January 4, 2021
Researchers discover brain cancer may develop when tissue healing runs amok, uncovering new approaches to combat the deadly disease
The healing process that follows a brain injury, such as an infection or a stroke, could spur tumour growth when the new cells generated are derailed by mutations, Toronto scientists have found. This discovery could lead to new therapy for glioblastoma patients who currently have limited treatment options with an average lifespan of 15 months after diagnosis.
The findings, published today in Nature Cancer, were made by an interdisciplinary team of researchers from OICR, the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research, The Hospital for Sick Children (SickKids) and the Princess Margaret Cancer Centre who are also on the pan-Canadian Stand Up to Cancer (SU2C) Canada Dream Team that focuses on a common brain cancer known as glioblastoma.
“Our data suggest that the right mutational change in particular cells in the brain could be modified by injury to give rise to a tumour,” says Dr. Peter Dirks, senior author of the study, OICR-supported researcher, Dream Team co-leader, and Head of the Division of Neurosurgery and a Senior Scientist in the Developmental and Stem Cell Biology program at SickKids. “We’re excited about what this tells us about how cancer originates and grows and it opens up entirely new ideas about treatment by focusing on the injury and inflammation response.”
The research group, led in part by OICR and Princess Margaret’s Dr. Trevor Pugh, applied the latest single-cell RNA sequencing and machine learning technologies to map the molecular make-up of the glioblastoma stem cells (GSCs), which Dirks’ team previously showed are responsible for tumour initiation and recurrence after treatment.
Equipped with these single-cell analysis methods, the research group was able to accurately differentiate and study different types of tumour cells. Through analyzing 26 tumours and nearly 70,000 cells, they found new subpopulations of GSCs that bear the molecular hallmarks of inflammation.
This finding suggests that some glioblastomas may start to form when the normal tissue healing process is derailed by mutations, possibly even many years before patients become symptomatic, Dirks says. Once a mutant cell becomes engaged in wound healing, it cannot stop multiplying because the normal controls are broken and this spurs tumour growth, according to the study.
The study’s authors, including co-leading researcher, Dr. Gary Bader from the Donnelly Centre as well as graduate students including Owen Whitley and Laura Richards, are now working to develop tailored therapies target these different molecular subgroups.
“There’s a real opportunity here for precision medicine.” says Pugh, who is Director of Genomics at OICR and the Princess Margaret Cancer Centre. “To dissect patients’ tumours at the single cell level and design a drug cocktail that can take out more than one cancer stem cell subclone at the same time.”
In addition to funding from the Stand Up To Cancer Canada Cancer Stem Cell Dream Team: Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks, the research was also funded by Genome Canada, the Canadian Institutes for Health Research, the Ontario Institute for Cancer Research, Terry Fox Research Institute, the Canadian Cancer Society and SickKids Foundation.
December 17, 2020
Dr. Jared Simpson and collaborators develop new nanopore-based methods to investigate two understudied aspects of disease biology
Studying DNA modifications may offer new insights into cancer – and the tools to read these changes are now in our hands.
In a recent publication in Nature Methods, OICR Investigator Dr. Jared Simpson and collaborators at Johns Hopkins University describe a new method to investigate two key aspects of disease biology, methylation and chromatin accessibility, simultaneously. These aspects can help describe how genes are organized and switched on and off in a cell, which may enable future progress in cancer research and discovery.
The group’s new method, coined nanoNOMe-seq, is built for nanopore sequencing – a fast, portable way to read long molecules of DNA. nanoNOMe serves as an additional tool that extends the utility of nanopore sequencing technologies.
“Our collaborators developed the lab protocols and we developed the analysis software to determine where DNA modifications occurred,” says Simpson. “Now, with this method, other researchers can investigate how DNA is modified within a cell to give an extra layer of information that the community can decode into new insights and discoveries.”
Dr. Michael Molnar, Scientific Associate in the Simpson Lab at OICR, led the development of the analysis software behind nanoNOMe.
“At times, it seemed like it might not be possible to develop a statistical model that could make sense of all the data,” says Molnar. “But we were able to persist and develop the nanoNOMe software, which showed a high degree of accuracy. We hope this method will enable others to discover long-range patterns and make new connections in sequencing data.”
nanoNOMe was first released as a preprint, which has already been cited in other scholarly articles including a tool for methylation pattern visualization, an analysis of human chromosome 8, and a published review on long-read sequencing among other publications. Simpson and Molnar’s collaborators plan to further investigate methylation and chromatin accessibility in human cancer cells with nanoNOMe.
