An Update from Dr. Alexandra Zorzi
Division Head, Paediatric Hematology/Oncology
Assistant Professor, Department of Paediatrics
Children's Hospital, London Health Sciences Centre
September 2021
This was quite a unique year with a number of challenges, especially in the research sphere. I think it is important to emphasize that we have continued to ensure that pediatric cancer research continues throughout the pandemic, ensuring access to clinical trials and novel investigations. In pediatric oncology, we felt that our research is too closely tied to patient care to not continue, and, thankfully, London Health Sciences Centre and Lawson Research Institute continue to support us in this regard. Our major obstacle remains personnel. We are very limited in clinical research assistants. As you can imagine, the impact of the pandemic on people’s lives has been major, and unfortunately committing to in-person work was no longer possible for some of our personnel. We are actively recruiting to fill those gaps.
The funding we receive from Childcan is all the more critical this year to ensure that we continue our mandate of ensuring all patients we serve within the Division of Pediatric Hematology Oncology have equal access and opportunity to participate in clinical trials and research initiatives at their home institution. Even our largest project, PROFYLE, is facing financial uncertainty with decreased funding from The Terry Fox Research Institute.
Our clinical research assistant (CRA) is so dedicated and inspired by our work. She is a perfect fit and embraced all of our initiatives. As a result, we have made a lot of progress in broadening the scope of research and clinical trials we offer here at Children's Hospital, London Health Sciences Centre. The CRA hired through our Childcan funds has actually been promoted to Clinical Research Coordinator and, at present, is running the unit mostly alone. We are actively recruiting but her leadership of and dedication to our research unit is outstanding.
I cannot emphasize ENOUGH that this research would NOT be possible without the support of Childcan and the CRA that it funds. Our ability to fund her position outside of the study grant dollars allows other centres to have access to funding so that they can launch some of these studies too. So Childcan is helping all Canadian children affected by childhood cancer have access to innovation. This is something to be very, very proud of.
RESEARCH
PROFYLE: Precision oncology for young people. This is a national tumour sequencing initiative to better characterize a child's tumour and identify its unique fingerprint. We hope to use this information to identify possible specific medications/treatment options for a patient’s tumour, use the information to follow the tumour’s response, gain information about the patient’s prognosis and understand the cause of the child's cancer. We have enrolled 305 patients. We are fully open and approved. There have been various results of this initiative for our local patients, including identifying patients that are at a genetic risk of developing cancer. We have further clarified or changed a diagnosis of patients that are enrolled, as well as discovered a targeted drug to match a tumour’s genetic make-up which has greatly impacted the patient and their prognosis. We have a handful of patients now on therapies we would not have thought or known to offer because of the findings this project generated! We have several targeted therapy ideas for clinical trials as a spin-off of this project, one of which I am hoping to lead. We have a spin-off study now open looking at the barriers to obtaining and prescribing these target agents to children in Canada (retrospective) which our site is participating in. Also, as part of this project, a LOT of advocacy to Health Canada around pediatric drug access and clinical trial availability in Canada is being done in partnership with parent advocacy groups like Ac2rn and Helena’s Hope.
Pharmacogenomic Predictors of Drug Response in Pediatric Oncology: This project aims to understand the patient’s genetics and drug response and/or the toxicity they experience to a drug. To date, we have enrolled almost 200 patients on the main study. We have over 100 who are the focus of a sub-study looking at the body’s ability to use a common medication in ALL therapy. We have just submitted a paper for publication, reviewing the impact of genotype on the occurrence of fever neutropenia in ALL patients. We will be presenting this at the POGO conference in November of 2021.
I am pleased to report that I was successful in obtaining an AMOSO grant to expand our personalized oncology research. As such, in June of 2021, I began recruiting to the pharmacogenomics of antiemetic therapy project. Our pilot data (obtained via Childcan funding) demonstrated that a third of patients will not achieve nausea control using our standard medication (Ondansetron) based on how their bodies metabolize drugs. We are currently conducting a prospective project that links Ondansetron concentration in the blood, the patient’s genotype for metabolizing the drug and their self-reported nausea diary. We are projecting project completion by the end of 2022.
I have partnered with our two clinical pharmacists to study kidney injury and Methotrexate. We have just completed data analysis and are in the process of submitting the paper. We are looking to expand this research to other diagnoses as well.
Pharmacometabolomic of Kidney Injury in Pediatric Patients: This project is looking to understand kidney injury caused by chemotherapy and identify markers in the patient’s urine that may predict which patients are at most risk. We have collaborated with other centres in Canada on this and are hoping to have some pilot data ready for publication this fall. The project got a little stalled due to funding, but we recently were awarded a very large CIHR grant so I think now it is full steam ahead. This project is being hampered slightly by approvals across the country but looks like we should be ready by fall.