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    Early Detection of Cancer Annual Conference- EDx22 – hosted by OHSU Knight Cancer Institute, The Canary Center at Stanford, and Cancer Research UK brought together great minds to collaborate in cancer early detection research!

    November 17, 2022

    This year’s sold-out conference had engaging discussions, talks from submitted abstracts, and opportunities to collaborate with experts from across the globe. There was also the opportunity to debate provocative early detection challenges.

    This year’s interesting Agenda and Speakers:

    Keynote: Population and tumor heterogeneity in cancer genome science
    Speaker: John Carpten, USC

    From models to mechanisms to humans
    Topic chairs: Simon Leedham & Victor Velculescu
    Speakers: Jos Jonkers, Ryan Schenck, Sabine Tejpar, Victor Velculescu

     Yeuk Pin Gladys Poon – The clonal evolution preceding leukemia development revealed using single-cell DNA sequencing

     Shiqin Liu – Shed Trop2 Extracellular Domain is a Potential Liquid Biomarker for High-risk Prostate Cancer and a Regulator of Prostate Cancer Progression

    Panel: How should we evaluate Multi Cancer Early Detection Tests?
    Moderator: Michelle Le Beau
    Speakers: Allan Hackshaw, Minetta Liu, Anne Mackie, Josh Ofman

    Emerging technologies for early detection and precision diagnosis
    Topic chairs: Rob West & Thuy Ngo
    Speakers: Brian Cunningham, Thuy Ngo, Mirabela Rusu, Rob West

     Jie Wang – Acoustic Fabrication of Living Cardiomyocyte-based Hybrid Biorobots

    Travis Moore – Robust CNV detection using single-cell ATAC-seq

    Great Debate 1: There is no such thing as over-diagnosis. Every diagnosis will help us better understand the biology of the cancer, eventually advancing early cancer detection and management.
    Speakers: Nora Pashayan & Eithne Costello

     

    Day 2, Opening remarks – Tanya Stoyanova, Canary Center at Stanford University

    Keynote Panel: A funding agency perspective on early detection
    Speakers: Karen Knudsen, Phil Castle, Catherine Elliott

    Microbiological risk factors for early detection
    Topic chairs: Xin Lu & Zhenzhen Zhang
    Speakers: Emma Allen-Vercoe, Curtis Huttenhower, Gabe Kwong and Zhenzhen Zhang

    Danielle Brasino – A New, Organ-on-Chip Platform to Study the Relationship Between Gut Microbiota and Distal Tumors

    Michael Fadel – Diagnostic performance of a non-invasive breath test for colorectal cancer: COlorectal BReath Analysis 1 (COBRA1) study

    Panel: What can we learn from trials that return unexpected results on mortality benefit from early detection biomarkers/tests?
    Moderator: Peter Johnson
    Speakers: Christine Berg, Usha Menon

    Great Debate 2: Single-organ cancer screening is failing public health – Multi-cancer early detection tests are the only way forward
    Speakers: Paul Limburg & Bob Steele

    Day 3, Opening remarks – George Hanna, Imperial College London

    Joshua Bull – Mathematical Tools for Spatial Analysis of Multiplex Medical Images

    Elinor Nemlander – Predicting lung cancer in never smokers, former smokers and current smokers using machine learning – results from a computer-based detailed symptom questionnaire given to patients investigated at a specialist lung clinic

    What is needed for an earlier cancer detection test to have clinical impact?
    Topic chairs: Tom Beer & Rebecca Fitzgerald
    Speakers: Hormuzd Katki, Larry Kessler, Chris Peters, Sharmila Anandasabapathy

    Conference closing remarks – George Hanna

    Early Detection of Cancer Annual Conference- EDx21 – hosted by Cancer Research UK, OHSU Knight Cancer Institute and the Canary Center at Stanford brought together the brightest minds in cancer early detection research!!

    November 29, 2021

    Highlighted excerpts of the conference include:

    Phil Jones, Ph.D., from the Wellcome Sanger Institute, showed how emerging tumors can be driven to extinction by competing clonal populations of cells.

    Irene Ghobrial, M.D., from Dana-Farber Cancer Institute, also focused on the precursor states, asking whether well-timed interventions can stop the advance to multiple myeloma, an incurable blood cell cancer.

    Minetta Liu, M.D., from Mayo Clinic, gave a whirlwind review of data from several companies readying multicancer, early-detection blood test for broad use, an indicator of the potential for rapid changes in screening practices.

    Mark Emberton, M.D., from University College London, asserted that blood tests will only ever serve as a triage tool for selecting patients for more informative imaging tests.

    Rebecca Fitzgerald, M.D., received the Don Listwin Award for Outstanding Contribution to Cancer Early Detection. She’s known for the development of the Cytosponge, which patients can swallow instead of undergoing an endoscopy.

    Shan Xiang Wang, Ph.D., from Stanford University, highlighted the advantages of giant magnetoresistive (GMR) sensors to look for cancer mutations in circulating DNA, such as EGFR in lung cancer. GMR is more sensitive than fluorescent PCR assays.

    Stephen Friend, M.D., Ph.D., from Oxford University, described studies underway collecting semi-continuous measurements via smartphone, smart ring and smart wristwatch.

    Daniel Heller, Ph.D., at Memorial Sloan Kettering Cancer Center, has developed sensors that can be placed inside the uterine cavity, like an IUD, to detect protein biomarkers of ovarian cancer that take too long to show up in blood.

    Hannah Brewer, Ph.D., from Imperial College London, gave an update on the Cancer Loyalty Card Study, which is tracking changes in medication purchases that could signal early signs of ovarian cancer.

    Aaron Grossberg, M.D., Ph.D., from the OHSU Knight Cancer Institute, asserted that single cells can’t tell the story without the context of what’s going on around them. Organisms have evolved to respond to localized threats in ways that change systemic physiology.

    Peter Kuhn, Ph.D., from the University of Southern California, countered that the single cell holds the necessary information, you just need to find the right cell, the needle in the haystack. It is not necessarily the cell that is a cancer cell, it could be a non-cancer cell that is indicative of the cancer.

    Stacey Fedewa, Ph.D., from the American Cancer Society, contrasted cancer screening among women in the United Kingdom, which provides healthcare to all permanent residents, and the United States, where many go uninsured and cancer screening is opportunistic and not organized with coordinated outreach. But in both countries, only about 4 in 10 women were up to date on cervical, breast and colorectal screenings, and 1 in 10 women in both countries said they received no cancer screening.