“If you’re interested in understanding how methylation relates to open chromatin, then you can use this protocol,” says Simpson. “This is opening a new space for the community to explore interactions between chromatin and DNA methylation.”
December 9, 2020
The tool can accurately distinguish real mutations from sequencing mistakes to improve the early detection of cancer
DNA mutations in cancer cells are caused by different processes, each of which leaves a genetic fingerprint that can provide clues to how the cancer develops. Researchers have now applied this understanding to reduce errors when reading DNA, allowing them to accurately and efficiently detect the smallest traces of mutated cells in the blood.
In a recent publication in Science Advances, an OICR-supported research group outlines a new and improved statistical model to reduce error rates in DNA sequencing data. They demonstrate that their model, called Espresso, outperforms current error suppression methods.
“When we isolate, amplify and try to read the individual building blocks of DNA, we encounter a lot of errors,” says Dr. Sagi Abelson, OICR Investigator, Assistant Professor at the University of Toronto and first author of the publication. “This is a major obstacle. The high error background makes it difficult to pinpoint authentic rare mutations. This is what Espresso aims to solve.”
To build an effective error-suppressing statistical model, the group assessed the different types of errors in their relative genomic contexts across more than 1,000 sequencing samples. Their approach was based on assessing the genetic fingerprints within these samples and mapping them to the regions around the errors to understand if the error was a true mistake, or if it was an important mutation.
“The key advantage of our method is that it allows scientists to read DNA more accurately without the need to duplicate efforts using a set of independent control measurements to estimate error rates,” says Abelson. “This means that researchers can be more efficient with their time and resources. They can do more with less. We’re proud to have developed methods that can make research more practical and simple, but also more effective, efficient and accurate.”
This model is built on Abelson’s prior research published in Nature, which discovered early indicators of acute myeloid leukemia (AML) in the blood up to 10 years before symptoms surfaced. With Espresso, the research group was able to develop and test a new strategy to predict leukemia development, which could predict up to 30 per cent of AML cases years before clinical diagnosis with extremely high specificity. Importantly, this study demonstrated that the risk of developing AML can be measured by looking into only a small number of genomic bases, which suggests a more practical route to clinical testing and implementation.
“This work builds on our prior research, which has shown that we can detect AML earlier than thought possible,” says Dr. John Dick, Senior Scientist at the Princess Margaret Cancer Centre, Co-lead of OICR’s Acute Leukemia Translational Research Initiative and co-senior author of the study. “With these methods, we’ve now shown that we can focus in on specific areas of DNA to detect those early traces of AML with higher accuracy than ever before.”
“These methods are essential to advancing personalized cancer care in practice,” says Dr. Scott Bratman, Senior Scientist at the University Health Network’s Princess Margaret Cancer Centre and co-senior author of the study. “With these tools, we can enable clinicians to treat cancer more effectively, tailor treatment decisions and monitor minimal residual disease. We look forward to furthering our research for patients today and those who will develop cancer in the future.”
December 2, 2020
Researchers at the University of Guelph and McMaster University create combination immunotherapy approach to treat breast tumours and other cancers
Over the last few decades, scientists have made significant progress in harnessing the immune system to treat cancers. Despite these advances, many types of cancer can still evade the immune system and current immunotherapies. Dr. Sam Workenhe is developing better treatment options for patients with these hard-to-treat diseases.
In his recent study, published in Nature Communications Biology, Workenhe and collaborators at the University of Guelph and McMaster University discovered a new combination immunotherapy approach for breast tumours and other cancers. Their approach leverages cancer-killing viruses, called oncolytic viruses, and chemotherapy to trigger tumour inflammation, stimulating the body’s immune system to control tumour growth. Their combination leveraged the oncolytic virus, oHSV-1, and the chemotherapy agent, Mitomycin-C.
The research team demonstrated the effectiveness of this treatment approach in mouse models of breast cancer. They found that that mice treated with this combination therapy lived approximately two months longer than untreated ones – a significant difference relative to the short lifespan of these mouse models.
