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.

Pectoralis Muscle Index as Predictor of Outcomes in Patients With Severe Blunt Chest Wall Injury.

INTRODUCTION: Sarcopenia has been shown to portend worse outcomes in injured patients; however, little is known about the impact of thoracic muscle wasting on outcomes of patients with chest wall injury. We hypothesized that reduced pectoralis muscle mass is associated with poor outcomes in patients with severe blunt chest wall injury. METHODS: All patients admitted to the intensive care unit between 2014 and 2019 with blunt chest wall injury requiring mechanical ventilation were retrospectively identified. Blunt chest wall injury was defined as the presence of one or more rib fractures as a result of blunt injury mechanism. Exclusion criteria included lack of admission computed tomography imaging, penetrating trauma, <18 y of age, and primary neurologic injury. Thoracic musculature was assessed by measuring pectoralis muscle cross-sectional area (cm2) that was obtained at the fourth thoracic vertebral level using Slice-O-Matic software. The area was then divided by the patient height in meters2 to calculate pectoralis muscle index (PMI) (cm2/m2). Patients were divided into two groups, 1) the lowest gender-specific quartile of PMI and 2) second-fourth gender-specific PMI quartiles for comparative analysis. RESULTS: One hundred fifty-three patients met the inclusion criteria with a median (interquartile range) age 48 y (34-60), body mass index of 30.1 kg/m2 (24.9-34.6), and rib score of 3.0 (2.0-4.0). Seventy-five percent of patients (116/153) were male. Fourteen patients (8%) had prior history of chronic lung disease. Median (IQR) intensive care unit length-of-stay and duration of mechanical ventilation (MV) was 18.0 d (13.0-25.0) and 15.0 d (10.0-21.0), respectively. Seventy-three patients (48%) underwent tracheostomy and nine patients (6%) expired during hospitalization. On multivariate linear regression, reduced pectoralis muscle mass was associated with increased MV duration when adjusting for rib score and injury severity score (ß 5.98, 95% confidence interval 1.28-10.68, P = 0.013). CONCLUSIONS: Reduced pectoralis muscle mass is associated with increased duration of MV in patients with severe blunt chest wall injury. Knowledge of this can help guide future research and risk stratification of critically ill chest wall injury patients.

Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.

PURPOSE: Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT). METHODS: Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported. RESULTS: 1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible. CONCLUSION: Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

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.

Hemolysis following wrap aortoplasty for Type A aortic dissection repair: Case report and review of the literature.

A Dacron wrap aortoplasty has been described as an adjunct to reduction ascending aortoplasty for the repair of Type A aortic dissections. We report a case of an uncomplicated hemiarch repair with wrap aortoplasty of the distal anastomosis which resulted in severe acute hemolysis. Despite only minimal focal graft deformation on imaging, the patient was found to have a flow gradient across the distal anastomosis, which was reduced by > 50% following release of the outer graft wrap. To our knowledge, only 29 additional cases of hemolytic anemia following aortic dissection repair have been described in the English literature. The reported mechanisms included aortic graft stenosis (50%), graft kinking (23%), external compression of the graft (20%), and a folded elephant trunk appendage (7%). The mean onset of hemolysis following aortic dissection repair occurred 32.2 ± 44.4 months after surgery, with only 16.7% of cases occurring within 2 weeks. This review details the clinical, laboratory, and imaging findings suggestive of mechanical hemolysis following aortic surgery.

Transdiaphragmatic Migration of a Spinal Fixation Rod into the Lung.

Adolescent idiopathic scoliosis may require surgical treatment for extreme curvature of the spine or loss of pulmonary function. We present a report of a 31-year-old woman with a history of scoliosis and anterolateral spinal fusion who developed chest pain and hemoptysis. Imaging revealed that a fixation rod had migrated cephalad, penetrating the diaphragm into the left lower lobe of the lung. The hardware was removed and lung repaired with good results. This is the first reported case of cranial spinal rod migration over a decade after initial implantation.

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.

Endobronchial Metastasis from Extrapulmonary Neoplasms: Analysis of Clinicopathologic Features and Cytological Evaluation by Bronchial Brushing.

PURPOSE: Bronchial brushings (BB) commonly aid in the diagnosis of primary lung cancer. However, the utility of this method in diagnosing endobronchial metastases (EBM) from extrapulmonic malignancies has not been thoroughly evaluated. The purpose of this study is to evaluate the sensitivity of BB in diagnosing EBM. METHODS: An institutional database was queried for all patients with cytologically or histologically confirmed extrapulmonary EBM identified by endobronchial biopsy between 1978 and 2013. Data were collected on patient demographics, histologic and cytologic diagnoses, time from primary malignancy to identification of EBM, and location of EBM. The sensitivity of BB for the diagnosis of EBM and the clinicopathologic features of extrapulmonary EBM were assessed. RESULTS: Fifty-six patients (33 females, 23 males; mean age 53 years) were identified with EBM. Diagnoses included lymphoma (21), breast adenocarcinoma (11), colonic adenocarcinoma (7), melanoma (6), renal cell carcinoma (RCC, 5), embryonal carcinoma (2), and 1 case each of tonsillar squamous cell carcinoma, thymic carcinoma, leiomyosarcoma, and sarcoma, not otherwise specified. The sensitivity of BB for identifying EBM was 85% overall and 94% for non-hematologic malignancies. The mean interval between primary diagnosis and EBM was 59 months (range 0-264 months). Excluding ten patients who had EBM at their initial presentation, lymphoma had the shortest (10 months) and RCC had the longest (264 months) mean interval between primary diagnosis and EBM. The mean time between EBM identification and death was 22.4 months (n = 24). CONCLUSION: Bronchial brushing is a sensitive technique for diagnosing non-hematologic extrapulmonic endobronchial metastases.