    Livia Giordano, M.D., Ph.D., from Centro di Riferimento per l’Epidemiologia e la Prevenzione Oncologica, , made clear the challenges of communication in cancer screening efforts. While it’s important to convey knowledge, inform risk perception to help people make choices that fit their values, Giordano said information is not enough. Communicators must consider emotions and trust.

    Robert Winn, M.D., from VCU Massey Cancer Center, illustrated how in the real world, the introduction of new technologies can create new health disparities, and for too long, medicine has avoided directly addressing the social determinants of health.

    Spencer Robinson, Ph.D., from York and Scarborough Teaching Hospitals NHS Foundation Trust, on a rapid diagnostic service that aims to give a single point of access to diagnosis for all patients who have serious nonspecific symptoms.

    Benjamin Ebert, M.D., Ph.D., from Harvard University, is finding ways to understand the risk of cancer in people with somatic mutations in blood cells, which are extraordinarily common.

    Hans Clevers, M.D., Ph.D., from the Hubrecht Institute, detailed the first patient-derived organoid model for cervical cancer.

    Thea Tlsty, Ph.D., from the University of California San Francisco, detailed efforts using bioengineered culture systems to reveal CAF signaling pathways that could be targeted for therapy or early detection.

    Carolyn Schutt Ibsen, Ph.D., from the OHSU Knight Cancer Institute, has developed a way to simulate, in an in vitro 3D model, the localized oncogene expression found in early-stage cancers.

    Panel discussion – Existing cancer therapies have largely been developed to treat advanced tumors. The panel discussed new therapeutic strategies that will be needed for people diagnosed with very early cancers or pre-cancerous lesions.

    Bissan Al-Lazikani, Ph.D., Institute of Cancer Research/MD Anderson Cancer Center, Early detection faces a signal-to-noise ratio problem that can only be solved by machine and massive, multimodal data mined by AI is the only way we’ll truly unravel the complexity of cancer early detection.

    Xin Lu, FRS F.Med.Sci., with Ludwig Cancer Research and the Oxford Centre for Early Cancer Detection, countered that AI-generated results lack meaning if they can’t be explained by a scientific hypothesis.

    The Early Detection of Cancer Conference- EDx21, hosted by:   Cancer Research UK, OHSU Knight Cancer Institute & Canary Center at Stanford. 

    Full daily recap from: Joe Rojas-Burke, Science Writer, OHSU Knight Cancer Institute

     Day 1

    Henry Scowcroft, a longtime science writer with Cancer Research UK, gained a shattering new perspective on the disease when his partner Zarah was diagnosed with stage IV bladder cancer at age 36. Scowcroft’s recently published memoir of the caregiving experience is interspersed with details of his science-minded effort to understand the disease that took his partner’s life. In the keynote talk, Scowcroft said he was driven to create something that would help others facing cancer, particularly those not privileged with medical knowledge and expert contacts. Caring for Zarah sensitized him to the burden of tests and treatments on cancer patients. He exhorted researchers to always include a focus on making a difference to the lived experience of people with cancer.
    When and where detection matters

    Cells with cancer-associated mutations become increasingly common with advancing age, but few ever give rise to invasive tumors. Why not? Phil Jones, Ph.D., at the Wellcome Sanger Institute, showed how emerging tumors can be driven to extinction by competing clonal populations of cells. In studies using mouse esophageal epithelium as a model, it was this competition that eliminated incipient tumors, not immune defenses. With deeper understanding, Jones said it could be possible to manipulate this competition of clones to stop cancer.

    Irene Ghobrial, M.D., from Dana-Farber Cancer Institute, also focused on the precursor states, asking whether well-timed interventions can stop the advance to multiple myeloma, an incurable blood cell cancer. Ghobrial is principal investigator of the PROMISE Study, the first to screen healthy people at risk for precursor conditions of multiple myeloma, including monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. The study aims to uncover why some patients progress to myeloma and others do not – and inform the development of screening and preventive treatment strategies. In earlier work, her group identified genetic alterations in smoldering multiple myeloma that could distinguish patients at high risk of progression to multiple myeloma.

    Breast cancers that emerge in young women within a few years after pregnancy are strikingly more dangerous. Pepper Schedin, Ph.D., with the OHSU Knight Cancer Institute, detailed how tumor cells are shaped by the postpartum environment to become more prone to metastasis. At the end of lactation, 80 to 90 percent of milk-secreting cells undergo programmed cell death, in a process called mammary gland involution. The early phase of gland involution resembles an acute inflammatory response that subsides and is followed by an immune response similar to what happens during wound healing. Schedin said mammary gland involution is an informative model for studying how factors outside of tumor cells drive cancer development.

    In the first lightning talk of the conference, Daniel Muñoz-Espin, Ph.D., from the University of Cambridge, explained how targeting senescent cells could be a way to prevent non-small cell lung cancer progression in people presenting with multifocal primary lesions in their lungs. Such lesions pose a treatment conundrum: most will progress to invasive cancer and there is no good way to stop them. Muñoz said accumulation of senescent cells is a common feature. In a mouse model, drug ablation of senescent cells decreased lung tumor burden and increased survival. In some of the mice, the treatment prevented cancer initiation.
    Great debate: Blood is the only detection medium that matters

    Minetta Liu, M.D., from Mayo Clinic, made the case for blood – an unpopular position going into the debate with the audience poll showing more than 90% disagreeing. Liu pointed out that existing modalities only screen for a few types of cancer. And some, like colonoscopy, are significantly invasive. Staying on schedule with all the separate screening tests is cumbersome for practitioners and, more importantly, burdensome for patients. Blood-based screening, in contrast, involves a point-of-care blood draw to screen for multiple cancers at once. Results so far suggest blood-based tests are pretty good at identifying the tissue of tumor origin to guide follow-up. Liu gave a whirlwind review of data from several companies readying multicancer, early-detection blood test for broad use, an indicator of the potential for rapid changes in screening practices.

