Ohno 2011.

Study characteristics
Patient sampling	Prospective consecutive patient series
Patient characteristics and setting	250 participants, mean age = 73 (range = 61 to 83) years, 136 males/114 females, Japan Histology of primary tumour Adenocarcinoma: N = 218; squamous cell: N = 23; adenosquamous cell carcinoma: N = 3; large cell carcinoma: N = 6; comorbidities: not reported Inclusion criteria Quote: "Between January 2009 and December 2010, 250 consecutive patients with T1 or T2 NSCLC as evaluated on chest radiographs or CT images at a nearby hospital underwent contrast material–enhanced multidetector CT, STIR turbo SE imaging, DW MR imaging, FDG‐PET/CT, and mediastinoscopy before thoracotomy or resection of the primary lesion or before thoracotomy for primary resection in conjunction with hilar and mediastinal sampling. All patients were followed up for more than 1 year." No other information reported Exclusion criteria None listed Previous tests None listed apart form those above Clinical setting Secondary/tertiary care
Index tests	All participants fasted for at least 6 hours before intravenous administration of FDG at a rate of 3.3 MBq per kilogram of body weight, and images were obtained from the skull to the mid thigh 60 minutes after completion of injection. All FDG PET‐CT examinations were performed with a commercially available PET‐CT scanner (Discovery ST; GE Healthcare, Milwaukee, WI, USA). Unenhanced CT was performed from the skull to the pelvic floor according to a standardised protocol, and immediately afterwards, PET was performed in the identical transverse field of view. All integrated PET‐CT examinations were performed within 60 minutes. Visual and quantitative assessment of FDG uptake was performed. To assess the validity of qualitative analysis of FDG PET‐CT images, 2 general radiologists, with 8 and 14 years of experience, prospectively evaluated all FDG PET‐CT images. These 2 general radiologists also had more than 3 years of experience with PET. The probability of lymph node metastasis was evaluated on a per‐node basis with the following 5‐point visual scoring system: 1 = definitely absent, 2 = probably absent, 3 = equivocal, 4 = probably present, and 5 = definitely present. Each reviewer assessed all lymph nodes twice. The final probability of lymph node metastasis was based on consensus of the 2 readers. For quantitative assessment of lymph node metastases on integrated FDG PET‐CT images, all SUVmax measurements were obtained from regions of interest drawn over mediastinal and hilar lymph nodes (range = 16 to 576 mm²) on the axial and coronal planes by the same chest radiologist and averaged to determine the final value for each lymph node. In addition, each investigator who performed quantitative or qualitative assessment with all modalities (see Inclusion criteria) had no knowledge of the results of pathologic examination or any other investigation and evaluated all examinations in random order Covariates Type of PET‐CT scanner: integrated PET‐CT scanner (Discovery ST; GE Medical systems) FDG dose: 3.3 MBq/kg Injection‐to‐scan time: 60 min Attenuation correction: yes Cut‐off values for test positivity (malignancy): The feasible threshold value of each method was determined as demonstration of the highest accuracy, sensitivity, or both, and this MAY be SUVmax ≥ 4 for qualitative assessment and SUVmax ≥ 2 for quantitative assessment (Tables 1 and 2 and Figures 3 and 4). These cut‐off values were not prespecified
Target condition and reference standard(s)	Pathologic findings in resected specimens. Cervical mediastinoscopy (supplemented by left anterior mediastinotomy if the tumour was in the left upper lobe) if CT findings suggested invasion of the superior mediastinum or enlarged nodes plus complete standard mediastinal nodal sampling (N = 23) or thoracotomy plus systematic ipsilateral hilar and mediastinal sampling at the locations specified by the regional lymph node classifications of the American Joint Committee on Cancer and the Union for International Cancer Control (N = 227)
Flow and timing	All participants were accounted for in the results. All participants received the reference standard. There were no uninterpretable results
Comparative
Notes	Philips Healthcare and a grant‐in‐aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology provided the study with financial, technical support, or both. None of the authors was an employee of Philips Healthcare, and the authors had full control over the data for the duration of this study 2 2‐by‐2s (qualitative and quantitative measurement): qualitative: TP = 14, FP = 0, FN = 7, TN = 229 quantitative: TP = 16, FP = 0, FN = 5, TN = 229 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?	Unclear
		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?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Unclear