Purpose Leiomyosarcoma (LMS) is a soft-tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single-nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods We evaluated cell-free DNA in plasma samples and paired genomic DNA from resected tumors from patients with LMS by ultra-low passage whole-genome sequencing. Sequencing reads were aligned to the human genome and CNAs that were identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in 11 (69%) of 16 patients with disease progression and total tumor burden greater than 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined after resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of patients with uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence, and differentiating benign and malignant smooth muscle tumors.
Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA
