Use of a novel donor lung scoring system as a tool for increasing lung recovery for transplantation.

OBJECTIVE: There is a critical shortage of donor lungs for transplantation. We previously developed a parsimonious, highly discriminatory nine-variable Lung Donor (LUNDON) acceptability score. We assess the utility of this score as a tool to improve lung recovery rates for transplantation. METHODS: We examined all brain-dead donors between 2014-2020 from three US organ procurement organizations and validated the score's predictive performance. We examined the trajectory of donors with low (<40) and high (>60) initial LUNDON scores, their corresponding lung recovery rates, factors contributing to score improvement using multivariable regression models, and one-year post-transplant recipient survival. RESULTS: Overall lung recovery was 32.4% (1410/4351). Validation of the LUNDON score in our cohort revealed a C statistic of 0.904 but required intercept calibration. Low initial LUNDON donors that improved to a high final score had an increase in lung recovery rate from 29.3% (1100/3765) to 86.8% (441/508), associated with lower BMI, management in specialized donor care facilities (SDCF), and more bronchoscopies. Donors with high initial and final LUNDON scores had lung recovery rate of 85.2% (98/115), associated with shorter lengths of stay. One-year survival was similar between recipients of low-to-high versus high-to-high LUNDON score donors (0.89 vs 0.84, p=0.2). CONCLUSIONS: The LUNDON score performs well as a predictor of lung recovery in a contemporary cohort but may require OPO-specific calibration. SDCF use, more bronchoscopies, and expediting time from brain death to organ procurement may improve lung utilization. The LUNDON score can be used to guide donor management to expand the donor pool.

Early-stage lung cancer in the era of lung cancer screening: VA outperforms other insurance models.

BACKGROUND: Lung cancer screening guidelines were introduced in the United States in 2013, with variable implementation. This study aimed to evaluate temporal diagnostic trends in non-small cell lung cancer (NSCLC) diagnosis since the introduction of these guidelines. METHODS: This retrospective cohort analysis used the VA Corporate Data Warehouse and the National Cancer Database. We evaluated temporal trends in the distribution of NSCLC stage at the time of diagnosis, including differences based on insurance coverage type (including uninsured, privately insured, Medicare, Medicaid, and VA coverage) with adjustment for clinically relevant variables. RESULTS: Among 1,450,965 patients diagnosed from 2006-2020, the proportion of NSCLC cases diagnosed at Stage I increased in all insurance groups (by 12.74%, 2%, 0.25%, and 2.57% for the VA, Medicare, Private Insurance, and Medicaid, respectively). If all insurance systems achieved the unadjusted stage distribution seen in the Veterans Health Administration, an additional 45,684 patients would be diagnosed with Stage I NSCLC and 65,933 fewer patients would be diagnosed with stage IV disease. CONCLUSIONS: For patients with any form of insurance, there has been an increase in the proportion of early-stage NSCLC (Stage I and II) and a corresponding decrease in the proportion of Stage III and IV since the introduction of national lung cancer screening guidelines. As the largest integrated "single-payer" healthcare system in the US, the VA dramatically outperforms other insurance types, perhaps attributable to universal coverage and robust lung cancer screening programs.

Erratum: Murine Left Pulmonary Hilar Clamp Model of Lung Ischemia Reperfusion Injury.

This corrects the article 10.3791/66232.

Factors associated with incomplete resection for large, locally invasive non-small cell lung cancer.

Background: Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied. Methods: We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome was to evaluate factors associated with incomplete resection (microscopic: R1, macroscopic: R2). Kaplan-Meier analysis and cox multivariable regression models were used to evaluate overall survival (OS), 90-day mortality, and factors associated with positive margins. Results: Among 2,368 patients identified, the median follow-up was 33.8 months [interquartile range (IQR), 12.6-66.5 months]. Most patients were white (86.9%) with squamous cell histology (47.3%). Major structures were involved in 26.4% of patients and chest wall invasion was seen in 73.6%. Four hundred and seventy-eight patients (20.2%) had an incomplete resection. Multivariable analysis revealed that black race [hazard ratio (HR) 1.568, 95% confidence interval (CI): 1.109-2.218] and major structure involvement (HR 1.412, 95% CI: 1.091-1.827) was associated with increased risk of incomplete resection and surgery at an academic hospitals (HR 0.773, 95% CI: 0.607-0.984), adenocarcinoma histology (HR 0.672, 95% CI: 0.514-0.878), and neoadjuvant chemotherapy (HR 0.431, 95% CI: 0.316-0.587) were associated with decreased risk of incomplete resection. The 5-year OS was 43.7% in the entire cohort and 28.8% in patients with positive margins and 47.5% in patients with an R0 resection. Positive margin was also associated with a significantly higher 90-day mortality rate (9.9% versus 6.7%). Conclusions: For patients with large, node-negative NSCLC invading nearby structures, R0 resection portends better survival. Treatment at academic centers, adenocarcinoma histology, and receipt of neoadjuvant chemotherapy are associated with R0 resection in this high-risk cohort.

