New research asks if clinical trials are losing sight of what matters most to cancer patients

Dr. Bishal Gyawali says research into new cancer drugs should focus on outcomes like quality of life and overall survival.

Cancer therapies should help people live longer or live better, and ideally they should do both.

“That’s just common sense,” says medical oncologist Dr. Bishal Gyawali.

But Dr. Gyawali’s research shows that clinical trials for new cancer drugs don’t always prioritize outcomes like quality of life and overall survival. And he worries oncology is losing sight of what matters most to cancer patients.

“What patients care about is how long they’ll live and how well they’ll live,” says Dr. Gyawali, an OICR Clinician Scientist and Associate Professor at Queen’s University. “But unfortunately, these outcomes are frequently not measured or even discussed in clinical trials.”

Dr. Gyawali’s latest research explores how quality-of-life outcomes are reported in clinical trials for new cancer drugs. He worked with colleagues at Queen’s University — including quality of life experts — to conduct a cohort study of recent Phase III trials and published their findings in JAMA Oncology.

To start, they had to exclude a large proportion of trials because the papers didn’t report on quality of life at all. Of studies that did, less than a quarter of therapies actually improved patients’ quality of life. That wasn’t surprising to Dr. Gyawali, who found in a 2018 study that just 42 per cent of cancer clinical trials reported on quality-of-life outcomes, and ones that did mostly reported no improvement.

What surprised Dr. Gyawali in his new study was that when drugs failed to improve quality of life, results were often presented with a favourable spin. Unchanged quality of life was described as “maintained” or “not worsened” in some journal articles, while decreases in quality of life were sometimes written off as “not clinically significant.”

“A patient wants their quality of life to improve,” Dr. Gyawali says. “How can I tell a patient that if you take this drug your quality of life will ‘not be worse?’”

Instead of focusing on quality-of-life outcomes, many studies reported on progression-free survival (PFS), a measure of how much tumours grow or shrink over a period of time. But Dr. Gyawali and colleagues found that improvements in PFS were not necessarily associated with improvements in quality of life. In fact, some cancer therapies that slowed the growth of tumours actually made patients’ quality of life worse and had no effect on how long they survived. Yet, these trials were still framed as successful.

Dr. Gyawali says that raises major questions about the value of PFS as an endpoint. “If a drug delays the growth of the tumour but does not improve survival and worsens quality of life, then we should call that drug harmful,” Dr. Gyawali says.

The JAMA Oncology study reinforces much of Dr. Gyawali’s recent work, which has taken a hard look at oncology research in the hopes of making it more patient-centred.

His interest in this area began shortly after he became a medical oncologist in 2017. He says his medical education in Nepal focused mainly on “textbook medicine,” and he didn’t initially question the evidence behind his textbooks. But studying oncology in Japan opened his eyes to evidence-based medicine, and he started digging deeper into the clinical trials underlying the drugs he was supposed to prescribe.

He says he found flaws in how some trials were structured and reported, which led to expensive cancer drugs that offered little benefit to patients being approved and prescribed. “It was like an epiphany when I first noticed this,” he says. “Then I started seeing it everywhere, and it became my major research theme.”

He approaches this research from various angles, looking at medical education, research processes and policy decisions to see why oncology research can sometimes “forget the bigger picture” of its impact on patients.

And this April, he and his Queen’s University collaborator Dr. Christopher Booth described some overarching problems in a Nature Medicine paper titled “Cancer treatments should benefit patients: a common-sense revolution in oncology.”

“Our overall theme is that cancer treatments should benefit patients and we’re losing sight of that,” Dr. Gyawali says. “So how can we bring the system back in line with what matters to patients?”

Among many recommendations, Drs. Gyawali and Booth suggest changes to medical education to improve doctors’ ability to critically assess literature, changes to clinical trials to focus more on patient-centred outcomes like quality of life and overall survival, and changes to the journal publishing process to ensure that studies are reported without hype or bias.

These and other changes could help ensure oncology is focused on what’s most important, Dr. Gyawali says, and make sure patients and their doctors have the best information to make decisions about their health. “I want a society where patients are more and more aware of these issues,” he says. “Their lives and well-being are literally at stake.”

Dr. Gyawali knows his research is sometimes seen as controversial, and says he gets mixed reactions from colleagues when his papers are published. But he doesn’t think it’s revolutionary to say that cancer therapies should benefit cancer patients.

“If cancer drugs can’t improve a patient’s chance of surviving or improve their quality of life, then we shouldn’t be using those drugs,” he says. “That shouldn’t be controversial.”

Building evidence for the landmark U.S. ban on menthol cigarettes

OICR Senior Investigator Dr. Geoffrey Fong’s research helped inform the newly proposed tobacco control policy.

When the U.S. Food and Drug Administration (FDA) announced in April 2022 that it was moving forward with a ban on menthol cigarettes, FDA Commissioner Dr. Robert Califf said the ban would help smokers quit, stop young people from starting smoking, and save lives.

He knows that in part because of OICR Senior Investigator Dr. Geoffrey Fong.

Dr. Fong is widely renowned for his research into the impact of policies to curb tobacco smoking — the greatest cause of preventable cancer in Ontario, in Canada and around the world. As Chief Principal Investigator of the International Tobacco Control Policy Evaluation Project (ITC Project) at the University of Waterloo, he led an evaluation of Canada’s recent menthol cigarette ban that was cited by the FDA as it explored a U.S. menthol ban.

Canada became one of the first countries to ban menthol cigarettes when all provinces introduced bans between 2015 and 2018, and then became the first country where a menthol ban has been evaluated on whether it leads smokers to quit.

Smoking kills about 45,000 Canadians every year, and public health authorities including the World Health Organization have long advocated for banning menthols, which have added flavouring and are popular among young smokers, women and some minority groups.

In their initial analysis published in April 2021, Dr. Fong and his ITC Project colleagues showed that banning menthol cigarettes made Canadian menthol smokers significantly more likely to quit than those who smoked non-menthol cigarettes. He presented these findings to colleagues at the FDA. Three weeks later, the FDA announced that it would develop a rule to ban menthol, citing the ITC study.

Now, on the same week of the FDA’s latest announcement, Dr. Fong and colleagues published a new analysis in Tobacco Control that projects the U.S. ban could lead 1.3 million American smokers to quit.

“This is an enormous, landmark decision by the FDA,” says Dr. Fong, who spoke about the decision with several major U.S. news outlets including the New York Times, Washington Post and NBC News. “It’s a major step in tackling the number one preventable cause of cancer and non-communicable diseases.”

This newest study builds on the ITC Project’s previous work by combining ITC data across 7 provinces with data from another project that also evaluated the impact of the menthol ban only in Ontario. Together, they found that 22.3 per cent of menthol smokers quit following the ban, compared to 15 per cent of non-menthol smokers. Applying that 7.3 per cent difference to the more than 18 million menthol smokers in the U.S. gave Dr. Fong and colleagues their 1.3 million estimate.

The menthol ban is likely to have a major impact on the health of Black Americans, who smoke menthols at much higher rates than other Americans and who have been targeted by aggressive menthol tobacco marketing. Dr. Fong’s research estimates that more than 381,000 Black smokers are likely to quit following the ban.

Although the policy has been formally proposed, it may take years before a ban comes into force. The proposal still needs to be finalized and will likely face strong pushback from tobacco companies.

The tobacco industry has a long history of suing countries that try to implement stronger policies, often attempting to discredit the evidence behind those policies. That’s why having comprehensive, population-level studies like Dr. Fong’s is particularly important to the success of these measures.

“Our study is the most complete evaluation of Canada’s menthol cigarette ban,” Dr. Fong said. “I think it can stand up to the challenges that will be coming.”

Predicting cancer evolution with deep learning algorithms

New proof-of-concept approach offers faster, more accurate inferences about tumour populations.

The prevalence of mutations in a tumour can provide clues about how the cancer has grown or evolved and how best to treat it.

But making predictions about the evolution of mutated tumours using a single DNA sequenced biopsy requires complex estimates, and current methods are either slow, or don’t always consider why certain subpopulations of cells proliferate more than others.

