TY - JOUR
T1 - Tumor-informed circulating tumor DNA stratifies recurrence risk and survival in anal squamous cell carcinoma
AU - Romesser, Paul B.
AU - Bercz, Aron
AU - Alvarez, Janet
AU - Kostrzewa, Caroline E.
AU - Adames, Angela
AU - Liu, Elisa K.
AU - Ho, Yu Jui
AU - Mohan, Natasha
AU - Reyngold, Marsha
AU - Yaeger, Rona
AU - Roth O’Brien, Diana A.
AU - Cuaron, John J.
AU - Zinovoy, Melissa
AU - Olinger, Christine
AU - Ravella, Revathi
AU - Lisanti, Jeanine
AU - Zambare, Wini
AU - Aushev, Vasily N.
AU - Sharma, Shruti
AU - Malhotra, Meenakshi
AU - Rivero-Hinojosa, Samuel
AU - Schauer, Nathan
AU - Jurdi, Adham
AU - Liu, Minetta C.
AU - Wu, Abraham
AU - Williams, Vonetta
AU - Connell, Louise
AU - Pappou, Emmanouil
AU - Rao, Devika
AU - Segal, Neil H.
AU - Paty, Philip B.
AU - Weiser, Martin R.
AU - Cercek, Andrea
AU - Marcet, Jorge
AU - Garcia-Aguilar, Julio
AU - Crane, Chris H.
AU - Gonen, Mithat
AU - Smith, J. Joshua
AU - Tuli, Richard
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12
Y1 - 2026/12
N2 - Patients with anal squamous cell carcinoma (ASCC) who fail chemoradiation (CRT) have poor outcomes, underscoring the need for biomarkers to guide risk stratification. In a real-world two-center cohort of 84 adults with non-metastatic ASCC treated with curative-intent CRT, we prospectively evaluate a tumor-informed circulating tumor DNA (ctDNA) assay (SignateraTM, Natera). Here we show that across 647 plasma specimens, ctDNA is positive at pre-treatment in 79% (61/77), including 89% (24/27) with stage III disease. End-of-treatment ctDNA positivity identifies patients with inferior one-year outcomes: 63% overall survival, 44% progression-free survival, and 39% locoregional failure. Conversely, patients who were ctDNA-negative at baseline or who cleared ctDNA during-treatment have 100% locoregional failure-free survival. During surveillance, ctDNA re-emergence precedes clinical or radiographic relapse in every case. These findings support the consideration of ctDNA as a dynamic, treatment-responsive biomarker warranting prospective validation for risk-adapted surveillance and adjuvant therapy in ASCC.
AB - Patients with anal squamous cell carcinoma (ASCC) who fail chemoradiation (CRT) have poor outcomes, underscoring the need for biomarkers to guide risk stratification. In a real-world two-center cohort of 84 adults with non-metastatic ASCC treated with curative-intent CRT, we prospectively evaluate a tumor-informed circulating tumor DNA (ctDNA) assay (SignateraTM, Natera). Here we show that across 647 plasma specimens, ctDNA is positive at pre-treatment in 79% (61/77), including 89% (24/27) with stage III disease. End-of-treatment ctDNA positivity identifies patients with inferior one-year outcomes: 63% overall survival, 44% progression-free survival, and 39% locoregional failure. Conversely, patients who were ctDNA-negative at baseline or who cleared ctDNA during-treatment have 100% locoregional failure-free survival. During surveillance, ctDNA re-emergence precedes clinical or radiographic relapse in every case. These findings support the consideration of ctDNA as a dynamic, treatment-responsive biomarker warranting prospective validation for risk-adapted surveillance and adjuvant therapy in ASCC.
UR - https://www.scopus.com/pages/publications/105035332184
UR - https://www.scopus.com/pages/publications/105035332184#tab=citedBy
U2 - 10.1038/s41467-026-69984-y
DO - 10.1038/s41467-026-69984-y
M3 - Article
C2 - 41748568
AN - SCOPUS:105035332184
SN - 2041-1723
VL - 17
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3241
ER -