January 8, 2021

Q&A with new OICR Investigator Dr. Shraddha Pai on uncovering the hidden differences between cancers

OICR is proud to welcome Dr. Shraddha Pai to its Computational Biology Program as a Principal Investigator. Here, Pai discusses current challenges in understanding diseases and what motivates her to tackle some of the biggest challenges in biomedical research.

What are some of the research questions you’re interested in?

I’m very driven to understand why different people with the same cancer type, have different outcomes and respond differently to the same treatment. As genomic assays get cheaper, we learn more about molecular interplay in different cells, and our population datasets become larger and mature, we are able to integrate different layers of the genome and cell types, to try to get at this question. For example, we now believe there are four main types of medulloblastoma with different underlying molecular networks and outcomes. This field of research is called ‘precision medicine’: using patient profiles to match them with the most effective treatment. But really this is just a new phrase to describe what doctors have been doing since the dawn of medicine; it just means that now we’re using powerful computers and algorithms to find patterns in much larger and complex genomic datasets. The principle is the same.

As a trainee in Dr. Gary Bader’s group, I led the development of an algorithm that integrates several types of patient data to classify patients by outcome.  Our method – called netDx – adapts the idea of recommender systems, used by Netflix and Amazon, to precision medicine. Just as one would ask Netflix to “find movies like this one”, netDx helps identify patients “with a treatment profile like this”. In a benchmark, netDx out-performed most other methods in predicting binary survival in four different types of cancer. Importantly, netDx is interpretable, and recognizes biological concepts like pathways. This makes it a useful tool to get mechanistic insight into why a predictor is doing well, and provides a way to understand the underlying biology and perhaps drive rational drug design.

I also have a special interest in understanding the link between epigenetics and disease, particularly as this pertains to the brain. Epigenetics refer to molecular changes that change how the genome behaves – for example, turning a gene on or off in a given cell type. My own previous research in mental illness has found epigenetic biomarkers related to psychosis, which explain the distinctive features of this condition. The same may be the case in certain types of cancers, particularly those of developmental origin.

How do you plan to unravel these complex layers of biology?

My research program has two main goals. The first is to build models for precision medicine – predicting disease risk, treatment response – starting with population-scale datasets that have several types of patient data. I’m hoping to use existing and emerging data such as UK BioBank, CanPath, ICGC-ARGO and the Terry Fox Research Institutes’ datasets, and ongoing clinical trials, to identify which clinical outcomes are easily amenable to our approaches. The models my group builds will incorporate prior knowledge about genome organization and regulation, so that these are interpretable. For example, we will use epigenomic maps of specific tissue types, or data from single-cell resolution maps, pathway information, to find and organize relevant needles in the genomic haystack. This feature will give us interpretability, which is key to increasing confidence in a model, as well as to improving the understanding of cellular pathways that affect disease and eventual drug development.

My second goal is to understand the epigenomic contributions – particularly developmental changes – to cancer risk, using a combination of molecular biological, genomic and analytic techniques.

As I work toward these goals, I hope to collaborate on complementary projects, such as identifying DNA methylation changes in circulating tumour DNA and improving how we subtype adult tumours. These projects will hopefully lead to new biomarkers, and ultimately improvements to how we diagnose and treat cancer.

Importantly, the software that my team builds will also be openly available to the research community, so others can apply my methods to different types of diseases. I’m excited to get started.

Your work applies beyond cancer. How do you traverse these different disease areas?

The reclassification of disease based on molecular or other biomarkers, and how disease subtype affects risk and treatment response, isn’t unique to cancer – the same research questions extend to other types of disease such as metabolic diseases, autoimmune diseases and mental illness. At the end of the day, we are looking at the same system organized at the molecular, cellular and organ-level, with similar principles of genomic regulation and perhaps similar considerations for drug discovery. Our algorithms are based on these general principles and can therefore be used to answer similar questions for different disease applications, or very different types of cancer. Of course, it’s important to collaborate with teams that have domain expertise to make sure the algorithms are “fine-tuned” for a particular application, and I look forward to benefitting from those partnerships.

What excites you about this type of work?

I’m excited to join a community where basic research is so strongly connected to clinical purpose. Personally, I am very motivated by the prospect of a positive impact on patients within my lifetime and feel that my group’s work is more likely to have a valuable impact in an environment that combines basic and translational research. That said, we’re only just beginning to see the benefits of precision medicine and many challenges remain to bring genomic knowledge into practice. I hope that I can create more useful methods and models for precision medicine and improved clinical decision-making in the coming decade.

