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Objective: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV 1 ) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV 1 /ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy., Background: 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 to II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV 1 /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 and colleagues' study., Results: In 946 patients, the ppoFEV 1 /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 ppoFEV 1 /ppoDLCO of 45% to 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 ppoFEV 1 and ppoDLCO values., Conclusions: The ppoFEV 1 /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: 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, 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. D.M. 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. B.J.P. has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic, serves as a consultant to CEEVRA, and has received institutional research support from Intuitive Surgical. M.J.B. is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. 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. S.S. is a member of the AstraZeneca Advisory Board. J.M.I. 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. D.R.J. 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. G.R. has financial relationships with Scanlan International, Medtronic, and Merck. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, 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.)

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.)

Objective: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC)., Background: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC., Methods: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS)., Results: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%., Conclusions: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence., Competing Interests: P.S.A. declares research funding from ATARA Biotherapeutics; Scientific Advisory Board Member and Consultant for ATARA Biotherapeutics, Abound Bio, Adjuvant Genomics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnston and Johnston, Orion pharma, OutpaceBio; Patents, royalties and intellectual property on mesothelin-targeted CAR and other T-cell therapies, which 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. His laboratory work is supported by grants from the National Institutes of Health (P30 CA008748, R01 CA236615-01, R01 CA235667, and U01 CA214195), the U.S. Department of Defense (BC132124, LC160212, CA170630, CA180889, and CA200437), the Batishwa Fellowship, the Cycle for Survival fund, the Comedy versus Cancer Award, the DallePezze Foundation, the Derfner Foundation, the Esophageal Cancer Education Fund, the Geoffrey Beene Foundation, the Memorial Sloan Kettering Technology Development Fund, the Miner Fund for Mesothelioma Research, the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. 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. David Restle and Jennie K. Choe are supported, in part, by the National Institutes of Health (T32CA009501-33). The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, 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: 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: We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences., Summary Background Data: GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinico-pathological and oncological differences between the 2 have not been fully evaluated., Methods: We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared., Results: In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC ( P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer ( P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001)., Conclusions: GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 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.)

Objective: To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival., Summary Background Data: pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint., Methods: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adeno-carcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis., Results: Among 788 patients, median follow-up was 37.5 months (range, 0.4210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival ( P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR., Conclusions: ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to >90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to > 90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies., (Copyright © 2020 Wolters Kluwer Health, 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: We sought to quantify and characterize long-term consequences of pneumonectomy, with particular attention to nononcologic mortality., Summary of Background Data: Pneumonectomy is associated with profound changes in cardiopulmonary physiology. Studies of long-term outcomes after pneumonectomy typically report generalized measures, such as disease-free and overall survival., Methods: Patients undergoing lobectomy or pneumonectomy for lung cancer at our institution from 2000 to 2018 were reviewed. Propensity-score matching was performed for 12 clinicopathologic factors. Ninety-day complications and deaths were compared. Five-year cumulative incidence of oncologic and nononcologic mortality were compared using competing risks approaches., Results: From 3339 lobectomy and 355 pneumonectomy patients identified, we derived 318 matched pairs. At 90 days, rates of overall complications were similar (46% for pneumonectomy vs 43% for lobectomy; P = 0.40), but rates of major complications (21% vs 13%; P = 0.005) and deaths (6.9% vs 1.9%; P = 0.002) were higher the pneumonectomy cohort. The cumulative incidence of oncologic mortality was not significantly different between cohorts (P = 0.9584). However, the cumulative incidence of nononcologic mortality was substantially higher in the pneumonectomy cohort for both date of surgery and 1-year landmark analyses (P < 0.0001 and P = 0.0002, respectively). Forty-five pneumonectomy patients (18%) died of nononcologic causes 1-5 years after surgery; pneumonia (n = 21) and myocardial infarction (n = 10) were the most common causes. In pneumonectomy patients, preexisting cardiac comorbidity and low diffusion capacity of the lungs for carbon monoxide were predictive of nononcologic mortality., Conclusions: Compared to lobectomy, excess mortality after pneumonectomy extends beyond 1 year and is driven primarily by nononcologic causes. Pneumonectomy patients require lifelong monitoring and may benefit from expeditious assessment and intervention at the initial signs of illness., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with PMNSGCTs undergoing resection and multidisciplinary management at a high-volume institution., Summary of Background Data: Outcomes after resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival., Methods: We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression., Results: In total, 113 patients were included [median age, 28 years (range, 16-65)]. Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/- necrosis (20%), viable nonteratomatous germ cell tumor +/- teratoma (41%), and secondary somatic-type malignancy +/- teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P < 0.001) and increasing postoperative STMs (HR, 4.98; P < 0.001) were associated with shorter PFS; necrosis on pathology (HR, 0.42, P = 0.043) was associated with longer PFS., Conclusions: In patients with PMNSGCT undergoing resection, completeness of resection, postoperative pathology, and postoperative STMs were associated with PFS. Induction bleomycin was not associated with pulmonary complications or mortality in patients undergoing resection. Patients undergoing second-line chemotherapy followed by resection have a poor prognosis, with long-term survival of 22%., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To improve understanding of sex differences in clinicopathologic characteristics, treatment and outcomes between male and female patients undergoing esophagectomy for esophageal cancer., Summary Background Data: Esophageal cancer is a male predominant disease, and sex has not been considered in previous studies as an important factor in diagnosis or management. Sex differences in demographics, clinicopathologic characteristics, and postoperative outcomes remain largely undefined., Methods: Retrospective review of 1958 patients (21% female) with esophageal cancer who underwent esophagectomy at a single institution between 1995 and 2017., Results: Most patients had adenocarcinoma (83%); however, the rate of squamous cell carcinoma was significantly higher in females (35% vs 11%, respectively; P < .0001). Females had a lower rate of smoking (62 vs 73%) and heavy alcohol use (12 vs 19%) but a higher rate of previous mediastinal radiation (8.4 vs 1.8%) (P < 0.001). Postoperative mortality and overall survival (OS) were similar between sexes. However, subanalysis of patients with locoregional disease (clinical stage II/III) demonstrated that females received neoadjuvant therapy less frequently than males and had worse OS (median OS 2.56 yrs vs 2.08; P = 0.034). This difference remained significant on adjusted analysis (HR 1.24, 95% CI 1.06-1.46)., Conclusions: Female patients had higher incidence of squamous cell carcinoma despite lower prevalence of behavioral risk factors. Among patients with locoregional disease, undertreatment in females may reflect treatment bias and history of previous mediastinal radiation. Esophageal cancer in females should be considered a unique entity as compared with the presentation and treatment of males.

