Evidence map›Paper›PMID 31692284›Full record

ArticleCancer medicine2019

Serial ultra-deep sequencing of circulating tumor DNA reveals the clonal evolution in non-small cell lung cancer patients treated with anti-PD1 immunotherapy.

Li Li, Yubo Wang, Weiwei Shi, Mengxiao Zhu, Zhulin Liu, Nuo Luo, Yanwu Zeng, Yong He

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 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

8 authors at 2 institutions in 1 country.

Li LiDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
Yubo WangDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
Weiwei ShiOrigiMed Co. Ltd, Shanghai, China.ORCID 0000-0001-8751-0684
Mengxiao ZhuDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
Zhulin LiuDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
Nuo LuoDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
Yanwu ZengOrigiMed Co. Ltd, Shanghai, China.ORCID 0000-0001-6341-8234
Yong HeDepartment of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.ORCID 0000-0003-4123-894X
Army Medical University · CNUnimed Medical Institute · CN

Funding

Natural Science Foundation of China 81472189Natural Science Foundation of China 81672284Natural Science Foundation of China 81672287
6 · The paper itself

Abstract

backgroundImmune-therapy with anti-PD1 inhibitors, such as pembrolizumab, is revolutionizing the treatment of non-small cell lung cancers (NSCLC). However, identifying patients for the potential therapeutic response and predicting therapy resistance and early relapse remains a challenge.

methodsBetween 2016 and 2018, 60 patients were treated with pembrolizumab, among who 12 NSCLC patients had both baseline (before treatment) and serial (on treatment) periodical circulating tumor DNA (ctDNA) samples. Those samples were sequenced on a 329 pan cancer-related gene panel. Analyses of tumor burden, blood tumor mutational burden (bTMB), maximum somatic allele frequency (MSAF), and tumor clonal structure were performed in association with clinical response. Candidate resistance mutations involved in relapse and metastases were further investigated.

resultsctDNA was detected and mutational profiling was performed for each patient. Those with a high baseline bTMB level showed significantly improved progression-free survival (PFS) after pembrolizumab treatment. Tumor burden and therapeutic response significantly correlated with the MSAF instead of the bTMB. Clone analysis detected tumor progression about 2-4 months ahead of computed tomography (CT) scan. One mutation in gene PTCH1 (Protein patched homolog 1) and two acquired anti-PD1 candidate resistance mutations of gene B2M (β2 microglobulin) were identified in association with distant metastasis. The evolutionary tree of a representative patient was also described.

conclusionThis pilot study showed that MSAF could be another good indicator of therapeutic response, and clonal analysis could be clinically useful in monitoring clonal dynamics and detecting remote metastasis and early relapse.

Indexed as

Biomarkers, TumorCirculating Tumor DNAAgedAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungCell Transformation, NeoplasticClonal EvolutionFemaleHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyMutationAntineoplastic Agents, ImmunologicalBiomarkers, TumorCirculating Tumor DNAPDCD1 protein, humanProgrammed Cell Death 1 ReceptorctDNAdistant metastasislung cancermaximum somatic allele frequencypembrolizumab

Identifiers

PMID31692284
PMCPMC6912064
OpenAlexW2986345377

What OpenQuestion holds

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Registered trials

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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.