This led a pair of researchers at the Ontario Institute for Cancer Research (OICR) to develop a new method for understanding and predicting cancer evolution that harnesses modern deep learning algorithms and incorporates evolutionary modeling.

TumE is a deep learning approach that analyzes the frequency of mutations in a biopsy — known as the variant allele frequency — to identify which subpopulation of mutated cells that are most “fit” and thus most likely to make a tumour stronger.

“We’re taking deep learning tools into the cancer genomic space and trying to find optimal methods for predicting and understanding cancer evolution,” says lead researcher Tom Ouellette, a PhD student at OICR based in Dr. Philip Awadalla’s lab.

TumE’s algorithm uses evolutionary modeling to distinguish between cases where highly “fit” cellular subpopulations are driving tumour growth versus cases where no one cell or subpopulation has a detectable advantage. This helps it make predictions about how many subpopulations are observed in a tumour biopsy, and which subpopulations and mutations will eventually take over.

Understanding which mutations will increase in frequency can provide insight for therapeutic intervention or for quantifying the aggressiveness of tumour growth.

TumE builds on two other methods for inferring the evolution of mutations — approximate Bayesian computation and mixture models — which have been used for several years but have limitations. When tested with simulated data and 88 whole genome sequence samples, as reported in PLOS Computational Biology, TumE generated inferences that were faster than approximate Bayesian computation and more accurate than mixture models.

Though it’s still at the proof-of-concept stage, Ouellette says that TumE offers a good foundation for quickly understanding the link between mutations and the evolutionary dynamics that drive cancer. With access to more data, he says the approach could be scaled up to make more complex predictions.

“With high-quality data and with minimal computational cost, we could use methods like TumE to find patterns and start making statistical estimates of which mutations lead to worse outcomes,” he says.

The advantage of deep learning is that, once something like TumE has been developed, it can be re-tuned to predict different things without having to start from scratch. Eventually, Ouellette says deep learning could be used to determine which mutations or subpopulation of cells are most deadly and should be targeted with precision cancer treatments, ultimately leading to better outcomes for patients.

“We’re trying to find methods that can be used quickly and concurrently with patient care,” he says. “I think this is a stepping stone to get there.”

TumE is publicly available for use at https://github.com/tomouellette/TumE

Two OICR innovations bolstered by investments from FACIT

Investments will support high-profile work led by Dr. Rima Al-awar and Dr. Lincoln Stein.

Groundbreaking projects in OICR’s Drug Discovery and Adaptive Oncology research themes are receiving support to advance made-in-Ontario innovations thanks to investments from FACIT.

The investments announced on April 27 will support work led by OICR’s Head of Therapeutic Innovation and Drug Discovery Dr. Rima Al-awar and Head of Adaptive Oncology Dr. Lincoln Stein.

Dr. Al-awar’s Drug Discovery team is working on a therapeutic platform that targets members of the WD40 repeat domain family of proteins, research that has garnered a lot of attention for its potential to enable new drug discoveries and intellectual property.

Dr. Stein’s team is applying deep data analytics, network association and informatics to better understand the cancer genome. Funding from FACIT will help researchers validate and optimize proprietary technology that helps prioritize tumour targets.

“Congratulations to Dr. Al-awar and Dr. Stein on receiving critical seed capital from FACIT,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Our world-leading Drug Discovery and Informatics teams are in a unique position to leverage an organic partnership and develop their integrated, competitive platform technologies.”

These new investments come through FACIT’s Prospects Oncology Fund, which provides seed-stage capital for Ontario-based innovations in oncology. FACIT’s review of Prospects Oncology Fund investments are complemented by third party expert reviews to support the best innovations in the province.

“The FACIT team is pleased to support these internationally renowned scientists and invest in product platforms with serious potential for the treatment of cancer,” FACIT President Dr. David O’Neill says.

FACIT and OICR are collaborators in translating cancer research discoveries to patients. Learn more about OICR and FACIT.

Adding another dimension to breast cancer screening

3D ultrasound prototype shows promise as point-of-care screening tool for women with dense breasts.

Researchers at Western University are hoping their 3D ultrasound system can help close a gap in breast cancer screening for the nearly 40 per cent of women with dense breasts.

