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BACKGROUND Measuring variation in perioperative outcomes to accurately discriminate performance between surgical providers may be limited by reliability. We aimed to evaluate reliability estimates of metrics associated with lung cancer resection. METHODS We performed a retrospective cohort study utilizing the 2015 National Cancer Database to identify patients undergoing lung cancer resection. Primary outcomes were reliability estimates for perioperative outcomes and for measures of adherence to clinical benchmarks, generated through hierarchical multi-level modeling techniques. RESULTS We identified 27,300 patients undergoing resection. Overall risk- and reliability-adjusted 30- and 90-day mortality rates were 1.7% and 3.3%, respectively; 61.0% and 41.1% of eligible patients received stage-appropriate adjuvant and neoadjuvant therapy. Video-assisted thoracoscopic surgery (VATS) was performed in 59.6% of cases with clinical stage I disease. The mean reliability of 30- and 90-day mortality was 0.11 (standard deviation (SD) 0.09) and 0.22 (SD 0.15), respectively; for performing VATS for stage I disease, 0.97 (SD 0.04). When stratified by hospital volume quartile, the mean reliability of 30-day mortality was 0.04 (SD 0.03) in the lowest and 0.20 (SD 0.10) in the highest quartile. Only 14% of hospitals met an established 0.7 reliability benchmark for 30- and 90-day mortality, but over 97% of hospitals exceeded these benchmarks for providing stage-appropriate systemic therapy and performing VATS for stage I disease. CONCLUSIONS Metrics used to compare lung cancer surgical performance between providers have varying levels of reliability. Reliability should be considered when profiling providers, which will become particularly important as lung cancer treatment under screening programs continues to expand.

The racial gap in surgical treatment for early-stage non-small cell lung cancer (NSCLC) has been narrowing at the population level, but it is unknown if this trend persists at the facility level.We queried the National Cancer Database Participant User File from 2006 to 2016 for patients with stage I NSCLC. Facilities were grouped by type, location, and resection volume. The cumulative surgery rate for Black and White patients in each group was calculated, and an incidence rate difference of receipt of surgery was determined. Logistic regression with estimation of marginal effects was used to assess the probability difference of receiving surgery in Black versus White patients in each year.In total, 315,474 patients were included; 287,585 (91.2%) were White and 27,889 (8.8%) were Black. The surgery rate was greater for White patients (60.2% vs 55.8%, P .001). For most groups, the surgery disparity narrowed over the study period. The disparity widened in community cancer programs; facilities in the New England, West North Central, and Pacific regions; and the lowest volume facilities. The probability difference for receiving surgery was significantly smaller in 2016 versus 2006 in the Middle Atlantic region and community cancer programs; the difference was unchanged for all other groupings.Trends in disparities in the use of resection for early-stage NSCLC are not universal across facility groupings. As efforts are made toward addressing racial disparities in surgical care for NSCLC, it will be important to remember that population-level analyses may mask lack of progress in certain facility groups.

Available therapies and clinical trials

Allelic fractions for all variants detected in tDNA and ctDNA* in patients for whom both plasma and tissue samples were obtained (n=50)

Summary of driver and resistance mutations in EGFR and ALK detected in ctDNA, tDNA, and both ctDNA and tDNA

Tissue next-generation sequencing gene coverage. A: Illumina TruSeq panel (47 genes), and B: Penn Precision Panel (20 genes)

Analysis of discordant EGFR driver and resistance mutations detected in tDNA or ctDNA

All mutations detected in patient ctDNA (n=102)

Circulating tumor DNA next-generation sequencing gene coverage

Total amount of cfDNA extracted from each patient sample

Purpose: The expanding number of targeted therapeutics for non–small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS.Experimental Design: A total of 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible.Results: We detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. Although ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible.Conclusions: Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution. Clin Cancer Res; 22(23); 5772–82. ©2016 AACR.

