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Although preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer.Outcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis.From 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups.In this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Background During the COVID-19 pandemic, patients with lung cancer may experience treatment delays. The objective of this study was to evaluate the impact of extended treatment delays on survival among patients with stage I typical bronchopulmonary carcinoid (BC), lepidic predominant adenocarcinoma (LPA) or invasive adenocarcinoma with a lepidic component (ADL). Methods Using National Cancer Database data (2004-2015), multivariable Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage I BC, LPA, and ADL. Propensity score–matched analyses compared the overall survival of patients who received “early” vs “delayed” surgery (ie, 0-30 vs 90-120 days after diagnosis) across the different histologic subtypes. Results During the study period, patients with stage I BC (n = 4947), LPA (n = 5340), and ADL (n = 6816) underwent surgery. Cox regression analysis of these cohorts showed a gradual steady increase in the hazard ratio the longer treatment is delayed. However, in propensity score–matched analyses that created cohorts of patients who underwent early and delayed surgery that were well-balanced in patient characteristics, no significant differences in 5-year survival were found between early and delayed surgery for stage I BC (87% [95% CI:77%-93%] vs 89% [95% CI: 80%-94%]), stage I LPA (73% [95% CI: 64%-80%] vs 77% [95% CI: 68%-83%]), and stage I ADL (71% [95% CI: 64%-76%] vs 69% [95% CI: 60%-76%]). Conclusions During the COVID-19 pandemic, for early-stage indolent lung tumors and part-solid ground glass lung nodules, a delay of surgery by 3-4 months after diagnosis can be considered.

BACKGROUND Enhanced recovery after surgery pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on postoperative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission. METHODS Patients who underwent a lobectomy for lung cancer between 2011 and 2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD 1) and patients discharged on POD 2 to 6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis. RESULTS Only 854 (3.8%) of 22,585 patients who met inclusion criteria were discharged on POD 1, although POD 1 discharge rates increased from 2.3% to 8.1% (P < .001) from 2011 to 2019, respectively. Median hospitalization for patients discharged on POD 2 to 6 was 4 days (interquartile range, 3 to 5 days). Patients' characteristics associated with a lower likelihood of POD 1 discharge were increasing age, smoking, or a history of dyspnea, whereas a minimally invasive approach was the strongest predictor of early discharge (adjusted odds ratio, 5.42; P < .001). Readmission rates were not significantly different for the POD 1 and POD 2 to 6 groups in univariate analysis (6.0% vs 7.0%; P = .269). Further, POD 1 discharge was not a risk factor for readmission in multivariable analysis (adjusted odds ratio, 1.10; P = .537). CONCLUSIONS Select patients can be discharged on POD 1 after lobectomy for lung cancer without an increased readmission risk, a finding supporting this accelerated discharge target inclusion in lobectomy enhanced recovery after surgery protocols.

In this era of value-based healthcare, costs must be measured alongside patient outcomes to prioritize quality improvement and inform performance-based reimbursement strategies. We sought to identify drivers of costs for patients undergoing minimally invasive esophagectomy for esophageal cancer.Patients who underwent minimally invasive esophagectomy for esophageal cancer from December 2008 to March 2020 were included. Our institutional Society of Thoracic Surgeons database was merged with financial data to determine inpatient direct accounting costs in 2020 US dollars for total, operative (surgery and anesthesia), and postoperative (intensive care, floor, radiology, laboratory, etc) services. A supervised machine learning quantitative method, the lasso estimator with 10-fold cross-validation, was applied to identify predictors of costs.In the study cohort (n = 240) most had ≥cT2 pathology (82%), adenocarcinoma histology (90%), and received neoadjuvant therapy (78%). Mean length of stay was 8.00 days (SD, 4.13) with 45% inpatient morbidity rate and no deaths. The largest proportions of cost were from the operating room (30%), inpatient floor (30%), and postanesthesia care/intensive care units (20%). Preoperative predictors of operative costs were age (-5.18% per decade [95% confidence interval {CI}, -9.95 to -0.27], P = .039), body mass index ≥ 30 (+12.9% [95% CI, 0.00-27.5], P = .050), forced expiratory volume in 1 second (-3.24% per 10% forced expiratory volume in 1 second [95% CI, -5.80 to -0.61], P = .017), and year of surgery (+2.55% [95% CI, 0.97-4.15], P = .002). Predictors of postoperative costs were postoperative renal failure (+91.6% [95% CI, 9.93-233.8], P = .022), respiratory failure (+414.6% [95% CI, 158.7-923.6], P .001), pneumonia (+136.1% [95% CI, 71.1-225.8], P.001), and reoperation (+60.5% [95% CI, 21.5-111.9], P = .001).Costs associated with minimally invasive esophagectomy are driven by preoperative risk factors and postoperative outcomes. These data enable surgeons and policymakers to reduce cost variation, improve quality through standardization, and ultimately provide greater value to patients.

