Surgical management of non-small cell lung cancer with limited metastatic disease involving only the brain.

OBJECTIVE: The optimal primary site treatment modality for non-small cell lung cancer with brain oligometastases is not well established. This study sought to evaluate the long-term survival of patients with non-small cell lung cancer with isolated brain metastases undergoing multimodal therapy with or without thoracic surgery. METHODS: Patients with cT1-3, N0-1, M1b-c non-small cell lung cancer with synchronous limited metastatic disease involving only the brain treated with brain stereotactic radiosurgery or neurosurgical resection in the National Cancer Database (2010-2017) were included. Long-term overall survival of patients who underwent multimodal therapy including thoracic surgery ("Thoracic Surgery") versus systemic therapy with or without radiation to the lung ("No Thoracic Surgery") was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching. RESULTS: Of the 1240 patients with non-small cell lung cancer with brain-only metastases who received brain stereotactic radiosurgery or neurosurgery and met study inclusion criteria, 270 (21.8%) received primary site resection. The Thoracic Surgery group had improved overall survival compared with the No Thoracic Surgery group in Kaplan-Meier analysis (P < .001) and after multivariable-adjusted Cox proportional hazards modeling (P < .001). In a propensity score-matched analysis of 175 patients each in the Thoracic Surgery and No Thoracic Surgery groups, matching on 13 common prognostic variables, thoracic surgery was associated with better survival (P = .012). CONCLUSIONS: In this national analysis, patients with cT1-3, N0-1, M1b-c non-small cell lung cancer with isolated limited brain metastases had better overall survival after multimodal therapy including thoracic surgery compared with systemic therapy without surgery. Multimodal thoracic treatment including surgery can be considered for carefully selected patients with non-small cell lung cancer and limited brain metastases.

Completeness of Resection and Long-Term Survival of Patients Undergoing Resection for Pathologic T3 NSCLC: An International Association for the Study of Lung Cancer Analysis.

INTRODUCTION: Currently, tumors with different histopathologic characteristics and oncologic outcomes comprise the T3 category of the eight edition TNM classification for lung cancers. To better understand the T3 category, we evaluated completeness of resection and long-term survival in patients undergoing resection for T3 NSCLC. METHODS: The International Association for the Study of Lung Cancer 1999 to 2010 database was queried for patients with pathologic T3N0M0 NSCLC who underwent lobectomy or pneumonectomy. The primary outcome evaluated was overall survival (OS) stratified by T3 descriptors and completeness of resection. RESULTS: Of 1448 patients with T3N0M0 tumors, 1187 (82.0%) had a single descriptor defining them as T3. T3 tumors with chest wall infiltration (CWI) or parietal pleura infiltration (PL3) had the highest rates of incomplete resection (9.8% and 8.4%, respectively), and those classified as T3 by size only had the lowest rate of incomplete resection (2.9%). Individual T3 descriptors were associated with significant differences in OS (p = 0.005). When tumors with similar survival and complete resection rates were grouped, patients with T3 tumors characterized by size or the presence of a separate nodule (SN) in the same lobe had better 5-year OS than patients with tumors characterized by PL3 or CWI (size/SN 60% versus CWI/PL3 53%, p = 0.017) independent of completeness of resection. CONCLUSIONS: Significant differences in 5-year OS were associated with size, SN, PL3, or CWI T3 descriptors. Subdividing pathologic T3N0M0 tumors according to the presence or absence of CWI or PL3 may increase the prognostic accuracy of tumor staging.

Shortage of thoracic surgeons in the United States: Implications for treatment and survival for stage I lung cancer patients.

