Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcomaResearch in context

Autor: Yiwei Fu, Yu Xu, Weihai Liu, Jiajun Zhang, Fen Wang, Qijie Jian, Gang Huang, Changye Zou, Xianbiao Xie, Albert H. Kim, Dimitrios Mathios, Fei Pang, Feng Li, Kai Wang, Jingnan Shen, Junqiang Yin
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: EClinicalMedicine, Vol 73, Iss , Pp 102697- (2024)
Druh dokumentu: article
ISSN: 2589-5370
DOI: 10.1016/j.eclinm.2024.102697
Popis: Summary: Background: Current surveillance modalities of osteosarcoma relapse exhibit limited sensitivity and specificity. Although circulating tumor DNA (ctDNA) has been established as a biomarker of minimal residual disease (MRD) in many solid tumors, a sensitive ctDNA detection technique has not been thoroughly explored for longitudinal MRD detection in osteosarcoma. Methods: From August 2019 to June 2023, 59 patients diagnosed with osteosarcoma at the First Affiliated Hospital of Sun Yat-sen University were evaluated in this study. Tumor-informed MRD panels were developed through whole exome sequencing (WES) of tumor tissues. Longitudinal blood samples were collected during treatment and subjected to multiplex PCR-based next-generation sequencing (NGS). Kaplan–Meier curves and Log-rank tests were used to compare outcomes, and Cox regression analysis was performed to identify prognostic factors. Findings: WES analysis of 83 patients revealed substantial mutational heterogeneity, with non-recurrent mutated genes accounting for 58.1%. Tumor-informed MRD panels were successfully obtained for 85.5% of patients (71/83). Among 59 patients with successful MRD panel customization and available blood samples, 13 patients exhibited positive ctDNA detection after surgery. Patients with negative post-operative ctDNA had better event-free survival (EFS) compared to those with positive ctDNA, at 1–6 months after surgery, after adjuvant chemotherapy, and more than 6 months after surgery (p
Databáze: Directory of Open Access Journals