Undergoing Lung Cancer Resection Research Articles

Comparison of a Risk Calculator With Frailty Indices in Patients Undergoing Lung Cancer Resection.

While frailty has gained attention for its utility in risk stratification, no studies have directly compared them to existing risk calculators. The objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other than home. Patients undergoing anatomic lung resection for primary, nonsmall cell lung cancer were identified within the ACS National Quality Improvement Program (ACS NSQIP) database. Tools were compared for discrimination in the primary outcomes. 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (IQR 59-74) years. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% CI). This included perioperative mortality (AUC 0.74, 95% CI 0.71-0.78), compared to RAI-rev (AUC 0.66, 95% CI 0.62-0.69) and 5-mFI (AUC 0.61, 95% CI 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes. ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection.

Comparison of a risk calculator with frailty indices in patients undergoing lung cancer resection.

Perioperative risk stratification is an essential component of preoperative planning for cancer surgery. While frailty has gained attention for its utility in risk stratification, no studies have directly compared it to existing risk calculators. Therefore, the objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other-than-home. Patients undergoing anatomic lung resection for primary, non-small cell lung cancer were identified within the American College of Surgeons National Quality Improvement Program (ACS NSQIP) database. The ACS-SRC, RAI-rev, and 5-mFI tools were used to predict adverse postoperative events. Tools were compared for discrimination in the primary outcomes. 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (interquartile range = 59-74) years. Cardiothoracic surgeons performed 89% and general surgeons performed 11.0% of the operations. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% confidence interval [CI]). This included perioperative mortality (AUC = 0.74, 95% CI = 0.71-0.78), compared to RAI-rev (AUC = 0.66, 95% CI = 0.62-0.69) and 5-mFI (AUC = 0.61, 95% CI = 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes. ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection.

The Impact of COVID-19 Infection Prior to Lung Resection on Postoperative Complications

BackgroundWe hypothesize that previous COVID-19 infection could be associated with postoperative complications (POCs) and outcomes of thoracic surgery for lung cancer. It is unknown whether the respiratory damage caused by COVID-19 infection is permanent. In addition, there is a lack of studies investigating POCs and prior COVID-19 infection in thoracic surgery. MethodsA retrospective study was performed on patients who underwent resections for lung cancer between May 2020 and July 2022. Variables relevant to the Society of Thoracic Surgeons database were collected, as well as COVID-19 status. The primary outcome was postoperative complications. ResultsA total of 361 patients underwent a resection for lung cancer. Patients with a prior COVID-19 infection (n = 21) had significantly more POCs than patients without a history of COVID-19 infection (n = 340, P < .05). Pneumothorax and infections requiring intravenous antibiotics were significantly enriched in patients with a prior COVID-19 infection. COVID-19 infection was independently associated with increased POCs at multivariable analysis (adjust odds ratio, 4.36; 95% CI, 1.48-12.8). Matched case-control analysis also reviewed similar findings, where COVID-19 infection was the only significant variable as a risk factor for POCs (P < .05). ConclusionsAfter a COVID-19 infection, patients undergoing lung cancer resections were at an increased risk of POCs. This suggests that a previous COVID-19 infection should be considered as a potential risk factor for complications after lung cancer resections.

Risk factors for enhanced recovery after surgery failure in patients undergoing lung cancer resection with concomitant cardiovascular disease: A single-center retrospective study

ObjectiveEnhanced recovery after surgery (ERAS) has been widely used in patients with lung cancer, and its effectiveness has been confirmed; however, some lung cancers with poor clinical outcomes lead to ERAS failure after radical resection. This study aimed to analyze risk factors associated with ERAS failure after radical resection in patients with lung cancer and concomitant cardiovascular disease. MethodsIn total, 198 patients who underwent ERAS following radical lung cancer surgery for concomitant cardiovascular disease between January 2022 and September 2023 were enrolled in this retrospective study. The patients were categorized into two groups based on the definition of ERAS failure: ERAS success group (n = 152) and ERAS failure group (n = 46). Univariate and multivariate analyses were performed to investigate the risk factors of ERAS failure. ResultsUnivariate analysis showed that gender, tumor location, operation time, estimated blood loss (EBL), suction drainage, and total cholesterol were associated with ERAS failure. Multivariate analysis showed that operation time (odds ratio [OR] = 1.015; P = 0.011) and suction drainage (OR = 3.343; P = 0.008) were independent risk factors for ERAS failure. ConclusionsOperation time and suction drainage were independent risk factors for ERAS failure after radical resection of combined cardiovascular lung cancer. Therefore, improving surgical efficiency and postoperative chest drain management are important for successful ERAS.

