Evidence map›Paper›PMID 37452374›Full record

ArticleBMC medicine2023

Individualized dynamic methylation-based analysis of cell-free DNA in postoperative monitoring of lung cancer.

Kezhong Chen, Guannan Kang, Zhihong Zhang, Analyn Lizaso, Stephan Beck, Iben Lyskjær, Olga Chervova, Bingsi Li, Haifeng Shen, Chenyang Wang and 6 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03634826 (A Prospective Study of Longitudinal Monitoring in Surgical Lung Cancer Patients by Circulating Tumor DNA and Its Methylation), which is not on this map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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.

NCT03634826 unknown statusnot on this map

A Prospective Study of Longitudinal Monitoring in Surgical Lung Cancer Patients by Circulating Tumor DNA and Its Methylation

TypeobservationalSponsorPeking University People's HospitalRan2018 to 2022Enrolled200ConditionsCarcinoma, Lung Cancer, NSCLC, Lung Neoplasm
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

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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 at 6 institutions in 2 countries.

Kezhong Chen *Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China. chenkezhong@pkuph.edu.cn.
Guannan Kang *Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China.
Zhihong Zhang *Burning Rock Biotech, Guangzhou, 510300, China.
Analyn LizasoBurning Rock Biotech, Guangzhou, 510300, China.
Stephan BeckUniversity College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK.
Iben LyskjærUniversity College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK.
Olga ChervovaUniversity College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK.
Bingsi LiBurning Rock Biotech, Guangzhou, 510300, China.
Haifeng ShenThoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China.
Chenyang WangBurning Rock Biotech, Guangzhou, 510300, China.
Bing LiBurning Rock Biotech, Guangzhou, 510300, China.
Heng ZhaoThoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China.
Xi LiBurning Rock Biotech, Guangzhou, 510300, China.
Fan YangThoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China. yangfan@pkuph.edu.cn.
Nnennaya KanuCancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK. n.kanu@ucl.ac.uk.
Jun WangThoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China. wangjun@pkuph.edu.cn.
Burning Rock Biotech (China) · CNPeking University · CNPeking University People's Hospital · CNUniversity College London · GBCRUK Lung Cancer Centre of Excellence · GBLondon Cancer · GB

Funding

Beijing Natural Science Foundation L222021CAMS Innovation Fund for Medical Sciences(CIFMS) 2022-I2M-C&T-B-120National Natural Science Foundation of China No.82072566National Natural Science Foundation of China No.92059203Peking University People's Hospital Research and Development Funds RZ2022-03Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences 2021RU002
6 · The paper itself

Abstract

backgroundThe feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative monitoring remains unestablished. We aim to investigate the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients.

methodsMatched tumor, tumor-adjacent tissues, and longitudinal blood samples from a cohort (MEDAL) were analyzed by ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort (n = 195) and validated in an independent cohort (DYNAMIC, n = 36).

resultsTumor-informed methylation status enabled an accurate recurrence risk assessment better than the tumor-naïve methylation approach. Baseline timMRD-scores were positively correlated with tumor burden, invasiveness, and the existence and abundance of somatic mutations. Patients with higher timMRD-scores at postoperative time-points demonstrated significantly shorter disease-free survival in the MEDAL cohort (HR: 3.08, 95% CI: 1.48-6.42; P = 0.002) and the independent DYNAMIC cohort (HR: 2.80, 95% CI: 0.96-8.20; P = 0.041). Multivariable regression analysis identified postoperative timMRD-score as an independent prognostic factor for lung cancer. Compared to tumor-informed somatic mutation status, timMRD-scores yielded better performance in identifying the relapsed patients during postoperative follow-up, including subgroups with lower tumor burden like stage I, and was more accurate among relapsed patients with baseline ctDNA-negative status. Comparing to the average lead time of ctDNA mutation, timMRD-score yielded a negative predictive value of 97.2% at 120 days prior to relapse.

conclusionsThe dynamic methylation-based analysis of peripheral blood provides a promising strategy for postoperative cancer surveillance.

trial registrationThis study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826). https://clinicaltrials.gov/ct2/show/NCT03634826 .

Indexed as

Cell-Free Nucleic AcidsCirculating Tumor DNALung NeoplasmsBiomarkers, TumorDNA MethylationHumansNeoplasm Recurrence, LocalBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNACirculating tumor DNA (ctDNA)DNA methylationLung cancerMinimal residual disease (MRD)Postoperative surveillance

Identifiers

PMID37452374
PMCPMC10349423
OpenAlexW4384343197

What OpenQuestion holds

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LicenceCC BY
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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.