Intravital Two-Photon Microscopy of the Transplanted Mouse Lung.

Complications after lung transplantation are largely related to the host immune system responding to the graft. Such immune responses are regulated by crosstalk between donor and recipient cells. A better understanding of these processes relies on the use of preclinical animal models and is aided by an ability to study intra-graft immune cell trafficking in real-time. Intravital two-photon microscopy can be used to image tissues and organs for depths up to several hundred microns with minimal photodamage, which affords a great advantage over single-photon confocal microscopy. Selective use of transgenic mice with promoter-specific fluorescent protein expression and/or adoptive transfer of fluorescent dye-labeled cells during intravital two-photon microscopy allows for the dynamic study of single cells within their physiologic environment. Our group has developed a technique to stabilize mouse lungs, which has enabled us to image cellular dynamics in naïve lungs and orthotopically transplanted pulmonary grafts. This technique allows for detailed assessment of cellular behavior within the vasculature and in the interstitium, as well as for examination of interactions between various cell populations. This procedure can be readily learned and adapted to study immune mechanisms that regulate inflammatory and tolerogenic responses after lung transplantation. It can also be expanded to the study of other pathogenic pulmonary conditions.

Murine Left Pulmonary Hilar Clamp Model of Lung Ischemia Reperfusion Injury.

Ischemia reperfusion injury (IRI) during lung transplantation is a major risk factor for post-transplant complications, including primary graft dysfunction, acute and chronic rejection, and mortality. Efforts to study the underpinnings of IRI led to the development of a reliable and reproducible mouse model of left lung hilar clamping. This model involves a surgical procedure performed in an anesthetized and intubated mouse. A left thoracotomy is performed, followed by careful lung mobilization and dissection of the left pulmonary hilum. The hilar clamp involves reversible suture ligation of the pulmonary hilum with a slipknot, which stops the arterial inflow, venous outflow, and airflow through the left mainstem bronchus. Reperfusion is initiated by careful removal of the suture. Our laboratory uses 30 min of ischemia and 1 h of reperfusion for the experimental model in the current investigations. However, these time periods can be modified depending on the specific experimental question. Immediately prior to sacrifice, arterial blood gas can be obtained from the left ventricle after a 4 min period of right hilar clamping to ensure that the PaO2 values obtained are attributed to the injured left lung alone. We also describe a method to measure cell extravasation with flow cytometry, which involves intravenous injection of a fluorochrome-labeled antibody specific for the cell(s) to be studied prior to sacrifice. The left lung can then be harvested for flow cytometry, frozen or fixed, paraffin-embedded immunohistochemistry, and quantitative polymerase chain reaction. This hilar clamp technique allows for detailed study of the cellular and molecular mechanisms underlying IRI. Representative results reveal decreased left lung oxygenation and histologic evidence of lung injury following hilar clamping. This technique can be readily learned and reproduced by personnel with and without microsurgical experience, leading to reliable and consistent results and serving as a widely adoptable model for studying lung IRI.

Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

B cells mediate lung ischemia/reperfusion injury by recruiting classical monocytes via synergistic B cell receptor/TLR4 signaling.

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.

Lobe-specific lymph node sampling is associated with lower risk of cancer recurrence.

Objective: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients. Methods: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data from operative and pathology reports for patients with clinical stage I NSCLC (2006-2016). For simplicity in comparison, we included patients who had right upper lobe (RUL) or left upper lobe (LUL) tumors. Based on modified European Society of Thoracic Surgeons guidelines, lobe-specific sampling was defined for RUL tumors (stations 2, 4, 7, and 10 or 11) and LUL tumors (stations 5 or 6, 7, and 10 or 11). Our primary outcome was the risk of cancer recurrence, as assessed by Fine and Gray competing risks modeling. Secondary outcomes included overall survival (OS) and pathologic upstaging. Analyses were adjusted for relevant patient, disease, and treatment variables. Results: Our study included 3534 patients with RUL tumors and 2667 patients with LUL tumors. Of these, 277 patients (7.8%) with RUL tumors and 621 patients (23.2%) with LUL tumors met lobe-specific assessment criteria. Comparatively, 34.7% of patients met the criteria for count-based assessment, and 25.8% met the criteria for station-based sampling (ie, any 3 N2 stations and 1 N1 station). Adherence to lobe-specific assessment was associated with lower cumulative incidence of recurrence (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.70-0.98) and a higher likelihood of pathologic upstaging (aHR, 1.49; 95% CI, 1.20-1.86). Lobe-specific assessment was not associated with OS. Conclusions: Adherence to intraoperative LN sampling guidelines is low. Lobe-specific assessment is associated with superior outcomes in early-stage NSCLC. Quality metrics that assess adherence to intraoperative LN sampling, such as the CoC Operative Standards manual, also should consider lobe-specific criteria.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.

