Circulating Tumor DNA in Patients with Early-Onset Systemic Sclerosis and Dermatomyositis
- 1Johns Hopkins University School of Medicine
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.
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BibTeX
@misc{mecoli2026circulating,
title = {{Circulating Tumor DNA in Patients with Early-Onset Systemic Sclerosis and Dermatomyositis}},
author = {C. A. Mecoli and Y. Wang and J. S. Kim and X. Wang and A. Woods and C. Douville and S. D. Curtis and M. Popoli and J. Ptak and L. Dobbyn and N. Silliman and M. B. Smith and L. Fisher and G. Leatherman and L. K. Hummers and L. Christopher-Stine and J. J. Paik and J. Albayda and F. M. Wigley and A. Rosen and L. Casciola-Rosen and C. Bettegowda and N. Papadopoulos and K. W. Kinzler and B. Vogelstein and A. A. Shah},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.26364657},
url = {https://www.medrxiv.org/content/10.64898/2026.11.06.26364657v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Circulating Tumor DNA in Patients with Early-Onset Systemic Sclerosis and Dermatomyositis
AU - C. A. Mecoli
AU - Y. Wang
AU - J. S. Kim
AU - X. Wang
AU - A. Woods
AU - C. Douville
AU - S. D. Curtis
AU - M. Popoli
AU - J. Ptak
AU - L. Dobbyn
AU - N. Silliman
AU - M. B. Smith
AU - L. Fisher
AU - G. Leatherman
AU - L. K. Hummers
AU - L. Christopher-Stine
AU - J. J. Paik
AU - J. Albayda
AU - F. M. Wigley
AU - A. Rosen
AU - L. Casciola-Rosen
AU - C. Bettegowda
AU - N. Papadopoulos
AU - K. W. Kinzler
AU - B. Vogelstein
AU - A. A. Shah
PY - 2026
DA - 2026/11/06
PB - medRxiv
DO - 10.64898/2026.11.06.26364657
UR - https://www.medrxiv.org/content/10.64898/2026.11.06.26364657v1
AB - 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.
ER -