The Impact of Adjuvant Hemithoracic Radiation on Outcomes in Patients With Stage I-III Malignant Pleural Mesothelioma: A Dual Registry Analysis.

BACKGROUND: The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood. OBJECTIVE: The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I-III MPM. METHODS: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (NCDB) (2004-2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed. RESULTS: A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62-2.11] and NCDB patients (HR 0.97; 95% CI 0.81-1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43-1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation. CONCLUSIONS: In this dual registry analysis of patients with resected stage I-III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation.

The Impact of Adjuvant Therapy on Survival After Esophagectomy for Node-negative Esophageal Adenocarcinoma.

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.

The Relationship Between Lymph Node Ratio and Survival Benefit With Adjuvant Chemotherapy in Node-positive Esophageal Adenocarcinoma.

BACKGROUND: We hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC. OBJECTIVE: The aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population. METHODS: The 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC. RESULTS: A total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79). CONCLUSIONS: In this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population.

Tumor Size, Histology, and Survival After Stereotactic Ablative Radiotherapy and Sublobar Resection in Node-negative Non-small Cell Lung Cancer.

BACKGROUND: Although SABR is increasingly emerging as an alternative to surgery for node-negative non-small cell lung cancer, there is poor understanding of patients who may most benefit SABR compared to surgery. OBJECTIVE: This study examined the relationship between tumor size and the comparative outcomes of SABR and sublobar resection in patients with node-negative non-small cell lung cancer. RESULTS: A total of 59,949 patients met study criteria: 19,888 (33%) underwent SABR, 33,052 (55%) wedge resection, and 7009 (12%) segmental resection. In multivariable regression, a significant 3-way interaction was found between histology, tumor size, and type of treatment. After stratification by histology, a significant interaction between tumor size and treatment was preserved for patients with adenocarcinoma and squamous cell carcinoma. Sublobar resection was associated with greater survival compared to SABR for tumor sizes greater than 6 and 8 mm for patients with adenocarcinoma and squamous cell carcinoma, respectively. SABR was associated with similar survival compared to sublobar resection for patients with papillary and large cell histology. CONCLUSIONS: In this National Cancer Database analysis, sublobar resection was associated with greater survival compared to SABR for lesions >6or 8 mm in patients with adenocarcinoma or squamous cell carcinoma; however, SABR was associated with similar survival compared to sublobar resection in patients with aggressive tumors including papillary and large cell histology. Histologic diagnosis in patients with even small tumors may enable better treatment selection in those who cannot tolerate lobectomy.

Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer.

BACKGROUND: Induction therapy for patients with cT2N0M0 esophageal cancer is controversial. We performed a retrospective cohort analysis of the National Cancer Database to examine the patterns of use of induction therapy for this population. METHODS: The National Cancer Database was queried for patients with cT2N0M0 esophageal cancer who underwent esophagectomy (2004-2015). Patients were stratified by upfront surgery or induction therapy. Overall survival was analyzed and a multivariable logistic regression performed to identify factors associated with receipt of induction therapy. RESULTS: Overall 2540 patients met study criteria: 1177 (46%) received upfront esophagectomy and 1363 (53%) received induction therapy. Patients receiving induction therapy were more likely to be younger, male, without comorbidities, privately insured, and treated at a nonacademic center. These patients were also less likely to be treated in highest volume surgery centers. In multivariable regression, factors independently associated with receipt of induction therapy included later year of diagnosis, increasing tumor size, and increasing tumor grade. Factors associated with upfront esophagectomy included advancing age, comorbidities, lack of insurance, geographic location, and highest volume centers. The receipt of induction chemotherapy was not associated with a survival benefit compared with no induction therapy. CONCLUSIONS: Several patient-, treatment center-, and tumor-related factors are associated with receipt of induction therapy for cT2N0M0 esophageal cancer, although induction therapy is not associated with a survival benefit. Further inquiry into these differences and the potential benefit or lack thereof of induction therapy should be conducted to provide more equitable and appropriate care for patients with esophageal cancer.