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.

Number of Ribs Resected is Associated with Respiratory Complications Following Lobectomy with en bloc Chest Wall Resection.

PURPOSE: Pulmonary lobectomy with en bloc chest wall resection is a common strategy for treating lung cancers invading the chest wall. We hypothesized a direct relationship exists between number of ribs resected and postoperative respiratory complications. METHODS: An institutional database was queried for patients with non-small cell lung cancer that underwent lobectomy with en bloc chest wall resection between 2003 and 2014. Propensity matching was used to identify a cohort of patients who underwent lobectomy via thoracotomy without chest wall resection. Patients were propensity matched on age, gender, smoking history, FEV1, and DLCO. The relationship between number of ribs resected and postoperative respiratory complications (bronchoscopy, re-intubation, pneumonia, or tracheostomy) was examined. RESULTS: Sixty-eight patients (34 chest wall resections; 34 without chest wall resection) were divided into 3 cohorts: cohort A = 0 ribs resected (n = 34), cohort B = 1-3 ribs resected (n = 24), and cohort C = 4-6 ribs resected (n = 10). Patient demographics were similar between cohorts. The 90-day mortality rate was 2.9 % (2/68) and did not vary between cohorts. On multivariate analysis, having 1-3 ribs resected (OR 19.29, 95 % CI (1.33, 280.72); p = 0.03), 4-6 ribs resected [OR 26.66, (1.48, 481.86); p = 0.03), and a lower DLCO (OR 0.91, (0.84, 0.99); p = 0.02) were associated with postoperative respiratory complications. CONCLUSIONS: In patients undergoing lobectomy with en bloc chest wall resection for non-small cell lung cancer, the number of ribs resected is directly associated with incidence of postoperative respiratory complications.

Minimally Invasive Pneumonectomy vs Open Pneumonectomy: Outcomes and Predictors of Conversion.

BACKGROUND: In the modern era, whether minimally invasive pneumonectomy for non-small cell lung cancer (NSCLC) provides a survival advantage over open pneumonectomy is unknown. METHODS: Patients who underwent pneumonectomy for NSCLC between 2015 and 2020 were queried from the National Cancer Database. Surgical approach was categorized as robot-assisted thoracoscopic surgery (RATS), video-assisted thoracoscopic surgery (VATS), or open pneumonectomy on an intention-to-treat basis. Propensity score matching was performed to balance patient cohorts. Univariate and multivariate regression analyses were used to examine the association between surgical approach and 30- and 90-day mortality, and a Cox proportional hazards model was used to assess overall survival. RESULTS: We identified 3784 patients, including 73% open (n = 2776), 19% VATS (n = 725), and 8% RATS (n = 283). The overall conversion rate from minimally invasive to open was 29.5% (n = 298). After propensity matching 212 patients per cohort, there were no differences between open, VATS, and RATS 30-day (9.4% vs 8.5% vs 7.5%, respectively; P = .807) or 90-day mortality (14.2% vs 12.3% vs 10.4%, respectively; P = .516). Median overall survival was similar among open (48 months; 95% CI, 35.6-64.1 months), VATS (51.0 months; 95% CI, 34.9-72.3 months), and RATS approaches (50 months; 95% CI, 42.6-NA months; P = .560). Multivariate analysis of the matched cohort found no association between approach and overall survival. RATS (odds ratio, 0.67; 95% CI, 0.47-0.94; P = .020) and neoadjuvant chemotherapy (odds ratio, 0.52, 95% CI, 0.27-0.98; P = .045) were found to be protective against conversion to open. CONCLUSIONS: Minimally invasive pneumonectomy can be performed with short-term and long-term survival that are equivalent to open pneumonectomy.

A real-world study evaluating the safety and utility of a two-row stapler reload on pulmonary vasculature.

Background: Endoscopic staplers are common surgical devices used for the ligation and division of vasculature in thoracic procedures. When a stapler ligates and divides pulmonary vasculature, potentially catastrophic intraoperative bleeding at the staple-line may occur. The aim of this study was to confirm the safety and discuss the utility of a two-row stapler reload, by assessing the incidence of clinically necessary intraoperative hemostatic intervention when applied to pulmonary vasculature in real-world applications. Methods: This study was designed as a prospective non-comparative registry study conducted in seven centers across the United States, to confirm the safety and performance of Signia™ Small Diameter Reloads (SDR) when used for indicated thoracic surgical procedures. The primary endpoint was the incidence of hemostatic intervention related to the ligation and division of pulmonary arteries and veins. A five-point Likert scale scored hemostasis of each SDR staple-line. Secondary endpoints included the incidence of device-related only adverse events (AEs), device deficiencies, and procedure-related hospital readmission up to and including 30 days post operation. Results: SDR was fired 302 times across pulmonary vasculature in 120 subjects. Three firings required clinically necessary hemostatic intervention for an intervention rate of 0.99% (3 of 302 firings). Moreover, 97.5% (117 of 120 subjects) had intact SDR staple-lines regardless of surgical access or stapler handle preference. Only 4 (3.3%) thoracoscopic and robotic procedures converted to open, but none were due to SDR staple-lines. There was no statistically significant difference between the Likert score of transected arteries compared to veins (P=0.61). There were no device deficiencies or device-only related AEs reported. Conclusions: In this study, the two-row stapler reloads demonstrated favorable safety and efficacy profiles when fired across hilar vessels in the thoracic space with a 99% hemostatic rate, independent of surgical access and stapler handle preference.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) continues its trajectory of growth and enhancement, solidifying its stature as a premier global thoracic surgical database. The past year witnessed a notable expansion with the inclusion of 10 additional participating sites, now totaling 287, augmenting the database's repository to more than 800,000 procedures. A significant stride was made in refining the data audit process, thereby elevating the accuracy and completeness metrics, a testament to the relentless pursuit of data integrity. The GTSD further broadened its research apparatus, with 15 scholarly publications, a 50% uptick from the preceding year. These publications underscore the database's instrumental role in advancing thoracic surgical knowledge. In a concerted effort to alleviate data entry exigencies, the GTSD Task Force also instituted streamlined data submission protocols, a move lauded by participant sites. This report delineates the recent advancements, volume trajectories, and outcome metrics and encapsulates the prolific research output emanating from the GTSD, reflecting a year of substantial progress and academic fecundity.

2024 Update of The Society of Thoracic Surgeons Short-term Esophagectomy Risk Model: More Inclusive and Improved Calibration.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) previously reported short-term risk models for esophagectomy for esophageal cancer. We sought to update existing models using more inclusive contemporary cohorts, with consideration of additional risk factors based on clinical evidence. METHODS: The study population consisted of adult patients in the STS-GTSD who underwent esophagectomy for esophageal cancer between January 2015 and December 2022. Separate esophagectomy risk models were derived for 3 primary end points: operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used, with predictors retained in models if P < .10. All derived models were validated using 9-fold cross-validation. Model discrimination and calibration were assessed for the overall cohort and specified subgroups. RESULTS: A total of 18,503 patients from 254 centers underwent esophagectomy for esophageal cancer. Operative mortality, morbidity, and composite morbidity or mortality rates were 3.4%, 30.5%, and 30.9%, respectively. Novel predictors of short-term outcomes in the updated models included body surface area and insurance payor type. Overall discrimination was similar or superior to previous STS-GTSD models for operative mortality (C statistic = 0.72) and for composite morbidity or mortality (C statistic = 0.62), Model discrimination was comparable across procedure- and demographic-specific subcohorts. Model calibration was excellent in all patient subgroups. CONCLUSIONS: The newly derived esophagectomy risk models showed similar or superior performance compared with previous models, with broader applicability and clinical face validity. These models provide robust preoperative risk estimation and can be used for shared decision making, assessment of provider performance, and quality improvement.

The STS 2024 Risk Models for Lung Cancer Resection: Continued Refinement and Improved Outcomes.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) has been used to develop risk models for patients undergoing pulmonary resection for cancer. Leveraging a contemporary and more inclusive cohort, we sought to refine these models. METHODS: The study population consisted of adult patients in the STS GTSD who underwent pulmonary resection for cancer between 2015 and 2022. Unlike previous models, non-elective operations were included. Separate risk models were derived for operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used with predictors retained in models if p<0.10. All derived models were validated using 9-fold cross validation. Model discrimination and calibration were assessed for the overall cohort and for surgical procedure, demographic, and risk factor subgroups. RESULTS: Data from 140,927 patients at 337 participating centers were included in the study. Overall operative mortality rate was 1.1%, major morbidity 7.3%, and composite morbidity or mortality 7.6%. Novel predictors of short-term outcomes included interstitial lung disease, DLCO, and payor status. Overall discrimination was superior to previous STS pulmonary resection models for operative mortality [C-statistic = 0.80] and for composite morbidity or mortality [C-statistic = 0.70]. Model discrimination was comparable and model calibration was excellent across all procedure- and demographic-specific sub-cohorts. CONCLUSIONS: Among STS GTSD participants, major morbidity and operative mortality rates remain low following pulmonary resection. The newly derived pulmonary resection risk models demonstrate superior performance compared to previous models, with broader real-life applicability and clinical face validity.