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Little is known about the factors that contribute to symptoms in nursing home residents with cancer. We compared rates of symptoms in residents with (n = 1,022) and without cancer (n = 9,910) and examined physiologic, psychologic and situational factors potentially related to symptoms in residents with cancer. Pain, shortness of breath, vomiting, weight loss, and diarrhea were significantly (p < .05) more prevalent in residents with cancer. Cancer treatments, comorbid illnesses, and situational factors were not consistently correlated with symptoms. Improved symptom control was especially needed for the 30% of residents with cancer who clinically deteriorated within 3 months of admission; physical dependence and deteriorating clinical status were associated with pain, shortness of breath, and weight loss. [ABSTRACT FROM AUTHOR]

The project reported here is the first in a series of cost analyses regarding the care planning process among 107 facilities. Process-based costing strategies and data envelopment analyses identified nursing facilities with efficient and less-efficient care planning processes. Having more people and more time devoted to the care planning process did not assure quality or efficiency. Efficiency varied across the nursing facilities and was not related to number of beds, profit status, or location; however, Medicare-certified facilities were less likely to be efficient. [ABSTRACT FROM AUTHOR]

The valid measurement of nurses' job satisfaction is critical because job satisfaction is important for the retention of qualified nurses to provide patient care in hospitals. Two studies were conducted to adapt the Stamps Index of Work Satisfaction (1997b) to measure work satisfaction at the patient care unit level for use by the National Database of Nursing Quality Indicators (NDNQI). In Study 1 (n = 918 RNs) exploratory factor analysis of data obtained using the NDNQI-Adapted Index replicated the conceptual dimensions of the Stamps measure. Associations with scores on Job Enjoyment were evidence that the Index measured the intended construct. Using theta, the reliability of the composite subscales was .91. The adapted Work Satisfaction subscale scores explained 46% of the variance in Job Enjoyment, with each subscale contributing uniquely (p < .001). In Study 2 (n = 2277 RNs) confirmatory factor analysis using structural equation modeling supported the 7-subscale structure for the Adapted Index (CFI [719] = .88; RMR = .05). Replication of associations between scores on the Index subscales and Job Enjoyment provided further evidence regarding validity of the data, since the Work Satisfaction subscales explained 56% of the variance in Job Enjoyment. The feasibility of using an on-line version of the Adapted-Index for data collection was demonstrated. The findings from the two studies indicate that the adapted Index of Work Satisfaction has a structure similar to the original instrument and is a reliable and valid measure of work satisfaction at the patient care unit level. [ABSTRACT FROM AUTHOR]

Research has indicated that using coping strategies is significantly related to resisting smoking during highly tempting situations. However little is known about the nature of coping during smoking cessation. The purpose of this study was to identify coping strategies used within the first 10 days of smoking cessation by having participants describe these strategies into a handheld tape recorder at the actual time of occurrence. The aim of a qualitative analysis of the narrative accounts was to create a descriptive taxonomy of smoking cessation strategies grounded in the participants' own terms. Over 3 consecutive days, 36 participants recruited from smoking cessation programs provided 477 narrative accounts of coping episodes. Seven major taxons--context, anticipatory efforts, awareness, urges, strategies, effects, and metaphors reflected the entire process participants described when dealing with the urge to smoke. This taxonomy, inductively derived from real time rather than retrospective data, provides a holistic picture of strategies used in the early stages of the quit experience. [ABSTRACT FROM AUTHOR]

An organizational dynamics paradigm is examined for effectiveness in predicting absenteeism among staff RNs in four hospitals. Different predictor variables were important within each hospital. Discussion is focused on the manager role and organizational policies related to criteria for excessive absence, incentives for attendance, and deterrents to absence. [ABSTRACT FROM AUTHOR]

This study used causal modeling to trace the effects of manager leadership characteristics on staff registered nurse (RN) retention in 4 urban hospitals. Unique to the study were the all-RN sample, using Leavitt's (1958) model of behavior within an organization to group variables, manager characteristics and unit structure variables as predictors, and focus on the work unit rather than the hospital. Effects of manager characteristics were traced to retention through work characteristics, job stress, job satisfaction, commitment, and intent to stay. Theoretical variables explained 22% of the retention variance. Manager consideration of staff and RN intent to remain directly affected retention; other variable effects passed through intent to stay. Different predictors were important to retention, unit separation, and turnover. [ABSTRACT FROM AUTHOR]

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21-27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15-20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRAS G12C PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD., Competing Interests: Declaration of interests G.R. has financial relationships with Scanlan, AstraZeneca, and Medtronic. S.S. is a member of the AstraZeneca Advisory Board. J.M.I. has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. M.J.B. is a consultant for AstraZeneca, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. B.T.L. has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants (institutional) from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. M.H.B. receives royalties from Globus Medical and DePuy Synthes. P.S.A. declares research funding from Atara Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPACT Bio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T cell therapies, which have been licensed to Atara Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T cell therapies to Atara Biotherapeutics and has associated financial interests. D.R.J. serves on a clinical trial steering committee for AstraZeneca and has research grant support from Merck., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC)., Summary Background Data: Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process., Methods: We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model., Results: In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876-0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P=0.20)., Conclusion: Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation., Competing Interests: Disclosures: Prasad S. Adusumilli declares research funding from ATARA Biotherapeutics, is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, Outpace Bio, has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T-cell therapies, which have been licensed to ATARA Biotherapeutics, and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. Daniel Gomez receives research funding from AstraZeneca and Varian. He has received personal fees from Varian, AstraZeneca, GRAIL, Johnson & Johnson, Medtronic, Physicians Education Resource, and Regeneron. Daniela Molena serves on a steering committee for AstraZeneca, as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Bernard J. Park serves as a consultant for Intuitive Surgical, CEEVRA, Medtronic, and Becton Dickinson. Matthew J. Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Andreas Rimner served on a steering committee for Merck, served as a consultant for AstraZeneca and Merck, and received grant support (institutional) from Varian Medical Systems, Boehringer Ingelheim, AstraZeneca, Merck, and Pfizer, payments from NIH/Coordinating Center for Clinical Trials. Valerie W. Rusch reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from NIH/Coordinating Center for Clinical Trials. Smita Sihag is a member of the AstraZeneca Advisory Board. James M. Isbell has served as an advisory board member for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. David R. Jones is a member of the Advisory Council for AstraZeneca and receives research grant support from Merck. Gaetano Rocco has financial relationships with Scanlan International, Medtronic, and Merck. The other authors have no conflict of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The newest Commission on Cancer standards recommend sampling 3 mediastinal and 1 hilar lymph node stations, 3 (N2) 1 (N1), for lung cancer resections. However, the relationship between the Commission on Cancer standards and outcomes has not been thoroughly investigated., Methods: A prospective institutional database was queried for clinical stage I-III lung resections before the implementation of the new standards. The relationship between the 3 (N2) 1 (N1) standard ("guideline concordant") and outcomes (upstaging, complications, receipt of adjuvant therapy, locoregional/distant recurrence, and survival) was assessed with multivariable models and stratified by stage., Results: Of 9289 pulmonary resections, 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared with nonconcordant, those that were guideline concordant had higher rates of nodal upstaging (21% vs 13%; odds ratio [OR], 1.32 [95% CI, 1.14-1.51]; P < .001) and in-hospital complications (34% vs 27%; OR, 1.17 [95% CI, 1.05-1.30]; P = .004) but similar adjuvant systemic therapy administration (19% vs 13%; OR, 1.09 [95% CI, 0.95-1.24]; P = .2; 98% chemotherapy). Locoregional and distant recurrences were not significantly improved with guideline concordance across clinical stage I, II, and III subsets. Overall survival was similar in clinical stages I and II, but improved survival was observed for guideline concordant clinical stage III patients (hazard ratio, 0.85 [95% CI, 0.74-0.97]; P = .02)., Conclusions: Sampling 3 (N2) 1 (N1) was associated with increased upstaging and complications but not with decreased recurrence or mortality in clinical stage I or II patients. Survival was improved for concordant, clinical stage III patients. Further study is indicated to determine the ideal lymph node sampling strategy across heterogeneous lung cancer patients., Competing Interests: Disclosures James Isbell reports a relationship with LumaCyte that includes: equity or stocks; with Roche that includes: board membership; and with Genetech Biotech Co Ltd that includes: board membership and funding grants. Daniela Molena reports a relationship with Genetech Biotech Co Ltd that includes: board membership and funding grants; with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory; with Johnson and Johnson Ltd that includes: consulting or advisory; with Bristol Myers Squibb Co that includes: consulting or advisory; and with Merck & Co Inc that includes: consulting or advisory. David Jones reports a relationship with Merck & Co Inc that includes: consulting or advisory; and with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory. Matthew Bott reports a relationship with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory. Prasad Adusumilli reports a relationship with Johnson and Johnson Ltd that includes: consulting or advisory; with Atara Biotherapeutics that includes: consulting or advisory; with Bayer Corporation that includes: consulting or advisory; with Carisma Therapeutics Inc that includes: consulting or advisory; with Imugene that includes: consulting or advisory; and with ImmPactBio that includes: consulting or advisory. Bernard Park reports a relationship with Intuitive Surgical Inc that includes: consulting or advisory; and with COTA, Inc that includes: consulting or advisory. Valerie Rusch reports a relationship with Genetech Biotech Co Ltd that includes: board membership and funding grants; with Intuitive Surgical Inc that includes: consulting or advisory; and with Genelux that includes: funding grants. Gaetano Rocco reports a relationship with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory; with Scanlan International Inc that includes: consulting or advisory; and with Medtronic that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Robotic-assisted bronchoscopy (RAB) is an emerging modality to sample pulmonary lesions. Cone-beam computed tomography (CBCT) can be incorporated into RAB. We investigated the magnitude and predictors of patient and staff radiation exposure during mobile CBCT-guided shape-sensing RAB., Methods: Patient radiation dose was estimated by cumulative dose area product (cDAP) and cumulative reference air kerma (cRAK). Staff equivalent dose was calculated based on isokerma maps and a phantom simulation. Patient, lesion and procedure-related factors associated with higher radiation doses were identified by logistic regression models., Results: A total of 198 RAB cases were included in the analysis. The median patient cDAP and cRAK were 10.86 Gy cm 2 (IQR: 4.62-20.84) and 76.20 mGy (IQR: 38.96-148.38), respectively. Among staff members, the bronchoscopist was exposed to the highest median equivalent dose of 1.48 μSv (IQR: 0.85-2.69). Both patient and staff radiation doses increased with the number of CBCT spins and targeted lesions (p < 0.001 for all comparisons). Patient obesity, negative bronchus sign, lesion size <2.0 cm and inadequate sampling by on-site evaluation were associated with a higher patient dose, while patient obesity and inadequate sampling by on-site evaluation were associated with a higher bronchoscopist equivalent dose., Conclusion: The magnitude of patient and staff radiation exposure during CBCT-RAB is aligned with safety thresholds recommended by regulatory authorities. Factors associated with a higher radiation exposure during CBCT-RAB can be identified pre-operatively and solicit procedural optimization by reinforcing radiation protective measures. Future studies are needed to confirm these findings across multiple institutions and practices., (© 2024 Asian Pacific Society of Respirology.)

