Penalized deep partially linear cox models with application to CT scans of lung cancer patients.

Lung cancer is a leading cause of cancer mortality globally, highlighting the importance of understanding its mortality risks to design effective patient-centered therapies. The National Lung Screening Trial (NLST) employed computed tomography texture analysis, which provides objective measurements of texture patterns on CT scans, to quantify the mortality risks of lung cancer patients. Partially linear Cox models have gained popularity for survival analysis by dissecting the hazard function into parametric and nonparametric components, allowing for the effective incorporation of both well-established risk factors (such as age and clinical variables) and emerging risk factors (eg, image features) within a unified framework. However, when the dimension of parametric components exceeds the sample size, the task of model fitting becomes formidable, while nonparametric modeling grapples with the curse of dimensionality. We propose a novel Penalized Deep Partially Linear Cox Model (Penalized DPLC), which incorporates the smoothly clipped absolute deviation (SCAD) penalty to select important texture features and employs a deep neural network to estimate the nonparametric component of the model. We prove the convergence and asymptotic properties of the estimator and compare it to other methods through extensive simulation studies, evaluating its performance in risk prediction and feature selection. The proposed method is applied to the NLST study dataset to uncover the effects of key clinical and imaging risk factors on patients' survival. Our findings provide valuable insights into the relationship between these factors and survival outcomes.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

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.

Stereotactic Body Radiotherapy Versus Delayed Surgery for Early-stage Non-small-cell Lung Cancer.

OBJECTIVE: To evaluate the overall survival of patients with operable stage IA non-small-cell lung cancer (NSCLC) who undergo "early" SBRT (within 0-30 days after diagnosis) versus "delayed" surgery (90-120 days after diagnosis). SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, national guidelines have recommended patients with operable stage IA NSCLC to consider delaying surgery by at least 3 months or, alternatively, to undergo SBRT without delay. It is unknown which strategy is associated with better short- and long-term outcomes. METHODS: Multivariable Cox proportional hazards modeling and propensity score-matched analysis was used to compare the overall survival of patients with stage IA NSCLC in the National Cancer Data Base from 2004 to 2015 who underwent "early" SBRT (0-30 days after diagnosis) versus that of patients who underwent "delayed" wedge resection (90-120 days after diagnosis). RESULTS: During the study period, 570 (55%) patients underwent early SBRT and 475 (45%) underwent delayed wedge resection. In multivariable analysis, delayed resection was associated with improved survival [adjusted hazard ratio 0.61; (95% confidence interval (CI): 0.50-0.76)]. Propensity-score matching was used to create 2 groups of 279 patients each who received early SBRT or delayed resection that were well-matched with regard to baseline characteristics. The 5-year survival associated with delayed resection was 53% (95% CI: 45%-61%) which was better than the 5-year survival associated with early SBRT (31% [95% CI: 24%-37%]). CONCLUSION: In this national analysis, for patients with stage IA NSCLC, extended delay of surgery was associated with improved survival when compared to early treatment with SBRT.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.

The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection.

Inflammation drives renal scarring in experimental pyelonephritis.

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.

Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.

Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high-yield modification of the ELP with myristic acid. The ELP's reversible phase behavior is retained upon myristoylation and can be tuned to span a 30-60 °C. Myristoylated ELPs provide a versatile platform for genetically pre-programming self-assembly into micelles of varied size and shape. Their lipid cores can be loaded with hydrophobic small molecules by passive diffusion. Encapsulated doxorubicin and paclitaxel exhibit cytotoxic effects on 4T1 and PC3-luc cells, respectively, with potencies similar to chemically conjugated counterparts, and longer plasma circulation than free drug upon intravenous injection in mice.

Recurrence After Complete Resection for Non-Small Cell Lung Cancer in the National Lung Screening Trial.

BACKGROUND: The objective of this study was to evaluate patterns, predictors, and long-term outcomes of recurrent disease after complete resection for early-stage non-small cell lung cancer (NSCLC) using the National Lung Screening Trial (NLST). METHODS: The frequency of recurrence in patients with pathologic stage I-II NSCLC who underwent complete resection (lobectomy or bilobectomy) in the NLST was evaluated. Predictors of increased risk of recurrence were assessed by Fine-Gray competing risks regression. RESULTS: Of the 497 patients meeting study inclusion criteria, 94 experienced a recurrence-a rate of 4.9 (95% CI, 4.0-6.0) per 100 person-years. The 5-year cumulative incidence of recurrence was 20.1% (95% CI, 16.5%-23.9%). Most patients experienced recurrences at distant sites alone (n = 47 [50.0%]) or at both locoregional and distant sites (n = 30 [31.9%]). The median time from resection to recurrence was 18.8 (10.6-30.7) months. The incidence rate of recurrence was significantly lower among patients with lung cancer detected by low-dose computed tomography screening during one of the three screening rounds of the NLST when compared with patients with lung cancer detected by chest radiography screening and patients with lung cancer not detected by any form of screening (ie, those diagnosed after a negative or missed screening exam and those diagnosed during follow-up after the three screening rounds of the NLST were completed) (P < .001). Median survival (from the date of recurrence) of patients with pathologic stage I and stage II disease who had recurrences at locoregional, distant, or both sites was 63.0, 23.1, and 9.8 months and 28.9, 8.7, and 10.2 months, respectively. CONCLUSIONS: In this analysis of NLST participants with completely resected stage I-II NSCLC, the 5-year cumulative incidence of recurrence was 20%. Nearly 82% of recurrences were at distant sites and associated with poor survival.