“Simply put, we wake up the immune system,” says Workenhe, Assistant Professor at the University of Guelph’s Ontario Veterinary College and an OICR Joseph and Wolf Lebovic Fellowship Program awardee. “Our study proves that aggressive tumours without immune cells can be made to render an immune response. Understanding how to design treatments that can potentially activate the immune system against cancer can revolutionize the current standards of care.”
Additionally, the study delineated the anticancer mechanisms of their approach, detailing how each element kickstarts an immune response against the tumours. Workenhe, who is a trained veterinarian and a virologist, is now applying these findings to further study immune responses and inflammatory cell death in tumours.
“A lot of people are excited about engineering viruses to inflame the tumour and improve cancer treatment,” says Workenhe. “The implications of these findings for human cancer therapy may be huge.”
This post was adapted from a University of Guelph news story.
December 1, 2020
A national consortium including the Ontario Institute for Cancer Research will expand development of a software platform for genomics and health data and apply it to COVID-19. The $5.1 million project, called COVID Cloud, is co-funded by Canada’s Digital Technology Supercluster and aims to increase Canada’s capacity to harness exponentially growing volumes of genomics and biomedical data to advance precision health. The platform will be used by data scientists and domain experts to help understand, predict, and treat COVID-19 with molecular precision. With a global death count of over 1.4 million people and record numbers of cases nationally, solutions that can help Canada respond to ongoing challenges of the pandemic are urgently needed.
“We are proud to continue to support this consortium’s groundbreaking work through our COVID-19 program,” said Sue Paish, CEO of the Digital Technology Supercluster. “This project shows how Canadian partnerships across multiple organizations and sectors can drive innovation, help us address global health issues, showcase Canadian expertise, and position us well to rebuild and grow our economy.”
The project — a collaboration between BioSymetrics, Centre of Genomics and Policy at McGill University, DNAstack, FACIT, Genome BC, Mannin Research, McMaster University, Microsoft Canada, Ontario Genomics, Ontario Institute for Cancer Research, Roche Canada, Sunnybrook Research Institute, and Vector Institute — brings together Canadian leaders in software engineering, artificial intelligence, cloud computing, genomics, infectious disease, pharmaceuticals, commercialization, and policy. It leverages past work of partners to address needs of infectious disease research with guidance from domain experts.
“Tools that allow us to interrogate SARS-CoV-2 at a molecular level are essential to addressing this global health crisis, both now and in the future,” said Dr. Samira Mubareka, a microbiologist and infectious diseases physician at Sunnybrook, whose team was one of the first in Canada to isolate the novel coronavirus. “The insights we will learn by analysing integrated datasets using technology platforms like COVID Cloud can increase our preparedness for future waves and outbreaks.” Dr. Mubareka will co-chair the project’s translational science efforts along with Dr. Gabriel Musso, Chief Scientific Officer for BioSymetrics. “The infrastructure developed by this initiative will propel collaborative Canadian drug discovery efforts for COVID-19,” said Musso, whose team will lead bioinformatics and computational drug discovery for the project.
A major goal of the project is to make it easy for producers of genomic and health data to share data responsibly over industry standards, and for researchers to harness the collective power of information shared through them. The project deliverables include a suite of software products powered by enterprise-grade implementations of standards developed by Global Alliance for Genomics & Health (GA4GH), protocols that are being designed to facilitate the responsible sharing of genomic and health data, which will help advance precision medicine initiatives around the world.
“The platform is being built on a foundation of open standards that will allow for distributed networks of genomics and biomedical data to be built,” said Dr. Marc Fiume, CEO at DNAstack, whose team will lead software engineering for the project. “We are excited to see these technologies breaking down barriers to data sharing, access, and analysis and create new opportunities for genomics-based discoveries for our partners.”
This project is responding to global demand for highly specialized, scalable, distributed software infrastructure to support collaborative genomics research — a need that has surged since the onset of the COVID-19 pandemic. “COVID-19 has accelerated digital transformation of many industries, especially in healthcare,” said Kevin Peesker, President of Microsoft Canada. “The incredible power of Cloud applied to COVID at scale is expanding development of an information superhighway to securely connect scientists in Canada and around the world to the data and compute power they urgently need to help us overcome one of the greatest global health crises of our time.”
The platform will be used to support a series of projects in partnership with Canadian academic, clinical, and pharmaceutical collaborators, which are being coordinated by Canadian genome centres, Genome British Columbia and Ontario Genomics. These initial projects are being prioritized based on urgency and potential impact on Canada’s response to the COVID-19 pandemic.