Mammography is the gold standard in breast cancer imaging, and regular mammograms can help detect breast cancer early when it is most treatable. But dense breast tissue can ‘mask’ tumours in a mammogram, increasing the chances that early stage cancers are missed.

Ultrasound is a potentially more effective screening option for women with dense breasts. Producing higher contrast images than mammography, standard 2D ultrasound images can help spot cancer independent of breast density. And new developments in 3D ultrasound technology could provide an even more detailed picture.

Western University’s Claire Park is first author of a paper in Medical Physics describing a 3D ultrasound prototype for whole-breast imaging. The method involves adding a clinician-controlled robotic arm to an existing 2D ultrasound system, taking 2D photos at different angles, and using custom software to synthesize them into 3D.

“By adding that three-dimensional information, we can better detect cancer, and better characterize the cancer we see,” says Park, a PhD candidate in Medical Biophysics at Western University’s Robarts Research Institute under Dr. Aaron Fenster, who is also Co-Director of OICR’s Imaging Program. “It also opens the possibility for imaging in auxiliary regions of the breast where other systems can’t see.”

Because the prototype is adaptable to any existing 2D ultrasound system — one of the most widely accessible imaging technologies — it has the potential to be rolled out widely and cost-effectively. It also performed well in early testing, producing highly accurate 3D images in volunteers and tissue-mimicking phantoms.

“The results were really encouraging,” Park says. “They show that our system could be used as an accurate alternative [to mammography].”

The study also demonstrated the system’s potential for point-of-care imaging. The prototype is small, fitting onto a medical cart, and Park says it could ultimately be portable enough to screen high-risk women at the bedside.

Though promising, this work is still in early stages. The research team is currently using what it learned from testing to optimize the prototype, working to reduce errors and iterating components to improve workflow. Ultimately, researchers hope to develop a robust protocol for whole-breast imaging and would ultimately like conduct a clinical trial.

For now, Park and her colleagues are encouraged by what their system could mean for a large number of women.

“There is an unmet clinical need for women with dense breasts,” says Park. “A system like ours that harnesses technology that is already readily available in the clinic could really address that need.”

Claire Park was one of six Ontario trainees working in cancer research to receive a 2022 Rising Stars Award.

Up-and-coming research trainees receive OICR Rising Stars awards

Winners of the 2022 awards are working on a range of cancer research projects across Ontario.

The Ontario Rising Stars in Cancer Research Network has recognized six outstanding research trainees with the 2022 Rising Stars Awards.

Supported by OICR, Rising Stars is a pan-Ontario network for trainees in cancer research at the graduate and postdoctoral levels. Its annual awards recognize Ontario trainees who demonstrate a high standard of scholarly achievement in cancer research as well as community engagement and leadership.

This year’s award winners are:

Master’s students

Aline Atallah, Queen’s University
Aline’s research is focused on characterizing the tumour immune microenvironment in bladder cancer to better understand the role of innate immune memory acquisition in the response to Bacillus Calmette-Guérin immunotherapy, with the ultimate goal of improving patient outcomes.

Anisha Hundal, University of Toronto
Anisha’s research investigates whether breast cancer cells deficient in homology-directed DNA double-strand break (DSB) repair employ microtubule-driven nuclear envelope invaginations to repair DSBs, and whether this mechanism may be exploited to limit cancer cell growth and survival.

PhD students

Nabanita Nawar, University of Toronto
Nabanita applies a multi-disciplinary drug discovery approach for therapeutic intervention of HDAC6, to explain its numerous and often contrasting roles in diseases, and design small molecules that can inhibit HDAC6 activity, and alleviate disease phenotypes.

Claire Park, Western University
Claire’s research is focused on developing systems to improve diagnostic and image-guided interventions for women at high-risk of developing breast cancer using PEM and (2D and 3D) ultrasound

Postdoctoral fellow

Dr. Emma Bell, Princess Margaret Cancer Centre (UHN)
As a bioinformatician, Emma combines biology, statistics, and information engineering, to ask biologically and clinically meaningful questions of genomics data. They aim to improve gynaecological healthcare outcomes for women, non-binary and trans people.

