Posts Tagged ‘early detection ovarian cancer’
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
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%.
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.
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.
The Early Detection of Cancer Conference events team
October 14, 2021
Canary Center continues as a world class facility, acting as a hub for innovative research, collaborations, cross-disciplined studies, and international partnerships.
After their train ride, our scientists gave an informative update at a recent meeting observing distancing measures. Subjects covered included the Canary Center at Stanford, Ovarian and Prostate Programs and examples of work from the lab of Dr. Joseph DeSimone, who has been appointed as the inaugural Sanjiv Sam Gambhir Professor in Translational Medicine.
Below are two highlights and a link to a 2-page report.
Canary Ovarian Initiative is focusing on the microenvironment of the fallopian tubes, high grade serous carcinoma originates in the fallopian tubes, to look for changes that signal cancer.
- Using bioinformatics and methylated DNA to determine origins of ovarian cancer.
- Looking for changes in the fallopian tubes decades before cancer can be diagnosed, especially for high risk women (i.e. BRCA mutations). Single cell sequencing – looking for changes in cells that can signal cancer early.
- Remaining patient-focused for compassion and team-focused for efficiency.
Prostate Cancer Team and the Prostate Active Surveillance Study (PASS), more than a decade on, helps patients in the study as well as informing the medical profession on ways to understand which men are at greatest risk, requiring aggressive treatment versus those who have slow growing cancer. Recent Pass accomplishments include:
- Advanced imaging with MRI.
- African Americans do not have worse outcomes in active surveillance
- Created models to predict non-progression.
- Fewer painful prostate biopsies.
- PASS Risk calculator to aid patients and physicians with decisions.
- High risk patients (BRCA mutation) personalized screening.
Read the full update report here:
Canary Foundation’s Ovarian Cancer Initiative: moving forward with matching specimen and imaging tissue in 3D
March 8, 2021
The Canary High Grade Serous Ovarian Cancer (HGSC) study is leveraging the expertise and resources of four institutions to study the microenvironmental factors that can lead fallopian tubes to develop this deadly type of ovarian cancer and thus provide a signal to alert for the presence of early disease. The Fred Hutchinson Cancer Research Center in Seattle, the University of Pennsylvania, the Van Andel Institute in Michigan, and the University of California San Francisco have built the infrastructure to share fallopian tube specimens, experimental and clinical data, and analytical teams.
The small pilot study goals are to ask whether it is possible to compare women carrying the BRCA mutations (who are at higher risk of developing ovarian cancer) compared to those who do not carry the mutation and determine whether it is possible to find a measurable difference in the microenvironment.
Based on their first results, the team is selecting a larger set of specimens, matched for clinical factors and BRCA mutation status, and will conduct RNA, DNA and methylome sequencing. The group is also comparing competing platforms for imaging the tissue expression in 3D so that differences along the length of the tube can be evaluated and tested for correlations with the genetic data.
The International Alliance for Cancer Early Detection (ACED) joins researchers from the United States and the United Kingdom in a $70 million partnership. Founded in 2019, ACED is a partnership with the Canary Center at Stanford University, CRUK, the University of Cambridge, the Knight Cancer Institute at Oregon Health and Science University (OHSU), University College London and the University of Manchester. The following is one study chosen for it’s innovative approach to early detection:
Stratifying Risk for Early Detection in Hereditary Breast and Ovarian cancer
Project Award, led by: Marc Tischkowitz, University of Cambridge; Allison Kurian, Canary Center at Stanford for Cancer Early Detection; and Gareth Evans, University of Manchester. Stanford Team: Allison Kurian, Alice Fan, James Ford
CanRisk is a cancer risk assessment tool which combines genetic, lifestyle, clinical and imaging data to calculate an individual risk estimate for women with high-risk mutations in BRCA1 and BRCA2. The ability to provide personalized cancer risk estimates will identify women at particularly high risk. Currently, the ranges of cancer risk estimates for women with hereditary mutations in breast cancer genes are wide and not personalized, so all women are given the same figures. Creating a customized approach can solve this problem.
By implementing personalized risk estimates, early detection strategies can be tailored for the individual, therefore identifying those at the highest risk. Once feasibility is assessed, women undergoing predictive testing for BRCA1, BRCA2, PALB2, ATM or CHEK2 in US and UK genetics centers will be randomized to conventional vs personalized risk estimate based on genetic/lifestyle/hormonal modifiers.
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.)
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.
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.
October 7, 2020
The Ovarian team has used these past months to hone and polish the infrastructure for the High Grade Serous Ovarian Cancer Initiative and to ensure that high quality molecular data can be generated from the samples. This includes both the pilot project that focuses on changes in the micro-environment, and the retrospective study that looks back at tissue.
Focus of the project
Our focus is to define the role of the fallopian tube micro-environment in the development of high grade serous ovarian cancer (fallopian tube being the most common ovarian cancer), with the ultimate objective to find targets for prevention and markers of early disease onset for early detection.
In order to develop a robust and innovative research plan, we invited a multidisciplinary team of roughly 25 world class ovarian cancer researchers from across the US and Canada to an initial two day planning meeting in March 2019 in Los Gatos, California. The meeting was highly successful. The number of promising ideas exceeded our available funding level. Over the ensuing months the Executive Committee worked to refine and finalize our research proposal and also put in place the necessary infrastructure to conduct our studies.
What problem is the team trying to solve? Our overall plan includes a series of innovate pilot studies specifically designed to demonstrate the power of our team and generate preliminary data that can be leveraged to compete for large grants by the end of a two year period. The research will be performed in two phases: first, a retrospective phase that involves analysis of previously collected, banked fallopian tube samples with associated clinical information, and second, a prospective study, that includes newly collected samples, each with the goal of identifying what changes in the molecular landscape signal cancer.
Our progress March – Summer 2020. During these past months, the team has finalized the infrastructure for the pilot program and has worked to ensure that the expected high quality molecular data from our samples can be achieved. The process for sample sharing has been completed. Additionally, reviews, discussions, and decisions have been held to work out a draft of the high-quality protocol necessary for all team members to follow. 6 potential sites have been identified. We are testing our data management processes. This includes a portal for sharing and annotating data among multiple investigators and analysts. Canary Foundation has experience in this field.
Next steps: the in-person clinical aspect of the pilot will resume when each of the participating sites are reopened. When further steps in reopening allow, clinical sites will be responsible for providing patient samples and annotated clinical and pathologic data in a timely and cost-effective way. Each site includes a collaborative PI who has a robust system in place for conducting translational research studies, banking samples and linking clinical information.
Additionally, steps are being taken to identify and put in place a central project manager. An interim plan is in place utilizing resources at the University of Pennsylvania.
Clinical data and sample coordination center: The University of Pennsylvania leader is Michael Feldman. We are working with the team at UPenn to write sample protocols and requirements and to finalize the overall collaboration agreement that will be signed by all institutions. The coordinating center will receive samples from clinical sites, perform quality control, and prepare and ship samples to molecular profiling sites. The center will also maintain the clinical database of participants linked to their sample information. The clinical data will be linked later to the molecular data for each of the samples and participants.
Clinical teams: when further steps in reopening allow, clinical sites will be responsible for providing patient samples and annotated clinical and pathologic data in a timely and cost-effective way.
Molecular profiling sites: Molecular analyses will include bulk RNA and DNA sequencing, global methylome profiling, proteomics with spatial profiling, single cell analyses using the Nanostring DSP platforms.
Data management and analysis center: We have multiple types of data that need to be securely stored and annotated. We are using a similar structure to that used by the large NIH-funded effort, TCGA. Raw data will be hosted in the data center managed by Adam Olshen at UCSF. We will run data analysis pipelines and upload processed data into a program that will function as a portal for sharing and annotating data among multiple investigators and analysts. Canary Foundation has experience in this field.
Shaping bioinformatics. Our leadership and analysis team leaders are enthusiastic about working together using Synapse and the Sage engineers. The associated infrastructure and analysis plan from our bioinformaticians Adam Olshen (UCSF) and
Hui Shen (Van Andel) has been reviewed and approved by the group.
Checking our system.