“The COVID Cloud is an incredible platform that brings together resources and capacity to enable timely and comprehensive genomic analysis of SARS-CoV-2 for our province and our country,” said Bettina Hamelin, President and CEO of Ontario Genomics, whose team leads the ONCoV Genomics Coalition. “This made-in-Canada solution will immediately accelerate Canada’s response to COVID-19, while being a technological springboard for translating genomic data analysis into actionable medical insights across other disease areas in years to come.”
For more information, visit dnastack.com/solutions/covid-cloud.
November 30, 2020
Researchers find 3-D structure of the genome is behind the self-renewing capabilities of blood stem cells
OICR-funded researchers open a new path to discover drivers of chemotherapy resistance and cancer relapse
Stem cells have the capability to self-renew and create other types of cells, but not all stem cells are equal. OICR-supported researchers at the Princess Margaret Cancer Centre, Drs. Mathieu Lupien and John Dick, have discovered a new way to distinguish the self-renewing capabilities of stem cells, revealing new ways to study the origins of cancer and cancer recurrence.
In their recently published study in Cell Stem Cell, Lupien, Dick and collaborators identified how some blood – or hematopoetic – stem cells can self-renew but others lose that ability. They found differences in the three-dimensional structure of the genetic information between different stem cell types.
DNA within each human cell, including stem cells, is coiled and compacted in a highly regulated way into structures called chromatin. Depending on how DNA is compacted into chromatin, some regions of DNA are accessible to gene-expressing cellular machinery while some aren’t, influencing how genes are expressed and how a cell may behave. The study group identified that this chromatin accessibility is a key component of a cell’s self-renewing capabilities and “stemness”.
“Enabled by the latest technologies, we found that the pattern of closed – or inaccessible – regions of DNA and the open or accessible regions differ between the long-term self-renewing stem cells and other more mature blood cell populations” says Lupien, Senior Scientist at the Princess Margaret Cancer Centre, Associate Professor at the University of Toronto and OICR Investigator.
The study discovered that the self-renewal capabilities are specifically linked to parts of the genome that bind a protein that is responsible for chromatin folding, called CTCF. As cancer researchers, Lupien and Dick are now applying these discoveries made in normal stem cells to study cancer stem cells. It is thought that if a cancer treatment cannot eliminate the cancer’s stem cells, these surviving self-renewing cells can give rise to recurrent tumours. With a better understanding of cancer stem cells, researchers can investigate the roots of cancer and how to potentially target or manipulate the mechanisms behind self-renewal.
This breakthrough study was made possible by Lupien’s expertise in epigenetics, the field that studies gene expression, Dick’s expertise in stemness and blood development, and the contributions of collaborators and trainees, including Drs. Naoya Takayama and Alex Murison who led the wet lab assays and bioinformatics analyses respectively.
“Understanding how stemness is controlled is key to being able to harness the power of stem cells for cell-based therapies, but also to understand how malignant cells perturb stemness to allow the cancer stem cells to continue to propagate tumor growth,” says Dick, Senior Scientist at the Princess Margaret Cancer Centre, Professor at the University of Toronto and lead of OICR’s Acute Leukemia Translational Research Initiative. “We look forward to furthering our understanding of hematopoiesis and bringing these insights closer to clinical application.”
November 24, 2020
As records are becoming more accessible and patients are becoming more engaged with their health data, who will make it all make sense?
Cancer patients are becoming increasingly involved with their care decisions and care systems are increasingly providing patients access to their test results, health data and relevant reports. These reports, however, can be dense, technical and confusing, leading to more questions than answers for patients and their caregivers. Dr. Nathan Perlis at the Princess Margaret Cancer Centre is dedicated to bridging this gap between patients and their health information.
“Traditional radiology and pathology reports were designed for a specific reason, to communicate results between experts in the field, from physician to physician,” says Perlis, Staff Urologist in the Department of Surgical Oncology at the Princess Margaret Cancer Centre and Assistant Professor at the University of Toronto. “We can’t expect that traditional forms will communicate information effectively with patients and caregivers. Our team recognized the need to design new documents to convey the most relevant information for patients in an easy-to-understand way.”
Perlis and collaborators – including OICR and Sinai Health’s Dr. Masoom Haider, UHN’s Healthcare Human Factors team and a group of patient partners – decided to address a key report used in making prostate cancer treatment decisions – the prostate magnetic resonance imaging (MRI) radiology report.
“Unlike a blood pressure measurement or a fever, prostate MRI results are difficult to interpret,” says Perlis. “This can cause unnecessary anxiety and confusion and barriers between patients and their care team. Our new patient-centred design addresses these concerns, providing a steppingstone for further discussion between patients and their clinicians.”
The team recently published their patient-centred radiology report design, coined PACERR, in the Canadian Urological Association Journal. Their design includes key elements including diagrams, a legend and a glossary to help make the MRI results more understandable. All elements of the form – including the format, layout and the language – were developed and evaluated in partnership with patients and caregivers. The group is now evaluating the form in a clinical trial.
In parallel, the group has recognized a key barrier to implementing these forms in practice. Creating these forms would significantly add to the reporting burden on radiologists. Perlis and collaborators have now set out to create a software package that can read a traditional standard report and automatically complete a tailored patient-centred report. As they develop this software, they hope to apply their learnings to other types of reports across different cancer types.
“Patient-centred communication tools are necessary for shared decision-making,” say Perlis. “We can imagine a future where patients are truly enabled and engaged in their health decisions and this work is a purposeful step toward that goal.”
This research was funded in part by OICR’s Investigator Awards Program.
November 18, 2020
Ontario cancer research leaders, Drs. Geoff Fong, Trevor Pugh and Lincoln Stein recognized as Highly Cited Researchers by Clarivate for their influential work
OICR is proud to celebrate the recognition of three Ontario cancer research leaders, Drs. Geoffrey Fong, Trevor Pugh and Lincoln Stein as Clarivate’s Highly Cited Researchers of 2020. This recognition demonstrates the incredible global impact of Ontario’s researchers and underscores the importance of sharing knowledge for greater progress around the world.
Fong, Pugh and Stein, who are senior OICR investigators and leaders, have led several international scientific collaborations that have uncovered valuable knowledge and informed disease control and management strategies in Canada and around the world.
- Dr. Geoffrey Fong leads the International Tobacco Control Policy Evaluation Project, which conducts cohort studies on the implementation of evidence-based tobacco control policies. The ITC Project has conducted studies in 29 countries, inhabited by more than 50 per cent of the world’s population.
- Dr. Trevor Pugh, who was recently named one of Canada’s Top 40 Under 40, leads highly-collaborative genomics studies that are focused on applying sequencing analysis in the clinic. His landmark cancer genome studies have advanced research across different cancer types and his work continues to make precision cancer medicine a reality.
- Dr. Lincoln Stein has led large international data sharing consortia, such as the International HapMap Consortium and the International Cancer Genome Consortium, which have led to highly-cited scientific tools and discoveries. The tools, data and knowledge resulting from these consortia have been used by tens of thousands of people around the world.
“We’re proud that cancer researchers here in Ontario are making a worldwide impact that will improve the prevention, diagnosis and treatment of cancer,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “I congratulate Drs. Fong, Pugh and Stein on this well-deserved recognition.”
The highly-anticipated annual list identifies researchers who demonstrated significant influence in their field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top one per cent by citations for field and publication year in the Web of Science citation index. Clarivate’s methodology draws on the data and analysis performed by bibliometric experts and data scientists at Clarivate’s Institute for Scientific Information.
The full 2020 Highly Cited Researchers list and executive summary can be found online here.
November 17, 2020
Dr. Brian Nieman takes a deep dive into the neurocognitive side effects of childhood leukemia treatment seeking new ways to improve the lives of survivors
Due to advances in the treatment of childhood acute lymphoblastic leukemia (ALL), more than 90 per cent of children diagnosed with the disease will live long and relatively healthy lives. However, there are still long-term neurocognitive side effects – or lasting effects – of treatment including attention, processing speed and motor coordination difficulties. Investigating these lasting effects at The Hospital for Sick Children (SickKids) is Dr. Brian Nieman, who is committed to further improving the lives of childhood leukemia survivors.
Recently published in Neuroimage: Clinical and Pediatric Research are two of Nieman’s latest studies on the neurocognitive impact of ALL treatment on growing children. In these studies, Nieman and collaborators discovered that many leukemia survivors have neurocognitive abilities that are comparable to other children but on average survivors are doing worse than their peers.
