Evidence map›Paper›PMID 23459720›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2013

An international collaboration to harmonize the quantitative plasma Epstein-Barr virus DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma.

Quynh-Thu Le, Qiang Zhang, Hongbin Cao, Ann-Joy Cheng, Benjamin A Pinsky, Ruey-Long Hong, Joseph T Chang, Chun-Wei Wang, Kuo-Chien Tsao, Ym Dennis Lo and 4 more

Abstract readClinical TrialMulticenter Study
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 4 pooled it
9.1field-weighted citation impact, top 1% 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

75 citing papers in PubMed, 4 syntheses or guidelines pooled it, 177 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Epstein-Barr virus-targeted therapy in nasopharyngeal carcinoma.Journal of cancer research and clinical oncology · 2015
    Trial
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Highly-multiplex detection of plasma cell-free human papillomavirus-16 DNA in oropharyngeal carcinoma.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2025
    Article

15 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

14 authors at 5 institutions in 3 countries.

Quynh-Thu LeDepartment of Radiation Oncology, Stanford University, 875 Blake Wilbur Dr., MC 5847, Stanford, CA 94305, USA. Qle@stanford.edu
Qiang Zhang
Hongbin Cao
Ann-Joy Cheng
Benjamin A Pinsky
Ruey-Long Hong
Joseph T Chang
Chun-Wei Wang
Kuo-Chien Tsao
Ym Dennis Lo
Nancy Lee
K Kian Ang
Anthony T C Chan
K C Allen Chan
RTOG Foundation · USChang Gung University · TWChinese University of Hong Kong · CNNational Taiwan University Hospital · TWMemorial Sloan Kettering Cancer Center · US

Funding

RTOG Foreign AccrualU10CA021661 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 1985 to 2013
$150.3M
NCI NIH HHS U10 CA021661NCI NIH HHS U10 CA21661
6 · The paper itself

Abstract

purposePersistently elevated posttreatment plasma EBV DNA is a robust predictor of relapse in nasopharyngeal carcinoma (NPC). However, assay standardization is necessary for use in biomarker-driven trials. We conducted a study to harmonize the method between four centers with expertise in EBV DNA quantitation. EXPERIMENTAL

designPlasma samples of 40 patients with NPC were distributed to four centers. DNA was extracted and EBV DNA copy number was determined by real-time quantitative PCR (BamHI-W primer/probe). Centers used the same protocol but generated their own calibrators. A harmonization study was then conducted using the same calibrators and PCR master mix and validated with ten pooled samples.

resultsThe initial intraclass correlations (ICC) for the first 40 samples between each center and the index center were 0.62 [95% confidence interval (CI): 0.39-0.78], 0.70 (0.50-0.83), and 0.59 (0.35-0.76). The largest variability was the use of different PCR master mixes and calibrators. Standardization improved ICC to 0.83 (0.5-0.95), 0.95 (0.83-0.99) and 0.96 (0.86-0.99), respectively, for ten archival frozen samples. For fresh plasma with spiked-in EBV DNA, correlations were more than 0.99 between the centers. At 5 EBV DNA copies per reaction or above, the coefficient of variance (CV) was less than 10% for the cycle threshold (Ct) among all centers, suggesting this concentration can be reliably used as a cutoff for defining the presence of detectable EBV DNA.

conclusionsQuantitative PCR assays, even when conducted in experienced clinical labs, can yield large variability in plasma EBV DNA copy numbers without harmonization. The use of common calibrators and PCR master mix can help to reduce variability.

Indexed as

Biomarkers, TumorCalibrationCarcinomaDNA, ViralEpstein-Barr Virus InfectionsHerpesvirus 4, HumanHumansInternational CooperationLaboratoriesNasopharyngeal CarcinomaNasopharyngeal NeoplasmsReal-Time Polymerase Chain ReactionReference StandardsReproducibility of ResultsSensitivity and SpecificityBiomarkers, TumorDNA, Viral

Identifiers

PMID23459720
PMCPMC3630245
OpenAlexW2138066012

What OpenQuestion holds

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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.