Landmark study uses OICR Genomics test to find early signs of cancer in blood

Dr. Trevor Pugh talks about his new paper in Cancer Discovery and how it could help transform screening for people with Li Fraumeni Syndrome (LFS).

People with Li Fraumeni Syndrome (LFS) can never really forget about cancer.

Being diagnosed with LFS, a rare genetic condition, comes with a near 100 per cent risk of developing cancer in your lifetime. And because the disease is hereditary, it also means your parents, siblings and children could face the same unfortunate odds.

Targeted cancer screening programs for people with LFS (as set out by the Toronto Protocol) have gone a long way toward catching cancer early and giving them some peace of mind. But the constant testing can be a burden in itself, especially for people live far away from major hospitals. And even an annual combination of tests that includes bloodwork, ultrasounds and a full-body MRI can’t always find cancer as soon as it develops.

That’s why a landmark study by researchers at OICR, UHN and SickKids and funded by the Terry Fox Research Institute has the potential to transform how people with LFS are screened for cancer and give them a better chance at surviving the disease.

In the study, published in Cancer Discovery, researchers were able to find early signs of cancer in blood samples from people with LFS months before cancer was detected by other tests.

The signs they found were tiny fragments of tumour DNA that circulate in the bloodstream called ‘cell-free DNA’. Cell-free DNA from cancer cells is often detectable before the actual tumour is visible. And because they are in the bloodstream, you only need a simple blood sample to find and analyze them, which is easier on the patient than a taking a biopsy or a having a full-body MRI.

“We were able to detect multiple different types of DNA changes in blood that were a telltale sign that cancer was developing somewhere in the body,” Dr. Trevor Pugh, Senior Scientist at and Director of OICR Genomics, said in a news release.

Pugh co-led the study with Dr. David Malkin (SickKids) and Dr. Raymond Kim (UHN and the Ontario Hereditary Cancer Research Network). He also oversaw the genetic testing and analysis, which was conducted by the OICR Genomics Program.

OICR News recently sat down with Pugh to discuss this work, what it could mean for people with LFS, and what happens next.

How did you first get involved in this project?

That began many years ago when I first met Raymond Kim from Princess Margaret and David Malkin from SickKids, who are frontline geneticists working directly with patients who have LFS and innovators in the world of clinical genetics.

What resonated with me in speaking to them was the experience of families with LFS. They undergo a huge amount of surveillance to try and find cancer, which is extremely important but can be challenging for them. Many families having to travel long distances and sometimes stay in Toronto for multiple days in a row and get tested.

At the same time, the technology to test blood for signs of cancer – sometimes called ‘liquid biopsies’ – was advancing. So, we wondered what impact liquid biopsies could have on people and families that undergo such intense cancer surveillance.

What did you find as part of this study?
We looked back at blood samples from people with LFS that were taken as part of their regular surveillance.

We first looked at people whose other tests showed they had developed cancer. Sure enough, most of their blood samples tested positive for cell-free DNA. Then we looked at people whose surveillance gave them a clean bill of health. Just over a third of those patients also had signs of cancer in their blood.

So, we had inkling is that what we’re detecting in their blood are the earliest signs of cancer that don’t get picked by other kinds of testing. This was now an opportunity to start combining our molecular data with imaging to see what kind of lead time we were getting.

What’s the next step in this work?
The next step is a clinical prospective study where we’ll try to answer the question “so what?”

In contrast to our past work, we will now be testing cell-free DNA more frequently, every four months, and delivering results back to the managing physicians and their patients. If we see a cancer signal, we will confirm the finding with a clinic visit similar to their regular annual surveillance. This will show us whether we can actually find cancer earlier than the current annual surveillance approach and inform what we can do with that information to help people get treated as quickly and effectively as possible.

This is the really exciting part of the work where we move from retrospective mode, where history is already written, into prospective mode where we can put our results into practice. This new project brought together a big multidisciplinary team, including multiple patient advocates, to roll this trial out across the country.

How could you see liquid biopsies changing the way people with LFS are screened?

As my colleagues and I wrote in another recent journal article, liquid biopsies have the potential to shift the paradigm in surveillance for people with LFS and other hereditary cancer syndromes.

If we get positive findings from our upcoming trial, I could see blood tests ultimately being added to surveillance protocols in between other more intense testing. Then, if the blood test is positive for cell-free DNA, it could be the ‘canary in the coal mine’ that triggers a full screening.

This could go a long way in easing the anxiety that comes with having LFS and knowing you’ll likely develop cancer at some point. It also could improve access to cancer screening for people who live outside of larger cities, because a blood test can be taken just about anywhere.

What was OICR Genomics’ role in the study?

OICR Genomics is the backbone that supported this major collaboration. We worked closely with partners to develop blood biopsy technology that fit the unique needs of the study, and we generated the data that drove this discovery.

As a lab, our team is tailor-made to support these kinds of studies. We do everything from tissue extraction to laboratory work, bioinformatics and reporting, which allows the research teams we partner with to focus on analyzing the data and on engaging with patients.

OICR Genomics will also work with partners to use this technology to support other cutting-edge clinical trials. That means our collaborative efforts will ultimately have an impact on patients at all stages of their journey with cancer.

Blood test detects tumours early in families with cancer

Researchers from The Hospital for Sick Children (SickKids), the Ontario Institute for Cancer Research (OICR) and University Health Network (UHN) have demonstrated that by analyzing patients’ blood samples, they are able to detect cancer earlier in individuals with Li-Fraumeni syndrome (LFS), an inherited condition with an almost 100 percent lifetime risk of developing cancer.

The research, led by Drs. Trevor Pugh and Raymond Kim at Princess Margaret Cancer Centre, UHN and OICR and Dr. David Malkin at SickKids, has been published in Cancer Discovery. The study, which was funded primarily by The Terry Fox Research Institute, would not have been possible without the generosity of the patients who participated.

Li-Fraumeni syndrome is an inherited condition associated with a very high risk of developing cancer —often tumours affecting the breast, soft tissue, brain and other organs. It is caused by changes in the TP53 gene, which encodes a protein that helps to prevent tumour formation and is commonly termed the “guardian of the genome.”

Cancerous cells and healthy cells release pieces of DNA into the blood. By analyzing these DNA fragments, researchers are developing methods to detect whether a tumour has developed in the body. Testing blood samples for signs of cancer – often called liquid biopsies – is an attractive screening approach compared to imaging methods, which require specialized machines, and biopsies, which are more invasive.

The research team analyzed 170 blood samples from 82 individuals with Li-Fraumeni syndrome collected over several years, as well as 30 blood samples from individuals without Li-Fraumeni syndrome, providing a proof-of-principle framework that may support the detection of specific cancers earlier for individuals with Li-Fraumeni syndrome.

For Luana Locke and her family, early detection is invaluable and has prolonged her life many times already. Luana was diagnosed with breast cancer at age 25 and later discovered that her mother, children and many members of her extended family carried the same TP53 genetic change.

Luana, who has since had sarcoma, lung cancer, thyroid cancer and skin cancer, and her children have regular screenings, blood tests, MRIs of the entire body, and ultrasounds at Princess Margaret Cancer Centre and SickKids, to detect cancers early. After years of these scans Luana’s daughter, Juliet, was diagnosed with leukemia at age 14, a condition they have since learned may have been detected months earlier with this new blood sample analysis.

“Even though I have LFS, I never really felt cancer anxiety until after I was diagnosed,” says Juliet. “While my check-ups are reassuring, getting more precise diagnoses earlier is the next level in care.”

Dr. Malkin has been monitoring Luana’s children for almost 20 years, including her son who was one of the first people to follow a cancer surveillance protocol known as the “Toronto Protocol,” while Dr. Kim has been monitoring Luana for almost 10 years.

“This is a full circle moment for us. From being part of the first Toronto Protocol to what may now be the next step in early detection and diagnosis for families with LFS, our family has relied on the advancements made at SickKids and The Princess Margaret,” says Luana. “Regular scans and check-ups are routine when you have LFS, but the ability to predict when and where cancers develop rather than react when one has already developed would be life changing.”

The team will conduct a clinical trial to further test this approach and screen patients in the hope of finding their cancer earlier. These patients will include those with different types of high-risk cancer predisposition syndromes, including Li-Fraumeni syndrome, Lynch Syndrome, and Hereditary Breast and Ovarian Cancer; all of which are brought under a nation-wide research consortium that Drs. Pugh and Kim founded in 2017.

This work was supported by the Terry Fox Research Institute (www.tfri.ca) and Terry Fox Foundation, Canadian Institutes for Health Research, TD Ready Challenge, the McLaughlin Centre at the University of Toronto, Shar Foundation, FDC Foundation, Bhalwani Family Charitable Foundation, Karen Green and

George Fischer Genomics and Genetics Fund, Lindy Green Family Foundation, The Devine/Sucharda Charitable Foundation, SickKids Foundation, The Garron Family Cancer Centre, Children Tumour Foundation, The Princess Margaret Cancer Foundation and the Ontario Institute for Cancer Research. This work would not have been possible without the generosity of the patients who participated in this study.

Quotes

“Until now, the ways we did surveillance in children with cancer or in children with a genetic predisposition to cancer have been burdensome to families and the health care system – relying on multiple visits to the clinic, imaging tests and imprecise blood tests,” says Dr. David Malkin, Staff Oncologist, Senior Scientist and Director of the Cancer Genetics Program at SickKids and a Professor of Paediatrics and Medical Biophysics at U of T. “Now, we can use a simple blood test to identify when, and sometimes where, a cancer is occurring. That is precision. These promising findings can be extended to all hereditary cancer syndromes to help improve the accuracy of cancer detection, especially for common tumour types, utilizing several analysis types that leverage different biological measurements.”

“We used a combination of genomic, fragmentomic and epigenetic methods to analyze patients’ blood samples at a molecular level,” says Dr. Trevor Pugh, Senior Scientist at Princess Margaret Cancer Centre and Director of the Ontario Institute for Cancer Research (OICR) Genomics Program, where blood samples were analyzed. “The key to these long, multi-year studies is keeping up the momentum and building infrastructure to enable comparisons of multiple types of data over time. Here, we were able to detect multiple different types of DNA changes in blood that were a telltale sign that cancer was developing somewhere in the body months before cancer would show up in imaging.”

“Each of these methods were able to detect cancer-associated signals in the samples, but the integration of multiple analysesprovides a more holistic view of tumour DNA events. This more robust approach is paramount in early cancer detection where the stakes are high.” says Dr. Raymond Kim, Medical Director of Cancer Early Detection at the PM’s Bhalwani Familial Cancer Clinic and lead of the Ontario Hereditary Cancer Research Network at OICR. “To improve the accuracy of early-stage cancer diagnoses, such genetic tests can be used to complement other clinical screening methods, and they can be performed at a higher frequency.”

For more information, or to speak to the researchers involved, please contact:

Marina Jimenez
Communications Director, Princess Margaret Cancer Centre
Email: marina.jimenez@uhn.ca

Sarah Warr
Senior Communications Advisor, The Hospital for Sick Children (SickKids)
Email: sarah.warr@sickkids.ca

Student researcher collaborating with Indigenous community to improve cancer screening

OICR is hosting Jayson Pomfret as part of a unique summer internship program.

Jayson Pomfret understands that meaningful cancer research happens in the community as well as at the lab bench.

Pomfret is an undergraduate student in Queen’s University’s Bachelor of Health Sciences program who wants to pursue a career in medicine and science. He also believes strongly in population health research, and he is pursuing that interest during a unique summer internship.

Pomfret is part of the BioCanRx Indigenous Student Summer Internship Program co-funded by OICR and based at Sunnybrook Hospital. He is spending his summer contributing to a research project that aims to revamp communications materials for cancer screening programs in the Sioux Lookout First Nation in Northwestern Ontario.

OICR News recently asked Pomfret about his goals for the internship and for his future.

Why did you decide to study health sciences?

I’ve had interest in health sciences and medicine since I was younger, and that interest solidified when I had the opportunity to do a youth exchange program in the Czechia. I was hosted by two different physicians and their families while in the Czechia and I got an inside look at what it’s like to balance clinical practice with research, public health advocacy and other non-clinical medical-related interests. The ability to blend a professional career in medicine with a personal drive to better public health and undertake important research astounded and interested me quite a lot.

The project you’re working on during your internship is focused on population health for the Sioux Lookout First Nation. Why did that project interest you?

I’ve done significant academic course work in global population health as well as Indigenous population health. This project interested me because it applies that population health lens to improve cancer screening in a community where it is very much needed. And, as an Indigenous student myself, I find it imperative to use my time and resources to conduct research that can directly benefit Indigenous populations.

Can you tell us more about the project?

Indigenous populations, and specifically the Indigenous population in Northwestern Ontario, are dying of cancers like colorectal cancer at a significantly higher rate than people in Southern Ontario. One of the best ways to remedy this inequity is through effective cancer screening. But the current letters and forms sent out to the Sioux Lookout community and other communities across Ontario about the colorectal cancer screening program are quite technical and are certainly not representative of Indigenous health needs or longstanding cultural health knowledge.

My research is focused on integrating cultural safety within the ways the colorectal screening program and other screening programs under Ontario Health are communicated to the communities under the healthcare oversight of the Sioux Lookout First Nations Health Authority. I think it’s necessary to overhaul those communication materials before we can look at other interventions, so that there can be a higher level of screening to address cancer inequities in a prophylactic manner.

Can you tell us more about ‘cultural safety’ and what it means in this project?

It boils down to a couple of things in this context. One aspect is data sovereignty, and the ability for Indigenous populations to control their own data, have access to that data, and own that data. I had the opportunity to travel to Thunder Bay and speak with members of the community regarding data sovereignty. What I heard was that the community has very little trust that their data will be protected, respected and represented accurately. So that trust needs to be rebuilt.

The other aspect is making sure communications strategies around cancer screening recognize and respect Indigenous knowledge and the sacred traditions of healthcare in those communities, which isn’t the case currently.

What are your goals for your internship?

Though it’s only a three-month internship, I’m hoping to make significant contributions to the project by building relationships with the community in Sioux Lookout and listening to their needs. I think that’s the most important thing, to listen to people and hear their priorities for cancer screening, instead of just trying to overhaul the screening program from the perspective of somebody who lives in Southern Ontario.

Personally, I hope to gain a whole new perspective on research and how it can lead to actionable policy outcomes. I think that will open a wide variety of different paths I can take with my career alongside medicine.

CanPath partnership sheds light on COVID-19 immunity across Canada

Study untangles relationship between vaccination status and infection risk.

New findings from a Canada-wide collaboration that includes CanPath (the Canadian Partnership for Tomorrow’s Health) show that more than three quarters of people in Canada now have immunity to the virus that causes COVID-19 through prior infection.

The study, published in the Canadian Medical Association Journal (CMAJ) by the COVID-19 Immunity Task Force (CITF), is the first peer-reviewed publication showcasing pan-Canadian estimates of seroprevalence, which refers to how many people have developed antibodies in response to infection or vaccination.

“We aimed to untangle the relationship between vaccination status – including the number of doses, brands, and time between doses – and infection risk while accounting for prior infection, adherence to recommendations from public health officials and other factors which impact immunity such as age,” says Dr. Kimberly Skead, National Scientific Coordinator for CanPath.

CanPath, which is hosted by OICR, is the country’s largest population health study. In 2020, CanPath and partners across the country were tasked by CITF and the Public Health Agency of Canada (PHAC) to develop and support a national COVID-19 serological surveillance study.

CanPath has since collected COVID-19 data from over 100,000 Canadians at three different time points up until March 2023.

“CanPath’s extensive participant base has been instrumental in enabling us to find these differences in exposure and immunity across Canada,” says Dr. Philip Awadalla, National Scientific Director for CanPath, Professor of Molecular Genetics at the University of Toronto and Director of Computational Biology at OICR. “The results from our studies, combined with the wealth of data and ongoing research from our collaborators, can contribute to different vaccine responses as the pandemic progresses.”

Using aggregate data from various collaborating pan-Canadian teams, the CITF estimated infection- and vaccine-related seroprevalence trends. In the pre-vaccination and vaccine roll-out phases, few people showed SARS-CoV-2 infection in their blood – 0.3 per cent and nine per cent respectively.

But in mid-June 2022, infection rates increased to 47 per cent. Then they increased to 75 per cent by March 2023. Infection appears to be slowing, though it continues to rise amongst older adults.

Researchers say that certain measures can be taken to ensure that our ongoing narrative remains one of resilience, adaptability, and safeguarding our collective well-being.

“Given the lingering risks of post-COVID conditions and the vulnerability of certain individuals to severe outcomes, a proactive approach is essential,” says Dr. Victoria Kirsh, Scientific Associate at the Ontario Health Study, Assistant Professor at the Dalla Lana School of Public Health. “To safeguard against future variants, it’s important to continue monitoring COVID-19’s spread and roll out booster campaigns ahead of upcoming waves.”

This was adapted from an article by CanPath (the Canadian Partnership for Tomorrow’s Health).

The Next Generation: Tom Ouellette

PhD student harnessing computational tools to make a difference for cancer patients.

Tom Ouellette wouldn’t have predicted that he’d pursue cancer research.

However, he had an interest in computational tools and wondered how they could be harnessed to study biological questions, which led him to undertake a PhD in Computational Biology at the University of Toronto. It wasn’t until he rotated into Dr. Philip Awadalla’s lab at OICR that Ouellette became passionate about studying cancer.

Now, he’s using that passion to build computational tools to predict how cancer progresses – tools that hopefully one day make a difference for cancer patients.

“I was confronted with this sobering fact that almost everyone will know someone that has cancer,” Ouellette says. “This turned my pure biological interest in cancer research to something where I want to build tools that matter for a patient’s journey.”

Find out more in Ouellette’s The Next Generation video.

OICR introduces groundbreaking test proven to find traces of cancer in blood

The highly sensitive Plasma Whole Genome Sequencing assay is available for clinical research studies for any tumour type through OICR’s accredited genomics lab.

A new blood test proven to detect residual signs of cancer could revolutionize how treatments are monitored and assessed, and it’s now available to research studies through the Ontario Institute for Cancer Research (OICR).

OICR Genomics’ Plasma Whole Genome Sequencing assay tests patients’ blood for the unique molecular fingerprint of thousands of mutations unique to their individual cancer. This broad approach enables highly sensitive detection of tiny pieces of tumour DNA that are shed into the bloodstream by cancer cells — a sign that cancer is still present even when it’s not detectable with other tests.

Tests that use blood samples, known as ‘liquid biopsies’, are an exciting alternative to traditional biopsies because collecting blood samples is easier and less invasive than surgical removal of tumour tissue.

“We have been sequencing whole genomes from tumours for three years now,” says Dr. Trevor Pugh, OICR Senior Investigator and Director of Genomics. “This test is an evolution of that capability to start looking for fragments of the cancer genome in blood at an extremely low level. Now, we can support a whole new type of clinical trial design whereby a blood sample can tell a physician very early on whether an initial treatment is working or whether a patient should be expedited to an alternate therapy.”

The test, which is currently only available to clinical trials, works in conjunction with OICR’s other genome sequencing services. Patients can have DNA from a tumour sample sequenced to help diagnose their cancer and direct them to a personalized treatment. Then they can have a blood sample taken during or after their treatment to see how effective it was, and whether their cancer is likely to recur.

Because the test can detect even a small number of cancer cells, it can help find cancer recurrence early so that it can be treated before it comes back fully.

Developed by OICR Genomics over the past 14 months, the Plasma Whole Genome Sequencing assay meets all standards for accuracy, sensitivity, specificity, and reproducibility. It adds to OICR Genomics’ world-leading genomics services, which include the latest in whole genome and transcriptome sequencing technology.

“The most challenging part of validating these tests is having matched, high-quality blood and tumour samples for comparison. We were fortunate to collaborate closely with the OCTANE study at the Princess Margaret Cancer Centre that had the foresight to bank blood plasma samples perfectly matched to the tissues used to validate our original tumour test,” Dr. Pugh added.

OICR Genomics is also the first lab in North America to be accredited by the three major accreditation organizations for whole genome and transcriptome sequencing: Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologists (CAP) and Accreditation Canada Diagnostics (ACD).

“This means that researchers and clinicians can feel confident that our services meet the highest possible standards,” says Dr. Carolyn Ptak, Senior Program Manager and Quality Assurance Lead for Genomics at OICR. “And this new assay is no exception.”

“This world-first assay is an exciting development for clinical research in Ontario and around the world, and a major step forward in our ability to provide personalized treatment to everyone with cancer,” says OICR President and Scientific Director Dr. Laszlo Radvanyi. “It is another example of how OICR is leading the charge in developing innovative and cutting-edge technologies that benefit cancer patients. Congratulations to OICR’s Genomics team and everyone who made this tremendous achievement possible.”

Find out more on the OICR Genomics website.

Ask a Cancer Researcher: What happens to samples donated to tumour banks?

Dr. Dianne Chadwick, Associate Director of the Ontario Tumour Bank (OTB), answers an interesting question from the public.

Before she had cancer surgery, Diana Lemaire was asked if she wanted to donate her tumour to a tumour bank so that it could be used in cancer research.

So she was wondering: what happens to tumours that are donated to a tumour bank?

Ontario Tumour Bank Associate Director Dr. Dianne Chadwick provides the answer in the latest instalment of our Ask a Cancer Researcher video series.

See her answer below and submit your own question if you’d like to be featured in an upcoming video.

The ‘incredible’ way the HPV virus causes cancer and what that means for treating it

OICR-supported research could open new avenues to treat cancers of the cervix, head and neck.

The human papillomavirus (HPV) is the driving force behind most cancers of the cervix, head and neck thanks to its unique ability to hijack the human chromosome.

OICR-supported research has uncovered new details about how that hijacking happens and could provide a roadmap for how to stop it.

“HPV has the incredible ability to integrate itself into a human’s chromosomes,” says Dr. Michael Hoffman, a Senior Scientist at Princess Margaret Cancer Centre who led the study with colleagues Dr. Mathieu Lupien (an OICR Investigator) and Dr. Scott Bratman. “Our study focuses on how that integration, and where it takes place, can contribute to cancer.”

The study, published in Genome Biology, describes how HPV DNA inserts itself into its host’s genome and ‘rewires’ the activity of nearby genes.

“When the rewired genes normally play a role in stopping abnormal growth, this can result in cancer,” Hoffman says.

The virus works on human cells by ‘loosening’ chromatin, a ‘package’ of DNA which is normally tightly packed into a cell’s nucleus. This gives the virus access to a cell’s DNA and allows it to make changes to the proteins that regulate cell growth.

“We found that by hijacking the epigenetic machinery of the cell, HPV can induce everlasting changes in a chromosome that predispose to cancer,” says Dr. Mehran Karimzadeh, first author of the study, who performed the research while a PhD student at Princess Margaret Cancer Centre.

Hoffman says his group’s findings about HPV changing human DNA are unique from other studies into HPV and cancer, which have focused largely on the role of HPV’s own DNA. By describing this pathway through which HPV causes certain cancers, this new study could help discover new ways to treat those cancers.

“What we discovered in this study, when combined with DNA sequencing technology, could lead to better assessment of cancer prognosis and more informed treatment decisions,” Hoffman says.

Paying it forward with a patient perspective

Carla Bossart-Pletzer joined OICR’s Patient and Family Advisory Council to help others with cancer overcome the odds, just like she did.

In a matter of a few weeks, Carla Bossart-Pletzer went from visiting the emergency department about a high fever and stubborn rash on her breast to learning she had one of the most aggressive forms of breast cancer.

It was a whirlwind with a shocking result: inflammatory triple negative breast cancer, which has a much lower survival rate than other types of breast cancer.

But Bossart-Pletzer barely had a chance to be shocked. Within days, she was starting chemotherapy to try and shrink her tumour before surgery — a new treatment approach that had only recently become the standard of care.

In the meantime, her scans for metastatic cancer came back clean. By the time she had surgery six months later, doctors found her tumour had shrunk to a fraction of its former size and no evidence of cancer remained her in lymph nodes.

In many ways, everything went right with Bossart-Pletzer’s cancer treatment. Her healthcare providers acted quickly, and her treatment did exactly what it was supposed to.

“All the systems went exactly as they should,” says Bossart-Pletzer, a designer and illustrator based in Sudbury. “Here I am, 18 months later, with no evidence of cancer.”

But her experience with cancer was far from perfect. She still had to go through a year and a half of aggressive treatment that left her with lingering side effects, and she found that the way things operated in the hospitals and cancer centres she visited didn’t feel quite right.

She’s also very aware that things could have gone very differently under other circumstances.

“I have this feeling. Maybe it’s survivor’s guilt,” Bossart-Pletzer says. “But I look at what cancer research has done for me, and how it has changed my future. Now, what can I do to ensure that other people have the same results?”

Just a year and a half since her diagnosis, Bossart-Pletzer is taking action to answer that question by becoming a Patient Advisor and building patient involvement at Health Sciences North in Sudbury and, more recently, joining OICR’s Patient and Family Advisor Council (PFAC). OICR News recently asked her about her early days on PFAC and what she hopes to achieve.

You mentioned that the success of your cancer treatment motivated you to want to give back. Can you tell us more about that?

I think a lot about why things worked so well for me. I know part of it is because I lived in Sudbury, where we have an impressive cancer centre and I was well connected to healthcare people. I also know it’s partly because, as a white woman, I was taken seriously by healthcare providers and was treated expeditiously. Because the reality is, when you look at the statistics with inflammatory breast cancer, it disproportionately affects women of colour in their thirties and forties and is almost always diagnosed at the metastatic stage. So, there’s a certain obligation I feel to make sure that system works as well for others as it did for me.

Is there any area of cancer research that you’re particularly interested in?

I’m still in the early days with OICR, but I’m finding I’m really interested in improving access to clinical trials. As somebody from Northern Ontario, it sometimes seems that people forget that Ontario continues north of Barrie. There’s a huge population of people up here that don’t have access to clinical trials that could help save their lives.

What other impact would you like to have as a patient partner?

I think there’s a misconception that cancer only happens to people under 18 or over 65. But there are unique challenges that come with being a young adult with cancer, and I’d like to bring more attention to them.

For example, I’m only just now able to return to work after a year and a half of treatment. Add that to being a mother in my 30s coming out of a pandemic, and it means every dollar is important. Unfortunately, I had to pay out of pocket for some parts of my treatment. And I was sometimes faced with choices like: do I pay for chemo pills, or do I put my kids in soccer?

How has being a mother influenced the way you approach being a patient partner?

As part of my breast cancer diagnosis, I found out that I have the BRCA1, MSH-6 and ATM genetic mutations, which are hereditary. I have a four-year-old daughter. What is her life going to look like in the future? What decisions is she going to have to make when she turns 18 because she’s scared of getting cancer like her mom? Will I still be alive to help her make those decisions? I don’t know. So, I’m in this window of opportunity to do what I can to make things better for her and for others who may get this cancer in the future.

Fecal transplants bolster melanoma treatment in unique clinical trial

A trial led by OICR Investigator Dr. Saman Maleki used fecal microbiota transplants (FMT) to improve how melanoma patients respond to immunotherapy.

People with advanced melanoma who get a fecal transplant before starting immunotherapy could have better results from treatment, according to a promising clinical trial.

In the trial, published in Nature Medicine, patients were given what is called a fecal microbiota transplant (FMT) from a healthy donor in the hopes of improving their gut health before starting immunotherapy, a new type of treatment that stimulates the body’s immune system to kill cancer.

Currently, immunotherapy works for less than half of patients with advanced melanoma, and side effects can be severe. But earlier research showed a healthy gut microbiome triggers a stronger response to immunotherapy.

“We need treatments for melanoma that we can add to existing immunotherapies to improve overall patient response without adding too much toxicity,” says lead investigator Dr. Saman Maleki, a Scientist at Lawson Health Research Institute, Assistant Professor at Western University’s Schulich School of Medicine and an OICR Investigator. “Our study shows that FMT could be a safe and effective option.”

A total of 20 patients from across Ontario and Quebec were recruited for the trial at the Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal (CHUM) and the Jewish General Hospital (JGH). They were given FMT in capsule form one week before starting immunotherapy.

About 65 per cent of participants saw their cancer improve during the trial, which is higher than the response rate expected from immunotherapy alone (30-40 per cent). Four patients had their cancer disappear completely during the trial — a result Maleki calls ‘remarkable’.

“We are very encouraged by the strong response profile that we observed in this cohort of patients,” he says.

The results also showed that using FMT this way is safe and doesn’t add any additional side effects beyond what is expected from immunotherapy. In fact, FMT may help reduce some immunotherapy side effects, and that potential is being explored in another different clinical trial.

Maleki and colleagues are already working on a larger clinical trial to further explore the effect of FMT and immunotherapy on melanoma. Similar studies are also underway using fecal transplants to treat renal cell carcinoma, lung cancer and uveal melanoma, and there are plans for trials that target pancreatic cancer and breast cancer.

“When I came up with the idea of prospective microbiome modulation in cancer patients in 2016, there was not much enthusiasm in the oncology community,” Maleki says. “Now, we’ve opened the door to using FMT in other cancers in early settings, which could potentially change how cancer patients are treated with immunotherapy drugs in the future.”

This research is supported in part through donor funding from London Health Sciences Foundation, Western University, the Lotte and John Hecht Memorial Foundation, the JGH Foundation, Canadian Cancer Society’s Impact Grant program, The Terry Fox Foundation and OICR’s Investigator Awards. More information is available in an announcement from the Lawson Health Research Institute.

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