Research Archives

Identifying Increased Risk for a Cancer Predisposition Syndrome

Posted on September 13, 2019 by Claire Slaughter

This POGO-funded research is helping children with its early detection of cancer predisposition syndromes.

Approximately 10% of children diagnosed with cancer have an underlying cancer predisposition
syndrome (syndrome), a condition (often inherited) that increases their risk of developing one or many cancers throughout their life. Genetic testing can be used to identify children with a syndrome, but to avoid unnecessary testing and possible delays, physicians need a way to determine which children to test.

There are over 125 syndromes known to be associated with cancer in children. In some cases, knowing whether a child has a specific syndrome will change the treatment. Identifying a syndrome also allows the healthcare team to develop a care plan to monitor the child for future cancers once treatment is complete, and to recommend monitoring for siblings.

In 2017, Dr. Catherine Goudie was awarded a POGO fellowship for her project “Identifying Children at Increased Risk for a Cancer Predisposition Syndrome: The McGill Interactive Pediatric Oncogenetic Guidelines.” Overseen by principal investigators Dr. David Malkin and Dr. William Foulkes, the project aims to develop an e-Health tool that doctors can use to help them decide which children should be referred for genetic testing.

Related Story : A Genetic Mutation: A Lifetime of Cancer Screening

Prior to becoming a POGO Fellow, Dr. Goudie and her team in Montreal spent three years building
approximately 90 algorithms for each type of childhood cancer. These yes/no questions relate to
items such as the age of the child, features of the tumour and family history. The first version of the
tumour algorithms was reviewed by genetic and oncology experts from Canada, the United States
and the United Kingdom.

The aim of the POGO-funded research was to support Dr. Goudie in her work to evaluate the performance of the tool with children at 11 Canadian hospitals. The evaluation was split into two streams.

Dr. Catherine Goudie, MD, FRCPC

“Our first priority was making sure this tool would do no harm,” says Dr. Goudie. “In order to do this, we looked at patients in Canada who have already been diagnosed with a cancer predisposition syndrome and who developed a cancer in childhood, meaning their physicians successfully identified the syndrome without our tool. We confirmed that our algorithms would have identified these children for genetic referrals at the time of their cancer diagnosis, therefore confirming that the tool performs at least as well as clinicians have.”

The second stream of the evaluation is ongoing and leverages precision medicine research at The Hospital for Sick Children and other hospitals in Canada and the US. These institutions are doing comprehensive genetic sequencing on pediatric cancer patients, meaning that all children undergo genetic evaluation regardless of whether they are suspected to have a syndrome.

“We will test our algorithm on the medical profiles of these children to determine if the tool indicates that the child should be referred for genetic assessment. We will then compare our results with those obtained from the patients who participated in the comprehensive genetic sequencing. Therefore, we are prospectively testing the performance of our tool.”

Dr. Goudie explains that, in most hospitals worldwide, the facilities, human resources, infrastructure, expertise, or funding to offer comprehensive genetic testing in all kids diagnosed with cancer are not available. Ultimately, the goal of the tool is to give children with a syndrome the opportunity to be diagnosed and treated appropriately. In addition, the tool can be used to educate medical professionals around the world.

Dr. Catherine Goudie received a prestigious clinical investigator award from the FRQ-S in Quebec and returned to Montreal in July 2018 to continue this research as a collaboration between the Montreal Children’s Hospital and The Hospital for Sick Children. The FRQ-S is a government organization that, annually, funds select clinician investigators in Quebec to do health research.

“For someone young like me, who doesn’t have a lot of experience, having POGO to support my work was a huge stepping stone. I am certain that POGO’s support and the credibility that this organization has internationally, helped me get this next award in Quebec. I am really grateful for this opportunity.”

This story was featured in POGO’s 2018 Community Impact Report.
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Is Overprotective Parenting Linked to Anxiety and Depression?

Posted on January 30, 2018 by Kelly Zorzi

#BellLetsTalk #mentalhealthawareness

Ms. Amanda Sherman, BA, MA, PhD(c), discusses her POGO-funded research study.

Your study looked at overprotective and overcontrolling parenting. Can you give us some examples of these two parenting styles?
I would define overprotection as a style of parenting that does not allow the child or emerging adult to experience stressful things. These parents might try to reduce harm even where the situation doesn’t require it. An overprotective parent might call their child’s friends to solve a problem or insist on driving them to destinations where they can easily walk or ride a bike. It is excessive care. Overcontrolling parenting has more to do with discipline and getting a child to behave in a specific way. A parent might say, “You can’t go out tonight because I don’t like some of your friends.” It is excessive control.

What is non-productive coping?
Coping strategies that are not effective in helping that person feel better (worrying, swearing,
avoidance and isolation, for example) are nonproductive because they may lead to more distress and anxiety. In children, one correlate of the development of anxiety disorders is overprotective parenting.

Are childhood cancer survivors more at risk for depression and anxiety?
When looking at levels of depression, we did not find that our sample differed significantly from normative populations; but we did find that anxiety levels were markedly higher than the general population—participants’ scores on our questionnaire were within one standard deviation from the mean score of people with anxiety disorders. That was surprising to me and something we don’t yet know how to account for. Maybe for this population so much of their childhood was focused on getting better, that learning to cope with stress was less important than getting by and managing their illness. Now they are emerging adults and they are facing the potential late effects of their childhood disease, as well as regular life stresses, and perhaps they are less equipped to cope. These are hard questions to answer.

