Women are Underrepresented in Non-small Cell Lung Cancer Clinical Trials: A Systematic Review.

PURPOSE: To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer. METHODS: An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words "carcinoma, non-small cell, lung" and "non-small cell lung cancer." Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student's t-test was used to compare the means of males and females. RESULTS: Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001). CONCLUSIONS: Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with 'Actionable' Pulmonary Nodules.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

Predicting Non-home Discharge After Lung Surgery: Analysis of the General Thoracic Surgery Database.

BACKGROUND: Anticipating the need for non-home discharge (NHD) enables improved patient counseling and expedites placement, potentially reducing length of stay and hospital readmission. The objective of this study was to create a simple, preoperative, clinical prediction tool for NHD using The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). METHODS: The STS GTSD was queried for patients who underwent elective anatomic lung cancer resection between 2009 and 2019. Exclusion criteria included age <18 years, percentage predicted diffusion capacity of the lung for carbon monoxide <20% or >150%, N3 or M1 disease, incomplete datasets, and mortality. The primary outcome was defined as discharge to an extended care, transitional care, rehabilitation center, or another hospital. Multivariable logistic regression was used to select risk factors and a nomogram for predicting risk of NHD was developed. The approach was cross-validated in 100 replications of a training set consisting of randomly selected two-thirds of the cohort and a validation set of remaining patients. RESULTS: A total of 35 948 patients from the STS GTSD met inclusion criteria. Final model variables used to derive the nomogram for NHD risk prediction included age (P < .001), percentage predicted diffusion capacity of the lung for carbon monoxide (P < .001), open surgery (P < .001), cerebrovascular history (P < .001), and Zubrod score (P < .001). The receiver operating characteristic curve, using sensitivities and specificities of the model, yielded area under the curve of 0.74. In 100 replicated cross-validations, out-of-sample area under the curve ranged from 0.72-0.76. CONCLUSIONS: Using readily available preoperative variables, our nomogram prognosticates the risk of NHD after anatomic lung resection with good discriminatory ability. Such risk stratification can enable improved patient counseling and facilitate better planning of patients' postoperative needs.

Conditional survival analysis of patients with resected non-small cell lung cancer.

Background: Conditional survival (CS) analyses provide an estimate of survival accounting for years already survived after treatment. We aim to evaluate the difference between actuarial and conditional survival in patients following lung resection for non-small cell lung cancer (NSCLC). In addition, CS analyses are used to examine whether prognosticators of survival change over time following surgery. Methods: Patients who underwent anatomic lung resection at a single institution for pathologic stage I-IIIA NSCLC between 2010 and 2021 were identified; those who underwent wedge resection for node-negative tumors ≤2 cm were also included. CS estimates were calculated as the probability of remaining disease-free after x years of nonrecurrence (CSx). Kaplan-Meier, log-rank, and Cox proportional hazard methods for examining CS were used for subgroup comparisons and assessing associations with baseline covariates. Results: Overall, 863 patients met the study inclusion criteria, with a median follow-up of 44.1 months. Conditional overall survival (OS) and disease-free survival (DFS) were greater than actuarial rates at all time points after surgery. At the time of resection, male sex (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.03 to 1.72; P = .032), tumor size >3 cm (HR, 1.17; 95% CI, 1.11-1.23; P < .001), node positivity (HR, 3.31; 95% CI, 2.52-4.33; P < .001), and American Joint Committee on Cancer stage (P < .001) were associated with DFS. However, if a patient lived 3 years without recurrence (CS3), these factors were no longer prognostic of DFS. Conclusions: Conditional survival analyses provide dynamic assessments of OS and DFS after NSCLC resection. After 3 years without recurrence, certain characteristics associated with DFS at the time of surgery no longer prognosticate recurrence.

The association between thoracic sarcopenia and survival is gender specific in early-stage lung cancer.

Background: Sarcopenia, as measured at the 3rd lumbar (L3) level, has been shown to prognosticate survival in cancer patients. However, many patients with early-stage non-small cell lung cancer (NSCLC) do not undergo abdominal imaging. We hypothesized that preoperative thoracic sarcopenia is associated with survival in patients undergoing lung resection for early-stage NSCLC. Methods: Patients who underwent anatomic resection for NSCLC between 2010-2019 were retrospectively identified. Exclusion criteria included induction therapy, less than 90 days of follow-up, and absence of computed tomography (CT) imaging. Cross sectional skeletal muscle area was calculated at the fifth thoracic vertebra (T5), twelfth thoracic vertebra (T12), and L3 level. Gender-specific lowest quartile values and previously defined values were used to define sarcopenia. Overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: Overall, 221 patients met inclusion criteria with a median body mass index (BMI) of 26.5 kg/m2 [interquartile range (IQR), 23.3-29.9 kg/m2], age of 69 years (IQR, 62.4-74.9 years), and follow-up of 46.9 months (IQR, 25.0-70.7 months). At the T5 level, sarcopenic males demonstrated worse overall survival [median 41.0 (IQR, 13.8-53.7) vs. 42.0 (IQR, 23.1-55.1) months, P=0.023] and disease-free survival [median 15.8 (IQR, 8.4-30.78) vs. 34.8 (IQR, 20.1-50.5) months, P=0.007] when compared to non-sarcopenic males. There was no difference in survival between sarcopenic and non-sarcopenic females when assessed at T5. Sarcopenia at T12 or L3 was associated with worse overall survival (P<0.05). Conclusions: Sarcopenia at T5 is associated with worse survival in males, but not females. When using upper thoracic vertebral levels to assess for sarcopenia, it is necessary to account for gender.

The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.

BACKGROUND: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and high rates of annual cancer deaths. Currently, low-dose computed tomography (LDCT) screening produces a high false discovery rate. This limitation has prompted research to identify biomarkers to more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research. Main Body: Multiple biomarkers within the IGF family have been investigated, most notably IGF-I and IGF binding protein 3. However, newer studies seek to expand this search to other molecules within the IGF axis. Certain studies have demonstrated these biomarkers are useful when used in combination with lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent treatment via systemic therapy. Despite these advances, additional knowledge of complex regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic and therapeutic purposes. CONCLUSIONS: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.

Definition and assessment of high risk in patients considered for lobectomy for stage I non-small cell lung cancer: The American Association for Thoracic Surgery expert panel consensus document.

OBJECTIVE: Lobectomy is a standard treatment for stage I non-small cell lung cancer, but a significant proportion of patients are considered at high risk for complications, including mortality, after lobectomy and might not be candidates. Identifying who is at risk is important and in evolution. The objective of The American Association for Thoracic Surgery Clinical Practice Standards Committee expert panel was to review important considerations and factors in assessing who is at high risk among patients considered for lobectomy. METHODS: The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an expert panel that developed an expert consensus document after systematic review of the literature. The expert panel generated a priori a list of important risk factors in the determination of high risk for lobectomy. A survey was administered, and the expert panel was asked to grade the relative importance of each risk factor. Recommendations were developed using discussion and a modified Delphi method. RESULTS: The expert panel survey identified the most important factors in the determination of high risk, which included the need for supplemental oxygen because of severe underlying lung disease, low diffusion capacity, the presence of frailty, and the overall assessment of daily activity and functional status. The panel determined that factors, such as age (as a sole factor), were less important in risk assessment. CONCLUSIONS: Defining who is at high risk for lobectomy for stage I non-small cell lung cancer is challenging, but remains critical. There was impressive strong consensus on identification of important factors and their hierarchical ranking of perceived risk. The panel identified several key factors that can be incorporated in risk assessment. The factors are evolving and as the population ages, factors such as neurocognitive function and frailty become more important. A minimally invasive approach becomes even more critical in this older population to mitigate risk. The determination of risk is a clinical decision and judgement, which should also take into consideration patient perspectives, values, preferences, and quality of life.

Cannabis Use Is Associated With Recurrence After Primary Spontaneous Pneumothorax.