Objective: To assess the association between the timing of surgery relative to the development of Covid-19 and the risks of postoperative complications. Summary Background Data: It is unknown whether patients who recovered from Covid-19 and then underwent a major elective operation have an increased risk of developing postoperative complications. Methods: The risk of postoperative complications for patients with Covid-19 undergoing 18 major types of elective operations in the Covid-19 Research Database was evaluated using multivariable logistic regression. Patients were grouped by time of surgery relative to SARS-CoV-2 infection; that is, surgery performed: (1) before January 1, 2020 (“pre-Covid-19”), (2) 0 to 4 weeks after SARS-CoV-2 infection (“peri-Covid-19”), (3) 4 to 8 weeks after infection (“early post-Covid-19”), and (4) ≥8 weeks after infection (“late post-Covid-19”). Results: Of the 5479 patients who met study criteria, patients with peri-Covid-19 had an elevated risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI): 4.06–10.27], respiratory failure (aOR, 3.36; 95% CI: 2.22–5.10), pulmonary embolism (aOR, 2.73; 95% CI: 1.35–5.53), and sepsis (aOR, 3.67; 95% CI: 2.18–6.16) when compared to pre-Covid-19 patients. Early post-Covid-19 patients had an increased risk of developing postoperative pneumonia when compared to pre-Covid-19 patients (aOR, 2.44; 95% CI: 1.20–4.96). Late post-Covid-19 patients did not have an increased risk of postoperative complications when compared to pre-Covid-19 patients. Conclusions: Major, elective surgery 0 to 4 weeks after SARS-CoV-2 infection is associated with an increased risk of postoperative complications. Surgery performed 4 to 8 weeks after SARS-CoV-2 infection is still associated with an increased risk of postoperative pneumonia, whereas surgery 8 weeks after Covid-19 diagnosis is not associated with increased complications.

The American Joint Committee on Cancer (AJCC) eighth edition TNM staging manual for NSCLC, derived from the International Association for the Study of Lung Cancer (IASLC) Staging Project, designates tumors with additional nodule(s) in the same lobe as T3. This study sought to externally validate the results of the IASLC, which showed a trend in improved survival for such tumors, but excluded treatment-based adjustment, by assessing whether these tumors have worse survival than T2b NSCLC.Overall survival of patients with T2b-T3, N0-3, M0 NSCLC (satisfying a single T descriptor of tumors4 cm but ≤5 cm in greatest dimension ["T2b"], tumors5 cm but ≤7 cm in greatest dimension ["T3-Size"], or tumors with additional nodule(s) in the same lobe ["T3-Add"]), according to the AJCC eighth edition, in the National Cancer Database (2010-2015), was evaluated using multivariable Cox proportional hazards modeling and propensity score matching.31,563 patients with T2b-T3, N0-3, M0 NSCLC met the study inclusion criteria. In multivariable-adjusted analysis, T3-Add tumors had improved overall survival compared with T3-Size tumors (Hazard Ratio = 0.86, 95% Confidence Interval: 0.82-0.89, p0.001) and similar survival compared with T2b tumors (Hazard Ratio = 1.04, 95% Confidence Interval: 0.97-1.12, p = 0.28). A propensity score-matched analysis of 2260 T3-Add and 2,260 T2b patients, well-balanced on 16 common prognostic covariates, including treatment type (surgery, chemotherapy, or radiation), revealed similar 5-year survival (53.4% versus 52.3%, p = 0.30).In this national analysis, T3-Add tumors had better survival than other T3 tumors and similar survival to T2b tumors. These findings may be taken into consideration for the AJCC ninth edition staging classifications.

BACKGROUND A Medicare effect has been described to account for increased health care utilization occurring at the age of 65 years. The existence of such an effect in cancer care, where it would be most likely to reduce mortality, has been unclear. METHODS Patients aged 61 to 69 years who were diagnosed with lung, breast, colon, or prostate cancer from 2004 to 2016 were identified with the Surveillance, Epidemiology, and End Results database and were dichotomized on the basis of eligibility for Medicare (61-64 vs 65-69 years). With age-over-age (AoA) percent change calculations, trends in cancer diagnoses and staging were characterized. After matching, uninsured patients who were 61 to 64 years old (pre-Medicare group) were compared with insured patients who were 65 to 69 years old (post-Medicare group) with respect to cancer-specific mortality. RESULTS In all, 134,991 patients were identified with lung cancer, 175,558 were identified with breast cancer, 62,721 were identified with colon cancer, and 238,823 were identified with prostate cancer. The AoA growth in the number of cancer diagnoses was highest at the age of 65 years in comparison with all other ages within the decade for all 4 cancers (P < .01, P < .001, P < .01, and P < .001, respectively). In a comparison of diagnoses at the age of 65 years with those in the 61- to 64-year-old cohort, the greatest difference for all 4 cancers was seen in stage I. In matched analyses, the 5-year cancer-specific mortality was worse for lung (86.3% vs 78.5%; P < .001), breast (32.7% vs 11.0%; P < .001), colon (57.1% vs 35.6%; P < .001), and prostate cancer (16.9% vs 4.8%; P < .001) in the uninsured pre-Medicare group than the insured post-Medicare group. CONCLUSIONS The age threshold of 65 years for Medicare eligibility is associated with more cancer diagnoses (particularly stage I), and this results in lower long-term cancer-specific mortality for all cancers studied. LAY SUMMARY Contributing to the current debate regarding Medicare for all, this study shows that the expansion of Medicare would improve cancer outcomes for the near elderly.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Background While stereotactic ablative radiotherapy (SABR) is increasingly emerging as an alternative to surgery for node-negative non-small cell lung cancer (NSCLC), 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 NSCLC. 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 three-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 NCDB analysis, sublobar resection was associated with greater survival compared to SABR for lesions >6 or 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.

The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent sleeve lobectomy for non-small-cell lung cancer (NSCLC). Outcomes of patients with cT1-T3, N0-N2, M0 NSCLC who underwent sleeve lobectomy in the National Cancer Data Base (NCDB) from 2010-2015 were assessed using Kaplan-Meier, propensity score-matching, and Cox proportional hazards analyses. An "intent-to-treat" analysis was performed. In the NCDB, 210 sleeve lobectomy patients met inclusion criteria (VATS 44 [21%], thoracotomy 166 [79%]). Nine (20%) of the VATS cases were converted to open. Compared to an open approach, VATS was associated with no significant differences in lymph nodes examined (median 9.5 vs 9.0; p = 0.72), length of stay (median 6 days vs 6 days; p = 0.36), 30-day mortality (4.5% vs 1.8%; p = 0.28), and 90-day mortality (6.8% vs 4.8%; p = 0.70). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [85%] vs open [79%]; log-rank p = 0.91) and in a propensity score-matched analysis of 86 patients (log-rank p = 0.75). Furthermore, a VATS approach was also not associated with worse survival in multivariable analysis (HR = 0.64; 95% CI [0.23-1.78]; p = 0.39). In this national analysis, a VATS approach for sleeve lobectomy for NSCLC was not associated with worse short-term or long-term outcomes when compared to an open approach.

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 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.

Existing guidelines for surveillance after non-small-cell lung cancer (NSCLC) treatment are inconsistent and have relatively sparse supporting literature. This study characterizes detection rates of metachronous and recurrent disease during surveillance with computed tomography scans after definitive treatment of early stage NSCLC.The incidence of metachronous and recurrent disease in patients who previously underwent complete resection via lobectomy for stage IA NSCLC at a single center from 1996 to 2010 were evaluated. A subgroup analysis was used to compare survival of patients whose initial surveillance scan was 6 ± 3 months (early) versus 12 ± 3 months (late) after lobectomy.Of 294 eligible patients, 49 (17%) developed recurrent disease (14 local only, 35 distant), and 45 (15%) developed new NSCLC. Recurrent disease was found at a mean of 22 ± 19 months, and new primaries were found at a mean of 52 ± 31 months after lobectomy (P .01). Five-year survival after diagnosis of recurrent disease was significantly lower than after diagnosis of second primaries (2.3% vs. 57.5%; P .001). In the subgroup analysis of 187 patients, both disease detection on the initial scan (2% [2/94] vs. 4% [4/93]; P = .44) and 5-year survival (early, 80.8% vs. late, 86.7%; P = .61) were not significantly different between the early (n = 94) and the late (n = 93) groups.Surveillance after lobectomy for stage IA NSCLC is useful for identifying both new primary as well as recurrent disease, but waiting to start surveillance until 12 ± 3 months after surgery is unlikely to miss clinically important findings.

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

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.

Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index (p = 0.001), higher hematocrit (p 12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48–12.3, p = 0.007) and MAP

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.

This article describes the experience with the endoscopically assisted fixation of the customized total temporomandibular joint (TMJ) prosthesis in TMJ Yang's system only through a modified preauricular approach. Twenty patients (23 joints) treated with the custom-made total TMJ prosthesis were retrospectively recruited. An endoscopically assisted technique was used through a modified preauricular approach to fix the mandibular component for all these patients. These reconstructions were evaluated by surgical records, clinical examinations, and radiographic observations. All patients had successful fixation of the prosthesis. No patient had permanent weakness of the facial nerve and malocclusion or any other severe complications. The mean operative time was 111 min per joint (range, 85-133 min). The average surgical bleeding was 195 ml per side. The mean follow-up period was 16.2 months (range, 5-32 months). The mean scores were 8.3 for surgical satisfaction and 9.2 for scar healing evaluation. All patients experienced positive clinical outcomes, with a mean 75.2% reduction in pain and 53.7% increase in mouth opening with significant differences (P

Background The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis. Methods We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework. Results Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option. Conclusions Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.

A right-sided pneumonectomy after induction therapy for non-small cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the effect of laterality on long-term survival after induction therapy and pneumonectomy using the National Cancer Data Base.Perioperative and long-term outcomes of patients who underwent pneumonectomy after induction chemotherapy, with or without radiotherapy, from 2004 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.During the study period, 1,465 patients (right, 693 [47.3%]; left, 772 [52.7%]) met inclusion criteria. Right-sided pneumonectomy was associated with significantly higher 30-day (8.2% [57 of 693] vs 4.2% [32 of 772], p0.01) and 90-day mortality (13.6% [94 of 693] vs 7.9% [61 of 772], p0.01), and right-sided pneumonectomy was a predictor of higher 90-day mortality (odds ratio, 2.23; p0.01). However, overall 5-year survival between right and left pneumonectomy was not significantly different in unadjusted (37.6% [95% confidence interval {CI}, 0.34 to 0.42] vs 35% [95% CI, 0.32 to 0.39], log-rank p = 0.94) or multivariable analysis (hazard ratio, 1.07; 95% CI, 0.92 to 1.25; p = 0.40). A propensity score-matched analysis of 810 patients found no significant differences in 5-year survival between the right-sided versus left-sided groups (34.7% [95% CI, 0.30 to 0.40] vs 34.1%, [95% CI, 0.29 to 0.39], log-rank p = 0.86).In this national analysis, right-sided pneumonectomy after induction therapy was associated with a significantly higher perioperative but not worse long-term mortality compared to a left-sided procedure.

OBJECTIVE To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC). BACKGROUND There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival. METHODS Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. RESULTS Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups. CONCLUSION In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.

Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS.A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB).Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003).We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Background To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant. Methods This was a 2.5-year retrospective evaluation using 3 years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI. Results There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p = .05) and a 17% reduction in Stage 2/3 acute kidney injury (p = .09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p = .03), achieving a central venous pressure of or less than 12 mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p = .03) and mean arterial pressure above 60 mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p = .05) in the first 48 h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p = .002). Conclusions This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.

Background The outcomes associated with receipt of adjuvant radiation in patients following surgery for malignant pleural mesothelioma (MPM) are poorly understood. Objective The objective of this study was to use two registries to compare the outcomes of patients receiving adjuvant radiation or no radiation following 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 (2004-2015). The primary outcome was overall survival (OS). Propensity score-matched and landmark subgroup analyses were performed. 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 (HR 1.14; 95%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. Conclusion 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.

Background Chemotherapy is a common treatment for patients with resected non-small cell lung cancer (NSCLC). However, there are few models for predicting the survival outcomes of these patients. Here, we developed a clinical nomogram for predicting overall survival (OS) in this cohort. Methods A total of 16,661 patients with resected NSCLC treated with chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified prognostic factors and integrated them into a nomogram. The model was subjected to bootstrap internal validation using the SEER database and external validation using a database in China and the National Cancer Database (NCDB). The model's predictive accuracy and discriminative ability were tested by calibration and concordance index (C-index). Results Age, sex, number of dissected lymph nodes, extent of surgery, N stage, T stage, and grade were independent factors for OS and were integrated into the model. The calibration curves for probability of 1-, 3-, and 5-year OS showed excellent agreement between the predicted and actual survivals. The C-index of the nomogram was higher than that of the Tumor-Node-Metastasis staging system for predicting OS (training cohort, 0.62 vs. 0.58; China cohort, 0.68 vs. 0.63; NCDB cohort, 0.59 vs. 0.57). Conclusions We developed a nomogram that can present individual prediction of OS for patients with resected NSCLC who are undergoing chemotherapy. This practical prognostic tool may help clinicians in treatment planning.