Introduction: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer., Methods: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models., Results: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001)., Conclusions: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform., Competing Interests: Disclosure Dr. Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Dr. Prasad S. Adusumilli serves as consultant for ATARA Biotherapeutics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, and Johnson & Johnson. Dr. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic, serves as a consultant to Ceevra, and has received institutional research support from Intuitive Surgical. Dr. Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Dr. Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr. Isbell has served as an advisory board member for AstraZeneca and Merck and as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity or ownership interest in LumaCyte. Dr. Rusch receives grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from the National Institutes of Health/Coordinating Center for Clinical Trials. Dr. Solomon serves as a consultant for GE Healthcare and Merck and on the data monitoring committee for Candel Therapeutics and Impact Biotech. Dr. Jones is a member of the Advisory Council for AstraZeneca and Advisory Committee for More Health, has been a speaker for DAVA Oncology, and receives research grant support from Merck. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Results of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown., Methods: Clinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS)., Results: Of 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray's P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups., Conclusions: Patients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients., Competing Interests: Disclosures James M. Isbell has served as an advisory board member for AstraZeneca and Merck; has served as an uncompensated steering board member for Genentech; has received travel support from Intuitive Surgical; and has equity or ownership interest in LumaCyte. Daniela Molena has served on a steering committee for AstraZeneca; has served as a consultant for Johnson & Johnson, Bristol Myers Squibb, AstraZeneca, and Boston Scientific; and has been an invited speaker for Merck and Genentech. Bernard J. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic; and has served as a consultant for Ceevra. Gaetano Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Valerie W. Rusch has received other support from DaVinci Surgery; has received nonfinancial support from Bristol Myers Squibb; and has received personal fees from the NIH Coordinating Center for Clinical Trials. Smita Sihag has served as a member of the AstraZeneca advisory board. David R. Jones has served as a member of the advisory council for AstraZeneca and the Advisory Committee for More Health; and has been a speaker for DAVA Oncology. Matthew J. Bott has served as a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Minimally invasive surgery (MIS) (video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery) for pulmonary resection is standard in early-stage non-small cell lung cancer because it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced non-small cell lung cancer (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well defined., Methods: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB through IIIB non-small cell lung cancer who had resection after neoadjuvant systemic therapy without radiation from 2013 to 2022. Patients were grouped by surgical approach; that is, open versus MIS. Successful MIS was defined by no conversion, R0 resection, and no major (grade 3 or greater) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank-sum test and Fisher exact test. (Multivariable regression analysis identified variables that contributed to successful MIS resection.) RESULTS: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by video-assisted thoracoscopic surgery and 88 (33%) by robot-assisted thoracoscopic surgery. The conversion rate was 16% (n = 43). Successful MIS resection was achieved in 77% of patients. Multivariable regression analysis showed that pretreatment clinical N stage was a significant determinant of success, but not pretreatment clinical T stage or type of neoadjuvant therapy., Conclusions: Following neoadjuvant systemic therapy for clinical stage IB or IIIB non-small cell lung cancer, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pretreatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection., Competing Interests: Conflict of Interest Statement Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a Scientific Advisory Board Member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion Pharma, and Outpace Bio; and holds patents, royalties, and intellectual property on mesothelin-targeted CAR and other T-cell therapies that have been licensed to ATARA Biotherapeutics, issued a patent method for detection of cancer cells using virus, and has pending patent applications on PD-1 dominant negative receptor, wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system. Memorial Sloan Kettering Cancer Center has licensed intellectual property related to mesothelin-targeted CARs and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. Dr Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Dr Isbell has served as an advisory board member for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. Dr Molena serves on a steering committee for AstraZeneca, as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr Sihag is a member of the AstraZeneca Advisory Board. Dr Rocco has received royalties from Scanlan International, has served as an uncompensated advisor for AstraZeneca, and has served as a consultant for Medtronic. Dr Jones is a member of the advisory council for AstraZeneca and receives research grant support from Merck. Dr Park has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, serves as a consultant to CEEVRA, and has received institutional research support from Intuitive Surgical. Dr Rusch reports unreimbursed participation in Data Safety and Monitoring Committees for Cancer Research UK MARS II and RAMONA trials. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Frailty, rather than age, is associated with postoperative morbidity and mortality. We sought to determine whether preoperative frailty as defined by a novel scoring system could predict the outcomes among older patients undergoing esophagectomy. Methods: We identified patients 65 years or older who underwent esophagectomy between 2011 and 2021 at our institution. Frailty was assessed using the MSK-FI, which consists of 1 component related to functional status and 10 medical comorbidities. We used a multivariable logistic regression model to test for the associations between frailty and short-term outcomes, with continuous frailty score as the predictor and additionally adjusted for age and Eastern Cooperative Oncology Group performance status. Results: In total, 447 patients were included in the analysis (median age of 71 years [interquartile range, 68-75]). Most of the patients underwent neoadjuvant treatment (81%), an Ivor Lewis esophagectomy (86%), and minimally invasive surgery (55%). A total of 22 patients (4.9%) died within 90 days of surgery, 144 (32%) had a major complication, 81 (19%) were readmitted, and 31 (7.2%) were discharged to a facility. Of the patients who died within 90 days, 19 had a major complication, yielding a failure-to-rescue rate of 13%. The risk of 30-day major complications (OR, 1.24 [95% CI, 1.09-1.41]; p = 0.001), readmissions (OR, 1.31 [95% CI, 1.13-1.52]; p < 0.001), and discharge to a facility (OR, 1.86 [95% CI, 1.49-2.37]; p < 0.001) increased with increasing frailty. Frailty and 90-day mortality were not associated. Conclusions: Frailty assessment during surgery decision-making can identify patients with a high risk of morbidity.

Objectives: The study objectives were to assess the outcomes of lung resection in patients with non-small cell lung cancer previously treated with nonoperative treatment and to identify prognostic factors associated with survival., Methods: Patients who underwent surgery (2010-2022) after initial nonoperative treatment at a single institution were identified from a prospectively maintained database. Exclusion criteria included metachronous cancer, planned neoadjuvant therapy, and surgery for diagnostic or palliative indications. Cox models were constructed for overall survival and event-free survival. Survival of patients with stage IV disease was compared with survival of a nonstudy cohort who did not undergo surgery., Results: In total, 120 patients met the inclusion criteria. Initial clinical stage was early stage in 16%, locoregionally advanced in 25%, and metastatic in 59% of patients. The indication for surgery was recurrence in 18%, local persistent disease in 23%, oligoprogression in 22%, and local control of oligometastatic disease in 38% of patients. Grade 3 or greater complications occurred in 5% of patients; 90-day mortality was 3%. Three-year event-free survival and overall survival were 39% and 73%, respectively. Male sex and lymphovascular invasion were associated with shorter event-free survival and overall survival; younger age and prior radiation therapy were associated with shorter overall survival. Patients with stage IV disease who received salvage lung resection had better overall survival than similar patients who received subsequent systemic therapy and no surgery., Conclusions: In this selected, heterogeneous population, lung resection after initial nonoperative treatment for non-small cell lung cancer was safe. Surgery as local consolidative therapy was associated with encouraging outcomes and should be considered for these patients., Competing Interests: Conflict of Interest Statement Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T-cell therapies, which have been licensed to