“We see that leukemia treatment has broad and lasting implications on the brain,” says Nieman, OICR Investigator and Senior Scientist at SickKids. “Determining when these key changes occur and which part of a child’s treatment is causative will be an important step in designing protective or rehabilitative strategies in the future.”
The study that was published in Neuroimage: Clinical was the first to investigate the impact of ALL treatment on the brains of survivors ages 8-18 using MRI. The study found extensive structural differences in the brain between survivors and their peers. The study published in Pediatric Research focused on quality of life measures, and identified the impact of leukemia treatment on IQ, behavioural measures, attention and cognitive abilities.
With this new knowledge and Nieman’s expertise in experimental mouse model imaging, he and collaborators are now investigating which chemotherapy drugs cause these lasting effects and when these developmental changes are occurring in a leukemia patient’s development. They strive to identify new strategies to protect and rehabilitate the developing child’s brain.
“Over the last few generations, we’ve seen childhood leukemia survival reach 90 per cent. Over the last few decades, we’ve seen a shift in practice that has allowed patients to experience fewer side effects. But these studies demonstrate that treatment isn’t ideal yet,” says Nieman. “The results that we’ve collected suggest that we could potentially help many leukemia patients and we’re committed to do so.”
November 13, 2020
Research team develops a Google maps-like algorithm to pinpoint when cancer patients may diverge from the standard course of treatment
Every cancer patient’s experience is unique but there are standard sequences of steps that help patients and their care teams navigate through screening, diagnosis, treatment and monitoring. These steps are published in pathway maps but are these maps followed in practice? Researchers supported by OICR’s Health Services Research Network, led by Drs. Timothy Chan and Claire Holloway, are working to answer that question.
Chan and collaborators at Ontario Health have developed new methods to measure the difference between a standard clinical pathway map and the actual care that a patient receives in practice. They leveraged real-world health data from Ontario patients to develop these methods, which could potentially be used to identify targets for quality-improvement initiatives.
“Pathway maps help optimize patient survival, healthcare costs and wait times at a population level,” says Holloway, co-principal investigator of the project and Provincial Clinical Lead of Disease Pathway Management (DPM) at Ontario Health.
“We have now derived a way to measure the alignment between actual care and the care described in a pathway map, analogous to measuring how a driver’s route differs from the Google Maps-suggested route,” says Chan, co-principal investigator of the project, Professor at the University of Toronto and Canada Research Chair in Novel Optimization and Analytics in Health.
To address this challenge, the team based their algorithm on an inverse optimization framework, a type of framework used to solve problems across a variety of disciplines, including telecommunications routing, medical radiation therapy planning, and investment portfolio management.
The research team first applied their methods to stage III colon cancer patient data and is now applying their methods to breast cancer care. The ultimate goal would be to use these methods across different cancer sites and potentially different diseases to help promote and implement best practices along the care continuum in Ontario’s healthcare system.
“We’re proud to apply our framework at a large scale to help provide meaningful quantitative measures of system efficiency and variation,” says Chan. “It’s exciting to see that these methods could allow Ontario Health to monitor and evaluate complex practice patterns at a population level.”
“Variations between a patient’s experience and the standard clinical pathway map isn’t necessarily a bad thing but it may prompt us to investigate further,” says Dr. Katharina Forster, Team Lead of DPM at Ontario Health. “We can look into why, when and where the variation is occurring. In this way these new methods and tools are allowing us to generate hypotheses about the causes of variation so we can better understand our care practices, make data-driven decisions and ultimately improve our cancer care system.”
“Ultimately, we’re looking to measure, monitor and improve our system across the province,” says Holloway. “Our rich data in Ontario and our capabilities in machine learning are outstanding. Thanks to OICR, we can bring these disciplines together to make a positive impact on our health system.”
The Health Services Research Network is co-funded by OICR and Cancer Care Ontario, now part of Ontario Health.
November 5, 2020
Study finds that every month delay in cancer treatment can raise risk of death by around 10 per cent
Research led by Dr. Timothy Hanna suggests that minimizing delays to treatment could improve cancer survival rates
Many countries have needed to defer cancer surgeries, radiotherapy and other treatments through the COVID-19 pandemic, which has brought the impact of treatment delays into sharp focus. In a study published today in The BMJ, Dr. Timothy Hanna and collaborators report that people whose cancer treatment is delayed by even four weeks have in many cases a six to 13 per cent higher risk of dying – a risk that keeps rising the longer their treatment does not begin.
