Harders 2012.

Study characteristics
Patient sampling	Prospective consecutive patient series
Patient characteristics and setting	114 participants, mean age = not reported (range = not reported) years, gender: not reported, Denmark Histology of primary tumour Not reported; comorbidities: not reported Inclusion criteria Quote: "Regional patients who were recently diagnosed with NSCLC were prospectively identified for inclusion over a 2‐ year study period. All patients received a CT as well as an FDG PET/CT examination, and all metastasis suspect lesions were biopsied. Based on all available data, that is the CT, the FDG PET/CT and the biopsy results, a multidisciplinary staging was made: If the patients were staged with T1, N0, M0 disease, they received surgery. If the patients were staged with T2‐T4, N0‐N3, M0 disease, they received a preoperative mediastinoscopy; if they were eventually staged with T2‐T4, N0‐N1, M0 disease, they received surgery. In all other instances the patients received oncological treatment" Exclusion criteria None listed Previous/all reported tests CT Clinical setting Departments of Radiology, Nuclear Medicine, Pulmonology, Oncology, Thoracic Surgery, and Pathology
Index tests	FDG PET‐CT examinations included the whole body and were performed with an integrated PET‐CT scanner (Siemens Biograph 40‐slice CT scanner; Siemens Healthcare, Erlangen, Germany). Participants were instructed to submit to 6 hours of fasting prior to the examination. Approximately 400 MBq FDG was injected intravenously. FDG PET‐CT scans were performed after a delay of 60 minutes. The FDG PET images were corrected for scatter and iteratively reconstructed. CT acquisition parameters were 40 x 3.0 mm collimation. No contrast medium was administered. 2 consultants in nuclear medicine did the FDG PET‐CT reviews. The reviewers were blinded to participant names, participant identifications, and clinical data Covariates Type of PET‐CT scanner: Siemens Biograph 40‐slice CT scanner (Siemens Healthcare, Erlangen, Germany) FDG dose: circa 400 MBq Injection‐to‐scan time: 60 min Attenuation correction: yes Cut‐off values for test positivity (malignancy): FDG uptake was compared with the background uptake of the liver. Thus, lymph node uptake was rated on a scale of 1 to 3: (1) no uptake, (2) probably increased uptake (i.e., below liver level uptake), (3) definitely increased uptake (i.e., at or above liver level uptake). A rating of 1 was considered normal; a rating of 2 or 3 was considered abnormal
Target condition and reference standard(s)	Tissue sampling from the participants' mediastinums. In participants who did not receive surgery, tissue sampling was obtained by preoperative mediastinoscopy with sampling from nodal stations 1, 2R/L, 3A, 4R/L, and 7; if necessary, it was obtained by anterior mediastinotomy from nodal stations 5 and 6. All mediastinoscopies/‐tomies (N = 25) were guided by both CT and FDG‐PET/CT examinations. In participants who received surgery (N = 89), tissue sampling was obtained by complete lymph node resection (i.e., resection of all visible and palpable mediastinal and hilar lymph nodes from nodal stations 2R; 4R; 7, 8, 9, 10, 11+ for right‐sided tumours; and 5, 6, 7, 8, 9, 10, 11+ for left‐sided tumours)
Flow and timing	All participants received the reference standard and were included in the analyses
Comparative
Notes	Funding: not reported Adverse events: not 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?	Unclear
		Unclear	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?	Unclear
Was a positive result defined?	Yes
		Unclear	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?	No
		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