Podcast Summary
Understanding Cancer Screening and Liquid Biopsies with Max Dean: Max Dean, a Stanford professor, discusses the importance of liquid biopsies in detecting cancer, even when the specific gene is unknown, and the role of sensitivity, specificity, negative predictive value, and positive predictive value in cancer screening.
Max Dean, a professor of radiation oncology and vice chair of research at Stanford University, is leading the charge in the field of liquid biopsies, which involve detecting circulating tumor DNA in the blood of cancer patients to predict recurrence and response to therapy. This is crucial because early detection can significantly improve patient outcomes. Max's research focuses on developing novel methods for detecting these biomarkers and understanding the molecular pathways and genes associated with cancer. He also specializes in lung cancer treatment and improving personalized therapies for patients. During this podcast episode, Max and Peter Atia, the host, discussed the importance of sensitivity, specificity, negative predictive value, and positive predictive value in understanding cancer screening and the role of liquid biopsies in detecting cancer, even when the specific gene is unknown. They also explored the current landscape and future possibilities of liquid biopsies, including cell-free DNA RNA signatures, methylation patterns, and mutation information. Overall, this episode provides valuable insights into the importance of early cancer detection and the potential of liquid biopsies in revolutionizing cancer treatment.
Joining Pat Brown's lab at Stanford: Choosing the right lab during PhD pivotal for future research opportunities, speaker joined Pat Brown's lab due to DNA microarrays innovation, faced challenges in RNA preservation, laid foundation for future work in immunology and oncology
During the PhD part of an MD-PhD program, the decision of which lab to join is a crucial moment, as it opens up new opportunities with the latest technology. The speaker chose Pat Brown's lab at Stanford due to his invention of DNA microarrays, which allowed measuring thousands of genes at once, revolutionizing the field. The speaker worked on various projects, including T cell activation and self RNA isolation, facing challenges in preserving RNA's instability. This experience laid the groundwork for future research, particularly in immunology and oncology, which gained increasing importance with the development of immunotherapy.
Purifying specific RNAs for diagnostic and therapeutic purposes: Scientists focused on isolating RNAs associated with secreted genes or surface proteins using a complex purification method, while the speaker's career choice was driven by a personal experience and a desire to improve healthcare for patients.
During research on RNA sequencing, scientists focused on purifying RNAs associated with secreted genes or surface proteins, which were important for diagnostic and therapeutic purposes. This involved a lengthy process of purifying RNAs attached to the endoplasmic reticulum, requiring specialized conditions and equipment to maintain RNA integrity. At the time, they could not directly gain insights into non-coding sequences, as their technique was geared towards measuring coding portions of genes. Later, this approach was used in early studies on long-known coding RNAs. The speaker, who had a PhD in three years and then went on to clinical rotations, was determined to become a physician and scientist, with a focus on oncology. This decision was influenced by his father's experience with lymphoma and the limited understanding and suboptimal treatments at the time. In summary, the research process involved a complex purification method to study specific RNAs, while the speaker's career choice was driven by a personal experience and a desire to improve healthcare for patients.
Experiences influenced career choice in radiation oncology: Speaker's experiences, including wife's research, enjoyment of technology, and desire to make a difference, led him to radiation oncology. Balanced clinical training and research during residency prepared him for faculty position at Stanford.
The speaker's decision to pursue a career in radiation oncology was influenced by his experiences, including his wife's research in the field, his enjoyment of the technology used, and the opportunity to make a difference in a less crowded research area. He was able to balance clinical training with research during his residency through a postdoc program, which prepared him for a faculty position. The Department of Radiation Oncology at Stanford, with its long history and focus on both patient care and research, was a natural fit for the speaker's goals. The field grew out of radiology and was led by Henry Kaplan, who made significant strides in curing Hodgkin's disease with radiation therapy. While the hype around radiation therapy as a cure-all for cancer didn't pan out, it marked the beginning of radiation oncology as a distinct specialty.
