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The lung represents a frequent site of spread for metastatic melanoma, which has historically been managed with surgical resection achieving promising outcomes. We hypothesized that the role of surgery in the management of melanoma pulmonary metastases (MPM) is evolving among the development of less invasive diagnostic and novel systemic therapeutic strategies.A single-center thoracic surgery database was reviewed and patients who underwent surgical resection of MPM between 1998 and 2019 were identified. Demographic, clinicopathologic, and surgical data were collected and analyzed, as were the annual volumes and indications for surgical resection. A Cochran-Armitage test was used to assess the trend in surgical indication.Three hundred and seventy seven surgical procedures for MPM were performed during the years of study in the care of 347 patients. Patients were predominantly male, with a mean age of 59.3 y. The mean number of annual resections was 17 and while this number initially increased from six in 1998 to a peak of 39 cases in 2008, a decline was subsequently observed. Diagnostic resection decreased from 22% in 1998-1999 to 5% at the peak of procedures in 2008-2009 and to 0 in 2018-2019 (P = 0.02). Curative resection increased from 44% in 1998-1999 to 73% in 2008-2009 (P 0.001) and remained the dominant reason for surgery in later years.Surgical indications in the management of MPM have transformed in conjunction with systemic modalities, and the volume of resections has decreased in the modern era. Despite innovations in systemic management and shifting goals of operative interventions, surgeons continue to play a vital role in caring for these patients with an advanced disease.

Summary Background A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). Methods This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0–2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov , NCT02357992 . Findings Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9–5·8). Overall survival was 91% (95% CI 85–98) at 3 years and 87% (79–95) at 5 years. SABR was tolerated well, with no grade 4–5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85–98) at 3 years and 84% (76–93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45–1·65], p=0·65) from a multivariable analysis. Interpretation Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Funding Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

Objectives Although colorectal cancer bowel segment location has been shown to independently predict the outcomes in early stage disease, it has not been previously studied in the setting of pulmonary metastases. We sought to determine whether colorectal cancer location affects survival after pulmonary metastasectomy. Methods Patients who had undergone pulmonary metastasectomy for colorectal cancer at a single institution from 2011 to 2018 were reviewed. Univariable and multivariable Cox regression analyses were performed to identify predictors of overall survival and disease-free survival. The Kaplan-Meier survival method was used to determine differences between groups. Results A total of 194 patients were evaluated. The median follow-up, survival time, and 5-year survival rate were 36.8 months, 75.8 months, and 57%, respectively, and 122 patients (63%) had experienced disease recurrence at any location. On univariable analysis, age, primary tumor location, pulmonary nodule size, ≥3 pulmonary nodules, and intrathoracic nodal disease were associated with overall survival. On multivariable analysis, patients with left-sided tumors experienced a survival benefit (hazard ratio, 0.31; P = .036). Kaplan-Meier analysis revealed a median survival time of 90 months (95% confidence interval, 82 months to not reached) compared with 55 months (95% confidence interval, 49 months to not reached) for patients with left-sided and rectal tumors, respectively, after metastasectomy (P = .078). Location was not associated with disease-free survival on Cox multivariable regression. Conclusions We found that left-sided colorectal cancer is associated with prolonged survival after pulmonary metastasectomy. Future investigations are required to determine the validity of such findings, including the effect of location in the prognostication for patients who are candidates for pulmonary metastasectomy.

BACKGROUND: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs. METHODS: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques. RESULTS: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications. CONCLUSION: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC. Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.

BACKGROUND: Mutations in the serine-threonine kinase LKB1/STK11 have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early-stage lung adenocarcinoma undergoing surgical therapy. METHODS: Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I-III, chemotherapy-naïve adenocarcinomas (1997–2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments. RESULTS: 104 patients met inclusion criteria. LKB1/STK11 expression (median H-score 102.9) was higher in women (median 123.3) than men (100.0, p=0.004) and in never-smokers (median 145.0) than former/current smokers (100.0, p=0.002). LKB1/STK11 expression was positively correlated with intratumoral infiltration of CD3(+) (r=0.351, P=0.005), CD4(+) (r=0.436, P

Introduction The standard of care for stage IIIA (N2) non–small-cell lung cancer (NSCLC) includes concurrent definitive chemoradiation (dCRT) followed by durvalumab, thus challenging the role of surgery in resectable patients. We assessed locoregional disease control and survival in patients with surgically resected and unresected stage IIIA (N2) NSCLC disease. Patients and Methods We conducted a retrospective analysis from prospectively collected databases at MD Anderson Cancer Center. Patients undergoing neoadjuvant chemotherapy and surgery or dCRT for clinical stage IIIA (N2) disease (2004-2014) were evaluated. Primary outcomes included locoregional disease control, disease-free survival (DFS), and overall survival (OS). Kaplan-Meier outcome analyses were performed. Results Of the 159 resected patients, the majority had lobectomy (82.4%), followed by pneumonectomy (11.9%) and sublobar resection (5.7%). The 30- and 90-day mortality rates were 0.6% and 1.3%, respectively. At median follow-up of 52.8 months, recurrence was 55.3%, with 44.0% having distant and 15.1% locoregional recurrence. At 5 years, OS was 50.8% and DFS was 33.1% Median OS was 61.2 months. A total of 366 patients underwent dCRT, with intensity-modulated radiation in 64.5%, proton therapy in 26.0%, and 3-dimensional conformal radiotherapy in 9.6%. The mean dose was 68.1 Gy. At median follow-up of 20.8 months, recurrence was 53.6%, with distant and locoregional recurrence of 40.7% and 30.3%, respectively. At 5 years, OS was 29.2% and DFS was 20.5%. Median OS was 27.5 months. Conclusion Stage IIIA (N2) NSCLC continues to be a heterogeneous disease, and patients with surgically resected and unresected disease represent different risk populations. Ongoing immunotherapy trials may further redefine treatment algorithms in this complex patient population.

Background and objectives It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. Methods Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. Results Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). Conclusions Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.

Background The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS). Methods We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS. Results There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS. Conclusion The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.

Background Approximately one third of needle biopsies that are performed to rule out malignancy of indeterminate pulmonary nodules detected radiologically during lung cancer screening are negative, thus exposing cancer-free patients to risks of pneumothorax, bleeding, and infection. A noninvasive confirmatory tool (eg, liquid biopsy) is urgently needed in the lung cancer diagnosis setting to stratify patients who should receive biopsy versus those who should be monitored. Methods A novel antigen-independent, 4-color fluorescence in situ hybridization (FISH)-based method was developed to detect circulating tumor cells (CTCs) with abnormalities in gene copy numbers in mononuclear cell-enriched peripheral blood samples from patients with (n = 107) and without (n = 100) lung cancer. Results Identification of CTCs using FISH probes at 10q22.3/CEP10 and 3p22.1/3q29 detected lung cancer cases with 94.2% accuracy, 89% sensitivity, and 100% specificity compared with biopsy. Conclusion The high accuracy of this liquid biopsy method suggests that it may be used as a noninvasive decision tool to reduce the frequency of unnecessary needle biopsy in patients with benign pulmonary lesions.

