Evidence map›Paper›PMID 34158359›Full record

Observational studyClinical cancer research : an official journal of the American Association for Cancer Research2021

Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma.

Justin M Burgener, Jinfeng Zou, Zhen Zhao, Yangqiao Zheng, Shu Yi Shen, Shao Hui Huang, Sareh Keshavarzi, Wei Xu, Fei-Fei Liu, Geoffrey Liu and 9 more

Open access · greenAbstract readObservational Study
In one paragraph

Observational study in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 2 pooled it
6.1field-weighted citation impact, top 2% 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

63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

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3 more citing papers are in PubMed but not listed here.

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

19 authors at 1 institution in 1 country.

Justin M BurgenerPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Jinfeng ZouPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Zhen ZhaoPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Yangqiao ZhengPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Shu Yi ShenPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0001-7036-2291
Shao Hui HuangPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-8072-4388
Sareh KeshavarziPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Wei XuPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Fei-Fei LiuPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0003-4344-6486
Geoffrey LiuPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-2603-7296
John N WaldronPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Ilan WeinrebPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Anna SpreaficoPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Lillian L SiuPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-3500-0540
John R de AlmeidaPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
David P GoldsteinPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Michael M HoffmanPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-4517-1562
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. scott.bratman@rmp.uhn.ca daniel.decarvalho@uhnresearch.ca.ORCID 0000-0002-8572-5259
Scott V BratmanPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. scott.bratman@rmp.uhn.ca daniel.decarvalho@uhnresearch.ca.ORCID 0000-0001-8610-4908
University Health Network · CA

Funding

CIHR 201512MSH-360794-228629CIHR FDN 148430
6 · The paper itself

Abstract

purposeCirculating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation. EXPERIMENTAL

designWe conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I-IVA human papillomavirus-negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls.

resultsCAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (

conclusionsTumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.

Indexed as

Circulating Tumor DNADNA MethylationHead and Neck NeoplasmsHumansMutationProspective StudiesSquamous Cell Carcinoma of Head and NeckCirculating Tumor DNA

Identifiers

PMID34158359
PMCPMC9401560
OpenAlexW3173578209

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.