Evidence map›Paper›PMID 31291995›Full record

Trial reportJournal for immunotherapy of cancer2019

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors.

Menno Tamminga, Sanne de Wit, T Jeroen N Hiltermann, Wim Timens, Ed Schuuring, Leon W M M Terstappen, Harry J M Groen

Abstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 4 pooled it
–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.

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

80 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Circulating Tumor Cells for the Monitoring of Lung Cancer Therapies.International journal of molecular sciences · 2025
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

20 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

7 authors.

Menno TammingaDepartment of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.0001, 9700, RB, Groningen, The Netherlands. m.tamminga@umcg.nl.ORCID 0000-0001-6508-2623
Sanne de WitDepartment of Medical Cell BioPhysics, Faculty of Sciences and Technology, University of Twente, Enschede, The Netherlands.
T Jeroen N HiltermannDepartment of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.0001, 9700, RB, Groningen, The Netherlands.
Wim TimensDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ed SchuuringDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Leon W M M TerstappenDepartment of Medical Cell BioPhysics, Faculty of Sciences and Technology, University of Twente, Enschede, The Netherlands.
Harry J M GroenDepartment of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.0001, 9700, RB, Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNon-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.

methodsPatients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch®. Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4-6 weeks after start of treatment. Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression.

resultsWe included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%). CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p < 0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate.

conclusionCTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Non-Small-Cell LungFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplastic Cells, CirculatingSurvival AnalysisTreatment OutcomeAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanCheckpoint inhibitorsCirculating tumor cells (CTC)Durable responseImmunotherapyLiquid biopsyNon-small cell lung cancer (NSCLC)Tumor derived extracellular vesicles (tdEV)

Identifiers

PMID31291995
PMCPMC6617698

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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.