Assessing quality of care in early stage resected stage non-small cell lung cancer (NSCLC): An evaluation of epidermal growth factor receptor (EGFR) testing and adjuvant (adj) therapy (tx).

8072 Background: In December 2020, the FDA approved the use of osimertinib in the treatment of stage IB-IIIA (ES) NSCLC patients (pts) with EGFR exon 19 deletions and exon 21 L858R mutations (EGRFm) following tumor resection. Using real-world data, we sought to understand EGFR testing rates among ES pts and whether pts received osimertinib in the adjuvant setting based on EGFRm. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care. From this database, we identified Stage IB – IIIA pts evaluated via medical chart curation who underwent lung cancer resection (R) between 12/1/2021 to 7/31/2023 (N = 803). We assessed adj treatment by stage, EGFR testing rates overall and by stage, EGFR testing rates by adjuvant treatment and non-adj treatment pts, timing of EGFR testing, and treatment rates with an EGFR TKI among EGFRm pts. Descriptive analyses were used and proportions were compared using a chi-squared test. Results: The mean age of the 803 ES R pts in the sample was 69 (SD = 8.3), 53.3% of the pts were female, , and 12% never smoked. We found adj treatment rates among ES R pts to be 56%; these were highest among stage IIIA (N = 245) pts at 70.2%, compared to stage IIB (N = 241) at 68.8%, stage IIA (N = 69) at 53.6% and stage IB (N = 240) at 31.7% (p &lt; 0.001). Among ES R pts, 70% (N = 563) were tested for EGFR; this rate was 78% (N = 455) among ES pts who were R and received adj treatment, compared to 59% (N = 348) among ES R pts who did not receive adj treatment (p &lt; 0.001). EGFR testing rates were highest among stage IIB pts at 76%, compared to stage IIIA pts at 73%, stage IIA pts at 72%, and stage IB pts at 60% (p &lt; .001). Among ES pts who were R and tested for EGFR (N = 563), 14% were tested before surgery, 38% were tested after surgery but before adj treatment, and 48% were tested after initiating adjuvant therapy. EGFRm was found in 10.4% of EGFR tested pts. Among EGFRm ES R pts (N = 59), 54% were treated with an EGFR TKI. EGFRm ES R pts treated with an adj EGFR TKI were highest among stage IIB pts (N = 14) at 93%, compared to stage IIA pts (N = 5) at 60%, stage IB pts (N = 20) at 45%, and stage IIIA pts (N = 20) at 35% (p &lt; 0.01). However, only 69% (N = 41) of EGFRm ES R pts received adj treatment (either chemotherapy or EGFR TKI) and among those pts, 78% (N = 32) received an EGFR TKI. Conclusions: Based on our findings using real-world data for EGFR testing and adjuvant osimertinib use, and in light of the published results from the ADAURA trial which showed disease free survival benefit (HR 0.2) and overall survival benefit (HR 0.49) of adjuvant osimertinib in ES NSCLC, we have identified an opportunity to improve patient outcomes following resection of ES NSCLC by increasing EGFR testing and encouraging treatment with EGFR TKI in exon 19 deletion or exon 21 L858R mutated pts.

Association Between Utilization of Services and Perioperative Outcomes for Lung Cancer Resection

IntroductionLung cancer resection has largely focused on perioperative outcomes (eg, mortality) to benchmark performance. While variations in perioperative outcomes and in utilization of services (eg, ambulatory procedures, hospitalization) have been independently demonstrated, there has been limited evaluation of associations between these outcomes. We evaluated the association between perioperative outcomes and utilization of services to evaluate provider performance across a broader context of care. Patients and MethodsThis was a retrospective cohort study of patients undergoing lung cancer resection in 2017 to 2019. We utilized hierarchical logistic regression models to determine risk- and reliability-adjusted mortality and risk-adjusted utilization of services, at the hospital-level. We then evaluated utilization of services across quartiles of perioperative mortality. ResultsA total of 15,168 patients across 297 hospitals underwent lung cancer resection. Mean risk- and reliability-adjusted 90-day mortality varied between 1.58% (95% CI, 1.54%-1.62%) and 2.74% (95% CI, 2.59%-2.90%) across quartiles. Risk-adjusted utilization of all ambulatory procedures was highest in the best performing (lowest mortality) quartile at 37.7% (95% CI, 33.6%-41.8%). Additionally, risk-adjusted inpatient utilization prior to and after surgery was lowest in the best performing quartile at 15% (95% CI, 13.7%-16.3%) and 19.3% (95% CI, 17.5%-21.0%), respectively. ConclusionsHospitals with the lowest perioperative mortality demonstrated trends towards using more outpatient resources prior to surgery, but fewer inpatient services surrounding lung cancer resection. This correlation highlights the importance of incorporating utilization of services in addition to other metrics to profile the efficiency and effectiveness of centers performing lung cancer resection across a broader spectrum of care.

Geographic Variation in the Utilization of Services Surrounding Lung Cancer Resection

BackgroundAs value-based care models continue to gain emphasis, along with the need for improved profiling across the continuum of lung cancer care, a better understanding of geographic variation in utilization of services surrounding episodes of care is needed. MethodsIn this retrospective cohort study of patients undergoing lung cancer resection from 2017 to 2019, we examined geographic variation in utilization of services surrounding episodes of lung cancer resection. We utilized hierarchical logistic regression models to determine risk-adjusted utilization of services. This study utilized inpatient and ambulatory databases across 4 states: New Jersey, Pennsylvania, Florida, and Maryland. All patients undergoing lung cancer resection were included. The primary outcome was risk-adjusted utilization of services. ResultsMean risk-adjusted utilization of ambulatory procedures across all hospital referral regions (HRRs) was 34.1% (95% CI 30.7%-37.6%), while the individual HRR utilization varied from 10.9% to 54.9% (P < .01). Mean risk-adjusted utilization of inpatient admissions in the 6 months prior to surgery was 15.3% (95% CI 13.9%-16.7%), ranging from 7.4% to 24.7% (P = .07) across HRRs. Finally, mean risk-adjusted utilization of inpatient hospitalizations in the 6 months following surgery was 19.4% (95% CI 17.7-21.0%), ranging from 10.0% to 33.6% (P = .19) across HRRs. ConclusionsOverall, we observed that utilization of ambulatory services varied significantly across HRRs, while inpatient utilization did not demonstrate significant variation. Given these findings, there may be geographic drivers of variation in the utilization of services surrounding lung cancer resection.

Evaluation of preoperative cardiopulmonary reserve and surgical risk of patients undergoing lung cancer resection.

Lung cancer represents the second most frequent neoplasm and the leading cause of neoplastic death among both women and men, causing almost 25% of all cancer deaths. Patients undergoing lung resection-both for primary and secondary tumors-require careful preoperative cardiopulmonary functional evaluation to confirm the safety of the planned resection, to assess the maximum tolerable volume of resection or to exclude surgery, thus shifting the therapeutic approach toward less invasive options. Cardiopulmonary reserve, pulmonary lung function and mechanical respiratory function represent the cornerstones of preoperative assessment of patients undergoing major lung resection. Spirometry with carbon monoxide diffusing capacity, split function tests, exercise tests and cardiologic evaluation are the gold standard instruments to safely assess the entire cardiorespiratory function before pulmonary resection. Although pulmonary mechanical and parenchymal function, together with cardiorespiratory compliance represent the mainstay of preoperative evaluation in thoracic surgery, the variables that are responsible for fitness in patients who have undergone lung resection have expanded and are being continually investigated. Nevertheless, because of the shift to older patients who undergo lung resection, a global approach is required, taking into consideration variables like frailty status and likelihood of postoperative functional deterioration. Finally, the decision to go ahead with surgery in fragile patients being consideredfor lung resection should be evaluated in a multispecialty preoperative discussion to provide a personalized risk stratification. The aim of this review is to focus on preoperative evaluation of cardiopulmonary reserve and surgical risk stratification of patients candidate for lung cancer resection. It does so by a literature search of clinical guidelines, expert consensus statements, meta-analyses, clinical recommendations, book chapters and randomized trials (1980-2022).