From Physician to Researcher: A Journey Inspired by Liquid Biopsies: A physician's firsthand experience with cancer limitations led them to pursue research in liquid biopsies for early detection and prediction.
The Department of Radiation Oncology at this institution has a long-standing tradition of valuing laboratory-based research, thanks to early pioneers like Henry Kaplan. This environment was particularly appealing to the speaker, who wanted to pursue a career as a physician-scientist. The speaker's interest in liquid biopsies didn't emerge immediately; instead, it evolved from following the data generated in their research. Initially, they planned to focus on a different area, but a clinical need led them to explore liquid biopsies. As a physician, the speaker saw firsthand the limitations of traditional imaging for predicting cancer recurrence and was frustrated by the reactive approach to cancer care. With current imaging technology, it's challenging to detect tumors smaller than one centimeter in diameter, which can contain a vast number of cancer cells. The speaker's research in this area aims to improve cancer detection and prediction by focusing on liquid biopsies.
The growth of tumors is non-linear and can spread beyond the localized tumor as micrometastatic disease.: Despite a tumor's small size, it can contain vast numbers of undetectable cancer cells that can spread and lead to fatal outcomes. Protein biomarkers for cancer detection have limitations due to their lack of specificity.
The growth of tumors is a non-linear process, meaning that the number of cells increases much faster than the diameter of the tumor might suggest. This is important because many cancers, including those of the lung, liver, pancreas, colon, and breast, can grow to a size of one centimeter or more without posing a direct threat to the organism. However, once cancer spreads beyond the localized tumor, it becomes much more difficult to treat, often resulting in a fatal outcome. This is known as micrometastatic disease or microscopic disease, and it can involve dozens or even hundreds of deposits in different organs, each containing tens of billions of cells that are still undetectable. Historically, protein biomarkers like PSA, CEA, and CA-99 have been used to detect cancer, but they have limitations, particularly in terms of specificity. These markers are not unique to cancer cells and can be produced by normal cells as well. As a result, low levels of these markers in the blood do not necessarily indicate the presence of cancer. The lack of specificity is a major challenge for protein-based approaches to cancer detection, and it was a key motivation for the development of liquid biopsy tests in the speaker's lab.
Understanding Sensitivity and Specificity in Diagnostic Tests: Sensitivity measures a test's ability to correctly identify individuals with a condition, while specificity measures its ability to correctly identify those without it. Both concepts are essential to evaluate diagnostic tests' effectiveness and manage expectations.
Sensitivity and specificity are crucial concepts in understanding the effectiveness of diagnostic tests. Sensitivity, also known as true positive rate, refers to the likelihood of a test correctly identifying individuals with a specific condition. For instance, if a test correctly identifies 85 out of 100 cancer patients, its sensitivity is 85%. However, no test is perfect, and even tests with high sensitivity will have some false negatives. Conversely, specificity, the inverse of sensitivity, is the likelihood of a test correctly identifying individuals without the condition. For example, if a test correctly identifies 999 out of 1000 individuals without cancer, its specificity is 99.9%. It's important to remember that sensitivity and specificity are interconnected, and focusing too much on one can negatively impact the other. In the context of lung cancer, it's the first leading cause of cancer deaths for men and the second leading cause for women. Understanding sensitivity and specificity is essential to evaluate the effectiveness of diagnostic tests and manage expectations regarding their limitations.
Lung cancer: The leading cause of cancer deaths despite decreasing incidence rates: Smoking is the primary risk factor for lung cancer, but other factors like pollution and genetics also contribute. Women and Asians have a higher risk, and PM2.5 in the air is linked to an increased risk of lung cancer.
Lung cancer, despite decreasing incidence rates due to decreasing smoking rates, remains the leading cause of cancer deaths. While smoking is the primary risk factor, other factors like pollution and genetics can also contribute. The most common types of lung cancer are non-small cell, with adenocarcinoma being the most common subtype in non-smokers. Women and Asians have a higher risk of developing lung cancer, and the causes are not yet fully understood. Particulate matter in the air, specifically PM2.5, is linked to an increased risk of all cause mortality and lung cancer, but more research is needed to establish a definitive causation. Overall, while progress is being made in reducing lung cancer deaths, it remains a significant health concern.