Extended Delay to Treatment for Stage III-IV Non-Small-Cell Lung Cancer and Survival: Balancing Risks During the COVID-19 Pandemic.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, patients may encounter lung cancer care delays. Here, we sought to examine the impact of extended treatment delay for stage III-IV non-small-cell lung cancer on patient survival. MATERIALS AND METHODS: Using National Lung Screening Trial (NLST) and National Cancer Data Base (NCDB) data, Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage III-IV lung adenocarcinoma and squamous cell carcinoma. In the NCDB, propensity score-matched analysis was used to compare cumulative survival in patients who received "early" versus "delayed" treatment (ie, 0-30 vs. 90-120 days following diagnosis). RESULTS: Cox regression analysis of the NLST (n = 392) and NCDB (n = 275,198) cohorts showed a decrease in hazard ratio the longer treatment was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed treatment for patients with stage IIIA, IIIB (T3-4,N2,M0), IIIC, and IV (M1B-C) adenocarcinoma and patients with IIIA, IIIB, IIIC, and IV squamous cell carcinoma (all log-rank P > .05). For patients with stage IIIB (T1-2,N3,M0) and stage IV (M1A) adenocarcinoma, delayed treatment was associated with improved survival (log-rank P = .03, P = .02). The findings were consistent in sensitivity analysis accounting for wait time bias. CONCLUSION: In this national analysis, for patients with stage III-IV adenocarcinoma and squamous cell carcinoma, an extended treatment delay by 3 to 4 months was not associated with significantly decreased overall survival compared to prompt treatment. These findings can be used to guide decision-making during the ongoing COVID-19 pandemic.

The Impact of Extended Delayed Surgery for Indolent Lung Cancer or Part-Solid Ground Glass Nodules.

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.

Early vs Delayed Surgery for Esophageal Cancer During the COVID-19 Pandemic.

BACKGROUND: During the coronavirus disease 2019 pandemic, national guidelines recommended that elective surgery for esophageal cancer be deferred by 3 months when hospital resources are limited. The impact of this delay on patient outcomes is unknown. We sought to evaluate the survival of patients with stage I and II/III esophageal cancer who undergo early vs delayed treatment. STUDY DESIGN: Using the National Cancer Database from 2010 to 2017, multivariable Cox proportional hazards modeling and propensity score-matched analysis were employed to compare survival of patients with stage I esophageal cancer who received early (0 to 4 weeks after diagnosis) vs delayed esophagectomy (12 to 16 weeks) and of patients with stage II/III esophageal cancer who-after receiving timely chemoradiation (0 to 4 weeks after diagnosis)-underwent early (9 to 17 weeks) vs delayed esophagectomy (21 to 29 weeks). RESULTS: For stage I esophageal cancer, 226 (41.7%) patients underwent early esophagectomy, and 316 (58.3%) patients underwent delayed esophagectomy. Propensity score matching created 2 groups of 134 patients with early or delayed esophagectomy, whose 5-year survival was comparable (hazard ratio [HR] 65.0% [95% confidence interval (CI) 55.2% to 73.2%] vs HR 65.1% [95% CI 55.6% to 73.1%], p = 0.50). For stage II/III esophageal cancer, 1,236 (86.1%) patients underwent early esophagectomy, and 200 (13.9%) underwent delayed esophagectomy. Propensity score matching created 2 groups of 130 patients; the early esophagectomy group had improved 5-year survival compared with the delayed esophagectomy group (HR 41.6% [95% CI 32.1% to 50.8%] vs HR 22.9% [95% CI 14.9% to 31.8%], p = 0.006). CONCLUSIONS: Early esophagectomy was associated with similar survival compared with delayed esophagectomy for patients with stage I esophageal cancer. For patients with stage II/III esophageal cancer, early esophagectomy was associated with improved survival relative to delayed esophagectomy.

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A nomogram for predicting overall survival in patients with resected non-small cell lung cancer treated with chemotherapy.

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.

Perioperative Outcomes and 5-year Survival After Open versus Thoracoscopic Sleeve Resection for Lung Cancer.

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.

Impact of Surveillance After Lobectomy for Lung Cancer on Disease Detection and Survival.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A Minimally Invasive Approach to Lobectomy After Induction Therapy Does Not Compromise Survival.

BACKGROUND: The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent lobectomy after induction therapy. METHODS: Outcomes of patients with T2-T4, N0, M0 and T1-T4, N1-N2, M0 non-small-cell lung cancer who received induction chemotherapy or chemoradiation followed by lobectomy in the National Cancer Data Base (2010-2014) were assessed using Kaplan-Meier, propensity score-matched, multivariable logistic regression and Cox proportional hazards analyses. RESULTS: In the National Cancer Data Base, 2887 lobectomy patients met inclusion criteria (VATS 676 [23%]; thoracotomy 2211 [77%]). Of the VATS cases, patients who underwent induction chemoradiation were more likely to undergo conversion (adjusted odds ratio 1.70, P = .05). Compared with an open approach, VATS was associated with decreased length of stay (median: 5 days vs 6 days, P < .01) and no significant differences in 30-day mortality (VATS [1.5% (n = 10)] vs open [2.6% (n = 58)]; P = .13) and 90-day mortality (VATS [3.7% (n = 25)] vs open [5.6% (n = 124)]; P = .14). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [50.3%] vs open [52.3%]; P = .83) and in a propensity score-matched analysis of 876 patients; furthermore, a VATS approach was not associated with worse survival in multivariable analysis (hazard ratio 1.02; 95% confidence interval 0.86-1.20; P = .83). CONCLUSIONS: In this national analysis, a VATS approach for lobectomy in patients who received induction therapy for locally advanced non-small-cell lung cancer was not associated with worse short-term or long-term outcomes when compared with an open approach.

The role of thoracoscopic pneumonectomy in the management of non-small cell lung cancer: A multicenter study.

OBJECTIVE: The objective of this study was to evaluate the impact of the video-assisted thoracoscopic (VATS) approach on the outcomes of patients who underwent pneumonectomy. METHODS: The effect of the surgical approach on perioperative complications and survival in patients who underwent pneumonectomy for nonmetastatic non-small cell lung cancer across 3 institutions (2000-2016) was assessed using multivariable logistic regression, Cox proportional hazards analysis, and propensity-score matching. Completion pneumonectomies were excluded from this study, and an "intent-to-treat" analysis was performed. RESULTS: During the study period, 359 patients met inclusion criteria and underwent pneumonectomy for nonmetastatic non-small cell lung cancer; 124 (35%) underwent pneumonectomy via VATS and 235 (65%) via thoracotomy. Perioperative mortality (VATS, 7% [n = 9] vs open, 8% [n = 19]; P = .75) and morbidity (VATS, 28% [n = 35] vs open, 28% [n = 65]; P = .91) were similar between the groups, even after multivariable adjustment. VATS showed similar 5-year survival when compared with thoracotomy in unadjusted analysis (47% [95% confidence interval (CI), 36-56] vs 33% [95% CI, 27-40]; P = .19), even after multivariable adjustment (hazard ratio, 0.76 [95% CI, 0.50-1.18]; P = .23). In a propensity score-matched analysis that balanced patient characteristics, there were no significant differences found in overall survival between the 2 groups (P = .69). CONCLUSIONS: Although the role of VATS pneumonectomy will likely become clearer as more surgeons report results, this multicenter study suggests that the VATS approach for pneumonectomy can be performed safely, with at least equivalent oncologic outcomes when compared with thoracotomy.

Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly.

Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials-fatty-acid-modified elastin-like polypeptides-using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a ß-sheet-forming peptide that is post-translationally functionalized with a C14 alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.

Surgical Outcomes After Neoadjuvant Chemotherapy and Ipilimumab for Non-Small Cell Lung Cancer.

BACKGROUND: The objective of this study was to evaluate the safety and feasibility of using neoadjuvant chemotherapy plus ipilimumab followed by surgery as a treatment strategy for stage II-IIIA non-small cell lung cancer. METHODS: From 2013 to 2017, postoperative data from patients who underwent surgery after neoadjuvant chemotherapy plus ipilimumab in the TOP1201 trial, an open label phase II trial (NCT01820754), were prospectively collected. The surgical outcomes from TOP1201 were compared with outcomes in a historical cohort of patients receiving standard preoperative chemotherapy followed by surgery identified from our institution's prospectively collected thoracic surgery database. RESULTS: In the TOP1201 trial, 13 patients were treated with preoperative chemotherapy and ipilimumab followed by surgery. In the historical cohort, 42 patients received preoperative chemotherapy by a platinum doublet regimen preoperative chemotherapy by a platinum doublet regimen without ipilimumab followed by lobectomy or pneumonectomy. The 30-day mortality in both groups was 0%. The most frequently occurring perioperative complications in the TOP1201 group were prolonged air leak (n = 2, 15%) and urinary tract infection (n = 2, 15%). The most common perioperative complication in the preoperative chemotherapy alone group was atrial fibrillation (n = 6, 14%). One patient (8%) had atrial fibrillation in the TOP1201 group. There was no apparent increased occurrence of adverse surgical outcomes for patients in the TOP1201 group compared with patients receiving standard of care neoadjuvant chemotherapy alone before surgery for stage II-IIIA non-small cell lung cancer. CONCLUSIONS: This report is the first to demonstrate the safety and feasibility of surgical resection after treatment with ipilimumab and chemotherapy in stage II-IIIA non-small-cell lung cancer.