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Introduction: Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation., Methods: First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group., Results: We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002)., Conclusion: CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

Introduction: We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis., Materials & Methods: We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis., Results: We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease., Conclusions: CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC., Methods: Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity., Results: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95% CI 0.01 to 4)., Conclusions: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.

Occupational and environmental carcinogens account for an important minority of cases of bronchogenic carcinoma. From a public health perspective, it is important to characterize occupational and environmental carcinogens and to define disease risk to reduce preventable lung cancer. From a clinician's perspective, it is important to distinguish individual cases of occupational lung cancer from nonoccupational cases, because cancer acquired from work may be compensable through worker's compensation claims and litigation. Important carcinogens include asbestos, radon daughters, diesel exhaust, and metals. Epidemiologic investigations identify excess cases of lung cancer in populations exposed to carcinogens. Experimental animal and ex vivo human research provide complementary information supporting causal relationships between exposure and carcinogenesis. Clinical challenges include proving that a given case of lung cancer is due to an occupational exposure. Research challenges include determining safe exposure thresholds. Only a small percentage of all chemicals used in industry have been extensively analyzed for their carcinogenic potential. Scientific and regulatory information about pulmonary occupational and environmental health and safety is available from several important agencies and organizations, including the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, the International Agency for Research on Cancer, the American Lung Association, and the Environmental Protection Agency.

Context: Focal pulmonary lesions are commonly encountered in clinical practice, and positron emission tomography (PET) with the glucose analog 18-fluorodeoxyglucose (FDG) may be an accurate test for identifying malignant lesions., Objective: To estimate the diagnostic accuracy of FDG-PET for malignant focal pulmonary lesions., Data Sources: Studies published between January 1966 and September 2000 in the MEDLINE and CANCERLIT databases; reference lists of identified studies; abstracts from recent conference proceedings; and direct contact with investigators., Study Selection: Studies that examined FDG-PET or FDG with a modified gamma camera in coincidence mode for diagnosis of focal pulmonary lesions; enrolled at least 10 participants with pulmonary nodules or masses, including at least 5 participants with malignant lesions; and presented sufficient data to permit calculation of sensitivity and specificity were included in the analysis., Data Extraction: Two reviewers independently assessed study quality and abstracted data regarding prevalence of malignancy and sensitivity and specificity of the imaging test. Disagreements were resolved by discussion., Data Synthesis: We used a meta-analytic method to construct summary receiver operating characteristic curves. Forty studies met inclusion criteria. Study methodological quality was fair. Sample sizes were small and blinding was often incomplete. For 1474 focal pulmonary lesions of any size, the maximum joint sensitivity and specificity (the upper left point on the receiver operating characteristic curve at which sensitivity and specificity are equal) of FDG-PET was 91.2% (95% confidence interval, 89.1%-92.9%). In current practice, FDG-PET operates at a point on the summary receiver operating characteristic curve that corresponds approximately to a sensitivity and specificity of 96.8% and 77.8%, respectively. There was no difference in diagnostic accuracy for pulmonary nodules compared with lesions of any size (P =.43), for semiquantitative methods of image interpretation compared with qualitative methods (P =.52), or for FDG-PET compared with FDG imaging with a modified gamma camera in coincidence mode (P =.19)., Conclusions: Positron emission tomography with 18-fluorodeoxyglucose is an accurate noninvasive imaging test for diagnosis of pulmonary nodules and larger mass lesions, although few data exist for nodules smaller than 1 cm in diameter. In current practice, FDG-PET has high sensitivity and intermediate specificity for malignancy.

Positron emission tomography imaging is useful for the characterization of the solitary pulmonary nodule and mediastinal staging. Potential future applications include extrathoracic staging to help to determine the ideal site for possible tissue diagnosis, to guide treatment plans, and to monitor the response to therapy and recurrence. Positron emission tomography may also predict prognosis. This review discusses the uses of positron emission tomography, the current literature, and the clinical guidelines for positron emission tomography imaging.