Background Opioids represent the mainstay for treating postsurgical pain but can cause significant morbidity in addition to dependency. The aim of the study was to determine the incidence of persistent opioid use after lung surgery. Methods Patients who underwent lung resection from 2008 to 2013 for non-small cell lung cancer were identified in the Surveillance, Epidemiology and End Results-Medicare database. Patients were categorized as being chronic, intermittent, or naive preoperative opioid users using information obtained from part D records. Persistent opioid use was defined as having a filled opioid prescription between 3 and 6 months after lung resection. Results A total of 6948 patients were identified, among whom 3946 (56.8%) were opioid naive, 2017 (29.0%) were intermittent opioid users, and 985 (14.2%) were chronic opioid users preoperatively. Persistent opioid use (3-6 months) after lung resection was high (31%), even among opioid-naive patients (17%). Among those who were previously opioid naive, independent predictors of persistent opioid use were receipt of adjuvant radiation or chemotherapy, less than 70 years of age, Charlson comorbidity score of 1 or 2, and residence in zip codes associated with lower education. Conversely, patients who underwent minimally invasive surgery were less likely to have persistent opioid use. Those with persistent opioid use after surgery did not show any trend toward returning to preoperative opioid utilization for at least the first postoperative year. Conclusions Opioid dependence after lung resection in the population over 65 years of age is high but was significantly lower among those who received minimally invasive surgery, in addition to other factors.

Enhanced Recovery After Surgery programs have been shown to effectively reduce opioid prescriptions at discharge after their implementation in several institutions, but little is known regarding the sustainability of this effect. Understanding opioid prescribing patterns after long-term implementation of Enhanced Recovery After Surgery initiatives may help guide further opioid prescription reduction and improvements. Our group aimed to determine whether reductions in opioid prescriptions at discharge are sustained in an Enhanced Recovery After Surgery program for thoracic surgery.This retrospective cohort included 2,081 patients undergoing thoracic surgery within a 4-year Enhanced Recovery After Surgery program from March 2016 through April 2020. Our Enhanced Recovery After Surgery protocol included a standardized multimodal analgesic regimen (ie, preoperative gabapentin, tramadol, intercostal nerve block with liposomal bupivacaine, and intraoperative acetaminophen, and ketorolac) and the rest of the interventions recommended by the Enhanced Recovery After Surgery society guidelines. Our primary outcomes were the presence of opioid prescriptions at discharge (hydrocodone, hydromorphone, and oxycodone) and the total opioid amount prescribed (morphine equivalent daily dose). Multilevel generalized linear models were used to account for surgeon variabilities and types of thoracic resection.Over the study period, the rate of opioid prescriptions at discharge reduced from 35% (Mar 2016) to 25% (Apr 2020), and the amount of opioid prescribed declined from 184 ± 321 morphine equivalent daily dose to 94 ± 251 morphine equivalent daily dose. In multilevel generalized linear models, there was a sustained downward trend in opioid prescriptions over the study period (β -11.8 morphine equivalent daily dose per year, P = .048), which was also directly correlated with the use of minimally invasive surgery (β -84.9 morphine equivalent daily dose for video-assisted thoracoscopic surgery, P.001; β -139.2 morphine equivalent daily dose for robotic-assisted thoracic surgery, P.001), intraoperative opioid administration (β -1.4 morphine equivalent daily dose per 1 morphine equivalent dose, P = .026), and the amount of postoperative acetaminophen (β -18.2 morphine equivalent daily dose per 1 g, P = .026). The sustained reduction of opioid prescriptions at discharge did not impact hospital readmission rates within 30 days (odds ratio 1.17, 95% confidence interval 0.86-1.59, P = .306). Subgroup analysis showed a significant, sustained decrease in hydromorphone (β -10.9 morphine equivalent daily dose per year, P = .004), but not for hydrocodone prescriptions (β -5.7 morphine equivalent daily dose per year, P = .168) or oxycodone (β +4.78 morphine equivalent daily dose per year, P = .183).Our Enhanced Recovery After Surgery program for thoracic surgery contributed to a sustained reduction of opioid prescriptions at discharge, which positively correlated with the duration of its implementation and the use of minimally invasive surgical techniques but was negatively impacted by the amount of intraoperative opioid administration.

Background Adenocarcinoma of the gastroesophageal junction (AEG) poses a management challenge, as preoperative prediction of occult mediastinal nodal metastasis is difficult. We sought to identify factors predictive of mediastinal involvement among patients undergoing trimodality therapy. Methods Patients undergoing trimodality therapy for Siewert II and III AEG at a single institution between 2000 and 2015 were identified. Mediastinal involvement was defined as pathologic nodal involvement after neoadjuvant chemoradiation (ypN+) in mediastinal stations or mediastinal recurrence 2 years or less after resection. Maximal χ2 analysis and Youden's J index were used to identify the pretreatment proximal tumor extent that best discriminated mediastinal involvement. Results In all, 204 patients (151 [74%] AEG II, 53 [26%] AEG III) were included, of whom 47 (23%) had clinical evidence of thoracic nodal disease. Thirty-one of the 204 patients (15%) met criteria for mediastinal involvement (24 of 31 ypN+, 10 of 31 mediastinal recurrence). Patients with mediastinal involvement had greater proximal tumor extent (median 2 cm [interquartile range, 1.0 to 3.0 cm] vs 1.4 cm [interquartile range, 0.7 to 3.0 cm], P = .030), were more frequently Siewert II lesions (27 of 31 [87.1%] vs 124 of 173 [71.7%], P = .071), and were more often observed to have clinical thoracic nodal metastasis (cN) evidence (13 of 31 [42%] vs 34 of 173 [20%], P = .007) than patients who did not. On multivariable analysis of patients with intrathoracic cN0, esophageal extent of 1.5 cm or greater was independently predictive of mediastinal involvement (odds ratio 5.46, P = .011), whereas Siewert classification was not (Siewert II odds ratio 3.48, P = .116). Conclusions Pretreatment proximal tumor extent, rather than Siewert classification, is an independent predictor of mediastinal involvement among AEG II/III patients without clinical evidence of mediastinal metastasis and should be considered during treatment planning.