Quantifying the risk of secondhand smoke exposure to lung cancer: Despite a clear link between smoking and lung cancer, accurately estimating the risk from secondhand smoke is difficult due to challenges in quantifying exposure and the lack of a reliable biomarker.
While the link between smoking and lung cancer is well-established, quantifying the risk from secondhand smoke exposure is challenging. Pack years, a metric used to estimate smoking history, is not perfect and can be difficult to determine accurately. The risk of lung cancer increases with the number of pack years smoked, but the relationship is not linear. The risk plateaus around 20-30 pack years for some studies. Secondhand smoke exposure is even harder to quantify, and there is no biomarker to measure it. Currently, secondhand smoke is not considered a criterion for lung cancer screening by LODO CT. The focus is on enriching the highest-risk population for screening to maximize the benefits while minimizing false positives. Understanding the sensitivity, specificity, and prevalence of a test is crucial to interpreting the results correctly. Low-dose CT has been a game-changer in lung cancer management in the last decade, but developing a reliable screening test for lung cancer has been a long and challenging process.
CT scans reduce lung cancer deaths but come with risks: The National Lung Screening Trial showed CT scans reduce lung cancer deaths by 20%, but the absolute risk reduction is small and radiation exposure is a concern
The National Lung Screening Trial showed that low-dose CT scans can significantly reduce lung cancer deaths, but it's not a perfect test and comes with a small radiation exposure. The trial found a relative risk reduction of about 20%, but the absolute risk reduction was small, in the single-digit percent range. However, interpreting the scan results can be complicated, affecting sensitivity and the number needed to treat. The amount of radiation from a low-dose CT scan is much less than traditional CT scans, but concerns about radiation risk remain. The medical community weighs the benefits of imaging against the known, yet difficult to quantify harms. The decision to image or not should be based on whether it's worth doing and will benefit the patient. For example, patients with lung cancer undergoing radiation therapy receive high doses of radiation. The radiation exposure from imaging is typically not tracked at the individual patient level.
Exploring liquid biopsies for early cancer detection: Researchers study circulating tumor cells (CTCs) in blood samples to diagnose cancer recurrences earlier, bypassing limitations of current imaging methods and improving patient outcomes
Early detection of cancer recurrence is crucial for effective treatment and improving patient outcomes. However, current imaging methods have limitations and can only detect cancer growth at later stages. This unmet need led researchers to explore liquid biopsies, specifically circulating tumor cells (CTCs), as a potential solution. The human body itself can serve as the final model for research, making it more applicable to clinical settings. Researchers can collect blood samples directly from patients and study CTCs for potential biomarkers, bypassing the need for mouse models. Startup funds provided the initial financial support for this research, as grants often require proof of concept before funding is granted. By collecting and studying CTCs in blood samples, researchers aim to diagnose recurrences earlier and ultimately improve patient outcomes.
Challenges in detecting and isolating circulating tumor cells: Despite promising potential, detecting and isolating CTCs for cancer diagnosis and treatment faces challenges such as scarcity, difficulty in purification, need for immediate processing, lack of specific markers, and difficulty in reproducing research results.
While the idea of detecting and isolating circulating tumor cells (CTCs) for cancer diagnosis and treatment is promising, the reality is that it comes with significant challenges. These challenges include the scarcity and difficulty of purifying CTCs, the need for immediate processing, and the lack of specific markers for certain types of cancer. Furthermore, reproducing research results can be difficult, and the publication system may be biased towards positive findings that are not always accurate. Despite these challenges, ongoing research continues in the field, and new techniques such as mass spectrometry are being explored to identify unique protein markers for cancer detection.
Scientific publishing prioritizes positive findings over negative ones, limiting our understanding of research validity: Negative findings, crucial for understanding research validity, are underrepresented in scientific publications due to economic factors and the prioritization of positive results, particularly in the field of CTCs where negative findings are important for predicting cancer recurrence.