OBJECTIVES: To evaluate whether there is a shortage of thoracic surgeons in the United States and whether any potential shortage is impacting lung cancer treatment and outcomes. DESIGN: Using the US Area Health Resources File and Surveillance Epidemiology End Results database, we assessed the number of cardiothoracic surgeons per 100,000 people and the number of stage I non-small cell lung cancer (NSCLC) diagnoses in the US in 2010 versus 2018. Changes in the percentage of patients diagnosed with stage I NSCLC who underwent surgery and stereotactic body radiotherapy and changes in overall survival of patients with stage I NSCLC from 2010 to 2018 in the National Cancer Database were evaluated using multivariable logistic regression and Cox proportional hazards modeling. RESULTS: From 2010 to 2018, the number of cardiothoracic surgeons per 100,000 people in the US decreased by 12% (P < .001), while the number of patients diagnosed with stage I NSCLC increased by 40% (P < .001). Over the same period, the percentage of patients who underwent surgery for stage I NSCLC decreased from 81.0% to 72.3% (adjusted odds ratio, 0.59; 95% confidence interval, 0.55-0.63); this decrease was similarly seen in a subgroup of young and otherwise healthy patients. Greater decreases in the percentage of patients who underwent surgery in nonmetropolitan and underserved regions corresponded with worse improvements in survival among patients in these regions from 2010 to 2018. CONCLUSIONS: Recent declines in the US cardiothoracic surgery workforce may have led to significantly fewer patients undergoing surgery for stage I NSCLC and worsening disparities in survival between different patient populations.

Surgery for M1A Non-Small-Cell Lung Cancer With Additional Pulmonary Nodules in a Contralateral Lobe.

INTRODUCTION: Limited consensus exists on the optimal treatment strategy for clinical M1a non-small-cell lung cancer (NSCLC) presenting as a primary tumor with additional intrapulmonary nodules in a contralateral lobe ("M1a-Contra"). This study sought to compare long-term survival of patients with M1a-Contra tumors receiving multimodal therapy with versus without thoracic surgery. METHODS: Overall survival of patients with cT1-4, N0-3, M1a NSCLC with contralateral intrapulmonary nodules who received surgery as part of multimodal therapy ("Thoracic Surgery") versus systemic therapy with or without radiation ("No Thoracic Surgery") in the National Cancer Database from 2010 to 2015 was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching. RESULTS: Of the 5042 patients who satisfied study inclusion criteria, 357 (7.1%) received multimodal therapy including surgery. In multivariable-adjusted analysis, the Thoracic Surgery cohort had better overall survival than the No Thoracic Surgery cohort (HR: 0.66, 95% CI: 0.56-0.79, P < 0.001). In a propensity score-matched analysis of 386 patients, well-balanced on 12 common prognostic covariates, the Thoracic Surgery group had better 5-year overall survival than the No Thoracic Surgery group (P = 0.020). In propensity score-matched analyses stratified by clinical N status, Thoracic Surgery was associated with better overall survival than No Thoracic Surgery for patients with cN0 disease and cN1-2 disease. CONCLUSIONS: In this national analysis, multimodal treatment including surgery was associated with better overall survival than systemic therapy with or without radiation without surgery for patients with M1a-Contra tumors. These preliminary findings highlight the importance of further evaluation of surgery in a multidisciplinary treatment setting for M1a-Contra tumors.

Segmentectomy versus lobectomy in the United States: Outcomes after resection for first primary lung cancer and treatment patterns for second primary lung cancers.

