Skip to main content
Premium Trial:

Request an Annual Quote

ESHG: High-Risk Pediatric Cancer Survival More Than Doubles in Australian Precision Medicine Trial


This article has been updated with additional information from Vanessa Tyrrell.

BERLN – Targeting cancer treatments based on multiomic profiling improved progression-free survival in pediatric patients with high-risk cancers, according to initial results from a trial in Australia presented here at the annual European Human Genetics Conference.

The results come from the Zero Childhood Cancer precision medicine program, spearheaded by Children's Cancer Institute and Kids Cancer Centre at Sydney Children's Hospital, Randwick, with participation from other pediatric cancer centers in Australia.

The program's initial trial ran from 2017 until 2022, focusing on identifying treatment options for children with high-risk or relapsed cancers who had less than a 30 percent survival chance. In a 2020 publication, the study researchers demonstrated that their approach — profiling patients' tumor and germline DNA using whole-genome sequencing, along with tumor RNA sequencing and DNA methylation analysis — could identify actionable targets.

Vanessa Tyrrell, leader of the Zero program and a professor at the Children's Cancer Institute, presented initial results for the first 384 high-risk cancer cases in a conference talk on Saturday.

More than 40 percent of patients received a treatment recommendation based on their multiomic profiling results, she said, and about a third of those had an objective response rate, while more than half showed an objective clinical benefit.

Importantly, two-year progression-free survival more than doubled from 11 percent to 27 percent in children who received molecularly guided therapy compared to those who previously received either unguided novel therapies or standard-of-care treatment.

Almost 90 percent of pediatric patients who fulfilled three criteria — having a high level of clinical evidence for their precision treatment, harboring a gene fusion, and being treated quickly — had two-year progression-free survival, she noted.

The study also identified genetic cancer risk. A total of 16 percent of patients were found to have germline cancer risk variants, and for half of them, their genomic risk was not previously detected by standard clinical testing. Almost 80 percent of the newly detected risk variants had implications for family members to reduce their cancer risk, such as increased surveillance.

A health economics study is currently under review. While analysis costs per patient were on the order of A$30,000 at the beginning of the Zero program, Tyrrell said, they have now fallen to less than half of that per patient.

In an email, she noted that cost is "a very fluid number" that depends on technology, turnaround time, data infrastructure, number and types of employees, sample volume and throughput, and degree of automation in the lab and analytical pipeline. She added that her team will continue to work on decreasing the cost of testing.

In light of the encouraging trial results, the Zero program recently expanded with A$67 million (US$44.6 million) in new funding from the Australian federal government and the Minderoo Foundation. Since last November, Zero has been open to all children with cancer in Australia, regardless of cancer type or risk. Starting in a few weeks, it will also enroll children with cancer from New Zealand, Tyrrell said.

Overall, Zero has enrolled more than 1,600 children to date, including more than 700 since the program expanded.