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Basic Science and Translational Research

(P 03) CONGRUENCE OF CIRCULATING TUMOR DNA & RADIOGRAPHIC RESPONSE IN BONE AND SOFT TISSUE SARCOMA

    Author(s)

  • Chahat Rana, MD/MPH

    Internal Medicine Resident
    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

    • Co-Author(s)

  • DW

    Daniel Wang, MD

    Medical Oncologist
    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

  • Amanda Dann, MD (she/her/hers)

    Assistant Professor of Surgery
    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

  • NA

    Nissy Alex, B.S

    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

  • SC

    Sanjay Chandrashekaran, MD

    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

Objective: The prognostic value of tumor-informed ctDNA (Signatera, Natera Inc) in advanced sarcoma remains unclear. We evaluated whether ctDNA offers prognostic insight by analyzing its congruence with radiography in real-world conditions.

Methods: We assessed congruence between ctDNA and imaging at serial timepoints in advanced sarcoma patients with ≥2 ctDNA assessments taken ±30 days of imaging. Congruence (true positive/negative) was determined by two methods (A) Discrete Pairings (DP): increasing/positive ctDNA vs progression/persistence or decreasing/negative ctDNA with clinical benefit; or (B) Positive Conversion (PC): surveillance patients with baseline negative ctDNA and no evidence of disease (NED) scans, with congruence determined at last follow-up by positive conversion with progression or persistent negativity with NED. DP includes patients on treatment.

Results: 32 patients (leiomyosarcoma-9, liposarcoma-5, Ewing-3, angiosarcoma-3, osteosarcoma-2, clear cell-2, spindle cell-2, other-6) from 5/2022-5/2025 met criteria (median follow-up 301 days, 5 ctDNA assessments). 15/32 received treatment, including chemotherapy (11), immunotherapy (6), radiation (3), and/or ablation (2). In DP (n=159), 87% (138/159) were congruent (69% sensitivity, 97% specificity, PPV 93%, NPV 84%) (Table 1). In PC, 17 patients (median follow-up 281 days) were analyzed: 10/17 remained NED (100% congruence (10/10)), 7 recurred (71% congruence (5/7)). Notably, 2/3 DP false positives progressed on follow-up scans; 14/18 false negatives became congruent with scans (median time to congruence: 5.7mo) while 4/18 became NED.

Conclusion: Tumor-informed ctDNA shows promise as a monitoring tool in sarcoma. While DP sensitivity was < 70%, most false negatives became congruent over time, indicating possible ctDNA lag. Further studies are ongoing to assess tumor-type and treatment effects on ctDNA shedding.

ctDNA Congruency by Discrete Pairings and Positive Conversion
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