Evidence map›Paper›PMID 40392096›Full record

Observational studyClinical cancer research : an official journal of the American Association for Cancer Research2025

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, Justin Rhoades, Kan Xiong, Laurel Walsh, Andjela Crnjac, Timothy Blewett, Yana Al-Inaya, Julia Mendel, Daniel A Ruiz-Torres, Vasileios Efthymiou and 6 more

Abstract readObservational Study
In one paragraph

Observational study in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Edward S SimDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0002-1632-286X
Justin RhoadesBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0002-0630-908X
Kan XiongBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0002-0639-5803
Laurel WalshBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0009-0008-5606-8166
Andjela CrnjacBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0009-0005-9651-4288
Timothy BlewettBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0009-0000-8750-8138
Yana Al-InayaDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0003-1881-2376
Julia MendelDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0009-0008-3257-171X
Daniel A Ruiz-TorresDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0001-6215-3369
Vasileios EfthymiouDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0001-6139-9535
Gjystina LumajDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0009-0009-1732-3299
William J BenjaminDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0003-4116-7408
G Mike MakrigiorgosDepartment of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.ORCID 0000-0001-7598-2406
Shervin TabriziBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0003-2780-8432
Viktor A AdalsteinssonBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0003-4555-2485
Daniel L FadenDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0001-5284-7762

Funding

Comprehensive minimal residual disease tracking in cancerR01CA221874 · NCI · DANA-FARBER CANCER INST · PI Viktor Adalsteinsson, G. Mike Makrigiorgos · 2018 to 2026
$2.5M
RESEARCH TRAINING IN OTOLARYNGOLOGYT32DC000020 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI JUNG, DAVID H, SIMONYAN, KRISTINA · 1990 to 2025
$2.4M
Dissecting temporal and spatial dynamics of immunotherapy resistanceK23DE029811 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2021 to 2025
$869k
Circulating HPV DNA as a Prediagnostic Marker of Oropharyngeal CancerR21CA267152 · NCI · UNIVERSITY OF KENTUCKY · PI FADEN, DANIEL, KUHS, KRYSTLE A. · 2022 to 2023
$431k
In vivo enrichment of cell-free DNA to boost sensitivity of circulating nucleic-acid based diagnosticsK08EB036081 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TABRIZI, SHERVIN · 2024 to 2025
$388k
Cell free HPV DNA detection in the diagnostic and surgical settingsR03DE030550 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2022 to 2023
$336k
Gerstner Family FoundationNational Institute on Deafness and Other Communication Disorders (NIDCD) T32DC000020National Institutes of Health (NIH) 2R01CA221874-04National Institutes of Health (NIH) K08EB036081NCI NIH HHS R01 CA221874NCI NIH HHS R21 CA267152NIBIB NIH HHS K08 EB036081NIDCD NIH HHS T32 DC000020NIDCR NIH HHS K23 DE029811NIDCR NIH HHS R03 DE030550
6 · The paper itself

Abstract

purposeAlthough 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

designWe 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.

resultsAmong 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.

conclusionsEarly 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.

Indexed as

Circulating Tumor DNAHead and Neck NeoplasmsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckWhole Genome SequencingAgedBiomarkers, TumorFemaleHumansMaleMiddle AgedMutationNeoplasm, ResidualPostoperative PeriodPrognosisProspective StudiesBiomarkers, TumorCirculating Tumor DNA

Identifiers

PMID40392096
PMCPMC12353190

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.