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Meta-Analysis
. 2020 Mar;122(7):1077-1084.
doi: 10.1038/s41416-020-0740-y. Epub 2020 Feb 4.

Diagnostic accuracy of circulating-free DNA for the determination of MYCN amplification status in advanced-stage neuroblastoma: a systematic review and meta-analysis

Ricky M Trigg  1   2 , Suzanne D Turner  1 , Jacqueline A Shaw  3 , Leila Jahangiri  4   5
Affiliations
Meta-Analysis

Diagnostic accuracy of circulating-free DNA for the determination of MYCN amplification status in advanced-stage neuroblastoma: a systematic review and meta-analysis

Ricky M Trigg et al. Br J Cancer. 2020 Mar.

Abstract

Background: MYCN amplification (MNA) is the strongest indicator of poor prognosis in neuroblastoma (NB). This meta-analysis aims to determine the diagnostic accuracy of MNA analysis in circulating-free DNA (cfDNA) from advanced-stage NB patients.

Methods: A systematic review of electronic databases was conducted to identify studies exploring the detection of MNA in plasma/serum cfDNA from NB patients at diagnosis using PCR methodology. Pooled estimates for sensitivity, specificity and diagnostic odds ratio (DOR) were calculated by conducting a bivariate/HSROC random-effects meta-analysis.

Results: Seven studies, with a total of 529 advanced-stage patients, were eligible. The pooled sensitivity of cfDNA-based MNA analysis was 0.908 (95% CI, 0.818-0.956), the pooled specificity was 0.976 (0.940-0.991) and the DOR was 410.0 (-103.6 to 923.7). Sub-grouped by INSS stage, the sensitivity for stage 3 and 4 patients was 0.832 (0.677-0.921) and 0.930 (0.834-0.972), respectively. The specificity was 0.999 (0.109-1.000) and 0.974 (0.937-0.990), respectively, and the DOR was 7855.2 (-66267.0 to 81977.4) and 508.7 (-85.8 to 1103.2), respectively.

Conclusions: MNA analysis in cfDNA using PCR methodology represents a non-invasive approach to rapidly and accurately determine MNA status in patients with advanced-stage NB. Standardised methodology must be developed before this diagnostic test can enter the clinic.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart for study selection based on PRISMA-DTA guidelines.
Fig. 2
Fig. 2. Estimated pooled sensitivity, specificity and hierarchical summary receiver operator characteristic (HSROC) curve in advanced-stage patients.
a Forest plots of sensitivity and specificity of cfDNA-based MNA analysis at diagnosis in NB patients with advanced-stage disease. b HSROC curve analysis for patients with advanced-stage (stage 3 and 4) disease.
Fig. 3
Fig. 3. Estimated pooled sensitivity, specificity and hierarchical summary receiver operator characteristic (HSROC) curve in stage 3 and stage 4 patients.
a, b Forest plots of sensitivity and specificity of cfDNA-based MNA analysis at diagnosis in NB patients with a stage 3 and b stage 4 disease. c, d HSROC curve analysis for patients with c stage 3 and d stage 4 disease.
Fig. 4
Fig. 4. Assessment of publication bias.
Deeks’ funnel plots of DOR for cfDNA-based MNA analysis in a stage 3 and 4, b stage 3 and c stage 4 NB patients. Each point represents the natural logarithm of the DOR of a study plotted against the square root of its effective sample size (ESS).
Fig. 5
Fig. 5
Quality assessment of studies by QUADAS-2.
See this image and copyright information in PMC

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