The current scientific publishing system prioritizes positive findings over negative ones, leading to potential selection bias and limiting our understanding of the validity of research. This issue is particularly significant in the field of circulating tumor cells (CTCs), where the sensitivity of preoperative tests is low, and many patients with early-stage cancer have no detectable CTCs. However, identifying patients with high levels of CTCs preoperatively can serve as a negative prognostic marker, predicting a higher risk of recurrence. Despite this, reproducing negative findings is not incentivized, and the economic factors make it challenging to publish such studies. Ideally, we would prioritize negative findings as much as positive ones to ensure the accuracy and reliability of scientific research. Additionally, the CTC field faces another complication as non-cancer patients can also have cells that appear as CTCs using current markers, adding complexity to the interpretation of results.
Distinguishing Cancer Cells from Normal Cells in Liquid Biopsy: CTCs and cfDNA are two different approaches in cancer diagnosis and monitoring via liquid biopsy. CTCs face challenges in distinguishing cancer cells from normal cells, while cfDNA shows promise but requires further development.
Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are two different approaches in the field of liquid biopsy for cancer diagnosis and monitoring. CTCs are cells that circulate in the bloodstream, originating from tumors. The challenge lies in distinguishing cancer cells from normal cells, as healthy patients can have epithelial cells with white blood cell marker expression in their circulation. This makes CTCs an imperfect tool for cancer screening or disease recurrence prediction. On the other hand, cfDNA refers to DNA molecules that circulate outside of cells in the blood plasma. The idea of using cfDNA for cancer detection came from the success in prenatal diagnostics, where fetal DNA can be detected in a mother's blood. Isolating cfDNA from the plasma is crucial for its application in cancer patients, as it allows for the analysis of tumor-specific genetic material. This approach holds more promise for cancer diagnosis, monitoring, and even determining the course of adjuvant therapy. However, it still requires further development to become a clinically viable tool.
Red blood cells keep and trap significant DNA in the bloodstream: In a healthy individual, 1-5 ng/mL of cell-free DNA comes from red blood cells, which protect DNA from enzymes by keeping it wrapped around core histones.
The majority of cell-free DNA in the blood comes from the cells in the red blood cell compartment, making up about 1-5 nanograms per milliliter in a healthy individual. This is because the small red blood cells of individuals like the speaker, who has beta thalassemia minor, keep and trap a significant amount of plasma within their cellular bodies. The DNA in the blood is primarily double-stranded and wrapped around core histones, which protect it from enzymes that break down DNA in the bloodstream. The origin of cell-free DNA is still a mystery, with most reviews suggesting it's largely due to apoptosis, but this is not definitively proven. Apoptosis is a controlled programmed cell death that occurs in our bodies, and during this process, the DNA is chopped up into small fragments. However, it's challenging to study the release of DNA from all tissues, making the exact mechanism of DNA eviction from cells uncertain.
Understanding Apoptosis and Cell-Free DNA in Plasma: Apoptosis is a programmed cell death process that generates cell-free DNA in plasma. Researchers distinguish cancer cells from others by focusing on unique mutations as markers.
Apoptosis, a programmed way of cells dying, plays a crucial role in our development and getting rid of sick cells. During apoptosis, cells chop up their proteins and DNA as part of the cleanup process. However, it's now understood that other mechanisms, such as DNase in the plasma, can also cause DNA fragmentation. In a normal person, the amount of cell-free DNA in 10 mLs of plasma is between 1 to 5 nanograms per mL. But in certain conditions, such as advanced cancer or trauma, the levels can be much higher. To distinguish cell-free DNA from the cell of interest, like a cancer cell, researchers focus on unique molecular properties, specifically the mutations that cause cancer. These mutations serve as markers for the cancer cell, allowing for its separation from other cells.
Identifying cancer mutations in circulating tumor DNA: Next-generation sequencing identifies cancer mutations in ctDNA, making it a reliable indicator for cancer diagnosis and monitoring. However, the challenge lies in finding these mutations amidst millions of normal DNA segments.
Circulating tumor DNA (ctDNA) mutations are an attractive biomarker for cancer diagnosis and monitoring due to their specificity to cancer cells. These mutations represent the molecular cause of the disease, and their absence in normal cells makes them a reliable indicator. The detection of these mutations is typically done through next-generation sequencing, which allows for the identification of millions of DNA sequences, each about 170 bases in length. While the vast majority of these sequences align with the patient's normal germline DNA, a small subset carries cancer-specific mutations. The high specificity and sensitivity of this approach make it an effective tool for detecting the presence of cancer cells, even when they represent a very small fraction of the total cell-free DNA in the blood. However, the challenge lies in the fact that the total cell-free DNA consists of millions of short segments, each unique to the patient's genome. Given that the cancer may only have a few hundred mutations in its genome, it seems improbable that a randomly selected 170-base segment would align with one of these mutations. This statistical problem is one of the major challenges in the field, and researchers are continuously working on improving the sensitivity and specificity of ctDNA analysis methods.
Advancements in detecting and analyzing cell-free DNA from cancer patients: Researchers use next-generation sequencing to detect multiple mutations in parallel, increasing sensitivity by tenfold and identifying trunkle mutations crucial for detection. Cell-free RNA is emerging but faces challenges in stability and lack of mutations.
Researchers have made significant strides in the field of detecting and analyzing cell-free DNA (cfDNA) from cancer patients since the mid-2000s. This advancement came about due to the limitations of earlier methods, which could only detect a small amount of cfDNA and relied on looking for specific mutations. By utilizing next-generation sequencing technology, researchers can now identify dozens of mutations in parallel, increasing sensitivity by tenfold. Furthermore, the presence of a trunkle or clonal mutation, which is a mutation present in all cancer cells, is crucial for detection. The field of cell-free RNA (cfRNA) is also emerging, but its instability and the fact that it may not contain mutations are current challenges. However, measuring cfRNA could provide valuable information about which genes are active in the cancer, which is crucial for understanding cancer development and potential treatments. The ultimate goal is to be able to diagnose and analyze a patient's cancer through a simple blood draw, potentially eliminating the need for invasive biopsies.
DNA and RNA in Cancer Diagnosis: A Comprehensive Liquid Biopsy Approach: DNA and RNA analysis in liquid biopsies offer complementary information for cancer diagnosis, monitoring, and treatment. Circular RNA and DNA methylation provide additional context beyond mutations, helping distinguish between different types and origins of cancer.
While DNA can provide valuable information for identifying mutations in tumors, it may not be sufficient on its own for accurately determining the origin and type of cancer in a patient. RNA, particularly circular RNA, offers complementary information that can help distinguish between different types of cancer and even between primary and metastatic tumors. The difference between cell-free DNA and circulating tumor DNA is that the former refers to all DNA in the circulation, while the latter is the cancer cell-derived fraction. DNA methylation, a chemical modification of DNA, can also provide valuable information about the origin of the DNA, as different tissues have distinct methylation patterns. However, methylation-based approaches have lower sensitivity compared to mutation-based methods, which can detect mutations at much lower frequencies. Researchers are continually improving the sensitivity of these methods, with recent advances allowing for the detection of circulating tumor DNA at levels as low as 1 in a million. Overall, a comprehensive liquid biopsy approach that utilizes both DNA and RNA analysis can provide valuable information for cancer diagnosis, monitoring, and treatment.
Liquid biopsy tests for early cancer detection face sensitivity challenges: Despite promising results, liquid biopsy tests for early cancer detection struggle with low sensitivity, particularly for early-stage cancers. Accurate reporting of sensitivity by stage and improving test performance are crucial.
