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* Exciting Update: The interest-free portion of the cash advance has recently been increased from $100,000 to $250,000, providing even more financial flexibility for farmers. In this episode of The Impact Farming Show, Tracy sits down with Dave Gallant, Vice President of Finance and APP Operations from the Canadian Canola Growers Association (CCGA), to discuss the CCGA Cash Advance Program, a financial tool that is helping farmers navigate today's elevated interest rates. Farmers often face challenges around managing cash flow, especially during unpredictable market conditions. The CCGA Cash Advance Program offers farmers up to $1,000,000 in working capital financing, with flexible terms designed to help farmers plan better and reduce borrowing costs. Key Topics Discussed in This Episode: What is a Cash Advance? Dave explains the Advance Payments Program (APP), which provides farmers with short-term financing to support their working capital needs. With up to $250,000 available interest-free and the rest at a reduced interest rate, this program is an attractive financial tool for many farmers. How Does the Cash Advance Work? The cash advance program provides up to $1,000,000 for financing across more than 50 commodities, including field crops, livestock, organic crops, and even honey. The two-part structure (interest-free and interest-bearing) helps manage costs effectively. Farmers can use both portions to support their operations. Who is the Canadian Canola Growers Association (CCGA)? Learn more about the CCGA, a farmer-founded, farmer-led association representing about 40,000 canola farmers. CCGA has been instrumental in advocating for farmers' needs and administering the Advance Payments Program since 1984. Practical Uses for the Cash Advance Program Dave and Tracy dive into how farmers can use the cash advance to support their operations during the growing season, providing flexibility in managing cash flow and financing their marketing plans. How to Apply for a Cash Advance If you're interested in applying for a cash advance, Dave outlines the steps involved and how the CCGA makes the process as simple and efficient as possible. Exciting Update: The interest-free portion of the cash advance has recently been increased from $100,000 to $250,000, providing even more financial flexibility for farmers. SHOW RESOURCES: CCGA Cash Advance Program: https://www.ccga.ca Episode 228: CCGA Cash Advance Program: The Financial Tool Farmers Are Looking For with Dave Gallant https://www.farmmarketer.com/Resources/ResourceItem?resourceItemId=493 Sign Up - If you enjoyed this episode, make sure to sign up as an Insider to get the latest updates, expert insights, and promotions from The Impact Farming Show: https://www.farmmarketer.com/impact_farming_show/sign-up =================================
In this JCO Precision Oncology Article Insights episode, Mitchell Elliot summarizes an editorial: “A Targeted Methylation–Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease” by Dr. Brandon A. Mahal, et al. published on August 29, 2024. TRANSCRIPT Mitchell Elliott: Hello and welcome to JCO Precision Oncology Article Insights. My name is Mitchell Elliott, a JCO Editorial Fellow. Today, I'll be discussing the article, “A Targeted Methylation–Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease,” by Mahal et al. Cancer overdiagnosis, particularly of low-risk conditions that are unlikely to cause harm, is a common issue in screening tests. In prostate cancer screening, overdiagnosis affects 23% to 42% of cases, often due to the prevalence of low-grade cancers and the low specificity of the prostate specific antigen or PSA tests. Data from previous studies have highlighted that men with low grade prostate cancer often die with prostate cancer and not of prostate cancer. Over diagnosis can lead to unnecessary treatments, increased patient anxiety, side effects, and excessive healthcare costs. Multicancer early detection, or MCED tests offer a new approach by detecting multiple cancer types from a single blood sample with low false positive rates, typically less than 2%, and they also have the ability to predict the cancer type from this one test. The GRAIL Galleri test, based on methylation patterns of circulating tumor DNA, showed high accuracy detecting over 50 cancer types, including prostate cancer, in the circulating cell free genome atlas or CCGA in PATHFINDER studies. This type of MCED test paradigm is being developed for use alongside traditional screening methods in adults over the age of 50. This study evaluated this particular MCED test ability to detect both indolent and aggressive prostate cancer, aiming to assess its potential to contribute to over diagnosis. This cohort was part of the circulating cell free genome atlas or CCGA study, a multicenter case control study with three phases to validate this particular MCED test. The CCGA enrolled 15,254 participants, of which 8,584 had cancer and 6,670 did not. Enrollment was carried out in 142 North American sites between 2016 and 2019. Eligibility for cancer cases required a confirmed diagnosis or high suspicion with planned biopsy or surgery within six weeks of enrollment. This study evaluated 420 recently diagnosed men with prostate cancer from substudy 3, the independent clinical validation arm. The PATHFINDER study was a prospective cohort study of 6,662 adults over the age of 50 enrolled from seven US health networks between December 2019 and December 2020. Participants underwent testing with the GRAIL Galleri test, with results shared with physicians and participants. The test indicated the presence or absence of a cancer signal and predicted the cancer signal of origin if detected. This study's prostate cancer cohort included 18 men diagnosed through MCED testing or PSA screening, excluding two with recurrent disease. PSA testing was not collected in this particular study. Detectability by the Gleason group, clinical stage, association of detection status with tumor methylation fraction, and overall survival were assessed in these studies. The results are broken down by each substudy evaluated. Substudy three of the CCGA enrolled a clinically relevant patient population. The median age of the men enrolled were 65. Ethnic diversity was not represented, however, in this cohort, with only 15% of participants reporting as non-white, non-Hispanic. It is important to note that only 8.4% of patients included in the study self-identified as black non-Hispanic, a particular group of participants with a higher incidence in more aggressive prostate cancer. The overall MCED test sensitivity for prostate cancer detection was low in 11.2% or 47 out of 420 patients included in this cohort. The cancer signal of origin prediction accuracy was 91.5% with 43 of 47 patients having prostate cancer predicted. The test did not detect any low-grade tumors. It detected 3 of 157 favorable or intermediate grade tumors as well as 4 of 78 unfavorable intermediate grade tumors, and finally 36 of 113 high grade tumors, typically, Gleason score 4 and 5. Detection increase was staged with only 3.2% or 3 of 95 of stage one disease detected with the MCED test, while 14.9% or 7 of 47 with stage 3 and 81.5% 22 out of 27 patients with stage four disease. Compared with expected overall survival estimated from the United States SEER database, non-detected cancer cases had roughly three times better overall survival with a hazard ratio of 0.263 with a 95% interval of 0.1 to 0.5 with a p value of less than 0.05, and detected case that had similar survival, the hazard ratio of 0.672 with a 95% interval crossing one and a p value of 0.2 when adjusted for age, Gleason grade, and clinical stage. This suggests that patients identified to be ctDNA positive at diagnosis have an overall worse outcome than those who are ctDNA negative, a consistent phenomenon with previous studies using the same or different tumor informed and diagnostic ctDNA assays. Next, the authors evaluated the outcomes in the PATHFINDER cohort of 18 participants. The characteristics of patients enrolled were similar to the previous cohort. Only one case was detected, which was between Gleason group 3 and 5, and had either stage 3 or stage 4 disease not defined in the manuscript. Because only a single case of prostate cancer was identified in PATHFINDER via this test, cancer signal of origin, predicted accuracy, tumor methylation fraction, and survival outcomes were not calculated. In summary, this test preferentially detected high grade and advanced stage prostate cancers, identifying 93% of Gleason grade 3 to 5 and 67% of stages 3 and 4 cases, while notably did not detect Gleason grade 1, having only 1.9% of Gleason grade 2 detected and 4.2% of stage 1 and stage 2 cancers overall. Importantly, around one third of the detected cases in substudy three of the CCGA, involved non metastatic disease, including stage 1 to stage 3 were Gleason grade 3 to 5, which are potentially curable. Prostate cancers that were not detected via this test had better survival rates after adjusting for age, grade and stage in the SEER database. This suggested that MCED testing is unlikely to contribute to the overdiagnosis of indolent prostate cancers. Additionally, a positive cancer signal with a predicted prostate origin strongly indicates the presence of aggressive disease, warranting immediate diagnostic investigation. One limitation of the study is the lack of representative inclusion of patients from diverse ethnic backgrounds. Overdiagnosis of prostate cancer due to PSA levels disproportionately affects black men, and the generalizability of these findings in the study is limited by the fact that over 85% of the study cohort was self-reported as white non-Hispanic. Further data is required to understand the biology of cancer in this community and limit the bias of molecular screening tests so they are effective regardless of ethnicity. Thank you for listening to JCO Precision Oncology Article Insights. This was a summary on “A Targeted Methylation–Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.” Please follow and subscribe on your favorite streaming platforms. For more podcasts from ASCO, visit www.asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this week's episode, Tracy speaks to Dave Gallant from the Canadian Canola Growers Association about the “CCGA Cash Advance Program: The Financial Tool Farmers Are Looking For.” Are you concerned about the current elevated interest rates? If so, you will not want to miss this episode, in which Tracy speaks to Dave Gallant about a powerful borrowing tool for Canadian farmers. In this episode, they discuss: Who is the Canadian Canola Growers Association and what does it do? Did you know that in addition to policy development and advocating for Canola Growers, the association is also the largest and most experienced Advance Payments Program administrator in Canada and strives to make the program as convenient as possible? Dave shares that the Advance Payments Program is a federal program administered by the Canadian Canola Growers Association. It offers Canadian farmers marketing flexibility through interest-free and low-interest cash advances. Tracy asks Dave how the CCGA Cash Advance Program terms compare to traditional banks. Interest-free loans? Yes. CCGA is offering up to $250,000* interest-free for all eligible commodities and the interest-bearing portion at prime rate less 0.25%. Tracy and Dave speak about how this program is a fantastic tool for young farmers because no extra collateral/security is needed to borrow. It makes financing more accessible for those starting out and helps them build up a credit borrowing history. Did you know that the CCGA Cash Advance program covers 50 eligible commodities, including all major field crops and livestock, as well as organic crops and cattle. Tracy asks Dave when farmers can apply. Is it once a year, or can farmers apply at different times throughout the year? Do crops need to be seeded, and calves need to be born to apply? Dave shares all the details with our audience. In addition to the unbeatable financial terms, Dave shares how the cash advance is really a powerful marketing tool for farmers. It allows farmers to sell when they want to, not when they need to for cash flow purposes. One thing Dave notes for our audience is that while this program is National across Canada, CCGA only lends to certain provinces. He shares those provinces, and for farmers outside these provinces, he gives details on where farmers can find other institutions that lend to their province. Dave gives a final call to action, details on the application process, and where and how farmers can apply. Are you interested in learning more about the CCGA Cash Advance Program? If so, you will want to tune into this episode and visit their website below. *********** RESOURCES CCGA Cash Advance Program First-time customers, be sure to check us out online: www.ccga.com/cash Follow us on Twitter @ccga_ca *********** SIGN UP If you enjoyed this episode, don't forget to sign up as an Insider so that you are first to know about all-new Impact Farming episodes, Expert Corner Segments, fantastic contests, and new promotions https://www.farmmarketer.com/impact_farming_show/sign-up
JCO PO author Dr. Eric Klein shares insights into his JCO PO article, “Performance of a Cell-Free DNA-Based Multi-Cancer Detection Test in Individuals Presenting with Symptoms Suspicious for Cancers” Host Dr. Rafeh Naqash and Dr. Klein discuss how a multi-cancer detection test may facilitate workup and stratification of cancer risk in symptomatic individuals. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Social Media Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are excited to be joined by Dr. Eric Klein, Emirates Professor and Chair at the Glickman Urological and Kidney Institute at the Cleveland Clinic Lerner College of Medicine. Dr. Klein is also a distinguished scientist at Grail and author of the JCO Precision Oncology article titled "Performance of a Cell-free DNA-based Multi-cancer Detection Test in Individuals Presenting with Symptoms Suspicious for Cancer." Our guest's disclosures will be linked in the transcript. For the sake of our conversation today, we'll refer to each other using our first names. It's great to have you here today, Eric, and welcome to our podcast. Dr. Eric Klein: Thanks, Rafeh. I'm happy to be here. Dr. Rafeh Naqash: So today, we're going to try to delve into this very interesting paper. We've had a couple of very interesting podcasts on liquid biopsies, or plan to have a few more. And this is a different aspect of liquid biopsy assessment, and the context here is early cancer detection. Now, the story as it starts, is based on the methylation profile of cancer. Can you tell us, for the sake of our listeners, as we have a very broad audience ranging from trainees to community academic oncologists, what do you understand by methylation profile on a cancer? Dr. Eric Klein: Sure. Happy to start with that. There are lots of cancer signals in the blood. Cancer cells secrete or otherwise supply the bloodstream with DNA that has methylation signals that are specific to cancer. That's a hallmark of cancer-specific mutations. You can look at chromosome fragments, you can look at proteins and mRNA and exosomes and that sort of thing. In Grail's development study, we focused on using methylation because that, as I mentioned, is a fundamental process. A fundamental property of cancer cells is altered methylation. And in our original development studies, that was the strongest signal, the one that allowed us to have the lowest limit of detection when cancer was present, and the one that allowed us to have the best predictive accuracy for the cancer signal origin. Some people think about that as predicting the tumor origin or the tumor type. And that's the basis of Grail's assay, a pan-cancer methylation profile. Dr. Rafeh Naqash: Excellent. And now to understand some of the methodology that you used here, before we go into the details because there's a lot of sensitivity and specificity obviously associated with any cancer detection test, and you want a high sensitivity and specificity. And the idea here is that this would help in triaging patients appropriately using this non-invasive tool. Could you tell us the patient population that you were trying to enroll in this study? And I think there is, again, background to other studies that you have done using the Grail test. Could you put that into context of this specific study? Dr. Eric Klein: Sure. The population in this particular publication was from substudy 3 of a much bigger study called the Circulating Cell-free Genome Atlas, or CCGA. That was a discovery, refinement, and validation study of this methylation-based signal. And in total, all three substudies together was about 15,000 people, and it was a case-control study. About 10,000 of the individuals enrolled had cancer and about 5000 were not known to have cancer and served as controls. In the first part of the study, substudy 1 of CCGA, we simply asked the question: In individuals with known cancer, could we detect a methylation-based signal? And the answer was ‘yes'. The second question was: In patients not known to have cancer, did we not see a signal? And by and large, the answer was ‘yes'. The second substudy was a refinement and validation of the original methylation-based test. And then this study, what we refer to colloquially as CCGA3, or substudy 3 of CCGA, was the final validation that underlies the methylation assay that is currently on the market. So, in CCGA3, we determined what the performance characteristics of this test were in a case-control fashion, and what we found, importantly, was that the specificity was very high, at 99.5%, which means the false-positive rate is only half a percent. We found that the overall sensitivity for detecting cancer varied by stage, but when you included all stages 1 to 4, the overall sensitivity for detecting known cancers was about 51%. We found that the ability of this methylation-based test to predict the correct cancer signal origin was right around 90%. And finally, the final performance characteristic was really important, which is the positive predictive value. So in individuals who had a positive signal detected, the positive predictive value was 43%, which compares very favorably to existing screening tests, all of which are below 10%. That was the background, and the development there was focused on eventually developing a test that will screen the general population, the asymptomatic population, at risk for developing cancer. This is a subset of CCGA3, or the substudy 3 of CCGA, where we looked at the performance characteristics of this test in individuals who had symptoms that could possibly be due to cancer and individuals who had underlying medical conditions that could result in a false positive, and individuals in particular over age 65, because the risk of cancer goes up over age 65. Dr. Rafeh Naqash: Thank you for explaining that. So, again, going to some of the finer details in this study, you mentioned some very important numbers here, 99%, 63%, or something in that range for sensitivity and specificity. Could you explain a little more on that based on the cancer types? As you mentioned, stage 4, when I read the paper, has more true positives likely based on or related to how much cell-free DNA is released in the tumor. The tumor burden may be playing a role there. Could you explain that a little more for our listeners? Dr. Eric Klein: A cancer that sheds cell-free DNA into the bloodstream is more likely to be aggressive, and that's been shown in multiple different studies using multiple different platforms. And the reason for that is that the ability to shed cell-free DNA into the bloodstream goes along with biologic processes that we know are related to tumor aggressiveness. So that's a higher mitotic rate, it's neovascularization or the angiogenic switch, it's the ability to be an invasive cancer. And so the fact that you can detect cell-free DNA in the bloodstream implies some degree of biologic aggressiveness, which is not to say that tumors that shed cell-free DNA into the bloodstream are not curable. They are, in fact, curable at the same rate as cancers in people who are not tested for cell-free DNA. We know that for sure. It's just a signal that is there for us to exploit for the detection of cancers in asymptomatic individuals. And the hope is when we screen the general population, the general asymptomatic population for cancer, as we do with mammography and colonoscopy and PSA and so forth, that we can detect cancers at earlier stages, when they are far easier to cure. So I mentioned in CCGA3 that the overall sensitivity across all stages for detecting the presence of known cancers was 51%. That varied from about 16% for stage 1 cancers to 40% for stage 2 cancers to over 80 and 90% for stage 3 and 4 cancers. Dr. Rafeh Naqash: Right. And again, to provide more background to this, what we've come to understand gradually, as you mentioned, is that shedding is an important event in cancer trajectory. Do you think detection of cancers that are likely positive, driver mutation positive, have a lesser tendency to shed and maybe resulting in lesser tendency to earlier detection also, or is that not something that's true? Dr. Eric Klein: No, I don't think it has anything to do with the presence of driver mutations. The methylation signal that we see is a reflection of the perturbation of methylation in normal cells. So normal cells turn genes on and off using methylation. That's well known. Cancer cells exploit that biologic process of methylation by - in a gross oversimplification, but in a way that makes it understandable - they use methylation to turn off all the genes that prevent cell growth and turn on all the genes that allow cells to proliferate and get all these other biologic properties that make them invasive and so forth. So it's really important to understand that the test that was used in this study and that was developed in CCGA3 measures a shared cancer signal across multiple different cancer types. In CCGA3, we were able to detect more than 50 different individual kinds of cancers. It's a shared cancer signal that is fundamental to the biology of cancers, not just a specific cancer, but cancers. Dr. Rafeh Naqash: I see. I think what I was trying to say, basically was, when we do liquid biopsies in the regular standard of care clinic, and you're trying to assess VAFs or variant allele frequencies for a certain mutation, you tend to see some of these BRAFs or EGFRs that are very low VAF, and the data that I've seen is that you treat irrespective of the low VAF, if it's a driving mutation process. If your VAF is 0.1%, you still treat it with a targeted inhibitor. The context that I was trying to put into this is it all depends on shedding. So this liquid biopsy that we currently use, whether other platforms that are out there, if you're not shedding as much cell-free DNA or circulating tumor DNA, you're probably not going to catch that subclone or clone that is a driver. So, does that play a role in your test also? If you have, let's say, a lung cancer that is an EGFR stage 4, if the shedding is low, following a general conceptual context that these driver mutation-positive tumors do have less shedding in general than the non-driver mutation-positive, would you think that would somehow impact the detection using your test or your approach? Dr. Eric Klein: So, generically speaking, any test that looks for a cancer signal in blood is going to have a lower limit of detection. So there are analytic variables that make it such that, if you have extremely low levels of cell-free DNA or your other target shed into the blood, it's not going to be detected by the test. That's an analytical issue. Having said that, it's important to distinguish the fact that this test that we're developing isn't really a liquid biopsy. A liquid biopsy, really, if you think about it, is on patients who have known cancer, and you're doing a biopsy of the blood to determine if you can see a signal in the blood. This test has been developed to screen asymptomatic individuals who are at elevated risk of cancer, who actually may not have cancer. So we don't really view it as a liquid biopsy. But conceptually, you are correct that every test is going to have an analytical lower limit of detection so that not every tumor that sheds minuscule amounts of cell-free DNA will be detected. But that's not really relevant to this particular paper, I would say. It's not really relevant to the performance characteristics that we saw in this population. Dr. Rafeh Naqash: Understood. Thank you for differentiating the usual liquid biopsy approach that we use currently in the clinic, and this approach, which is meant more for detection in asymptomatic individuals. Going to some of the results, could you highlight some of the interesting findings that you had in this paper as far as performance is concerned? Dr. Eric Klein: Sure. Let me put it in a clinical context because we were just discussing asymptomatic individuals. That's what the test is ultimately meant for - screening