In an analysis from a Children’s Oncology Group trial (AREN0533) reported in the Journal of Clinical Oncology, Madanat-Harjuoja et al found that the analysis of circulating tumor DNA (ctDNA) in children with stage III or IV Wilms tumor demonstrated high levels of agreement in identifying risk markers found in tumor biopsies. Patients with undetectable ctDNA showed trends toward improved survival outcomes.
The analysis included 50 patients with Wilms tumor with banked pretreatment serum, urine, and tumor biopsy specimens available. Next-generation sequencing was used to detect ctDNA. Copy-number changes in 1q, 16q, and 1p, and single-nucleotide variants in serum and urine were compared with findings in tumor biopsy.
Key Findings
ctDNA was detected in the serum of 41 (82%) and urine of 13 (26%) of the 50 patients. Agreement between serum ctDNA detection and tumor sequencing results was as follows: 77% for 1q gain, 88% for 16q deletions, and 70% for 1p deletions. Agreement between urine ctDNA detection and tumor sequencing results was as follows: 89% for 1q gain, 75% for 16q deletions, and 77% for 1p deletions.
Sequencing also showed that single-nucleotide variants detected in tumors could be identified in ctDNA. The most commonly mutated genes were CTNNB1 and WT1. The majority of single-nucleotide variants detected in tumors were also detected at a lower allelic fraction in ctDNA, but detection of some single-nucleotide variants also suggested subclonal heterogeneity within the patient.
Compared with patients without detectable ctDNA in the serum, those with detectable ctDNA exhibited trends toward worse 4-year event-free survival (80% vs 100%, P = .14) and 4-year overall survival (83% vs 100%, P =.20). Patients with vs without ctDNA detected in urine had 4-year event-free survival of 77% vs 89% (P = .39) and 4-year overall survival of 77% vs 91% (P = .13).
The investigators concluded, “ctDNA demonstrates promise as an easily accessible prognostic biomarker with potential to detect tumor heterogeneity. The observed trend toward more favorable outcome in patients with undetectable ctDNA requires validation. ctDNA profiling should be further explored as a noninvasive diagnostic and prognostic tool in the risk-adapted treatment of patients with Wilms tumor.”
Brian D. Crompton, MD, of Dana Farber/Boston Children’s Cancer and Blood Disorders Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