I’m especially excited to be at OICR because of the Institute’s access to clinical trials, strong genomics and computational biology program, and pharmacology team. If my group can find promising biomarkers and leads, we can work with OICR collaborators in the Genomics and Drug Discovery groups to move from basic research to application.

Read more about Dr. Shraddha Pai.

January 4, 2021

Brain cancer linked to tissue healing, study finds

A brain scan showing a top down view of a cross-section with a glioblastoma tumour highlighted in red. (Hellerhoff, Wikimedia Commons)

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

nanoNOMe: New dual-purpose tool added to the Swiss Army knife of DNA sequencing

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

Innovative tool pinpoints rare mutations that indicate the earliest phases of leukemia development

Dr. Sagi Abelson
Dr. Sagi Abelson, OICR Investigator, Assistant Professor at the University of Toronto and first author of the publication.

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 3, 2020

Happy holidays from OICR

A holiday message from Dr. Laszlo Radvanyi, OICR’s President and Scientific Director:

This year has presented immense challenges and hardships for people around the world, including cancer patients, researchers, clinicians and many others in the OICR community.

As I reflect on what has transpired over 2020, I think the most lasting memory will be the amazing adaptability of our staff, funded researchers, leadership and partners that has allowed us to continue pressing ahead in the fight against cancer, all while contributing to COVID-19 research and staying safe. I thank everyone for their remarkable contributions to cancer research during this difficult time and for being part of the historic scientific campaign against COVID-19, while keeping our cancer focus solidly intact.

While the year did not go as anyone planned, we have continued to make a difference for cancer patients by advancing cutting-edge solutions for preventing, screening, diagnosing and treating cancer. Of particular note this year was the Pan-Cancer Analysis of Whole Genomes (PCAWG) project coming to its climax, generating astounding insights into cancer genomics that are fueling entirely new ways to approach cancer such as developing new tools and approaches to interrogate the role of non-coding regions of the genome. This project is emblematic of the efforts of OICR researchers across our programs to collaborate and find truly novel solutions to the many challenges we face in improving the lives of cancer patients. The scientific network of investigators we fund has also made tremendous contributions, including advancing new drug targets and cell therapy approaches against cancer as well as inroads in understanding cancer therapeutic resistance via cancer stem cells and uncovering novel molecular subsets of cancers, such as pancreatic cancer.

Earlier this year a positive international external review found that OICR is making a true impact and is on the right track, having built a firm foundation to reinforce our model and take the next steps in furthering our impact. Through consultations with our stakeholders, we have developed a bold and visionary new strategic plan that will expand our focus on early cancer detection and intervention as well as strengthen our growing and successful drug discovery efforts. This plan builds not only on our current momentum, but also further deepens collaborations with our provincial, national and global partners.

Of course, our progress thus far would not be possible without the support of the Government of Ontario through the Ministry of Colleges and Universities – I thank them for their continued investment in made-in-Ontario cancer innovations and belief in our vision of “cancer solved together”. I also thank our partners in cancer research and care at cancer centres, research institutes and universities across Ontario for their continued collaboration and engagement. Together we have continued to perform world class research, improve cancer care and bring real economic benefits to Ontario’s economy.

In closing, I note that many of us will not be able to celebrate the holidays as we have in years past. While this is unfortunate, we must focus on the good we are doing for ourselves, our loved ones and our communities by doing our part for public health. I wish happy holidays and a happy new year to all as we look forward to a much brighter year ahead. Please take care and stay safe.

Sincerly,

Dr. Laszlo Radvanyi
President and Scientific Director, OICR

December 2, 2020

Study uncovers new approach to mobilize the immune system against hard-to-treat breast cancers

Dr. Sam Workenhe. (University of Guelph)

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

Consortium secures $5.1 million to expand genomics platform for COVID research

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

Drs. Mathieu Lupien and John Dick.

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 25, 2020

Cancer research through COVID: A drug discovery student’s perspective

Despite disruptions, cancer researchers across Ontario are continuing to make scientific progress in labs and at home. Here, Vivian discusses her master’s project, discovering drug targets for future immunotherapies.

November 24, 2020

Simplifying confusing medical documents one form at a time

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.

Dr. Nathan Perlis.

“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

Three OICR researchers named to this year’s Highly Cited Researchers list

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

Towards healthier lives for childhood leukemia survivors

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.

Dr. Brian Nieman.

“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.”

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