Molecular analysis can improve diagnostic accuracy and guide treatment decisions for pediatric patients with central nervous system (CNS) tumors and other cancers, according to researchers.

The researchers performed molecular analyses on tumor samples collected via the Pediatric Targeted Therapy (PTT) 2.0 registry. The findings were presented at the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO) by Jonas Ecker, MD, of Hopp Children’s Cancer Center Heidelberg in Germany.

The PTT 2.0 registry included patients younger than 22 years of age whose disease had relapsed or progressed after standard care. The patients had to have formalin-fixed paraffin-embedded (FFPE) samples of their primary or recurrent tumor as well as a blood sample. 

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Using these samples, the researchers performed DNA methylation array, sequencing of 130 genes, RNA sequencing in select cases, and a pathway-specific immunohistochemistry panel (p-AKT, p-ERK, p-S6, and PD-L1). 

A tumor board discussed the molecular results and provided diagnostic information and treatment recommendations to the centers that submitted patients’ samples. The researchers also collected follow-up information on patients via questionnaires that were sent at 3, 6, 12, 18, and 24 months. 

There were 263 patients whose samples were analyzed, and follow-up was completed for 193 of those patients. Most patients (n=175) had CNS tumors, but some had sarcomas and other solid tumors. The patients’ median age at the time of sample submission was 10 years. The median turnaround time from sample submission to completion of the final report was 47 days.

The researchers were able to attribute a specific diagnosis to about 70% of patients with CNS tumors, Dr Ecker said. In roughly 10% of cases, the diagnosis was the same as the diagnosis made by the submitting center. For about 80% of patients, methylation array led to refinement of the diagnosis. For about 5%, the methylation classifier suggested a change in diagnosis. 

Of the 193 patients who completed follow-up, 60% had a targeted therapy recommendation. MEK and mTOR inhibitors were the most common potential treatment options for the patients with CNS tumors.

There were 26 patients (22%) who ultimately received a matched treatment. One did so on a clinical trial, and the remaining 25 patients were treated via a compassionate use program. The most common reasons for not receiving matched therapy were receiving chemotherapy instead or having stable disease or progressive disease. 

There were 3 patients who received only the recommended targeted therapy. The remaining patients received the targeted therapy in combination with surgery, radiotherapy, and/or chemotherapy. 

Three patients were still in complete response at last follow-up, but about half of patients had progressive disease. Eight patients had died.

Dr Ecker said these results suggest that molecular analysis of pediatric tumors using FFPE and blood is feasible in a real-world setting, provides a diagnostic benefit, and identifies potentially actionable targets that can impact clinical decision-making.

He acknowledged that the clinical benefit remains unclear. However, he and his colleagues recommend that all pediatric patients with brain tumors be included in molecular diagnostic programs, and he noted that the PTT 2.0 registry remains open. 


Ecker J, Selt F, Sturm D, et al. The Pediatric Targeted Therapy 2.0 registry: Robust molecular diagnostics for precision oncology. Presented at ISPNO 2022; June 12-15, 2022. Abstract OTHR-32.