Dr. David Cook, Lunenfeld-Tanenbaum Research Institute
Residual disease following treatment remains a challenge for effective cancer treatment. David applies single-cell genomics to understand how cancer cells adapt to treatment and learn to tolerate therapies.

Award-winning co-op student makes her mark on pancreatic cancer research

Undergrad Laura Bumbulis was named the University of Waterloo Faculty of Mathematics Co-op Student of the Year for her work with OICR.

In just four months as a co-op student with OICR’s Pancreatic Cancer program (PanCuRx), Laura Bumbulis helped identify gene mutations in pancreatic cancer and make tumour analysis more efficient.

Not bad for someone who hadn’t studied biology since Grade 11.

Bumbulis joined OICR in the summer of 2021 as an undergraduate student from the University of Waterloo’s Faculty of Mathematics.

“I wasn’t always interested in health sciences, but my interest grew from wanting to have a positive impact on society,” says Bumbulis, who is studying for a double major in statistics and combinatorics/optimization.

At OICR, Bumbulis was tasked with learning how to analyze genome sequencing data and automate PanCuRx’s data analysis workflow. She finished that with time to spare ⁠— while helping streamline the team’s data analysis process ⁠— and was given the more challenging job of studying genetic mutation patterns in tumour samples that were exposed to chemotherapy.

Bumbulis excelled once again, implementing a new algorithm that identified mutation patterns the team hadn’t previously been able to find, providing new insight on how pancreatic adenocarcinoma develops. This work will be written up and submitted for publication and Bumbulis will be named as an author.

Bumbulis’ ability to learn on the fly and apply her knowledge of informatics to solve complex problems earned praise from her supervisors.

“Laura far exceeded our expectations during her work term,” says Dr. Faiyaz Notta, who co-leads the PanCuRx program with Dr. Steven Gallinger. “She worked on highly technical projects that are far beyond what can usually be accomplished in a co-op term.”

Her achievements also earned her recognition from her university, which named her the Faculty of Mathematics Co-op Student of the Year.

Bumbulis is proud she was able to quickly brush up on the science, despite not having a background in biology, and contribute to the program’s important work. She credits the PanCuRx team for supporting her and helping build her confidence.

She expects to complete her undergraduate program in 2023 and then plans to pursue a research-based master’s degree, and she says her experience at OICR will serve her well.

“It was really exciting to have that view into cancer research,” she says, “and it was inspiring to see how everyone’s work was making an impact on people’s lives.”

OICR Genomics earns internationally recognized accreditation

Stamp of approval from Accreditation Canada Diagnostics (formerly IQMH) will provide more opportunities to support clinical trials.

New internationally recognized accreditation for OICR Genomics demonstrates the program’s commitment to quality and safety and places it among the top genomics laboratories worldwide.

OICR Genomics earned ISO 15189 Medical Laboratory accreditation from Accreditation Canada Diagnostics — formerly known as the Institute for Quality Management in Healthcare (IQMH) Centre for Accreditation — which audits labs against some of the strictest standards in the world.

“This shows that OICR Genomics is operating at the highest level,” says Carolyn Ptak, Genomics Program Manager and Quality Assurance Lead. “It is a mark of excellence, informing collaborators that we take all necessary measures to produce high-quality deliverables.”

Earning ISO 15189 accreditation from IQMH requires labs to prove high standards in safety, assay validation, equipment, personnel training, analytical techniques and other measures. OICR Genomics is one of just a handful of labs around the world to be accredited for a combined whole genome and transcriptome sequencing assay — a highly complex assay in high demand for modern genomics research.

“We selected our existing validated assays to meet the needs of collaborators, and we will continue to expand and refine our service menu as these needs evolve,” says Ptak.

Accreditation comes after a three-year quality improvement journey that saw OICR Genomics build new infrastructure and reimagine how the lab operates. The hard work of the genomics team and vision of OICR leadership also helped earn the lab accreditation from the College of American Pathologists (CAP) in January 2021.

With many clinical trials requiring labs to be accredited by at least one internationally recognized organization, the stamp of approval from Accreditation Canada and CAP makes OICR Genomics an ideal option for researchers needing all sorts of different assays.