While liquid biopsy tests for early cancer detection, such as Grail's method using methylation patterns of cell-free DNA, show promising results, they still face challenges in achieving high sensitivity, especially for early-stage cancers. For instance, the sensitivity for stage one lung cancer is reportedly 5% or less. It's crucial to report sensitivity accurately by stage and even within stages to avoid bias. A test with 50% sensitivity and 99.5% specificity might seem impressive, but it's only a slight improvement over the pretest probability for individuals without cancer. Negative predictive value, which is more relevant for patients without cancer, is a more important metric. However, the lack of mutational information in patients without known cancers limits the potential of these tests beyond being a "parlor trick." It's essential to continue researching and improving these tests to make them more effective in detecting early-stage cancers in individuals without prior knowledge of the disease.
Ensuring Effectiveness of Cancer Screening Tests: While cancer screening tests can detect cancer early, their effectiveness in saving lives and not just increasing diagnoses is crucial. Tests can miss certain types of early-stage cancers and have high false positive rates, leading to false reassurance, unnecessary anxiety, and additional testing costs.
While cancer screening tests, such as CT scans and circulating tumor DNA (ctDNA) assays, can detect cancer at earlier stages, it's crucial to ensure these tests are effective in saving lives and not just increasing diagnoses. The tests can miss certain types of early-stage cancers that have already spread to other organs, leading to false reassurance and unnecessary anxiety for patients. Furthermore, the high false positive rate can result in additional testing and unnecessary costs to the healthcare system. Researchers emphasize the need for large randomized trials to prove the cancer-specific survival benefits of these tests, but commercial interests and the high cost and time investment of such trials hinder progress. The complexity of cancer stages and the heterogeneity of early-stage cancers add to the challenge. The FDA has approved only a few liquid biopsies for specific uses, such as identifying mutations in patients with advanced disease, and the ethical dilemma of withholding potentially life-saving tests from patients remains a topic of debate.
Identifying mutations in advanced cancer patients through Liquid Biopsy tests: Liquid biopsy tests, like those from SoilScan and Foundation Medicine, help identify mutations in advanced cancer patients, agreeing with biopsy results, but are not suitable for early cancer screening or determining if a patient is cured after treatment. They require a high tumor burden and follow both FDA approval and CLIA certification processes.
Liquid biopsy tests, such as those offered by SoilScan and Foundation Medicine, are primarily designed for identifying mutations in patients with advanced stages of cancer who cannot undergo invasive biopsies. These tests are not suitable for early cancer screening or detection, nor do they determine if a patient is cured after treatment. The tests work by detecting circulating tumor DNA in the blood, and they have a high agreement with biopsy results. However, they require a high tumor burden for optimal performance. The regulatory landscape for diagnostic tests in the US includes both FDA approval and CLIA certification. FDA approval involves a rigorous evaluation process, while CLIA certification allows labs to develop and offer tests within their facilities, which can expedite patient access. Companies like SoilScan and Grail follow this route before obtaining FDA clearance. There are around 30 other companies currently working on similar technologies.
Early cancer detection through blood tests: Liquid biopsy shows promise in detecting microscopic cancer cells, increasing effectiveness of adjuvant therapy, and potentially curing more patients.
The future of cancer detection and treatment may lie in the early identification of minimal residual disease through blood tests. Current advancements in technology and clinical trials allow for the detection of microscopic cancer cells, even when they are not yet clinically detectable through imaging. This approach, known as liquid biopsy, has shown promise in increasing the effectiveness of adjuvant therapy and potentially curing more patients. While challenges remain, particularly in the case of pancreatic cancer, researchers are hopeful that this approach will lead to a future where cancer can be detected and treated at an earlier stage, ultimately improving patient outcomes.
Identifying high-risk cancer patients with liquid biopsies: Liquid biopsies, specifically ctDNA tests, can help identify high-risk patients in need of adjuvant therapy in various cancers, potentially minimizing over-treatment and improving patient outcomes.