The incidence of persistent opioid use after lung surgery is high. Although adverse effects by opioids have been well described, it is unknown whether persistent opioid use is associated with worse survival. Patients who received a lobectomy for stage I NSCLC from 2007 to 2013 were identified from the Surveillance, Epidemiology and End Results-Medicare database. Opioid use was ascertained through records of prescriptions filled through part D. Patients were matched 2:1 according to their likelihood of persistent opioid use, which was defined as any opioid prescription filled 3 to 6 months after surgery. Two thousand eight hundred eighty-four patients were identified. The incidence of persistent opioid use 3 to 6 months after surgery was 27.0%. After matching, persistent opioid use was associated with worse overall survival (P < 0.001) and cancer-specific survival (P < 0.001). Those who used the lowest quartile of opioids, which was often manifested as a single opioid prescription, showed similar overall survival as no opioid use (HR 1.27, 95% confidence interval [CI] 0.93-1.72). However, the second and third quartiles of opioid use were associated with decreased overall survival (HR 1.53, 95% CI 1.14-2.03 and HR 1.39, 95% CI 1.04-1.86, respectively) that was nonetheless less severe than the highest quartile of opioid use (HR 2.50, 95% CI 1.95-3.21). Age, sex, marital status, comorbidity, tumor size, tumor grade, and radiation were also associated with worse overall survival, with chemotherapy use and video-assisted thoracoscopic surgery being associated with improved overall survival. Persistent opioid use 3 to 6 months after lobectomy is independently associated with worse overall survival and worse cancer-specific survival.

Background and objectives Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. Methods Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. Results 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. Conclusions Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.

Background Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D. Methods Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis. Results Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P = .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P = .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P = .029), macroscopic complete resection (HR, 0.41; P = .004), adjuvant radiation therapy (HR, 0.57; P = .019), and more recent operative years (HR, 0.93; P = .011)—but not P/D—to be associated with better survival. Asbestos exposure (HR, 2.35; P = .003) and pathologic nodal disease (HR, 1.61; P = .048) were associated with worse survival. Conclusions In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.

Purpose:Malignant pleural mesothelioma (MPM) is considered an orphan disease with few treatment options. Despite multimodality therapy, the majority of MPMs recur and eventually become refractory to any systemic treatment. One potential mechanism underlying therapeutic resistance may be intratumor heterogeneity (ITH), making MPM challenging to eradicate. However, the ITH architecture of MPM and its clinical impact have not been well studied.Experimental Design:We delineated the immunogenomic ITH by multiregion whole-exome sequencing and T-cell receptor (TCR) sequencing of 69 longitudinal MPM specimens from nine patients with resectable MPM, who were treated with dasatinib.Results:The median total mutation burden before dasatinib treatment was 0.65/Mb, similar with that of post-dasatinib treatment (0.62/Mb). The median proportion of mutations shared by any given pair of two tumor regions within the same tumors was 80% prior to and 83% post-dasatinib treatment indicating a relatively homogenous genomic landscape. T-cell clonality, a parameter indicating T-cell expansion and reactivity, was significantly increased in tumors after dasatinib treatment. Furthermore, on average, 82% of T-cell clones were restricted to individual tumor regions, with merely 6% of T-cell clones shared by all regions from the same tumors indicating profound TCR heterogeneity. Interestingly, patients with higher T-cell clonality and higher portion of T cells present across all tumor regions in post-dasatinib–treated tumors had significantly longer survival.Conclusions:Despite the homogeneous genomic landscape, the TCR repertoire is extremely heterogeneous in MPM. Dasatinib may potentially induce T-cell response leading to improved survival.

Background Adjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC. Methods Data were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI. Results A total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis. Conclusions This is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.

Background We have previously demonstrated that Enhanced Recovery After Surgery protocols are associated with a reduction in pulmonary complications. As a component of enhanced recovery pathways, intercostal nerve blocks with liposomal bupivacaine are increasingly utilized, but the extent to which this element may contribute to such outcomes has not been evaluated. Methods Patients undergoing lung resection for stage I to III non-small cell lung cancer at a single institution from 2006 to 2017 were examined for major postoperative pulmonary morbidity, defined as pneumonia, acute respiratory distress syndrome, respiratory arrest, reintubation, bronchoscopy, or need for discharge with oxygen. Pharmacy records were queried for administration of liposomal bupivacaine via posterior intercostal nerve block. Patients treated with and without liposomal bupivacaine were compared in a logistic regression to determine the impact on pulmonary morbidity. Results A total of 2865 patients were identified, including 860 (30%) who were treated with liposomal bupivacaine via posterior intercostal block. Pulmonary morbidity occurred in 455 (16%). Adoption of liposomal bupivacaine analgesia occurred over several years, beginning in 2012 to full adoption by 2017. Liposomal bupivacaine management was associated with a reduction in pulmonary complications, as compared with nonuse (odds ratio, 0.63; P = .006). Additional factors associated with the occurrence of pulmonary morbidity were age, body mass index, smoking, spirometry values, and operative blood loss. Conclusions As a component of an active enhanced recovery program, liposomal bupivacaine is associated with a reduction in major pulmonary complications, and utilization should be evaluated on a hospital-by-hospital basis.

Background As strategies promoting enhanced recovery protocols and opioid minimization techniques are increasingly prioritized, use of nonsteroidal antiinflammatory drugs continues to rise. Whether this prevalent use poses increased risk for bleeding or renal dysfunction in surgical populations after extensive dissection and fluid shifts is unclear. Methods We reviewed records of patients undergoing esophagectomy for a diagnosis of esophageal adenocarcinoma at a single institution from 2006 to 2018 for ketorolac administration during the postoperative hospital admission, as well as the occurrence of postoperative events, defined as the need for blood product transfusion and/or acute kidney injury. Results We identified 1019 patients, 123 of whom experienced postoperative events (12%). Ketorolac was administered to 686 (67%). Furthermore, ketorolac use steadily increased over the study period; 36 of 72 patients received this medication in 2006 (49%), and 76 of 83 in 2018 (92%). Multivariable logistic regression failed to identify a relationship between ketorolac administration (assessed as a binary covariate) and postoperative events (P = .657). Additional examination for a dose-response relationship using the cumulative total dose from the time of surgery to discharge also did not demonstrate a relationship with postoperative events (P = .829). In an effort to evaluate a more homogeneous population, we performed a subgroup analysis using only patients treated with trimodality therapy, which showed similar findings. Conclusions Ketorolac has become a staple of multimodal postesophagectomy analgesic regimens. Importantly, this medication does not pose risk for acute kidney injury or bleeding after surgery.

Background To examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities. Results Median follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n=131) and HR (n=84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P=0.08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P>0.2 for all). Field size was not associated with OS, PFS, or LRR (P>0.40 for all). LRR rates were 20% for HR and 26% for WM groups (P=0.30). There was no significant difference in patterns of initial site of LRR between groups (P>0.1). WM fields (OR 3.73, P=0.001) and concurrent chemotherapy (OR 3.62, P=0.001) were associated with grade ≥2 toxicity. Conclusions Locoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of high-risk PORT fields.

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcome. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2mm2, necrosis, lymphatic invasion and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlate with clinical outcome. Based on our analysis, we consider that the separation of low and intermediate grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of over grading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcome.