The effect of extent of resection on outcomes in patients with limited stage small cell lung cancer.

BACKGROUND: There is poor understanding of the comparative effectiveness of lobar and sublobar resections for limited-stage small cell lung cancer (SCLC). We analyzed the National Cancer Database to examine the outcomes of patients undergoing wedge resection (WR), segmentectomy (SR), and lobectomy (LB) for limited-stage SCLC. METHODS: Patients with cT1-2N0M0 SCLC (2004-2015) who underwent definitive surgery were identified and stratified by extent of resection: WR, SR, or LB. The primary outcome was overall survival (OS) and secondary outcomes were margin-positive resection (>R0) and pathologic nodal upstaging. RESULTS: A total 1948 patients met study criteria: 619 (32%) underwent WR, 96 (5%) SR, and 1233 (63%) LB. Patients receiving LB were more likely to be younger, have fewer comorbidities, and be privately insured. The unadjusted 5-year OS of WR, SR, and LB patients was 31% (95% confidence interval [CI], 27-35), 35% (95% CI, 25-49), and 45% (95% CI, 42-49), respectively. In a multivariable Cox model, WR was associated with worse OS (hazard ratio, 1.53; 95% CI, 1.31-1.79) and SR similar OS (hazard ratio, 1.20; 95% CI, 0.87-1.67) compared with LB. SR was associated with similar survival compared with LB in a propensity score-matched multivariable analysis as well. WR was also associated with greater odds of >R0 resection compared with LB. CONCLUSIONS: In this study, patients with limited-stage SCLC undergoing WR experienced worse survival compared with those undergoing LB; survival was similar between segmentectomy and LB.

Impact of Age on Surgical Outcomes for Locally Advanced Esophageal Cancer.

BACKGROUND: Older patients are often considered high-risk surgical candidates for locally advanced esophageal cancer, and the benefit of surgery in this population is unclear. This national analysis examines the effect of age on esophagectomy outcomes and compares surgery versus chemoradiation in older patients. METHODS: The National Cancer Database was used to identify patients with clinical stage II to III esophageal adenocarcinoma undergoing surgery or definitive chemoradiation between 2004 and 2015. Restricted cubic splines were used to examine the relationship between age and survival after esophagectomy, and maximally selected rank statistics were used to identify an age at which survival worsened. We used Cox proportional hazard models including an interaction term between age and treatment to compare overall survival, as well as survival of patients receiving esophagectomy versus definitive chemoradiation. RESULTS: Of 17,495 patients, 11,680 underwent esophagectomy and 5815 received chemoradiation. Survival after esophagectomy worsened with increasing age and decreased considerably after age 73 (hazard ratio = 1.05, 95% confidence interval, 1.04-1.06, per increasing year after 73 versus hazard ratio = 1.01, 95% confidence interval, 1.00-1.01, per increasing year to 73; both P < .001). Chemoradiation was increasingly used over surgery as age increased. The interaction between age and treatment was significant, and a graph of this interaction demonstrated a survival benefit for surgery over chemoradiation at most ages, including octogenarians. CONCLUSIONS: Survival worsens with age after esophagectomy for locally advanced esophageal cancer. However, esophagectomy is associated with improved survival compared with definitive chemoradiation at most ages, including octogenarians. Esophagectomy may be considered over chemoradiation for patients who can tolerate surgery regardless of age.

The Effect of Tumor Size and Histologic Findings on Outcomes After Segmentectomy vs Lobectomy for Clinically Node-Negative Non-Small Cell Lung Cancer.