asymptomatic individuals. But a common problem in oncology is this: patients present to primary care physicians with vague or nonspecific symptoms. Someone with COPD, for example, who presents with a cough, the cough could be due to the COPD, but if they have an underlying lung cancer, the cough could also be due to the lung cancer. Or someone presents with GI symptoms, could be related to cancer, or it could be related to a whole host of other things. And so there is a challenge for primary care physicians to sort out who might have cancer and who does not, particularly if they present with vague symptoms. In fact, most cancer diagnoses in the United States and Great Britain are actually found by primary care providers. In this paper, we looked retrospectively, after the fact, in CCGA3, the case-control study that we did, to see how this methylation-based test performed in individuals who had symptoms that could be associated with cancer, or could be due to cancer, or might not be, might be due to other things. What we found was that the performance characteristics were as good or better in this symptomatic population, where the physician is facing a diagnostic dilemma, as they were in the asymptomatic population. This is really important, specificity false negative rate across all the patients in the study was the same as it was in CCGA3. It was 99.5%. Again, the false positive rate was only 0.5%. We found, however, that overall sensitivity was better in the symptomatic population, and it was 64% instead of, or as compared to 43% in the asymptomatic population. That is not surprising because some patients who present with symptoms are more likely to have cancer. We also looked at a subset of patients who had GI cancers because that's a very, very common presenting symptom in primary care practice, and this test performs exceptionally well for detecting GI cancers. We found that the overall sensitivity was 84%. Finally, and importantly, in terms of the clinical utility of a blood-based test to detect cancer and direct a diagnostic workup, what we call the clinical signal origin accuracy - the likelihood or prediction that a positive signal was related to a particular tumor type - overall accuracy in this population was 90%. So if you had a cancer signal detected and you had a clinical signal of origin assigned to it, let's say, the test came back with cancer signal detected, the CSO prediction was GI cancer, the overall accuracy in actually finding a GI cancer was 90%. Actually, it was a little higher for GI cancers, but overall, for all cancers, it was 90%. Dr. Rafeh Naqash: You mentioned that GI cancers had a very high sensitivity, around 84% or so. Is that, again, related to the tumor shedding compared to some other tumor types? Dr. Eric Klein: Yes, there is a broad range of shedding across tumor types. So if you look at our data from CCGA, cancers like thyroid, prostate, and kidney do not shed a lot of cell-free DNA into the bloodstream, whereas GI cancers, hematologic malignancies, ovarian and pancreatic cancers shed much more cell-free DNA, and therefore their sensitivity for detection of those cancers is better. Dr. Rafeh Naqash: What would be the alternate approach? Your sensitivity here is 64%, which is pretty good, but it's not perfect. So the patients who potentially would be missed using this test, what would be the alternate approach capturing those patients also and hopefully avoiding a missed cancer diagnosis? Dr. Eric Klein: Well, it would be whatever the standard workup is that a primary care physician orders for someone who has vague symptoms. So, he idea here was to develop this, what we call a diagnostic aid for cancer detection in the symptomatic population. The idea here is to make the workups more efficient and to lend a greater degree of certainty as to what the diagnostic pathway ought to be. So, if you have a patient with vague symptoms and you're not sure if they are due to cancer or not, you might order a pretty broad diagnostic evaluation that might not end up finding cancer. In fact, if you take all the patients in a primary care setting, only about 7% of those individuals have cancer. Whereas, if you have a blood test that has a sensitivity of 64% and a positive predictive value of 75%, and you did that blood test early in the diagnostic workup and it was positive, you can do a much more tailored and perhaps a more efficient evaluation in speeding the diagnostic resolution. Dr. Rafeh Naqash: As you mentioned, perhaps avoid unnecessary testing, which adds to the overall cost burden in the healthcare field. Dr. Eric Klein: Correct. This was tested in another study called SYMPLIFY, which was done in a similar population of patients as this study - symptomatic patients presenting with vague symptoms or GI symptoms or weight loss, fatigue, those sorts of things, to primary care practice in the UK. And that was a prospective study. And the performance characteristics were very similar to what we saw in this study, although the overall positive predictive value in that study was 75% if you look at all cancers. And that would be very useful to a primary care physician and a patient to know what the likelihood of their having cancer is at the time they present or within a few days of presenting. Dr. Rafeh Naqash: Absolutely. And perhaps, to complement this approach with some of the other diagnostic approaches, maybe the possibility of detecting cancer earlier increases. So this is likely complementary and not necessarily the one-stop-shop. Dr. Eric Klein: It's important to understand that even in the symptomatic population, this is a screening test. And so, like all screening tests, if you have a positive mammogram that shows a nodule, you need to have a diagnostic workup to prove whether or not you have cancer. This blood test does not make the diagnosis of cancer; it simply helps direct a diagnostic evaluation that's necessary to confirm whether or not cancer is present or absent. That's true for both the asymptomatic and symptomatic populations. Dr. Rafeh Naqash: Could you tell us a little bit more about the CSO prediction in the general context of oncology and NGS, or the whole transcriptome sequencing that we do these days? We often see on a report that says,“What is the likely tumor of origin?” if you have an unclear primary. Can you explain that in the context of the approach that you guys use for CSO prediction? How does it differ from methylation versus mRNA prediction of tumor of origin or cell of origin? Dr. Eric Klein: Methylation has a rich signal in it, and it can distinguish cancer cells from a non-cancer signal, and using a second algorithm, specific methylation patterns that are specific to given lineages can identify lung cancer versus colon cancer versus liver cancer. Dr. Rafeh Naqash: Understood. Do you see this as becoming an approach that could be used, using, for example, urine or other sources that we can easily acquire versus blood? Dr. Eric Klein: Possibly. There is a lot of work in the field looking at urine-based markers for cancers, particularly, obviously, urologic cancers. And so there are already some products on the market made by other companies using methylation and other specific mutation patterns, for example, in urine to detect bladder cancer and to determine bladder cancer aggressiveness. It is an area of active investigation. Dr. Rafeh Naqash: This is definitely an exciting field, and the way the entire field of liquid biopsies in general is moving as it's detecting cancers or identifying mutations, and then implementing appropriate approaches, whether it is more screening or more treatment and all the drugs, etc. Are there any other interesting future approaches that you guys are planning as part of this paradigm shift that I envision will hopefully happen in the next few years? Dr. Eric Klein: Yes, as a company, Grail is focused on using this methylation-based technology across the entire cancer spectrum. So that's screening asymptomatic individuals, it's helping to direct diagnostic workups in individuals who present with symptoms to primary care practice, and also in the post-diagnostic space and all the possible uses there. So the detection of minimal residual disease and the decision on whether or not additional treatment is necessary, predicting response to particular therapeutic agents, or even choosing the correct therapeutic agents. All of that is under development. Dr. Rafeh Naqash: Definitely exciting. Now, the last portion of this podcast is specifically meant to highlight your career and know a little bit more about you. Could you tell us about your career trajectory and how you shifted focus towards a biomarker-driven approach? Dr. Eric Klein: Sure. Biomarkers have been a part of my career for a long time. I am trained as a urologic oncologist and did my residency in urology at the Cleveland Clinic and a fellowship at Sloan Kettering. At the dawn of the molecular biology era, the lab I worked in bought one of the very first PerkinElmer RT PCR machines for $5,000. It took up a whole desktop. I got very interested in genomic science at that time. So I spent well over 30 years practicing urologic oncology at the Cleveland Clinic, primarily focusing on prostate cancer. In the course of my career, I had the opportunity to work on a number of blood-based, urine, and tissue-based biomarkers. I have always been interested in understanding how our ability to measure molecules in blood and urine can help improve patient outcomes either through a streamlined diagnostic process or understanding of the biology of the disease better, picking the appropriate therapy, and so forth. In the course of that, I worked with someone at a company called Genomic Health in developing a biopsy-based RT PCR gene expression assay that helped select men for active surveillance. That individual subsequently joined Grail and he came knocking on my door in 2016 when Grail was just getting started to tell me about this exciting new technology. He said, “This isn't about urologic cancers in particular, but would you be interested in helping us accrue patients