Young, male, brain cancer patient wearing a hat/head covering is sitting in bed With a Toy Dog. Image signifies use of precision cancer therapy to improve outcomes.
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Results from the first 384 participants of the Australian Zero Childhood Cancer national precision medicine program (ZERO) show a precision medicine approach achieved significant survival benefits in children with high-risk cancer.

Speaking at the European Human Genetics Conference in Berlin this week, ZERO program leader Vanessa Tyrrell, also associate professor at the University of New South Wales in Sydney, explained that the early success of the ZERO program resulted in it being rolled out nationwide to all children with cancer late last year.

“We’re doing this to learn whether this model will benefit all children with cancer, irrespective of their type, stage or risk,” Tyrell explained.

“The ZERO2 trial is now open nationally at all pediatric oncology centers in Australia and I’m really absolutely delighted to say that within the next few weeks, we will have ZERO open in New Zealand as well.”

Whole genome, transcriptome and DNA methylation analysis is carried out for each child enrolled in the ZERO trial. Since the first ZERO trial began in children with high-risk cancer in 2017, defined as a less than 30% chance of survival, Tyrell reports that more than 1600 patients have been enrolled.

A paper was published in Nature Medicine in 2020 detailing data from the first 250 patients. It showed that the molecular basis of the cancer was identified in 94% of the children taking part, 71% of which had therapeutic targets.

At the conference, Tyrell presented findings from over 18 months of follow-up of the first 384 children enrolled in the ZERO trial.

The results show that progression-free survival and overall survival at two years were 27% and 38%, respectively, in the children given precision guided therapy, as opposed to a respective 11% and 24% in those not given precision therapy.

“Of the children who received precision treatment, 43% received a recommendation, 33% of those who received it had an objective response rate, and a remarkable 55% showed protective clinical benefit,” said Tyrell.

She added that almost half the variants uncovered in the study would not have been found if standard of care procedures had been followed.

Of the children enrolled in the study at the time of analysis, 116 formed part of a rare tumor cohort. Of these, diagnostic uncertainty was cited as a reason for enrollment in 38 patients, need for further molecular characterization in 39 children, and an unknown prognosis in 39 children.

Overall, 76% clarified or changed diagnosis, 20.5% had a molecular refinement of their diagnosis and in the unknown prognosis group, 54% had a tier 1 or 2 recommendation and 44% had other “clinically meaningful” results.

Tyrell also noted that three factors seemed to improve outcomes in the study, good quality clinical data and genetic characterization of the cancer, having a structural variant (mostly fusion genes), and early treatment. If the children had all three of these factors, then two-year progression free survival was as high as 88%.

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