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

Clinical Implications of Removing Race-Corrected Pulmonary Function Tests for African American Patients Requiring Surgery for Lung Cancer

Removal of race correction in pulmonary function tests (PFTs) is a priority, given that race correction inappropriately conflates race, a social construct, with biological differences and falsely assumes worse lung function in African American than White individuals. However, the impact of decorrecting PFTs for African American patients with lung cancer is unknown. To identify how many hospitals providing lung cancer surgery use race correction, examine the association of race correction with predicted lung function, and test the effect of decorrection on surgeons' treatment recommendations. In this quality improvement study, hospitals participating in a statewide quality collaborative were contacted to determine use of race correction in PFTs. For hospitals performing race correction, percent predicted preoperative and postoperative forced expiratory volume in 1 second (FEV1) was calculated for African American patients who underwent lung cancer resection between January 1, 2015, and September 31, 2022, using race-corrected and race-neutral equations. US cardiothoracic surgeons were then randomized to receive 1 clinical vignette that differed by the use of Global Lung Function Initiative equations for (1) African American patients (percent predicted postoperative FEV1, 49%), (2) other race or multiracial patients (percent predicted postoperative FEV1, 45%), and (3) race-neutral patients (percent predicted postoperative FEV1, 42%). Number of hospitals using race correction in PFTs, change in preoperative and postoperative FEV1 estimates based on race-neutral or race-corrected equations, and surgeon treatment recommendations for clinical vignettes. A total of 515 African American patients (308 [59.8%] female; mean [SD] age, 66.2 [9.4] years) were included in the study. Fifteen of the 16 hospitals (93.8%) performing lung cancer resection for African American patients during the study period reported using race correction, which corresponds to 473 African American patients (91.8%) having race-corrected PFTs. Among these patients, the percent predicted preoperative FEV1 and postoperative FEV1 would have decreased by 9.2% (95% CI, -9.0% to -9.5%; P < .001) and 7.6% (95% CI, -7.3% to -7.9%; P < .001), respectively, if race-neutral equations had been used. A total of 225 surgeons (194 male [87.8%]; mean [SD] time in practice, 19.4 [11.3] years) were successfully randomized and completed the vignette items regarding risk perception and treatment outcomes (76% completion rate). Surgeons randomized to the vignette with African American race-corrected PFTs were more likely to recommend lobectomy (79.2%; 95% CI, 69.8%-88.5%) compared with surgeons randomized to the other race or multiracial-corrected (61.7%; 95% CI, 51.1%-72.3%; P = .02) or race-neutral PFTs (52.8%; 95% CI, 41.2%-64.3%; P = .001). Given the findings of this quality improvement study, surgeons should be aware of changes in PFT testing because removal of race correction PFTs may change surgeons' treatment decisions and potentially worsen existing disparities in receipt of lung cancer surgery among African American patients.

Comparison of failure to rescue in younger versus elderly patients following lung cancer resection

ObjectiveFailure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients. MethodsPatients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80 years) cohort. ResultsOf the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n = 139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n = 39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P < .001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P = .01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P = .028). ConclusionsFTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

Surgical Apgar Score can help predict postoperative cardiopulmonary complication and reoperation in lung cancer resection