for this big clinical trial we're doing, CCGA, and determine if this technology would be useful in some way in helping patients.” And being the curious individual that I am, I said, “Sure.” And so I helped accrue lots of patients to CCGA. The results were shared, and I was quite excited by them and continued to work with the company on other studies, including PATHFINDER and some others, and eventually became a consultant for them. When I reached what I thought was the end of my clinical career by choice, I decided to step away from clinical practice, I had the opportunity to join Grail as a scientist, and that's where it's been. And what I would say, in the big picture, is this: as a surgeon, I was able to help a lot of patients on an individual basis. So I did about 10,000 major cancer operations in my career. So I helped those 10,000 people. As an academician, I was able to make certain observations and publish them in a way that taught people about different kinds of surgical techniques and how they may work better, and so I was able to expand my impact beyond the patients that I actually touched. When I heard about and understood what Grail was trying to do, I thought, “Wow, if we could develop a screening test that detects lots of cancers that we don't screen for - about 70% of all cancer deaths in the US are from cancers that we have no screening tests for - and if the screening population in the United States, individuals between ages 50 and 79, that's how CMS defined screening populations, well over 100 million a year, if this works, think about the impact that that could have.” That is really why I got excited about it. It fit my scientific interest, and I could see the big picture. Dr. Rafeh Naqash: Thank you for giving us some insights about your personal career. It is definitely a very interesting topic. I learned a lot, and hopefully, our listeners will find it equally interesting. Thank you again for being here today. Dr. Eric Klein: My pleasure. Thank you for having me. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to rate and review this podcast, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not reflect the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Thanks for tuning in to this Friday edition of RealAg Radio! Host Shaun Haney is joined by RealAgriculture's Lyndsey Smith and Kelvin Heppner as they discuss the threats from Russia, along with the Bank of Canada and the Federal Reserve, plus the Ontario announcement and much more! We will also have a spotlight interview with... Read More
Thanks for tuning in to this Friday edition of RealAg Radio! Host Shaun Haney is joined by RealAgriculture's Lyndsey Smith and Kelvin Heppner as they discuss the threats from Russia, along with the Bank of Canada and the Federal Reserve, plus the Ontario announcement and much more! We will also have a spotlight interview with... Read More
More than five years in the making, the Canadian Canola Growers Association (CCGA) is happily looking to the future of the biofuel industry after the federal government published the new Clean Fuel Regulation (CFR),replacing the Clean Fuel Standard. Steve Pratte, senior manager of transportation and biofuel policy with the CCGA, shares why the organization is pleased... Read More
Hour 2 People think the Brunswick News should have silenced a voice they don't agree with, including a former CCGA president. WGIG-AM and FM in Brunswick, GA
On this episode of Impact Farming, we sit down with Dave Gallant to discuss the benefits of cash advance programs. Learn how using a cash advance program can help your business succeed. You don't need to tie up collateral on your land, buildings or equipment and no down payment is needed. How would $100,000.00 of interest-free borrowing help your business?
A CCGA board member resigns in the wake of the basketball team's kneeling during the national anthem. We congratulate local organizations and we talk about Trump's Asia trip and the media's attempts to trip him up...
The discussion of the CCGA team kneeling continues.
Janet Morgan discusses how growers can utilize the cash advance program
Steve Pratte provides an update on the transportation backlog
Rick White discusses the policy work of the CCGA
Details on the program from Janet Morgan with the CCGA
Rick White from CCGA with an update
Saudações científicas queridos ouvintes! Preparem seus chapéus pensadores! Liguem o Boguscópio! Separem as cartinhas! Pois eu Alexandre NerdMaster, Brunno Costa do Podcastinboteco, Sr. Seu Panda do Cruzador Fantasma, Cleverson do Baú Pirata e Andrei Fernandes do Mundo Freak tentamos explicar para a infante Clarice Sena, do CCGA, como é o melhor programa educativo da televisão […]
Janet Morgan from the CCGA with details on the program
An update on the cash advance program from CCGA
Janet Morgan from the CCGA explains the application process
The CCGA cash advance program has provisions for unharvested grain this year
CCGA Executive Director Rick White explains the program
Kara Gray from CCGA with an update on the ongoing rail service review