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and that will have far-reaching implications for how clinicians diagnose and manage these rare and often debilitating malignancies, a leading European researcher reported at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“These pediatric neuronal/glioneuronal tumors are quite heterogeneous in terms of the number of different tumors and subclasses of tumors going into these groups, but they have some molecular features in common,” said David T.W. Jones, PhD, of Hopp Children’s Cancer Center in Heidelberg, Germany. “Together they represent quite a sizable portion of all childhood brain tumors, so it’s important to recognize and understand them.”
Dr. Jones noted that updated WHO classifications would add six new descriptions to the category of mixed glioneuronal tumors and one to the list of neuronal tumors. A working group of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, known as cIMPACT-NOW, has recommended the expanded classifications for central nervous system tumors.
“The molecular understandings of pediatric neuro-glial tumors are critical in their management,” Roger Packer, MD, senior vice president of the Center for Neuroscience and Behavioral Health at Children’s National in Washington, said in an interview, especially as treatments targeting specific molecular structures emerge. “For those with tumors not amenable to safe, total resections, there’s little evidence that radiation or chemotherapy are effective, and molecular-targeted therapy, guided by the molecular genetic composition, increases the safe use of these new agents.”
Dr. Jones noted that “as a minimum” molecular diagnostics of pediatric low-grade glioneuronal and neuronal tumors should include a BRAF gene mutation and fusion status, as well as FGFR1 mutation plus fusion or rearrangement status.
“Ideally,” he added, “it should also have a broader copy number profile, whether that’s based on sequencing or SNP arrays or DNA methylation rate, a global DNA methylation profile to get those global molecular patterns, and also wider gene and RNA sequence to pick up some of those rarer alterations that may not be covered by targeted BRAF and FGFR1 mutations.”
The updated tumor classification will evolve to include novel tumor classes, as well as links or overlaps between the tumor classes and their characteristic underlying kinetic alterations, he noted. “Some of these profiling measures will actually be required to generate a fully WHO-compatible pathological diagnosis,” Dr. Jones said.
“This group of tumors are now just better molecularly characterized than it was 5 years ago, so in the last few years we’ve really made tremendous progress in understanding what alterations are driving some of these tumors,” he said. “That knowledge is now providing a basis for improved diagnosis and also for starting to plan more targeted treatment strategies.”
But, he added, there’s still a lot to learn about how these oncogenic mechanisms drive tumor pathogenesis. “What is the clinical costs when we really start getting down into defining these distinct molecular groups?” he said. “What are their different responses to treatment depending on different levels, where the MEKi [mitogen-activated protein kinase inhibitor] pathway might be activated and, for example, response to treatment of different subclasses of one tumor?”
Large, collaborative clinical studies will be needed to get those answers, he said.
“There are certainly some therapeutic opportunities arising in this group of tumors now, but in order to really translate those into a clinical benefit, we’re really going to need some careful planning of international studies because of the relative rarity of some of these groups,” he said.
Dr. Jones has no relevant financial relationships to disclose.
and that will have far-reaching implications for how clinicians diagnose and manage these rare and often debilitating malignancies, a leading European researcher reported at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“These pediatric neuronal/glioneuronal tumors are quite heterogeneous in terms of the number of different tumors and subclasses of tumors going into these groups, but they have some molecular features in common,” said David T.W. Jones, PhD, of Hopp Children’s Cancer Center in Heidelberg, Germany. “Together they represent quite a sizable portion of all childhood brain tumors, so it’s important to recognize and understand them.”
Dr. Jones noted that updated WHO classifications would add six new descriptions to the category of mixed glioneuronal tumors and one to the list of neuronal tumors. A working group of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, known as cIMPACT-NOW, has recommended the expanded classifications for central nervous system tumors.
“The molecular understandings of pediatric neuro-glial tumors are critical in their management,” Roger Packer, MD, senior vice president of the Center for Neuroscience and Behavioral Health at Children’s National in Washington, said in an interview, especially as treatments targeting specific molecular structures emerge. “For those with tumors not amenable to safe, total resections, there’s little evidence that radiation or chemotherapy are effective, and molecular-targeted therapy, guided by the molecular genetic composition, increases the safe use of these new agents.”
Dr. Jones noted that “as a minimum” molecular diagnostics of pediatric low-grade glioneuronal and neuronal tumors should include a BRAF gene mutation and fusion status, as well as FGFR1 mutation plus fusion or rearrangement status.
“Ideally,” he added, “it should also have a broader copy number profile, whether that’s based on sequencing or SNP arrays or DNA methylation rate, a global DNA methylation profile to get those global molecular patterns, and also wider gene and RNA sequence to pick up some of those rarer alterations that may not be covered by targeted BRAF and FGFR1 mutations.”
The updated tumor classification will evolve to include novel tumor classes, as well as links or overlaps between the tumor classes and their characteristic underlying kinetic alterations, he noted. “Some of these profiling measures will actually be required to generate a fully WHO-compatible pathological diagnosis,” Dr. Jones said.
“This group of tumors are now just better molecularly characterized than it was 5 years ago, so in the last few years we’ve really made tremendous progress in understanding what alterations are driving some of these tumors,” he said. “That knowledge is now providing a basis for improved diagnosis and also for starting to plan more targeted treatment strategies.”
But, he added, there’s still a lot to learn about how these oncogenic mechanisms drive tumor pathogenesis. “What is the clinical costs when we really start getting down into defining these distinct molecular groups?” he said. “What are their different responses to treatment depending on different levels, where the MEKi [mitogen-activated protein kinase inhibitor] pathway might be activated and, for example, response to treatment of different subclasses of one tumor?”
Large, collaborative clinical studies will be needed to get those answers, he said.
“There are certainly some therapeutic opportunities arising in this group of tumors now, but in order to really translate those into a clinical benefit, we’re really going to need some careful planning of international studies because of the relative rarity of some of these groups,” he said.
Dr. Jones has no relevant financial relationships to disclose.
and that will have far-reaching implications for how clinicians diagnose and manage these rare and often debilitating malignancies, a leading European researcher reported at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“These pediatric neuronal/glioneuronal tumors are quite heterogeneous in terms of the number of different tumors and subclasses of tumors going into these groups, but they have some molecular features in common,” said David T.W. Jones, PhD, of Hopp Children’s Cancer Center in Heidelberg, Germany. “Together they represent quite a sizable portion of all childhood brain tumors, so it’s important to recognize and understand them.”
Dr. Jones noted that updated WHO classifications would add six new descriptions to the category of mixed glioneuronal tumors and one to the list of neuronal tumors. A working group of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, known as cIMPACT-NOW, has recommended the expanded classifications for central nervous system tumors.
“The molecular understandings of pediatric neuro-glial tumors are critical in their management,” Roger Packer, MD, senior vice president of the Center for Neuroscience and Behavioral Health at Children’s National in Washington, said in an interview, especially as treatments targeting specific molecular structures emerge. “For those with tumors not amenable to safe, total resections, there’s little evidence that radiation or chemotherapy are effective, and molecular-targeted therapy, guided by the molecular genetic composition, increases the safe use of these new agents.”
Dr. Jones noted that “as a minimum” molecular diagnostics of pediatric low-grade glioneuronal and neuronal tumors should include a BRAF gene mutation and fusion status, as well as FGFR1 mutation plus fusion or rearrangement status.
“Ideally,” he added, “it should also have a broader copy number profile, whether that’s based on sequencing or SNP arrays or DNA methylation rate, a global DNA methylation profile to get those global molecular patterns, and also wider gene and RNA sequence to pick up some of those rarer alterations that may not be covered by targeted BRAF and FGFR1 mutations.”
The updated tumor classification will evolve to include novel tumor classes, as well as links or overlaps between the tumor classes and their characteristic underlying kinetic alterations, he noted. “Some of these profiling measures will actually be required to generate a fully WHO-compatible pathological diagnosis,” Dr. Jones said.
“This group of tumors are now just better molecularly characterized than it was 5 years ago, so in the last few years we’ve really made tremendous progress in understanding what alterations are driving some of these tumors,” he said. “That knowledge is now providing a basis for improved diagnosis and also for starting to plan more targeted treatment strategies.”
But, he added, there’s still a lot to learn about how these oncogenic mechanisms drive tumor pathogenesis. “What is the clinical costs when we really start getting down into defining these distinct molecular groups?” he said. “What are their different responses to treatment depending on different levels, where the MEKi [mitogen-activated protein kinase inhibitor] pathway might be activated and, for example, response to treatment of different subclasses of one tumor?”
Large, collaborative clinical studies will be needed to get those answers, he said.
“There are certainly some therapeutic opportunities arising in this group of tumors now, but in order to really translate those into a clinical benefit, we’re really going to need some careful planning of international studies because of the relative rarity of some of these groups,” he said.
Dr. Jones has no relevant financial relationships to disclose.
FROM CNS-ICNA 2020