ATARA Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK Cancer Center has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. Dr Rocco has financial relationships with Scanlan International, Medtronic, and Merck. Dr Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol Myers Squibb, Merck, and Genentech. Dr Park is a consultant for Intuitive Surgical, Medtronic, AstraZeneca, and CEEVRA. Dr Bott is a consultant for AstraZeneca. Dr Rusch reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from National Institutes of Health/Coordinating Center for Clinical Trials. Dr Sihag is a member of the AstraZeneca Advisory Board. Dr Isbell has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. Dr Chaft serves as a consultant for AstraZeneca, Bristol Myers Squibb, Flame Biosciences, Regeneron-Sanofi, Guardant Health, and Arcus Biosciences and receives institutional research funding from AztraZeneca, Bristol Myers Squibb, Merck, and Novartis. Dr Li has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. Dr Gomez reports research funding from Merck, AstraZeneca, Varian, and Bristol Myers Squibb and serves on the advisory boards of MedLearning Group, Medtronic, GRAIL, Johnson & Johnson, AstraZeneca, and Varian. Dr Rimner is a consultant for AstraZeneca, Merck, and MoreHealth, serves as an advisory board member for Merck, and reports institutional grant support from Varian Medical Systems, AstraZeneca, Merck, Pfizer, and Boehringer Ingelheim. Dr Jones serves as a consultant for Merck, AstraZeneca, Genentech, and DAVA Oncology. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aims to answer the question of whether adding mobile cone-beam computed tomography (mCBCT) imaging to shape-sensing robotic-assisted bronchoscopy (ssRAB) translates into a quantifiable improvement in the tool-lesion relationship., Methods: Data from 102 peripheral lung lesions with ≥2 sequential mCBCT orbital spins and from 436 lesions with 0-1 spins were prospectively captured and retrospectively analysed. The primary outcome was the tool-lesion relationship status across the first and the last mCBCT spins. Secondary outcomes included 1) the change in distance between the tip of the sampling tool and the centre of the lesion between the first and the last spins and 2) the per-lesion diagnostic yield., Results: Compared to lesions requiring 0-1 spins, lesions requiring ≥2 spins were smaller and had unfavourable bronchus sign and intra-operative sonographic view. On the first spin, 54 lesions (53%) were designated as non-tool-in-lesion (non-TIL) while 48 lesions (47%) were designated as TIL. Of the 54 initially non-TIL cases, 49 (90%) were converted to TIL status by the last spin. Overall, on the last spin, 96 out of 102 lesions (94%) were defined as TIL and six out of 102 lesions (6%) were defined as non-TIL (p<0.0001). The mean distance between the tool and the centre of the lesion decreased from 10.4 to 6.6 mm between the first and last spins (p<0.0001). The overall diagnostic yield was 77%., Conclusion: Targeting traditionally challenging lung lesions, intra-operative volumetric imaging allowed for the conversion of 90% of non-TIL status to TIL. Guidance with mCBCT resulted in a significant decrease in the distance between the tip of the needle to lesion centre., Competing Interests: Conflict of interest: B.C. Husta has received speaker honoraria from Intuitive Surgical and Siemens Healthineers. B.C. Husta is national co-principal investigator for a study sponsored by Intuitive Surgical. P.S. Adusumilli declares research funding from ATARA Biotherapeutics; has served as a Scientific Advisory Board Member and Consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion Pharma and Outpace Bio; and has patents, royalties and intellectual property on mesothelin-targeted CAR and other T-cell therapies, which have been licensed to ATARA Biotherapeutics (issued patent for a method for detection of cancer cells using virus, and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system); Memorial Sloan Kettering Cancer Center has licensed intellectual property related to mesothelin-targeted CARs and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. R.P. Lee has received speaker honoraria from Intuitive Surgical. B.J. Park has received speaker honoraria from CEEVRA, AstraZeneca, Medtronic and Intuitive Surgical. G. Rocco has financial relationships with Medtronic, Merck, AstraZeneca, CEEVRA and Scanlan International. M.J. Bott has received speaker honoraria from Intuitive Surgical, and serves as a consultant for AstraZeneca and Iovance Biotherapeutics. M. Chawla serves on an advisory board for Intuitive Surgical. O. Kalchiem-Dekel is an associate editor of this journal. All other authors have no conflicts to disclose., (Copyright ©The authors 2024.)

Background: Despite surgical resection, long-term survival of patients with resectable non-small cell lung cancer (NSCLC) remains poor. Adjuvant chemotherapy, the standard of care for locally advanced NSCLC, provides a marginal 5.4% benefit in survival. Immune checkpoint inhibitors (ICIs) have shown a significant survival benefit in some patients with advanced NSCLC and are being evaluated for perioperative use in resectable NSCLC., Methods: We conducted a literature search using the PubMed online database to identify clinical trials of immunotherapy in resectable NSCLC and studies analyzing biomarkers and immune priming strategies., Results: Building on previous phase I and II trials, randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab in the treatment of NSCLC with improvement of event-free/disease-free survival of 24% to 42%, leading to United States Food and Drug Administration approval of these drugs in the treatment of resectable NSCLC. Three additional phase III trials have also recently reported the use of immunotherapy both before and after surgery, with pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. Perioperative ICI therapy has comparable perioperative morbidity to chemotherapy alone and does not impair surgical outcomes., Conclusions: Perioperative immunotherapy, in combination with chemotherapy, is safe and improves outcomes in patients with resectable NSCLC. Questions regarding patient selection, the need for adjuvant ICI therapy after neoadjuvant chemoimmunotherapy, and the duration of perioperative immunotherapy remain to be answered by future trials., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA lung adenocarcinoma., Methods: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA lung adenocarcinoma (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive lung adenocarcinoma, or with follow-up of less than 2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing., Results: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs 29%; P = .047). Patients with late recurrence had more aggressive pathologic features (International Association for the Study of Lung Cancer grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence., Conclusions: Late recurrence of lung adenocarcinoma after resection is more common than previously reported. Patients without disease more than 2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more aggressive follow-up., Competing Interests: Conflict of Interest Statement B.J.P. has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, consultants for CEEVRA, and has received research support from Intuitive Surgical. P.S.A. declares research funding from ATARA Biotherapeutics, is a scientific advisory board member/consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio, has patents, royalties, and intellectual property on T-cell therapies, licensed to ATARA Biotherapeutics, and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. M.S.K. has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T-cell therapies to ATARA Biotherapeutics. D.M. serves on a steering committee for AstraZeneca, consults for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. S.S. serves on the AstraZeneca Advisory Board. M.J.B. consults for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. G.R. has financial relationships with Scanlan International, AstraZeneca, and Medtronic. J.M.I. has served on advisory boards for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. D.R.J. serves on the Advisory Council for AstraZeneca and receives research grant support from Merck. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aging is associated with a decline in the number and fitness of adult stem cells 1-4 . Aging-associated loss of stemness is posited to suppress tumorigenesis 5,6 , but this hypothesis has not been tested in vivo . Here, using physiologically aged autochthonous genetically engineered mouse models and primary cells 7,8 , we demonstrate aging suppresses lung cancer initiation and progression by degrading stemness of the alveolar cell of origin. This phenotype is underpinned by aging-associated induction of the transcription factor NUPR1 and its downstream target lipocalin-2 in the cell of origin in mice and humans, leading to a functional iron insufficiency in the aged cells. Genetic inactivation of the NUPR1-lipocalin-2 axis or iron supplementation rescue stemness and promote tumorigenic potential of aged alveolar cells. Conversely, targeting the NUPR1- lipocalin-2 axis is detrimental to young alveolar cells via induction of ferroptosis. We find that aging-associated DNA hypomethylation at specific enhancer sites associates with elevated NUPR1 expression, which is recapitulated in young alveolar cells by inhibition of DNA methylation. We uncover that aging drives a functional iron insufficiency, which leads to loss of stemness and tumorigenesis, but promotes resistance to ferroptosis. These findings have significant implications for the therapeutic modulation of cellular iron homeostasis in regenerative medicine and in cancer prevention. Furthermore, our findings are consistent with a model whereby most human cancers initiate in young individuals, revealing a critical window for such cancer prevention efforts.