“Our goal is to offer the highest quality genomic assays for basic, translational and clinical research,” says Dr. Trevor Pugh, OICR Senior Investigator and Director of Genomics.

“By holding all of our work to this high standard, our users are assured of receiving highly reproducible and accurate data to power their research programs, including innovative new clinical trials. This high-level of operation would not have been possible without the dedication and tight integration of laboratory, informatics, and quality assurance teams who worked tirelessly on meticulously detailed documentation and extensive validation experiments required for accreditation.”

OICR Genomics is a part of the Joint Genomics Program of the University Health Network (UHN) and OICR, an integrated initiative to support basic, translational and clinical research.

Researchers interested in collaborating with OICR Genomics should contact:

Dr. Carolyn Ptak
Program Manager and QA Lead, OICR Genomics
Carolyn.Ptak@oicr.on.ca

New Chair of patient advisory council taking OICR patient partnership into next phase

Diana Lemaire takes over as Chair of OICR’s Patient and Family Advisory Council from inaugural Chair Antonia Palmer.

Diana Lemaire approached her diagnosis and treatment for stage three colon cancer the same way she approaches most things in life: by asking questions, looking for solutions and framing life changes as new adventures.

“I was very mindful and curious throughout my treatment,” says Lemaire, who underwent surgery and chemotherapy in 2015 and dealt with complications. “Is the quality of care as excellent as others claim it is? How well are processes undertaken?”

These were the same types of questions she has asked over the last 25 years of her career supporting hospital administration, with a focus on evaluation and improving processes. But she says the perspective she gained from the other side of the healthcare system was an awakening.

“Patients and care providers tend to see and experience healthcare very differently. Patients may bring worldviews, expectations, and assumptions that are inconsistent with those of care providers,” she says. “Based on their experience of receiving care, patients may see opportunities for improvement that care providers, researchers and others don’t recognize as they view their work through a very different lens.”

That perspective is what drove Lemaire to become a champion for patient partnership, hoping to bring more diverse perspectives to the table. She began as a patient partner with the London Regional Cancer Program and then the Lawson Health Research Institute, and now she will apply her natural curiosity, experience and unique perspective as Chair of OICR’s Patient and Family Advisory Council (PFAC).

“Patient partnership has really come into its own and there are innovative ways for patient partners to become integrated into OICR’s work,” says Lemaire, who has been a member of OICR’s PFAC since it launched in early 2021.

Lemaire takes over from inaugural Chair Antonia Palmer, who is stepping away after helping form the PFAC and leading it through its first year.

“OICR and the PFAC have come a long way in such a short time, and I’ve loved being a part of it,” says Palmer, an experienced patient partner whose two-year-old son was diagnosed with stage four high-risk neuroblastoma in 2009.

Palmer will now focus on her role as Executive Director of Kindred Foundation and other volunteer commitments, but she says she will be paying close attention to OICR’s progress.

“I think OICR’s PFAC has the potential to play a huge role in the patient partnership space within Canada and even internationally,” she says. “I can’t wait to see what this amazing group accomplishes, and I’m going to continue to watch and learn from them.”

OICR President and Scientific Director Dr. Laszlo Radvanyi says OICR is lucky to work with tremendous patient partners as it continues to strengthen the voice of patients in Ontario cancer research.

“I want to express my deepest thank you to Antonia for her time and tremendous effort in helping to build a foundation for authentic, impactful patient partnerships across all of OICR’s research programs,” Dr. Radvanyi says. “We welcome Diana as Chair of PFAC to build on this success and take us into our next exciting phase of our patient partnership.”

For Lemaire, partnering with OICR was a natural fit. She has a lifelong interest in research and a Master of Science degree in epidemiology and biostatistics. She says that contributing to cancer research is also a way of honouring her cancer journey and that of others.

“Cancer was a unique and life-changing experience, and I want to apply the knowledge I have gained from that experience to benefit others,” she says. “Being a patient partner is a way of using that knowledge and experience to pay it forward.”

***

OICR will soon launch its first organization-wide patient partnership plan, setting out its priorities and activities for the coming years. More news will be published shortly.

Mammography innovator changing how we see cancer

Dr. Martin Yaffe’s research on imaging technologies has helped make breast cancer screening more accurate and improve outcomes for women affected by the disease.

Over nearly half a century researching medical imaging, Dr. Martin Yaffe has literally changed the way we see breast cancer.

He has pioneered new technologies like digital mammography that revolutionized breast cancer screening, and he continues to push forward innovations to detect cancer earlier and diagnose it more precisely.

“I’ve always been interested in early detection of cancer and applying new techniques, because early detection saves lives,” says Dr. Yaffe, a Senior Scientist at Sunnybrook Hospital Research Institute, Professor of Medical Biophysics and Medical Imaging at the University of Toronto and Co-Director of OICR’s Imaging Program.

Finding new ways to see cancer

Dr. Yaffe’s contributions to detecting cancer started back when he was a PhD student at the University of Toronto in the 1970s. Computed tomography (CT) was just being introduced at the time, and he worked on developing some of the underlying hardware for the CT scan, which remains one of the most versatile tools for diagnosing illness.

Then in the early 2000s, after years of research and development, Dr. Yaffe and his collaborators introduced a technique to capture digital images from mammograms. In a huge clinical trial published in the New England Journal of Medicine, they showed that digital mammography was more accurate than film, bringing about a seismic shift in breast cancer screening.

“Since then, nearly all breast imaging done almost everywhere in the world is digital,” Dr. Yaffe says.

More recently, Dr. Yaffe’s lab is harnessing a new three-dimensional imaging tool called tomosynthesis to help identify the deadliest forms of breast cancers. The ongoing TMIST trial compares 3D breast tomosynthesis to standard digital mammography, trialing this new technique against the one Dr. Yaffe helped develop two decades ago.

Unmasking hidden cancers

Dr. Yaffe’s latest project aims to shine light on some of the hardest-to-find breast cancers.

By studying breast density, he found that having dense, fibrous breast tissue puts women at higher risk of developing breast cancer and makes cancer harder to see in standard mammograms.

So Dr. Yaffe’s lab developed a tool that uses artificial intelligence to analyze mammograms and predict the chances that a woman’s breast tissue is “masking” underlying cancer.

In a study funded by OICR’s Pre-Clinical Acceleration Team Awards (Pre-CATA), the tool will be tested in six sites across Europe and North America beginning in the next few months.

Dr. Yaffe hopes this technology will lead to a more precise approach to breast cancer screening. Women with a higher risk of masking can be sent for additional screening, reducing the chances of missing cancers without sending all women for unnecessary and expensive testing.

“If we can identify the group of women who are at high risk and would benefit from other types of imaging, then we’ve done something good,” he says.

Making a visible impact

Dr. Yaffe’s research has earned him several accolades over the years, including an honourary doctorate and an appointment to the Order of Canada. Just a few months ago, he was named to the Royal Society of Canada, one of the country’s highest individual honours in the arts and sciences.

While he appreciates the recognition, he says his motivation comes from improving outcomes for women with breast cancer. Mortality rates for breast cancer have been declining since the 1980s thanks in large part to improvements in screening.

“If a woman participates in an early detection program, chances are her breast cancer is going to be found earlier, smaller, and she will be less likely to die,” Dr. Yaffe says.

He’s also inspired by his colleagues and by seeing how researchers from different disciplines work together. He is currently collaborating across OICR on projects comparing the biomarker and molecular signatures of tumour cells with biomarkers derived from breast imaging.

“It’s a wonderful environment at OICR,” he says. “I get to work with smart, creative people with lots of enthusiasm and great ideas.”

Nearly five decades into his career, Dr. Yaffe helped cancer care evolve from a “blunt” approach where everyone gets the same intervention, to an increasingly precision approach where care is tailored to an individual’s unique needs.

“I think precision medicine is the right way to go and I’m excited about it,” he says. “It has been gratifying to be a part of what has happened so far [and] sometimes I wish I was 30 years younger so I can see everything that is going to happen next.”

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Finding new ways to see cancer

Unmasking hidden cancers

Making a visible impact