Resected Early Stage Non-small Cell Research Articles

EP07.04-29 Hyperspectral Multiplex Immunohistochemistry and Recurrence in Resected Early Stage Non-small Cell Lung Cancer

EP07.04-29 Hyperspectral Multiplex Immunohistochemistry and Recurrence in Resected Early Stage Non-small Cell Lung Cancer

90P Disease-free survival (DFS) as a predictor of overall survival (OS) in completely resected early stage non-small cell lung cancer (NSCLC)

Evidence based on clinical trials has shown a very good correlation between DFS and OS in completely resected NSCLC patients (pts) with adjuvant therapy. This study assessed the relationship between DFS and OS in real-world pts and disease burden associated with recurrence.

How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Abstract 2028: Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer

Abstract Background: Although randomized trials demonstrated survival benefit of adjuvant chemotherapy, previous reports have suggested that its use in elderly populations for early stage non-small cell lung cancer (NSCLC) was infrequent. Oncologists often hesitate to offer adjuvant chemotherapy in resected early stage non-small cell lung cancer for elderly population. The status of adjuvant chemotherapy in this population is unknown for recent decades. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database which represents about 28% of the US population, we examined the incidence of chemotherapy in resected stage II-III NSCLC between 2004 and 2015. Staging was determined according to the American Joint Committee on Cancer (AJCC) 6th version. Cases were grouped by age (20-69, 70-79, and 80+). Trends in use of chemotherapy by age group was assessed by univariate and multivariate analyses. Results: A total of 35,009 were selected as surgically resected stage II-III NSCLC. Use of chemotherapy was 66.9%, 48.2%, 25.0% in age 20-69, 70-79, 80+, respectively. Multivariate analysis demonstrated that younger age (20-69) and recent year (2010-2015) of diagnosis were associated with increased use of chemotherapy. Chemotherapy use increased from 2004 to 2015 by 11.0%, 18.3%, and 11.3% in age 20-69, 70-79, 80+, respectively. In the age 70-79 group, increased use of chemotherapy was greater in stage II (24.3%) than stage III (14.1%). Five-year overall survival in age 70-79 group mildly increased by 7.6% from 2004 to 2011. Conclusion: This study suggests that use of adjuvant chemotherapy in elderly population increased primarily in age 70-79. Few patients in age 80+ receive adjuvant chemotherapy even in recent years. This study not only informs oncologists of current status but also suggests further research on very elderly populations. Citation Format: Takefumi Komiya, Emily Powell, Achuta Kumar Guddati. Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2028.

Liver kinase B1 correlates with prognosis and epithelial-mesenchymal transition of resectable early stage non-small cell lung cancer.

BackgroundRecent evidences support that low expression of liver kinase B1 (LKB1) triggers epithelial-mesenchymal transition (EMT) through induction of Zinc finger E-box binding homeobox 1 (ZEB1) expression, which downregulates E-cadherin in human lung cancer cell lines. However, the clinicopathological significance of LKB1, EMT, salt-inducible kinase 1 (SIK1), ZEB1 and their relationship in early stage non-small cell lung cancer (ES-NSCLC) patients remain to be determined. In this study, the correlation among expression of LKB1, risk of distant metastasis, prognostic significance, and EMT in ES-NSCLC after surgery was investigated by immunohistochemistry.MethodsCase notes and pathology records of 103 patients with ES-NSCLC were retrospectively analyzed. Immunohistochemical staining was employed to detect LKB1, EMT biomarkers (E-cadherin and vimentin), SIK1 and ZEB1 expression in ES-NSCLC tissues.ResultsLKB1 expression is associated with distant metastasis after treatment (P=0.017). LKB1-high expression group has better overall survival (OS) (P=0.000) and disease-free survival (DFS) (P=0.000). LKB1 expression is correlated with E-cadherin (r=0.231, P=0.019), vimentin (r=−0.225, P=0.022), SIK1 (r=0.218, P=0.027) and ZEB1 (r=−0.242, P=0.014).ConclusionsOur findings suggest that LKB1-high expression is possibly associated with favourable prognosis and LKB1 expression is correlated with EMT and expression of SIK1 and ZEB1.

Prediction of Postoperative Clinical Outcomes in Resected Stage I Non-Small Cell Lung Cancer Focusing on the Preoperative Glasgow Prognostic Score.

Background: The Glasgow Prognostic Score (GPS), which consists of albumin and C-reactive protein (CRP), may predict overall survival (OS) in cancer patients. The aim of this retrospective analysis was to evaluate the clinical impact of the preoperative GPS on patients with resected early stage non-small cell lung cancer (NSCLC). Methods: 300 patients with curatively resected stage I NSCLC were followed-up for OS, recurrence-free survival (RFS), cancer-specific survival (CSS), and death from other causes. Results: 229 patients (76%) had a preoperative GPS of 0, and 71 (24%) a GPS ≥ 1. The three-year probabilities of RFS, OS, CSS, and death from other causes were 81%, 84%, 88%, and 96% in patients with GPS = 0, and 79%, 74%, 91%, and 82% in patients with a GPS ≥ 1, respectively. GPS ≥ 1 was significantly associated with a higher risk of death from other causes (p = 0.022), serving as an independent predictor of death from other causes (p = 0.034). Pathologically elevated CRP levels (CRP > 5 mg/L) were found in 91 patients (30%). The mean CRP level was 7.88 ± 15.80 mg/L (0.5–135.6 mg/L). Pre-treatment CRP level was significantly associated with coronary heart disease (p < 0.0001), histology (p = 0.013), tumor size (p = 0.018), tumor stage (p = 0.002), and vascular invasion (p = 0.017). Conclusion: The preoperative GPS predicts adverse survival outcomes in patients with resected stage I NSCLC.

P1.17-30 Sex and Age-Associated Survival Following Resected Early Stage Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most common malignant tumour, and a leading cause of mortality worldwide. Rising rates of NSCLC have been observed among females, but nonetheless females also are often observed to possess better prognosis across all stages of disease. We aimed to assess the impact of biological sex along with age at diagnosis on the outcome of NSCLC patients with resected early-stage disease. A 15-year population-based retrospective analysis was conducted on de novo early stage (AJCC 7th edition, Stage I or II) patients between 1999-2014, whose primary tumor was surgically resected. Demographic, clinical characteristics, treatment modalities and outcome data were extracted from the institutional Glans-Look Lung Cancer Database, and univariate analysis, including Kaplan-Meier survival, alongside multivariate Cox regression was performed to compare outcomes by sex and determine prognostic factors associated with survival. 872 early-stage resected NSCLC patients were identified. Median age at diagnosis 65.9 years (IQR: 59.1-72.6), 56% female, 76% ‘ever’ smokers, 68% Stage I, 91% oncologic resection (9% wedge resection). Median overall survival (mOS) for all early-stage resected cases was 93 months (95% CI: 81.9 – 105.4) with a 5-year survival rate of 62.5%. Females exhibited superior survival outcomes to males (105.4 months vs. 77.5 months, log-rank p=0.002), as did those <75 years at diagnosis compared to those ≥75 years (103.9 vs. 76.2 months, log-rank p <0.001). Best and worst survival outcome was observed in females under age 75, and males over age 75, respectively (mOS 114.3 vs. 64.5 months; 5-year survival: 67.9% vs. 50.5%). No difference in rate of recurrence (overall) or rate of metastatic recurrence between males and females was identified (39% vs. 36%, p=0.214; 19% vs. 16%, p=0.591). After controlling for confounding variables, a reduced risk of mortality was found for females (HR: 0.8, p=0.016), age under 75 years at diagnosis (HR: 0.6, p <0.001) and stage I presentation (HR: 0.6, p<0.001). Females experience significantly longer mOS, in particularly females under the age of 75 years at diagnosis. After adjusting for confounding factors, we found significantly reduced mortality risk for females aged under 75 years at diagnosis, and Stage I disease. Despite possessing the poorest outcomes among this cohort, males ≥75 years still possessed a 5-year survival rate of 50%, suggesting that surgical resection is a highly effective treatment option for suitable NSCLC patients, regardless of age.

Postoperative adjuvant therapy for resectable early non-small cell lung cancer: A protocol for a systematic review and meta-analysis.

Background:Lung cancer is one of the most common malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer diagnosed. For patients with resectable early stage non-small cell lung cancer, routine postoperative adjuvant therapy can significantly prolong overall patient survival and reduce the risk of cancer recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the postoperative chemotherapy strategy of lung cancer patients has changed a lot. To evaluate the efficacy of postoperative adjuvant therapy (platinum-based chemotherapy, platinum-based chemotherapy plus molecular targeted therapy, platinum-based chemotherapy plus anti-angiogenic agents, or platinum-based chemotherapy plus immunotherapy) with or without radiotherapy for patients with NSCLC, we will conduct a systematic review and meta-analysis of the published or unpublished relevant randomized controlled trials.Methods:We will search PubMed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2019. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) and quasi-RCTs studies will be included. We will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval.Results:The results of this study will be published in a peer-reviewed journal.Conclusion:This study will comprehensively compare the efficacy of platinum-based chemotherapy with that of molecular targeted therapy and immunotherapy for patients after surgery with resectable early NSCLC. Since large-sample randomized trials meeting the inclusion criteria of this study may be insufficient, we will consider incorporating some high-quality small-sample-related trials, which may lead to high heterogeneity and affect the reliability of the results.