The eighth edition of the staging manual for non-small cell lung cancer reclassified tumors7 cm as stage IIIA (T4 N0); previously, such tumors without nodal disease were considered stage IIB (T3 N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared with primary surgery.The National Cancer Database was queried for patients with non-small cell lung cancer with tumor size7 cm who underwent surgical resection from 2010 to 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgical resection (IC group) were compared with patients undergoing primary surgery (PS group). Propensity score matching was performed.In total, 1610 patients with cT4 N0 disease on the basis of tumor size7 cm and no tumor invasion underwent surgical resection: 1346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity score matching, the IC group had a higher rate of pN0 (78.4% vs 66.0%; P.001) and less lymphovascular invasion (13.9% vs 26.3%; P .001), but longer postoperative stays (6 days vs 5 days; P.001) and higher 30-day mortality (3.5% vs 0%; P = .002). Median 5-year survival was similar between the IC and PS groups (53.5% vs 62.2%; P = .075), and IC was not independently associated with survival (hazard ratio, 1.45; P = .146).Patients with cT4 N0 non-small cell lung cancer on the basis of tumor size7 cm and no tumor invasion of major structures have similar overall survival with either induction chemotherapy or primary surgery. Induction chemotherapy should not be routinely given for this subset of stage IIIA patients.

Background: The number of lung cancer resections performed annually in the United States has not been previously assessed. The objective of this study is to estimate the total number of lung cancer resections performed every year in the U.S. Methods: The number of lung cancer resections performed in the United States in 2016 and 2017 was estimated by using indirect multiplier methods based on the number of lung cancer resections in the National Cancer Data Base (NCDB) and the proportion of lung cancer cases captured by the NCDB using the United States Cancer Statistics Data Set as reference. Results: In 2016, 37,128 lung cancer resections were documented in the NCDB and the NCDB captured 65.2% of incident lung cancer cases in the U.S. In 2017, 36,882 lung cancer resections were documented in the NCDB and the NCDB captured 65.1% of incident lung cancer cases in the U.S. Based on these metrics, an estimated 57,000 lung cancer resections were performed in 2016 and an estimated 56,600 lung cancer resections were performed in 2017 in the U.S. Of these lung cancer resections, an estimated 10,300 (18.2%) wedge resections, 2,800 (4.9%) segmentectomies, 40,000 (70.6%) lobectomies, 80 (0.14%) bronchial sleeve resections, 1,400 (2.5%) extended lobectomies, 1,600 (2.8%) pneumonectomies, and 40 (0.07%) extended pneumonectomies were performed in 2017. Conclusion: Based on this national analysis, an approximately 56,000 to 57,000 lung cancer resections are performed in the U.S. annually. Lobectomies are the most common lung cancer operations performed in the U.S. Funding Information: None. Declaration of Interests: None. Ethics Approval Statement: Approval dated 2/2/21, Massachusetts General Hospital IRB, Institutional Review Board Number: 2020P004110.

Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non–small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

The purpose of this study was to evaluate practice patterns and outcomes for patients 80 years or older with esophageal cancer using a nationwide cancer data base. Practice patterns for patients 80 years or older with stage I-IV esophageal cancer in the National Cancer Data Base from 2004 to 2014 were analyzed. Overall survival associated with different treatment strategies were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazard models. In the study period, 40.5% and 46.2% of patients with stage I adenocarcinoma and squamous cell carcinoma, respectively, did not receive any treatment at all. Less than 11% (196/1,865) of patients with stage I-II disease underwent esophagectomy, even though surgery was associated with a better 5-year survival compared to no treatment (stage I: 47.3% [95% confidence interval [CI] 36.2–57.6%] vs 14.9% [95% CI: 11.2–19.1%]; stage II: 29.3% [95% CI 20.1–39.1%] vs 1.2% [95% CI: 0.1–5.5%]). Of the 1,596 (37.7%) patients with stage III disease who received curative-intent treatment (surgery or chemoradiation), the 5-year survival was significantly better than that of patients who received no treatment (11.9% [95% CI: 9.7–14.4% vs 4.3% [95% CI: 1.9–8.3%]). In this national analysis of patients 80 years and older with esophageal cancer, over 40% of patients with stage I disease did not receive treatment. Patients with stage I-III disease had better survival and risks and benefits of treatment for elderly patients should be discussed in a multidisciplinary setting.

The objective of this study was to compare long-term outcomes of open vs minimally invasive (MIS) segmentectomy for early stage non-small-cell lung cancer (NSCLC), which has not been previouslyevaluated using national studies. Outcomes of open vs MIS segmentectomy for clinical T1, N0, M0 NSCLC in the National Cancer Data Base (2010-2015) were evaluated using propensity score matching. Of the 39,351 patients who underwent surgery for stage IA NSCLC from 2010 to 2015, 770 underwent segmentectomy by thoracotomy and 1056 by MIS approach (876 thoracoscopic [VATS], 180 robotic). The MIS to open conversion rate was 6.7% (n = 71). After propensity score matching, all baseline characteristics were well-balanced between the open (n = 683) and MIS (n = 683) groups. When compared to the open group, the MIS group had shorter median length of stay (4 vs 5 days, P0.001) and lower 30-day mortality (0.6% vs 1.9%, P = 0.037). There were no significant differences between MIS and open groups with regard to 30-day readmission (5.0% vs 3.7%, P = 0.43), or upstaging from cN0 to pN1/N2/N3 (3.1% vs 3.6%, P = 0.89). The MIS approach was associated with similar long-term overall survival as the open approach (5-year survival: 62.3% vs 63.5%, P = 0.89; multivariable-adjusted hazard ratio: 0.99, 95% Confidence Intervial (CI): 0.82-1.21, P = 0.96). In this national analysis of open vs MIS segmentectomy for clinical stage IA NSCLC, MIS was associated with shorter length of stay and lower perioperative mortality, and similar nodal upstaging and 5-year survival when compared to segmentectomy via thoracotomy. MIS segmentectomy does not appear to compromise oncologic outcomes for clinical stage IA NSCLC.