Objective: Shape-sensing robotic-assisted bronchoscopy is an emerging technology for the sampling of pulmonary lesions. We seek to characterize the shape-sensing robotic-assisted bronchoscopy learning curve at an academic center., Methods: Shape-sensing robotic-assisted bronchoscopy procedures performed by 9 proceduralists at a single institution were analyzed. Cumulative sum analyses were performed to examine diagnostic sampling and procedure time over each operator's first 50 cases, with the acceptable yield threshold set to 73%., Results: During the study period, 442 patients underwent sampling of 551 lesions. Each operator sampled 61 lesions (interquartile range, 60-63 lesions). Lesion size was 1.90 cm (interquartile range, 1.33-2.80 cm). The median procedure time for single-target cases decreased from 62 minutes during the first 10 cases to 39 minutes after case 40 (P < .001). The overall diagnostic yield was 72% (range, 58%-83%). Six of 9 operators achieved proficiency over the study period. An aggregated cumulative sum analysis of those who achieved competency demonstrated a steep improvement between lesions 1 and 21 and crossing of the competency threshold by lesion 25. Temporal analysis of yield-related lesion characteristics demonstrated that at approximately lesion 20, more challenging lesions were increasingly targeted, as evidenced by smaller target size, higher rates of unfavorable radial endobronchial ultrasound views, and a negative bronchus sign., Conclusions: Skills acquisition in shape-sensing robotic-assisted bronchoscopy is variable. Approximately half of proceduralists become facile with the technology within 25 lesions. After the initial learning phase, operators increasingly target lesions with more challenging features. Overall, these findings can inform certification and competency standards and provide new users with expectations related to performance over time., Competing Interests: Conflict of Interest Statement Dr Boot has received consulting fees from Astra-Zeneca and Intuitive Surgical, speaker honoraria from Intuitive Surgical, and research funding from Obsidian Biotherapeutics. Dr Husta has received speaker fees from Intuitive Surgical and Siemens Healthineers. Dr Adusumilli received research funding from ATARA Biotherapeutics, is a Scientific Advisory Board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion Pharma, and Outpace Bio, and holds patents, royalties and intellectual property on mesothelin-targeted CAR and other T-cell therapies that have been licensed to ATARA Biotherapeutics, issued patent method for detection of cancer cells using virus, and pending patent applications on PD-1 dominant negative receptor, wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system. Dr Beattie has received consultant and speaker fees from Intuitive Surgical. Dr Park has received speaker honoraria from Intuitive Surgical and Medtronic and is a stockholder with CEEVRA. Dr Jones is a member of the Advisory Council for AstraZeneca and receives research grant support from Merck. Dr Chawla is a member of the Ion Medical Advisory Board for Intuitive Surgical. Dr Rocco has financial relationships with Medtronic, Merck, and Scanlan International. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: There is a lack of knowledge regarding the use of prognostic features in stage I lung adenocarcinoma (LUAD). Thus, we investigated clinicopathologic features associated with recurrence after complete resection for stage I LUAD., Methods: We performed a retrospective analysis of patients with pathologic stage I LUAD who underwent R0 resection from 2010 to 2020. Exclusion criteria included history of lung cancer, induction or adjuvant therapy, noninvasive or mucinous LUAD, and death within 90 days of surgery. Fine and Gray competing-risk regression assessed associations between clinicopathologic features and disease recurrence., Results: In total, 1912 patients met inclusion criteria. Most patients (1565 [82%]) had stage IA LUAD, and 250 developed recurrence: 141 (56%) distant and 109 (44%) locoregional only. The 5-year cumulative incidence of recurrence was 12% (95% CI, 11%-14%). Higher maximum standardized uptake value of the primary tumor (hazard ratio [HR], 1.04), sublobar resection (HR, 2.04), higher International Association for the Study of Lung Cancer grade (HR, 5.32 [grade 2]; HR, 7.93 [grade 3]), lymphovascular invasion (HR, 1.70), visceral pleural invasion (HR, 1.54), and tumor size (HR, 1.30) were independently associated with a hazard of recurrence. Tumors with 3 to 4 high-risk features had a higher cumulative incidence of recurrence at 5 years than tumors without these features (30% vs 4%; P < .001)., Conclusions: Recurrence after resection for stage I LUAD remains an issue for select patients. Commonly reported clinicopathologic features can be used to define patients at high risk of recurrence and should be considered when assessing the prognosis of patients with stage I disease., Competing Interests: Conflict of Interest Statement Dr Rocco has financial relationships with Scanlan International, AstraZeneca, and Medtronic. Dr Molena serves on a steering committee for AstraZeneca, consults for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr Park has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, consults for CEEVRA, and has received research support from Intuitive Surgical. Dr Chaft consults for AstraZeneca, Bristol-Myers Squibb, Merck, Regeneron-Sanofi, Guardant Health, and Lily and receives research funding from AztraZeneca, Bristol-Myers Squibb, Merck, and Beigene. Dr Bott consults for AstraZeneca, Iovance Biotherapeutics, Intuitive Surgical, and receives research support from Obsidian Therapeutics. Dr Rusch reports grant support from Genelux and Genentech, and travel support from Intuitive Surgical and National Institutes of Health/Coordinating Center for Clinical Trials. Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on T-cell therapies licensed to ATARA Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. Dr Sihag serves on the AstraZeneca advisory board. Dr Isbell has served on advisory boards for AstraZeneca and Merck; as an uncompensated steering board member for Genentech; has received research support from ArcherDx/Invitae, Guardant Health, GRAIL, Intuitive Surgical; has received travel support from Intuitive Surgical; and has equity/ownership interest in LumaCyte. Dr Jones serves on the advisory council for AstraZeneca and receives research grant support from Merck. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy., Summary Background Data: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment., Methods: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al., Results: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values., Conclusions: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation., Competing Interests: The authors have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used., Methods: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery., Results: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m 2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m 2 ). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy)., Conclusion: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