Smoking exposure-induced bronchus-associated lymphoid tissue in donor lungs does not prevent tolerance induction after transplantation.

The presence of bronchus-associated lymphoid tissue (BALT) in donor lungs has been suggested to accelerate graft rejection after lung transplantation. Although chronic smoke exposure can induce BALT formation, the impact of donor cigarette use on alloimmune responses after lung transplantation is not well understood. Here, we show that smoking-induced BALT in mouse donor lungs contains Foxp3+ T cells and undergoes dynamic restructuring after transplantation, including recruitment of recipient-derived leukocytes to areas of pre-existing lymphoid follicles and replacement of graft-resident donor cells. Our findings from mouse and human lung transplant data support the notion that a donor's smoking history does not predispose to acute cellular rejection or prevent the establishment of allograft acceptance with comparable outcomes to nonsmoking donors. Thus, our work indicates that BALT in donor lungs is plastic in nature and may have important implications for modulating proinflammatory or tolerogenic immune responses following transplantation.

Utilizing computed tomography volumetry for size matching prior to lung transplantation: a case series.

Background: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value. Case Description: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly overestimated both donor and recipient lung volumes quantified by CT volumetric analysis. All recipients underwent successful LT without necessary graft downsizing. Conclusions: This is an initial report of prospectively utilizing CT volumetry as an adjunct to decision-making regarding suitability of donor lungs. In these cases, CT volumetry facilitated the confident acceptance of donor lungs that were initially predicted to be oversized based on other clinical measures.

Characteristics of donor lungs declined on site and impact of lung allocation policy change.

OBJECTIVE: National and institutional data suggest an increase in organ discard rate (donor lungs procured but not implanted) after a new lung allocation policy was introduced in 2017. However, this measure does not include on-site decline rate (donor lungs declined intraoperatively). The objective of this study is to examine the impact of the allocation policy change on on-site decline. METHODS: We used a Washington University (WU) and our local organ procurement organization (Mid-America Transplant [MTS]) database to abstract data on all accepted lung offers from 2014 to 2021. An on-site decline was defined as an event in which the procuring team declined the organs intraoperatively, and the lungs were not procured. Logistic regression models were used to investigate potentially modifiable reasons for decline. RESULTS: The overall study cohort comprised 876 accepted lung offers, of which 471 donors were at MTS with WU or others as the accepting center and 405 at other organ procurement organizations with WU as the accepting center. At MTS, the on-site decline rate increased from 4.6% to 10.8% (P = .01) after the policy change. Given the greater likelihood of non-local organ placement and longer travel distance after policy change, the estimated cost of each on-site decline increased from $5727 to $9700. In the overall group, latest partial pressure of oxygen (odds ratio [OR], 0.993; 95% confidence interval [CI], 0.989-0.997), chest trauma (OR, 2.474; CI, 1.018-6.010), chest radiograph abnormality (OR, 2.902; CI, 1.289-6.532), and bronchoscopy abnormality (OR, 3.654; CI, 1.813-7.365) were associated with on-site decline, although lung allocation policy era was unassociated (P = .22). CONCLUSIONS: We found that nearly 8% of accepted lungs are declined on site. Several donor factors were associated with on-site decline, although lung allocation policy change did not have a consistent impact on on-site decline.

Development and validation of the lung donor (LUNDON) acceptability score for pulmonary transplantation.

There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.

Pulmonary Carcinoid Tumorlet in the Explanted Lungs for Lung Transplantation: A Case Series of 15 Patients.

BACKGROUND: Pulmonary carcinoid tumorlet (PCT) is defined as small proliferation of neuroendocrine cells that invade the adjacent basement membrane. It is often associated with chronic pulmonary inflammatory processes. However, the characteristics of PCT in end-stage lung diseases remain unclear. METHODS: We conducted a retrospective cohort study of the explanted lungs after transplantation at our institution between January 1999 and October 2020. Patients who underwent re-transplantation were excluded. RESULTS: Pulmonary carcinoid tumorlet was incidentally discovered in the explanted lungs from 15 patients (1.1%) out of 1367 lung transplants performed during the study period. Nine patients (60.0 %) were women, with a median age of 59 years (IQR: 57-62) at transplant. Underlying pulmonary indications for lung transplantation were chronic obstructive pulmonary disease (9/15, 60.0%), interstitial lung disease (2/15, 13.0%), pulmonary vascular disease (2/15, 13.0%), alpha-1 antitrypsin deficiency (1/15, 7.0%), and bronchiectasis (1/15, 7.0%). Of the patients who underwent bilateral lung transplantation (13/15, 86.7%), PCT was found in the right lung in 10 patients (10/13, 76.9%). Thirteen patients had one lesion, 1 patient had 2 lesions and 1 patient had multiple lesions. CONCLUSION: Our study shows that PCT is generally uncommon, but when it occurs, it occurs more frequently on the right side and in female patients with end-stage pulmonary disease. Chronic obstructive pulmonary disease may be a predisposing factor for developing PCT.

