Published: February 2019
For an update on Stefany’s story, click here to see what Stefany is doing now.

A game-changing cancer treatment

Stefany Dupont’s leukemia symptoms have disappeared. Her cancer was put into complete remission by a revolutionary new treatment called CAR T-cell therapy. This emerging form of immunotherapy has the potential to transform how cancer patients are treated in Canada and around the world.

Daunting odds

Stefany was first diagnosed with acute lymphoblastic leukemia (ALL) when she was just 13 years old. Children with leukemia are given a strict chemotherapy protocol that effectively cures more than 90 percent of patients. Unfortunately, this was not the case with Stefany.

She was in remission for five years but, in 2010, her leukemia came back. By then she was 18, an adult, and began receiving treatment at The Ottawa Hospital. In 2015, she received chemotherapy followed by a hematopoietic bone marrow stem cell transplant. She was on the mend until a year and a half later when she had another relapse. Adults with leukemia who relapse after a transplant have less than a 10 percent chance of survival.

“Stefany was unlucky enough to relapse within two years of her transplant,” said Dr. Jill Fulcher, Stefany’s doctor, who specializes in malignant hematology and is a clinician-investigator at The Ottawa Hospital. “But her leukemia came back with a blast and she was very sick. Palliative management was all we had to offer patients with ALL who relapsed so soon post-transplant.”

Dr. Jill Fulcher stands behind Stefany listening with stethoscope — Hematologist Dr. Jill Fulcher confirms that Stefany Dupont is in remission over one year after her CAR T-cell therapy. Previously, Stefany was given a 10 to 20 percent chance of survival, pre-CAR T-cell treatment.

New hope

Dr. Fulcher and her colleague Dr. Natasha Kekre, a hematologist and associate scientist at The Ottawa Hospital, knew that clinical trials in the United States, using CAR T-cell immunotherapy, showed promising results in children and adolescents with leukemia and blood cancers, putting many into long-lasting remission.

For patients like Stefany who are extremely sick and out of options, CAR T-cell therapy offers new hope. That’s why Dr. Kekre is leading the charge to bring CAR T-cell immunotherapy to The Ottawa Hospital.

Giving Canadians access to leading-edge treatments

As one of Canada’s leading research and treatment centres, equipped with world-leading expertise, The Ottawa Hospital is ideally positioned to help bring this innovative treatment to Canada, and to Canadian patients. The Ottawa Hospital is one of the first hospitals in Canada to participate in internationally-led CAR-T trials, and the Hospital is now playing a lead role in a made-in-Canada CAR-T research program.

“Our goal is to build Canadian expertise and capacity for innovation in the promising CAR-T field through both laboratory research and clinical trials,” said Dr. Kekre, who is working with a team across the country. “This could lead to better CAR-T therapies that work for more kinds of cancer, as well as innovative approaches for providing CAR-T therapy in the Canadian system.”

A key component of the program is a clinical trial using the first made-in-Canada CAR T-cell therapy. This trial is expected to open at The Ottawa Hospital and BC Cancer in 2019.

From translational research to trial design to manufacturing, The Ottawa Hospital, alongside BC Cancer, is ideally positioned to shepherd this complex trial of an experimental therapy to our patients.

“It’s well recognized that Ottawa is a world leader in clinical trials and innovative trial designs,” said Dr. Manoj Lalu, associate scientist and anesthesiologist at The Ottawa Hospital who is part of the CAR-T team. “Many of the guidelines produced internationally around trial design and reporting originate from The Ottawa Hospital.”

Hematologist Natasha Kekre — Dr. Natasha Kekre is working with other hospitals across Canada to develop a “made-in-Canada” approach for CAR-T cancer therapy.

About CAR-T Therapy

CAR T-cell therapy harnesses the power of a patient’s own immune cells, known as T-cells, to treat their cancer. T-cells play a critical role in the immune system by killing abnormal cells, such as cells infected by germs or cancer cells. In some cancers, like acute lymphoblastic leukemia (ALL), cancerous cells become invisible to the T-cells that are meant to kill them. In CAR-T therapy the T-cells are collected and reprogrammed in the lab to recognize and destroy the cancerous cells.