    Arguing the contrary, Mark Emberton, M.D., from University College London, asserted that blood tests will only ever serve as a triage tool for selecting patients for more informative imaging tests. He said imaging more reliably delivers consistent results while blood test findings can vary considerably from day to day. He said imaging captures a range of attributes – location, volume, morphology, and more – that can’t be derived from a blood test. And imaging, he said, seems to land at a point in tumor development when cancers have the clear potential to become dangerous, while blood tests might detect too many indolent, non-threatening cases invisible on imaging scans. In the end, Liu swayed 19% to her side while support for Emberton’s position dropped to 81%.

    Day 2

    Rebecca Fitzgerald, M.D., received the Don Listwin Award for Outstanding Contribution to Cancer Early Detection. She’s known for the development of the Cytosponge, which patients can swallow instead of undergoing an endoscopy. Fitzgerald and her team published work showing the device can increase by 10-fold the identification of Barrett’s esophagus, a precursor to esophageal cancer, compared to standard of care. Fitzgerald talked about the power of collaboration, taking risks and the rise of early detection as a hot topic for researchers in an interview with Cancer Research UK.

    Presentations kicked off with a session on emerging technologies for detecting and interpreting early signals of cancer. Stanford University’s Shan Xiang Wang, Ph.D., highlighted the advantages of giant magnetoresistive  (GMR) sensors to look for cancer mutations in circulating DNA, such as EGFR in lung cancer. GMR is more sensitive than fluorescent PCR assays – and less costly, he said. And GMR can show responses to therapy within two weeks, while CT imaging can take two months or more. Wang’s team is also using GMR to find methylated DNA targets in the blood as a way to detect liver cancer in patients with liver cirrhosis, which produces methylation signatures that are difficult to distinguish from cancer.

    Can smartphones and wearables help triage the use of expensive and more invasive tools for cancer early detection? Stephen Friend, M.D., Ph.D., from Oxford University, described studies underway with the nonprofit 4YouandMe. Researchers will collect semi-continuous measurements via smartphone, smart ring and smart wristwatch. They will retrospectively analyze relative changes of multi-modal data streams among those who did and did not demonstrate new tumor growth.

    Most ovarian cancers are detected dangerously late. Daniel Heller, Ph.D., at Memorial Sloan Kettering Cancer Center, has developed sensors that can be placed inside the uterine cavity, like an IUD, to detect protein biomarkers of ovarian cancer that take too long to show up in blood. In mouse models of ovarian cancer, the carbon nanotube based optical sensors were stable for at least a month after implantation and reliably detected HE4 protein.

    In lightning talk, Hannah Brewer, Ph.D., from Imperial College London, gave an update on the Cancer Loyalty Card Study, which is tracking changes in medication purchases that could signal early signs of ovarian cancer. Her team has recruited 117 women diagnosed with ovarian cancer (cases) and 420 women without ovarian cancer (controls). Comparison of loyalty card data of cases and controls has revealed an increase in purchases of pain and indigestion medications prior to diagnosis, suggesting it might be feasible to use such data to prompt medical screening.
     

    Great Debate: Emergent properties of the ecosystem are how we’ll understand cancer; a focus on a single cancer cell’s biology is misguided

    Single cells can’t tell the story without the context of what’s going on around them, asserted
    Aaron Grossberg, M.D., Ph.D., from the OHSU Knight Cancer Institute. Organisms have evolved to respond to localized threats in ways that change systemic physiology, he said. Given that the probability of a positive finding in cancer screening is every low, even if cancer is present, he said that bio-amplification of the signal may be an essential process for detecting cancer. And knowing the prevalence of cancer-associated mutations in non-cancerous tissues, the state of single cells may be misleading without also knowing the state of the microenvironment.

    Peter Kuhn, Ph.D., from the University of Southern California, countered that the single cell holds the necessary information, you just need to find the right cell, the needle in the haystack. It is not necessarily the cell that is a cancer cell, it could be a non-cancer cell that is indicative of the cancer, he added. Kuhn changed a few minds; before the debate 75% agreed with Grossberg and 25% disagreed. After, 72% agreed and 28% disagreed.

    Early detection in the real world

    Starting the day’s final session, Stacey Fedewa, Ph.D., from the American Cancer Society, contrasted cancer screening among women in the United Kingdom, which provides healthcare to all permanent residents, and the United States, where many go uninsured and cancer screening is opportunistic and not organized with coordinated outreach. But in both countries, only about 4 in 10 women were up to date on cervical, breast and colorectal screenings, and 1 in 10 women in both countries said they received no cancer screening.

    Livia Giordano, M.D., Ph.D., from Centro di Riferimento per l”Epidemiologia e la Prevenzione Oncologica, made clear the challenges of communication in cancer screening efforts. It is essential to maximize informed choice to participate but also informed choice not to participate in screening, just as it is essential to minimize disinformed participation in addition to minimizing involuntary non-participation. While it’s important to convey knowledge, inform risk perception to help people make choices that fit their values, Giordano said information is not enough. Communicators must consider emotions and trust.

    In the real world, the introduction of new technologies can create new health disparities, pointed out Robert Winn, M.D., of VCU Massey Cancer Center. He traced the history of Richmond, Virginia, to illustrate how generations of societal policies have marginalized populations to create health disparities, from segregationist real estate practices, to the concentration of polluting industries in poor neighborhoods. For too long, he said, medicine has avoided directly addressing the social determinants of health.

    The day concluded with a lightning talk on a rapid diagnostic service presented by Spencer Robinson, Ph.D., from York and Scarborough Teaching Hospitals NHS Foundation Trust. The service aims to give a single point of access to diagnosis for all patients who have serious nonspecific symptoms. General practitioners refer patients. A triage clinician determines those who will receive a default workup including a CT scan and a trans-nasal endoscopy. Robinson said 336 referrals have resulted in 27 cancer diagnoses, including, in order of prevalence, metastases of unknown origin, pancreatic tumors, gynecologic cancers and lymphomas.

    Day 3

    Our final day started with a session on models and systems to inform detection. Harvard University’s Benjamin Ebert, M.D., Ph.D., is finding ways to understand the risk of cancer in people with somatic mutations in blood cells, which are extraordinarily common. Access to hundreds of thousands of exomes from peripheral blood is making it possible to trace the path from clonal hematopoesis of indeterminate potential to life-threatening cancer, and to identify events that signal escalating risk. Abnormal blood count is one such event.

    Hans Clevers, M.D., Ph.D., at the Hubrecht Institute, detailed the first patient-derived organoid model for cervical cancer, developed in his lab by Kadi Lohmussaar, Ph.D. Ordinary Pap sampling provides enough starting material to grow either healthy organoids or cervical cancer tumoroids. The organoids reproduce gene expression patterns of the organ, as the tumoroids mimic the mutations, gene expression and histology of patient tumors.

    Cancer associated fibroblasts, or CAFs, play a role in malignant initiation and progression. Thea Tlsty, Ph.D., from the University of California San Francisco, detailed efforts using bioengineered culture systems to reveal CAF signaling pathways that could be targeted for therapy or early detection. In an air-liquid interface culture system, bronchial epithelial cells grown alongside CAFs acquire squamous characteristics. Adding stress signaling triggers high-grade neoplasia. The next step will be to reproduce the development of full-on cancer.

    The session closed with a lighting talk by Carolyn Schutt Ibsen, Ph.D., from the OHSU Knight Cancer Institute. Her team has developed a way to simulate, in an in vitro 3D model, the localized oncogene expression found in early-stage cancers. The system uses lipid-monolayer gas-core microbubbles containing plasmid DNA. Directed ultrasound releases the plasmid DNA from the microbubbles so that only cells in ultrasound focal zone are transfected.

    What do we do once we detect early?

    Existing cancer therapies have largely been developed to treat advanced tumors. This panel of experts discussed the new therapeutic strategies that will be needed for people diagnosed with very early cancers or pre-cancerous lesions. Chair Charles Swanton, Ph.D., from the Francis Crick Institute/UCL, highlighted a daunting challenge: advances in early detection are revealing that some early-stage cancers can be as deadly as later stage disease. Tom Beer, M.D., at the OHSU Knight Cancer Institute, noted encouraging data suggesting that multi-cancer early detection blood tests might be better at detecting aggressive disease than indolent. Susan Galbraith, M.D., Ph.D., from AstraZeneca, highlighted the need for well tolerated therapies for patients diagnosed with early-stage disease. Avi Spira, M.D., with Johnson & Johnson said localized delivery of drugs could be one way to minimize toxicity. Usha Menon, M.D., University College London, expressed hope for linking screening trials with treatment trials; subjects found to have early disease could be randomized to trials of various treatments. All agreed that understanding the biology of early stage and pre-malignant disease will be critical to finding therapeutic targets for treating early cancers and intercepting pre-malignant disease with less toxic treatments.

    Great debate:   It’s time to give up on human hypothesis-driven research; massive, multimodal data mined by AI is the only way we’ll truly unravel the complexity of cancer early detection

    Relying on hypothesis-driven research is like wandering through an infinite jungle hoping to stumble on the correct path, asserted Bissan Al-Lazikani, Ph.D., Institute of Cancer Research/MD Anderson Cancer Center. Early detection faces a signal-to-noise ratio problem, she said, that can only be solved by machine. She pointed to the development of BRAF inhibitors. BRAF emerged as a worthwhile target from computational analysis of massive amounts of DNA sequencing data, not from a scientist’s hypothesis about that particular signaling pathway.

    Xin Lu, FRS F.Med.Sci., with Ludwig Cancer Research and the Oxford Centre for Early Cancer Detection, countered that AI-generated results lack meaning if they can’t be explained by a scientific hypothesis. A machine learning algorithm may find complex patterns linked to early cancer, but without a hypothesis to explain them, it’s impossible to validate the truth, Lu said. And AI requires a starting point and training data to learn from, which Lu said requires a human-generated hypothesis about the way the world works.

    Going in, 82% of the audience sided with Lu, and 18% with Al-Lazikani. After the debate, Lu’s support dropped to 54% and 46% agreed with Al-Lazikani.

    It’s been a productive three days!

    On behalf of Cancer Research UK, the OHSU Knight Cancer Institute and the Canary Center at Stanford, thank you for joining us for the 2021 Early Detection of Cancer Conference.

    Farewell,

    The Early Detection of Cancer Conference events team

    Canary Foundation Welcomes Dr. Joseph DeSimone

    November 22, 2020

    Dr. Joseph DeSimone

    We welcome Professor Joseph M. DeSimone, PhD. in the position of the Sanjiv Sam Gambhir Professor in Translational Medicine. We are fortunate to have such creative and capable leadership as our work together in cancer early detection continues.

    From the Stanford Press Release: The Stanford Department of Radiology is proud to announce Professor Joseph M. DeSimone as the inaugural Sanjiv Sam Gambhir Professor in Translational Medicine. A shining example of achievement, Joe has been described as “an igniter of innovation”. He has received international recognition as a scientist, inventor, and entrepreneur, earning major accolades including the U.S. Presidential Green Chemistry Challenge Award, the 2017 Heinz Award, and the Lemelson-MIT Prize. He is one of only 25 individuals elected to all three U.S. National Academies—the National Academy of Sciences, Medicine, and Engineering. In 2016, President Obama presented him with the National Medal of Technology and Innovation, the highest honor in the U.S. for achievement and leadership in advancing technological progress. Read more here.

    Joe and his lab have made significant scientific breakthroughs in science and medicine including next-generation approaches to cancer treatment and diagnosis, implantable drug delivery devices, green chemistry, and most recently in 3D printing technology for medical devices tailored to an individual patient’s needs. A dedicated educator and strong advocate for bringing a broader diversity of perspectives into research, he has mentored over 80 students through PhD completion at Univ. of North Carolina and North Carolina State Univ. (his former 30-year career), half of whom were women and members of underrepresented groups in STEM.

    As an avid researcher and innovator, Joe has authored over 370 scientific publications with over 42,000 citations to his work, and is a named inventor on over 200 issued patents. Additionally, he brings a unique ability to transfer novel solutions from his lab to the world through the companies he co-founded.

     

     

     

    Early Detection of Cancer Annual Conference – hosted by Cancer Research UK, OHSU Knight Cancer Institute and the Canary Center at Stanford brought together the brightest minds in cancer research with a record 600 registrants!

