Morikawa 2009.

Study characteristics
Patient sampling	Prospective consecutive patient series
Patient characteristics and setting	93 participants, mean age = 66.1 (SD = 10.9) years, 76 males/17 females, Japan Histology of primary tumour Adenocarcinoma: N = 39; squamous cell: N = 28; NSCLC NOS: N = 3; adenosquamous cell carcinoma: N = 1; small cell carcinoma: N = 4; malignant lymphoma: N = 3; melanoma (mediastinal lymph node involvement): N = 1; benign: N = 14 (sarcoidosis: N = 11, interstitial pneumonitis: N = 2, pneumoconiosis: N = 1); comorbidities: none reported Inclusion criteria Participants with known or suspected lung cancer and mediastinal and hilar lymph node swelling detected by chest CT. Mediastinal and hilar lymph nodes were assessed if the short axis diameter on transaxial chest CT images > 10 mm Exclusion criteria Participants with blood glucose levels > 126 mg/dL at the time of the FDG injection Previous tests None reported apart from chest CT Clinical setting Secondary/tertiary care
Index tests	FDG PET‐CT examinations were performed with a whole‐body scanner (Discovery LS; GE Healthcare). All participants fasted overnight (minimum 12 hours) before radiotracer administration. FDG PET images from the skull through the mid thigh were obtained 50 minutes after injection of 185 MBq FDG and CT‐based attenuation correction was performed. CT‐based attenuation correction factors were then applied to the emission data, and the attenuation‐corrected emission images were reconstructed using an ordered‐subset expectation maximisation iterative reconstruction algorithm. The reconstructed images were converted to SUV images using patient body weight and a dose of FDG (tumour activity concentration/injected dose/body weight). An experienced radiologist and nuclear medicine physician without knowledge of histopathologic or other radiologic data independently and prospectively interpreted FDG images . Semiquantitative analysis of the FDG uptake was based on region‐of‐interest analysis that produced maximal SUV and mean SUV. Swollen lymph nodes were evaluated using FDG PET‐CT. The same radiologist and experienced nuclear medicine physician drew a region of interest over each mediastinal or hilar lymph node at the most active site on FDG PET‐CT images. The optimal thresholds of maximal and mean SUV were determined using receiver operating characteristics curve‐based analysis, and a maximal SUV of 4.1 and a mean SUV of 3.5 were adopted as optimal cut‐off values for analysis. Covariates Type of PET‐CT scanner: integrated PET‐CT scanner (Discovery LS; GE Healthcare) FDG dose: 185 MBq Injection‐to‐scan time: 50 min Attenuation correction: yes Cut‐off values for test positivity (malignancy): maximal SUV of 4.1 and a mean SUV of 3.5. These were not prespecified
Target condition and reference standard(s)	Surgical resection, mediastinoscopy, or TBNA (surgical confirmation always obtained in cases of negative TBNA). 137 lymph nodes were studied (in the 93 participants), of which 82 were malignant, and 55 were benign. 19 malignant and 37 benign lymph nodes were diagnosed using surgery or mediastinoscopy, and 63 malignant and 18 benign lymph nodes were diagnosed using TBNA (no corresponding participant‐based information reported)
Flow and timing	All participants were accounted for in the results. All participants received the reference standard. There were no uninterpretable results.
Comparative
Notes	The 21st Century COE program 'Biomedical Imaging Technology Integration Program' funded by the Japan Society for the Promotion of Science supported the study Adverse events: none reported
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Low	Low
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
Was there a pre‐specified cut‐off value?	No
Was a positive result defined?	Yes
		High	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		Low	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low