Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma

Maggie Zhou, Nam Bui, Richa Rathore, Sumedha Sudhaman, Giby V. George, Allyson K. Malashevich, Meenakshi Malhotra, Minetta C. Liu, Alexey Aleshin, Kristen N. Ganjoo

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4–6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19–346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention.

Original languageEnglish (US)
Article number157
JournalCancers
Volume15
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • circulating tumor DNA
  • leiomyosarcoma
  • soft tissue sarcomas

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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