How the KiCS research program is changing childhood cancer care

The text comes in on a Friday afternoon.  

A baby girl is at The Hospital for Sick Children (SickKids) with a tumour on her heart. Two open-heart surgeries have already taken place, but because of its location, they can't remove the whole tumour. A heart transplant is beginning to feel like the only path left.  

Across the bridge in the Peter Gilgan Centre for Research and Learning, research labs are winding down for the weekend. The message reaches Dr. Adam Shlien, a Senior Scientist who has never met this little girl.   

He talks to his team and everyone agrees. Samples are pulled, analysts delay their weekend, and sequencing begins. The next day he responds to Dr. David Malkin, the patient's oncologist: "We found it."  

They identified what's called a cryptic fusion, a mutation in the gene of the tumour that is not detectable in standard testing, allowing them to enroll her in a clinical trial for a drug that targets her specific genetic change. 

"What happened next felt like a miracle," says the family. "In just five weeks, the tumour had reduced by half. They gave our daughter the chance to keep living." 

Now, more than a year later, she continues to show signs of improvement.  

For many programs, that story would be the culmination. For the SickKids Cancer Sequencing Program (KiCS), a pioneering research program that has transformed how childhood cancers are understood, diagnosed and treated, it's the point. 

This year marks the 10th anniversary of KiCS. What began as an ambitious idea has blossomed into a decade of impact, influencing care not only at SickKids, but across Canada and beyond. 

Early beginnings  

In 2016, the field of paediatric cancer genomics was still taking shape. New technology was emerging, but most of the time, childhood cancers were treated largely the same way.  

Malkin, alongside Shlien and colleagues across research and clinical care, saw an opportunity: sequence the tumours of children facing the toughest cancers, inform their care, learn for the next generation.  

The vision was beyond the scope of a traditional research program.  

"We were very insistent that there be the return of data clinically, if not in real-time, as close to real-time as possible," says Malkin. "It had to benefit the children we were seeing in clinic."   

Shortly after Dr. Anita Villani, Staff Oncologist, joined the troupe and Villani, Shlien and Malkin became co-directors, each representing a critical piece of the program: clinical care, research, and translation. 

KiCS becomes the home of PROFYLE, a national precision oncology initiative  

In 2017,  SickKids welcomed PROFYLE, a national precision oncology initiative supported by the Terry Fox Research Institute, under its roof. Where the KiCS program focuses on patients at SickKids, PROFYLE supports tumour sequencing for children across Canada, facilitated by the established KiCS infrastructure. 

According to Reem Khan, KiCS' Program Manager, the addition of PROFYLE is emblematic of its ambition to deliver equitable access to care, whether you’re in the GTA or not.  

The blossoming of the Shlien lab and our understanding of paediatric cancer  

As KiCS was maturing, as was the research. New expertise and technologies in genomics, RNA sequencing and machine learning expanded what the Shlien lab could do, and new findings began to emerge.   

In late 2022, the team published an analysis in Nature Cancer of the first 300 patients sequenced, showing at least one clinically actionable variant in 56 per cent of patients and included important implications for family members and relatives by identifying cancer predisposition genes in 17 per cent of patients with a previously undiagnosed variant. Later in 2023, they published in Nature Medicine, showing how they could use the sequencing data and a machine learning algorithm to create an "atlas" of cancer. More recently in Nature, they shared the groundwork for earlier detection of treatment resistance, alongside other findings to guide more precise care.  

Unlike typical research labs, Shlien believes the focus of the lab to provide direct impact to patient care has solidified a culture of research excellence.  

"When graduate students, analysts and scientists know the data they are analyzing belongs to children currently receiving care, it becomes personal for all of us," said Shlien. "That, in effect, changes how science gets done."  

From research to clinic and back again  

While some KiCS milestones were loud, others came softly, quietly influencing the way care was delivered.  

Over the years, the program gradually moved from delivering research findings to delivering clinical findings right away. This means the sequencing itself moved from research equipment to clinically approved equipment, facilitating a direct connection to each child's medical record with more immediately actionable insights. Before this change, research findings always had to be validated again with a clinical test, adding time and additional barriers to returning results to patients.  

"It was a very big step," says Villani. "That shift required scientists, clinicians, pathologists, laboratory medicine experts, analysts and genetic counsellors to work together in ways few programs had attempted before." 

During this shift, dedicated clinical expertise, like from Dr. Sarah Cohen-Gogo, Staff Oncologist and Clinician-Investigator, and Rose Venier, Genetic Counsellor, came on board to help patients understand sequencing results, and connect them to information or potential treatment opportunities.   

"Once we have a result that we may be able to action, we try and move quickly," says Cohen-Gogo. "We get in touch with the family and we explain what innovative drug options might be available."   

Assisting in these efforts is a multidisciplinary team called the Molecular Tumour Board that helps review cases, debate findings, and determine what a result means for each child.  

"It is a beautiful marriage of teamwork and bringing together exquisite expertise," said Villani. "If you isolated any one of those groups, the program would not be the same." 

That marriage has created the model for integrating care and research to deliver tailored treatment, laying the foundation for Precision Child Health, SickKids' movement to deliver individualized care for every child.  

For one patient, for every patient  

Since KiCS launched, hundreds of families have contributed samples, shared data and consented to participate in KiCS. While not every patient benefits from a finding that could change the course of their treatment, together they have created one of the richest paediatric cancer datasets in the country. It's their contribution that improves cancer care for the next generation.  

As a result, many families describe a powerful sense of altruism in participating, beyond their own child’s benefit.  

"Owen's trajectory was so unique," says Casey, dad of 12-year-old Owen, a participant in KiCS. "If they can use any information from him to help other kids, we're all for that."  

The decade ahead  

Beneath the science and sequencing machines, KiCS has always been about something much simpler: What else can we do for this child? 

Now, while still asking the same question, Malkin, Shlien and Villani are looking ahead.

"You don't do this once and stop," says Shlien. "It's a movement where you learn from the research lab, bring it to the clinic, learn from it and then do it again." 

“The original vision for KiCS is yet to be realized,” says Malkin. “With the right resources, we can create a world where we offer sequencing to every child with cancer, not just those with cancers that are hard to treat.”  

"We're going to keep pushing the frontier to the next level,” adds Villani. “That's what we're really excited about."  

KiCS is supported by the Garron Family Cancer Centre through funding from SickKids Foundation, including generous philanthropic support from key donors like CIBC and other partners.