BackgroundBleeding due to lung resection increases the risk of cardiopulmonary complications and hospital stay. Surgical massive bleeding is associated with a high rate of mortality. In this study, our aim is to determine the effectiveness of Surgical Apgar Score in predicting complications and reoperation in the short term. Peroperative data of 405 patients aged 18–82 who underwent lung resection (pneumonectomy, lobectomy, wedge) and were operated consecutively were recorded.ResultsPulmonary complication developed in 38 (9.4%) of the patients, cardiac complication in 104 (25.7%), acute kidney failure in 8 (1.9%), and cerebrovascular accident in 1 (0.2%). Reoperation was performed in 24 (5.9%) patients due to bleeding. The Surgical Apgar Score was found to predict postoperative complications well for a value of < 6 (area under the curve = 0.745, 95%CI 0.710–0.7770, p < 0.001). When Surgical Apgar Score were evaluated together with receiver operating characteristic, the ability of Surgical Apgar Score to predict reoperation was found to be statistically significant (area under the curve = 0.777, 95%CI 0.671–0.883, p < 0.001. Accordingly, age, resection type, blood loss, heart rate, SAS score, intraoperative blood transfusion, and postoperative blood transfusion were independent risk factors affecting the development of complications. It was determined that the only independent risk factor affecting the development of mortality was postoperative blood transfusion. It was determined that the independent risk factors affecting ICU development were resection type, blood loss, SAS score, and postoperative blood transfusion.ConclusionIn our study, the Surgical Apgar Scoring System was found to be sufficient in predicting cardiac and respiratory complications. Patients with a low postoperative Surgical Apgar Score should be followed carefully in terms of postoperative complications and reoperation. Surgical Apgar Score can be a useful scoring method in predicting the prognosis of patients who underwent lung cancer resection in the postoperative period.

Risk stratification of postoperative pulmonary complications in elderly patients undergoing lung cancer resection: a propensity score-matched study.

In China, lung cancer mainly affects the elderly population. Surgery remains the standard treatment for lung cancer in elderly patients, however, postoperative pulmonary complications (PPCs) are major contributors to morbidity and mortality following lung resection. This study aimed to identify perioperative predictors of PPCs among elderly patients undergoing pulmonary resection for lung cancer to provide evidence for better prevention and intervention for PPCs. A retrospective study was conducted with 456 patients (age >65 years) undergoing pulmonary resection for lung cancer in Yunnan, China from January 2016 to March 2019. Propensity score matching (PSM) was performed to compare preoperative data and clinical characteristics between the PPC and non-PPC groups, followed by binary logistic regression to evaluate predictors of PPCs. Pulmonary complications occurred in 142/456 (31.1%) patients age >65 years, with pneumonia being the most common event (21.7%). Both PSM and binary logistic regression analysis identified American Society of Anesthesiologists (ASA) class <II [odds ratio (OR): 0.177, 95% confidence interval (CI): 0.037-0.854] and video-assisted thoracoscopic surgery (VATS) (OR: 0.576, 95% CI: 0.334-0.992) as protective factors for PPCs. PPCs following lung cancer resection in elderly patients were associated with a higher ASA classification and open thoracotomy. An adequate and comprehensive evaluation of the operative strategies and enhanced recovery methods should be implemented among elderly patients undergoing lung resection with an ASA class > II or those undergoing an open thoracotomy to help prevent the occurrence of PPCs.

Large retrospective validation study of metabolomic biomarkers for resectable lung cancer detection and risk assessment.