Precision medicine approaches for managing patients with metastatic castrate-resistant prostate cancer (mCRPC) are lacking. Non-invasive approaches for molecular monitoring of disease are urgently needed, especially for patients suffering from bone metastases for whom tissue biopsy is challenging. Here we utilized baseline blood samples to identify mCRPC patients most likely to benefit from abiraterone plus prednisone (AAP) or enzalutamide. Baseline blood samples were collected for circulating tumor cell (CTC) enumeration and qPCR-based gene expression analysis from 51 men with mCRPC beginning treatment with abiraterone or enzalutamide. Of 51 patients (median age 68 years [51–82]), 22 received AAP (abiraterone 1000 mg/day plus prednisone 10 mg/day) and 29 received enzalutamide (160 mg/day). The cohort was randomly divided into training (n = 37) and test (n = 14) sets. Baseline clinical variables (Gleason score, PSA, testosterone, and hemoglobin), CTC count, and qPCR-based gene expression data for 141 genes/isoforms in CTC-enriched blood were analyzed with respect to overall survival (OS). Genes with expression most associated with OS included MSLN, ARG2, FGF8, KLK3, ESRP2, NPR3, CCND1, and WNT5A. Using a Cox-elastic net model for our test set, the 8-gene expression signature had a c-index of 0.87 (95% CI [0.80, 0.94]) and was more strongly associated with OS than clinical variables or CTC count alone, or a combination of the three variables. For patients with a low-risk vs. high-risk gene expression signature, median OS was not reached vs. 18 months, respectively (HR 5.32 [1.91–14.80], p = 0.001). For the subset of 41 patients for whom progression-free survival (PFS) data was available, the median PFS for patients with a low-risk vs high-risk gene expression signature was 20 vs. 5 months, respectively (HR 2.95 [1.46–5.98], p = 0.003). If validated in a larger prospective study, this test may predict patients most likely to benefit from second-generation antiandrogen therapy.

Treatment guidelines for stage I–III esophageal cancer indicate that management should include surgery in appropriate patients. Variations in utilization of surgery may contribute to racial differences observed in survival. We sought to identify factors associated with racial disparities in surgical resection of esophageal cancer and evaluate associated survival differences. Patients diagnosed with stage I–III esophageal cancer from 2004 to 2015 were identified using the National Cancer Database. Matched patient cohorts were created to reduce confounding. Multivariate logistic regression was used to identify factors associated with receipt of surgery. Multi-level modeling was performed to control for random effects of individual hospitals on surgical utilization. A total of 60,041 patients were included (4402 black; 55,639 white). After 1:1 matching, there were 5858 patients evenly distributed across race. For all stages, significantly fewer black than white patients received surgery. Black race independently conferred lower likelihood of receiving surgery in single-level multivariable analysis (OR (95% CI); stage I, 0.67 (0.48–0.94); stage II, 0.76 (0.60–0.96); stage III, 0.62 (0.50–0.76)) and after controlling for hospital random effects. Hospital-level random effects accounted for one third of the unexplained variance in receipt of surgery. Risk-adjusted 1-, 3-, and 5-year mortality was higher for patients who did not undergo surgery. Black patients with esophageal cancer are at higher risk of mortality compared to white patients. This increased risk may be influenced by decreased likelihood of receiving surgical intervention for resectable disease, in part because of between-hospital differences. Improving access to surgical care may improve disparities in esophageal cancer survival.

Purpose: Our institution's hepatopancreaticobiliary surgery service (HPBS) has demonstrated low rates of venous thromboembolism (VTE). We sought to determine whether the HPBS's regimented multimodal VTE prophylaxis pathway, which includes the use of mechanical prophylaxis, pharmacological prophylaxis, and ambulation, plays a role in achieving low VTE rates. Methods: We compared pancreatic surgeries in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) participant user file with our institution's data from 2011 to 2016 using univariate, multivariate, and matching statistics. Results: Among 36,435 NSQIP operations, 850 (2.3%) underwent surgery by the HPBS. The HPBS achieved lower VTE rates than the national cohort (2.0% vs. 3.5%, p = 0.018). Upon multivariate analysis, having an operation performed by the HPBS independently conferred lower odds of VTE incidence in the matched cohort (odds ratio = 0.530, p = 0.041). Conclusions: We identified an independent correlation between the HPBS and decreased VTE incidence, which we believe to be due to strict adherence to and team participation in a high risk VTE prophylaxis pathway, including inpatient pharmacological prophylaxis, thromboembolic deterrent stockings, sequential compression devices, and mandatory ambulation.

