Evidence map›Paper›PMID 38806586›Full record

ArticleNPJ precision oncology2024

Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis.

Tej D Azad, Shigeki Nanjo, Michael C Jin, Jacob J Chabon, David M Kurtz, Aadel A Chaudhuri, Ian D Connolly, Angela Bik-Yu Hui, Chih Long Liu, David Merriott and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
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

27 authors.

Tej D Azad *Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7823-4294
Shigeki Nanjo *Department of Medicine, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8356-9849
Michael C Jin *Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Jacob J ChabonStanford Cancer Institute, Stanford University, Stanford, CA, USA.
David M KurtzStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Aadel A ChaudhuriDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-3115-3061
Ian D ConnollyDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.
Angela Bik-Yu HuiStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Chih Long LiuStanford Cancer Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6577-5427
David MerriottStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Ryan KoStanford Cancer Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2123-9702
Christopher YooStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Justin CarterStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Emily ChenStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Rene BonillaStanford Cancer Institute, Stanford University, Stanford, CA, USA.
Akito HataDepartment of Medical Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan.
Nobuyuki KatakamiDepartment of Medical Oncology, Takarazuka City Hospital, Hyogo, Japan.
Kei IrieDepartment of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, Kobe, Japan.
Seiji YanoDepartment of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
Ross OkimotoDepartment of Medicine, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4467-8476
Trever G BivonaDepartment of Medicine, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5734-4128
Aaron M NewmanStanford Cancer Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1857-8172
Michael IvDepartment of Radiology, Stanford University, Stanford, CA, USA.
Seema NagpalDepartment of Neurology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0289-2319
Melanie Hayden GephartMayo Clinic Comprehensive Cancer Center, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-2965-9231
Ash A AlizadehStanford Cancer Institute, Stanford University, Stanford, CA, USA. arasha@stanford.edu.ORCID http://orcid.org/0000-0002-5153-5625
Maximilian DiehnStanford Cancer Institute, Stanford University, Stanford, CA, USA. diehn@stanford.edu.ORCID http://orcid.org/0000-0003-2032-0581

Funding

Molecularly-based outcome and toxicity prediction after radiotherapy for lung cancerR01CA254179 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2020 to 2024
$3.1M
Developing a genomic approach for cancer screeningDP2CA186569 · NCI · STANFORD UNIVERSITY · PI DIEHN, MAXIMILIAN · 2013 to 2013
$2.4M
Noninvasive monitoring of lung cancer patients treated with radiotherapyR01CA188298 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2015 to 2019
$1.8M
NCI NIH HHS DP2 CA186569NCI NIH HHS R01 CA188298NCI NIH HHS R01 CA254179U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA188298U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA254179
6 · The paper itself

Abstract

Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment. CSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%; P < 0.0001). Concentrations of tumor DNA in CSF and plasma were positively correlated (Spearman's ρ, 0.45; P = 0.03). For LMD diagnosis, cytology was 81.8% sensitive and CSF-tDNA was 91.7% sensitive. CSF-tDNA was also strongly prognostic for overall survival (HR = 7.1; P = 0.02). Among patients with progression on targeted therapy, resistance mutations, such as EGFR T790M and MET amplification, were common in peripheral blood but were rare in time-matched CSF, indicating differences in resistance mechanisms based on the anatomic compartment. In the osimertinib cohort, patients with CNS progression had increased CSF-tDNA VAFs at follow-up LP. Post-osimertinib CSF-tDNA VAF was strongly prognostic for CNS progression (HR = 6.2, P = 0.009). Detection of CSF-tDNA in lung cancer patients with suspected LMD is feasible and may have clinical utility. CSF-tDNA improves the sensitivity of LMD diagnosis, enables improved prognostication, and drives therapeutic strategies that account for spatial heterogeneity in resistance mechanisms.

Identifiers

PMID38806586
PMCPMC11133465

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.