Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background: Systemic sclerosis (SSc) and dermatomyositis (DM) are autoimmune diseases that have been proposed as models of cancer immunoediting. Autoantibody-defined subsets show divergent cancer risks, yet malignancy often remains clinically occult. We tested whether circulating tumor DNA (ctDNA) can reveal subclinical cancer in new-onset SSc and DM. Methods: We prospectively recruited adults with recent SSc or DM onset. Plasma ctDNA was assessed using a targeted next-generation sequencing panel covering commonly mutated cancer genes. Patients were followed for 18-24 months on average. ctDNA positivity was correlated with subsequent cancer diagnoses. Findings: Among 134 patients (69 SSc, 65 DM), cancer was diagnosed in six (4.5%; three SSc, three DM). ctDNA was detected in four of these six patients (67%) a median of 13 months (range 1.4-17) before clinical diagnosis; in three of four patients, mutations detected in plasma matched those subsequently identified in the same patients primary tumors. ctDNA was also detected in 16 of 128 patients without a cancer diagnosis. ctDNA positivity conferred an 11.4-fold higher risk of malignancy relative to ctDNA negativity and yielded a negative predictive value of 98% and a positive predictive value of 20% for cancer within the observation window. Interpretation: ctDNA testing identified most cancers that emerged within 18 months in new-onset SSc and DM and stratified near-term cancer risk. These findings support larger, interventional trials to determine whether ctDNA-guided surveillance improves timeliness of cancer detection, optimizes imaging and biopsy strategies, and enhances outcomes in patients with SSc and DM.
Source: medRxiv
Authors: Christopher A Mecoli, Yuxuan Wang, Ji Soo Kim, XingYao Wang, Adrianne Woods, Christopher Douville, Sam D Curtis, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Matthew B Smith, Lauren Fisher, Gwen Leatherman, Laura K Hummers, Lisa Christopher-Stine, Julie J Paik, Jemima Albayda, Fredrick M Wigley, Antony Rosen, Livia Casciola-Rosen, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Ami A Shah
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225384314