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Quartuccio et al. J Cancer Metastasis Treat 2021;7:14 I http://dx.doi.org/10.20517/2394-4722.2020.118 Page 3 of 13
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with thyroid cancer by means of F-FDG PET/CT. The following search string was used for the literature
search: (“positron emission tomography” OR “PET” OR “positron emission tomography/computer
tomography” OR “PET/CT”) AND [(“differentiated” OR “papillary” OR “follicular” OR “Hurthle cell” OR
“anaplastic” OR “dedifferentiated” OR “poorly differentiated”) AND (“cancer” OR “carcinoma”)] AND
(“fluorodeoxyglucose” OR “FDG”) AND “thyroid”.

The literature search was updated until 22 August 2020. No date limit or language restriction was applied.
All identified references were exported to a reference management software (Endnote v. X7.5, Clarivate
Analytics).

Study selection
An investigator screened the titles and abstracts of the retrieved entries. Only original articles were selected.
After excluding duplicates and non-original articles, the full text of the remaining articles was retrieved
to verify the following inclusion criteria: (1) a study cohort or a subset of a minimum 10 patients with
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differentiated thyroid cancer undergoing F-FDG PECT/CT; (2) presence of data regarding at least the
detection rate of non-lymph node metastases; and (3) absence of other malignancies in the patient history.
The choice of excluding articles with fewer than 10 patients and organs was made to mitigate the so-called
small-study effect, for which, in brief, the observations could be due to methodological flaws, outcome
reporting bias, and clinical heterogeneity.

The references of the retrieved articles were also screened for additional studies.

Data extraction
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For our primary outcome (accuracy of F-FDG PET/CT), we selected articles from which it was possible
to retrieve the number of true positive (TP), false negative (FN), false positive (FP), and true negative (TN)
cases on a per-patient or per-lesion basis. Lesions were grouped according to the involved organ (e.g, lung
or bone). Articles providing only the number of TP or FN cases were used only for the determination of
the DR of hematogenous metastases on a per-patient and per-lesion basis.

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For the secondary outcome (comparison of diagnostic performance of F-FDG PET/CT with other
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imaging tests), pooled DR of F-FDG PET/CT was compared with that of other imaging tests using N - 1
Chi-squared test .
[15]
Methodological quality assessment
The methodological quality of the studies was assessed using version 2 of the “Quality Assessment of
[16]
Diagnostic Accuracy Studies” tool (QUADAS-2) , which comprises four domains: patient selection, index
test, reference standard, and flow and timing. The concerns about the risk of bias or applicability were
described as low, high, or unclear.

Statistical analysis
Statistical analysis was carried out using MedCalc Statistical Software version 19.1.3 (MedCalc Software,
Ostend, Belgium; https://www.medcalc.org; 2020), Open Meta analyst (available online at http://www.
[17]
cebm.brown.edu/openmeta/downloads/open_meta_analyst_win8.zip) , and MetaDisc v. 1.4 (available at
[18]
http://www.hrc.es/investigacion/metadisc_en.htm) .
The I statistic was used to measure the degree of inconsistency across studies, with I values of 25%, 50%,
2
2
and 75% representing low, moderate, and high substantial heterogeneity. Interpretation of heterogeneity
was carried out at a significance level of P = 0.05. The choice of fixed or random effects model was made
on the basis of the degree of inconsistency, selecting the random effects model in the case of moderate and
high substantial heterogeneity.