Purpose: Primary spontaneous pneumothorax (PSP) is a frequently encountered entity that carries a high rate of recurrence. The current study aims to investigate if cannabis use at time of initial PSP is associated with disease recurrence. Methods: Patients presenting with PSP between 2010 and 2018 at a single institution were identified. Exclusion criteria included secondary pneumothorax, severe chronic lung disease, lung cancer, and lost to follow-up. Patients were compared relative to their cannabis usage with Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. Results: Overall, 67 patients (53 male) met inclusion criteria with a median body mass index (BMI) of 21.5 kg/m2 (IQR 19.1-25.2) and age of 34 years (IQR 22-53). Initial treatment consisted of chest tube in 42 patients (63%), video-assisted thoracoscopic surgery wedge resection in 19 patients (28%), and observation in 6 patients (9%). Cannabis users (n = 28; 42%) had a higher rate of tobacco use (79 vs. 38%; p = 0.005), lower BMI [21.0 kg/m2 (IQR 18.3-23.1) vs. 22.2 kg/m2 (IQR 19.9-28.6), p = 0.037], and were more likely to require intervention at first presentation compared with non-marijuana users. Cannabis use was associated with PSP recurrence when adjusting for tobacco use, BMI, and height (OR 1.85, 95% CI 1.38-18.3, p = 0.014). Conclusion: There is a high rate of cannabis usage in patients presenting with PSP. Cannabis usage is associated with PSP recurrence and eventual need for operative intervention.

Redefining the Risk of Surgery for Clinical Stage IIIA (N2) Non-Small Cell Lung Cancer: A Pooled Analysis of the STS GTSD and ESTS Registry.

BACKGROUND: Management of clinical stage IIIA-N2 (cIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. We evaluated treatment strategies and outcomes in cIIIA-N2 NSCLC patients who underwent pulmonary resection in The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) and the European Society of Thoracic Surgeons (ESTS) Registry. METHODS: The STS GTSD and ESTS Registry were queried for patients who underwent pulmonary resection for cIIIA-N2 NSCLC between 2012 and 2016. Demographic variables, treatment strategies, and outcome measures were collected and analyzed. Significance of differences was determined using the χ2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. RESULTS: Pulmonary resection was performed in 4279 cIIIA-N2 NSCLC patients (2928 STS GTSD; 1351 ESTS). Induction therapy was administered to 49%. Lobectomy was performed in 67.1% and pneumonectomy in 13%. Lobectomy was associated with 19.2% major morbidity and 1.6% operative mortality, while pneumonectomy was associated with 34.1% and 5%, respectively. Induction therapy was associated with a higher rate of major morbidity or mortality than upfront surgery (23.2% vs 19.5%, p = 0.004), driven by pneumonectomy (40.7% vs 30.3%, p = 0.012) rather than lobectomy (20.3% vs 18.8%, p = 0.31). CONCLUSIONS: Pulmonary resection for cIIIA-N2 NSCLC is associated with low rates of operative morbidity and mortality, with lobectomy having lower morbidity and mortality than pneumonectomy. Induction therapy, particularly chemoradiotherapy, is associated with a higher rate of composite morbidity or mortality than upfront surgery in pneumonectomy patients but not lobectomy patients.

Sarcopenia after induction therapy is associated with reduced survival in patients undergoing esophagectomy for locally-advanced esophageal cancer.