Background Previous studies have highlighted important biologic and survival-related differences among men and women with non-small cell lung cancer (NSCLC). However, differences in perioperative or short-term outcomes have not been as well characterized. In this study, we investigated differences in the perioperative period and postoperative emergency department (ED) visits among men and women after lobectomy for stage I NSCLC. Methods A retrospective review was performed of patients who underwent a lobectomy for clinical stage I NSCLC at a single institution from 2010 to 2015. Results We identified 559 patients for inclusion, including 293 women (52%) and 266 men (48%). Women were more likely to present with clinical T1 status (p = 0.005) and to undergo a minimally invasive operation (p = 0.058). To reduce confounding, 206 case-matched pairs were identified. After matching, no differences were found in length of stay (p = 0.551) or pulmonary complications (p = 0.509); however, men experienced more cardiac complications (18% versus 7%, p = 0.001). Of importance, although rates of 30- and 90-day ED visits between sexes were similar (p = 0.531, p = 0.890, respectively) and no sex-related differences were found in presenting symptom on return to the ED (p = 0.478), women were more likely to be readmitted after presenting to the ED within 30 days (p = 0.038). Conclusions Women demonstrated an increased likelihood of being admitted after presenting to the ED within 30 days after discharge, indicating important differences between men and women in the short-term period after lobectomy. Further research will be required to further understand the cause for these differences.

Objective Though interest in expansion of the use of less-invasive therapies among operable non-small-cell lung cancer (NSCLC) patients is growing, it is not clear that post-treatment surveillance has been comparable between treatment modalities. We sought to characterize institutional surveillance patterns after NSCLC therapy with stereotactic body radiation therapy (SBRT) and lobectomy. Methods NSCLC patients treated with lobectomy or SBRT (2005 to 2016) at a single institution were identified. Natural language processing searched data fields within axial surveillance imaging reports for findings suggestive of recurrence. Duration and patterns of institutional surveillance were compared between the 2 groups. Results Three thousand forty-two patients (73.5% lobectomy, 26.5% SBRT) met inclusion criteria. Patients had a longer median duration of surveillance after lobectomy (28.0 months vs SBRT 12.3 months, P < 0.001) and were more likely to undergo histopathological evaluation of clinically suspected relapse (206/274 [75.2%] vs SBRT 54/113 [47.8%], P < 0.001). Patients with clinical suspicion of recurrence had longer durations of institutional surveillance than those who did not among both cohorts (lobectomy 44.4 months vs 25.9, P < 0.001; SBRT 27.9 vs 10.3, P < 0.001). Landmark analyses at 1 and 3 years after therapy identified associations between receipt of lobectomy and ongoing surveillance at each time point (1 year odds ratio [OR] 2.10, P < 0.001; 3 years OR 1.71, P < 0.001) among all patients and those with documented stage I disease. Conclusions We identified potential heterogeneity in institutional surveillance patterns after treatment of NSCLC with 2 therapeutic modalities. As less-invasive treatment options for operable patients expand, it will be critical to implement rigorous surveillance paradigms across all modalities.

BACKGROUND: Recurrence rates are high for patients who have undergone two-stage hepatectomy (TSH) for bilateral colorectal liver metastases, and there is no established treatment approach for recurrent disease. This study aimed to determine the feasibility, safety, and prognostic impact of surgical resection for recurrence after TSH and the prognostic role of RAS mutation in this cohort. METHODS: The study included 137 patients intended to undergo TSH for bilateral colorectal metastases during 2003–2016. Clinicopathologic factors were compared using univariate and multivariate analysis. RESULTS: One hundred eleven patients (81%) completed TSH. The median recurrence-free survival in these patients was 12 months. Of the 83 patients with subsequent recurrence, 31 (37%) underwent resection for recurrence, and 11 underwent multiple resections for recurrence. Forty-eight operations were performed for recurrence: 23 repeat hepatectomies, 14 pulmonary resections, 5 locoregional resections, and 6 concurrent resections in multiple organ sites. The median overall survival (OS) among patients with recurrence was 143 months for patients who underwent resection and 49 months for those who did not (P

Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT).EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions.Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16-0.52; P 0.0001).PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

Enhanced recovery after surgery (ERAS) pathways aim to improve postoperative recovery through evidence-based practices, including early ambulation, multimodal opioid-sparing analgesia, and reduction of surgical stress. This study evaluated outcomes after implementation of ERAS in patients undergoing resection for pulmonary malignancy.A retrospective review compared outcomes for patients undergoing pulmonary resection for primary lung cancer. Analysis was performed between three periods: pre-ERAS (January 1, 2006, to December 31, 2011), transitional period with elements of ERAS (January 1, 2012, to August 31, 2015), and full implementation of ERAS (September 1, 2015, to December 31, 2016).We analyzed 2,886 lung resections (pre-ERAS, n = 1615; transitional, n = 929; ERAS, n = 342). For all patients, length of stay decreased in the ERAS and transitional periods compared with pre-ERAS (4 [3] versus 4 [3] versus 5 [3] days, p0.001). Pulmonary complications were decreased with ERAS compared with transitional and pre-ERAS (19.9% versus 28.2% versus 28.7%, p = 0.004). Cardiac complications decreased with ERAS (12.3% versus 13.1% versus 18.1%, p = 0.001). There was less thoracic epidural use (2.9% versus 44.5% versus 75.5%, p0.001). There were no differences in hospital readmission (p = 0.772) or mortality rates (p = 0.417). After thoracotomy, ERAS was associated with decreased length of stay, fewer intensive care unit readmissions, and decreased frequency of pneumonia, atrial arrhythmias, and need for home oxygen (all p0.05). ERAS was independently associated with decreased pulmonary (p = 0.046) and cardiac (p = 0.001) complications on logistic regression after thoracotomy but not minimally invasive operations.ERAS was associated with improved postoperative outcomes, including decreased length of stay and pulmonary and cardiac morbidity after thoracotomy, but not after minimally invasive operations. ERAS safety was demonstrated by low rates of adverse events without effect on hospital readmission or perioperative deaths.

Ground glass opacities pose diagnostic challenges, and even after malignancy is confirmed, prognosis is often unclear. We sought to identify clinicoradiographic features that could predict aggressive tumor biology in lung adenocarcinoma with associated ground glass components.A retrospective review of patients with resected lung adenocarcinoma from 2008 to 2013 was performed. Detailed radiographic features were reviewed by two radiologists. Logistic regression was used to identify risks of poor differentiation or a composite outcome of nodal metastases and lymphovascular invasion.In all, 79 patients met criteria for analysis. Larger tumor size (p = 0.04), increasing solid component (p = 0.01), pleural tags (p = 0.03), spiculation (p = 0.01), lobulation (p0.05), history of coronary artery disease (p = 0.04), and increasing number of pack-years smoking (p0.05) were associated with poorly differentiated tumors. However, after adjustment for size of the solid component, the associations between pleural tags, spiculation, and lobulation with poorly differentiated tumors were negated, whereas number of pack-years and history of coronary artery disease remained statistically significant (p = 0.01 and p = 0.03, respectively). There were no identified clinical or radiographic features associated with lymphovascular invasion/nodal metastasis.Several radiographic features were associated with aggressive tumor biology, a well-known finding. However, we found that none of these radiographic features remained relevant after we adjusted for the size of the solid component, indicating that radiographic features are not as important as previously believed. Further research will be required to identify reliable markers associated with favorable tumor biology. These studies will ultimately be critical in informing prognosis or guiding extent of resection.

