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.

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.

Comparison of failure to rescue in younger versus elderly patients following lung cancer resection.

Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients. Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80 years) cohort. Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n = 139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n = 39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P < .001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P = .01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P = .028). Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

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.

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.

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.

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.

Sublobar resection is associated with decreased survival for patients with early stage large-cell neuroendocrine carcinoma of the lung.

OBJECTIVES: Sublobar resection (SLR) for early non-small-cell lung carcinoma (NSCLC) has been shown to have a survival rate similar to that of lobectomy. Large-cell neuroendocrine carcinoma (LCNEC) of the lung, although treated like an NSCLC, has a poor prognosis compared to NSCLC. We sought to determine if outcomes are poor in patients with early stage LCNEC treated with SLR versus lobectomy. METHODS: We searched for patients with pathological stage I LCNEC ≤3 cm within the National Cancer Database between 2004 and 2014. Propensity score matching was used to compare the 5-year overall survival rate of patients having SLR (wedge or segmentectomy) to that of patients having a lobectomy. Patients were matched for age, node sampling, comorbidity score, tumour size, insurance status and other factors. Patients who received neoadjuvant therapy were excluded. Kaplan-Meier methods were used for analysis. RESULTS: A total of 1011 patients met the inclusion criteria: 263 were treated with SLR (223 wedges and 40 segmentectomies) and 748 patients, with lobectomy. Patients who received SLR were older, had more comorbidities and smaller tumours. On unadjusted Kaplan-Meier analysis, patients who had SLR had decreased 5-year overall survival compared to those who had a lobectomy (37.9% vs 56.6%, P < 0.001). Propensity score matching (1:1) across 12 demographic and tumour variables yielded 185 patients per group with 34 segmentectomies and 151 wedge resections in the SLR cohort. On Kaplan-Meier analysis of the matched cohort, patients who had SLR had a worse 5-year overall survival rate compared to those who had a lobectomy (41.5% vs 60.3%; P = 0.001). CONCLUSIONS: SLR for early stage LCNEC is associated with a lower 5-year overall survival rate compared to lobectomy on unadjusted and propensity matched analyses.

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.

Adjuvant Therapy for Patients With Early Large Cell Lung Neuroendocrine Cancer: A National Analysis.

BACKGROUND: Current guidelines do not routinely recommend adjuvant therapy for resected stage I large cell lung neuroendocrine cancer (LCNEC). However, data regarding the role of adjuvant therapy in early LCNEC are limited. This National Cancer Database (NCDB) analysis was performed to improve the evidence guiding adjuvant therapy for early LCNEC. METHODS: Overall survival (OS) of patients with pathologic T1-2a N0 M0 LCNEC who underwent resection in the NCDB from 2003 to 2015 was evaluated with Kaplan-Meier and multivariable Cox proportional hazards analyses. Patients who died within 30 days of surgery and with more than R0 resection were excluded. RESULTS: Of 2642 patients meeting study criteria, 481 (18%) received adjuvant therapy. Adjuvant chemotherapy in stage IB patients was associated with a significant increase in OS (hazard ratio, 0.67; 95% confidence interval, 0.50 to 0.90). However, there was no significant difference in survival between adjuvant chemotherapy and no adjuvant therapy for stage IA LCNEC (hazard ratio, 0.92; 95% confidence interval, 0.75 to 1.11). Adjuvant radiotherapy, whether alone or combined with chemotherapy, was not associated with a change in OS. In subgroup analysis, patients receiving adjuvant chemotherapy after lobar resection for stage IB LCNEC had a significant survival benefit compared with patients not receiving adjuvant therapy. CONCLUSIONS: In early-stage LCNEC, adjuvant chemotherapy appears to confer an additional overall survival advantage only in patients with completely resected stage IB LCNEC and not for patients with completely resected stage IA LCNEC.

Induction Chemotherapy is Not Superior to a Surgery-First Strategy for Clinical N1 Non-Small Cell Lung Cancer.

BACKGROUND: Guidelines recommend primary surgical resection for non-small cell lung cancer (NSCLC) patients with clinical N1 disease and adjuvant chemotherapy if nodal disease is confirmed after resection. We tested the hypothesis that induction chemotherapy for clinical N1 (cN1) disease improves survival. METHODS: Patients treated with lobectomy or pneumonectomy for cT1-3 N1 M0 NSCLC from 2006 to 2011 in the National Cancer Data Base were stratified by treatment strategy: surgery first vs induction chemotherapy. Propensity scores were developed and matched with a 2:1 nearest neighbor algorithm. Survival analyses using Kaplan-Meier methods were performed on the unadjusted and propensity-matched cohorts. RESULTS: A total of 5,364 cN1 patients were identified for inclusion, of which 565 (10.5%) were treated with induction chemotherapy. Clinical nodal staging was accurate in 68.6% (n = 3,292) of patients treated with surgical resection first, whereas 16.3% (n = 780) were pN0 and 10.7% (n = 514) were pN2-3. Adjuvant chemotherapy was given to 60.9% of the surgery-first patients who were pN1-3 after resection. Before adjustment, patients treated with induction chemotherapy were younger, with lower comorbidity burden, were more likely to be treated at an academic center and to have private insurance (all p < 0.001), but were significantly more likely to have T3 tumors (28.7% vs 9.9%, p < 0.001) and to require pneumonectomy (23.5% vs 18.5%, p = 0.005). The unadjusted and propensity-matched analyses found no differences in short-term outcomes or survival between groups. CONCLUSIONS: Induction chemotherapy for cN1 NSCLC is not associated with improved survival. This finding supports the currently recommended treatment paradigm of surgery first for cN1 NSCLC.