BACKGROUND: The interaction between tumor size and the comparative prognosis of lobar and sublobar resection has been defined poorly. RESEARCH QUESTION: The purpose of this study was to characterize the relationship between tumor size and the receipt of segmentectomy or lobectomy in association with overall survival in patients with clinically node-negative non-small cell lung cancer (NSCLC). STUDY DESIGN AND METHODS: The 2004-2015 National Cancer Database (NCDB) was queried for patients with cT1-3N0M0 NSCLC who underwent segmentectomy or lobectomy without neoadjuvant therapy or missing survival data. The primary outcome was overall survival, which was evaluated using multivariate Cox proportional hazards including an interaction term between tumor size and type of surgery. RESULTS: A total of 143,040 patients were included: 135,446 (95%) underwent lobectomy and 7594 (5%) underwent segmentectomy. In multivariate Cox regression, a significant three-way interaction was found among tumor size, histologic results, and type of surgery (P < .001). When patients were stratified by histologic results, lobectomy was associated with significantly improved survival compared with segmentectomy beyond a tumor size of approximately 10 mm for adenocarcinoma and 15 mm for squamous cell carcinoma that was recapitulated in subgroup analyses. No interaction between tumor size and type of surgery was found for patients with neuroendocrine tumors. INTERPRETATION: In this NCDB study of patients with node-negative NSCLC, we found different tumor size thresholds, based on histologic results, that identified populations of patients who least and most benefitted from lobectomy compared with segmentectomy.

Patterns of Care in Neoadjuvant Chemoradiotherapy for Node-Positive Esophageal Adenocarcinoma.

BACKGROUND: The aims of this study were to examine the factors associated with use of neoadjuvant chemoradiotherapy (NCR) for patients with locally advanced esophageal cancer and to evaluate the effect of NCR on survival. METHODS: The 2004 to 2015 National Cancer Database was used to identify patients with cT1-4aN1-3M0 (stage II-IVA) esophageal adenocarcinoma who underwent esophagectomy. Patients were stratified by receipt of NCR. A multivariable logistic regression was performed to examine factors associated with NCR, and survival between the 2 groups was compared using a multivariable Cox model. RESULTS: Of 8076 patients meeting the study criteria, 1616 (20%) did not receive NCR and 6460 (80%) did. In a multivariable regression, factors associated with receipt of NCR were a later year of diagnosis, treatment in a high-volume center, and clinical stage III disease. Factors associated with nonreceipt of NCR were increasing age, comorbidities, and treatment in a Middle Atlantic, South Central, or Pacific state. Receipt of trimodality therapy was associated with improved survival compared with other or no perioperative therapies (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74-0.87). CONCLUSIONS: Numerous personal-, demographic-, and treatment center-related factors account for variability in NCR for clinically node-positive esophageal adenocarcinoma, although neoadjuvant therapy was associated with a survival benefit. Further efforts are needed to identify reasons for these differences and design interventions to provide more equitable care for patients with esophageal cancer.

Effect of Lymph Node Assessment on Outcomes in Surgery for Limited Stage Small Cell Lung Cancer.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend surgery for limited stage small cell lung cancer (SCLC). However, there is no literature on minimum acceptable lymph node retrieval in surgery for SCLC. METHODS: The National Cancer Database was queried for adult patients undergoing lobectomy for limited stage (cT1-2N0M0) SCLC from 2004 to 2015. Patients with unknown survival, staging, or nodal assessment, and patients who received neoadjuvant therapy were excluded. The number of lymph nodes assessed was studied both as a continuous variable and as a categoric variable stratified into distribution quartiles. The primary outcome was overall survival and the secondary outcome was pathologic nodal upstaging. RESULTS: A total of 1051 patients met study criteria. In multivariable analysis, only a retrieval of eight to 12 nodes was associated with a significant survival benefit (hazard ratio 0.73; 95% confidence interval, 0.56 to 0.98). However, when modeled as a continuous variable, there was no association between number of nodes assessed and survival (hazard ratio 1.00; 95% confidence interval, 0.98 to 1.02). The overall rate of pathologic nodal upstaging was 19%. Modeled as a continuous variable, more than seven lymph nodes assessed at time of resection was significantly associated with nodal upstaging in multivariable regression (odds ratio 1.03; 95% confidence interval, 1.01 to 1.06). CONCLUSIONS: In this study, there was no clear difference in survival based on increasing the number of lymph nodes assessed during lobectomy for limited stage SCLC. However, the number of retrieved lymph nodes was associated with pathologic nodal upstaging. Therefore, patients may benefit from retrieval of more than seven lymph nodes during lobectomy for SCLC.