    October 26, 2020

    Highlights of the conference include:

    • DON LISTWIN AWARD for Outstanding Contribution to Cancer Early Detection was awarded posthumously to Sanjiv Sam Gambhir, Canary Center Director, an internationally recognized pioneer in molecular imaging who dedicated his career to developing methods of early disease detection.
    • Jon Emery (University of Melbourne) Cancer screening intensity should be matched to an individual’s risk of getting cancer. He described efforts to use genetic testing to help patients make informed decisions on colorectal cancer screening.
    • Amelie Lutz (Stanford University) is developing an ultrasound guided molecular imaging method for detecting ovarian cancer using microbubbles that target tumor angiogenesis.  They’re focusing on whether the KDR labeled microbubbles actually detect the VEGFR2 expression in the tumor vasculature and whether the KDR bubbles can help to differentiate benign vs malignant (NIH grant work). Her talk highlighted how their team tackled the tricky part where the in vivo imaging has to be matched with the ex vivo histology, and how it required close communication between the imager, the surgeon and the pathologist. So far they have results from 7 patients, planning to go up to 50 (results matched in 6/7 cases).
    • Stefano Avanzini (Stanford University) is using mathematical models to estimate the size tumors must reach to become detectable by tumor DNA circulating in blood.
    • Parag Mallick (Stanford University) explained how tools such as saliency mapping are making it possible to understand how the machines reach their conclusions – building confidence and potentially revealing biological insights. He also showed examples of Artificial Intelligence tools for biomarker discovery that extract and create knowledge from massive, unstructured data sets.
    • Cancer Research United Kingdom released an early detection road map, published in the Lancet (pdf): https://www.cancerresearchuk.org/sites/default/files/early_detection_diagnosis_of_cancer_roadmap.pdf
    • KEYNOTE TALK • Dinah S. Singer (National Cancer Institute) began with a rundown of the NCI’s response to COVID-19 pandemic, from virus-focused research initiatives to the ways the agency is flexing to support grantees. She concluded with an overview of the cancer early detection programs the agency has underway, such as the Early Detection Research Network (now focusing on Artificial Intelligence and machine learning to integrate omic data to find biomarkers), and The Human Tumor Atlas Network (HTAN), a massive effort to map the complex ecosystems of cancer – and pave the way for advances in prevention, early detection and treatment.

    Brief from The Early Detection of Cancer Conference  #EDx2020   –   recaps the entire conference, from their website: http://earlydetectionresearch.com    October 6-8, 2020

    Recapping day one

    We’re glad you made it to the 2020 Early Detection of Cancer Conference. We’re looking forward to more eye-opening presentations, well-argued debates and networking opportunities. Before jumping back into it, here’s a quick recap of day one:

    Caroline Dive (University of Manchester, CRUK Manchester Institute) brought us up to speed on efforts to improve lung cancer screening by combining CT imaging with a liquid biopsy. (Her team is running an observational cohort study to test whether blood biomarkers can detect lung cancer recurrence earlier than standard of care clinical surveillance.) The field has no shortage of potential biomarkers to choose from, including: circulating tumor cells, tumor DNA, RNA, and tumor educated platelets. Progress, Dive said, will hinge on a deeper understanding of early disease biology and pre-clinical models that more accurately represent the early stages of cancer.

    To that end, Anton Berns (Netherlands Cancer Institute) highlighted the promise of autochthonous tumor models, that is, tumors induced in lab animals, in which it is possible to study early tumor formation in the presence of an intact immune system. With such models, researchers can switch particular oncogenes and tumor-suppressor genes on or off in a given tissue and compare cancer development. Berns said his team’s mouse models closely recapitulate the phenotype of human cancers including small cell lung cancer, and may help identify specific early biomarkers of dangerous tumors.

    The first session closed with two lightning talks: Naoki Oshimori (OHSU Knight Cancer Institute) described how a mouse model of squamous cell carcinoma enabled his team’s discovery of a signaling loop between tumor-initiating cells and nearby non-cancer cells that generates the niche microenvironment that is required for invasive progression and drug resistance. Jennifer Munkley (Newcastle University Biosciences Institute) gave an update on the GlycoScore blood test for prostate cancer, which looks for specific glycans (sugars that attach to proteins, lipids, and other glycans on cells). Tested in more than 600 patient samples, a three-glycan test distinguished between benign tissue and prostate cancer with high sensitivity and specificity, she said.

    Reflecting on COVID-19 The COVID-19 pandemic, as in all of medicine, has posed severe challenges for cancer screening. Participants in a special panel discussion called out opportunities the pandemic has created. When it became unfeasible for patients to visit the clinic for melanoma screening, Sancy Leachman (OHSU Knight Cancer Institute) and colleagues came up with an alternative: dermatoscopes that attach to a mobile phone, which high-risk patients can borrow and transmit images of suspicious lesions. It’s become a permanent option for rural patients and those who can’t easily travel. For patients with throat symptoms calling for endoscopy, Rebecca Fitzgerald (Cambridge University, MRC Cancer Unit) said her center began cautiously testing an alternative: the Cytosponge, a small mesh sponge within a soluble gelatin capsule that is swallowed and retrieved to collect esophageal cells. Kevin Monahan (St. Marks Hospital) said his team learned the cost of halting colonoscopy procedures and is working to safely maintain the service for symptomatic patients even if a pandemic second wave hits hard. Jackie Shannon (OHSU Knight Cancer Institute) said the pandemic has brought wide attention to long entrenched inequalities and health disparities, perhaps enough to drive much-needed policy changes and enduring efforts to reach underserved populations.

    Leveraging risk stratification Cancer screening intensity should be matched to an individual’s risk of getting cancer. Jon Emery (University of Melbourne) described efforts to use genetic testing to help patients make informed decisions on colorectal cancer screening. He said it’s looking feasible to start to implement genetic risk stratification in the general practice setting. In the future, results will be even better with decision support tools that include risk factors such as diet, smoking, screening history, and medication use.

    Julia Hipsley-Cox (University of Oxford) and colleagues are drawing upon the UK health system’s deep and detailed patient records to develop risk stratification algorithms to target cancer screening resources to people at highest risk and most likely to benefit from interventions (you can check them out at www.qcancer.org). Other tools are designed to be integrated into electronic medical record systems.

    The day ended with two more lightning talks: Rebecca Landy (National Cancer Institute) noted a huge disparity in lung cancer screening guidelines: 32% of African Americans who developed lung cancer would have been eligible for CT screening, compared with 56% of whites. She showed how an individualized risk calculator (the LYFS-CT model) can effectively eliminate this disparity. Tom Callender (University College London) presented findings on the impact of MRI prior to biopsy on age-based and risk-tailored screening for prostate cancer.