Amanda Sherman, BA, MA, PhD(c)

Ms. Amanda Sherman, BA, MA, PhD(c) was the recipient of the 2013 POGO Fellowship Award. Her research focused on maternal overprotection/overcontrol and its relationship to coping strategies, anxiety and depression in survivors of childhood cancer. Her study looked at 109 survivors aged 18-30 attending the POGO AfterCare Clinic at Princess Margaret Cancer Centre. POGO AfterCare Clinics monitor survivors at regular intervals so that potential long-term effects of treatment can be identified as early as possible.

You are doing your PhD in psychology. How did your career path lead you to study childhood cancer patients?
I did a practicum placement with Norma D’Agostino at Princess Margaret, where I was doing therapy exclusively with young adult survivors of childhood cancer. We noticed that problems with lack of autonomy, separating from parents and non-productive coping strategies kept coming up.

What can we take away from this research?
Now that we have this evidence that says overprotective parenting and anxiety are an issue in this population, we can target those parents and teach them how to socialize coping in their children. Even the oncologist can spend five minutes asking the parents and children a few targeted questions to
determine if there is a bigger issue, flag it, and refer the family to a psychologist to help them develop better coping skills.

What do you hope will come from your study?
This is preliminary research but even posing the question is opening doors and people are looking for potential issues when perhaps they weren’t looking for them before. Next steps from a research standpoint: our measure of overprotective and overcontrolling parenting needs to be validated and the study needs to be replicated with a non-cancer control group. I want to disseminate this research any way I can.

What does this POGO Fellowship Award do for your career?
This grant has allowed me to have time, space and community to do research. What I have enjoyed so much about POGO is how open minded everyone is about psychosocial issues, and psychosocial development. It has been nice to be accepted and encouraged for studying these kinds of issues, and working with medical professionals has helped provide a different perspective. It has been humbling, rewarding and encouraging at the same time.

An Economic Evaluation of a Promising New Treatment for High-Risk Leukemia

Posted on December 15, 2017 by Kelly Zorzi

POGO-FUNDED RESEARCH: An Economic Evaluation of CAR-T Therapy

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and for most patients, the standard chemotherapy protocol works very well with an overall cure rate of 90%. But, there is a subset of this population that is treatment resistant. For these young patients, a relatively new therapy called chimeric antigen receptor T-cells (CAR-T) therapy may be the answer.

CAR-T therapy uses the patient’s own immune system to do the work of destroying the ALL cancer cells. It starts with harvesting immune cells called T-cells from a patient’s blood. Millions of copies of these cells are grown in a lab—engineered to recognize, target and destroy the cancer cells—then infused into the patient’s bloodstream. Once back in the patient’s body, the cells divide and increase in number, creating a massive army against leukemia cells. Importantly, unlike an infusion of a drug, these cells can remain in the body indefinitely, providing constant surveillance against ALL’s return. The results to date are promising, but not without significant risk.

“Like most cancer therapies, CAR-T cell treatment can have severe and potentially fatal side effects,” says Dr. Alexandra Zorzi, pediatric oncologist at Children’s Hospital, London Health Sciences Centre. “The ‘activation’ of your own immune system can lead to the release of too many cytokines, which can result in laboured breathing, high fevers, and potentially life-threatening decrease of blood flow to internal organs.”

But when it works, it works miracles. At least that is what we know in the short term. “CAR-T cell therapy has the potential to be a major game changer in childhood ALL,” says Dr. Paul Gibson, medical officer with POGO. The early results have shown remarkable response rates, even in children who have been heavily treated for ALL previously. Not only is the response rate impressive, but so are the sustained remissions many patients are experiencing. “This is the first true gene therapy in childhood cancer therapy,” says Dr. Gibson. “While very expensive upfront, it may not only save lives, but save children from needing to be treated many more times in the future.”

Currently, this therapy is only offered at the Children’s Hospital of Philadelphia. The cost to send an Ontario patient for treatment is close to $500,000, not including the cost to families who often have to leave work and home for several months.

Petros Pechlivanoglou, PhD

In 2016, POGO awarded Dr. Petros Pechlivanoglou with a seed grant for his project “Economic Evaluation of CAR-T Therapy for Children with High Risk Relapsed ALL.” Dr. Pechlivanoglou and his co-investigators—Drs. Sumit Gupta, Jason Pole, Paul Nathan, Tal Schechter-Finkelstein and Wendy Ungar, together with PhD student Jill Furzer—are using statistical and mathematical modelling to determine the value of CAR-T therapy from a clinical and economic perspective. What is the trade-off between the treatment’s effectiveness and its cost to the Canadian healthcare system and society overall? Where should we focus our efforts to collect more evidence in the future? And, how will this information be used to inform policy decisions?

“This economic evaluation of CAR-T therapy is only one example of new therapies,” says Dr. Petros Pechlivanoglou. “As new cancer innovations emerge, both in the pediatric and the adult world, we are going to have this challenge of understanding the ‘value-for-money’ proposition again and again. This grant will help us tease out the methods needed to find timely answers to such questions and make prioritization decisions about future clinical, economic and policy research.”
– Petros Pechlivanoglou, PhD

Dr. Petros Pechlivanoglou is a scientist at The Hospital for Sick Children Research Institute and assistant professor at the University of Toronto. His research focuses on methods around the use of health decision analysis, administrative data and prediction modelling in economic evaluation, and the health economics of pediatric oncology and pre-term birth.

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This POGO-funded research is helping children with its early detection of cancer predisposition syndromes.