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1.
J Surg Oncol ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32356321

RESUMO

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

2.
J Thorac Oncol ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389639

RESUMO

INTRODUCTION: PD-L1 expression may vary in different disease sites and at different time points of disease course. We aimed to investigate PD-L1 heterogeneity and its impact on the predictive value on immune checkpoint inhibitor (ICI) therapy in NSCLC patients. METHODS: PD-L1 expression was analyzed in 1,398 NSCLC patients. The predictive value of PD-L1 on ICIs in 398 patients with metastatic NSCLC was assessed. RESULTS: PD-L1 was significantly associated with biopsy sites (P = 0.004). Adrenal, liver and lymph node (LN) metastases had highest PD-L1 expression as a continuous variable and at 1% or 50% cutoff. PD-L1 expression was lower in bone and brain metastases. Among 112 patients with 2 specimens tested, 55 (49%) had major changes in PD-L1 falling into different clinically relevant categories (< 1%, 1-49%, ≥ 50%) at different time points. Prior ICI therapy was associated with significant decrease in PD-L1 compared to treatment-naïve counterparts (P = 0.015). Patients with metastatic NSCLC treated with ICI (n = 398) were divided into three cohorts based on biopsy sites: lung (n = 252), LN (n = 85) and distant metastasis (DM, n = 61). Higher PD-L1 in lung or DM specimens was associated with significantly higher response rate, longer progression-free survival and overall survival. However, PD-L1 in LN biopsies was not associated with either response or survival. CONCLUSION: PD-L1 varies substantially across different anatomic sites and changes during clinical course. PD-L1 from different biopsy sites may have different predictive value for benefit from ICIs in NSCLC.

3.
J Immunother Cancer ; 8(1)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32350118

RESUMO

BACKGROUND: The biological underpinnings of the prognostic and predictive significance of a relative neutrophilia in patients with non-small lung cancer (NSCLC) are undefined. We sought to comprehensively examine the relationships between circulating and intratumoral neutrophil populations and features of the immune contexture in patients undergoing NSCLC resection. METHODS: Preoperative soluble cytokine and angiogenic factors; tumor multiplex immunofluorescence; RNA, whole exome, and T-cell receptor sequencing; and flow cytometry were analyzed for relationships with populations of circulating (from complete blood counts) and intratumoral neutrophils (transcriptional signatures) in a prospectively enrolled resected NSCLC cohort (n=66). In a historical cohort (n=1524), preoperative circulating neutrophil and lymphocyte counts were analyzed for associations with overall survival (OS). RESULTS: Circulating neutrophil populations were positively correlated with increased tumor burden, and surgical tumor resection was followed by a subsequent reduction in peripheral neutrophil counts. Expansion of the circulating neutrophil compartment was associated with increased levels of pro-granulopoietic (IL-1ß, IL-17A, TNFα, IL-6) and TH2-associated (IL-5, IL-13) cytokines. Tumors with high intratumoral neutrophil burden were marked by a blunted T-cell response characterized by reduced expression of cytotoxic T-cell genes (CD8A, CD8B, GZMA, GZMB), decreased CD3+CD8+ cell infiltration, and diminished expression of IFNγ-related genes. The associations between increased intratumoral neutrophil burden and reduced CD3+CD8+ infiltration persisted after adjustment for tumor size, histology, mutational burden, and PD-L1 expression. In 1524 patients, elevated preoperative circulating neutrophil count was independently associated with worse OS (main effect HR 1.82, 95% CI 1.24 to 2.68, p=0.002). CONCLUSIONS: Our findings demonstrate that neutrophil expansion reflects protumorigenic and immunosuppressive processes that manifest as worse OS in patients undergoing NSCLC resection. These results justify further investigation of therapeutic strategies targeting neutrophil-associated immune evasion.

