Taking strides towards a world with ZERO childhood cancer

The expansion of a world-leading program for young Australians is expected to add volumes to the understanding of childhood cancer, for the benefit of all children diagnosed with cancer in the future.

One such child is Kristian Kozul, treated as part of the Zero Childhood Cancer Precision Medicine Program (ZERO), backed by Minderoo Foundation and led in partnership by Children’s Cancer Institute and Kids Cancer Centre at Sydney Children’s Hospital, Randwick, together with all nine of Australia’s children’s hospitals and with trial sponsor ANZCHOG.

Proof of the life-saving power of personalised medicine, Kristian Kozul defied the devastating prognosis delivered to him before his second birthday, when five months of chemotherapy had failed to shrink an aggressive brain cancer.

Today, more than five years later, Kristian recently started school.

Kristian began suffering seizures as a 15-month-old baby, but their cause could not be determined until a biopsy at Melbourne’s Royal Children’s Hospital revealed a rare brain tumour, known as anaplastic astrocytoma.

Kristian began intensive treatment but despite five months of gruelling chemotherapy, his tumour had not shrunk but instead had grown.

Kristian was given less than a year to live – an unimaginable prognosis for a young child. With Kristian too young for radiation therapy, and having no other options available to them, his parents Marie and Steve agreed to him doing a genomic sequencing test as part of ZERO.

The test was successful in identifying a rare genetic mutation and in November 2017, Kristian, then two years old, was enrolled in a clinical trial open at Sydney Children’s Hospital to test a drug targeting that same mutation. After just weeks of treatment, an MRI scan showed that his tumour had stopped growing.

Professor David Eisenstat, Head of Department, Children’s Cancer Centre, The Royal Children’s Hospital, Melbourne, said: “Without the targeted therapy ZERO identified, it is unlikely Kristian would have survived. To see him doing so well today is beyond all our expectations.”

Kristian’s mother, Marie, said: “Kristian continues to grow and develop each day. He has come such a long way and continues to amaze us. We know that if it wasn’t for ZERO, our little boy wouldn’t be with us today, and we couldn’t be more grateful.”

ZERO uses sophisticated genomic mapping to identify the molecular changes driving each child’s cancer, making recommendations for targeted treatments.

Minderoo Foundation supported ZERO with an initial $5 million grant in 2017 towards the first national clinical trial for patients with aggressive cancer and a less than 30 per cent chance of survival. In 2020 Minderoo committed a further $12.2 million to support the program’s expansion for all cancers and access for all patients.

“Minderoo Foundation believes ZERO gives children like Kristian and young adults with cancer the greatest chance of not only surviving their disease but also thriving in later life,” said Aileen Boyd-Squires, Head of Personalised Cancer Care for the Foundation’s Collaborate Against Cancer initiative.

“Collaboration is critical to a precision medicine approach for children with cancer and we are so pleased to support each of the hospitals in the ZERO network with additional staff resourcing, and to help build the digital infrastructure for this complex program. We’re proud to support the program’s expansion and to partner with the ZERO team.”

By the end of this year, all children and young people diagnosed with cancer in Australia will have the opportunity to access genomic sequencing as part of ZERO.

A true team effort, ZERO includes all nine of Australia’s children’s hospitals, the national clinical trial sponsor ANZCHOG as well as 22 national and international research partners, and is based on the premise that every child’s cancer is unique.

Sophisticated genomic analysis is performed for each child enrolled on ZERO, allowing scientists to look for genetic alterations that may be driving the cancer’s growth, then search for drugs capable of targeting those alterations. This information is returned to the clinicians treating the child, to help inform their decision-making.

“The expansion of ZERO to be available to all Australian children with cancer is something we’ve all been working towards for a long time, so it’s extremely exciting to now see it unfolding,” said Professor Michelle Haber AM, Executive Director of Children’s Cancer Institute.

“Analysing each child’s cancer at a genomic level is providing unprecedented and extremely valuable insights into childhood cancer. For example, finding out which genetic changes drive these cancers will allow us to develop new targeted therapies matched to these changes. In the expanded ZERO, genomic analysis will occur from the time of diagnosis for every child enrolled, allowing us to track the way each child’s cancer changes in response to treatment.

“Analysing the cancer journey of up to 1000 young Australians each year in this way will add volumes to our understanding of childhood cancer, for the benefit of all children diagnosed with cancer in the future.

“The more children who participate in ZERO, the more we learn. In this way, children being treated for cancer today are actually helping the children of tomorrow.”