Young patients with refractory cancers may benefit from early molecular testing to guide treatment decisions, according to researchers. 

The team found that tumor sequencing could effectively identify actionable genetic alterations, which could then be used to assign patients to trials of molecularly targeted therapies. 

These results, from the Pediatric MATCH trial ( Identifier: NCT03155620), were published in the Journal of Clinical Oncology

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The researchers reported results in 1000 patients, ages 1 to 21 years. The patients had refractory solid tumors, non-Hodgkin lymphomas, and/or histiocytic disorders. There were slightly more male (55.6%) than female patients, and 40.6% of the cohort consisted of adolescent and young adult patients (ages 15-21 years). 

Next-generation tumor sequencing and limited immunohistochemistry were used to identify actionable alterations and assign patients to appropriate phase 2 clinical trials. 

At least 1 actionable alteration was detectable in 31.5% of the 1000 tumors screened. The researchers identified 343 actionable alterations in all. The most common of these were mutations or fusions in BRAF (4.2%), SMARCB1 loss/mutations (3.9%), CDK4 amplification (3.1%), FGFR1 mutations/fusions (2.9%), and NF1 mutations (2.4%).

Based on these findings, 28.4% of patients were assigned to a treatment arm in a relevant trial, and 13.1% of patients were ultimately enrolled in a relevant trial. 

There were no significant differences in the rate of matching to a treatment arm or the rate of trial enrollment by patient sex, age, race, or ethnicity. Patients with previous molecular testing were more likely to be matched (P <.001) and enrolled (P =.039). Patients with central nervous system tumors were more likely to be matched (P <.001) but not more likely to be enrolled (P =.253). 

These results provide a useful snapshot of the spectrum of refractory tumor histologies and their key molecular features, according to the researchers. However, they noted that more comprehensive analyses, including exome, whole genome, and transcriptome sequencing, could greatly advance this area of medicine.

When examining the most frequently identified nonactionable alterations, the researchers found that many of the most frequent alterations found in pediatric solid tumors — TP53 and CTNNB1 mutations, MYC and MYCN amplifications, and EWSR-FLI1 fusions — remain therapeutic challenges and are associated with high mortality.

“Novel strategies for targeting these genes and related pathways will be necessary to dramatically increase the potential clinical benefit of precision oncology strategies for childhood patients with cancer,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Parsons DW, Janeway KA, Patton DR, et al. Actionable tumor alterations and treatment protocol enrollment of pediatric and young adult patients with refractory cancers in the National Cancer Institute–Children’s Oncology Group Pediatric MATCH trial. J Clin Oncol. Published online March 30, 2022. doi:10.1200/JCO.21.02838