    Thank you for joining us. Please accept our sincere apologies for the technical challenges. Don’t forget: the video library will be updated each day with recordings of the meeting sessions.

    Recapping day two

    We have three more sessions lined up, but first here’s a recap of Wednesday.

    Risk-tailored screening is a way to fit the intensity of testing to an individual’s risk of getting cancer. Hilary Robbins (International Agency for Research on Cancer) focused on the job of generating evidence that will be needed to establish risk-tailored cancer screening, presenting examples from lung cancer and breast cancer. Randomized clinical trials are not the way forward, she said, given the large numbers of subjects and lengthy follow-up needed just to answer a limited number of questions in only one context.

    A cancer blood test developed by GRAIL, Inc., is being evaluated for its ability to detect more than 20 types of cancer and predict tissue of tumor origin. GRAIL Vice President Eric Fung highlighted the clinical studies that have led the company to focus on DNA methylation patterns for its multi-cancer early detection test undergoing a multicenter clinical trial due for completion in early 2021.

    Two lightning talks closed the session: Amelie Lutz (Stanford University) is developing an ultrasound guided molecular imaging method for detecting ovarian cancer using microbubbles that target tumor angiogenesis. Stefano Avanzini (Stanford University) is using mathematical models to estimate the size tumors must reach to become detectable by tumor DNA circulating in blood. (For lung cancer, he estimates a median tumor detection size of 2 cm, which is a 43% decrease compared with the median size of diagnosed cancers in the SEER database.)

    KEYNOTE TALK

    Dinah S. Singer (National Cancer Institute) began with a rundown of the NCI’s response to COVID-19 pandemic, from virus-focused research initiatives to the ways the agency is flexing to support grantees. She concluded with an overview of the cancer early detection programs the agency has underway, such as the Early Detection Research Network (now focusing on AI and machine learning to integrate omic data to find biomarkers), and The Human Tumor Atlas Network (HTAN), a massive effort to map the complex ecosystems of cancer – and pave the way for advances in prevention, early detection and treatment.

    GAMBHIR HONORED WITH DON LISTWIN AWARD

    Sanjiv Sam Gambhir was an internationally recognized pioneer in molecular imaging who dedicated his career to developing methods of early disease detection. The director of the Canary Center at Stanford died of cancer on July 18. He was honored with the Don Listwin Award in a ceremony with heartfelt and moving remembrances from Utkan Demirci (Stanford University) and Iain Foulkes (Cancer Research UK). The Listwin Award was established last year to recognize a sustained contribution to, or singular achievement in, the cancer early detection field. The award is named in honor of Don Listwin, founder and chairman of the Canary Foundation.

    Recap of the final day

    The third and final day kicked off with some eye-opening updates from the world of AI and machine learning.

    Lily Peng and Sunny Jansen (Google Health) expounded on three overlooked requirements for building successful AI models: data of high quality, not just quantity; human-centered usability, not just model accuracy; cost-effectiveness, not just excellent performance.

    AI systems are becoming adept at reading radiology images and pathology slides to correctly classify lesions as cancer or benign. Parag Mallick (Stanford University) explained how tools such as saliency mapping are making it possible to understand how the machines reach their conclusions – building confidence and potentially revealing biological insights. He also showed examples of AI tools for biomarker discovery that extract and create knowledge from massive, unstructured data sets.

    Two lightning talks concluded the session: Freya Woods (Swansea University) showed how AI can improve the sensitivity and specificity of cancer detection by Raman spectroscopy, which her group is developing as a triage tool in the diagnosis of colorectal cancer. Rawen Kader (University College London) and colleagues have developed a neural network to assist real time decision-making during colonoscopy by classifying polyps as pre-cancerous or not, with a randomized clinical trial in the offing.

    GREAT DEBATES

    Should genomic risk stratification be part of early detection? Gareth Evans (Manchester University) made the case that it must, noting that polygenic risk scores robustly predict risk for several common cancers and can be used to fit the intensity of screening to a person’s risk of getting cancer. Cristian Tomasetti (Johns Hopkins University) argued that, while genomic risk stratification is useful for some cancer types, many others have no known inherited factors. He asserted that the development of affordable and minimally invasive multi- cancer blood tests will reduce the need for genetic risk stratification. Before the debate, 60% of meeting attendees agreed with Evans, and 40% agreed with Tomasetti. The ratio shifted to 50:50 after.

    Before approving new early detection approaches for clinical use, should we require evidence of a cancer-specific mortality benefit from at least two randomized controlled trials? Harry De Koning (Erasmus University Medical Centre) pointed to the conflicting findings of clinical trials of screening methods such as PSA for prostate cancer to make the affirmative case. Steve Skates (Harvard University) asserted that requiring such evidence unnecessarily delays the use of early detection advances, and costs too much, when there are faster and less costly trial endpoints, such as reduction in late-stage diagnoses. In the poll of meeting attendees, agreement with De Koning dropped from 32% pre- debate to 20% percent after, with many deciding that it’s too much to ask for randomized trials showing mortality benefit.

    On behalf of the Canary Center at Stanford, Cancer Research UK and the OHSU Knight Cancer Institute, thank you for joining us for the 2020 Early Detection of Cancer Virtual Conference. With luck, we’ll be able to meet in person at next year’s meeting. For now, the organizing committee has decided to be optimistic and start preparing for an in-person gathering in London.

    Our prostate cancer team has big news from the Prostate Active Surveillance Study (PASS) – a new publication in JAMA Oncology!

    October 7, 2020

    Our prostate cancer team has more than a decade of experience working remotely from various institutions. During the time of the pandemic, the team has moved forward on important fronts.

    Big News –PASS has a new publication in JAMA Oncology! A scientific paper was recently published in the premiere publication JAMA Oncology: The Journal of the American Medical Association. JAMA is a rigorously peer-reviewed medical journal. The principal investigator Matthew R. Cooperberg is on Canary’s Prostate Active Surveillance Study (PASS) team. Many familiar names from the team are seen on the study. The study shows an important way of determining risk assessment that can aid in deciding how often to monitor and other decisions.  To hear an interview with Dr. Cooperberg, click here:
    https://edhub.ama-assn.org/jn-learning/audio-player/18536720

    Tissue Microarray.  The team studies the progression of prostate cancer using high-through analysis of multiple cases. Work in this area during the pandemic has included the review of new proposals and project progress from partners, including ones from Austria and Canada. The work has included data analysis, correcting missing data, and arranging tissue shipment.