The National Lung Screening Trial (NLST) established a role for lung cancer screening. Mortality benefits with screening are predicated on successful treatment with low surgical mortality. Given variations observed in perioperative outcomes after lung cancer resection, it remains unknown whether benefits observed in the NLST are generalizable to a broader population. We sought to determine whether NLST perioperative outcomes are reflective of contemporary practice in a national cohort.We identified patients diagnosed with non-small cell lung cancer who underwent lung resection in the 2014 to 2015 National Cancer Database (NCDB) and the NLST. We compared demographic and cancer characteristics in both datasets. We used hierarchical logistic regression to compare 30-day and 90-day postoperative mortality across facilities in both datasets.In all, 65054 patients in NCDB and 1003 patients in the NLST treated across 1119 NCDB hospitals and 33 NLST hospitals were included. After risk and reliability adjustment, mean 30-day and 90-day mortality were significantly higher among NCDB hospitals (mean 30-day, 2.2 [95% confidence interval (CI), 2.2 to 2.2] vs 1.8 [95% CI, 1.8 to 1.8], P .001; mean 90-day, 4.2 [95% CI, 4.2 to 4.3] vs 2.9 [95% CI, 2.9 to 2.9], P.001). Variation in risk- and reliability-adjusted 30-day mortality (95% CI, 1.1% to 4.9%) and 90-day mortality (95% CI, 2.6% to 9.7%) was observed among NCDB hospitals. Adjusted mortality was similar among NLST facilities (30 days, 1.8% to 1.8%; 90 days, 2.9% to 2.9%).Risk- and reliability-adjusted postoperative mortality varies widely in a national cohort compared with outcomes observed in the NLST. Efforts to minimize this variation are needed to ensure that benefits of lung cancer screening are fully realized in the United States.

Treatment guidelines for stage I-III esophageal cancer indicate that management should include surgery in appropriate patients. Variations in utilization of surgery may contribute to racial differences observed in survival. We sought to identify factors associated with racial disparities in surgical resection of esophageal cancer and evaluate associated survival differences.Patients diagnosed with stage I-III esophageal cancer from 2004 to 2015 were identified using the National Cancer Database. Matched patient cohorts were created to reduce confounding. Multivariate logistic regression was used to identify factors associated with receipt of surgery. Multi-level modeling was performed to control for random effects of individual hospitals on surgical utilization.A total of 60,041 patients were included (4402 black; 55,639 white). After 1:1 matching, there were 5858 patients evenly distributed across race. For all stages, significantly fewer black than white patients received surgery. Black race independently conferred lower likelihood of receiving surgery in single-level multivariable analysis (OR (95% CI); stage I, 0.67 (0.48-0.94); stage II, 0.76 (0.60-0.96); stage III, 0.62 (0.50-0.76)) and after controlling for hospital random effects. Hospital-level random effects accounted for one third of the unexplained variance in receipt of surgery. Risk-adjusted 1-, 3-, and 5-year mortality was higher for patients who did not undergo surgery.Black patients with esophageal cancer are at higher risk of mortality compared to white patients. This increased risk may be influenced by decreased likelihood of receiving surgical intervention for resectable disease, in part because of between-hospital differences. Improving access to surgical care may improve disparities in esophageal cancer survival.

To determine the feasibility of liquid biopsy for monitoring of patients with advanced melanoma, cell-free DNA was extracted from plasma for 25 Stage III/IV patients, most (84.0%) having received previous therapy. DNA concentrations ranged from 0.6 to 390.0 ng/ml (median = 7.8 ng/ml) and were positively correlated with tumor burden as measured by imaging (Spearman rho = 0.5435, p = .0363). Using ultra-deep sequencing for a 61-gene panel, one or more mutations were detected in 12 of 25 samples (48.0%), and this proportion did not vary significantly for patients on or off therapy at the time of blood draw (52.9% and 37.5% respectively; p = .673). Sixteen mutations were detected in eight different genes, with the most frequent mutations detected in BRAF, NRAS, and KIT. Allele fractions ranged from 1.1% to 63.2% (median = 29.1%). Among patients with tissue next-generation sequencing, nine of 11 plasma mutations were also detected in matched tissue, for a concordance of 81.8%.