Liquid biopsies, specifically Circulating Tumor DNA (ctDNA) tests, hold promise for identifying high-risk patients in need of adjuvant therapy in various cancers such as colorectal, breast, and prostate. These tests are most beneficial in cases where a subset of patients is at risk for recurrence, and they can potentially minimize over-treatment and toxicity for those at lower risk. The tests are already being used in colorectal cancer, and studies are underway for breast and prostate cancer. However, breast and prostate cancers present challenges due to their low levels of circulating tumor DNA. If these approaches prove effective, they could lead to a future where adjuvant therapy is only given when the test is positive, reducing the number of missed cases and improving patient outcomes. Additionally, these tests could help avoid over-treatment by identifying patients who are at lower risk for recurrence and do not require adjuvant therapy.
Identifying Early-Stage Cancer with Liquid Biopsies: Liquid biopsies show promise in detecting cancer early, but challenges include over-treatment and limited mutation databases. A mutation-based method, like LungClip, uses machine learning to analyze mutation properties and distinguish cancer from age-related mutations, improving accuracy.
Liquid biopsies have the potential to revolutionize cancer screening by identifying cancer at its earliest stages, but there are challenges such as over-treatment and the need for robust databases of mutations for every tumor. A promising approach is using a mutation-based method, such as the LungClip method, which sequences both cell-free DNA and leukocyte DNA to distinguish mutations from age-related mutations. Machine learning algorithms analyze mutation properties, like mutation presence, gene location, and DNA fragment length, to determine the likelihood of a sample being from a patient with cancer. While this method isn't a catalog of mutations due to the uniqueness of every cancer, it uses as much information as possible to improve accuracy. Future developments may involve combining this approach with methylation and other analytes to create the most effective cancer screening test.
Determining the sensitivity of ctDNA detection in early-stage lung cancer: Researchers are investigating the potential of using Circulating Tumor DNA (ctDNA) for early detection of lung cancer, with hopes of increasing sensitivity while maintaining high specificity. The current experiment aims to measure ctDNA shedding in stage one patients, providing insight into the test's potential performance.
The detection of Circulating Tumor DNA (ctDNA) in early-stage lung cancer using a combination of methods is still in the research phase. The sensitivity and specificity of this approach are not yet definitively known, but there's hope that it could significantly increase the current 20% sensitivity and maintain high specificity. The current experiment aims to determine the amount of ctDNA shedding in stage one lung cancer patients using a highly sensitive method. Once this data is available, researchers will have a better understanding of the potential sensitivity and specificity of this integrated approach. This test could be particularly useful for cancers without current screening tests, such as pancreatic cancer, where even an imperfect test could be helpful. However, it's important to note that the test's performance should be compared to existing screening tests, and it should at least match or exceed their capabilities for widespread adoption.
Promising landscape for liquid biopsies despite current limitations: Liquid biopsies show potential but need high sensitivity and specificity tests for early stage cancer. Companies and NIH are investing in research to improve accuracy.
While liquid biopsies have shown promise in cancer diagnosis and monitoring, they currently don't match the accuracy of traditional tests. The main use of liquid biopsies is therefore in practical or health system considerations, such as low dose CT scans. However, there is a need for high sensitivity and specificity tests for early stage cancer, and many companies are working towards this goal. The NIH recognizes the potential of liquid biopsies and has increased funding for research in this area. Despite the challenges, the landscape for liquid biopsies is promising, and there is a lot of interest and progress being made. It's important to continue pushing for clinical science and proof of decreased cancer-specific deaths before fully embracing the technology.
Dr. Peter Attia's Informational Podcast: Listeners should not rely on the podcast for medical advice and should consult healthcare professionals for any medical concerns.
Dr. Peter Atia's podcast, which can be found on Twitter, Instagram, Facebook, and various podcast platforms, is for general informational purposes only. It does not establish a doctor-patient relationship or provide medical advice. Users should not rely on the information provided as a substitute for professional medical advice, diagnosis, or treatment. They should consult their healthcare professionals for any medical conditions they have. Dr. Atia discloses potential conflicts of interest on his website and takes them seriously. The content is intended to educate and inform, but users should exercise caution and seek professional help when necessary. The use of the information and materials linked to the podcast is at the user's own risk.
