Abstract 3662: Cell-free DNA dynamics following neuroblastoma resection
Authors: Honeyman Joshua N. , Chi Andrew , Modak Shakeel , Cardenas Fiorella Iglesias , La Quaglia Michael P. , Shukla Neerav N. , Gerstle J. Ted 
Published: March 2024

Introduction: Prior studies have demonstrated the utility of circulating tumor DNA (ctDNA) as a biomarker in the postoperative period for oncologic risk stratification. However, its utility may be limited in the early postoperative period by surgical trauma causing an increase in total cell-free DNA (cfDNA) due to tissue destruction, inflammation, and wound healing. No studies have identified the optimal timing of postoperative sample collection in pediatric patients undergoing resection of high-risk neuroblastoma. The purpose of this study is to assess the postoperative dynamics of cfDNA following neuroblastoma resection to determine optimal timing for ctDNA investigations.

Methods: An institutional database of banked cell-free DNA samples was retrospectively queried for patients with a diagnosis of neuroblastoma who had blood samples collected prior to resection and postoperative samples collected within 2 months of the operation. Plasma was collected from whole blood samples. cfDNA was extracted from plasma samples using the QIAGEN QIAsymphony SP system, and samples were quantified using the Advanced Analytical Fragment Analyzer Automated CE System with the High Sensitivity Genomic DNA Analysis Kit.

Results: Seventeen patients were identified undergoing 18 total operations and 37 total blood draws yielding cfDNA. There were 12 male and 5 female patients. Median age at operation was 5.5 years (range 1.4y to 20.5y). Two patients were INRG stage L2, and 15 patients were stage M. Operative indications were primary tumor resection in 10 patients and resection of recurrence/progression in 8 patients. Three postoperative samples were drawn within 10 days of the operation, and 16 samples were collected between postoperative weeks 4 and 6. There was a statistically significant difference (p=0.029) in cfDNA yield between each timepoint sampled: preoperative (median 6ng/mL, range 2-30ng/mL), 0-10 days postop (median 34ng/mL, range 15 - 85 ng/mL), and 4-6 weeks postop (median 6ng/mL, range 2 - 17ng/mL). Pairing the pre- and post-operative samples for each patient, those drawn within 10 days had a median increased yield of 180% (range +67% to +652%) while the samples collected at 4-6 weeks had a median decreased yield of 23% (range -55% to +491%; p = 0.047). Of note, there were three outliers in the 4-6 week group who had increases in cfDNA yield of &gt;200%. On further review of these charts, each patient was being treated for obstructive uropathy at the time the postoperative sample was collected.

Conclusion: Plasma cfDNA yield increases in the early postoperative period before dropping by postoperative week 6. Tumor resection may be associated with an overall decrease in total cfDNA. Postoperative renal pathology may cause a persistent elevation in cfDNA. Further studies are necessary to clarify the role of ctDNA in the management of patients with neuroblastoma.

Citation Format: Joshua N. Honeyman, Andrew Chi, Shakeel Modak, Fiorella Iglesias Cardenas, Michael P. La Quaglia, Neerav N. Shukla, J. Ted Gerstle. Cell-free DNA dynamics following neuroblastoma resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3662.