3071 Background: Cancer can be regarded as a metabolic disease and many studies published aimed at identifying robust metabolites for lung cancer diagnosis using plasma samples. Regardless of the lung cancer staging, most of these studies were performed on relatively small sample sizes. The purpose of this study is to validate whether a panel of metabolomic biomarkers would improve risk assessment for lung cancer detection in 800 plasma samples from patients that underwent lung cancer resection, and to understand the potential role and intersection between lung cancer and other lung diseases. Methods: A blinded case-control study was performed using plasma samples from 586 patients with biopsy-confirmed lung cancer compared to 214 controls from the same institutional biorepository to evaluate the performance of a 5+ metabolites biomarker panel for lung cancer detection. The control group consists of 90 healthy individuals and 124 with other non-neoplastic lung diseases including asthma, COPD, bronchiectasis and COVID. The lung cancer subgroups include early-stage (Stage I &amp;II) adenocarcinoma and squamous cells carcinoma, advanced stages (Stage III &amp; IV) NSCLC and neuroendocrine tumors. In this study, plasma metabolic profiles were performed using different liquid chromatography methods coupled with a targeted and quantitative mass spectrometry approach. Metabolite concentrations, clinical data, and smoking history were used to develop logistic regression models to identify lung cancer at different stages using significant biomarkers. The area under the receiver operator characteristic curves (AUC), sensitivities and specificities at selected cut off points were calculated for each cancer stage. Results: Univariate and multivariate statistical analyses confirmed the performance of our 5+ metabolites panel (β-HBA, PC aa C38:0, PC ae C40:6, citric acid, tryptophan, and etc.) as being significantly different between controls and lung cancer cases. Linear regression model using metabolites alone yielded an AUC of 0.89 for lung cancer at all stages. When adding smoking status, the models achieved an AUC of 0.91 with sensitivity of 91% and specificity over 78% using a risk prediction threshold of 0.657. Conclusions: The blood-based metabolites panel validated on our current retrospective study exhibited robust performance for resectable lung cancer detection and risk assessment. This metabolomic panel assay demonstrates potential diagnostic applications and clinical utility for patient selection that require further follow-up and confirmation using LDCT or other lung imaging modalities. The inclusion of other lung diseases in the control group is more representative of a real clinical setting suggesting that this blood-based assay could be offered to the medical community. Further studies may also confirm its utility in the context of a lung cancer screening program.

Financial Toxicity in Patients With Resected Lung Cancer.

To describe financial toxicity (FT) in patients with resected lung cancer and identify risk factors in this population. FT describes the financial burden associated with cancer care and its impact on the quality of survivorship. Few prior studies have examined FT in patients with lung cancer. Patients who underwent lung cancer resection at our institution between January 1, 2016 and December 31, 2021, were surveyed to gather demographic information and evaluate FT using a validated questionnaire. A multivariable model was built to identify risk factors for FT. Of the total, 1477 patients were contacted, of whom 463 responded (31.3%). Most patients were stage I (n = 349, 75.4%) and lobectomy was performed often (n = 290, 62.8%). There were 196 patients (42.3%) who experienced FT. Upon multivariable analyses, divorced marital status [odds ratio (OR) = 3.658, 95% CI: 1.180-11.337], household income <$40,000 (OR = 2.544, 95% CI: 1.003-6.455), credit score below 739 (OR = 2.744, 95% CI: 1.326-5.679), clinical stage >I (OR = 2.053, 95% CI: 1.088-3.877), and change in work hours or work cessation (all P < 0.05) were associated with FT. Coping mechanisms, such as decreased spending on food or clothing and increased use of savings or borrowing money, were more likely to be reported by patients experiencing FT than those who did not ( P < 0.001). Patients undergoing lung cancer resection often experienced significant financial stress with several identifiable risk factors. FT should be considered early in the care of these patients to alleviate detrimental coping mechanisms and enhance their quality of survivorship.

Abstract 4651: Comparison of the tumor and lymph node immune microenvironment in early non-small cell lung cancer through multimodal single cell sequencing

