Molecular profiling appears to improve the diagnosis and survival of children with high-risk cancer

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Cancer is the leading cause of disease-related deaths in children in most developed countries, and at least a quarter of these patients are diagnosed with aggressive, high-risk cancers or recurrent cancers, with an expected five-year survival of less than 30%. An accurate diagnosis can be difficult, and survivors often suffer lifelong side effects due to the toxic treatments required to cure them.

Now, researchers from Australia have shown that using precision medicine not only makes it possible to make more accurate diagnoses, but also that using accurately guided, targeted treatments earlier improves two-year progression-free survival in young cancer patients. Their results will be presented at the annual conference European Society for Human Genetics.

Associate Professor Vanessa Tyrrell, Director of the Zero Childhood Cancer National Precision Medicine Program (ZERO), a joint initiative of Children’s Cancer Institute and Kids Cancer Centre, Children’s Hospital, Randwick, Australia, and colleagues from the nine pediatric cancer centers in Australia, Since 2017 more than 1,600 children participated in the program.

Previously, ZERO was limited to children with high-risk cancer, but recently expanded to be open to all children diagnosed with cancer in Australia, a trial the team calls ZERO2.

“After discovering that more than 70% of children with high-risk cancer could benefit from personalized medicine, we felt we should see if this benefit could also be applied to other types of childhood cancer,” says Prof. Tyrrell.

“To date, we have recruited more than 700 children for this second trial, which we plan to continue for at least another four years.”

ZERO’s first national clinical trial, which ran from 2017 to 2022, has already produced results related to a child’s predisposition to cancer via germline gene variants (genomic cancer risk in children).

These variants were found in about 16% of children at high risk for cancer. The use of Whole Genome Sequencing (WGS) was more sensitive for the detection of germline cancer predisposition variants than standard clinical testing pathways; more than half had not previously been identified through standard clinical care because the patients did not meet testing criteria.

Paired tumor-germline molecular profiling increased the diagnosis of germline cancer predisposition and assisted in genetic counseling for the families receiving these results. The cancer risk findings led to high (nearly 67%) referral rates to cancer genetic services and subsequently to the detection of family members at risk for cancer. All first-degree relatives underwent testing where recommended.

“This is not surprising to me as these children have been diagnosed with cancer at such a young age,” says Prof. Tyrrell.

“We also found that almost 70% of these germline variants were not previously known to be associated with the cancer type the patients presented with. This, together with the fact that more than half of the genetic findings on cancer risk increased susceptibility to developing a second cancer.” cancer after chemotherapy, has significant implications for both treatment choices and ongoing surveillance.”

Of the newly identified variants, 80% also had implications for cancer surveillance/risk reduction for family members. This is a much higher yield than found in standard clinical practice and has significant implications for both patients and families, the researchers say.

They now aim to continue improving the application of precision medicine over time, focusing on the identification of novel targets that cause individual cancers; matching these goals with more effective, less toxic treatments and developing more effective, less invasive ways to monitor how a child’s cancer behaves; accelerating access to clinical trials as the ability to identify more targets and link them to treatments expands; and transferring precision medicine from research to standard healthcare systems.

“Just seven years ago, these goals seemed unlikely to most people, and encouraging children’s enrollment in ZERO was initially a challenge. Today, physicians and families demand this precision medicine model as the standard of care for all their high-risk patients. relapsed, rare and non-diagnostic patients,” says Prof. Tyrrell.

In addition to identifying treatable cancers, ZERO also aims to identify novel genomic signatures, molecular targets and biomarkers that could lead to the development of more effective treatments. The researchers have already succeeded in characterizing new causes of cancer and identifying targeted drugs that could be effective in specific patients with specific changes in their tumors.

“Furthermore, there have been cases where we have shown that new changes were also sensitive to another targeted drug that we did not expect, potentially offering the patient more therapeutic options.”

“The tools needed to implement precision medicine on a larger scale are not cheap, but their undeniable promise in better stratifying diagnosis and identifying the most likely effective targeted treatments for an individual’s cancer, along with reducing of costs as technologies, computing capabilities and automation improve makes me believe that multiomic profiling, which drives research-driven clinical care, will be the gold standard in the future, not only in cancer, but also in many other diseases,” concludes Prof. Tyrrell.

Professor Alexandre Reymond, from the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, and chair of the conference, said: “By sequencing our genome in its entirety, we can do much more than look under the proverbial lamppost. human genetic society, ESHG should strive to make this standard clinical care.”

More information:
Executive Summary No. PL3.1 Zero Childhood Cancer National Precision Medicine Program: Improving Outcomes for Children at High Risk for Cancer Using Comprehensive, Integrated Multiomic Profiling

Provided by the European Society of Human Genetics

Quote: Molecular profiling found to improve diagnosis and survival of children with high-risk cancer (2024, May 31), retrieved May 31, 2024 from -survival-children. html

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