Purpose: The expanding number of targeted therapeutics for non–small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS. Experimental Design: A total of 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible. Results: We detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. Although ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible. Conclusions: Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution. Clin Cancer Res; 22(23); 5772–82. ©2016 AACR.

Importance The clinical implications of adding plasma-based circulating tumor DNA next-generation sequencing (NGS) to tissue NGS for targetable mutation detection in non–small cell lung cancer (NSCLC) have not been formally assessed. Objective To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting. Design, Setting, and Participants This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine clinical management. Plasma NGS was performed using a 73-gene commercial platform. Patients were enrolled at the Hospital of the University of Pennsylvania from April 1, 2016, through January 2, 2018. The database was locked for follow-up and analyses on January 2, 2018, with a median follow-up of 7 months (range, 1-21 months). Main Outcomes and Measures The number of patients with targetable alterations detected with plasma and tissue NGS; the association between the allele fractions (AFs) of mutations detected in tissue and plasma; and the association of response rate with the plasma AF of the targeted mutations. Results Among the 323 patients with NSCLC (60.1% female; median age, 65 years [range, 33-93 years]), therapeutically targetable mutations were detected inEGFR,ALK,MET,BRCA1,ROS1, RET, ERBB2,orBRAFfor 113 (35.0%) overall. Ninety-four patients (29.1%) had plasma testing only at the discretion of the treating physician or patient preference. Among the 94 patients with plasma testing alone, 31 (33.0%) had a therapeutically targetable mutation detected, thus obviating the need for an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue NGS or were unable to have tissue NGS, a therapeutically targetable mutation was detected in tissue alone for 47 patients (20.5%), whereas the addition of plasma testing increased this number to 82 (35.8%). Thirty-six of 42 patients (85.7%) who received a targeted therapy based on the plasma result achieved a complete or a partial response or stable disease. The plasma-based targeted mutation AF had no correlation with depth of Response Evaluation Criteria in Solid Tumors response (r = −0.121;P = .45). Conclusions and Relevance Integration of plasma NGS testing into the routine management of stage IV NSCLC demonstrates a marked increase of the detection of therapeutically targetable mutations and improved delivery of molecularly guided therapy.

OBJECTIVES: A malignant pleural effusion (MPE) is a common complication in non-small cell lung cancer (NSCLC) with important staging and prognostic information. Patients with MPEs are often candidates for advanced therapies, however, the current gold standard, cytological analysis of pleural fluid samples, has limited sensitivity. We aimed to demonstrate the feasibility of non-invasive enumeration and immunophenotyping of EpCAM-positive cells in pleural fluid samples for the diagnosis of a MPE in NSCLC patients. MATERIALS AND METHODS: Pleural fluid specimens were prospectively collected from patients with NSCLC and the CellSearch® technology was utilized for the enumeration of pleural EpCAM-positive cells (PECs) and determination of PD-L1 expression on PECs from pleural fluid samples. The diagnostic performance of the enumeration of single PECs and PEC clusters was assessed using receiver operating characteristic (ROC) curves. The Kaplan-Meier method and Cox proportional hazards model was used to assess the impact of PECs and PEC clusters on overall survival (OS). RESULTS: 101 NSCLC patients were enrolled. The median number of PECs was significantly greater in the malignant (n=84) versus non-malignant group (n=17) (730 PECs/mL vs 1.0 PEC/mL, p

To assess trends in utilization and perioperative outcomes of laparoscopic and open abdominal wall hernia repair. Using the ACS-NSQIP database between 2009 and 2012, patients were identified as having an ICD-9 diagnosis of an umbilical, ventral, or incisional hernia as well as a CPT code for a laparoscopic or open abdominal wall hernia repair. A coarsened exact matching procedure was utilized to create a matched cohort to mitigate selection bias. Thirty-day outcomes analysis was done for the aggregate and matched cohorts. Subcategory analysis was performed for inpatient/outpatient status, strangulated/incarcerated hernias, initial/recurrent repairs, and hernia type (umbilical, ventral, incisional). Chi-square analysis was performed to determine the statistical significance of each comparison. In total, 112,074 qualifying patients were identified, 86,566 (77.24 %) open and 25,508 (22.76 %) laparoscopic. Patients undergoing laparoscopic repair were more likely to have preexisting comorbidities, but less likely to experience any postoperative morbidity (11.74 vs. 7.25 %, P