BACKGROUND: The impact of sarcopenia on the outcome of esophageal cancer patients remains unknown in North American populations. The current study aims to investigate if sarcopenia at the time of esophagectomy for locally-advanced esophageal cancer (LAEC) is associated with survival. METHODS: Patients who underwent induction therapy followed by esophagectomy for LAEC between 2010-2018 at a single institution were identified. Exclusion criteria included follow-up less than 90 days and distant metastatic disease at the time of surgery. Demographic, treatment, and outcome data were retrospectively collected. Computed tomography (CT) scans following induction therapy were analyzed to calculate skeletal muscle index (SMI). Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier and Cox Proportional Hazard regression analysis. RESULTS: Overall, 52 patients met inclusion criteria with a median BMI of 25 (IQR, 22.4-29.1) kg/m2 and age of 65 (IQR, 57-70) years. Sarcopenia was present in 75% (39/52) of patients at the time of surgery. Sarcopenic patients had a lower median BMI and higher median age when compared to non-sarcopenic patients. There was no difference in gender, race, stage, operative technique, post-operative complications, or hospital length of stay between sarcopenic and non-sarcopenic patients. With a median follow-up of 24.9 months, patients with sarcopenia at the time of esophagectomy had worse OS [median 24.3 (IQR, 9.9-34.5) vs. 50.9 (IQR, 25.6-50.9) months, P=0.0292] and DFS [median 11.7 (IQR, 6.4-25.8) vs. 29.4 (IQR, 12.8-26.7) months, P=0.0387] compared to non-sarcopenic patients. CONCLUSIONS: Sarcopenia is associated with reduced overall and DFS in patients undergoing esophagectomy for LAEC.

Understanding barriers to lung cancer screening in primary care.

BACKGROUND: Low-dose computed tomography (LDCT) scan for lung cancer screening is underutilized. Studies suggest that up to one-third of providers do not know the current lung cancer screening guidelines. Thus, identifying the barriers to utilization of LDCT scan is essential. METHODS: Primary care providers in three different healthcare settings in the United States were surveyed to assess provider knowledge of LDCT scan screening criteria, lung cancer screening practices, and barriers to the utilization of LDCT scan screening. Fisher's Exact, Chi-Squared, and Kruskal-Wallis tests were used to compare provider responses. Multivariable logistic regression was used to test the association between provider characteristics and the likelihood of utilizing LDCT scan for lung cancer screening. RESULTS: The survey was sent to 614 providers, with a 15.7% response rate. Overall, 29.2% of providers report never ordering LDCT scans for eligible patients. Providers practicing at a community or academic hospital more frequently order LDCT scans than those practicing at a safety net hospital. Academic- and community-based providers received a significantly higher mean knowledge score than safety net-based providers [academic 6.84 (SD 1.33), community 6.72 (SD 1.46), safety net 5.85 (SD 1.38); P<0.01]. Overall, only 6.2% of respondents correctly identified all six Centers for Medicare and Medicaid Services eligibility criteria when challenged with three incorrect criteria. Common barriers to utilization of LDCT scan included failure of the electronic medical record (EMR) to notify providers of eligible patients (54.7%), patient refusal (37%), perceived high false-positive rate leading to unnecessary procedures (18.9%), provider time constraints (16.8%), and lack of insurance coverage (13.7%). CONCLUSIONS: Provider knowledge of lung cancer screening guidelines varies, perhaps contributing to underutilization of LDCT scan for lung cancer screening. Improved provider education at safety net hospitals and improving EMR-based best practice alerts may improve the rate of lung cancer screening.

A Prolonged Air Leak Score for Lung Cancer Resection: An Analysis of The Society of Thoracic Surgeons General Thoracic Surgery Database.

BACKGROUND: The objective of this study was to create a simple preoperative tool to assess the risk of prolonged air leak (PAL) using The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). METHODS: The STS GTSD was queried for patients who underwent elective lung cancer resection between 2009 and 2016. Exclusion criteria included pneumonectomy, sleeve lobectomy, chest wall resection, bilateral procedures, and patients with incomplete data sets. The primary outcome was PAL exceeding 5 days. Multivariable logistic regression was used to identify risk factors for a PAL. Model coefficients were used to generate a PAL score (PALS). The approach was cross-validated in 100 replications of a training set consisting of two-thirds of the cohort that was randomly selected and a validation set of remaining patients. RESULTS: A total of 52,198 patients from the STS GTSD met inclusion criteria, with an overall rate of PAL of 10.4% (n = 5453). Final variables incorporated into the PALS included body mass index of 25 kg/m2 or less (7 points), lobectomy or bilobectomy (6 points), forced expiratory volume in 1 second of 70% predicted or less (5 points), male sex (4 points), and right upper lobe procedure (3 points). A cumulative PALS exceeding 17 points stratified patients as high-risk or low-risk for PAL (19.6% vs 9% rate of PAL) with a cross-validated mean negative predictive value of 91%, positive predictive value of 19%, sensitivity of 30%, specificity of 85%, and correctly classifies 79% of patients. CONCLUSIONS: The PALS is a simple preoperative clinical tool that can reliably risk-stratify patients for PAL who are undergoing lung cancer resection.

Improved False-Positive Rates and the Overestimation of Unintended Harm from Lung Cancer Screening.

BACKGROUND: Concern over high false-positive rates and the potential for unintended harm to patients is a critical component of the lack of widespread adoption of lung cancer screening. METHODS: An institutional database was used to identify patients who underwent lung cancer screening between 2/2015 and 2/2018 at Rush University Medical Center and Rush Oak Park Hospital. Reads were executed by dedicated thoracic radiologists and communicated using the Lung Imaging Reporting and Data System (Lung-RADS V.1). RESULTS: Six hundred and four patients were screened over the study period. We identified 21 primary lung cancers and 8 incidental cancers. We identified a false-positive rate of 17.5%. Only 9 patients underwent further investigative workup for benign disease (5.3%); however, only 4 (2.9%) of those patients were found to have inflammatory or infectious lesions, which are common mimickers of lung cancer. Excluding Lung-RADS category 3 for the purpose of quantifying risk of unintended harm from unnecessary procedures, we found a 6.9% false-positive rate, while diagnosing 25% of all Lung-RADS category 4 patients with primary lung cancer. CONCLUSION: False-positive rates in lung cancer screening programs continue to decline with improved radiologic expertise. Additionally, false-positive reporting overestimates the risk of unintended harm from further investigative procedures as only a percentage of positive findings are generally considered for tissue diagnosis (i.e., Lung-RADS category 4).

Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions.

BACKGROUND: This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions. METHODS: Conditioned media from the NSCLC cell lines H358 and H1703 were immunoblotted for soluble isoforms of major histocompatibility complex (MHC) class I (ABC) and II (DRB1, DMB, and DQ) antigens. Sera from 25 patients with benign and 25 patients with malignant lesions were similarly evaluated to appraise the potential diagnostic value. RESULTS: Higher concentrations of soluble HLA class I molecules were observed in conditioned medium for the highly-invasive H1703 cell line, relative to the more indolent H358 cells. Evaluation of these markers against a cohort of 50 cases demonstrated that patients with malignant lesions possess higher levels of HLA class I and II molecules relative to those with benign lesions (p < 0.05), with exception to the primary isoform, DQA1, which was suppressed in malignancies. An analysis of biomarker performance via ROC analysis revealed promising performance (AUC > 0.75) for DMB and the 26 kDa isoform of DQ in distinguishing lesion pathology. CONCLUSIONS: Soluble HLA molecules may have diagnostic value for early-stage NSCLC. Validation studies are currently underway using sera from a lung cancer screening cohort.

Development of bead based multiplexed immunoassay for evaluation of midkine, syndecan-1, and ANGPTL4 in patient serum.

BACKGROUND: Angiogenesis is associated with tumor progression in a range of malignancies. Herein, we develop custom immunobead assays for several mechanistically important targets and evaluated these against sera from cohorts of non-small cell lung cancer (NSCLC) patients. METHODS: Antigen "capture" antibodies for midkine, syndecan-1, and ANGPTL4 were independently conjugated to MagPlex® Microspheres using standard carbodiimide/NHS-based chemistry. These reagents served as the basis for quantitative sandwich assay assembly using biotinylated detection antibodies and R-phycoerythrin-conjugated streptavidin reporter system. Standard curves were created using dilution series of recombinant target proteins with assay performance characteristics calculated, accordingly. Finally, we evaluated a range of serum samples from NSCLC patients (n = 32) to verify assay performance. RESULTS: Multiplexed assays for midkine, syndecan-1, and ANGPTL4 were developed with three orders of magnitude in dynamic range, excellent intra- and inter-assay precision, and accuracy parameters (<10%, and <15% variability, respectively). Detection and quantifications limits were suitable for the three assays to efficiently evaluate sera across a range of disease stages with a four-fold dilution factor. CONCLUSION: We successfully developed and analytically validated a 3-plex immunobead assay for quantifying midkine, syndecan-1, and ANGPTL4 in patient sera. This multiplexed assay will provide an important tool for future studies delineating the role of angiogenesis in lung cancer progression.

Serum Biomarkers May Prognosticate Recurrence in Node-Negative, Non-Small Cell Lung Cancers Less Than 4 Centimeters.

BACKGROUND: A significant proportion of patients who undergo lung resection for less than 4 cm non-small cell lung cancer (NSCLC) will die of disease recurrence within 5 years. The ability to identify patients at greatest risk for recurrence may help individualize treatment and surveillance regimens and improve outcomes. We hypothesized that a serum-based biomarker panel could help risk stratify patients with node-negative NSCLC less than 4 cm for recurrence after lung resection. METHODS: An institutional biorepository of more than 1,800 cases was used to identify patients with resected, node-negative NSCLC less than 4 cm in size. Clinical and radiographic data were collected. Preoperative serum specimens were evaluated in a blinded manner for 47 biomarkers that sampled biological processes associated with metastatic progression, including angiogenesis, energy metabolism, apoptosis, and inflammation. Receiver-operating characteristics curves and log rank tests were used to evaluate individual biomarkers with respect to recurrence, followed by random forest analysis to generate and cross validate a multiple-analyte panel to risk stratify patients for recurrence. RESULTS: The cohort included 123 patients with a median follow-up of 58.2 months; 23 patients had recurrences. A seven-analyte panel consisting of human epididymis protein 4, insulinlike growth factor-binding protein 1, beta-human chorionic gonadotropin, follistatin, prolactin, angiopoietin-2, and hepatocyte growth factor optimally identified patients with disease recurrence with a cross-validated specificity of 91%, sensitivity of 22%, negative predictive value of 83%, positive predictive value of 36%, and accuracy of 78%, providing an area under the receiver-operating characteristics curve of 0.70. CONCLUSIONS: Serum-based biomarkers may be useful for risk stratifying patients with node-negative NSCLC less than 4 cm for recurrence after lung resection.

Durability of Silicone Airway Stents in the Management of Benign Central Airway Obstruction.

PURPOSE: The literature is devoid of a comprehensive analysis of silicone airway stenting for benign central airway obstruction (BCAO). With the largest series in the literature to date, we aim to demonstrate the safety profile, pattern of re-intervention, and duration of silicone airway stents. METHODS: An institutional database was used to identify patients with BCAO who underwent rigid bronchoscopy with dilation and silicone stent placement between 2002 and 2015 at Rush University Medical Center. RESULTS: During the study period, 243 stents were utilized in 63 patients with BCAO. Pure tracheal stenosis was encountered in 71% (45/63), pure tracheomalacia in 11% (7/63), and a hybrid of both in 17% (11/63). Median freedom from re-intervention was 104 (IQR 167) days. Most common indications for re-intervention include mucus accumulation (60%; 131/220), migration (28%; 62/220), and intubation (8%; 18/220). The most common diameters of stent placed were 12 mm (94/220) and 14 mm (96/220). The most common lengths utilized were 30 mm (60/220) and 40 mm (77/220). Duration was not effected by stent size when placed for discrete stenosis. However, 14 mm stents outperformed 12 mm when tracheomalacia was present (157 vs. 37 days; p = 0.005). Patients with a hybrid stenosis fared better when longer stents were used (60 mm stents outlasted 40 mm stents 173 vs. 56 days; p = 0.05). CONCLUSION: Rigid bronchoscopy with silicone airway stenting is a safe and effective option for the management of benign central airway obstruction. Our results highlight several strategies to improve stent duration.