Permissive Hypertension and Collateral Revascularization May Allow Avoidance of Cerebrospinal Fluid Drainage in Thoracic Endovascular Aortic Repair.

BACKGROUND: The utility of cerebrospinal fluid drainage (CSFD) for prevention of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) remains unclear. We previously published our institutional algorithm restricting preoperative CSFD to patients deemed high risk for SCI. Since that publication, our algorithm has evolved with preoperative CSFD avoided in all patients undergoing isolated descending TEVAR with or without arch involvement (+/- arch TEVAR). This study evaluated the updated algorithm in a contemporary cohort. METHODS: Patients who underwent TEVAR for descending aortic +/-arch pathology between February 2012 and September 2018 at a single center were identified from an institutional aortic surgery database. The algorithm includes left subclavian artery (LSA) revascularization in cases of coverage with no preservation of antegrade flow, permissive hypertension, and use of evoked potential monitoring. The primary end points were SCI or postoperative CSFD. RESULTS: During the study interval, 225 patients underwent descending +/- arch TEVAR. CSFD was used before TEVAR in 2 patients (0.9%) in violation of the algorithm, and they were excluded from the study cohort. Endograft coverage below T6 occurred in 81%. The LSA was fully covered in 100 patients (47%), all of whom underwent LSA revascularization. Following the updated algorithm, the incidence of temporary or permanent SCI was 0%. No patient required postoperative CSFD. CONCLUSIONS: A restrictive lumbar CSFD algorithm, including permissive hypertension and LSA revascularization in the setting of descending +/- arch TEVAR, appears safe, with a 0% incidence of SCI in 223 consecutive patients treated during a 6.5-year interval. We recommend consideration of further prospective study to evaluate this algorithm.

The Role of Neoadjuvant Chemotherapy in Patients With Resectable Malignant Pleural Mesothelioma-An Institutional and National Analysis.

BACKGROUND: There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM. METHODS: Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004-2015 NCDB was used to identify MPM patients with clinical stage I-IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models. RESULTS: A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR. CONCLUSIONS: In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM.

Aortic valve repair with a newly approved geometric annuloplasty ring in patients undergoing proximal aortic repair: early results from a single-centre experience.

OBJECTIVES: Aortic insufficiency (AI) is common in patients with proximal aortic disease, but limited options exist to facilitate aortic valve repair (AVr) in this population. This study reports 'real-world' early results of AVr using newly FDA-approved trileaflet and bicuspid geometric annuloplasty rings for patients with AI undergoing proximal aortic repair (PAR) in a single referral centre. METHODS: All patients undergoing AVr with a rigid internal geometric annuloplasty ring (n = 47) in conjunction with PAR (ascending +/- root +/- arch) were included. Thirty-six patients underwent AVr with a trileaflet ring, and 11 patients underwent AVr with a bicuspid ring. The rings were implanted in the subannular position, and concomitant leaflet repair was performed if required for cusp prolapse identified after ring placement. RESULTS: The median age was 58 years [interquartile range (IQR) 46-70]. PAR included supracoronary ascending replacement in 26 (55%) patients and remodelling valve-sparing root replacement with selective sinus replacement in 20 (42%) patients. Arch replacement was performed in 38 (81%) patients, including hemi-arch in 34 patients and total arch in 4 patients. There was no 30-day/in-hospital mortality. Preoperative AI was 3-4+ in 37 (79%) patients. Forty-one (87%) patients had zero-trace AI on post-repair transoesophageal echocardiography, and 6 patients had 1+ AI. The median early post-repair mean gradient was 13 mmHg (IQR 5-20). Follow-up imaging was available in 32 (68%) patients at a median of 11 months (IQR 10-13) postsurgery. AI was ≤1+ in 97% of patients with 2+ AI in 1 patient. All patients were alive and free from aortic valve reintervention at last follow-up. CONCLUSIONS: Early results with geometric rigid internal ring annuloplasty for AVr in patients undergoing PAR appear promising and allow a standardized approach to repair with annular diameter reduction and cusp plication when needed. Longer-term follow-up will be required to ensure the durability of the procedure.