    PASS Central Review. Decisions have been made on reviewing cases.

    Meetings and communications. The prostate team has been disciplined in meeting remotely and communicating long distances since it’s formation in 2006. A group meeting was held in June and follow up ensued. Additionally, their annual November in-person meeting has been approved to move to a virtual format.

    Enrolling men. PASS enrolls men to keep a steady level of patients as some men rotate out of the program, 2000 being the current number of enrollees. Enrollment is on hold due to the pandemic.

    Other action of the Prostate Team include:

    1. Reviewing new proposals for Canary TMA (pathology)
    2. Progress on approved projects for Canary TMA (pathology) has been made with data having been submitted from a number of groups and a shipment of tissue samples having been coordinated to an international partner.
    3. Concordance project for PASS central review (pathology), coordinated decision making on review of cases.
    4. Papers: read and commented on meeting submissions and manuscripts in progress.
    5. Administrative: we have held an all-team PASS and prostate pathology group meetings, distributed notes & action items. Plan approved to move November 20 meeting to virtual format.

    Canary’s Prostate Active Surveillance Study (PASS) receives $6.7M NCI grant to support growth of the multi-center study!

    December 2, 2019

    PASS was established in 2008 with funding from the Canary Foundation, demonstrating how we invest in promising early research!

    “PASS was launched with six participating centers in 2008,” said PASS Deputy Director Dr. Lisa Newcomb, a Hutch cancer prevention researcher. “With this grant, we’ll be up to 11 sites. Fred Hutch is the centralized repository — specimens are sent to the Hutch from all the sites — and we have procedures for sharing the data and the specimens among the group [members] and with other researchers.”

    The grant is designed to support the infrastructure of the PASS cohort, including the collection of follow-up data, management of the database and management of the biospecimen repository.

    PASS participants are all early-stage prostate cancer patients who chose active surveillance, not immediate surgery or radiation, to manage their cancer. In active surveillance, patients receive regular PSA (prostate-specific antigen) testing, biopsies and digital-rectal exams to monitor whether the cancer grows or becomes more aggressive.

    According to research, more than 30% of men have slow-growing prostate cancer and won’t necessarily benefit from radical treatments that can cause debilitating side effects such as urinary incontinence and impotence. Data from patients with early-stage prostate cancers who choose active surveillance can provide key insights into who’s most at risk from their cancers, and when.

    Using the cohort for risk-prediction modeling, Newcomb said, could help “determine who either harbors or will progress to a bad cancer, which cancers are aggressive and which really aren’t.”

    “We want to help identify the men who can go home and not worry about their cancer. We’re looking at both ends of the spectrum — making active surveillance less active and identifying the people who will benefit from treatment early.”  – Dr. Lisa Newcomb

    “We are thrilled,” said Newcomb regarding the transition from Canary Foundation support to NCI funding.

    Fred Hutch has had a longstanding relationship with the Canary Foundation and has been the recipient of many grants from the foundation powering work in early detection. The fifth floor of Fred Hutch’s Arnold Building, home to its Public Health Sciences Division, is named for the foundation.

    At present, participating sites for PASS include the University of California, San Francisco; Stanford University; Emory University; Beth Israel Deaconess Medical Center/Harvard Medical School; University of Michigan; University of Texas Health Science Center, San Antonio; Eastern Virginia Medical School; Veterans Affairs Puget Sound Health Care System; University of Washington and University of British Columbia.

    Interested in PASS? Contact Dr. Lisa Newcomb or go to https://canarypass.org/

    Interested in accessing Canary PASS Active Surveillance Risk Calculators? The PASS Risk Calculators provide estimates of how likely a man is to have more aggressive cancer in the future. These tools are intended to be useful for clinicians and their patients as they determine optimal methods of active surveillance. Access the risk calculators: https://canarypass.org/pass-risk-calculator/

    To read the full article by Diane Mapes, a staff writer at Fred Hutchinson Cancer Research Center, please go to: https://www.fredhutch.org/en/news/center-news/2019/11/prostate-cancer-study-nci-funding-grant.html

    The Early Detection of Cancer Conference at Stanford!

    October 9, 2019

    Canary Center at Stanford, Cancer Research UK, and the OHSU Knight Cancer Institute, hosted the Early Detection of Cancer Conference September 24 – 26 at the Frances C. Arrillaga Alumni Center, Stanford, California. Approximately 370 attendees, from 120 institutions, and 11 countries outside of the USA (including Australia, Canada, China, Finland, France, Great Britain, India, Netherlands, South Korea, Switzerland, and Ukraine) brought forth their latest findings and ideas. The annual Conference brings together experts in early detection from multiple disciplines to share ground breaking research and progress in the field.

    The conference is part of a long-term commitment to invest in early detection research, to understand the biology behind early stage cancers, find new detection and screening methods, and enhance uptake and accuracy of screening.

    The talks ventured widely, from finding ways to extract more information from cell-free DNA in blood, to building cohorts of people at high risk of cancer to prospectively study the emergence of disease, to the role of the tumor micro-environment and the immune system in cancer early detection, and going beyond traditional risk factors to better select populations for targeted cancer screening.

    Highlights of this year’s conference included: More »

    Project Baseline aims to map human health

    February 3, 2019

    What if we could view changes in the body earlier than early to warn of possible disease? That is the aim of Project Baseline, to map human health. The New York Times published “Project Baseline Aims to Ward Off Illness Before We Get Sick” by Anahad O’Connor (Oct 2018).  The study is recruiting 10,000 adults. And each will be examined and followed for at least four years. So the goal is to discover the earliest warning signs of cancer, heart disease and other killers. Participants, the first of whom was enrolled in 2017, are called Baseline Explorers.

    Project Baseline is the result of conversations in 2013, led by Google X’s Andrew Conrad. He consulted with Dr. Sam Gambhir, MD, chair of Radiology at Stanford University and director of the Canary Center for Cancer Early Detection. And also with Robert M. Califf, MD, professor of Cardiology in the School of Medicine, Duke University.

    Conrad (now CEO of Verily, a spin out of Google X) was interested in exploring with these two notable healthcare thought leaders, one in cancer and the other in cardiology, about how to create what has become a landmark study. Both had deep experience in working with large patient cohorts and focus on early detection of disease. The project has formed teams across the country.