OBJECTIVE: The study objective was to identify whether the results of JCOG0802 could be generalized to US clinical settings. METHODS: Patients diagnosed with clinical stage IA (≤2 cm) non-small cell lung cancer who underwent segmentectomy versus lobectomy (2004-2017) in the National Cancer Database were identified. Overall survival of patients in the National Cancer Database was assessed using propensity score-matched analysis. A separate analysis of the Surveillance Epidemiology End Results database was conducted to evaluate treatment patterns of second primary lung cancers among patients who underwent segmentectomy versus lobectomy for a first primary lung cancer. RESULTS: Of the 23,286 patients in the National Cancer Database meeting inclusion criteria, 1397 (6.0%) underwent segmentectomy and 21,889 (94.0%) underwent lobectomy. In a propensity score-matched analysis of all patients in the study cohort, there were no significant differences in overall survival between patients undergoing segmentectomy versus lobectomy (5-year overall survival: 79.9% [95% CI, 76.7%-82.0%] vs 81.8% [95% CI, 78.7%-84.4%], log-rank: P = .72). In subgroup analyses by tumor grade and histologic subtype, segmentectomy was associated with similar overall survival compared with lobectomy in all subgroups evaluated. In a propensity score-matched analysis of patients in the Surveillance Epidemiology End Results database, there were no significant differences in treatment patterns of second primary lung cancers between patients who underwent segmentectomy and patients who underwent lobectomy for their first primary lung cancer. CONCLUSIONS: In this national analysis of US patients diagnosed with stage IA (≤2 cm) non-small cell lung cancer, there were no significant differences in overall survival between segmentectomy and lobectomy in the overall cohort or in subgroup analyses by tumor grade or histologic subtype.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revisions of the T-Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: An international database was created by the International Association for the Study of Lung Cancer to inform on the ninth edition of the TNM classification of lung cancer. The present analyses concern its T component. METHODS: Data on 124,581 patients diagnosed with lung cancer from January 1, 2011 to December 31, 2019 were submitted to the International Association for the Study of Lung Cancer database. Of these, 33,982 met the inclusion criteria for the clinical T analysis, and 30,715 met the inclusion criteria for the pathologic postsurgical analysis. Survival was measured from the date of diagnosis or operation for clinically and pathologically staged tumors, respectively. T descriptors were evaluated in univariate analysis and multivariable Cox regression analysis adjusted for age, sex, pathologic type, and geographic region. RESULTS: Comprehensive survival analysis revealed that the existing eighth edition T component criteria performed adequately in the ninth edition data set. Although pathologic chest wall or parietal pleura involvement (PL 3) yielded a worse survival compared with the other T3 descriptors, with a similar survival as T4 tumors, this difference was not observed for clinical chest wall or PL 3 tumors. Because of these inconsistent findings, no reallocation of chest wall or PL 3 tumors is advised. CONCLUSIONS: The T subcommittee members proposed not to implement any changes and keep the current eighth-edition T descriptors for the ninth edition.

Role of sex in lung cancer risk prediction based on single low-dose chest computed tomography.

A validated open-source deep-learning algorithm called Sybil can accurately predict long-term lung cancer risk from a single low-dose chest computed tomography (LDCT). However, Sybil was trained on a majority-male cohort. Use of artificial intelligence algorithms trained on imbalanced cohorts may lead to inequitable outcomes in real-world settings. We aimed to study whether Sybil predicts lung cancer risk equally regardless of sex. We analyzed 10,573 LDCTs from 6127 consecutive lung cancer screening participants across a health system between 2015 and 2021. Sybil achieved AUCs of 0.89 (95% CI: 0.85-0.93) for females and 0.89 (95% CI: 0.85-0.94) for males at 1 year, p = 0.92. At 6 years, the AUC was 0.87 (95% CI: 0.83-0.93) for females and 0.79 (95% CI: 0.72-0.86) for males, p = 0.01. In conclusion, Sybil can accurately predict future lung cancer risk in females and males in a real-world setting and performs better in females than in males for predicting 6-year lung cancer risk.

Update on Lung Cancer Screening Guideline.

Lung cancer screening has been shown to reduce lung cancer mortality and is recommended for individuals meeting age and smoking history criteria. Despite the expansion of lung cancer screening guidelines in 2021, racial/ethnic and sex disparities persist. High-risk racial minorities and women are more likely to be diagnosed with lung cancer at younger ages and have lower smoking histories when compared with White and male counterparts, resulting in higher rates of ineligibility for screening. Risk prediction models, biomarkers, and deep learning may help refine the selection of individuals who would benefit from screening.

The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the N Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: The accurate assessment of nodal (N) status is crucial to the management and prognostication of nonmetastatic NSCLC. We sought to determine whether the current N descriptors should be maintained or revised for the upcoming ninth edition of the international TNM lung cancer staging system. METHODS: Data were assembled by the International Association for the Study of Lung Cancer on patients with NSCLC, detailing both clinical and pathologic N status, with information about anatomical location and individual station-level identification. Survival was calculated by the Kaplan-Meier method and prognostic groups were assessed by a Cox regression analysis. RESULTS: Data for clinical N and pathologic N status were available in 45,032 and 35,009 patients, respectively. The current N0 to N3 descriptors for both clinical N and pathologic N categories reflect prognostically distinct groups. Furthermore, single-station N2 involvement (N2a) exhibited a better prognosis than multistation N2 involvement (N2b) in both clinical and pathologic classifications, and the differences between all neighboring nodal subcategories were highly significant. The prognostic differences between N2a and N2b were robust and consistent across resection status, histologic type, T category, and geographic region. CONCLUSIONS: The current N descriptors should be maintained, with the addition of new subdescriptors to N2 for single-station involvement (N2a) and multiple-station involvement (N2b).

