Evidence map›Paper›PMID 42154530›Full record

Trial reportThe Journal of clinical investigation2026

Genome-wide variation in cell-free DNA end-motif entropy predicts immunotherapy response in head and neck cancer.

Ravi Bandaru, Hailu Fu, Haizi Zheng, Jocelyn Liang, Li Wang, Shuchi Gulati, Benjamin H Hinrichs, Mingxiang Teng, Bin Zhang, Masha Kocherginsky and 10 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02641093 (Phase II Investigation of Adjuvant Combined Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma), which is not on this map. Not yet cited in PubMed.

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

NCT02641093 phase2active not recruitingnot on this map

Phase II Investigation of Adjuvant Combined Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma

TypeinterventionalSponsorTrisha Wise-DraperRan2016 to 2026Enrolled96ConditionsHead and Neck CancerArmsPembrolizumab, Surgery, Radiation Therapy, Cisplatin
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Ravi BandaruDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Hailu FuDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Haizi ZhengDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jocelyn LiangDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Li WangDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Shuchi GulatiDivision of Hematology/Oncology, and.
Benjamin H HinrichsDepartment of Pathology, University of Cincinnati, Cincinnati, Ohio, USA.
Mingxiang TengDepartment of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, USA.
Bin ZhangDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Masha KocherginskyDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
De-Chen LinCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
David A HildemanDivision of Immunobiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Francis P WordenUniversity of Michigan Cancer Center, Ann Arbor, Michigan, USA.
Matthew OldDepartment of Otolaryngology, Ohio State University, Columbus, Ohio, USA.
Neal E DunlapDepartment of Radiation Oncology, University of Louisville, Louisville, Kentucky, USA.
John M KaczmarDivision of Hematology/Oncology, Medical University of South Carolina, Charleston, South Carolina, USA.
Maura L GillisonThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Dalia El-GamalDivision of Hematology/Oncology, and.
Trisha Wise DraperDivision of Hematology/Oncology, and.
Yaping LiuDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Funding

Inferring 1D and 3D epigenomes by cell-free DNA fragmentation patterns.R56HG012360 · NHGRI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LIU, YAPING · 2022 to 2022
$569k
NHGRI NIH HHS R56 HG012360
6 · The paper itself

Abstract

BACKGROUNDMinimally invasive biomarkers predicting the immunotherapy response in head and neck squamous cell carcinoma (HNSCC) remain an unmet clinical need.METHODSIn a prospective, multi-institutional phase II trial, we performed whole-genome sequencing of 185 longitudinal plasma cell-free DNA (cfDNA) samples from 68 patients with locally advanced, surgically resectable HNSCC who received neoadjuvant and adjuvant pembrolizumab. We developed the regional motif diversity score (rMDS), a fragmentomic metric that quantifies the entropy of cfDNA 5'-end motifs across genomic regions.RESULTSUnsupervised analysis showed that rMDS robustly distinguished responders from nonresponders, outperforming established fragmentomic metrics and copy number alterations while remaining independent of technical confounders. Longitudinal rMDS changes localized to regions enriched for immune-, lectin-, and keratinization-related genes - hallmarks of squamous cell carcinoma - reflecting tumor-peripheral immunity interplay during treatment. The most dynamic regions clustered at telomere-proximal loci, suggesting a link between telomere biology and cfDNA fragmentation. An rMDS-based machine learning classifier achieved AUC 0.89-0.99 across validation settings, with the highest accuracy after treatment, outperforming PD-L1 expression and tumor fraction in matched samples. Predicted responders showed improved disease-free survival (log-rank P = 0.035; HR 2.67, 95% CI 1.03-6.92).CONCLUSIONrMDS represents a biologically meaningful and clinically actionable biomarker for the immunotherapy response in HNSCC, and merits integration into future risk assessment frameworks.TRIAL REGISTRATIONClinicalTrials.gov NCT02641093.FUNDINGNational Human Genome Research Institute (NHGRI), NIH grant R56HG012360; startup funds from Cincinnati Children's Hospital Medical Center, Northwestern University, and Robert H. Lurie Comprehensive Cancer Center; Science Olympiad Alumni Research Grant, Science Olympiad USA Foundation; Merck Sharp & Dohme Corp.

Indexed as

Antibodies, Monoclonal, HumanizedCell-Free Nucleic AcidsHead and Neck NeoplasmsImmunotherapySquamous Cell Carcinoma of Head and NeckAgedBiomarkers, TumorEntropyFemaleHumansMaleMiddle AgedProspective StudiesAntibodies, Monoclonal, HumanizedBiomarkers, TumorCell-Free Nucleic AcidspembrolizumabCancer immunotherapyEpigeneticsGeneticsHead and neck cancerOncology

Identifiers

PMID42154530
PMCPMC13322381

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Registered trials

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.