4.
Clin Lung Cancer ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32279936

RESUMO

INTRODUCTION: We have suggested that major pathologic response (MPR) could serve as a surrogate endpoint for survival and provide rapid means of comparing different neoadjuvant treatment regimens. Here, we confirm that MPR is predictive of long-term overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy and surgical resection, to assess agreement on MPR between 2 observers, and to determine the minimum number of slides needed to obtain an accurate determination of MPR. PATIENTS AND METHODS: We identified 151 patients with NSCLC who had been treated with neoadjuvant chemotherapy followed by complete surgical resection from 2008 to 2012. Tissue specimens were retrospectively evaluated by 2 pathologists who had been blinded to patients' treatment and outcome. We assessed the relationships between MPR and OS, the levels of agreement between the pathologists, and determined the number of slides needed to obtain an accurate determination of MPR. RESULTS: Our results reveal that MPR examined by either observer 1 (experienced) or by observer 2 (trained) was significantly predictive of long-term OS after neoadjuvant chemotherapy. MPR was associated with long-term OS in patients with NSCLC undergoing neoadjuvant chemotherapy on multivariable analysis (hazard ratio 2.68; P = .01). The levels of agreement between 2 pathologists were high after direct in-person training by one pathologist or the other (R2 = 0.994). Our data suggest that at least 3 slides should be read to accurately determine MPR. CONCLUSIONS: MPR is significantly predictive of long-term OS in neoadjuvant chemotherapy-treated patients with NSCLC. MPR may serve as a surrogate endpoint for evaluating novel chemotherapies and immunotherapy response in biomarker-driven translational clinical trials.

5.
Gastric Cancer ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32347396

RESUMO

BACKGROUND: As cancer patients are surviving longer, more patients manifest brain metastases (BRMs). However, the rate of BRMs from upper gastrointestinal cancer is unclear. We therefore evaluated the frequency and prognostic effect of BRMs in this setting. METHODS: We analyzed records of 2348 patients who were treated between January 2002 and December 2016 for upper gastrointestinal cancer, including esophageal and gastroesophageal junction adenocarcinoma (EAC; proximal EAC, Siewert types I and II), esophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC; Siewert type III and stomach cancer) in our Gastrointestinal Medical Oncology Database. Frequency, risk factors, and survival after BRMs were evaluated. RESULTS: Of 2348 patients, 68 (2.9%) had BRMs upon follow-up. The BRM rates were as follows: proximal EAC, 4.8%; Siewert type I, 5.9%; Siewert type II, 2.2%; Siewert type III, 0.7%; ESCC: 1.2%; and stomach cancer, 0%. Among EAC patients, Siewert type I and lymph node metastases were independent the risk factors for BRMs in the multivariable analysis. The median overall survival (OS) in the 68 patients with BRMs was only 1.16 years (95% CI 0.78-1.61). However, OS for patients who had a solitary BRM, who had BRM but no other distant metastasis, or who underwent surgery or stereotactic radiosurgery favorable. CONCLUSION: Patients with proximally located adenocarcinoma, or with lymph node metastases are at a higher risk for BRMs and patients fare better after treatment of isolated BRM.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32300858

RESUMO

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor 18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) 18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each 18F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated 18F-FDG SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57+ cell density, and increased T cell exhaustion gene signature. Elevated SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.

7.
J Clin Oncol ; 38(14): 1569-1579, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32160096

RESUMO

PURPOSE: Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer. METHODS: This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up). RESULTS: This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial's stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar. CONCLUSION: For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

8.
Clin Cancer Res ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193228

RESUMO

PURPOSE: Nintedanib enhances the activity of chemotherapy in metastatic NSCLC. In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint. EXPERIMENTAL DESIGN: Eligible patients had stage IB (≥4 cm)-IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg PO bid (28 days), followed by 3 cycles of cisplatin (75 mg/m2), docetaxel (75 mg/m2) q21 days plus nintedanib, followed by surgery. With 33 planned patients, the study had 90% power to detect an MPR increase from 15% to 35%. RESULTS: 21 patients (stages I/II/III, N=1/8/12) were treated. One of 15 patients treated with nintedanib 200 mg achieved MPR (7%, 95% CI 0.2%-32%). Best ORR in 20 evaluable patients was 30% (6/20, 95% CI 12%-54%). 12-month RFS and OS were 66% (95% CI 47%-93%) and 91% (95% CI, 79%-100%), respectively. Most frequent treatment-related G3-4 toxicities were transaminitis and electrolyte abnormalities. Based on an interim analysis the study was discontinued for futility. Higher levels of CD3+ and cytotoxic CD3+CD8+ T cells were found in treated tumors of patients who were alive than in those who died (652.8 vs. 213.4 cells/mm2, P=0.048; 142.3 vs. 35.6 cells/mm2, P=0.018). CONCLUSIONS: Although tolerated, neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared to chemotherapy historical controls. Additional studies of the combination in this setting are not recommended. Post-treatment levels of tumor infiltrating T cells were associated with patient survival. Use of MPR facilitates the rapid evaluation of neoadjuvant therapies.

9.
J Thorac Oncol ; 15(5): 709-740, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32004713

RESUMO

Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.

