1. Monitoring pediatric CNS non-germinomatous germ cell tumors via cerebrospinal fluid circulating tumor DNA.
- Author
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Zhang YT, Jin XM, Zhong XD, and Chang J
- Subjects
- Humans, Male, Female, Child, Retrospective Studies, Adolescent, Child, Preschool, Prognosis, Survival Rate, Follow-Up Studies, Infant, Neoplasm, Residual cerebrospinal fluid, Testicular Neoplasms, Neoplasms, Germ Cell and Embryonal cerebrospinal fluid, Neoplasms, Germ Cell and Embryonal blood, Neoplasms, Germ Cell and Embryonal mortality, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal pathology, Circulating Tumor DNA cerebrospinal fluid, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Biomarkers, Tumor cerebrospinal fluid, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Central Nervous System Neoplasms cerebrospinal fluid, Central Nervous System Neoplasms blood, Central Nervous System Neoplasms mortality, Central Nervous System Neoplasms genetics, Central Nervous System Neoplasms diagnosis
- Abstract
Background: Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS)., Methods: Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively., Results: The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p < .05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p < .05)., Conclusions: CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
- Published
- 2024
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