BRCA1-associated protein 1 (BAP1) has emerged as a major tumor suppressor gene in diverse cancer types, notably in malignant pleural mesothelioma (DPM), and has also been identified as a germline cancer predisposition gene for DPM and other select cancers. However, its role in the response to DNA damage has remained unclear. Here, we show that BAP1 inactivation is associated with increased DNA damage both in Met-5A human mesothelial cells and human DPM cell lines. Through proteomic analyses, we identified PRKDC as an interaction partner of BAP1 protein complexes in DPM cells and 293 T human embryonic kidney cells. PRKDC encodes the catalytic subunit of DNA protein kinase (DNA-PKcs) which functions in the nonhomologous end-joining (NHEJ) pathway of DNA repair. Double-stranded DNA damage resulted in prominent nuclear expression of BAP1 in DPM cells and phosphorylation of BAP1 at serine 395. A plasmid-based NHEJ assay confirmed a significant effect of BAP1 knockdown on cellular NHEJ activity. Combination treatment with X-ray irradiation and gemcitabine (as a radiosensitizer) strongly suppressed the growth of BAP1-deficient cells. Our results suggest reciprocal positive interactions between BAP1 and DNA-PKcs, based on phosphorylation of BAP1 by the latter and deubiquitination of DNA-PKcs by BAP1. Thus, functional interaction of BAP1 with DNA-PKcs supports a role for BAP1 in NHEJ DNA repair and may provide the basis for new therapeutic strategies and new insights into its role as a tumor suppressor., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort., Methods: All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors., Results: In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates., Conclusions: The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To investigate the association between operative time and postoperative outcomes., Background: The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully., Methods: Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects., Results: In total, 1651 patients were included. The median age was 68 years (interquartile range, 61-74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7-3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures ( P =0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20-1.57; P <0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21-1.64; P <0.0001). Operative time was also associated with longer hospital length of stay (β, 1.09; 95% CI, 1.04-1.14; P =0.001)., Conclusions: Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection., Materials and Methods: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM- (residual tumor >1 mm from the CRM), CRM-close (residual tumor >0 to 1 mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per the Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications., Results: Of the 519 patients included, 351 (68%) had CRM-, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival [DFS; CRM+ vs. CRM-: hazard ratio (HR), 1.53 [95% CI, 1.03-2.28]; P =0.034] and overall survival (OS; CRM+ vs. CRM-: HR, 1.97 [95% CI, 1.32-2.95]; P <0.001). Survival was not significantly different between CRM-close and CRM-. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP-: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P =0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P =0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P =0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P =0.11)., Conclusion: CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM- were similar., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Pedicled flaps (PFs) have historically served as the preferred option for reconstruction of large chest wall defects. More recently, the indications for microvascular-free flaps (MVFFs) have increased, particularly for defects in which PFs are inadequate or unavailable. We sought to compare oncologic and surgical outcomes between MVFFs and PFs in reconstructions of full-thickness chest wall defects., Methods: We retrospectively identified all patients who underwent chest wall resection at our institution from 2000 to 2022. Patients were stratified by flap reconstruction. End points were defect size, rate of complete resection, rate of local recurrence, and postoperative outcomes. Multivariable analysis was performed to identify factors associated with complications at 30 days., Results: In total, 536 patients underwent chest wall resection, of whom 133 had flap reconstruction (MVFF, n = 28; PF, n = 105). The median (interquartile range) covered defect size was 172 cm 2 (100-216 cm 2 ) for patients receiving MVFF versus 109 cm 2 (75-148 cm 2 ) for patients receiving PF (P = .004). The rate of R0 resection was high in both groups (MVFF, 93% [n = 26]; PF, 86% [n = 90]; P = .5). The rate of local recurrence was 4% in MVFF patients (n = 1) versus 12% in PF patients (n = 13, P = .3). Postoperative complications were not statistically different between groups (odds ratio for PF, 1.37; 95% confidence interval, 0.39-5.14]; P = .6). Operative time >400 minutes was associated with 30-day complications (odds ratio, 3.22; 95% confidence interval, 1.10-9.93; P = .033)., Conclusions: Patients with MVFFs had larger defects, a high rate of complete resection, and a low rate of local recurrence. MVFFs are a valid option for chest wall reconstructions., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective is to determine how the COVID-19 pandemic affected care for patients undergoing thoracic surgery for cancer., Background: The COVID-19 pandemic accelerated the adoption of telemedicine., Methods: Characteristics and outcomes of new patients seen between March 1 and June 30, 2019, and the same period in 2020 were compared. Patients who did not undergo surgery were excluded. Patients who had a telemedicine visit (new and established) in the 2020 period were asked to complete a survey., Results: In total, 624 new patients were seen in 2019 versus 299 in 2020 (52% reduction); 45% of patients (n=136) in 2020 were seen via telemedicine. There was no statistically significant difference in time to surgery, pathological upstaging, or postsurgical complications between 2019 and 2020. In total, 1085 patients (new and established) had a telemedicine visit in 2020; 239 (22%) completed the survey. A majority replied that telemedicine was equivalent to in-person care (77%), did not impair care quality (84%), resulted in less stress (69%) and shorter waits (86%), was more convenient (92%), saved money and commuting time (93%), and expanded who could attend visits (91%). Some patients regretted the loss of human interaction (71%). Most would opt for telemedicine after the pandemic (60%), although some would prefer in-person format for initial visits (55%) and visits with complex discussions (49%). Only 21% were uncomfortable with the telemedicine technology., Conclusions: Telemedicine enabled cancer care to continue during the COVID-19 pandemic without delays in surgery, cancer progression, or worsened postoperative morbidity and was generally well received., Competing Interests: M.J.B. is a consultant for AstraZeneca. J.M.I. has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. B.J.P. has served as a proctor for Intuitive Surgical and a consultant for COTA. V.W.R. reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from NIH/Coordinating Center for Clinical Trials. D.R.J. serves as a consultant for AstraZeneca and on a Clinical Trial Steering Committee for Merck. G.R. has a financial relationship with Scanlan. D.M. serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol Myers Squibb, Merck, and Genentech. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Molecular diagnostic assays require samples with high nucleic acid content to generate reliable data. Similarly, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) requires samples with adequate tumor content. We investigated whether shape-sensing robotic-assisted bronchoscopy (ssRAB) provides adequate samples for molecular and predictive testing., Methods: We retrospectively identified diagnostic samples from a prospectively collected database. Pathologic reports were reviewed to assess adequacy of samples for molecular testing and feasibility of PD-L1 IHC. Tumor cellularity was quantified by an independent pathologist using paraffin-embedded sections. Univariable and multivariable linear regression models were constructed to assess associations between lesion- and procedure-related variables and tumor cellularity., Results: In total, 128 samples were analyzed: 104 primary lung cancers and 24 metastatic lesions. On initial pathologic assessment, ssRAB samples were deemed to be adequate for molecular testing in 84% of cases; on independent review of cellular blocks, median tumor cellularity was 60% (interquartile range, 25%-80%). Hybrid capture-based next-generation sequencing was successful for 25 of 26 samples (96%), polymerase chain reaction-based molecular testing (Idylla; Biocartis) was successful for 49 of 52 samples (94%), and PD-L1 IHC was successful for 61 of 67 samples (91%). Carcinoid and small cell carcinoma histologic subtype and adequacy on rapid on-site evaluation were associated with higher tumor cellularity., Conclusions: The ssRAB platform provided adequate tissue for next-generation sequencing, polymerase chain reaction-based molecular testing, and PD-L1 IHC in >80% of cases. Tumor histology and adequacy on intraoperative cytologic assessment might be associated with sample quality and suitability for downstream assays., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE)., Background Data: A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy., Methods: We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019. SE was defined as esophagectomy performed >90 days after chemoradiation ("for time") and esophagectomy performed for recurrence after curative-intent chemoradiation ("for recurrence"). The odds of postoperative serious complications were assessed by multivariable logistic regression. The relationship between SE and OS and DFS were quantified using Cox regression models., Results: Of 1137 patients identified, 173 (15%) underwent SE. Of those, 61 (35%) underwent SE for recurrence, and 112 (65%) underwent SE for time. The odds of experiencing any serious complication [odds ratio, 2.10 (95% CI, 1.37-3.20); P =0.001] or serious pulmonary complication [odds ratio, 2.11 (95% CI, 1.31-3.42); P =0.002] were 2-fold higher for SE patients; SE patients had a 1.5-fold higher hazard of death [hazard ratio, 1.56 (95% CI, 1.25-1.94); P <0.0001] and postoperative recurrence [hazard ratio, 1.43 (95% CI, 1.16-1.77); P =0.001]. Five-year OS for nonsalvage esophagectomy was 45% [(95% CI, 41.6%-48.6%) versus 26.5% (95% CI, 20.2%-34.8%) for SE (log-rank P <0.001)]. Five-year OS for SE for time was 27.1% [(95% CI, 19.5%-37.5%) versus 25.2% (95% CI, 15.3%-41.5%) for SE for recurrence ( P =0.611)]., Conclusions: SE is associated with a higher risk of serious postoperative complications and shorter DFS and OS., Competing Interests: M.J.B. is a consultant for AstraZeneca. D.H.I. reports research funding to Memorial Sloan Kettering from Astellas, Eli Lilly, Pieris, and Taiho and consulting for AstraZeneca, Amgen, Bayer, Bristol-Myers Squibb, and Roche. J.M.I. has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. B.J.P. has served as a proctor for Intuitive Surgical and as a consultant for COTA. Y.Y.J. reports grant funding from Bayer, Bristol-Myers Squibb, Cycle for Survival, US Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, US National Cancer Institute, and RGENIX; consulting fees from AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Imugene, Merck, Merck Serono, Michael J Hennessy Associates, Paradigm Medical Communications, Pfizer, RGENIX, Seagen, and Zymeworks; honoraria from AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Imugene, Merck, Merck Serono, Michael J Hennessy Associates, Paradigm Medical Communications, Pfizer, RGENIX, Seagen, and Zymeworks; and stock or stock options for RGENIX. G.R. has a financial relationship with Scanlan, AstraZeneca, and Medtronic. V.W.R. reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from NIH/Coordinating Center for Clinical Trials. A.J.W. reports stock and other ownership interests in Simphotek, consulting or advisory roles for AstraZeneca, MORE Health, and NanoVi, research funding from CivaTech Oncology, and travel, accommodations, and expenses from CivaTech Oncology. D.R.J. serves as a consultant for AstraZeneca and on a Clinical Trial Steering Committee for Merck. D.M. serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol-Myers Squibb, Merck, and Genentech. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC., Summary of Background Data: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy., Methods: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression., Results: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group., Conclusions: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pulmonary nodules (lesions <3 cm in size) are commonly identified on computed tomographic scans, but radiographic features alone are inadequate to reliably differentiate between benign and malignant etiologies. Therefore, tissue biopsy remains the standard approach to determine the appropriate treatment course for many patients with pulmonary nodules. Although percutaneous biopsy is highly accurate, it poses substantial risks of procedural complications, including pneumothorax and bleeding. Robotic bronchoscopy has recently been developed to overcome many of the limitations of previous navigational platforms. Here, we explore the currently available systems for robotic bronchoscopy-in particular, electromagnetic-navigation robotic-assisted bronchoscopy and shape-sensing robotic-assisted bronchoscopy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

About 50% of patients with early-stage, surgically resected lung cancer will develop distant metastasis. There remains an unmet need to identify patients likely to develop recurrence and to design innovative therapies to decrease this risk. Two primary isoforms of BRMS1, v1 and v2, are present in humans. Using next-generation sequencing of BRMS1 on matched human noncancerous lung tissue and non-small cell lung cancer (NSCLC) specimens, we identified single-nucleotide polymorphism (SNP) rs1052566 that results in an A273V mutation of BRMS1v2. This SNP is homozygous ( BRMS1v2 A273V/A273V ) in 8% of the population and correlates with aggressive biology in lung adenocarcinoma (LUAD). Mechanistically, we show that BRMS1v2 A273V abolishes the metastasis suppressor function of BRMS1v2 and promotes robust cell invasion and metastases by activation of c-fos-mediated gene-specific transcriptional regulation. BRMS1v2 A273V increases cell invasion in vitro and increases metastases in both tail-vein injection xenografts and LUAD patient-derived organoid (PDO) intracardiac injection metastasis in vivo models. Moreover, we show that BRMS1v2 A273V fails to interact with nuclear Src, thereby activating intratumoral c-fos in vitro. Higher c-fos results in up-regulation of CEACAM6 , which drives metastases in vitro and in vivo. Using both xenograft and PDO metastasis models, we repurposed T5224 for treatment, a c-fos pharmacologic inhibitor investigated in clinical trials for arthritis, and observed suppression of metastases in BRMS1v2 A273V/A273V LUAD in mice. Collectively, we elucidate the mechanism of BRMS1v2 A273V/A273V -induced metastases and offer a putative therapeutic strategy for patients with LUAD who have this germline alteration.