Outcomes of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first 30 days after lung transplantation and is also associated with worse long-term outcomes. Outcomes of patients with PGD grade 3 requiring extracorporeal membrane oxygenation (ECMO) support after lung transplantation have yet to be well described. We sought to describe short- and long-term outcomes for patients with PGD grade 3 who required ECMO support. METHODS: This is a single-center retrospective cohort study of patients undergoing lung transplantation. We stratified patients with PGD grade 3 into non-ECMO, venoarterial (VA) ECMO, and venovenous (VV) ECMO groups after transplantation. We then compared the outcomes between the groups. RESULTS: Of 773 lung transplant recipients, PGD grade 3 developed in 204 (26%) at any time in the first 72 hours after lung transplantation. Of these, 13 (5%) required VA ECMO and 25 (10%) required VV ECMO support. The 30-day, 1-year, and 5-year survival in the VA ECMO group was 62%, 54%, and 43% compared with 96%, 84%, and 65% in the VV ECMO group and 99%, 94%, and 71% in the non-ECMO group. Multivariable Cox regression analysis showed that VA ECMO was associated with increased mortality (hazard ratio, 2.37; 95% CI, 1.06-5.28; P = .04). CONCLUSIONS: Patients who required VA ECMO support for PGD grade 3 have significantly worse survival compared with those who did not require ECMO and those who required VV ECMO support. This suggests that VA ECMO treatment of patients with PGD grade 3 after lung transplantation can be a predictable risk factor for mortality.

Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non-Small Cell Lung Cancer.

Importance: Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. Objective: To develop a practical surgical quality score for patients diagnosed with clinical stage I NSCLC who received definitive surgical treatment. Design, Setting, and Participants: This retrospective cohort study used a uniquely compiled data set of US veterans diagnosed with clinical stage I NSCLC who received definitive surgical treatment from October 2006 through September 2016. The data were analyzed from April 1 to September 1, 2022. Based on contemporary treatment guidelines, 5 surgical QMs were defined: timely surgery, minimally invasive approach, anatomic resection, adequate lymph node sampling, and negative surgical margin. The study developed a surgical quality score reflecting the association between these QMs and overall survival (OS), which was further validated in a cohort of patients using data from the National Cancer Database (NCDB). The study also examined the association between the surgical quality score and recurrence-free survival (RFS). Exposures: Surgical treatment of early-stage NSCLC. Main Outcomes and Measures: Overall survival and RFS. Results: The study included 9628 veterans who underwent surgical treatment between 2006 and 2016. The cohort consisted of 1446 patients who had a mean (SD) age of 67.6 (7.9) years and included 9278 males (96.4%) and 350 females (3.6%). Among the cohort, 5627 individuals (58.4%) identified as being smokers at the time of surgical treatment. The QMs were met as follows: timely surgery (6633 [68.9%]), minimally invasive approach (3986 [41.4%]), lobectomy (6843 [71.1%]) or segmentectomy (532 [5.5%]), adequate lymph node sampling (3278 [34.0%]), and negative surgical margin (9312 [96.7%]). The median (IQR) follow-up time was 6.2 (2.5-11.4) years. An integer-based score (termed the Veterans Affairs Lung Cancer Operative quality [VALCAN-O] score) from 0 (no QMs met) to 13 (all QMs met) was constructed, with higher scores reflecting progressively better risk-adjusted OS. The median (IQR) OS differed substantially between the score categories (score of 0-5 points, 2.6 [1.0-5.7] years of OS; 6-8 points, 4.3 [1.7-8.6] years; 9-11 points, 6.3 [2.6-11.4] years; and 12-13 points, 7.0 [3.0-12.5] years; P < .001). In addition, risk-adjusted RFS improved in a stepwise manner between the score categories (6-8 vs 0-5 points, multivariable-adjusted hazard ratio [aHR], 0.62; 95% CI, 0.48-0.79; P < .001; 12-13 vs 0-5 points, aHR, 0.39; 95% CI, 0.31-0.49; P < .001). In the validation cohort, which included 107 674 nonveteran patients, the score remained associated with OS. Conclusions and Relevance: The findings of this study suggest that adherence to intraoperative QMs may be associated with improved OS and RFS. Efforts to improve adherence to surgical QMs may improve patient outcomes following curative-intent resection of early-stage lung cancer.

Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer.

OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.

Comparison Between Veteran and Non-Veteran Populations With Clinical Stage I Non-small Cell Lung Cancer Undergoing Surgery.

OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.