Evidence map›Paper›PMID 41270698›Full record

ArticleESMO open2025

Whole-exome ctDNA sequencing reveals intratumoral heterogeneity and drivers of relapse in locally advanced head and neck cancer.

G Bruixola, J Martín-Arana, F Gimeno-Valiente, J A Carbonell-Asins, B García-Micó, B Martínez-Castedo, D González-Camblor, N Grimalt, M García-Bartolomé, C Alfaro-Cervelló and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

G BruixolaDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
J Martín-AranaDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
F Gimeno-ValienteCancer Evolution and Genome Instability Laboratory, University College London Cancer Institute, London, UK.
J A Carbonell-AsinsBiostatistics Unit, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.
B García-MicóDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
B Martínez-CastedoDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
D González-CamblorDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
N GrimaltDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
M García-BartoloméDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
C Alfaro-CervellóDepartment of Pathology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
V EscorihuelaOtorhinolaryngology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.
M E IglesiasOral and Maxillary Surgery Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.
M MaroñasRadiation Oncology Department, Hospital Clinico Universitario de Valencia, University of Valencia, Valencia, Spain.
D DualdeRadiology Department, Hospital Clinico Universitario de Valencia, University of Valencia, Valencia, Spain.
A CervantesDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: andres.cervantes@uv.es.
N TarazonaDepartment of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: noetalla@incliva.es.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mechanisms underlying tumor evolution and treatment resistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are not fully understood. This study used whole-exome sequencing (WES) of paired tumor tissue and circulating tumor DNA (ctDNA) to analyze intratumoral heterogeneity (ITH) and clonal dynamics at diagnosis and relapse. PATIENTS AND

methodsBetween January 2017 and September 2022, we enrolled 152 patients with LA-HNSCC treated with radical chemoradiotherapy. Tumor tissue and plasma samples were collected at baseline and at relapse. WES was carried out on DNA extracted from tissue, plasma, and germline samples. Oncogenic variants were analyzed to evaluate tumor evolution and ITH. Concordance, pathway alterations, and associations with survival were examined.

resultsOut of the 152 patients selected, 81 were excluded based on clinical criteria. Of the 71 remaining patients, 37 had the complete set of samples of adequate quality for analysis. The most frequent mutations involved TP53 (48%), KMT2D (34%), and NOTCH1 (34%) at diagnosis. Pathogenic germline variants, including actionable mutations in BRCA2, CHK2, and KIT, were identified in 13.5% of cases. Concordance between tissue and plasma was low (median 11.8% at baseline, 12.4% at relapse), with up to 67% of oncogenic variants found only in ctDNA. Longitudinal analysis revealed limited overlap (10.3%) between baseline and relapse ctDNA, with some emerging resistance-associated mutations in PI3K-mTORC2 and ATM-CHK2 pathways. Alterations in IL6-JAK-STAT3 and RHO GTPase pathways were enriched in locoregional relapses (adjusted P < 0.001). Mutations in MMP15 and PTPRE were linked to shorter locoregional progression-free survival, whereas PDE2A mutations were associated with prolonged progression-free survival.

conclusionsWES of ctDNA uncovers extensive ITH and identifies molecular drivers of resistance not captured by tissue biopsies. These findings support the use of plasma ctDNA analysis to monitor tumor evolution and personalize follow-up in LA-HNSCC, especially given the anatomical complexity that often limits repeated tissue sampling.

Indexed as

Circulating Tumor DNAExome SequencingHead and Neck NeoplasmsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckAdultAgedBiomarkers, TumorFemaleHumansMaleMiddle AgedBiomarkers, TumorCirculating Tumor DNAbiomarkersctDNAintratumor heterogeneityLA-HNSCCprecision medicine

Identifiers

PMID41270698
PMCPMC12670099

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.