ~170 base pair fragments are typically wrapped around histones in nucleosomes. They carry DNA sequence with specific methylation patterns, which #machinelearning models can use to detect whether the cfDNA is from cancer and the likely tissue of origin of that cancer.    There are still real challenges. While Galleri is excellent at ruling out cancer, more than half of positive results are false positives—requiring follow-up tests and potentially causing unnecessary worry. That’s true for all current screening tools, including mammograms. And not all cancers are equally detectable. But the test is improving—and more data will come from ongoing validation across populations and tumor types.    Access is another hurdle. Galleri is available for private purchase but isn’t covered by most insurers and hasn’t yet received FDA approval—though submission is planned for 2026. Broad adoption will require regulatory review, payer engagement, clinician education, and smart care pathways.    In 2017, the team Johnson & Johnson Innovative Medicine made a large investment in Grail’s Series B. That early support helped lay the foundation—and now, it’s paying off.    This is a powerful reminder of what’s possible when we aim high.   Breakthroughs like this don’t come from incrementalism. They come from bold bets on hard problems. That mindset is badly needed across the healthcare industry.    Let’s all aim high.    https://lnkd.in/duHv9Nfw    #oncology #cancerscreening #genomics #boldscience #futureofhealth

A small prospective study using the ARIC cohort evaluated plasma samples from 52 individuals—26 of whom were later diagnosed with cancer and 26 controls—to assess the potential of multicancer early detection (MCED) testing. At the time of sample collection, 8 participants tested positive, all of whom were diagnosed with cancer within four months, indicating high short-term predictive value. Remarkably, in six of these cases, earlier blood samples collected 3.1 to 3.5 years prior to diagnosis were available, and four showed the same cancer-associated mutations, albeit at much lower levels (8.6–79 times lower mutant allele fractions). These findings demonstrate that circulating tumor DNA (ctDNA) can be detected years before clinical diagnosis, underscoring the promise of highly sensitive assays for ultra-early cancer detection and offering a benchmark for advancing MCED technologies to catch cancer at its most treatable stage. #cancer #detection #ctDNA

Have you heard of minimal residual disease testing? 🤔 💠 Minimal residual disease (MRD) testing is a tool that is used for finding any remaining disease following cancer treatment, monitoring response to treatment, and to guide potential adjustments to the care plan. 💠 MRD testing first achieved FDA approval for use in blood cancers, such as leukemia and lymphoma. 💠 MRD has grown in use in more recent years for solid tumors, such as breast cancer. ✔ One of the advances in cancer care is the ability to detect Circulating Tumor DNA via minimal residual disease testing. 💡 Circulating tumor DNA (ctDNA) is a DNA fragment actively secreted by tumor cells or released into the circulatory system during the process of apoptosis or necrosis of tumor cells. 💡 Frankly, this all gets a tad complex, but the takeaway is that ctDNA testing is a minimally invasive technique that can be used to characterize individual cancer biology and monitor disease. 💡 ctDNA testing is performed via a liquid biopsy - A blood sample. Obtaining blood sample is safe, inexpensive, and easy to repeat. 💡 ctDNA can detect the recurrence of cancer before it is found in imaging, such as PET/CT. 💡 The European Society Of Medical Oncology (ESMO) recommendations endorse ctDNA testing in routine clinical practice for tumor genotyping to direct molecularly targeted therapies in patients with metastatic cancer. 📝 ctDNA technologies are still being investigated, but preliminary research has demonstrated that it can be a sensitive and specific approach to breast cancer surveillance of disease recurrence. 💠 At our breast cancer clinic, we frequently utilize ctDNA tests manufactured by Guardant, Tempus, and Signatera. I think it is an exciting development in oncology treatment and I look forward to further research on its efficacy! References: 📙 National Cancer Institute 📘 Journal of Clinical Oncology 📗 Nature Partner Journals 📔 European Society Of Medical Oncology (ESMO) _____________________________________________________________________ Charlotte Goor – 🩺Registered Nurse. ⚖Legal Nurse Consultant. 📧 Charlotte@ExpertCareLNC.com 💻http://ExpertCareLNC.com

Watch out, Structural Variants are coming to MRD testing! The goal of minimal residual disease (MRD) testing is to determine how much disease remains in cancer patients after it is treated. In hematologic cancers, MRD tests using PCR were first seen in the late 1980’s. These tests targeted the IG-TR gene rearrangements that were common in lymphoid malignancies. PCR allowed oncologists to ditch using Southern blots to detect these changes and improvements in MRD tests led to quantitative PCR based versions in the late 90’s. But, the challenge with using PCR for this sort of testing is you need to know what you’re looking for to detect it! Fortunately, the advent of massively parallel sequencing in the early 2000’s gave us a new tool for tracking cancer progression and finding unique markers of disease. But the use of high throughput sequencing as a diagnostic in oncology has been prohibitively expensive until more recently. The use of tumor-informed high-throughput sequencing based MRD assays really began in 2018 with Natera’s publication of their Signatera product which is a single-nucleotide polymorphism (SNP) based test. It uses a patients’ own tumor tissue to develop a SNP fingerprint that is then assayed longitudinally (over months/years) after cancer removal to see if that DNA signature reappears in a patient’s blood sample. But SNPs aren’t the only kinds of mutations that turn up in cancers! They’re also full of large structural variants (SV) like gene deletions, duplications and other large genomic rearrangements. The researchers behind today’s paper showed that these SVs can also be used to generate fingerprints that perform as well as or better than their SNP based counterparts! To do this they whole genome sequenced tumor tissue from breast cancer patients to identify tumor specific structural variants and created a 16 marker fingerprint. They then developed primers to the SV breakpoints to make an individualized digital PCR (dPCR) assay for each patient. dPCR allowed them to detect single molecules without having to spend a bunch of money sequencing stuff they don’t care about! In the figure below you can see that their hard work paid off! A and B) Show representative plots of ctDNA detection before surgery (green area), at surgery (black dashed line), after surgery and during chemo (pink and purple) and at detection of disease recurrence (red dashed line) C and D show that the detection of ctDNA in the neoadjuvant setting (before tumor was removed) was associated with poorer prognosis and E and F) that the same was true in the adjuvant setting (after the tumor was removed). This test detected 100% of cancer recurrence with a median lead time in early breast cancer of 417 days. That’s 417 more days to try to figure out how to delay the cancer a second time! ### Elliot MJ, et al. 2025. DOI: 10.1158/1078-0432.CCR-24-3472 Disclosure: I have received consulting fees from SAGA Diagnostics

🎗️ Transforming Cancer Care with AI: The Game-Changing Power of CHIEF 🎗️ Harvard Medical School introduced CHIEF (Clinical Histopathology Imaging Evaluation Foundation), an advanced AI model set to revolutionize cancer diagnosis, treatment guidance, and survival predictions across 19 cancer types. This versatile tool, detailed in Nature, opens new possibilities for patient care and personalized treatment. CHIEF was initially trained on 15 million unlabeled images and then further refined on 60,000 whole-slide images, allowing it to interpret both specific sections and broader image context for a holistic understanding. 🔬 Broad Diagnostic Capabilities Across Multiple Cancers Trained for multiple tasks, CHIEF detects cancer cells, predicts outcomes, and analyzes molecular profiles. Achieving 94% accuracy, it surpasses existing models, proving highly adaptable in varied clinical settings. 🧬 Advanced Molecular Profiling CHIEF efficiently fills gaps in traditional DNA sequencing by analyzing cellular patterns to predict genetic mutations. It achieved over 70% accuracy in identifying 54 key cancer genes, making treatment personalization quicker and more accessible worldwide. 📉 Predicting Patient Survival with Accuracy CHIEF forecasts survival with precision, distinguishing patients with high versus low survival rates based on histopathology. It outperformed other models by 8-10%, aiding early identification of patients for targeted treatments. 📊 Novel Insights into Tumor Behavior Beyond diagnostics, CHIEF uncovers new insights, identifying cellular patterns linked to survival, such as higher immune cell presence, potentially guiding future biomarker development for cancer aggressiveness. 🧩 Future Steps for Enhancing CHIEF Plans include additional training on rare diseases, expanding molecular data, and refining its ability to predict outcomes for emerging therapies. Summary: CHIEF exemplifies AI’s transformative potential in cancer care, making diagnostics faster, more accurate, and tailored. This powerful tool offers hope for patients and oncologists alike by advancing personalized cancer treatment. #AIinHealthcare #HarvardMedical #CancerDiagnosis

A New Blood Test Detects Cancer Recurrence Months Before Scans Introduction: A Breakthrough in Early Cancer Surveillance Standard imaging like CT scans can’t always detect cancer recurrence early enough to intervene effectively. Now, a new type of blood test offers the potential to spot the return of cancer months—sometimes even a year—before tumors are visible on scans. This could transform how survivors like Jennifer Feenstra, a lung cancer patient in remission, are monitored after treatment. ⸻ How the Blood Test Works and What It Detects • Detects Molecular Residue: These tests identify tiny fragments of tumor DNA, known as circulating tumor DNA (ctDNA), in the bloodstream—essentially molecular breadcrumbs left by cancer cells before they re-form into a tumor. • Earlier Than Imaging: Studies suggest ctDNA can signal recurrence up to 12 months before it’s visible via CT or other imaging methods, giving oncologists a critical head start in reinitiating treatment. • Real-World Usage Already Underway: Although these tests aren’t yet universally recommended, some patients and oncologists are already using them to stay ahead of potential recurrence, even without formal clinical guidelines in place. ⸻ What Experts Are Debating • To Test or Not to Test? • There’s growing interest, but also caution, especially around false positives and psychological toll—being told cancer might return without a visible tumor can create anxiety. • Currently, oncologists must weigh the benefits of early detection against the risk of overtreatment or unnecessary worry. • Insurance and Accessibility Issues: • Not all insurance providers cover these advanced tests yet, and clinical guidelines have not fully caught up with the technology. • Ongoing clinical trials are underway to clarify when and how these blood tests should be integrated into standard post-cancer care. ⸻ Why This Matters: A New Era of Post-Cancer Monitoring This emerging technology could redefine how we monitor cancer remission, making it more proactive than reactive. For survivors, the test offers hope of earlier intervention and better outcomes. But it also raises urgent questions about when it’s appropriate to act, how to manage results, and ensuring access isn’t limited by cost or geography. As science advances, thoughtful implementation will be key. Keith King https://lnkd.in/gHPvUttw