10.
Ann Thorac Surg ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006477

RESUMO

Bronchial stenosis after chest surgery is a rare event. In upper lobectomy it is likely due to the upward movement of the remaining lobe (s) with torsion of the bronchus and edema. This case report describes the use of existing tools and prosthesis to create a novel miniature Y stent for a stenotic lobar bronchus that rapidly bifurcates, not allowing the insertion of a standard bronchial stent.

11.
J Surg Oncol ; 121(6): 984-989, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077113

RESUMO

BACKGROUND AND OBJECTIVES: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM. METHODS: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. RESULTS: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. CONCLUSIONS: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Análise Mutacional de DNA , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Medicina de Precisão , Proteínas Proto-Oncogênicas p21(ras)/genética
12.
Clin Lung Cancer ; 21(1): 37-46.e7, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31447303

RESUMO

BACKGROUND: Local consolidative therapy (LCT) to optimize disease control is an evolving management paradigm in non-small-cell lung cancer (NSCLC) patients who present with a limited metastatic disease burden. We hypothesized that LCT to all sites of disease would be associated with improved overall survival (OS) among patients with synchronous oligometastatic NSCLC. PATIENTS AND METHODS: Patients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤ 3 synchronous metastases were identified. Intrathoracic nodal disease was counted as one site. Landmark and propensity-adjusted Cox regression analyses were performed to identify factors associated with OS. RESULTS: Of 194 patients, 143 (74%) had 2 or 3 sites of metastasis. LCT was delivered to all sites of disease in 121 patients (62%), to some but not all sites in 52 (27%), and were not used in 21 (11%). Comprehensive LCT was independently associated with improved OS (hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.46-0.97; P = .034), with the greatest therapeutic effect among patients without thoracic nodal disease, bone metastases, or > 1 metastatic site. Among patients who underwent comprehensive LCT, tumor histology (squamous: HR = 2.32; 95% CI, 1.28-4.22; P = .006), intrathoracic disease burden (T3-4: HR = 1.67; 95% CI, 0.97-2.86; P = .065; N3: HR = 1.90; 95% CI, 0.90-4.03; P = .093), and bone metastases (HR = 1.74; 95% CI, 1.02-3.00; P = .044) were associated with poor OS. CONCLUSION: Comprehensive LCT was associated with improved OS in this large cohort of patients with synchronous oligometastatic NSCLC. These results support ongoing prospective efforts to characterize the therapeutic benefits associated with this management strategy.

13.
Ann Thorac Surg ; 109(2): 358-366, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31550464

RESUMO

BACKGROUND: High tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are leading biomarkers in metastatic non-small cell lung cancer (NSCLC) and predict favorable response to checkpoint inhibitors. We sought to identify clinicopathologic characteristics associated with elevated TMB and PD-L1 expression among patients who underwent resection for NSCLC. METHODS: NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project. Multiplex immunofluorescence quantified densities (cells/mm2) of CD3+, CD3+CD8+, CD3+CD8+PD-1+, malignant cells (MCs), MCsPD-L1+, CD68+, CD68+PD-L1+, and CD20+ cells. Whole-exome sequencing quantified TMB (mutations/megabase). TMB and MCsPD-L1+ were dichotomized according to the median of each. RESULTS: A total of 55 patients completed multiplex immunofluorescence and whole-exome sequencing profiling. In this sample, 41.8% (23 of 55) had pathologic stage I disease. Median TMB and MCsPD-L1+ were 3.91 and 0.62 cells/mm2, respectively. TMB was higher among smokers (P = .001) and tumors with lymphovascular invasion (LVI) (P = .051). TMB was positively correlated with densities of MCsPD-L1+ (r = 0.293, P = .030), CD68+PD-L1+ (r = 0.289, P = .033), and CD20+ (r = 0.310, P = .043) cells. The density of MCsPD-L1+ was associated with increased CD3+CD8+ (r = 0.319, P = .018) and CD68+PD-L1+ (r = 0.371, P = .005) cells. Patients with PD-L1HighTMBHigh tumors (30.9%, 17 of 55) had higher intratumoral densities of CD3+, CD3+CD8+, CD68+, CD68+PD-L1+, and CD20+ cells. On multivariable analysis LVI was associated with synchronous elevated TMB and PD-L1 expression (odds ratio 3.53, P = .039). CONCLUSIONS: NSCLC tumors with elevated TMB and PD-L1 expression are associated with LVI and increased intratumoral immune cell infiltration. These findings may potentially improve patient selection for checkpoint inhibitor therapy trials in the adjuvant setting.