Abstract Background/Purpose: Previous studies have analyzed the tumor and local immune microenvironments in lung cancers and suggest immune modulation is associated with worse clinical outcome. However, the tumor-immune microenvironment in early stage lung tumors and lymph nodes (LNs) have not been fully described. We aim to compare cell states in the immune microenvironments between lung tumors and LNs through multi-modal profiling of the transcriptome and surface proteins. Methods: Needle biopsy samples were taken from 10 treatment-naive early stage lung cancer patients undergoing lung cancer resections. Tissues were obtained from normal lung, lung tumor, and multiple mediastinal LNs, and processed for scRNA-seq including labeling with Total-Seq C CITE-seq panel to quantify the levels of 130 cell surface proteins. In total, 76,721 cells (4,462 normal lung; 39,019 tumor; 33,240 LN) were identified with a median of 1,673 genes and 92 protein features detected per cell. Protein expression was decontaminated through the decontX algorithm. Weighted-Nearest Neighbor analysis from the Seurat R package was applied to integrate the CITE-seq and RNA-seq level data for clustering cells into subpopulations. Results: Six broad cell populations were identified including T/NK, myeloid (CD14+), B (CD19+), mast (TPSAB1+), pDC (IRF8+), and epithelial (EPCAM+) cells. Among 8 CD4+ T lymphocyte subpopulations and 11 CD8+ T lymphocyte subpopulations observed through clustering, a naïve CD4+ and a CD8+ T subpopulation (LEF1+, TCF7+) was observed respectively. These naïve T lymphocyte populations displayed increased proportions in LNs in comparison to tumors. In addition, 5 of the 8 observed CD4+ T lymphocyte populations were enriched in LNs. Immune populations enriched in LNs were largely shared and uniform across different patients. In contrast, a single CD4+ and CD8+ T lymphocyte subpopulation displayed expression of T lymphocyte exhaustion markers (TIGIT+, LAG3+, PD-1+) and were enriched in tumors. 6 of the 11 observed CD8+ T lymphocyte populations were enriched in tumor samples in comparison to LNs. Two alveolar macrophage populations (MARCO+) were enriched in normal lung tissue, in which one showed a heightened stress response. Conclusion: Single-cell profiling reveals diversity in immune cell populations between LNs, tumor, and adjacent normal tissue in early-stage LUAD. The results suggest the composition of immune cell type is fairly consistent across LNs but more heterogeneous in the tumor and adjacent normal tissue in early-stage patients. In the future, we aim to determine if these immune subpopulations are associated with survival, recurrence, aggressiveness, and predict responses for neoadjuvant treatments, which could improve prognosis and patient quality of life. Citation Format: Zhanhao Xi, Yusuke Koga, Shannon McDermott, Jennifer Beane, Sarah A. Mazzilli, Kei Suzuki, Joshua D. Campbell. Comparison of the tumor and lymph node immune microenvironment in early non-small cell lung cancer through multimodal single cell sequencing. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4651.

Surgical Approach and Persistent Opioid Use in Medicare Patients Undergoing Lung Cancer Resection

BackgroundRobotic and video-assisted thoracoscopic surgery (VATS) approaches for lung resection are associated with decreased inpatient opioid use compared with open surgery. Whether these approaches affect outpatient persistent opioid use remains unknown. MethodsNon-small cell lung cancer patients aged 66 years or more who underwent lung resection between 2008 and 2017 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Persistent opioid use was defined as filling an opioid prescription 3 to 6 months after lung resection. Adjusted analyses were performed to evaluate surgical approach and persistent opioid use. ResultsWe identified 19,673 patients: 7479 (38%) underwent open surgery, 10,388 (52.8%) VATS, and 1806 (9.2%) robotic surgery. Persistent opioid use was 38% in the entire cohort, including 27% of opioid naïve patients, and highest after open surgery (42.5%), followed by VATS (35.3%) and robotic (33.1%, P < .001). In multivariable analyses, robotic (odds ratio 0.84; 95% CI, 0.72-0.98; P = .028) and VATS (odds ratio 0.87; 95% CI, 0.79-0.95; P = .003) approaches were both associated with decreased persistent opioid use compared with open surgery in opioid naïve patients. At 12 months, patients resected using a robotic approach had the lowest oral morphine equivalent per month compared with VATS (133 vs 160, P < .001) and open surgery (133 vs 200, P < .001). Among chronic opioid patients, surgical approach was not associated with postoperative opioid use. ConclusionsPersistent opioid use after lung resection is common. Both robotic and VATS approaches were associated with decreased persistent opioid use compared with open surgery among opioid naïve patients. Whether a robotic approach yields additional long-term advantages over VATS warrants further investigation.

Hospital-Level Segregation Among Medicare Beneficiaries Undergoing Lung Cancer Resection

BackgroundRecent research has raised concern that health care segregation, the high concentration of racial groups within a subset of hospitals, is a key contributor to persistent disparities in surgical care. However, to date the extent and effect of hospital level segregation among patients undergoing resection for lung cancer remains unclear. MethodsWe used 100% Medicare fee-for-service claims to evaluate the degree of hospital-level racial segregation for patients undergoing resection for lung cancer between 2014 and 2018. Hospitals serving a high volume of minority patients were defined as the top decile of hospitals by volume of racial and ethnic minority beneficiaries served. Multivariable logistic regression analysis was used to compare surgical outcomes between hospitals serving high vs low volumes of minority patients. ResultsA total of 122,943 patients were included, with racial/ethnic composition of 360 American Indian or Native American (0.3%), 2077 Asian or Pacific Islander (1.7%), 1146 Hispanic or Latino (0.9%), 8707 non-Hispanic Black (7.1%), and 108,665 non-Hispanic White patients. Overall, 31.6%, 15.9%, 15.0%, and 7.8% of all hospitals performed 90% of lung cancer resection for Black, Asian, Hispanic, and Native American patients, respectively. Hospitals performing higher volumes of operations for racial and ethnic minorities had higher mortality (3.9% vs 3.1%; odds ratio [OR], 1.19; 95% CI, 1.15-1.23; P < .001), complications (18.1% vs 15.9%; OR, 1.17; 95% CI, 1.14-1.19; P < .001), and readmissions (11.7% vs 11.2%; OR, 1.04; 95% CI, 1.02-1.05; P < .001) for resections for lung cancer. ConclusionsOur findings suggest that a small proportion of hospitals provide a disproportionate amount of surgical care for racial and ethnic minorities with lung cancer with inferior surgical outcomes.

Abstract P075: Comparison of the tumor and lymph node immune microenvironment in early non-small cell lung cancer through multimodal single cell sequencing

Abstract Background/Purpose: Previous studies have analyzed the tumor and local immune microenvironments in lung cancers and suggest immune modulation is associated with worse clinical outcome. However, the tumor-immune microenvironment in early-stage lung tumors and lymph nodes (LNs) have not been fully described. We aim to compare cell states in the immune microenvironments between lung tumors and LNs through multi-modal profiling of the transcriptome and surface proteins. Methods: Needle biopsy samples were taken from 10 treatment-naive early-stage lung cancer patients undergoing lung cancer resections. Tissues were obtained from normal lung, lung tumor, and multiple mediastinal LNs, and processed with scRNA-seq along with the Total-Seq C panel to quantify the levels of 130 cell surface proteins. In total, 98,337 cells (4,661 normal lung; 52,119 tumor; 42,117 LN) were identified with a median of 1,401 genes and 23 protein features detected per cell. Weighted-Nearest Neighbor analysis from the Seurat R package was applied to integrate the CITE-seq and RNA-seq level data for clustering cells into subpopulations. Results: Six broad cell populations were identified including T/NK, myeloid (CD14+), B (CD19+), mast (TPSAB1+), pDC (IRF8+), and epithelial (EPCAM+) cells. Protein expression measured with CITE-seq revealed additional T cell populations not captured by scRNA-seq. Preliminary results have identified cell populations enriched in LNs, which include naive CD4+ (CD4, FHIT, LEF1, CCR7) and CD8+ T cells (CD8A, TCF7, LEF1, CD27, CCR7). Additionally, we have identified numerous other CD8+ T-cell subpopulations enriched in tumors, including resident memory CD8+ T cells (KLRC1, ITGAE, ITGA1, VIM, JUN). Furthermore, immune populations enriched in LNs were similarly shared across different patients, while those enriched in tumors displayed patient-level specificity. Conclusion: Single-cell profiling reveals diversity in immune cell populations between LNs, tumor, and adjacent normal tissue in early-stage LUAD. The results suggest the composition of immune cell type is consistent across LNs but more heterogeneous in the tumor and adjacent normal tissue. In the future, we aim to determine if these markers for various immune subpopulations are associated with survival, recurrence, aggressiveness, and predict responses for neoadjuvant treatments, which could improve prognosis and patient quality of life. Citation Format: Zhan Xi, Yusuke Koga, Shannon McDermott, Jennifer E. Beane, Sarah A. Mazzilli, Kei Suzuki, Joshua D. Campbell. Comparison of the tumor and lymph node immune microenvironment in early non-small cell lung cancer through multimodal single cell sequencing. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P075.

Should all patients receive extended thromboprophylaxis after resection of primary lung cancer?

ObjectiveThe optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis. MethodsWe reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups. ResultsSeven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli. ConclusionsPatients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.