The effect of age on survival after endoscopic resection versus surgery for T1a esophageal cancer.

BACKGROUND: Endoscopic resection has emerged as a treatment option for T1a esophageal cancer, but the impact of age on patient selection for surgery versus endoscopic resection has not been well studied. We hypothesized that endoscopic resection would be associated with improved survival compared with surgery in older patients with early esophageal cancer and worse survival in younger patients. METHODS: The National Cancer Database was used to identify patients with cT1aN0M0 esophageal cancer (2010-2015) treated with endoscopic resection or esophagectomy. The relationship between age and treatment effect on survival was modeled with an interaction term in a Cox proportional hazards regression. The primary outcome was overall survival. RESULTS: A total of 831 patients met study criteria: A total of 448 patients (54%) underwent endoscopic resection, and 383 patients (46%) underwent esophagectomy. In a multivariable Cox model, the interaction term between patient age and type of treatment was nonsignificant (P = .11), suggesting that age did not influence the effect of endoscopic resection compared with surgery on survival. In 285 propensity score-matched patients receiving endoscopic resection or surgery, surgery was associated with similar survival compared with endoscopic resection (hazard ratio, 1.40; 95% confidence interval, 0.97-2.03). CONCLUSIONS: Endoscopic resection was associated with similar survival compared with surgery in patients with cT1a esophageal cancer regardless of age. Endoscopic resection can be considered for patients at low risk of nodal involvement across all age groups as an alternative to surgery for T1a esophageal cancer.

The Role of Adjuvant Therapy in Patients With Margin-Positive (R1) Esophagectomy: A National Analysis.

BACKGROUND: We performed a nationwide analysis to assess the impact of adjuvant therapy on survival after a microscopically margin-positive (R1) resection for esophageal cancer. METHODS: The National Cancer Database was used to identify patients with R1 resection for esophageal cancer (2004-2015). Patients were grouped by type of adjuvant therapy. Patients who had other margin status, M1 disease, neoadjuvant chemotherapy and radiation, missing survival, and no or unknown treatment were excluded. The primary outcome was overall survival. A 1:1 propensity score-matched sensitivity analysis was also performed comparing patients who received no adjuvant therapy with those who received adjuvant chemoradiation. RESULTS: Of 546 patients, 279 (51%) received adjuvant therapy and 267 (49%) did not. Patients receiving adjuvant therapy were more likely to be younger, have more advanced pathologic stage, have nonsquamous histology, and have shorter hospitalization. In multivariable analysis, adjuvant chemotherapy, radiation, and chemoradiation were all associated with improved survival compared with no adjuvant therapy. In a propensity score-matched analysis of 123 patient pairs, adjuvant chemoradiation was associated with improved survival compared with no adjuvant therapy (adjusted HR: 0.30; 95% CI: [0.22, 0.40]). CONCLUSIONS: Adjuvant therapy is associated with improved survival compared with no adjuvant therapy in patients with R1 resection for esophageal cancer even after adjustment for pathologic stage. Adjuvant therapy should be considered in patients with incompletely resected esophageal cancer in concordance with national guidelines.

Effect of time to surgery on outcomes in stage I esophageal adenocarcinoma.

BACKGROUND: There are limited data on the safe interval from diagnosis to surgery in patients with stage I esophageal adenocarcinoma. We hypothesized that increased time to surgery would be associated with worse survival and increased nodal upstaging. METHODS: The National Cancer Database was used to identify patients with cT1N0M0 esophageal adenocarcinoma (2004-2015) who underwent esophagectomy without induction therapy. The primary outcome was survival, and the secondary outcomes were the rate of margin-positive resection and pathologic nodal upstaging. Time to surgery was modeled as a categoric variable, dividing patients into quartiles (Q1-4), and as a continuous variable using piecewise linear splines centered on 50 and 100 days. RESULTS: A total of 2495 patients met study criteria. When examined in quartiles, there was no difference in survival between groups based on time to surgery in both unadjusted and multivariable analyses. As a continuous variable, increasing time to surgery less than 50 days was associated with improved survival (hazard ratio, 0.99; 95% confidence interval, 0.98-1.00), and time to surgery greater than 100 days was associated with worse survival (hazard ratio, 1.00; 95% confidence interval, 1.00-1.01) and increased margin-positive resection (odds ratio, 1.01; 95% confidence interval, 1.00-1.02). Treatment at a high-volume center, government insurance, and diagnosis and treatment at different centers were associated with surgery beyond 100 days. CONCLUSIONS: Increasing time to surgery greater than 100 days is associated with worse outcomes in patients with stage I esophageal adenocarcinoma. In this patient population, esophagectomy should be offered as soon as safely possible.

The influence of adjuvant therapy on survival in patients with indeterminate margins following surgery for non-small cell lung cancer.

BACKGROUND: The significance of indeterminate margins following surgery for non-small cell lung cancer (NSCLC) is unknown. We evaluated the influence of adjuvant therapy on survival in patients whose cancer showed indeterminate margins. METHODS: Patients whose cancer showed indeterminate margins following surgery for NSCLC were identified in the National Cancer Database between 2004 and 2015, and stratified by receipt of adjuvant treatment. The primary outcome was overall survival, which was evaluated with multivariable Cox proportional hazards. RESULTS: Indeterminate margins occurred in 0.31% of 232,986 patients undergoing surgery for NSCLC and was associated with worse survival compared with margin negative resection (adjusted hazard ratio, 1.53; 95% confidence interval, 1.40-1.67). Anatomic resection was protective against the finding of indeterminate margins in logistic regression. Amongst 553 patients with indeterminate margins, 343 (62%) received no adjuvant therapy, 96 (17%) received adjuvant chemotherapy, 33 (6%) received adjuvant radiation, and 81 (15%) received adjuvant chemoradiation. Any mode of adjuvant therapy was not associated with improved survival compared with no further treatment. CONCLUSIONS: The finding of indeterminate margins is reported in 0.31% of patients undergoing curative-intent surgery for NSCLC. This was associated with worse overall survival compared with complete resection and not mitigated by adjuvant therapy. The risks and benefits of adjuvant therapy should be carefully considered for patients with indeterminate margins after surgery for NSCLC.

Outcomes of surgery versus chemoradiotherapy in patients with clinical or pathologic stage N3 non-small cell lung cancer.

BACKGROUND: Because surgery is rarely recommended, there is minimal literature comparing the outcomes of surgery and chemoradiation in stage N3 non-small cell lung cancer (NSCLC). We examined the outcomes of definitive chemoradiation versus multimodality therapy, including surgery, for patients with clinical and pathologic stage N3 NSCLC. METHODS: The National Cancer Database was used to identify patients with clinical stage T1 to T3 N3 M0 NSCLC and clinical stage T1 to T3 Nx M0 with pathologic stage N3 NSCLC who were treated with either definitive chemoradiation or surgery between 2004-2015. A 1:1 propensity score-matched analysis was used to compare outcomes for both treatment groups in each analysis. The primary outcome was overall survival. RESULTS: In 935 matched patient pairs with clinical stage N3 NSCLC, surgery was associated with worse survival (hazard ratio, 1.52; 95% confidence interval, 1.12-2.05) compared with chemoradiation at 6 months, but was associated with a significant survival benefit after 6 months (hazard ratio, 0.54; confidence interval, 0.47-0.63) in multivariable analysis. In 281 pairs of patients with pN3 NSCLC, surgery had similar survival compared with chemoradiation at 6 months (hazard ratio, 1.71; 95% confidence interval, 0.92-3.19), but was associated with improved survival after 6 months (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). The complete resection rate was 80% and 73% for patients with clinical stage N3 and pathologic stage N3 disease, respectively. CONCLUSIONS: In patients with clinical or pathologic stage N3 NSCLC, surgery is associated with similar or worse short-term but improved long-term survival compared with chemoradiation. In a selected group of patients with stage N3 NSCLC, surgery may have a role in multimodal therapy.

