Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Aug 14;31(16):3494-3502.
doi: 10.1158/1078-0432.CCR-25-0307.

Early Postoperative Minimal Residual Disease Detection with MAESTRO Is Associated with Recurrence and Worse Survival in Patients with Head and Neck Cancer

Edward S Sim  1 , Justin Rhoades  2 , Kan Xiong  2 , Laurel Walsh  2 , Andjela Crnjac  2 , Timothy Blewett  2 , Yana Al-Inaya  1 , Julia Mendel  1 , Daniel A Ruiz-Torres  1 , Vasileios Efthymiou  1 , Gjystina Lumaj  1 , William J Benjamin  1 , G Mike Makrigiorgos  3 , Shervin Tabrizi  2   4   5 , Viktor A Adalsteinsson  2 , Daniel L Faden  1   2
Affiliations
Observational Study

Early Postoperative Minimal Residual Disease Detection with MAESTRO Is Associated with Recurrence and Worse Survival in Patients with Head and Neck Cancer

Edward S Sim et al. Clin Cancer Res. .

Abstract

Purpose: Although ctDNA is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed for accurate MRD detection at clinically relevant time points. Ultrasensitive MRD detection early after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics are poorly understood.

Experimental design: We applied minor allele-enriched sequencing through recognition oligonucleotides (MAESTRO), a whole-genome, tumor-informed, mutation enrichment sequencing assay, in a pooled testing format called MAESTRO-Pool, to plasma samples from patients with HNSCC collected shortly after surgery and during surveillance. We evaluated whether early MRD detection could predict outcomes.

Results: Among 24 patients with predominantly human papillomavirus-independent (95.8%) HNSCC, rapid ctDNA clearance occurred by the first postoperative sample (1-3 days postoperatively) in nine patients without an event (recurrence or death). Thirteen of fifteen patients with an event were MRD-positive (positive predictive value = 92.9%; negative predictive value = 80%) with a median tumor fraction (TFx) of 54 parts per million (ppm; range 6-1,177 ppm). In the first and last samples of the early postoperative window, 8/13 and 10/13 patients, respectively, had TFx below 100 ppm, the detection limit of leading commercial assays. Early MRD detection correlated with worse overall survival (HR, 8.3; 95% confidence interval, 1.1-66.1; P = 0.02) and event-free survival (HR, 27.4; 95% confidence interval, 3.5-214.5; P < 0.0001) independent of high-risk pathology.

Conclusions: Early postoperative MRD detection by MAESTRO was associated with recurrence and worse survival. Given the ultralow TFxs observed, ultrasensitive assays will be essential for reliable MRD detection during early postoperative time points to enable personalized adjuvant therapy decision-making in HNSCC. See related article by Bryan et al., p. 3483.

PubMed Disclaimer

Conflict of interest statement

S.T. has received or receives consulting fees and has stock options with Amplifyer Bio and receives honorarium from Rapid Novor. V.A.A. and G.M.M. are co-inventors on a patent application covering the MAESTRO MRD test licensed to Exact Sciences and receive research funding from Exact Sciences which was not involved in this study. V.A.A is also a co-founder and advisor of Amplifyer Bio which was not involved in this study. D.L.F receives salary support from NIH/NIDCR K23 DE029811, NIH/NIDCR R03 DE030550 and NIH/NCI R21 CA267152. D.L.F has received research funding or in-kind funding from Bristol-Myers Squibb, Calico, Predicine, BostonGene, Neogenomics and Haystack (Quest). He has received consulting fees from Merck, Noetic, Chrysalis Biomedical Advisors, Arcadia, and Focus. None of these sources relate to the work in this manuscript. The remaining authors declare no conflicts of interest.

Update of

References

    1. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2025: Head and Neck Cancers [Internet] 2024. Nov. Available from: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
    1. Rettig EM, D’Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015;24:379–96. - PubMed
    1. Nenclares P, Rullan A, Tam K, Dunn LA, St. John M, Harrington KJ. Introducing Checkpoint Inhibitors Into the Curative Setting of Head and Neck Cancers: Lessons Learned, Future Considerations. Am Soc Clin Oncol Educ Book. Wolters Kluwer; 2022;511–26. - PubMed
    1. Chen Y, Zhong N-N, Cao L-M, Liu B, Bu L-L. Surgical margins in head and neck squamous cell carcinoma: A narrative review. Int J Surg Lond Engl. 2024;110:3680–700. - PMC - PubMed
    1. Ng SP, Pollard C, Berends J, Ayoub Z, Kamal M, Garden AS, et al. Utility of Surveillance Imaging in Patients with Head and Neck Cancer Treated with Definitive Radiotherapy. Cancer. 2019;125:1823–9. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources