World-first results from a new Australian study have shown that precision medicine – where treatment is targeted to the individual based on genetic factors – can improve outcomes in children with deadly brain cancer.
Published this week in the high-impact journal Nature Communications, the study focused on a group of brain cancers known as ‘H3K27-altered diffuse midline glioma’ (DMG), highly aggressive brain tumours mainly affecting young children which are almost always fatal, often within a year of diagnosis.
“Our study is the first to show that precision-guided therapy can significantly extend survival in children with these cancers,” said Professor David Ziegler, Chair of Clinical Trials for the Zero Childhood Cancer Program, and co-senior author on the paper.
“These results have important implications for how these children are treated. They also suggest that a change in practice should be considered, whereby every child with this type of cancer has a biopsy taken at diagnosis for genomic analysis.”
The study included sixty-eight children enrolled on the Zero Childhood Cancer Program (ZERO), Australia’s national precision medicine program for children with cancer, jointly led by Children’s Cancer Institute and Kids Cancer Centre at Sydney Children’s Hospital, Randwick, and involving all of Australia’s children’s hospitals.
Tumour samples from each child were analysed to identify genetic alterations, or variants, driving the cancer’s growth. On the basis of the results, a suitable targeted therapy (precision-guided therapy) was able to be recommended for 74% of the children.
Results showed that, of the children who received a ZERO-recommended (precision-guided) therapy, more than half (52%) derived clinical benefit, either their tumour shrunk, or their disease stabilised. Strikingly, the median overall survival of children in this group was close to double that of children who did not receive a precision-guided therapy (21.3 months versus 12.1 months).
Another important finding of the study was that this in-depth molecular profiling, including both whole genome sequencing and RNA sequencing, not only enabled a targeted therapy to be identified in most cases, but also led to a change in diagnosis in a substantial proportion of patients.
“We were able to revise the diagnosis of eleven children after the genomic analysis of their biopsy,” said Dr Neevika Manoharan, Paediatric Haematologist/Oncologist at Sydney Children’s Hospital, and co-senior author on the study. “In seven of these children, the analysis showed that they actually did not have DMG, although their scans looked typical for this type of cancer. Critically, some of these children were found to have highly targetable tumour drivers, meaning that ZERO could recommend a targeted therapy for them.”
The study’s results are sure to provide much-needed hope for the families of children diagnosed with these devastating cancers.
“DMG are virtually impossible to treat and despite many different approaches being tried over the years, the cure rate remains near zero,” said Dr Dong-Anh Khuong-Quang, Paediatric Oncologist at The Royal Children's Hospital at Melbourne, co-senior author. “Families will be heartened by this study which shows we now have a way to extend survival.”
“Ultimately, as more precision-guided therapies become available and are incorporated into treatment protocols, we hope to see further improvements in the outlook for children with these cancers.”
Find out more about ZERO at https://www.zerochildhoodcancer.org.au.
The Zero Childhood Cancer Program is made possible thanks to joint funding from the Australian Federal Government Department of Health and the Minderoo Foundation and is sponsored by the Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG).
This work was supported through funding from the National Health and Medical Research Council, New South Wales State Government, Australian Cancer Research Foundation, Kids Cancer Alliance, Tour de Cure, Steven Walter Children’s Cancer Foundation, Hyundai Help 4 Kids Foundation, Lions International Foundation, Cure Brain Cancer Foundation, The Kids Cancer Project and Luminesce Alliance.