Persistent race- and sex-based disparities in lung cancer screening eligibility.

OBJECTIVE: To evaluate race- and sex-based disparities in lung cancer screening eligibility under the 2013 US Preventive Services Task Force, 2021 US Preventive Services Task Force, and National Comprehensive Cancer Network lung cancer screening guidelines. METHODS: Participants in the Southern Community Cohort Study with a smoking history diagnosed with lung cancer from 2002 to 2021 were identified for analysis. Differences in age at lung cancer diagnosis and smoking characteristics were evaluated among 4 groups: Black men, Black women, White men, and White women. RESULTS: A total of 2011 patients with lung cancer met study inclusion criteria, of whom 968 (48.1%) were women and 1248 (62.1%) were Black. Under the 2013 guideline, Black men with lung cancer were significantly less likely to be eligible for screening when compared with White men with lung cancer (37.7% vs 62.4%; P < .001), and Black women with lung cancer were significantly less likely to be eligible for screening when compared with White women with lung cancer (27.8% vs 56.7%; P < .001). Under the 2021 guideline, 62.6% of Black and 73.8% of White men (P < .001) with lung cancer would have been eligible for screening, resulting in an 11.2 percentage point difference in screening eligibility between Black and White men. Under the 2021 guideline, 50.3% of Black and 74.9% of White (P < .001) women with lung cancer would have been eligible for screening; notably, there remained a 24.6 percentage point difference in screening eligibility between Black and White women. In multivariable-adjusted analysis, under the 2021 USPSTF guideline, Black men with lung cancer had 46% lower odds of being eligible for screening compared with White men with lung cancer (multivariable-adjusted odds ratio [aOR], 0.54; 95% CI, 0.39-0.76; P < .001) and Black women with lung cancer had 66% lower odds of being eligible for screening compared with White women with lung cancer (aOR, 0.34; 95% CI, 0.25-0.46; P < .001). The National Comprehensive Cancer Network guideline increased the proportion of patients with lung cancer eligible for screening in each group. CONCLUSIONS: In this analysis of patients with lung cancer in the Southern Community Cohort Study, there remained a large gap in lung cancer screening eligibility between Black and White men and women under the 2021 US Preventive Services Task Force guideline. Only 50% of Black women and 63% of Black men diagnosed with lung cancer would have qualified for screening.

Induction chemoimmunotherapy with surgery versus concurrent chemoradiation followed by immunotherapy for stage III-N2 non-small cell lung cancer.

OBJECTIVE: Despite the growing relevance of immunotherapy for non-small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for locally advanced NSCLC. This study evaluated the overall survival of patients with stage III-N2 NSCLC undergoing induction chemoimmunotherapy with surgery (CT/IO+Surgery) and definitive concurrent chemoradiation followed by immunotherapy (cCRT+IO). METHODS: Patients with cT1-3, N2, M0 NSCLC in the National Cancer Database (2013 to 2019) were included and stratified by treatment regimen: CT/IO+Surgery or cCRT+IO. Overall survival was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching on 10 prognostic variables. RESULTS: Of the 3382 patients who met the study eligibility criteria, 3289 (97.3%) received cCRT+IO and 93 (2.8%) received CT/IO+Surgery. The 3-year overall survival of the entire cohort was 58.2% (95% CI, 56.2% to 60.1%). Multivariable-adjusted Cox proportional hazards modeling demonstrated better survival after CT/IO+Surgery than after cCRT+IO (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.32 to 0.84; P = .007). In a 3:1 variable ratio propensity score-matched analysis of 223 patients who received cCRT+IO and 76 patients who received CT/IO+Surgery, 3-year overall survival was 63.2% (95% CI, 55.9% to 70.2%) after cCRT+IO and 77.2% (95% CI, 64.6% to 85.7%) after CT/IO+Surgery (P = .029). CONCLUSIONS: In this national analysis, multimodal treatment including immunotherapy was associated with a 3-year overall survival rate of 58.2% for all patients with stage III-N2 NSCLC and 77.2% for patients who underwent chemoimmunotherapy followed by surgery. These results should be considered hypothesis-generating and demonstrate the importance of developing a randomized trial to evaluate the role of surgery versus chemoradiation for locally advanced NSCLC in the modern immunotherapy era.