14.
Oncogene ; 39(4): 801-813, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31554935

RESUMO

The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compounds 1 and 2 (Pac 1 and 2) did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A-associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.

15.
Ann Thorac Surg ; 109(2): 404-411, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31539514

RESUMO

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

16.
Clin Cancer Res ; 26(4): 892-901, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31694833

RESUMO

PURPOSE: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value. EXPERIMENTAL DESIGN: Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced stage incurable disease who received first-line chemotherapy. RESULTS: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 patients with LCNEC were classified into small-cell lung cancer (SCLC)-like and non-small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared with pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared with etoposide-platinum or pemetrexed-platinum in patients with NSCLC-like LCNEC. CONCLUSIONS: Genomic subtyping has potential in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC.

17.
Innovations (Phila) ; 15(1): 57-65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31875755

RESUMO

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

18.
Artigo em Inglês | MEDLINE | ID: mdl-31857153

RESUMO

Lung cancer patients are at risk for venous thromboembolism (VTE). Preoperative heparin administration may increase the risk of bleeding requiring reoperation. The purpose of this study was to evaluate preoperative heparin's effect on reoperation for bleeding. A retrospective review compared outcomes for patients undergoing pulmonary resection for primary lung cancer from January 2006 to April 2018. Preoperative heparin was administered at the discretion of the attending surgeon. Comparisons were performed between preoperative subcutaneous heparin (5000 U) and no heparin groups. A total of 3325 lung resections were reviewed, 1.4% (n = 48) required reoperation for bleeding. VTE occurred in 1.1% (n = 38). Four hundred sixty-four patients (14.0%) did not receive preoperative heparin. The preoperative heparin group had increased rates of prior thoracic surgery (5.1% [n = 146] vs 1.7% [n = 8], P < 0.001), minimally invasive approach (40.2% [n = 1150] vs 10.6% [n = 49], P < 0.001), and sublobar resections (17.7% [n = 506] vs 10.6% [n = 49], P < 0.001). There were no differences in blood loss/transfusions. Reoperation for bleeding was significantly increased in the preoperative heparin group (1.6% [n = 47] vs 0.2% [n = 1], P = 0.017). There were no differences in VTE (1.5% [n = 7] vs 1.1% [n = 31], P = 0.424). On logistic regression, preoperative heparin was independently associated with increased reoperation for bleeding (odds ratio 8.13, P = 0.039); however, preoperative heparin was not independently associated with VTE. Preoperative heparin was associated with increased reoperation for bleeding. VTE rates are low after pulmonary resection for lung cancer and are not decreased by preoperative heparin. Preoperative heparin use should be determined by risk factor stratification for VTE and reoperation for bleeding in patients undergoing lung cancer resection.

19.
J Thorac Dis ; 11(Suppl 15): S2043-S2045, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31632824
20.
J Thorac Dis ; 11(8): 3391-3398, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31559043

RESUMO

Background: Thymic neuroendocrine tumors (NETs) are rare malignancies often treated in a multidisciplinary fashion. However, evidence for adjunctive therapy is limited, and predictors of survival and recurrence are not well established. Methods: Patients treated for thymic NETs at a single center from 1975 to 2018 were reviewed. Variables collected pertained to tumor factors, stage, and treatments, including surgery. Univariate and multivariate regression analyses were used to determine predictors of overall survival (OS) and recurrence. Results: We identified treated 49 patients, among whom 36 (73%) were male with a median age of 46 years. Surgical resection was pursued in 41 (84%) patients, and chemotherapy and radiation therapy were used in 27 (55%) and 21 (43%) instances as either neoadjuvant, adjuvant, or definitive therapy. Median tumor size was 6.5 centimeters and most tumors were intermediate-grade. During a median follow-up time of 60.8 months following surgical resection, disease recurrence was observed in 29 (71%) patients and median survival time was 83.7 months. In Kaplan-Meier analysis for survival, surgical resection was associated with a longer survival time (P=0.002), while receipt of neoadjuvant therapy was associated with poorer survival. Larger tumor size was associated with recurrence following resection (P=0.047). Conclusions: Thymic NETs represent a heterogeneous disease with variable survival. While we are unable to report clear evidence that supports the use of adjunctive therapies, surgery is important to survival. Additionally, it is likely that those receiving induction chemotherapy represent a unique cohort with advanced or aggressive disease. Among surgical candidates, tumor size predicts disease recurrence.

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