- Testing of infrastructure and logistics with a small set of samples will include:
- Assessing technical issues
- Management of resources
- Rapid course correction procedures
- Generating first data set
- Send samples through the pipeline (10 BRCA mutation carriers)
- Check quality control measures on data set
Working as a team. Part of the strategy is to demonstrate our ability to work together and generate data so that we are able to apply for additional support from external agencies (e.g. government or foundations). The team is actively making connections to seek out the best funding opportunities as part of our future plan, and the breadth of expertise in the team and their ability to work well together go a long way in securing future funding.
September 16, 2020
Over the years, Canary Foundation has helped researchers develop successful ways of working together over distance, and we draw on that experience during these times.
A message on the Canary Center re-opening from:
Dr. Utkan Demirci, Co-Director, Canary Center at Stanford
Dr. Ryan Spitler, Deputy Director of the Precision Health and Integrated Diagnostics Center
Dr. Sharon Pitteri, Associate Professor, Canary Center at Stanford
We discover ways to move forward while staying safe. From the very early arrival of COVID-19, we have been able to successfully keep the Canary Center vibrant with virtual interactions and with safety in mind. We have implemented measures for social distancing, and staggered laboratory shifts as we follow the guidance on re-opening stages from the Radiology department and Stanford University. We are using our time out of the lab well. Many researchers have taken this hard-to-find time to focus on data analysis, writing manuscripts, reading scientific literature, and developing new ideas for future projects. We also are exploring intersecting dimensions between cancer and COVID-19 related research. We have asked ourselves this question: how are we uniquely positioned to contribute to the pandemic crisis through the work we are doing in cancer early detection?
We look after each other. Everyone working in the Center has committed to the safety and well-being of every other Canary member. This is key. Each research group also has their own independent safety plan to ensure they are aware of their colleagues as well as their specific research needs. Collectively, we have been building up our research efforts in phases.
We will continue to push forward to detect cancer before it strikes and support COVID-19 related efforts. Take our Smart Toilet system. The Smart Toilet system is a wave-of-the-near-future method of collecting important changes in biodata to serve personalized medicine. We have been able to modify our Smart Toilet system originally designed for early cancer detection to also be used as a screening tool to detect COVID-19. This approach enhances longitudinal testing and serves to detect very small, early changes. Unnecessary exposure is also limited for the patient and the health care provider who normally must come in close proximity for a nasal swab that often triggers a cough or sneeze.
Human health is our passion and one that burns strongly no matter what challenges we face.
To better envision the opening of the Canary Center, please enjoy this brief video.
Remembering Sanjiv Sam Gambhir, MD, PhD, Stanford University Radiology Chair, Director of the Canary Center at Stanford for Cancer Early Detection
August 4, 2020
Sam’s image: forever in our hearts.
November 23, 1962 – July 18, 2020
“The body is a mystery.” This is something you don’t expect to hear from a distinguished worldwide leading expert in radiology, who developed cutting edge imaging tests to spot disease early inside the body using new and repurposed technologies in highly innovative ways. You would think such a person would tout how much we do know. And yet, this is exactly what we would hear from our good friend and guide Sanjiv Sam Gambhir. He believed that the reason cancer seemed to take so many different characteristics in each individual person was because we know so little about the body. It was times like this you would be moved by just how humble Sam was. Add to that just how important Sam has been to Canary Foundation’s mission, and you understand why we will miss him as a beloved partner and visionary for cancer early detection.
We met Sam during the first year Don Listwin founded Canary Foundation in 2004. Don had lost his mother several years before to misdiagnosed ovarian cancer and had decided to use his time and resources to try to impact the common problem of misdiagnosis. Don and cancer research Nobel Laureate Lee Hartwell had earlier conversations about cancer being an engineering problem, where answers were out there but not being brought together to sensible resolution. Canary Foundation went on to develop multi-institutional, multi-disciplined teams providing them with start-up funds to work together towards common goals. They then gather enough results to attract further funding from larger grantors and the government.
