NEW YORK (GenomeWeb) – While molecularly profiling cancer patients' tumors via next-generation sequencing is an increasingly common practice and can be used to guide patients' treatment, particularly in refractory cancers, it is less common in pediatric patients.
The UK's Institute of Cancer Research and Royal Marsden NHS Foundation Trust aim to change that with the launch of a pilot project to offer an 81-gene NGS panel to 400 pediatric cancer patients.
While the initial aim is to develop best practices and to assess the reliability and usefulness of the test, the ultimate goal is to demonstrate that such testing can lead to improved outcomes and to make it part of the standard of care in the UK.
Sally George, a clinical fellow at ICR, told GenomeWeb that the team has already begun the pilot at Royal Marsden and plans to roll it out to 20 other hospitals that are part of the UK's Children’s Cancer and Leukemia Group over the next year.
At the Royal Marsden, the test is first offered to patients at diagnosis. The results do not inform initial treatment and patients continue on standard-of-care treatment, but if a patient relapses, then the researchers consider the sequencing results. George said that ideally, they also sequence a sample from the patient's relapsed tumor "because mutation status can change," but it is not always possible to obtain a biopsy from the patient's relapse tumor. "When a patient relapses, we have to consider the risk and benefits to the patient of obtaining the sample," she said.
The test costs £250 ($352), and the National Institute for Health Research Royal Marsden Biomedical Research is providing funding for the pilot. The UK charity Christopher's Smile funded the development of the panel test, which was designed by ICR researchers.
As the pilot, which is anticipated to last around two years, rolls out across the UK, George said she anticipates that testing will be centralized, with one or two hubs performing the NGS panel.
Results of the sequencing are returned to patients' clinicians, and for patients who relapse, a tumor board meets to discuss potential available clinical trials based on the patient's mutational profile, George said.
The 81-gene panel covers genes commonly mutated in children's solid tumors. It was necessary to design a different panel from the types used in adult cancers, she said, because while some genes do overlap, "existing adult tumor panels don't cover all the genes and regions that are relevant for pediatric tumors."
Cancer in children is a very different disease from adult forms of cancer, George said. For instance, many pediatric cancers are developmental diseases, with the most common tumor type being neuroblastoma. "You don't see that in adults," She said.
Even among children, there is significant variation, and in fact, the trial will only be open to children under the age of 14 because older teenagers tend to have different tumors with different mutational profiles.
Another challenge will be getting access to targeted therapies. Pharmaceutical companies rarely run clinical trials of cancer drugs in children because the number of pediatric patients is typically much smaller than that of adult patients. And in general, George said, there is a "reluctance to carry out trials in children," but "if you actually speak to the parents, there is a clear need for studies like this and a big drive from parents to get access to these technologies."
George said the researchers have been engaging with pharmaceutical companies to gain access to drugs and available clinical trials. The hope is that this pilot will help drive multi-arm clinical trials for targeted therapies in pediatric cancers.
Louis Chesler, the study leader and a professor of pediatric cancer biology at ICR, said in a statement that obtaining targeted therapies for children with cancer has been challenging, even though such agents have the potential to improve survival. However, he said that he hopes that this study will "help to drive forward the use of targeted drugs in children, and make the case very clearly that they should be more widely available, as they have been for adults."
George said that following the initial 400-patient pilot, the researchers would like to expand testing, with a next step likely being to run a larger trial within the UK's Stratified Medicine Program.
As part of scaling the pilot up to run nationally, the researchers are working on protocols to optimize banking and preservation of samples.
They would also like to do a similar trial for blood-based cancers, leukemia and lymphoma, in pediatric patients. Those are not included in this initial trial, she said, because the spectrum of mutations found in solid versus liquid tumors is completely different.
The mutational spectrum in liquid tumors is also similar between adults and children, and in general, there are fewer mutations for liquid tumors. As such, she said, researchers would aim to design a panel that could cover both adult and pediatric leukemias and lymphomas.
While trials for targeted therapies for pediatric cancers have lagged behind ones for adults, the UK trial and others like it may signal a shift.
For instance, in the US, the National Institutes of Health plans to launch a pediatric cancer trial this year — a counterpart to the MATCH trial it is running for adult cancers — and will use a targeted NGS panel to enroll patients into one of several drug trials. Also, Columbia University Medical Center plans to make genomic sequencing available for free to patients 18 years of age or younger who have cancers with a 50 percent or greater chancer of relapse.