Outcomes for Surgery in Large Cell Lung Neuroendocrine Cancer.

INTRODUCTION: There are limited small, single-institution observational studies examining the role of surgery in large cell neuroendocrine cancer (LCNEC). We investigated the outcomes of surgery for stage I to IIIA LCNEC by using the National Cancer Database. METHODS: Patients with stage I to IIIA LCNEC were identified in the National Cancer Database (2004-2015) and grouped by treatment: definitive chemoradiation versus surgery. Overall survival, by stage, was the primary outcome. Outcomes of surgical patients were also compared with those of patients with SCLC or other non-small cell histotypes. RESULTS: A total of 6092 patients met the criteria: 96%, 94%, 75%, and 62% of patients received an operation for stage I, II, IIIA, and cN2 disease, respectively. Complete resection was achieved in at least 85% of patients. The 5-year survival rates for patients undergoing an operation for stage I and II LCNEC were 50% and 45%, respectively. Surgical patients with stage IIIA and N2 disease had 36% and 32% 5-year survival rates, respectively. When compared with stereotactic body radiation in stage I disease and chemoradiation in patients with stage II to IIIA disease, surgery was associated with a survival benefit. Patients with LCNEC who underwent an operation generally experienced worse survival by stage than did those with adenocarcinoma but experienced improved survival compared with patients with SCLC. Perioperative chemotherapy was associated with improved survival for pathologic stage II to IIIA disease. CONCLUSIONS: Surgery is associated with reasonable outcomes for stage I to IIA LCNEC, although survival is generally worse than for adenocarcinoma. Surgery should be offered to medically fit patients with both early and locally advanced LCNEC, with guideline-concordant induction or adjuvant therapy.

Surgery Is Associated With Survival Benefit in T4a Esophageal Adenocarcinoma: A National Analysis.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend consideration of surgery for clinical T4a esophageal adenocarcinoma. There are limited data on the outcomes of patients with T4a adenocarcinoma treated with surgery vs definitive chemoradiation, however. METHODS: The National Cancer Database was used to identify patients from 2010-2015 with clinical T4aN0-3M0 esophageal adenocarcinoma, and grouped by receipt of surgery (with or without perioperative therapy) or definitive, concurrent chemoradiation. Patients receiving incomplete definitive therapy or with missing survival information were excluded. Overall survival was evaluated with Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 182 patients in the study, 85 (47%) underwent esophagectomy and 97 (53%) underwent chemoradiation. In the surgery cohort, 79 patients (93%) received perioperative chemotherapy. Unadjusted and multivariable analyses demonstrated a significant survival benefit associated with surgery compared with definitive chemoradiotherapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21, 0.50). A 1:1 propensity score-matched analysis of 63 patient pairs also revealed a significant overall survival benefit with surgery compared with chemoradiotherapy alone (hazard ratio 0.26; 95% confidence interval 0.16, 0.43). CONCLUSIONS: In this national analysis, surgery for cT4a esophageal adenocarcinoma was associated with improved outcomes when compared with definitive chemoradiation. Surgery should be considered for medically fit patients with cT4aN0-3M0 esophageal adenocarcinoma.