“This type of immunotherapy research is groundbreaking,” said Dr. Kekre, “but it is important to remember that CAR-T therapy is still very new and there can be serious side effects. We need more research to learn about this therapy and make it work for even more people.”

A well-deserved reprieve

CAR-T treatment was not yet available in Canada when Stefany needed it. So, her only option at the time was to try to join a CAR-T clinical trial at the Children’s Hospital of Philadelphia. Since the hospital’s clinical trial was still accepting patients with ALL up to 25 years of age, Stefany was eligible to participate.

Three months following Stefany’s CAR T-cell infusion in Philadelphia, she had a bone marrow biopsy that showed she was in remission — her treatment was working.

Three months after that, Stefany went on a well-deserved trip.

“After the sixth month waiting time, I went to Australia,” said Stefany. She visited Sydney, Brisbane, Melbourne, went scuba diving at the Great Barrier Reef, and hang-gliding over the shores of Byron Bay. It was a wonderful break after the intensive treatment.

“It is a really good sign that Stefany has remained in remission for over 2 years after having CAR T-cell therapy,” said Dr. Fulcher. “Without this therapy, she definitely would not be with us today.”

Unique biotherapeutics facility

CAR-T therapy needs to be individually manufactured for each patient, using a patient’s own cells combined with large amounts of highly pure virus to deliver the CAR gene. The Ottawa Hospital’s Biotherapeutics Manufacturing Centre is ideally positioned to manufacture this kind of therapy because it has the most advanced system to make the clinical grade virus needed to create CAR T-cells for clinical trials. This is the only facility in Canada that has produced this kind of virus for clinical trials.

“With our unique manufacturing facility, our expertise in clinical trials and our world-class cancer and hematology programs, The Ottawa Hospital is ideally positioned to lead the way in developing the next generation of CAR-T therapy,” said Dr. Rebecca Auer, Director of Cancer Research at The Ottawa Hospital.

“The Ottawa Hospital is ideally positioned to lead the way in developing the next generation of CAR-T therapy.” – Dr. Rebecca Auer

“Patients with ALL, lymphoma, and other blood cancers could benefit from this experimental treatment,” said Dr. Kekre. The hope is that one day CAR T-cell therapy may also be a treatment for a variety of cancers, such as breast and colorectal cancer. It is through clinical trials conducted at The Ottawa Hospital that innovative cancer treatments will be discovered and will continue to offer hope to patients like Stephany.

Organizations such as BioCanRx, the Canada Foundation for Innovation, and the Government of Ontario have supported The Ottawa Hospital’s CAR-T research and the Biotherapeutics Manufacturing Centre, but additional funding is essential to make this program a reality.

January 2023 update:

It’s been a rollercoaster of a ride for Stefany in the last year. Since December 2021, she’s struggled with lung infections, which she developed as a result of being immunocompromised and because, since 2017, she has important scarring on her lung. Such scars are the result of what happened to her while she was on a months-long waiting list to get to the CAR-T program in Philadelphia. “My [leukemic] condition got worse, I contracted pneumonia with no functional immune system, and despite overcoming it, I was left with considerable scarring on my lung, putting it at risk for various infections.”

It’s for this reason, Stefany is grateful to hear patients in a Canadian-first clinical trial at our hospital are getting access to CAR T-cell therapy right here in Ottawa. “Thankfully, the participants don’t have to go through what I’ve gone through with pneumonia and the waiting,” says Stefany.

She is slowly improving and is hoping to become a schoolteacher in the future. Stefany’s currently tutoring students and has given presentations on social justice topics to secondary school students. She’s also been enjoying some travel recently, including a nature expedition that supports youth affected by cancer and is looking forward to trips to Mexico and Costa Rica in 2023.

Learn more about the Canadian-Led Immunotherapies in Cancer (CLIC) research program, funded by BioCanRx, the Canadian Institutes of Health Research, The Ottawa Hospital Foundation, BC Cancer, BC Cancer Foundation, the Ontario Institute for Cancer Research, the Ottawa Regional Cancer Foundation and the Leukemia and Lymphoma Society of Canada.

The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.

Categories: Biotherapeutics, Clinical Trials, Immunotherapy, World-Leading Research

The “seeds” are one millimetre by three millimetres, a third the size of a grain of rice, and made of platinum. These tiny seeds, created by researchers at The Ottawa Hospital, improve the CyberKnife robot’s accuracy in detecting and delivering precise doses of radiation to tumours in the brain and body.

Hand holding a grain of rice and platinum seed — *Platinum seeds, a third the size of a grain of rice, are improving the accuracy of CyberKnife treatments.*

CyberKnife uses X-rays and complex precision software to track and focus radiation directly to the tumour. With accuracy of less than a millimetre, there is virtually no radiation spill over to normal tissue. As a result, patients have much better responses to this type of treatment compared with traditional radiation where a larger area is targeted.

“Because CyberKnife delivers a high dose, it’s considered similar to surgery without using a scalpel, so no blood loss, no pain, no ICU stay, or recovery time,” said Dr. Vimoj Nair, one of the radiation oncologists trained to prescribe CyberKnife treatment.

Ninety percent of CyberKnife treatments are for malignant or benign brain tumours, but CyberKnife’s image guidance system can also treat tumours in organs that move constantly, such as the lungs, kidneys, liver, prostate gland, and lymph nodes. It can precisely align the radiation beam to the tumour even when it moves. But radiation oncologists and researchers at The Ottawa Hospital are refining techniques to further enhance the performance of this state-of-the-art technology to improve patients’ outcomes. These techniques are ultimately changing radiosurgery practice.

*Radiation oncologist Dr. Vimoj Nair said platinum seeds improve the accuracy of CyberKnife radiosurgery.*

“One unique thing that the CyberKnife research team at The Ottawa Hospital has come up with are in-house designed platinum MRI-compatible seeds that can be implanted around the moving tumour,” said Dr. Nair, who is also a clinician investigator at The Ottawa Hospital and an assistant professor at University of Ottawa. “We can see the tumour and the seeds better on the MRI, and the CyberKnife software can detect and track the motion of the tumour with the help of these seeds. The robotic arm of the CyberKnife matches the target motion to treat the tumour more accurately while the patient breaths normally.”

The Ottawa Hospital is one of the first centres in North America to use these platinum seeds. In the past, oncologists used tiny gold seeds, but they were difficult to see in the MRI sequences used to view the tumour. This made the treatment planning less accurate. Dr. Janos Szanto, medical physicist, and Dr. Len Avruch, radiologist (now retired), were the initial brains who took platinum wire (otherwise destined to be jewelry), cut it into minute pieces, and then put through a sterilization process to ensure the seeds were appropriate for insertion into the human body. It worked. They were visible to the naked eye, more visible in an MRI than the gold seeds, and could be detected by CyberKnife.

Julie Gratton with patient beside CyberKnife robot — *Radiation therapist Julie has delivered CyberKnife treatments since 2010.*

“The benefit of this technique is we see both our target and seeds more clearly together, which provides the best use of advanced imaging and improves the accuracy,” said Dr. Nair, who called the discovery novel research and application that positions The Ottawa Hospital very favourably on the world stage.

Dr. Nair was the first author on the research paper published about the platinum seeds. He said that researchers and clinicians are continually sharing innovative CyberKnife techniques they’ve developed, like this one, at conferences and with other health centres across Canada and globally. In September 2018, he gave presentations on The Ottawa Hospital practices on clinical uses of CyberKnife at a conference in India.

“We can see the tumour and the seeds better on the MRI, and the CyberKnife software can detect and track the motion of the tumour with the help of these seeds.”

Read more about the history of the community-funded CyberKnife at The Ottawa Hospital.

The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.

Categories: Innovation and Technology, Technology, Technology

When a routine mammogram identified a small tumour, Rita Nattkemper was given an innovative option to mark its location for the surgery. A radioactive seed, the size of a pinhead, was injected directly into the tumour in her breast.

“All I have to say is it’s a painless procedure to get this radioactive seed in and it helps the doctor with accuracy,” said Rita. “And as he removes the mass, he’ll be removing the seed at the same time.”

For the last 20 years, when a woman had a breast cancer tumour that was too small to feel or be seen in surgery (called a non-palpable tumour), she had to have a wire (known as a harpoon) implanted at the tumour site to locate it for the surgeon. The wire, which stuck out of the woman’s breast, had to be inserted the morning of her surgery. Then, women had to wait uncomfortably for surgery with the wire sticking out of their breast. To add to the discomfort, many women had to fast overnight to prepare for surgery, causing many to faint in the radiology suite at the sight of the wire protruding from their breast.

The procedure also posed other problems.

“Sometimes the wire moved. And sometimes, because of the location of the tumour, the wire might overshoot or undershoot the tumour, so ultimately there was an enormous amount of guess work involved in taking out a breast cancer tumour properly,” said Dr. Carolyn Nessim, surgical oncologist, and clinician-investigator in the Cancer Therapeutics Program at The Ottawa Hospital.

Dr. Nessim, and other breast oncology surgeons, wanted to find a better option.

Dr. Carolyn Nessim surgical oncologist and clinician investigator at The Ottawa Hospital and assistant professor at the University of Ottawa, led The Ottawa Hospital team in developing a radioactive seed program here in Ottawa.

That was where radioactive seeds came in. Radioactive seeds have been used for many years to treat prostate cancer. Multiple seeds are implanted in the prostate, where they emit radiation and kill the cancer. Then a procedure was developed for breast cancer patients using a radioactive seed to mark the exact location of small breast-cancer tumours. Using a mammogram for guidance, a radiologist places one seed, so tiny it can be safely injected with a needle, inside the tumour. It emits a very small amount of radiation that is picked up in the operating room with a small, handheld Geiger counter. After the piece of breast tissue with the radioactive seed is removed, the seed is separated from the tissue and appropriately disposed of, with every seed being accounted for.

Realizing the benefits of this procedure, The Ottawa Hospital began a radioactive seed program in 2015. One of the main benefits is that the seed can be placed up to a week before surgery, which makes the day of the operation easier for patients. A woman doesn’t have to wait for surgery with a wire sticking out her breast. From a logistical point of view, it’s easier to organize the procedure days in advance, and means more efficiency in the operating room. Dr. Nessim led a research study comparing seeds to wires, which showed the benefit of seeds.

“The results of the radioactive seed program have been uniformly excellent,” said Dr. Erin Cordeiro, breast surgical oncologist and senior clinician-investigator at The Ottawa Hospital. “We did a study that found that radioactive seeds were more cost effective and decreased wait times for patients on the day of surgery when compared to wires. And the patient experience has also been wonderful. Patients are very supportive of this.”

Rita agrees. She said the surgeon and radiologist both explained the procedure and put her at ease about it.

“I felt a minor pinch, and that was all I felt,” Rita said immediately after the procedure. “And the radiologist had the screen turned, so I could see where she put in the needle and left the seed. It was very easy, very quick, and very painless.”

Dr. Cordeiro said women are often concerned about the seed’s radioactivity, but the staff reassures patients the procedure is completely safe. The amount of radiation that is emitted in the week the patient has the implanted seed is less than having two mammograms.

“A woman can continue to hug her children and do everything in life she would normally do,” said Dr. Cordeiro. “No concerns from that point of view. It’s an extremely safe procedure. The vast majority of women have no concerns.”

Over the past year, 355 radioactive seed procedures have been performed at The Ottawa Hospital. Only two patients have refused the seeds and opted for the traditional wire instead.

Because of the program’s radioactive element, there were stringent guidelines around starting the program.

A multidisciplinary team of nuclear medicine, radiation safety experts, radiologists, pathologists, surgeons, technicians, and nurses were involved.

Key members of the team, led by Dr. Nessim, went to the Mayo Clinic in Rochester, N.Y., to learn how to implement the program. They then ran 15 training sessions for staff at The Ottawa Hospital. The radioactive seed program now “runs like a well-oiled machine,” said Dr. Nessim.

The Ottawa Hospital was the third centre in Canada to have a radioactive seed program, and is a leader in the procedure. Other health centres across the country are now adopting it and looking to The Ottawa Hospital for guidance in successfully implementing their program.

The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.

Categories: Cancer, Cancer, Cancer, Cancer, Innovation and Technology, Technology

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