Registry to focus on cardiotoxicity after childhood cancer

Research

By Mardi Chapman

22 Jan 2020

The Australian and New Zealand Cardio-Oncology Registry (ACOR) is calling for clinicians to refer children, adolescents and young adult survivors of childhood cancer to the registry and biobank.

The registry aims to provide the infrastructure to systematically document the cancer therapy-related cardiac dysfunction (CTRCD) phenotype following exposure to chemotherapy and other cardiotoxic drugs.

It will also support laboratory-based research into genetic and other biomarkers to help detect at-risk children early, and also hopefully identify cardioprotective molecules.

The use of cardiac MRI for early detection of cardiac dysfunction is another area of interest for the registry.

In a recent article in the Internal Medicine Journal, the ACOR steering committee wrote that it would also look to establish the cost effectiveness of newly established cardio-oncology clinics and help guide policy decisions. 

“As the largest and only population-based cardiotoxicity database of paediatric and AYA oncology patients in the world, and the first paediatric registry that will document cardiotoxicity in response to both chemotherapy and novel targeted therapies using a prospective and longitudinal approach, the study has unique potential to improve our understanding of CTRCD in the modern era. This represents a significant advance over the current localised and ad hoc approach to monitoring CTRCD,” it said.

The registry, chaired by Associate Professor Rachel Conyers, was established in Australia in 2018 and expanded to include New Zealand in 2019. It currently involves 12 partner institutes across five Australian states and New Zealand and is coordinated by the Murdoch Children’s Research Institute (MCRI).

Co-chair of ACOR, Associate Professor David Elliott, told the limbic the registry builds on an existing MCRI cohort of about 300 patients.

Associate Professor Elliott,  an Honorary Senior Research Fellow in the University of Melbourne’s Department of Paediatrics, said some of the genetic work and stem cell modelling for cardioprotective molecules was already underway. 

“We expect over the next couple of years to publish some of that work and we have also got an imaging arm that is looking at cardiac MRI and trying to see if we can correlate changes in cardiac function and output by MRI which isn’t usually done in kids.”

He said the work was aimed at improving practice and follow-up of children with cancer and ultimately improving their outcomes.

“It’s a relatively new field and paediatric cancer is quite rare so it hasn’t been followed extensively.” 

“At the moment, when someone presents in the clinic, we don’t know who is going to be susceptible to cardiac damage and who isn’t. And because we don’t have all their retrospective samples, we can’t go and quickly sequence people.” 

“So if we could identify a genetic diagnostic then we could do it quite quickly because the genetic technologies are available.”

He said one of the powers of the biobank was that when other groups publish on CTRCD, findings could quickly be validated in an Australian and New Zealand cohort.

“…and hopefully get to a point where we have a diagnostic screen almost straight away, stratify patients and monitor them more closely after their chemotherapy.”

Associate Professor Elliott urged clinicians who knew of relevant cases to get in contact with ACOR. 

“One of the things we would like to do is follow up on people who are a bit older now and have presented later – so they have survived childhood chemo and have then come back. We can’t necessarily identify those people,” he said. 

The 2018-19 annual report from ACOR stated the first 33 registrants were mostly female (61%) with haematological cancer diagnoses of ALL (46%), AML (12%) and Hodgkin lymphoma (12%) accounting for most of the cohort.

Ewing sarcoma (6% of the cohort) was the most common solid cancer. 

Most patients had been administered anthracyclines (84.5%) and to date, seven of those  patients have developed CTRCD. An eight patient who developed CTRCD was on a checkpoint inhibitor at enrolment.

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