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<p>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 (Signatera<sup>TM</sup>, 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.</p>

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Tumor-informed circulating tumor DNA stratifies recurrence risk and survival in anal squamous cell carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月26日

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  • Paul B. Romesser,
  • Aron Bercz,
  • Janet Alvarez,
  • Caroline E. Kostrzewa,
  • Angela Adames,
  • Elisa K. Liu,
  • Yu-Jui Ho,
  • Natasha Mohan,
  • Marsha Reyngold,
  • Rona Yaeger,
  • Diana A. Roth O’Brien,
  • John J. Cuaron,
  • Melissa Zinovoy,
  • Christine Olinger,
  • Revathi Ravella,
  • Jeanine Lisanti,
  • Wini Zambare,
  • Vasily N. Aushev,
  • Shruti Sharma,
  • Meenakshi Malhotra,
  • Samuel Rivero-Hinojosa,
  • Nathan Schauer,
  • Adham Jurdi,
  • Minetta C. Liu,
  • Abraham Wu,
  • Vonetta Williams,
  • Louise Connell,
  • Emmanouil Pappou,
  • Devika Rao,
  • Neil H. Segal,
  • Philip B. Paty,
  • Martin R. Weiser,
  • Andrea Cercek,
  • Jorge Marcet,
  • Julio Garcia-Aguilar,
  • Chris H. Crane,
  • Mithat Gonen,
  • J. Joshua Smith,
  • Richard Tuli

摘要

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.