e16529 Background: Prostate cancer is the most common cancer in men in the U.S., with 30% 5-year overall survival (OS) for patients (pts) with metastases. To take a precision medicine approach to the management of metastatic castrate-resistant prostate cancer (mCRPC), we developed a blood circulating tumor cell (CTC)-based test to identify mCRPC pts most likely to benefit from abiraterone (abi) or enzalutamide (enza). Methods: In this multi-institution prospective study, men with mCRPC were enrolled prior to starting abi (1,000 mg/d plus prednisone 10 mg/d) or enza (160 mg/d). At baseline (BL), 12 w, and progression, blood samples were collected for CellSearch-based CTC enumeration and qPCR-based gene expression analysis. Results: 69 pts (median age 68 y [50-82]) received abi (n = 25) or enza (n = 44) and had evaluable blood samples. Consistent with prior publications, among 43 pts with BL CTC > 0, clearance of detectable CTCs (BL CTCs > 0 and 12 w CTCs = 0), was achieved in 24 patients (55.8%), and was associated with greater median OS (31 mo vs. 18 mo, log-rank p = 0.03). The 43 pts with BL CTC > 0 were then randomly divided into training (n = 31) and validation (n = 12) sets. Baseline gene expression data for the training set was used to develop a model to predict CTC clearance, starting with a panel of 141 expressed genes/isoforms including those associated with prostate cancer. Of the models tested, random forest yielded the best performance, with respective training and validation set sensitivity of 0.7 and 1, specificity 0.75 and 0.71, AUC 0.88 and 0.91. Top genes identified include those previously associated with disease – HOXB13, ESRP2, KLK3, GRHL2, and KRT19, among others. Conclusions: A gene expression signature from a baseline blood sample with CellSearch-enriched CTCs can predict clearance of detectable CTCs in response to abi/enza with high AUC and may give insight into molecular mechanisms of response. A prospective study with a larger number of patients will be required to further validate our findings. Ultimately, this blood test has the potential to select the patients most likely to benefit from second-generation antiandrogen vs. non-hormonal systemic treatment.

Introductory Sentence indicating purpose of study: Circulating tumor cell (CTC) clusters have been shown to have higher metastatic potential than single CTCs in breast, pancreatic, and other cancers, yet these clusters have not been extensively described in metastatic castrate-resistant prostate cancer (MCRPC). Here we sought to determine the feasibility of capturing and characterizing CTC clusters in prostate cancer patients. Description of Experimental Procedures: Fifty-five blood samples from 29 MCRPC patients, ages 50 to 81 (median age 68), were obtained prior to the patient starting or switching to androgen receptor inhibitor or 17 alpha lyase inhibitor therapies. Eighteen patients received enzalutamide and 11 received abiraterone. The majority of patients had a Gleason score > 7 (22; 75.9%), bone metastases (19; 65.5%), and an ECOG status of 0 (21; 72.4%). All patients had previously undergone, or were receiving at time of enrollment, androgen deprivation therapy. Eleven patients (37.9%) had been on a prior 2nd generation anti-androgen therapy. CTC single cells and clusters (2 or more cells together in one image) were enumerated using the CellSearch system and stained to detect expression of androgen receptor (AR), glucocorticoid receptor (GR), and neuroendocrine (NE) markers. Summary of Data: Five or more single CTCs, a measure which has previously been associated with an unfavorable prognosis, were detected in 13 of 29 patients (44.8%), and in 19 of 55 blood samples (34.5%). Altogether, a total of 282 CTC clusters was detected, with 1 or more clusters found in 10 patients (34.5%) and 13 samples (23.6%). The number of clusters per 7.5ml of blood ranged from 0-150, and clusters contained anywhere from 2 to 16 cells. Most CTC clusters (268; 95.0%) contained only CTCs and no leukocytes. Just over half the detected clusters (162; 57.4%) contained only 2 CTCs. Cluster staining patterns were fairly homogenous with 29.4% of clusters having uniform expression of either AR, GR, or NE markers, i.e., all CTCs in the cluster expressed the marker of interest. Most clusters (67.7%) were uniformly marker negative and the remaining 2.8% demonstrated a mix of marker positive and marker negative CTCs. Serum Chromogranin A levels, as determined by standard of care clinical blood testing, were found to be positively associated with the number of CTC clusters per 7.5ml of blood (p Statement of Conclusions: The capture and characterization of CTC clusters in the blood of MCRPC patients can be successfully performed using the CellSearch system. Further investigation into the clinical implications of these clusters is warranted, including whether cluster characteristics are associated with more aggressive disease. Citation Format: Samantha L. Savitch, Stephanie S. Yee, Devon Soucier, Denis Smirnov, Chandra Rao, Steve Gross, Ravi K. Amaravadi, David J. Vaughn, Naomi B. Haas, Erica L. Carpenter. Capture and characterization of circulating tumor cell clusters in patients with metastatic castrate-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 758. doi:10.1158/1538-7445.AM2017-758

