Bryant 2006a.

Study characteristics
Patient sampling	Prospective consecutive patient series
Patient characteristics and setting	397 participants, median age = 67 (range = 23 to 82) years, 251 males/146 females, US Histology of primary tumour Not reported; comorbidities: not reported Inclusion criteria Participants who presented to 1 surgeon with an indeterminate pulmonary nodule or biopsy‐proven NSCLC and who underwent integrated FDG PET‐CT at the authors' institution from January 2003 to December 2004 Exclusion criteria Participants < 19 years old with type I diabetes, Pancoast tumour, T4 tumour from mediastinal invasion or from malignant effusion, neoadjuvant chemotherapy or radiation, or biopsy‐proven metastatic (M1) disease Previous tests Participants were clinically TNM‐staged based on the FDG PET‐CT results Clinical setting Cardiothoracic surgery unit
Index tests	The FDG PET‐CT scans were performed on an integrated FDG PET‐CT scanner (GE Discovery LS PET‐CT scanner; Milwaukee, WI, USA). Participants were asked to fast for 4 hours and then subsequently received 555 MBq (15 mCi) of FDG intravenously followed by PET after 1 hour. The scans were performed from the skull base to mid‐thigh level. The CT examination was used for attenuation correction of PET images. The scanning time for emission PET was 5 minutes per bed position. The most recent CT scan of the chest was also available for visual correlation. Maximum SUV (maxSUV) of the primary lung lesion and of each suspicious lymph node station was determined by drawing regions of interest on the attenuation‐corrected FDG‐PET images around it. The maxSUV within the selected region of interest was used throughout the study exclusively, and N2, N3, or M1 areas with maxSUV ≥ 2.5 were considered suspicious Covariates Type of PET‐CT scanner: integrated FDG‐PET‐CT scanner (GE Discovery LS PET‐CT Scanner; Milwaukee, WI, USA) FDG dose: 555 MBq (15 mCi) Injection‐to‐scan time: 60 min Attenuation correction: yes Cut‐off values for test positivity (malignancy): maxSUV ≥ 2.5
Target condition and reference standard(s)	All suspicious N2, N3, or M1 areas (maxSUV ≥ 2.5) were biopsied prior to pulmonary resection. Mediastinoscopy was used to biopsy suspicious lymph nodes in the paratracheal area (stations 2R, 4R, 2L, and 4L) and the superior portion of the subcarinal lymph node. Either video‐assisted thoracoscopic surgery (VATS) or endoscopic transoesophageal ultrasound (EUS) was used to biopsy suspicious posterior aortopulmonary window lymph nodes, subcarinal lymph nodes, perioesophageal nodes, and inferior pulmonary ligament nodes. Microscopic disease was defined as tumour invasion of ≤ 2 mm or disease only detected on immunohistochemical staining. The latter was performed in selected cases only as per the pathologist's discretion. In general, there were 2 slices per lymph nodes used
Flow and timing	All participants were accounted for in the results. Apart from 26/397 participants whose data were not included (because of proven M1 disease/T4 tumour/Pancoast tumour or refusal of definitive surgery), all the remaining participants received verification using the reference standard
Comparative
Notes	26/397 participants had proven M1 disease/T4 tumour/Pancoast tumour or refused definitive surgery and their data were not included The paper makes no mention of potential sources of support. The data appear to have been gathered as part of normal practice 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?	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?	Yes
Was a positive result defined?	Yes
		Low	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?	No
		Unclear