Molecular residual disease (MRD) detection using bespoke circulating tumor DNA (ctDNA) assays in localized soft tissue sarcoma (STS): A multicenter study.
Authors: Aisha Alshibany, Maggie Zhou, Emilie AK Warren, Kristen N. Ganjoo, Elizabeth Demicco, Jordan Feeney, Jasmine Lee, David Benjamin Shultz, Erik Spickard, Nam Bui, Kenneth Cardona, Abdulazeez Salawu, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2024)

11537 Background: Surgery and (neo)adjuvant radiotherapy (RT) are the mainstay curative treatments for localized STS. Despite treatment, up to 50% of STS patients experience metastatic relapse, and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative-intent treatment of STS is a potential biomarker for MRD and may identify patients who are likely to benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: This multicentre prospective study enrolled patients with localized, high-risk (grade ≥ 2, size ≥ 5 cm) STS. Blood samples were collected at diagnosis, post- radiotherapy, post-surgery, and at serial longitudinal time points for up to 2 years. Standard radiologic follow-up was performed concurrently. Whole exome sequencing of tumor tissue was carried out to identify patient-specific, single nucleotide variants. Personalized, and tumor-informed multiplex PCR next-generation sequencing-based ctDNA (Signatera) assays were used to track ctDNA in serial plasma samples. The primary endpoint was ctDNA detection rate of &gt;70% at diagnosis. Secondary endpoints were MRD detection after local therapy and correlation of ctDNA detection with disease relapse. Results: A total of 76 subjects (female n = 43; median age [range]: 58 [21- 84] years) were included in this study from Princess Margaret Cancer Center, Stanford University, and Emory University. The most common STS types observed were leiomyosarcoma (LMS, n = 28), liposarcoma (n = 14), (predominantly dedifferentiated [n = 6]), and myxofibrosarcoma (n = 11). Among 38 pts who had blood samples collected at baseline (time of surgery), ctDNA was positive in 30/38 (79%). A baseline sample prior to radiotherapy was collected in 24 pts. Following neoadjuvant radiotherapy, 8/24 pts (33%) who were ctDNA positive at baseline became ctDNA negative, while 29/30 became ctDNA-negative after surgical resection. Median follow-up was 19 months, and 19/76 pts (25%) experienced disease recurrence Among these 19 pts, ctDNA was detected in all pts with baseline studies. ctDNA was detected at or before radiologic recurrence in 9/19 pts (47%), predominantly LMS 4/9, with a median lead time of 64.8 days (range: 0-197 days). ctDNA was detected in 14/38 patients at baseline with no radiological recurrence during follow-up period. Conclusions: Personalized, tumor-informed ctDNA assays can detect MRD and has prognostic value after definitive therapy, surgery and (neo)adjuvant radiotherapy, in localized STS patients. Additional studies are ongoing to evaluate ctDNA as a predictive biomarker for benefit from AST in STS. Clinical trial information: NCT03818412 .