    Seeking to create a baseline of health

    Traditional trials focus on those who have a disease. So Project Baseline, as the name implies, mainly enrolls healthy individuals gathering enormous amounts of information. Baseline equips enrollees with wearable technology from Verily that tracks sleep patterns, heart rhythms and physical activity. The team is developing tools and technologies to collect, organize, analyze and curate the data.

    And investigators are determining the best ways to share data with participants that is helpful to them. They are looking at how they can engage with their medical professionals.

    Canary Foundation and the Canary Center at Stanford for Cancer Early Detection

    Dr. Gambhir has served as Canary Foundation’s scientific director for more than a decade. He led the development of the Canary Center at Stanford for Cancer Early Detection.  The Canary Center is a partnership forged in 2008 between Stanford University and Canary Foundation under the leadership of Don Listwin, based on the foundation’s mission. And interesting to know,  Canary Center is the first program Stanford has focused entirely on cancer early detection.

     

    American Cancer Society Report January 2019 is hopeful. Yet it motivates us to work harder at finding better tests

    January 16, 2019

    The new American Cancer Society report shows us that cancer deaths have dropped  by 27% since their peak in 1991. The decrease is attributed to early detection, better treatments and a reduction in smoking rates. The ACS report also points to a socio-economic disparity in the numbers, based on broad county and area reports collected by Surveillance, Epidemiology, and End Results (SEER – a National Cancer Institute source of epidemiologic information on the incidence and survival rates of cancer in the United States, where access to education and healthcare remains a problem. Additionally, lower incidence has been slower in cancers such as lung and prostate. Also, rates of new cases rose for pancreatic and other cancers. While the overall decline in rates is great news, we must keep up the momentum to create early detection tests to save lives as cancer remains the second cause of death in the United States (22% in 2016), and a major health issue worldwide.

    The report states that in 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. From the report: “…the Lifetime probability of being diagnosed with invasive cancer is 39.3 % for men and 37.7% for women. Prostate, lung and colorectal cancers (CRCs) account for 42% of all cases in men, with prostate cancer alone accounting for nearly 1 in 5 new diagnoses. For women, the 3 most common cancers are breast, lung, and colorectum, which collectively represent one-half of all new diagnoses; breast cancer alone accounts for 30% of all new cancer diagnoses in women. The reasons for the excess overall risk in men are not fully understood, but partly reflect differences in environmental exposures, endogenous hormones, and probably complex interactions between these influences.”

    Canary Foundation has been on the forefront of stimulating the field of cancer early detection globally by demonstrating cancer early detection tests as well as hosting scientific symposiums, mentoring researchers choosing the early detection path, and forging important national and international partnerships. To address access problems, Canary’s investments have focused, when possible, on cost-effective tests as a path to bridging the socio-economic disparities.  Examples can be found in are our funded studies in enhance ultrasound using microbubbles, where ultrasound is found in doctor’s offices worldwide, representing an imaging modality in development useful for multiple cancers that is low-cost, non- invasive and with the additional benefit of not using radiation.

     

    Canary funds four collaborative studies that pair faculty at Stanford with faculty at the University of Cambridge

    February 15, 2018

    Cancer early detection researchers develop future collaborations on a punting excursion in Cambridge, UK in September 2017.

    Canary Foundation was ahead of the cancer early detection wave when it started in 2004. Since then, academic institutions, such as the University of Cambridge in the UK and the University of Calgary in Canada, have looked to Canary for advice as they build out their own cancer early detection programs.

    This year, one such collaboration is taking shape in dynamic ways. Canary’s partnership with the University of Cambridge has resulted in four promising studies that partner researchers from Cambridge with researchers from Stanford. These projects, jointly funded by Canary Foundation and the Cancer Research UK Cambridge Centre, will explore innovative ways to detect prostate, lung, esophageal and renal cancers at an early stage.

    In order to receive seed grants for these projects, applications had to include faculty at both Stanford and Cambridge. By fostering this transatlantic collaboration, Canary hopes to bring outstanding academic and clinical researchers from the US and UK together to tackle some of the most challenging questions in detecting cancer sooner.

    The awards were announced at Cambridge’s third annual early detection symposium on January 15. You can read more about these collaborations below or by watching the video.

    “A multi-modal approach to discover novel blood-based biomarkers for early detection of poor prognosis prostate cancer”

    Tanya Stoyanova, an assistant professor of radiology at the Canary Center, is partnering with Vincent Gnanpragasam, an urologist at Cambridge University Hospitals, to identify different types of tumors in men with prostate cancer. The goal is to distinguish between aggressive tumors that would require immediate treatment, and slow-growing tumors that may not need treatment immediately but could be monitored closely so that any changes in the tumor can be picked up and acted upon. Their project will use data from a number of sources including tumor DNA found circulating in the blood, protein molecules found in cancer cells, and MRI imaging of the tumor.

    “Early cancer detection through transcriptomic analysis of host immune cells”

    Tom Soh, a professor of radiology at the Canary Center, is exploring new ways to detect early-stage lung cancer through his partnership with Robert Rintoul, a thoracic consultant at Cambridge University Hospitals. The pair is studying the immune cells in blood samples to see if there are particular signals that could be used to identify lung cancer early.

    “Levitating a sponge for the early detection of Esophageal Adenocarcinoma”

     Utkan Demirci, a professor of radiology at the Canary Center, is working with Rebecca Fitzgerald, Cambridge’s early detection program co-lead, to detect early signs of esophageal cancer. They will use a new nanotechnology developed by Demirci that separates different types of cells using a magnetic field. The technology will be applied to the mixture of cells collected from patients that are given a Cytosponge test developed by Fitzgerald that can diagnose Barrett’s esophagus – a common condition that, in some cases, develops into esophageal cancer.

     “Early detection of renal cell carcinoma using DNA methylation markers in urine”

    Olivier Gevaert, an assistant professor of medicine and of biomedical data science at Stanford, and John Leppert, an associate professor of urology at Stanford, are teaming up with Charlie Massie, a group leader in Cambridge’s early detection program. They will study whether it is possible to detect the early stages of a type of kidney cancer (Renal Cell Carcinoma) using biomarkers found in urine. Their research will look at specific signals in the DNA cells called methylation.

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