University of Texas El Paso (UTEP) Researchers Develop Low-Cost Microfluidic Device that Detects Cancer in an Hour. October 24, 2024 Excerpt: “Our new biochip is low-cost — just a few dollars — and sensitive, will make accurate disease diagnosis accessible to anyone,” said XiuJun (James) Li, Ph.D., a UTEP professor of chemistry and biochemistry. “It is portable, rapid and eliminates need for specialized instruments.” The microfluidic device can perform multiple functions using very small amounts of fluids. The device uses an innovative, fabricated paper designed in a ‘polymer-pond’ structure in which patient blood samples are introduced into tiny wells. The paper captures cancer protein biomarkers within blood samples in just a few minutes. The paper subsequently changes color, and the intensity of the color indicates the type of cancer detected and disease progression. Note: Li explained the most commonly used commercial method of cancer biomarker detection, ELISA, requires costly instrumentation and can take twelve hours or longer to process a sample. This delay is heightened in rural areas in the U.S. or developing countries where patient samples must be transported to larger cities with specialized instruments. “If you can detect biomarkers early, before cancer spreads, you increase a patients’ chance of survival,” Li said. “Delays in testing, in regions that do not have access to expensive tools and instruments, can be very bad for a patient’s prognosis.” Research has focused on prostate and colorectal cancers, but Li said the method devised could be applicable to a wide variety of cancer types. According to study results, the device is also about 10 times more sensitive than traditional methods without using specialized instruments. The device can detect cancer biomarkers present in smaller quantities, typical of cancer in early stages. A less sensitive device may not pick up on the smaller quantities, Li said. The prototype will need to be finalized and tested on patients in clinical trial, which could take several years, prior to final review, assessment and approval by US Food and Drug Administration (FDA) for use by physicians. Refer to enclosed announcement for further information and direct link to journal Lab on a Chip (2024). A paper-in-polymer-pond (PiPP) hybrid microfluidic microplate for multiplexed ultrasensitive detection of cancer biomarkers† Sanjay S. Timilsinaa  and  XiuJun Li https://lnkd.in/e6rdy25P

Barks and Bytes: Startup Combines AI and Dogs to Detect Cancer with 94% Accuracy via Breath Test >> 🐶SpotitEarly just raised $20.3M to expand into the U.S. with a novel breath-based cancer screening test combining AI and trained dogs 🐶The at-home test involves breathing into a mask for three minutes. The sealed sample is then analyzed by both canines and AI to detect volatile organic compounds (VOCs) linked to early-stage cancers 🐶 Their “bio-hybrid” approach tracks the dog’s behavior via sensors and cameras, feeding data into an AI model that interprets both physical and behavioral signals 🐶In a two-year, double-blind clinical study of over 1,300 participants, the test achieved 93.9% sensitivity and 94.3% specificity across breast, lung, colorectal, and prostate cancers 🐶Early-stage cancer detection was similarly strong, with 94.8% sensitivity for stage 0–2 cases, offering a promising alternative to traditional screenings. 🐶SpotitEarly’s breath test offers a non-invasive, more accessible alternative to traditional screenings like mammograms, colonoscopies, and liquid biopsies, which often face barriers around comfort, access, and early-stage accuracy #digitalhealth #AI

🧠 #AI just hit a 99 percent bullseye on brain tumor diagnosis no scalpel needed A Berlin-based team trained the crossNN model to read epigenetic “bar-codes” in cerebrospinal fluid. In early trials it identified 170-plus tumor types with 97 - 99 percent accuracy, published in Nature Cancer (Jun 2025). How the breakthrough works • Tiny spinal-fluid sample → nanopore sequencer • AI maps DNA-methylation patterns → unique tumor fingerprint • Result in hours, not days, sparing patients risky biopsies Why this matters 1. Earlier answers, safer care. No open-skull surgery for a diagnosis. 2. Precision from day one. Treatment starts with an exact tumor label. 3. Doorway to liquid biopsy oncology. The same epigenetic playbook could spot metastases before scans ever show a mass. Reality check Multicenter clinical trials are under way. We still need validation across diverse populations and hospital setups. But the signal is loud AI is shrinking the distance between suspicion and certainty. 💬 Would you trust an AI liquid biopsy for a faster diagnosis? Share your thoughts below and tag a colleague who needs to see this future arriving today. Source : Charité – Universitätsmedizin Berlin, Nature Cancer #AIinHealthcare #CancerDiagnostics #BrainTumor #LiquidBiopsy #PrecisionMedicine #DrGPT