“We know that delay matters and now we understand how much it matters,” says Hanna, Radiation Oncologist at the Cancer Centre of Southeastern Ontario, Faculty of Queen’s Cancer Research Institute, OICR Clinician Scientists and lead of the study. “With these data, we can now quantify the impact of treatment delays – including those that we’re experiencing now throughout the COVID-19 pandemic.”
The research group reviewed and analyzed relevant studies from around the world that were published over the last two decades. They found that there was a significant impact on a person’s risk of death if their treatment was delayed, whether the treatment was surgical, chemotherapy or radiotherapy. They observed this impact across all seven types of cancer analyzed – breast, bladder, colon, rectum, lung, cervix and head and neck cancers.
For example, with cancer surgery, they saw a six to eight per cent increase in the risk of death for every four-week treatment delay, meaning that a three-month delay could increase the risk of death by about 25 per cent. The impact was even greater for specific treatments – such as bowel cancer chemotherapy – where a three-month delay could cause a 44 per cent increase in risk of death.
“As we move towards the second COVID-19 wave in many countries, the results emphasize the need to prioritize cancer services including surgery, drug treatments and radiotherapy as even a four-week delay can significantly increase the risk of cancer death,” says Dr. Ajay Aggarwal, co-lead of the study from King’s College London and the London School of Hygiene and Tropical Medicine.
Hanna hopes this study will help inform cancer treatment backlog management and prioritization. His prior work on prioritizing treatment during COVID-19, published in Nature Reviews Clinical Oncology, has been incorporated into health system planning and management in Ontario and around the world.
“The impact of cancer treatment delays will persist long after the threat of this pandemic subsides,” says Hanna. “As a clinician, a patient, an administrator or a decision-maker in our cancer care system, these results should encourage us all to put resources and efforts in place to minimize system level delays in cancer treatment.”
November 4, 2020
OICR-supported research study investigates the symptoms experienced by patients undergoing lung cancer treatment using a decade’s worth of data
In 2010, the Edmonton Symptom Assessment System (ESAS) was rolled out in all cancer centres in Ontario to improve cancer symptom management. ESAS allows patients to self-report on the severity of nine common cancer-associated symptoms throughout their treatment, enabling their care team to better monitor symptoms in real time. The data from the initiative was collected in a central repository over the past decade and now Drs. Natalie Coburn and Alexander Louie, among other researchers, are tapping into the data to study how lung cancer patients feel and how their symptoms are managed.
“This initiative represents a shift towards greater focus on symptoms of cancer and patient quality of life,” says co-lead investigator Dr. Natalie Coburn, Senior Scientist in Evaluative Clinical Sciences and Surgical Oncologist at Sunnybrook’s Odette Cancer Centre. “We believe that improving symptom management through cancer care is important, not only for supporting the patients themselves, but also for building a more efficient and effective healthcare system.”
Through their preliminary analyses, they’ve discovered key insights that may help guide their future research into lung cancer symptom management. They observed that symptoms often improve over the course of treatment but worsen late in disease progression. Early results also debunk the common misconception that nausea is a universal and pervasive side effect of chemotherapy treatments. The thought of having severe nausea can cause stress for a lot of patients, but knowing it may not be as severe as they think can be a big deciding factor when clinicians discuss their choices of care. They found that tiredness and fatigue are often much more common than nausea, but symptoms are generally not as severe as patients expect.
“With this real-world dataset, we can focus in on exactly when patients are feeling worse and find new ways to help patients feel better throughout treatment,” says co-lead Dr. Alexander Louie, Scientist in Evaluative Clinical Sciences and Radiation Oncologist at Sunnybrook’s Odette Cancer Centre. “Our research is helping discover new areas of improvement so that ultimately, we can develop and implement interventions to better support symptom management.”
The research team is now in the process of meeting with patient groups and collaborators to establish priorities for future analyses.
“We have a strong, multi-disciplinary team working on this initiative including clinicians, analysts and patients who each bring their own expertise to the table,” says Victoria Delibasic, a lead Research Coordinator of the team. “We’re proud that this research is empowering the community to help people with cancer thanks to the real-world data from those who have lived through similar experiences.”