Improving the chances for children with high-risk cancers: new study raises bar in personalised medicine

A world-first study led by Australian scientists and clinicians has found a way to improve the therapy options, and therefore the survival chances, of children with high-risk cancers. More than 1000 children and adolescents aged 0-19 are diagnosed with cancer each year in Australia, and in those with high-risk cancers, the survival rate is less than 30%.

The study is the first to demonstrate that the practice of pre-clinical testing – developing laboratory models based on each patient’s cancer, then using these models to test potential therapies – significantly increases treatment options for children with high-risk cancer when compared to genetic testing of patient tumours alone.

In recent years, the field of personalised medicine has seen treatments matched to individual patients with a precision that has never before been possible, and there is a move worldwide towards using personalised treatment approaches for children with cancer. Australia is home to one of the most comprehensive programs of this kind − the Zero Childhood Cancer Personalised Medicine Program (ZERO), jointly led by Children’s Cancer Institute and the Kids Cancer Centre at Sydney Children’s Hospital, Randwick.

So far, ZERO and other personalised medicine programs for children with cancer have been based on analysing each child’s cancer at a genomic level to find out what is driving the growth of the cancer and how it might best be targeted. This information is then used to provide treatment recommendations to the patient’s oncologist. Using this approach, ZERO has led to some remarkable results over the past six years, and building on this success, the Program is now being progressively expanded to be available to all young people diagnosed with cancer in Australia.

Published this week in the prestigious international medical journal EMBO Molecular Medicine, research by the ZERO team has now shown that personalised medicine results can be significantly improved by adding preclinical testing to the diagnostic platform on which treatment recommendations are based. Using data from 56 children with high-risk cancer enrolled in the ZERO pilot study (TARGET) and treated at Sydney’s two children’s hospitals between 2015 and 2017, the researchers found that pre-clinical testing not only revealed additional drug sensitivities − identifying treatment options in 10 patients that were not identified by genetic testing− but also proved a good predictor of clinical response in patients.

“We were surprised to find that preclinical testing, in many instances, proved even more accurate than molecular analysis in predicting patient response to the recommended therapy,” said Professor Glenn Marshall AM, Clinical Lead of ZERO and co-senior author on the paper. “Adding preclinical testing can therefore not only provide independent proof of drug efficacy suggested by molecular analyses, but also help avoid the use of ineffective treatments.”

Providing such proof may be an important step toward improving the clinical uptake of these treatment recommendations by oncologists, with past research suggesting that insufficient evidence is one of the main reasons oncologists choose not to adopt the treatment recommendations provided for their patients.

One family who has benefited from personalised medicine through the ZERO Program is the Giteau family. Kristy Giteau − a former national women’s rugby player, and sister of ex-Wallaby Matt Giteau − is mother to Ka’ili, a courageous little girl who was diagnosed with a rare kidney cancer in 2019. Treated at the Kids Cancer Centre at Sydney Children’s Hospital, Randwick, Ka’ili initially responded well to therapy, but her cancer grew aggressively, and she relapsed in June 2020. Facing extremely limited treatment options, she joined ZERO. Researchers were able to identify a specific drug that both genetic analysis and preclinical drug testing showed was specifically targeted to her cancer. Her doctors were then able to begin treatment with this drug. Ka’ili is now in remission and doing well.

“I’m so thankful for the world-class treatment Ka’ili received,” said Kristy. “Without ZERO, I dread to think what options we would have been left with. All the testing done on Ka’ili’s cancer led to finding a treatment that worked for her, and I couldn’t be more grateful.”

According to Associate Professor David Ziegler, Clinical Trial Lead for ZERO and co-senior author on the paper, while not every child treated using a personalised medicine approach experiences a positive outcome, future research is likely to lead to further improvements.

“Our research strongly suggests that adding preclinical testing to the diagnostic platform has the potential to improve clinical outcomes for children with high-risk cancer,” he said. “We believe this is a major advance in the field, and one that will provide fresh hope to children with cancer and their families.”

This article was originally published by the Children’s Cancer Institute. ACRF is one of the founding funders of the Zero Childhood Cancer program, a $1.5 million grant was awarded to the project in 2014.