Introduction: Malignant pleural effusions (MPE) occur as a frequent complication of advanced non-small cell lung cancer (NSCLC), and denote a poor prognosis. Cytological evaluation of MPEs has a sensitivity of only 40-60%. The CellSearch technology (Janssen Diagnostics, LLC) is an FDA approved method of detecting rare circulating tumor cells (CTCs) in blood. Assessment of pleural fluid samples using CellSearch provides an approach to enrich often undetectable CTCs and phenotype these cells for markers of interest. PD-L1 staining of tumor tissue is essential for determining patient candidacy for checkpoint inhibitor therapy, however, tissue can often be difficult to obtain. Here, we demonstrate the feasibility of applying the CellSearch CTC enrichment platform to measure PD-L1 expression and enumerate tumor cells in MPE of NSCLC patients. Methods: This was a single center, prospective observational study of NSCLC patients with a pleural effusion. The anti-human CD274 (PD-L1) antibody (Biolegend) was used as a marker with the CellSearch CXC CTC kit and was detected in the open 4th channel of the CellTracks Analyzer. Determination of CTC PD-L1 expression was validated through peripheral blood spiking experiments. 7.5ml of pleural fluid was collected from NSCLC patients, preserved in CellSave tubes and processed within 72 hours. Identification and enumeration of CTCs was performed using the CellTracks Analyzer. We then compared CellSearch results to conventional cytological analysis. Results: Pleural effusion samples from 66 patients between the ages of 43 and 80 (median=69) were obtained following thoracentesis. The majority of patients were former (40; 60.6%) or never (21; 31.8%) smokers. At the time of effusion, 23 (34.8%) patients were on a therapeutic regimen: 10 (15.2%) were receiving chemotherapy, 9 (13.6%) were on an EGFR or ALK TKI, and 5 (7.6%) were on a checkpoint inhibitor. CTCs were detected in 63 of 66 samples using the CellSearch system. Among the 66 pleural effusions, cytological evaluation determined 40 samples were malignant and 26 were benign. CellSearch detected more CTCs in patients with a MPE (median 1798, range: 7 to 114,920) compared to patients with a benign effusion (median 8, range: 0 to 953; p=0.005). In the MPE group, 18 (45.0%) samples demonstrated >10% PD-L1 positivity with 9 (22.5%) samples showing >50% PD-L1 positivity. Conclusion: The CellSearch CTC enumeration and characterization platform can be successfully adapted for detection of CTCs in MPE of NSCLC patients. Our preliminary results suggest this approach may be a useful, non-invasive diagnostic adjunct for the determination of a MPE and assessment of PD-L1 expression in NSCLC patients. Further study is warranted to determine what role this test could play in assessing patients for checkpoint inhibitor therapy and its relationship with tissue based tests. Citation Format: Jeffrey C. Thompson, Samantha L. Savitch, Ryan Fan, Stephanie S. Yee, Christian A. Powers, Gordon Yu, Lauren Gebrian, Chandra Rao, Steve Gross, Michael Feldman, Anil Vachani, Erica L. Carpenter. Characterization of tumor cells and assessment of PD-L1 expression in pleural effusions of metastatic non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3736. doi:10.1158/1538-7445.AM2017-3736