Lee 2009a.

Study characteristics
Patient sampling	Prospective consecutive? patient series
Patient characteristics and setting	182 participants, mean age = 60.7 (SD = 10.8) years, 126 males/56 females, South Korea Histology of primary tumour Adenocarcinoma: N = 93; squamous cell: N = 66; bronchioloalveolar carcinoma: N = 5; large cell carcinoma: N = 7; cancer NOS: N = 11; comorbidities: not reported Inclusion criteria Participants who underwent preoperative FDG PET‐CT and subsequent surgical resection of NSCLC between March 2004 and February 2006 Exclusion criteria None listed, but participants with metastatic lesions on preoperative PET‐CT images and participants who had had neoadjuvant chemotherapy or radiotherapy for contralateral or bulky mediastinal node metastases before thoracotomy or mediastinoscopy were excluded Previous/all tests All participants underwent a contrast‐enhanced CT scan of the thorax and FDG PET‐CT scan as part of staging work‐up. No further information provided Clinical setting Secondary setting The inclusion of only participants who received surgery narrows the range of patients who would receive PET‐CT in practice, namely, patients (clinically) with suspected resectable non‐small cell lung cancer, a proportion of whom would have N2 or N3 disease already on PET‐CT
Index tests	PET‐CT was performed using a Gemini PET‐CT system (Philips, Milpitas). All participants fasted for at least 6 h before the PET‐CT scan, and only glucose‐free water was allowed. An intravenous injection of 5.18 MBq of FDG/kg of body weight was administered, and participants rested for 60 min before imaging. PET‐CT data were obtained with participants in the supine position. Attenuation correction was done based on CT data. 2 experienced nuclear medicine physicians evaluated all PET‐CT images. During evaluation of CT images, the short axis of mediastinal lymph nodes was measured and positive nodes were defined as those with a short axis diameter greater than 1 cm. In addition to size, the presence of calcification was considered on non‐contrast CT images Covariates Type of PET‐CT scanner: Gemini PET‐CT system (Philips, Milpitas) FDG dose: 5.18 MBq of FDG/kg Injection‐to‐scan time: 60 min Attenuation correction: yes Cut‐off values for test positivity (malignancy): Integrated PET‐CT images were evaluated visually. The maxSUVs were measured in all lymph nodes with increased FDG uptake. First, mediastinal lymph nodes with focally increased FDG uptake higher than mediastinal blood pool uptake were judged as positive, taking the SUVs of the lymph nodes into consideration. On a second interpretation of PET‐CT images, calcified high‐attenuation lymph nodes (defined as nodes with higher attenuation than that of the mediastinal vascular structures and more than 70 HU on non‐contrast CT images) were interpreted as benign, irrespective of FDG uptake. Furthermore, bilateral symmetric paratracheal nodes on FDG PET images with a hilar or interlobar nodal distribution with similar FDG uptake or mediastinal nodes with a symmetric hilar or interlobar nodal distribution with similar FDG uptake were also judged as benign. Even though the attenuation of some lymph nodes with a typical distribution pattern was lower than 70 HU, all the lymph nodes in the participants with this pattern were interpreted as benign
Target condition and reference standard(s)	Thoracotomy was performed in 169 of 182 participants. Mediastinoscopic biopsy without thoracotomy was performed in the remaining 13 participants because of a pathological high N‐stage found on mediastinoscopic biopsy. An additional mediastinoscopic biopsy was performed in 31 of the 169 participants in whom thoracotomy was performed, and the remaining 138 participants had thoracotomy only. All the mediastinal nodes that were positive on FDG PET‐CT images or on contrast‐enhanced CT images were sampled or dissected at thoracotomy, mediastinoscopic biopsy, or both
Flow and timing	All participants were accounted for in the results. All participants underwent surgical staging. There were no results that uninterpretable results
Comparative
Notes	No details of funding were reported. However, the study was probably not externally funded because although this data collection was prospective, it appears to be collected as part of normal practice The participant population comes from a region with a high prevalence of granulomatous disease 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?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Unclear	High
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
		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?	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