SUMMARY There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal ( 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66–0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

This study investigated the influence of facility volume on long-term survival in patients with esophageal cancer treated with esophagectomy.Patients treated with esophagectomy for cT1 3N0 3M0 adenocarcinoma or squamous cell carcinoma of the mid-distal esophagus in the National Cancer Database between 2006 and 2013 were stratified by annual facility esophagectomy volume dichotomized as more/less than both 6 and 20. Patient characteristics associated with facility volume were evaluated using logistic regression, and the influence of facility volume on survival was evaluated with Kaplan-Meier curves, Cox proportional hazards methods, and propensity matched analysis.Of 11,739 patients who had esophagectomy at 1018 facilities where annual volume ranged from 1 to 47.6 cases, 4262 (36.3%) were treated at 44 facilities with annual esophagectomy volume 6 and 1515 (12.9%) were treated at 7 facilities with annual volume 20. Higher volume was associated with significantly better 5-year survival for both annual volume6 (47.6% vs 40.2%; P .001) and annual volume 20 (47.2% vs 42.3%; P .001), which persisted in propensity matched analyses as well as Cox multivariable analysis (hazard ratio, 0.81; 95% confidence interval, 0.74-0.89; P .001 for facility volume 6 and hazard ratio, 0.78; 95% confidence interval, 0.65-0.95; P = .01 for facility volume 20). In Cox multivariable analysis that considered facility volume as a continuous variable, higher volume continued to be associated with better survival (hazard ratio, 0.93 per 5 cases; 95% CI, 0.91-0.96; P .001).Esophageal cancer patients treated with esophagectomy at higher volume facilities have significantly better long-term survival than patients treated at lower volume facilities.

Surgery is the standard of care for early stage non-small cell lung cancer. There is significant debate about the type of operation most effective for lung cancer. Minimally invasive techniques like video-assisted (VATS) and robot-assisted thoracoscopic surgery (RATS) have been shown to reduce postoperative complications and shorten hospitalization. However, there remains skepticism about their oncologic effectiveness when compared to an open approach, though recent literature suggests no differences in upstaging or survival between VATS and thoracotomy. The extent of resection for early lung cancer also remains a matter of debate. Lobectomy remains the preferred operation and is associated with better survival and lower locoregional recurrence, but there is increased interest in the role of sublobar resections. Sublobar resections have similar mortality to lobar resections in small ground glass-predominant tumors. We examine the literature surrounding these controversies in this review.

Treatment guidelines recommend surgical resection in select cases of stage IV non-small-cell lung cancer (NSCLC) but are based on limited evidence. This study evaluated outcomes associated with surgery in stage IV disease.Factors associated with survival of stage IV NSCLC patients treated with surgery in the National Cancer Date Base (2004-2013) were evaluated using multivariable Cox proportional hazards analyses. Outcomes of the subset of patients with cT1-2, N0-1, M1 and cT3, N0, M1 disease treated with surgery or chemoradiation were evaluated using Kaplan-Meier analyses.The five-year survival of all stage IV NSCLC patients who underwent surgical resection (n=3098) was 21.1%. Outcomes were related to the locoregional extent of the primary tumor, as both increasing T status (T2 HR 1.30 [p0.001], T3 HR 1.28 [p0.001], and T4 HR 1.28 [p0.001], respectively, compared to T1) and nodal involvement (N1 HR 1.34 [p0.001], N2 HR 1.50 [p0.001], and N3 HR 1.49 [p0.001], respectively, compared to N0) were associated with worse survival. Outcomes were also related to the extent of surgical resection, as pneumonectomy (HR 1.58, p0.001), segmentectomy (HR 1.36, p=0.009), and wedge resection (HR 1.70, p0.001) were all associated with decreased survival when compared to lobectomy. The five-year survival of cT1-2, N0-1, M1 and cT3, N0, M1 patients was 25.1% (95% CI: 22.8-27.5) after surgical resection (n=1761) and 5.8% (95% CI: 5.2-6.5) after chemoradiation (n=8180).Surgery for cT1-2, N0-1, M1 or cT3, N0, M1 disease is associated with a 5-year survival of 25% and does not appear to compromise outcomes when compared to non-operative therapy, supporting guidelines that recommend surgery for very select patients with stage IV disease. However, surgery provides less benefit and should be considered much less often for stage IV patients with mediastinal nodal disease or more locally advanced tumors.

Background Because the relationship between the timing of surgery following diagnosis of lung cancer and survival has not been precisely described, guidelines on what constitutes a clinically meaningful delay of resection of early-stage lung cancer do not exist. This study tested the hypothesis that increasing the time between diagnosis and lobectomy for stage IA squamous cell carcinoma (SCC) would be associated with worse survival. Methods The association between timing of lobectomy and survival for patients with clinical stage IA SCC in the National Cancer Data Base (2006-2011) was assessed using multivariable Cox proportional hazards analysis and restricted cubic spline (RCS) functions. Results The 5-year overall survival of 4,984 patients who met study inclusion criteria was 58.3% (95% CI, 56.3-60.2). Surgery was performed within 30 days of diagnosis in 1,811 (36%) patients, whereas the median time to surgery was 38 days (interquartile range, 23, 58). In multivariable analysis, patients who had surgery 38 days or more after diagnosis had significantly worse 5-year survival than patients who had surgery earlier (hazard ratio, 1.13 [95% CI, 1.02-1.25]; P = .022). Multivariable RCS analysis demonstrated the hazard ratio associated with time to surgery increased steadily the longer resection was delayed; the threshold time associated with statistically significant worse survival was ∼90 days or greater. Conclusions Longer intervals between diagnosis of early-stage lung SCC and surgery are associated with worse survival. Although factors other than the timing of treatment may contribute to this finding, these results suggest that efforts to minimize delays beyond those needed to perform a complete preoperative evaluation may improve survival.

Background This study examined the association of extent of lung resection, pathologic nodal evaluation, and survival for patients with clinical stage I (cT1–2N0M0) adenocarcinoma with lepidic histologic features in the National Cancer Data Base. Methods The association between extent of surgical resection and long-term survival for patients in the National Cancer Data Base with clinical stage I lepidic adenocarcinoma who underwent lobectomy or sublobar resection was evaluated using Kaplan-Meier and Cox proportional hazards regression analyses. Results Of the 1991 patients with cT1–2N0M0 lepidic adenocarcinoma who met the study criteria, 1544 underwent lobectomy and 447 underwent sublobar resection. Patients treated with sublobar resection were older, more likely to be female, and had higher Charlson/Deyo comorbidity scores, but they had smaller tumors and lower T status. Of the patients treated with lobectomy, 6% (n = 92) were upstaged because of positive nodal disease, with a median of seven lymph nodes sampled (interquartile range 4–10). In an analysis of the entire cohort, lobectomy was associated with a significant survival advantage over sublobar resection in univariate analysis (median survival 9.2 versus 7.5 years, p = 0.022, 5-year survival 70.5% versus 67.8%) and after multivariable adjustment (hazard ratio = 0.81, 95% confidence interval: 0.68–0.95, p = 0.011). However, lobectomy was no longer independently associated with improved survival when compared with sublobar resection (hazard ratio = 0.99, 95% confidence interval: 0.77–1.27, p = 0.905) in a multivariable analysis of a subset of patients in which only those patients who had undergone a sublobar resection including lymph node sampling were compared with patients treated with lobectomy. Conclusions Surgeons treating patients with stage I lung adenocarcinoma with lepidic features should cautiously utilize sublobar resection rather than lobectomy, and they must always perform adequate pathologic lymph node evaluation.

Pectoral nerve blocks (PECs) can reduce intraprocedural anesthetic requirements and postoperative pain. Little is known about the utility of PECs in reducing pain and narcotic use after pacemaker (PM) or implantable cardioverter-defibrillator (ICD) placement in children.The purpose of this study was to determine whether PECs can decrease postoperative pain and opioid use after PM or ICD placement in children.A single-center retrospective review of pediatric patients undergoing transvenous PM or ICD placement between 2015 and 2020 was performed. Patients with recent cardiothoracic surgery or neurologic/developmental deficits were excluded. Demographics, procedural variables, postoperative pain, and postoperative opioid usage were compared between patients who had undergone PECs and those who had undergone conventional local anesthetic (Control).A total of 74 patients underwent PM or ICD placement; 20 patients (27%) underwent PECs. There were no differences between PECs and Control with regard to age, weight, gender, type of device placed, presence of congenital heart disease, type of anesthesia, procedural time, or complication rates. Patients who underwent PECs had lower pain scores at 1, 2, 6, 18, and 24 hours compared to Control. PECs patients had a lower mean cumulative pain score [PECs 1.5 (95% confidence interval [CI] 0.8-2.2) vs Control 3.1 (95% CI 2.7-3.5); P.001] and lower total opioid use [PECs 6.0 morphine milligram equivalent (MME)/mPECs reduce postoperative pain scores and lower total opioid usage after ICD or PM placement. PECs should be considered at the time of transvenous device placement in children.

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 oncologic efficacy of minimally invasive thymectomy for thymoma is not well characterized. We compared short-term outcomes and overall survival between open and minimally invasive (video-assisted thoracoscopic and robotic) approaches using the National Cancer Data Base.Perioperative outcomes and survival of patients who underwent open versus minimally invasive thymectomy for clinical stage I to III thymoma from 2010 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Predictors of minimally invasive use were evaluated using multivariable logistic regression. Outcomes of surgical approach were evaluated using an intent-to-treat analysis.Of the 1223 thymectomies that were evaluated, 317 (26%) were performed minimally invasively (141 video-assisted thoracoscopic and 176 robotic). The minimally invasive group had a shorter median length of stay when compared with the open group (3 [2-4] days vs 4 [3-6] days, P .001). In a propensity score-matched analysis of 185 open and 185 minimally invasive (video-assisted thoracoscopic + robotic) thymectomy, the minimally invasive group continued to have a shorter median length of stay (3 vs 4 days, P .01) but did not have significant differences in margin positivity (P = .84), 30-day readmission (P = .28), 30-day mortality (P = .60), and 5-year survival (89.4% vs 81.6%, P = .20) when compared with the open group.In this national analysis, minimally invasive thymectomy was associated with shorter length of stay and was not associated with increased margin positivity, perioperative mortality, 30-day readmission rate, or reduced overall survival when compared with open thymectomy.

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.

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p < 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p < 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.

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.

Although malignant pleural mesothelioma (MPM) is generally a disease associated with more advanced age, the association of age, treatment, and outcomes has not been well-characterized. We evaluated the impact of age on outcomes in patients with MPM to provide data for use in the treatment selection process for elderly patients with potentially resectable disease.Overall survival (OS) of patients younger than 70 and 70 years or older with Stage I to III MPM who underwent cancer-directed surgery or nonoperative management in the Surveillance, Epidemiology, and End Results database (2004-2010) was evaluated using multivariable Cox proportional hazard models and propensity score-matched analysis.Cancer-directed surgery was used in 284 of 879 (32%) patients who met inclusion criteria, and was associated with improved OS in multivariable analysis (hazard ratio, 0.71; P = .001). Cancer-directed surgery was used much less commonly in patients 70 years and older compared with patients younger than 70 years (22% [109/497] vs. 46% [175/382]; P .001), but patients 70 years and older had improved 1-year (59.4% vs. 37.9%) and 3-year (15.4% vs. 8.0%) OS compared with nonoperative management. The benefit of surgery in patients 70 years and older was observed even after propensity score-matched analysis was used to control for selection bias.Surgical treatment is associated with improved survival compared with nonoperative management for both patients younger than 70 years and patients aged 70 years or older.

// Nicole L.K. Pershing 1, * , Chi-Fu J. Yang 2, * , MengMeng Xu 1 , Christopher M. Counter 1, 3 1 Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA 2 Department of Surgery, Duke University School of Medicine, Durham, NC, USA 3 Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA * These authors have contributed equally to this work Correspondence to: Christopher M. Counter, email: count004@mc.duke.edu Keywords: nitric oxide synthase, nitric oxide, non-small cell lung cancer, RAS, preclinical trial Received: December 07, 2015 Accepted: May 12, 2016 Published: June 7, 2016 ABSTRACT Oncogenic mutations in the gene KRAS are commonly detected in non-small cell lung cancer (NSCLC). This disease is inherently difficult to treat, and combinations involving platinum-based drugs remain the therapeutic mainstay. In terms of novel, pharmacologically actionable targets, nitric oxide synthases (NOS) have been implicated in the etiology of KRAS -driven cancers, including lung cancer, and small molecular weight NOS inhibitors have been developed for the treatment of other diseases. Thus, we evaluated the anti-neoplastic activity of the oral NOS inhibitor L-NAME in a randomized preclinical trial using a genetically engineered mouse model of Kras and p53 mutation-positive NSCLC. We report here that L-NAME decreased lung tumor growth in vivo, as assessed by sequential radiological imaging, and provided a survival advantage, perhaps the most difficult clinical parameter to improve upon. Moreover, L-NAME enhanced the therapeutic benefit afforded by carboplatin chemotherapy, provided it was administered as maintenance therapy after carboplatin. Collectively, these results support the clinical evaluation of L-NAME for the treatment of KRAS mutation-positive NSCLC.