Objective: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC)., Background: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons., Methods: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes., Results: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS., Conclusions: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment., Competing Interests: All authors declare no conflicts of interest.

Purpose: Endoscopic biopsy after chemoradiation therapy (CRT) for esophageal cancer has been used to determine response to treatment. We wanted to determine if endoscopic biopsy can accurately establish evidence of local pathologic complete response (pCR) in patients undergoing CRT., Methods: We queried a prospectively maintained database for patients seen at Memorial Sloan-Kettering Cancer Center from 1996 to the present who underwent, (1) CRT for local-regionally advanced esophageal cancer, (2) post-CRT endoscopic biopsy, and (3) esophagectomy. Data points included pathology of post-CRT endoscopy and surgical specimens, tumor histology, and survival. Correlations were analyzed by the chi2 test and one-way analysis of variance. Survival comparisons were assessed using the Kaplan-Meier method and log-rank analysis., Results: One hundred fifty-six patients were identified. Over 80% of patients received cisplatin-based chemotherapy and 5040 cGy of radiation. One hundred eighteen patients had no tumor identified on endoscopic biopsy. A negative biopsy at endoscopy was a poor predictor of pCR (negative predictive value: 31%), with 69% having local disease at esophagectomy. A positive biopsy was predictive of residual disease (positive predictive value: 95%). Negative endoscopic biopsy better predicted a pCR for squamous cell carcinomas versus adenocarcinomas (P[r] < 0.001). Nodal status of surgical specimens was not correlated with post-treatment endoscopic findings. Survival was equivalent after surgery in patients with a negative endoscopic biopsy versus patients with positive pathology., Conclusion: A negative endoscopic biopsy is not a useful predictor of a pCR after CRT, final nodal status, or overall survival.

Objective: To determine whether the length of esophageal resection or the operative approach influences outcome for patients with adenocarcinoma of the gastroesophageal junction (GEJ)., Summary Background Data: While R0 resection remains the mainstay of curative treatment of patients with GEJ cancer, the optimal length of esophageal resection remains controversial., Methods: Patients with Siewert I, II, or III adenocarcinoma who underwent complete gross resection without neoadjuvant therapy were identified from a prospectively maintained database. Proximal margin lengths were recorded ex vivo as the distance from the gross tumor edge to the esophageal transection line. Operative approaches were grouped into gastrectomy (limited esophagectomy) or esophagectomy (extended esophagectomy)., Results: From 1985 through 2003, 505 patients underwent R0/R1 gastrectomy (n = 153) or esophagectomy (n = 352) without neoadjuvant treatment. There were no differences in R1 resection rate, number of nodes examined or operative mortality between gastrectomy and esophagectomy. Univariate analysis found >3.8 cm to be the ex vivo proximal margin length (approximately 5 cm in situ) most predictive of improved survival. Multivariable analysis in patients who underwent R0 resection with >or=15 lymph nodes examined (n = 275) found the number of positive lymph nodes, T stage, tumor grade, and ex vivo proximal margin length >3.8 cm to be independent prognostic factors. Subset analysis found that the benefit associated with >3.8 cm margin was limited to patients with T2 or greater tumors and