Purpose: Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood., Experimental Design: All cases of metastatic lung cancer treated with PD-(L)1 blockade at Memorial Sloan Kettering were reviewed. In acquired resistance (complete/partial response per RECIST, followed by progression), clinical patterns were distinguished as oligo (OligoAR ≤ 3 lesions of disease progression) or systemic (sAR). We analyzed the relationships between patient characteristics, burden/location of disease, outcomes, and efficacy of therapeutic interventions., Results: Of 1,536 patients, 312 (20%) had an initial response and 143 developed AR (9% overall, 46% of responders). OligoAR was the most common pattern (80/143, 56%). Baseline tumor mutational burden, depth of response, and duration of response were significantly increased in oligoAR compared with sAR (P < 0.001, P = 0.03, P = 0.04, respectively), whereas baseline PD-L1 and tumor burden were similar. Post-progression, oligoAR was associated with improved overall survival (median 28 months vs. 10 months, P < 0.001) compared with sAR. Within oligoAR, post-progression survival was greater among patients treated with locally-directed therapy (e.g., radiation, surgery; HR, 0.41; P = 0.039). Fifty-eight percent of patients with oligoAR treated with locally-directed therapy alone are progression-free at last follow-up (median 16 months), including 13 patients who are progression-free more than 2 years after local therapy., Conclusions: OligoAR is a common and distinct pattern of acquired resistance to PD-(L)1 blockade compared with sAR. OligoAR is associated with improved post-progression survival and some cases can be effectively managed with local therapies with durable benefit., (©2022 American Association for Cancer Research.)

Background: Isolated local recurrence after curative esophagectomy for esophageal cancer is a rare event. Although it is potentially curable, management can be challenging., Methods: We retrospectively reviewed all patients undergoing esophagectomy for esophageal adenocarcinoma (EAC) from 2000 to 2019. Date of recurrence was defined as the date at which the initial abnormal surveillance study result or symptomatic presentation led to further workup and subsequent pathologic diagnosis of recurrence. Overall survival after recurrence was estimated using Kaplan-Meier methods and compared between treatment groups using the log-rank test., Results: Of the 1370 patients with EAC who underwent esophagectomy in our cohort, 531 (39%) developed recurrence of their disease. The 5-year cumulative incidence of recurrence was 2.7% (95% CI, 2.0%-3.6%) for local, 6.3% (95% CI, 5.2%-7.8%) for regional, and 22.0% (95% CI, 20.0%-24.4%) for distant recurrences. On univariable and multivariable competing-risk regression analysis, advanced pT stage, signet ring histology, and serious complication were independently associated with local recurrence. Patients with local recurrence treated with definitive therapy had a median survival after recurrence of 19.1 months (95% CI, 11.4-33.2 months) compared with 10.6 months (95% CI, 8.5-14.2 months) for chemotherapy or radiotherapy alone and 1.73 months (95% CI, 0.23-15.6 months) for no treatment (P < .001)., Conclusions: Isolated local recurrence occurred in only 3% of patients. Advanced T stage, signet cell histology, and serious complication were risk factors for recurrence. Although complex surgical resection is required, in very select cases, more aggressive treatment may be warranted., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to determine the extent of lymphadenectomy that optimizes staging and survival in patients with locally advanced EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy., Summary of Background Data: Several studies have found that a more extensive lymphadenectomy leads to better disease-specific survival in patients treated with surgery alone. Few studies, however, have investigated whether this association exists for patients treated with neoadjuvant chemoradiotherapy., Methods: We examined our prospective database and identified patients with EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy between 1995 and 2017. Overall survival (OS) and DFS were estimated using Kaplan-Meier methods, and a multivariable Cox proportional hazards model was used to identify independent predictors of OS and DFS. The relationship between the total number of nodes removed and 5-year OS or DFS was plotted using restricted cubic spline functions., Results: In total, 778 patients met the inclusion criteria. The median number of excised nodes was 21 (interquartile range, 16-27). A lower number of excised lymph nodes was independently associated with worse OS and DFS (OS: hazard ratio, 0.98; confidence interval, 0.97-1.00; P = 0.013; DFS: hazard ratio, 0.99; confidence interval, 0.98-1.00; P = 0.028). Removing 25 to 30 lymph nodes was associated with a 10% risk of missing a positive lymph node. Both OS and DFS improved with up to 20 to 25 lymph nodes removed, regardless of treatment response., Conclusions: The optimal extent of lymphadenectomy to enhance both staging and survival after chemoradiotherapy, regardless of treatment response, is approximately 25 lymph nodes., Competing Interests: The authors declare no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non-small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC., Methods: We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points., Results: In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy., Conclusions: Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis., Methods: All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors., Results: Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)-was associated with increased risk of recurrence., Conclusions: One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Anatomical resection-often by lobectomy-is the standard of care for patients with early stage NSCLC. With increased diagnosis, survival, and prevalence of persons with early stage NSCLC, the incidence of second primary NSCLC, and consequently, the need for contralateral lobectomy for a metachronous cancer, is increasing. Perioperative outcomes after contralateral lobectomy are unknown., Methods: Among patients who underwent contralateral lobectomy for second primary NSCLC during 1995 to 2020, we evaluated 90-day mortality and major morbidity (Clavien-Dindo grades 3-5) rates and their association with clinicopathologic variables, including the year of contralateral lobectomy and duration between lobectomies., Results: A total of 98 patients underwent contralateral lobectomy for second primary NSCLC; 51 during an early time period (1995-2009) and 47 from a late time period (2010-2020). There were five mortalities and 23 patients with major morbidities after contralateral lobectomy; both rates decreased in 2010 to 2020 compared with 1995 to 2009 (mortality 10%-0%, major morbidity 35%-11%). Major morbidity was associated with an interval of less than 1 year between lobectomies, a diffusing capacity of the lung for carbon monoxide <80%, and right lower lobe resections. Mortality was associated with squamous cell carcinoma. Patients who underwent contralateral lobectomy for stage I NSCLC had 74% (95% confidence interval: 64%-85%) 3-year overall survival and 15% (95% confidence interval: 6.5%-24%) 3-year lung cancer cumulative incidence of death., Conclusions: Contralateral lobectomy for second primary early stage NSCLC was associated with poor outcomes before 2010. Since 2010, perioperative and long-term outcomes of contralateral lobectomy have been comparable with reported outcomes after unilateral lobectomy., (© 2022 The Authors.)