Sam filled a vital role in the “workflow” as an imaging expert, and much more. He helped solidify our mission to develop tests to curb cancer deaths by finding tumors early, then isolating their location through imaging, followed by removal or targeted treatment. He quickly became the leader of the science teams using his expert skills in convening the lead researchers in the field.
What was it about Sam that made his complex science and vision understandable? Sam was relaxed as he described a full and brilliant universe of information, knowing exactly what metaphors to use to get his ideas across. For instance, Sam eagerly described his work in imaging as using “molecular spies” that could sleuth out cancer tumors, then send back a signal that greatly enhanced a physician’s ability to “spot” the cancer in the imaging.
Sam laughed easily and liked to poke good humored fun at his colleagues. He was mild mannered and didn’t jockey for the spotlight as one with his level of mastery might. He liked pop music and was genuinely interested in what you had to say. While none of this is written in leadership training books, it all worked well in moving the science forward.
In 2008, Canary Foundation and Stanford University signed partnership papers that sealed the deal on an agreement where both institutions would bring resources to create the Canary Center at Stanford for Cancer Early Detection. Sam led Stanford and kept his eye on the potential that would become the first worldwide center focused on cancer early detection. The Canary Center opened doors in 2009 and would grow to attract world-class researchers. We have accomplished much with Sam at our side. Canary Foundation has since mentored those working on opening international centers at Cambridge United Kingdom and the University of Calgary, Canada. Our annual symposium, the first of its kind that attracted young and seasoned researchers to a collaborative forum, has become, with Sam’s help, a prestigious multi-institutional event now organized by national and global partners.
Sam’s big strategy, like Canary Foundation’s, has always been to mentor both new and seasoned scientists. His lab and the Canary Center have been a dynamic place of productivity, exchange, energy and solution-based translational research. The seeds of his work will continue to grow and flourish by those he has taught and inspired.
Sam has been an extraordinary partner. “It is amazing what you can accomplish through collaboration,” Sam said just last September at the Early Detection of Cancer Conference. We wholeheartedly agree.
All of this is to say, Sam has been a good friend to Canary Foundation and a visionary of a bright future for helping those with a cancer diagnosis.
The world will not be the same without him.
Canary’s new: High Grade Serous Ovarian Cancer Initiative. HGSOC is the most common and lethal form of ovarian cancer.
February 4, 2020
Ovarian cancer remains the most lethal gynecologic malignancy in the United States. In 2018, over 22,000 new cases were diagnosed and 14,000 women lost their lives to the disease.
Ovarian cancer is made up of distinct subtypes. High grade serous ovarian carcinoma is 70% of cases, and is the most lethal subtype accounting for over 60% of ovarian cancer deaths.
People who have inherited mutations in BRCA genes are at higher risk for certain types of cancer, including HGSOC. In looking very carefully at the fallopian tubes removed from BRCA mutation carriers, the discovery was made that the fallopian tube was a site of origin for HGSOC – not the ovary itself, but the fallopian tube. This understanding over the past 15 years represents a paradigm shift in the origin of the HGSOC and opportunity for us to better understand how the cancer develops and design better strategies for early detection and prevention.
80% of HGSOC are diagnosed at a late stage!
We want to eliminate deaths from HGSOC by early detection and prevention.
There are currently no effective methods for early detection for ovarian cancer. Substantial progress has been made in identifying the putative precursor lesions for ovarian cancers.
Our focus is to define the role of the fallopian tube microenvironment in the development of high grade serous ovarian cancer, with the ultimate objective to find targets for prevention and markers of early disease onset for early detection. We are tackling the problem from multiple directions to ensure the greatest probability of success.
It is unclear which precursor lesions are likely to progress and/or be associated with invasive disease. A critical knowledge gap is how the various constituents of the fallopian tube microenvironment impact tumor development or progression.
Achieving our goals requires a multi-institutional, multi-disciplinary effort. The team we assembled is made up of gynecologic oncologists, molecular biologists, epidemiologists, pathologists and bioinformaticians. The team is world class and has the requisite expertise to capitalize on complementary molecular profiling. Our research plan leverages powerful, broad-based discovery approaches to tackle this difficult challenge of early detection.
Dr. Heidi Aumen explains more: