NEW YORK – Glioma brain tumors found in adolescent and young adult patients may fall into higher- or lower-risk subgroups depending on features such as tumor grade and the presence or absence of certain alterations, according to new research from an international team led by Canadian investigators.
Their findings, published in Nature Cancer on Wednesday, "give insight into the origins of these tumors and offer opportunities for novel treatment strategies aimed at altering the natural behavior of these gliomas, called 'cancer interception,'" Julie Bennett, a physician and neuro-oncology researcher with the Hospital for Sick Children (SickKids) and the Princess Margaret Cancer Centre, who co-leads the Canadian Adolescent and Young Adult Neuro-Oncology Network, said in an email.
For their study, Bennett and her colleagues generated droplet digital PCR, targeted panel sequencing, and array-based methylation profiling data on tumor samples from up to 1,456 glioma patients. In addition, they brought in clinical data and copy number variants (CNV) gleaned from whole-genome sequencing of tumor samples and matched normal blood samples from a subset of 37 mismatch repair-proficient patients.
The study participants ranged in age from infancy to 39 years and were treated at Toronto hospitals between early 2000 and mid-2019, though the analyses largely centered on gliomas found in 873 patients between the ages of 15 and 39.
While past studies uncovered distinctive pediatric-glioma and adult-glioma alterations that can inform treatment and prognosis, molecular changes affecting the biology, location, treatment response, and prognostic outlook for adolescents or young adults with glioma have been less fully investigated.
"There have not been any large studies focused on the molecular characteristics of the [adolescent and young adult glioma] population in the past," Bennett noted.
With their multiomic analyses, the investigators saw extensive heterogeneity for adolescent and young adult gliomas, which ranged from tumors with features that resembled pediatric glioma cases to tumors with adult-type glioma features. Nearly one-third of tumors were enriched for alterations implicated in pediatric glioma cases, for example.
The investigators also saw signs that the low-grade gliomas found in adolescent and young adult patients often showed up in different locations in the brain compared to low-grade gliomas found in children, consistent with distinct cellular origins.
They noted that individuals with low-grade tumors and pediatric glioma-like alterations tended to have better progression-free survival and overall outcomes relative to cases involving adult-type glioma alterations, suggesting targeted treatment options with reduced toxicity in some low-risk adolescent or young adult cases.
Even so, the team highlighted a set of adolescent or young adult tumors that appeared to be particularly prone to becoming more aggressive high-grade glioma tumors as patients age, including tumors containing the BRAF p.V600E mutation, mutant IDH, or alterations involving the FGFR gene.
Based on these and other results, the author suggested that additional research may lead to combination treatments for improving outcomes in patients with high-grade tumors and called for clinical efforts aimed at recognizing pediatric glioma-like tumors in the adolescent and young adult patient group.
"These findings demonstrate unique vulnerabilities and differences in tumor behavior based on age at diagnosis and cell of origin," the authors wrote. "Further work is needed to detect tumors and intervene at earlier stages of tumorigenesis to prevent malignant transformation, with the potential to alter the natural history of these tumors."