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ARTICLE

Circulating Tumor DNA and microRNA–Based Liquid Biopsy for Longitudinal Treatment Monitoring and Recurrence Prediction in Pediatric Sarcomas: A Prospective Cohort Study

Maher Kurdi1,*, Amber Hassan2, Bashar Reda3, Anas Nooh3, Mohammed Alsobaie4, Alaa Alkhotani5, Dahlia S. Mirdad6, Majid Almansouri7, Khalid Khashoggi8, Manal Halwani9, Motaz Fadul1, Humaira Waseem10,11, Siti S. Maidin10, Muhammed Imtiaz Farid12
1 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
2 Department of Neurogenetics, Istituto Neurologico Nazionale a Carattere Scientifico, IRCCS, Pavia, Italy
3 Department of Orthopedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
4 Department of Surgery, Doctor Suliman Fakeeh Hospital, Jeddah, Saudi Arabia
5 Department of Pathology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
6 Department of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
7 Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
8 Department of Radiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
9 Department of Emergency Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
10 Department of Data Science, INTI International University, Nilai, Malaysia
11 Department of Quality Enhancement Cell, Fatima Jinnah Medical University, Lahore, Pakistan
12 Primary & Secondary Health care Department, Maryam Nawaz Health Center, Pakpattan, Pakistan
* Corresponding Author: Maher Kurdi. Email: email

Oncology Research https://doi.org/10.32604/or.2026.078833

Received 08 January 2026; Accepted 23 March 2026; Published online 15 April 2026

Abstract

Background: Pediatric sarcomas are aggressive malignancies characterized by marked biological heterogeneity and a high risk of relapse. Standard surveillance relies on imaging and invasive biopsies, which may fail to detect early molecular disease. Liquid biopsy using circulating tumor DNA (ctDNA) and microRNAs offers a minimally invasive strategy for longitudinal monitoring. This study aimed to evaluate dynamic changes in ctDNA and circulating microRNAs during treatment and examined their associations with treatment response, disease recurrence, and survival outcomes. Methods: This prospective cohort study included 100 pediatric patients with histologically confirmed sarcomas. Serial peripheral blood samples were collected at diagnosis, during treatment, at treatment completion, and during follow-up. Plasma-derived ctDNA and miRNAs were quantified using droplet digital Polymerase Chain Reaction (PCR) and quantitative Reverse Transcriptase-PCR (qRT-PCR). Associations between biomarker levels, clinical and radiologic response, recurrence, and survival outcomes were analysed using correlation analyses. Results: The mean age at diagnosis was 10.5 ± 4.9 years, with a male predominance (59.0%). The most common tumor subtype was Ewing sarcoma (49.0%), followed by rhabdomyosarcoma (27.0%) and osteosarcoma (24.0%). Both ctDNA and circulating miRNA concentration declined significantly from baseline to the end of treatment (p < 0.001 for both). End-of-treatment biomarker levels showed weak and insignificant correlations with clinical response, radiologic response, and survival outcomes (all p > 0.05). In multivariable analysis, disease recurrence status was strongly associated with survival, as expected; however, circulating biomarker levels did not independently predict outcome (Odds ratio (OR) = 0.04, 95% Confidence Interval (CI): 0.01–0.15; p < 0.001). Conclusions: ctDNA and microRNA levels showed dynamic, treatment-related changes in pediatric sarcomas, reflecting therapeutic response at the population level. However, single end-of-treatment measurements were not predictive of outcomes. These findings support liquid biopsy for longitudinal monitoring rather than static prognostication and emphasize the need for prospective validation of serial biomarker approaches.

Keywords

Pediatric sarcoma; liquid biopsy; circulating tumor DNA; microRNA; treatment monitoring; longitudinal surveillance

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