A national survey of occupational musculoskeletal injuries in cardiothoracic surgeons.

OBJECTIVE: There is growing concern that surgeons are at increased risk for work-related orthopedic injuries due to poor ergonomics. We conducted a survey of North American cardiothoracic surgeons to evaluate the prevalence of occupational injury, as well as perceptions and use of ergonomic techniques. METHODS: Cardiothoracic surgeons identified through the Cardiothoracic Surgery Network were asked to complete a 33-question survey assessing their musculoskeletal health, as well as their perceptions and use of ergonomic techniques in the operating room and office. RESULTS: Among 600 cardiothoracic surgeons, the prevalence of occupational musculoskeletal injuries was 64%, with 30% of affected surgeons requiring time away from work and 20% requiring surgery or the use of narcotics. Cervical spine injury (35%, n = 216) was the most common injury due to operating, followed by lumbar spine injury (30%, n = 180). In multivariable-adjusted analysis, cardiac surgeons were more likely than thoracic surgeons to experience occupational musculoskeletal injuries (adjusted odds ratio, 1.8 [1.2-2.8], P < .01). Notably, 90% of surgeons (n = 536) reported thinking that their institution did not provide sufficient ergonomics education or support, and only 35% (n = 205) thought that the cardiothoracic surgical community is supportive of implementing ergonomics techniques in the operating room and office. CONCLUSIONS: In this survey analysis, cardiothoracic surgeons reported experiencing work-related orthopedic injuries at an alarmingly high rate, leading to significant time away from work and for many to retire from surgery over a decade early. These findings underline a critical need for institutions to prioritize ergonomics education and implement ergonomics-directed techniques in the operating room and office.

Wedge Resection Versus Segmentectomy for Older Patients With Stage IA Non-Small-Cell Lung Cancer.

INTRODUCTION: Anatomic lung resection remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), but wedge resection may offer similar survival in older adult patients. The objective of this study was to evaluate the survival of patients aged 80 y and older undergoing wedge resection versus segmentectomy for stage IA NSCLC using a large clinical registry. METHODS: Patients aged 80 y and older in the National Cancer Database who underwent wedge resection or segmentectomy for cT1a-b N0 M0 NSCLC between 2004 and 2018 were identified for an analysis. Survival was assessed using multivariable Cox proportional hazards analysis, propensity-score matching, and inverse probability weighting. A subgroup analysis of patients who underwent lymph node evaluation with their wedge resection or segmentectomy was also performed. RESULTS: Of the 2690 patients identified, 2272 (84%) underwent wedge resection and 418 (16%) underwent segmentectomy. Wedge resection was associated with worse 5-year overall survival relative to segmentectomy in multivariable-adjusted (adjusted Hazard Ratio: 1.26, [1.06-1.51], P = 0.01) and propensity score-matched analysis (49% [95% confidence interval {CI}: 42%-55%] versus 59% [95% CI: 52%-65%], P = 0.02). Among a subgroup of 1221 wedge resection and 347 segmentectomy patients who also received intraoperative lymph node evaluation, however, there were no significant differences in 5-year survival in multivariable-adjusted (adjusted Hazard Ratio: 1.12, [0.90-1.39], P = 0.31) or propensity score-matched analysis (55% [95% CI: 48%-62%] versus 61% [95% CI: 54%-68%], P = 0.10). CONCLUSIONS: In this national analysis, there were no significant differences in survival between older adult patients with stage IA NSCLC who underwent wedge resection versus segmentectomy when a lymph node evaluation was performed.

Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment.

BACKGROUND: No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. METHODS: This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. RESULTS: There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. CONCLUSIONS: The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.

Postoperative radiotherapy with modern techniques does not improve survival for operable stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: This study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) who underwent complete resection. METHODS: The overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded. RESULTS: A total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not. CONCLUSIONS: In this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

Safety and feasibility of minimally invasive lobectomy after neoadjuvant immunotherapy for non-small cell lung cancer.

