Targeted DNA Sequencing for Tailored Therapies in Children with Extracranial Solid Tumors

Next-generation sequencing (NGS) is instrumental for clinical decisions on molecularly targeted therapy (TT). In pediatric oncology, TT is a relatively rare choice administered chiefly on a tumor-agnostic basis. The investigation enrolled 304 pediatric patients with extracranial solid tumors that were diagnosed and treated in 2018-2023. Tumor DNA was sequenced using a customized QiaSeq panel (Qiagen, Hilden, Germany) of genes known to be relevant for pediatric solid tumors, including <i>ALK</i>, <i>BRAF</i>, <i>BRCA1/2</i>, <i>EGFR</i>, <i>FGFR1</i>, <i>KIT</i>, <i>MAP2K1/2</i>, <i>NF1</i>, <i>PDGFRA/B</i>, <i>PIK3CA</i>, <i>PTEN</i>, <i>PTPN11</i>, RAS family genes, etc. The assay allowed detection of nucleotide substitutions and small insertions/deletions, as well as gene copy number alterations. TT sensitivity predictors were identified in 120/304 cases (39.5%): Tier II in 83 patients, Tier IB in 32 patients (almost always ALK in neuroblastoma, <i>n</i> = 31) and Tier IA in 5 patients: BRAF p.V600E (<i>n</i> = 3) and NF1 aberrations (<i>n</i> = 2). TT commenced in 21/304 cases (6.9%), often first-line or as a first relapse therapy (14/21 cases), combined with chemotherapy (TT-CT) in 13 cases. The median of TT duration was 10.9 (range 0.8-43.5) months for single-mode and 12.3 (0.3-61.5) months for TT-CT. Clinical benefit rate was achieved in 14/21 patients (66.7%). At the time of writing, nine patients (42.8%) have no progression and are still on treatment for 30.4 months (range 10.3-40.5) after the start of TT. The median time to the best response to TT was 6 (range 0.8-12.3) months. The tolerance was generally good: the therapy was discontinued for toxicity in only one case. The study provides a TT-focused prospective analysis still rare in pediatric oncology. The outcomes indicate satisfactory tolerance and promising efficacy of TT, prompting an update of current treatment standards for several pediatric cancers.