Evidence map›Paper›PMID 36410685›Full record

Trial reportInternational journal of radiation oncology, biology, physics2023

Outcomes Stratification of Head and Neck Cancer Using Pre- and Post-treatment DNA Methylation From Peripheral Blood.

David C Qian, Bryan C Ulrich, Gang Peng, Hongyu Zhao, Karen N Conneely, Andrew H Miller, Deborah W Bruner, Ronald C Eldridge, Evanthia C Wommack, Kristin A Higgins and 8 more

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in International journal of radiation oncology, biology, physics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 49% of its field
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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Impact of anthracycline-based chemotherapy on RB1 gene methylation in peripheral blood leukocytes and biomarkers of oxidative stress and inflammation in sarcoma patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Article
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

18 authors at 3 institutions in 1 country.

David C QianDepartment of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Bryan C UlrichDepartment of Medicine, Massachusetts General Hospital, Boston, MA.
Gang PengDepartment of Biostatistics, Yale School of Public Health, New Haven, CT.
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, New Haven, CT.
Karen N ConneelyDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA.
Andrew H MillerDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.
Deborah W BrunerNell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA.
Ronald C EldridgeNell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA.
Evanthia C WommackDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.
Kristin A HigginsDepartment of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Dong M ShinDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Nabil F SabaDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Alicia K SmithDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.
Barbara BurtnessSection of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Henry S ParkDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT.
William A StokesDepartment of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Jonathan J BeitlerDepartment of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Canhua XiaoNell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA. Electronic address: canhua.xiao@emory.edu.
Emory University · USYale University · USMassachusetts General Hospital · US

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Ragini Reiney Kudchadkar · 2009 to 2026
$47.5M
Institutional Career Development CoreKL2TR002381 · NCATS · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Anandi Nayan Sheth · 2017 to 2026
$14.1M
Neuro HPA Project 1U54AG062334 · NIA · EMORY UNIVERSITY · PI Ighovwerha Ofotokun · 2018 to 2026
$12.2M
Epigenetic Mechanisms of Inflammation and Fatigue in Head and Neck Cancer PatientsR01NR015783 · NINR · EMORY UNIVERSITY · PI XIAO, CANHUA · 2016 to 2018
$1.5M
Fatigue in Head and Neck Cancer: Role of pro- and anti-inflammatory signalingR00NR014587 · NINR · EMORY UNIVERSITY · PI XIAO, CANHUA · 2015 to 2017
$706k
Fatigue in Head and Neck Cancer: Role of pro- and anti-inflammatory signalingK99NR014587 · NINR · EMORY UNIVERSITY · PI XIAO, CANHUA · 2013 to 2014
$180k
NCATS NIH HHS KL2 TR002381NCATS NIH HHS UL1 TR002378NCI NIH HHS P30 CA138292NIA NIH HHS U54 AG062334NINR NIH HHS K99 NR014587NINR NIH HHS R00 NR014587NINR NIH HHS R01 NR015783
6 · The paper itself

Abstract

purposeEstablished prognostic factors for head and neck squamous cell carcinoma (HNSCC) mostly consist of clinical and tumor features assessed before treatment. We report a novel application of DNA methylation in peripheral blood before and after radiation therapy to further improve outcomes stratification. METHODS AND MATERIALS: Peripheral blood samples from patients with nonmetastatic HNSCC were obtained for methylation analysis 1 week before and 1 month after radiation therapy. Patients were randomized 1:1 to a Discovery Cohort or a Validation Cohort. In the Discovery Cohort, associations between genome-wide methylation change (posttreatment minus pretreatment) and recurrence-free survival (RFS) as well as overall survival (OS) were evaluated using Cox regression. A methylation risk score (MRS) was then constructed from methylation levels at the top associated sites, filtered for residing within the regulatory regions of genes expressed in cells of hematopoietic lineage. The prognostic value of MRS was separately assessed in the Discovery and Validation Cohorts.

resultsBetween December 2013 and September 2018, 115 patients participated in this study. Human papilloma virus negative status, oral cavity cancer, gastrostomy tube insertion, and higher neutrophil count before radiation therapy were associated with shorter RFS and OS (P < .05). Genes downstream of the methylation sites comprising MRS are HIF1A, SF1, LGALS9, and FUT5, involved in hypoxia response, blood cell maturation, and immune modulation. High MRS (in the top third) was significantly associated with worse RFS (hazard ratio [HR], 7.1; 95% confidence interval [CI], 1.4-35.5; P = .016) and OS (HR, 15.9; 95% CI, 1.6-153.6; P = .017) in the Discovery Cohort, independent of the aforementioned risk factors. These findings were replicated in the Validation Cohort, for which high MRS also independently predicted worse RFS (HR, 10.2; 95%, CI 2.4-43.4; P = .002) and OS (HR, 3.7; 95% CI, 1.3-10.4; P = .015).

conclusionsWe successfully trained and validated a signature of DNA methylation in peripheral blood before and after radiation therapy that stratified outcomes among patients with HNSCC, implicating the potential for genomics-tailored surveillance and consolidation treatment.

Indexed as

Carcinoma, Squamous CellHead and Neck NeoplasmsBiomarkers, TumorDNA MethylationHumansPrognosisSquamous Cell Carcinoma of Head and NeckBiomarkers, Tumor

Identifiers

PMID36410685
PMCPMC12272450
OpenAlexW4309661431

What OpenQuestion holds

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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.