OBJECTIVE: The objective of this study was to evaluate the feasibility of minimally invasive surgery (MIS) and perioperative outcomes following neoadjuvant immunotherapy for resectable non-small cell lung cancer (NSCLC). METHODS: Patients with stage I to III NSCLC treated with immunotherapy with or without chemotherapy or chemotherapy alone prior to lobectomy were identified in the National Cancer Database (2010-2018). The percentage of operations performed minimally invasively, conversion rates, and perioperative outcomes were evaluated using propensity-score matching. Propensity-score matching was also used to compare perioperative outcomes between patients who underwent an open lobectomy and those who underwent an MIS lobectomy after neoadjuvant immunotherapy. RESULTS: Of the 4229 patients identified, 218 (5%) received neoadjuvant immunotherapy and 4011 (95%) received neoadjuvant chemotherapy alone. There was no difference in the rate of MIS lobectomy among patients who received immunotherapy compared with those who received chemotherapy alone in propensity score-matched analysis (60.8% vs 51.6%; P = .11). There also were no significant differences in the rate of conversion from MIS to open lobectomy (14% vs 15%, P = .83; odds ratio, 1.1; 95% confidence interval, 0.51-2.24) or in nodal downstaging, margin positivity, 30-day readmission, and 30- and 90-day mortality between the 2 groups. In a subgroup analysis of only patients treated with neoadjuvant immunotherapy, there were no differences in pathologic or perioperative outcomes between patients who underwent open lobectomy and those who underwent MIS lobectomy. CONCLUSIONS: In this national analysis, neoadjuvant immunotherapy for resectable NSCLC was not associated with an increased likelihood of the need for thoracotomy, conversion from MIS to open lobectomy, or inferior perioperative outcomes.

An Investigation of Cancer-Directed Surgery for Different Histologic Subtypes of Malignant Pleural Mesothelioma.

BACKGROUND: The role of cancer-directed surgery in the treatment of stage I-IIIA malignant pleural mesothelioma (MPM) by histologic subtypes remains controversial. The objective of this study was to evaluate the survival of the different histologic subtypes for stage I-IIIA MPM stratified by cancer-directed surgery and nonoperative management. RESEARCH QUESTION: How is the histologic subtype, clinical stage, and use of cancer-directed surgery for MPM associated with overall survival? STUDY DESIGN AND METHODS: Overall survival of patients with stage I-IIIA epithelioid, sarcomatoid, and biphasic MPM in the National Cancer Database from 2004 through 2017 who underwent cancer-directed surgery (ie, surgery with or without chemotherapy or radiation) or chemotherapy with or without radiation (nonoperative management) was evaluated using Kaplan-Meier analysis, multivariable Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS: Of 2,285 patients with stage I-IIIA MPM who met inclusion criteria, histologic subtype was epithelioid in 71% of patients, sarcomatoid in 12% of patients, and biphasic in 17% of patients. Median survival was 20 months in the epithelioid group, 8 months in the sarcomatoid group, and 13 months in the biphasic group (P < .01). Among patients who underwent surgery, median survival was 25 months in the epithelioid group, 8 months in the sarcomatoid group, and 15 months in the biphasic group (P < .01). In multivariable Cox proportional hazards analyses, surgery was associated with improved survival in the epithelioid group (P < .01) but not in the sarcomatoid (P = .63) or biphasic (P = .21) groups. These findings were consistent in propensity score-matched analyses for each MPM histologic type. INTERPRETATION: In this national analysis, cancer-directed surgery was found to be associated with improved survival for stage I-IIIA epithelioid MPM, but not for biphasic or sarcomatoid MPM.

Open, Video- and Robot-Assisted Thoracoscopic Lobectomy for Stage II-IIIA Non-Small Cell Lung Cancer.

BACKGROUND: This study compares the short- and long-term outcomes of open vs robotic vs video-assisted thoracoscopic surgery (VATS) lobectomy for stage II-IIIA non-small-cell lung cancer (NSCLC). METHODS: Outcomes of patients with stage II-IIIA NSCLC (excluding T4 tumors) who received open and minimally invasive surgery (MIS) lobectomy in the National Cancer Database from 2010 to 2017 were assessed using propensity score-matched analysis. RESULTS: A propensity score-matched analysis of 4652 open and 4652 MIS patients demonstrated a decreased median length of stay associated with MIS compared with open lobectomy (5 vs 6 days; P < .001). There were no significant differences in 30-day mortality, 30-day readmission, or overall survival between the open and MIS groups. A propensity score-matched analysis of 1186 VATS and 1186 robotic patients showed that compared with VATS, the robotic approach was associated with no significant differences in 30-day mortality, 30-day readmission, and overall survival. However, the robotic group had a decreased median length of stay compared with VATS (4 vs 5 days; P < .001). The conversion rate was also significantly lower for robotic compared with VATS lobectomy (8.9% vs 15.9%, P < .001). CONCLUSIONS: No significant differences were found in long-term survival between open and MIS lobectomy and between VATS and robotic lobectomy for stage II-IIIA NSCLC. However, the MIS approach was associated with a decreased length of stay compared with the open approach. The robotic approach was associated with decreased length of stay and decreased conversion rate compared with the VATS approach.

Drivers of Cost Associated With Minimally Invasive Esophagectomy.

BACKGROUND: In this era of value-based healthcare, costs must be measured alongside patient outcomes to prioritize quality improvement and inform performance-based reimbursement strategies. We sought to identify drivers of costs for patients undergoing minimally invasive esophagectomy for esophageal cancer. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer from December 2008 to March 2020 were included. Our institutional Society of Thoracic Surgeons database was merged with financial data to determine inpatient direct accounting costs in 2020 US dollars for total, operative (surgery and anesthesia), and postoperative (intensive care, floor, radiology, laboratory, etc) services. A supervised machine learning quantitative method, the lasso estimator with 10-fold cross-validation, was applied to identify predictors of costs. RESULTS: In the study cohort (n = 240) most had ≥cT2 pathology (82%), adenocarcinoma histology (90%), and received neoadjuvant therapy (78%). Mean length of stay was 8.00 days (SD, 4.13) with 45% inpatient morbidity rate and no deaths. The largest proportions of cost were from the operating room (30%), inpatient floor (30%), and postanesthesia care/intensive care units (20%). Preoperative predictors of operative costs were age (-5.18% per decade [95% confidence interval {CI}, -9.95 to -0.27], P = .039), body mass index ≥ 30 (+12.9% [95% CI, 0.00-27.5], P = .050), forced expiratory volume in 1 second (-3.24% per 10% forced expiratory volume in 1 second [95% CI, -5.80 to -0.61], P = .017), and year of surgery (+2.55% [95% CI, 0.97-4.15], P = .002). Predictors of postoperative costs were postoperative renal failure (+91.6% [95% CI, 9.93-233.8], P = .022), respiratory failure (+414.6% [95% CI, 158.7-923.6], P < .001), pneumonia (+136.1% [95% CI, 71.1-225.8], P < .001), and reoperation (+60.5% [95% CI, 21.5-111.9], P = .001). CONCLUSIONS: Costs associated with minimally invasive esophagectomy are driven by preoperative risk factors and postoperative outcomes. These data enable surgeons and policymakers to reduce cost variation, improve quality through standardization, and ultimately provide greater value to patients.

Induction Therapy Is Not Associated With Improved Survival in Large cT4 N0 Non-Small Cell Lung Cancers.

BACKGROUND: The eighth edition of the staging manual for non-small cell lung cancer reclassified tumors >7 cm as stage IIIA (T4 N0); previously, such tumors without nodal disease were considered stage IIB (T3 N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared with primary surgery. METHODS: The National Cancer Database was queried for patients with non-small cell lung cancer with tumor size >7 cm who underwent surgical resection from 2010 to 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgical resection (IC group) were compared with patients undergoing primary surgery (PS group). Propensity score matching was performed. RESULTS: In total, 1610 patients with cT4 N0 disease on the basis of tumor size >7 cm and no tumor invasion underwent surgical resection: 1346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity score matching, the IC group had a higher rate of pN0 (78.4% vs 66.0%; P < .001) and less lymphovascular invasion (13.9% vs 26.3%; P < .001), but longer postoperative stays (6 days vs 5 days; P < .001) and higher 30-day mortality (3.5% vs 0%; P = .002). Median 5-year survival was similar between the IC and PS groups (53.5% vs 62.2%; P = .075), and IC was not independently associated with survival (hazard ratio, 1.45; P = .146). CONCLUSIONS: Patients with cT4 N0 non-small cell lung cancer on the basis of tumor size >7 cm and no tumor invasion of major structures have similar overall survival with either induction chemotherapy or primary surgery. Induction chemotherapy should not be routinely given for this subset of stage IIIA patients.