Introduction Window of opportunity trials in malignant pleural mesothelioma (MPM) are challenging but can yield important translational information about a novel agent. Methods We treated patients with MPM (N = 24) with 4 weeks of oral dasatinib followed by surgery with or without radiotherapy and then an optional 2 years of maintenance dasatinib. The primary end point was biomarker modulation of phosphorylated (p) Src Tyr419 . Results For all patients, the median progression-free survival (PFS) was 7.5 months and the median overall survival was 19.1 months. No significant responses were seen after 4 weeks of dasatinib therapy; however, modulation of median p-Src Tyr419 immunohistochemistry (IHC) scores was seen: the median pretreatment score was 70 (interquartile range 37.5–110), and the median posttreatment score was 41.9 (interquartile range 4.2–60) ( p = 0.004). A decrease in p-Src Tyr419 levels after dasatinib correlated with improved median PFS (6.9 months versus 0.94 months [ p = 0.03]), suggesting that p-Src Tyr419 is a viable pharmacodynamic biomarker for dasatinib in MPM. Platelet-derived growth factor receptor (PDGFR) pathway analysis correlated high PDGFR beta [PDGFRB) level (in the cytoplasm [hazard ratio] (HR) = 2.54, p = 0.05], stroma [HR = 2.79, p = 0.03], and nucleus [HR = 6.79, p = 0.023]) with a shorter PFS. Low (less than the median) cytoplasmic p-PDGFR alpha IHC levels were predictive of a decrease in positron emission tomography/computed tomography standard uptake values levels after dasatinib therapy ( p = 0.04), whereas higher-than-median IHC scores of PDGFRB (cytoplasmic [HR = 2.8, p = 0.03] and nuclear [HR = 6.795, p = 0.02]) were correlated with rising standard uptake values levels. Conclusions In conclusion, there was no significant efficacy signal, and dasatinib monotherapy will not continue to be studied in MPM. However, our study demonstrated that PDGFR subtypes (platelet-derived growth factor receptor alpha and PDGFRB) may have differential roles in prognosis and resistance to antiangiogenic tyrosine kinase inhibitors and are important potential therapeutic targets that require further investigation.

Purpose: Determine the 1-year progression-free survival (PFS) rate among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy versus those receiving control adjuvants. Experimental Design: This double-blind, controlled, two center phase II trial randomized MPM patients after surgery and another treatment modality to galinpepimut-S with GM-CSF and Montanide or GM-CSF and Montanide alone. An improvement in 1-year PFS from 50% to 70% was the predefined efficacy threshold, and 78 patients total were planned. The study was not powered for comparison between the two arms. Results: Forty-one patients were randomized. Treatment-related adverse events were mild, self-limited, and not clinically significant. On the basis of a stringent prespecified futility analysis (futility = ≥10 of 20 patients on one arm experiencing progression < 1 year), the control arm closed early. The treatment arm was subsequently closed because of the resultant unblinding. The PFS rate at 1 year from beginning study treatment was 33% and 45% in the control and vaccine arms, respectively. Median PFS was 7.4 months versus 10.1 months and median OS was 18.3 months versus 22.8 months in the control and vaccine arms, respectively. Conclusions: The favorable safety profile was confirmed. PFS and OS were greater in those who received vaccine, but the trial was neither designed nor powered for comparison between the arms. On the basis of these promising results, the investigators are planning a larger randomized trial with greater statistical power to define the optimal use and benefit of galinpepimut-S in the treatment of MPM. Clin Cancer Res; 23(24); 7483–9. ©2017 AACR.

Background Perioperative management of antiplatelet therapy for patients undergoing pulmonary resection must balance the risk of cardiovascular events with that of hemorrhage. An optimal approach has not been defined in this population. We sought to characterize outcomes of patients undergoing pulmonary lobectomy on antiplatelet therapy with clopidogrel. Methods A prospective institutional database was retrospectively reviewed to identify all patients undergoing pulmonary lobectomy from 2007 to 2015 who received perioperative clopidogrel. Patients were grouped according to the timing of clopidogrel discontinuation before operation: group I, 5 days or less; group II, 6 to 14 days; and group III, more than 14 days. Analyses were performed to assess the effect of timing of discontinuation on adverse events. Results Sixty-two patients were identified and included in the analysis. The indication for clopidogrel was coronary artery disease in 44 patients (71%), 35 (56%) of whom had prior stent placement. The overall incidences of transfusion and major cardiovascular events were 16% (10 of 62) and 6.5% (4 of 62), respectively. Non-ST elevation myocardial infarctions occurred in 4 patients. Three were in patients with stents, all placed more than 1 year before the operation. There were no significant differences identified in estimated blood loss, operative duration, or perioperative deaths. Conclusions No significant outcome differences in perioperative cardiovascular or hemorrhagic events were identified among the groups. Although these findings suggest that clopidogrel may be discontinued shortly before the operation with limited risk of bleeding, we also found that holding therapy for more than 14 days preoperatively may be safe in appropriately selected patients.

Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even50% would show resistance to standard multimodality therapy with poorer long-term outcomes.Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC.SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival.We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.

Patients with persistent N2 disease after induction have poor survival. Many of these patients may have had mediastinoscopy before induction therapy, making reassessment of the mediastinum by repeat mediastinoscopy hazardous and inaccurate. The sensitivity and specificity of endobronchial ultrasonography and nodal fine-needle aspiration in this setting is unclear. In this study, we sought to identify the clinical predictors of persistent N2 disease after induction therapy, which may help in selecting the patients most likely to benefit from surgical resection.A retrospective review of a prospective database (1990 to 2014) was performed to identify patients who had surgical resection after induction therapy for clinical stage IIIA-N2 non-small cell lung cancer. Multivariable logistic regression analysis was performed to determine independent predictors of persistent N2 disease.203 patients (56% female; median age 64 years) underwent potentially curative lung resection after induction therapy. Ninety-seven patients (48%) had pathologic nodal downstaging (pN0/N1), which was associated with significantly better overall survival compared with patients with persistent N2 disease (5 years, 56% versus 35%, p = 0.047). Univariate and multivariate analysis showed that upper or middle lobe location and less than 60% reduction of N2 SUVmax were independent predictors of persistent N2 disease.Patients with upper lobe tumors and less than 60% reduction in N2 SUVmax are more likely to have persistent N2 disease, which is often associated with poor survival rates. These clinical prognostic criteria may help surgeons in stratifying patients and properly selecting optimal surgical candidates.

Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT).Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization.RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264).Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.

Background We aimed to evaluate the impact of collagen matrix in the reconstruction of the diaphragm. Methods We queried the electronic medical record for patients who had resection of the diaphragm and simultaneous pulmonary resection between 1999 and 2016. All reconstructions were performed with either polytetrafluoroethylene or acellular dermal matrix. We evaluated the rate of empyema and herniation in each group. Results A total of 208 patients met inclusion criteria. Polytetrafluoroethylene was used in 168 cases (80.8%) and dermal matrix in 40 cases (19.2%). Dermal matrix was used in 8 extrapleural pneumonectomies (5.4%), in 26 pleurectomy decortications (55.3%), and in 6 other types of resections (40%). Follow-ups were for a median of 15.0 months in the polytetrafluoroethylene group and 11.6 months in the dermal matrix group. Patients in the dermal matrix group had a chest tube for a median of 2.5 days longer than patients with polytetrafluoroethylene ( p = 0.006). Empyema occurred in 11 polytetrafluoroethylene reconstructions (6.5%) and 3 dermal matrix reconstructions (7.5%) ( p = 0.735). Seven patients (63.6%) with polytetrafluoroethylene infection required removal of the graft, whereas none in the dermal matrix group needed removal ( p = 0.351). There were nine herniations in the polytetrafluoroethylene group and four in the dermal matrix group ( p = 0.281), all were acute and due to anchorage failure. Conclusions Although infection rates were similar between polytetrafluoroethylene and acellular dermal matrix, re-operation for removal was not necessary in the latter. The use of a thick acellular dermal matrix may be a reasonable option when diaphragmatic reconstruction is potentially associated with a higher risk of infection.

Purpose We report our single-institution experience with stereotactic ablative radiotherapy (SABR) for adrenal metastasis and identify factors influencing outcomes, patterns of failure, and dosimetric thresholds for toxicity. Methods and materials We identified patients with adrenal metastases treated with SABR from 2009 to 2015. Toxicity was evaluated with Common Terminology Criteria for Adverse Events v4.0. Local failures were categorized as in-field, marginal, or out-of-field. New or progressive disease outside the treated adrenal gland was considered distant failure. Survival and time to local and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were evaluated with a Cox proportional hazards model. Fisher's exact tests were used to compare toxicity between dosimetric thresholds. Results Forty-three patients with 49 adrenal metastases (84% from lung) were treated with SABR to a median prescribed dose of 60 Gy in 10 fractions. Median overall survival time was 19 months, and 1- and 2-year rates were 65% and 42%, respectively. Bilateral adrenal metastases were associated with worse overall survival ( P = .01). Median progression-free survival (PFS) time was 6 months, with most progressions being distant failure (most often to brain or bone). PFS was better in patients with a solitary adrenal metastasis ( P = .03). Median time to local failure was not reached; the 1-year freedom from local failure rate was 74%. Nine failures were in field and 1 was marginal; no local failures occurred in lesions treated with biologically equivalent doses of >100 Gy. No patient experienced grade 3-5 toxicity. Low-grade gastrointestinal toxicity was common, but grade 2 toxicity was avoided in patients with a maximum stomach-bowel point dose of ≤50 Gy ( P = .03). Low-grade adrenal insufficiency was common with bilateral treatment. Conclusion SABR was well tolerated and resulted in good 1-year local control; PFS was promising for patients with solitary metastases. Low-grade toxicity was common, but can be minimized with strict dosimetric constraints.

To identify risks factors associated with acute kidney injury (AKI) after esophageal cancer surgery.This was a retrospective study.Single academic center.Subjects with non-metastatic esophageal cancer. Patients were excluded if they were younger than 18 years and had missing data.Primary outcome of the study was AKI according to AKI Network criteria. Demographic and perioperative variables were compared in patients with and without AKI. A multivariate Cox proportional model was used to assess the association between perioperative variables and AKI; p0.05 was considered statistically significant. AKI was found in 107 (11.9%) of the 898 patients included in the study. The multivariate analysis also showed that BMI (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.11), number of comorbidities (OR 1.52, 95% CI 1.20-1.93, p = 0.001), and preoperative creatinine concentrations (OR 2.37, 95% CI 1.14-4.92, p = 0.02) were independent predictors for AKI. The use of dexamethasone was associated with a reduced risk for AKI.In support of previous reports in the literature, the authors found that AKI was not an uncommon complication after esophageal surgery. Obesity, cardiovascular comorbidities, and high preoperative concentrations were predictors of AKI. Dexamethasone administration during surgery appeared to have a protective effect. This finding opens an opportunity to further study in a randomized controlled trial the efficacy of dexamethasone in the prevention of AKI.

Background Current evidence supports the curative resection of colorectal cancer and synchronous liver and lung metastases in selected patients.1,2 This video shows simultaneous left colectomy, bilobar liver resection, and lung metastasectomy via a transdiaphragmatic approach for stage IV colorectal cancer.3 PATIENT: A 57-year-old man with a stage IV colonic adenocarcinoma was considered for simultaneous resection of primary, liver, and lung metastases without thoracic incision. The tumor mutational status was KRAS, NRAS, and BRAF wild-type, and the patient underwent preoperative chemotherapy. Technique After performing a midline laparotomy, atypical liver resection of segments 8/4a was performed under the guidance of intraoperative ultrasonography and intermittent Pringle maneuver using the two-surgeon's technique. A small capsular lesion in segment 3 also was intraoperatively detected and resected. Lung metastasectomy of the right lower lobe was performed via a transdiaphragmatic approach using an endoscopic stapler. Sigmoid colectomy with transanal circular-stapled anastomosis was performed. Duration of surgery and blood loss were 358 min and 400 ml, respectively. Histopathological examination showed metastatic colonic adenocarcinoma with negative surgical margins and final stage was T3N2aM1b. The patient was discharged on postoperative day 6 without complication. He was alive and free of disease at 90-day follow-up. Conclusions Simultaneous colon, liver, and lung resection via a transdiaphragmatic approach is a feasible and safe surgical strategy in selected patients with peripheral lung metastases and favorable tumor biology.4 This surgical strategy avoids thoracic incision, multiple operations, and may reduce the healthcare costs and the recovery time to early implement postoperative therapy.

Objectives Recent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential. Methods Records of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak. Results A total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak. Conclusions Ketorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.

SUMMARY The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Background and objectives While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. Methods Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). Results A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. Conclusions After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.

Objective We sought to identify whether chronic opioid users are at increased risk for complications or hospital readmission following lobectomy for non–small cell lung cancer. Methods The National Cancer Institute Surveillance, Epidemiology, and End Results-Medicare database was queried to identify patients older than age 65 years who received a lobectomy for non–small cell lung cancer. Chronic opioid users were identified through Medicare Part D records and were defined as those with >120 cumulative days of opioid supply for the year before surgery. A systematic 1:2 propensity matching was performed among chronic opioid users. Results Six thousand four hundred thirty-seven patients were identified, among whom 3627 (56%) were opioid naive, 1866 (29%) were intermittent opioid users, and 944 (15%) were chronic opioid users. After propensity matching, 30-day mortality and 90-day mortality were nearly 2-fold higher among chronic opioid users compared with nonchronic users. In addition, length of stay and hospital charges were increased among chronic opioid users (median, 6 vs 7 days and mean increase, $12,526, respectively). Multivariable analysis revealed that intermittent opioid users and chronic opioid users were associated with an increased risk of 90-day hospital readmission compared with opioid-naive patients (odds ratio, 1.35; 95% confidence interval, 1.07-1.71 and odds ratio, 1.72; 95% confidence interval, 1.40-2.12, respectively), predominantly burdened by infectious, renal, and pulmonary causes. Conclusions Patients who chronically use opioids before lobectomy represent high-risk patients. The risk of 30- and 90-day mortality, length of stay, hospital charges, and 90-day readmission after lobectomy among chronic opioid users are substantially elevated.

SUMMARY Endoscopic mucosal resection (EMR) can be an effective therapy for superficial esophageal cancer. Many patients with cT2 invasion by endoscopic ultrasound (EUS) receive surgery but are subsequently found to have superficial disease. The purpose of this study was to investigate the safety profile and the added value of attempting EMR for EUS-staged cT2N0 esophageal cancer. A retrospective review was performed at a single institution from 2008 to 2017. Patients who were staged cT2N0 by EUS were identified from a prospectively maintained surgical database. Among 75 patients identified for analysis, 30 underwent an attempt at EMR. No perforations or other immediate complications occurred. EMR was more likely to be attempted among older patients (P = 0.001) with smaller tumor size (P < 0.001) and diminished SUVmax (P = 0.001). At the time of treatment, EMR was successful in clearing all known disease among 17/30 patients, with 12 representing pT1a or less and 5 representing pT1b with negative margins. Among the 17 patients for whom EMR was able to clear all known disease, there were no recurrences or cancer-related deaths. Although all the patients were staged as cT2N0 by EUS, many patients were identified by EMR to have superficial disease. There were no perforations or other adverse events related to EMR. Furthermore, EMR cleared all known disease among 17 patients with no known recurrences or cancer-related deaths. The results indicate that EMR for cT2N0 esophageal cancer is a safe diagnostic option that is therapeutic for some.

Background Emerging technologies for prosthetic reconstruction after chest wall resection have yielded a wide variety of reconstructive options for thoracic surgeons. The ideal chest wall reconstruction and its impact on perioperative outcomes has not been well defined. Our goal was to determine whether mesh characteristics such as rigidity or absorbability altered perioperative pulmonary and infectious outcomes. Methods Our institutional database was queried for patients who underwent chest wall resection and reconstruction for primary or secondary chest wall tumors between the years 1998 and 2013. A focused chart review supplied clinical and perioperative variables. The main study outcomes focused on perioperative pulmonary and wound/implant infectious complications. Univariate and multivariate analyses were performed to identify variables associated with outcome. Results We identified 1,096 patients who underwent chest wall resection during the study period, of which 427 required chest wall reconstruction. Pulmonary complications occurred in 24% (n = 102 of 427) of patients. We observed no significant difference in pulmonary complications between those that had a rigid versus flexible chest wall reconstruction ( p = 0.401; OR, 1.43; 95% CI, 0.83–2.43). The odds of pulmonary complications increased with each additional resected rib (OR, 1.43; 95% CI, 1.2–1.71). Multivariable analysis identified the number of resected ribs (OR, 1.26; 95% CI, 1.00–1.59) and concomitant lobectomy (OR, 3.59; 95% CI, 1.62–7.92) as variables associated with perioperative pulmonary morbidity. Infectious complications occurred in 13 patients and were not predicted by the use of permanent versus absorbable prosthetic materials ( p = 0.575). Conclusions The type of reconstructive material, whether with rigid, flexible, permanent, or biologic characteristics, does not appear to influence perioperative pulmonary or infectious wound complications. Rather, the number of resected ribs and the concomitant lung parenchymal resection predict pulmonary morbidity following chest wall resection. Depending on the circumstances, an effective chest wall reconstruction can be achieved with either rigid or flexible prosthetic material.

Background After hospital discharge, patients may have questions or complaints that surface or remain inadequately addressed. However, the dominant concerns and indications for further intervention among recently discharged patients after pulmonary resection have not been well described. The aims of this study were to characterize dominant concerns of pulmonary resection patients after discharge and to elucidate any relevant risk factors for their development. Methods A single-institution, retrospective review was conducted of all patients who underwent pulmonary resection over a 12-month period and included records of standardized, nurse-initiated follow-up phone calls to discharged patients. Records of postdischarge telephone calls were reviewed, and data collected pertaining to complaints requiring counseling over the phone or escalation to higher care level. Demographic, operative, and hospital data were examined by multivariate analyses to assess predictors of need for counseling or escalation of care. Results In all, 523 patients underwent pulmonary resection during the study, and 245 (46.8%) had nursing-documented telephone conversations at 4.6 days (±0.18) days after discharge. Among those reached, 81 (33.1%) had problems requiring counseling during the call; 31 (12.7%) reported concerns requiring escalation of care, handled by subsequent telephone call for 7 (22.6%), clinic appointment for 22 (71.0%), or emergency room referral for 2 (6.5%). Age, sex, race, and residential proximity to the hospital did not predict need for counseling nor escalation of care. Conclusions Patient complaints after pulmonary resection were frequent, with most problems resolved by telephone counseling. Despite highly prevalent concerns, predictors of need for counseling or care escalation were not identified, suggesting ongoing utility in the practice of telephoning all patients. Further, this study serves as a needs assessment, highlighting the importance of patient education and discharge planning.

Background Management of superior sulcus non-small cell lung cancer (NSCLC) continues to evolve, with preoperative chemoradiotherapy (CXRT) followed by surgical intervention supported by several studies. Rates of pathologic complete response (pCR) have varied, and previous attempts to identify clinical predictors of pCR have been unsuccessful. We analyzed our experience with resected superior sulcus NSCLC to elucidate clinical features suggestive of pCR among patients after preoperative treatment. Methods A multiinstitutional retrospective review was performed in patients who underwent resection for superior sulcus NSCLC between January 1988 and July 2013. Data pertaining to comorbidities, staging, therapy, imaging, and outcomes were collected. Logistic regression was performed to identify predictors of survival and pCR. Results During the study, 102 patients underwent preoperative therapy, consisting of CXRT in 75 (73.5%), chemotherapy in 15 (14.7%), and radiotherapy in 12 (11.8%). After median follow-up of 18.0 months, overall and disease-free survivals were 51.0% and 45.1%, respectively. On multivariate regression, independent predictors of survival included pCR ( p = 0.001; hazard ratio [HR], 0.243; 95% confidence interval [CI], 0.106–0.555) and age ( p = 0.007; HR, 1.049; CI, 1.013–1.085). Among those who received CXRT, 24 of 75 (32%) achieved pCR. Multivariate regression analysis of the CXRT group revealed that pCR was independently predicted by extent of size reduction on imaging ( p = 0.015; HR, 1.042; CI, 1.008–1.078), with histologic examination showing a trend toward significance ( p = 0.073). Conclusions Preoperative chemoradiation frequently resulted in pCR, and treatment response on imaging was associated with the likelihood of achieving pCR. Future investigations are warranted to further predict pCR from preoperative clinical variables such as symptom resolution, as identification of accurate predictors may ultimately permit the application of selective surgical intervention in superior sulcus NSCLC.

Background Advances in perioperative and operative management hold great promise for improving perioperative outcomes in patients undergoing resection for early stage non-small cell lung cancer (NSCLC). The objective of this study was to evaluate time trends in the incidence of perioperative outcomes and to identify predictors of pulmonary complication in early stage NSCLC resection patients. Methods An institutional database was reviewed to identify patients with primary, clinical stage I and II NSCLC who underwent resection from 1998 to 2016. Rates of perioperative pulmonary complication, pneumonia, and cardiovascular complication; and 30-day and 90-day mortality were calculated for each year. Joinpoint regression was used to calculate annual percentage change (APC) and to evaluate time trends in rates of these outcomes. Multivariable logistic regression was conducted to identify predictors of pulmonary complication. Results Of the 3045 patients identified, 80% had stage I and 20% had stage II NSCLC. From 1998 to 2016, there was no trend in the rate of pulmonary complication, but there was a significant downward trend in the rates of pneumonia (APC −3.7), cardiovascular complication (APC −3.5), 30-day mortality (APC −9.8), and 90-mortality (APC −7.4). Older age, male sex, smoking status, percentage of predicted forced expiratory volume in 1 second and percentage of diffusion capacity of lung for carbon monoxide, and intraoperative blood transfusion were identified as predictors of pulmonary complication. Conclusions Decrease in the rates of perioperative outcomes parallels improvements in patient selection and perioperative management of early stage NSCLC resection patients. Predictors of pulmonary complication could be used to improve selection criteria for surgery and to reduce the incidence of pulmonary complication in these patients.

Enhanced recovery after surgery integrates multiple evidence-based interventions to accelerate postoperative recovery. We hypothesized that enhanced recovery after surgery would also facilitate adjuvant chemotherapy for non-small cell lung cancer.An enhanced recovery after surgery pathway was implemented at a single institution, starting with a transitional rollout in 2012 and full rollout in 2015. Patients with clinical stage I or II non-small cell lung cancer without induction therapy and who were pathologic nodal positive or had 5-cm or larger tumor size were selected for analysis. Dates analyzed were pre-enhanced recovery after surgery (2006-2011), transitional (2012-8/2015), and enhanced recovery after surgery (9/2015-2017). Interrupted time series was used to analyze trends in time to receive adjuvant chemotherapy after resection by era. Logistic regression was used to determine factors associated with receiving 4 or more cycles of adjuvant chemotherapy.A total of 471 patients were identified. The interval between lung resection and commencing adjuvant chemotherapy was progressively shorter after the transition era (P = .041). The rate of receiving adjuvant chemotherapy progressively increased (from 40% pre-enhanced recovery after surgery, to 50% transition era, to 62% enhanced recovery after surgery era, P .001). Multivariable regression revealed the enhanced recovery after surgery era (odds ratio, 3.6, P .001), the transitional era (odds ratio, 2.01, P = .007), pN status, tumor grade and histology, age, and preoperative performance status were associated with completing adjuvant therapy. The surgical approach, whether open or thoracoscopic, was not associated with completing adjuvant chemotherapy.Enhanced recovery after surgery was associated with facilitated delivery of adjuvant chemotherapy, with a shortened interval to receive adjuvant chemotherapy and a higher rate of receiving 4 or more cycles.

It is unclear whether the enhanced dexterity and visualization of the surgical robot lessens morbidity and influences staging or survival. We compared outcomes of robotic-assisted lobectomy (RAL) with thoracoscopic video-assisted lobectomy (VAL) or open lobectomy (OL) of non-small cell lung cancer.Using a prospective surgical database, perioperative and cancer-related outcomes of patients who received a lobectomy for non-small cell lung cancer from 2011 to 2017 were analyzed. Outcomes between each surgical approach were compared using inverse probability of treatment weighting generated from the inverse of the propensity score.There were 831 patients: 106 RAL, 301 VAL, and 424 OL. More RAL patients than VAL received neoadjuvant therapy (16% vs 6%, P = .001), but less than OL (28% vs 16%, P = .014). After adjustment, RAL was associated with longer operative times, less blood loss, and improved nodal harvest (all P.02). There were no differences in morbidity, nodal upstaging, or mortality between surgical approaches. Length of stay was shorter with RAL vs OL (P.01). Unadjusted cost was higher after RAL vs VAL (P = .003), but after adjustment, cost differences disappeared.Robotic-assisted lobectomy was associated with improved nodal harvest and less blood loss as compared with VAL or OL. Length of stay was shorter with RAL as opposed to OL. Unexpectedly, cost was not higher with RAL. The profile of patients who received RAL more closely approximated OL, suggesting RAL may allow typical thoracotomy patients to receive minimally invasive surgery after adequate training and experience.

Objective During resection of pulmonary metastases, the need to spare lung parenchyma is often weighed against the increased risk of local recurrence if an inadequate surgical margin is obtained. We sought to identify risk factors for local recurrence after wedge resection of pulmonary metastases of a colorectal origin. Methods A retrospective study of patients who underwent a wedge resection for colorectal pulmonary metastases from 2006 to 2016 was performed. Cox regression with robust variance was used to estimate the risk of local recurrence per nodule treated. Results We identified 335 patients who underwent 679 wedge resections. The 2-year local recurrence risk for each nodule was 11.8% (95% confidence interval, 8.9%-14.6%), and the 5-year risk was 20.6% (95% confidence interval, 16.2%-24.8%). Longer margin length decreased the risk of local recurrence (hazard ratio, 0.434 per additional cm of length; P = .015), whereas larger tumor size increased this risk (hazard ratio, 1.520 per additional cm of size; P = .012). However, other factors tested, including tumor grade, KRAS mutation status, and response to induction chemotherapy, did not affect recurrence risk. A pathologic margin length of at least half the tumor size was estimated to result in a local recurrence rate Conclusions Among surgically resected colorectal pulmonary metastases, technical factors related to margin length and tumor size were associated with the risk of local recurrence, whereas tumor grade and KRAS status were not. However, the increased risk of local recurrence with larger tumors was diminished with a sufficient margin length.