Kim 2007.

Study characteristics
Patient sampling	Prospective consecutive? patient series
Patient characteristics and setting	674 participants, mean age = 61 (range = 30 to 90) years, 502 males/172 females, South Korea Histology of primary tumour Adenocarcinoma: N = 333; squamous cell: N = 271; bronchioloalveolar carcinoma: N = 14; adenosquamous: N = 7; large cell neuroendocrine carcinoma: N = 29; sarcomatoid carcinoma: N = 15 (pleomorphic carcinoma: N = 14, spindle cell carcinoma: N = 1); NSCLC NOS: N = 5; comorbidities: not reported, but 218 (of the 674) participants had a past medical history of pulmonary tuberculosis (as determined at clinical or imaging studies) Inclusion criteria Participants referred for surgery for NSCLC between March 2003 and March 2006 Exclusion criteria None listed, but participants were excluded because conventional staging studies or integrated whole‐body PET‐CT suggested extra‐thoracic metastasis (N = 41), because they received chemotherapy (N = 6) or chemoradiotherapy (N = 20) before surgical staging at another hospital, or because they had carcinoids (N = 5) or salivary gland type tumours (N = 10) Previous/all tests Conventional lung cancer staging on the basis of clinical information, stand‐alone chest CT with intravenous injection of 100 mL of iopamidol (Iopamiron 300; Bracco, Milan, Italy), and an integrated whole‐body PET‐CT study Clinical setting Tertiary setting The inclusion of only participants who were referred for surgery and the exclusion of participants with extra‐thoracic metastasis based on PET‐CT 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	All participants fasted for at least 6 hours before the PET‐CT examination, although oral hydration with glucose‐free water was allowed. After a normal blood glucose level in the peripheral blood was ensured, participants received an intravenous injection of 370 MBq (10 mCi) of FDG and then rested for 45 min before undergoing imaging. Image acquisition was performed with an integrated PET/CT device (Discovery LS, GE Medical Systems). The participants were scanned from the head to the pelvic floor and were allowed normal shallow respiration during the acquisition of the non‐contrast‐enhanced CT scans. PET‐image data sets were reconstructed iteratively using the ordered subsets expectation maximisation algorithm and by applying the segmented measured attenuation correction to the CT data. Coregistered images were displayed by using software (eNTEGRA; GE Medical Systems) that allowed image fusion and analysis. 1 chest radiologist and 1 nuclear medicine physician, both unaware of clinical, stand‐alone CT and pathologic results, together prospectively evaluated integrated PET‐CT datasets. Decisions were reached by consensus Covariates Type of PET‐CT scanner: integrated PET‐CT device (Discovery LS; GE Medical Systems) FDG dose: 370 MBq (10 mCi) Injection‐to‐scan time: 45 min Attenuation correction: yes, segmented measured attenuation correction to the CT data Cut‐off values for test positivity (malignancy): Mediastinal nodes with an increased glucose uptake and a distinct margin were considered positive for malignancy. Nodes were regarded as having an increased glucose uptake when they demonstrated FDG uptake at a level greater than that of the surrounding mediastinal tissue. Calcification was regarded as present when nodular, laminated, or diffuse and when the attenuation was 200 household unit (HU). A highly attenuating node was defined as 1 that appeared to have a higher attenuation than mediastinal vascular structures with an attenuation of 70 HU using a region of interest (ROI)‐based measurement. Even if glucose uptake was high (higher than the background activity), calcified lymph nodes or lymph nodes with a higher attenuation than surrounding great vessels on the CT images of integrated PET‐CT were regarded as benign
Target condition and reference standard(s)	Surgical staging included mediastinoscopy (N = 121), mediastinoscopy plus thoracotomy (N = 309), and thoracotomy alone (N = 244). In 121 participants, only mediastinoscopic nodal staging results were available because curative resection was deferred on account of the presence of positive nodes indicating neoadjuvant concurrent chemoradiation therapy (N = 108) or because participants denied surgery (N = 13) in spite of negative nodes on mediastinoscopic evaluation. Tumour resection and extensive mediastinal lymph node dissection with thoracotomy were performed on 553 participants. During mediastinoscopy, the 2R, 4R, 2L, 4L, and 7 ATS lymph node map areas were routinely sampled, and during thoracotomy, according to the routine surgical protocol, surgeons dissected all visible and palpable lymph nodes accessible in the mediastinum irrespective of size. Specifically, all encountered lymph nodes were removed from 10R, 9, 8, 7, 4R, 3, and 2R, the ATS lymph node map areas for tumours of the right lung, and from areas 10L, 9, 8, 7, 6, 5, and 4L for the left lung. When necessary, especially when an imaging study suggested possible nodal metastasis in other nodal stations other than those included in routine lymph node dissection, group 1 (highest mediastinal) or 2L (when tumours were located in the left lung) nodes were also evaluated during mediastinoscopy or thoracotomy. In the 553 participants of the surgical tumour resection group, 389 participants underwent lobectomy, 72 participants underwent bilobectomy, 14 participants underwent sleeve lobectomy, and 78 participants underwent pneumonectomy. The mean time interval between the index test and reference standard was 13 days (range = 1 to 42 days; median = 7 days)
Flow and timing	All participants were accounted for in the results. All participants received the reference standard. There were no 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 This study was performed in a tertiary referral centre of a TB‐endemic country, where TB is still a serious public health problem and the incidence of active TB was as high as 73 per 100,000 population (intermediate burden country according to World Health Organization classification) in 2005 At least, 38 of the 674 participants belonged to the patient population of Shim 2005 (as reported in Kim 2006) 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?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low