Clinical outcomes of stereotactic body radiotherapy for de novo pulmonary tumors in patients with completely resected early stage non-small cell lung cancer.

PurposeFollowing surgery for early stage non-small-cell lung cancer (NSCLC), de novo pulmonary tumors are common. This study aimed to assess the efficacy, patterns of failure, and toxicity of stereotactic body radiotherapy (SBRT) in the treatment of de novo pulmonary tumors following curative resection of early stage NSCLC.Patients and methodsWe reviewed the medical data of patients who had received definitive intent SBRT for small lung cancer at Zhongshan Hospital, Fudan University, between June 2011 and December 2017. Patients who had experienced complete resection for prior early stage NSCLC before SBRT were identified for further analysis. Incidences of locoregional recurrence (LR) and distant metastasis (DM) were evaluated using the alternative cumulative incidence competing risk method. The probability of survival was estimated using the Kaplan–Meier method.ResultsA total of 33 patients with 36 lesions were eligible and included in this study. The median follow-up time was 32 months. Estimated incidences of LR and DM were 37.62% and 15.92%, respectively, at 1 year and 48.02% and 21.23%, respectively, at 2 years. The progression-free survival and overall survival of all patients were 62.40% and 90.30%, respectively, at 1 year and 52.00% and 69.90%, respectively, at 2 years. In all, 26 patients experienced grade 1 SBRT-related toxicity, 11 patients experienced grade 2 SBRT-related toxicity, and three patients experienced grade 3 toxicity. There were no grade 4/5 toxicities or SBRT-related deaths during the follow-up period.ConclusionSBRT appears to be a safe and potentially effective alternative therapeutic option for de novo pulmonary tumors following early stage NSCLC radical resection, despite impaired pulmonary reserve.

Postoperative Radiation Therapy for Incompletely Resected Stage I NSCLC: An Analysis of the National Cancer Database

The use of post-operative radiation therapy (PORT) in incompletely resected early stage non-small cell lung cancer (NSCLC) is controversial. This study evaluates survival outcomes after PORT in incompletely resected Stage I NSCLC, using a large national patient registry. Patients diagnosed with pathologic Stage I NSCLC treated definitively by surgery with positive surgical margins (microscopic, macroscopic, or not otherwise specified residual tumor) were identified in the National Cancer Database (NCDB). Patients receiving PORT dose ≥45 Gy were included in the analysis. Survival rates were estimated using Kaplan-Meier analysis. Univariate and multivariate Cox regression models were used to identify factors with significant impact on survival. Between 2004 and 2012, a total of 1,915 Stage I NSCLC patients were identified who met study criteria, with 388 (20.3%) receiving PORT. The percentage of patients receiving PORT did not change significantly over the study period, ranging each year between 15.8-24.7%. With median follow-up of 35.2 months, median survival was 51.6 months for all patients. Median survival for patients receiving PORT was 46.4 months, compared to 55.3 months for patients receiving surgery alone (p=0.11). On multivariate analysis, adjusting for age, gender, race, insurance status, Charlson comorbidity score, T stage, and receipt of adjuvant chemotherapy, PORT was associated with worse survival compared to no PORT (HR 1.18; 95% CI, 1.02-1.37; p=0.027). Compared to surgery alone, adjuvant chemotherapy was associated with improved survival on multivariate analysis (HR 0.61; 95% CI, 0.49-0.75; p<0.0001), whereas receipt of both PORT and chemotherapy was not associated with a statistically significant difference in survival vs. surgery alone (HR 0.93; 95% CI, 0.74-1.18; p=0.56). In this large national patient registry, PORT was offered in 20% of incompletely resected Stage I NSCLC. Addition of PORT was associated with worse survival compared to surgery alone, whereas adjuvant chemotherapy was associated with improved survival.

Abstract A64: Mast cell expressed FcεR beta subunit (MS4A2) is prognostic in lung adenocarcinoma

Abstract Background: The context of immune cell infiltrates within the tumor is associated with cancer prognosis. The type of immune cells and their activation state can provide mediators that either promote or inhibit tumor growth. A growing body of evidence suggest the presence of innate immune cells play a role in shaping early tumor growth. In attempts to gain insight into the immune networks that regulate tumorigenesis, we used genome wide expression datasets of patients with resected early stage non-small cell lung cancer (NSCLC) to identify immune-related genes associated with patient survival. Methods: Gene expression analysis was conducted on microarray datasets from 128 early-stage NSCLC adenocarcinoma resected tumor samples. Limiting analysis to immune-related genes, we identified a minimum gene set that is prognostic for lung adenocarcinoma and validated the gene signature in additional published microarray NSCLC datasets. Using pathway analysis and immunohistochemistry (IHC), we identified a role for mast cell-expressed IgE receptor beta subunit, MS4A2, in lung adenocarcinoma progression. Results: From an immune-related gene list, we identified a minimal gene signature that was able to separate patients into high or low-risk survival groups. This gene signature was shown to be prognostic for NSCLC adenocarcinoma in nine validation datasets (n=1264, hazard ratio 2.07, 95% confidence interval 1.69-2.53, p&amp;lt;0.0001). Pathway analysis of differentially expressed genes within high or low-risk survival subgroups reveals gene ontologies and immune signatures that are enriched for IgE receptor signaling and mast cells in patients with favourable prognosis. Univariate analysis shows that the IgE receptor complex genes, as well as mast cell specific protease, mast cell carboxypeptidase A, are highly prognostic for survival. We are currently using IHC of matched patient samples to validate receptor localization. Conclusion: By limiting gene expression analysis to immune-related genes, we identified a minimal gene set that indicate an important role for IgE receptor signaling and mast cells in favourable lung cancer prognosis. Our data highlights the importance of innate immune cells in shaping lung cancer development. Citation Format: Dalam Ly, Chang-Qi Zhu, Michael Cabanero, Ming-Sound Tsao, Li Zhang. Mast cell expressed FcεR beta subunit (MS4A2) is prognostic in lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A64.

Upregulated mrna expression of mtor in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy

Upregulated mrna expression of mtor in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy

Adjuvant Therapy of Resected Non-small Cell Lung Cancer: can We Move Forward?

Twenty years ago, an individual patient data meta-analysis of eight cisplatin-based adjuvant chemotherapy (AC) studies in completely resected early stage non-small cell lung cancer (NSCLC) demonstrated a 13% reduction of the risk of death favoring chemotherapy that was of borderline statistical significance (p=0.08). This marginal benefit boosted a new generation of randomized trials to evaluate the role of modern platinum-based regimens in resectable stages of NSCLC and, although individual studies generated conflicting results, overall they contributed to confirm the role of AC which is now recommended for completely resected stage II and III NSCLC, mostly 4cycles, while subset analyses suggested a benefit in patients with large IB tumors. Cisplatin-based therapy was the core regimen of those adjuvant clinical trials and even if a substitution with other platinum-derived was also suggested, mainly based on extrapolated data from studies in advanced disease, cisplatin was confirmed to be slightly superior to carboplatin and is still the drug of choice in the adjuvant setting. Currently, any attempt to improve efficacy of cisplatin-based chemotherapy through antiangiogenic drugs association or pharmacogenomics approaches have failed, while results of additional studies are eagerly awaited. In the context of promising targeted therapies, even if several randomized trials in the advanced setting evaluated tyrosine kinase inhibitors (TKis) versus platinum-based chemotherapy and showed impressive results, clinical experience with TKIs in the adjuvant setting is still limited and most of the trials have not required patients to be molecularly tested for the drug-specific molecular predictive factor. At the present time, the role of targeted agents as adjuvant approaches remains largely not investigated. Finally, with the negative experience of the use of vaccines in this setting, the integration of immunotherapy (mainly immunocheckpoint inhibitors) in platinum-based schedules has just started to be evaluated, representing a potential future clinical option, but still far from clinical practice.

980 Characterization of tumor infiltrating lymphocytes in resectable early stage non-small cell lung cancer

980 Characterization of tumor infiltrating lymphocytes in resectable early stage non-small cell lung cancer

A population-based study of the resource utilization and costs of managing resectable non-small cell lung cancer

ObjectivesSurgical resection and adjuvant chemotherapy have become standard of care for treating resectable early stage non-small cell lung cancer (NSCLC). The purpose was to describe and compare the overall and regional resource utilization and costs of resected NSCLC treated with and without adjuvant chemotherapy. Materials & MethodsA population-based retrospective cohort study of resected NSCLC patients, diagnosed between 2004 and 2006 (representing the cohort immediately affected by the change in clinical practice) was performed using administrative data. Patients were followed for four years from the date of surgery. The healthcare system perspective was used, and cost estimates (2012 US$) were derived from administrative data and the literature. Results3354 patients were included. The average cost per patient treated with surgery and adjuvant chemotherapy was $37,860.88 and was significantly higher than the average cost per patient treated with surgery alone $32,221.45 (p<0.0001). Among regions, the costs of patients treated with surgery and chemotherapy ($32,672–$45,453) and the costs of those treated with surgery alone ($28,679–$36,845) varied significantly (p<0.0001). Rates of chemotherapy, the proportion of patients who received any imaging scans, hospitalizations, specialist visits, emergency room visits, mean number of imaging scans, general physician visits, and blood transfusions all varied significantly among geographic regions. ConclusionsThis population-based study demonstrates an average cost per patient similar to that shown in randomized controlled trials; however, costs for either treatment approach varied by geographic region. Understanding the regional variation in costs and resource utilization is important with respect to delivering optimal treatment in a cost-effective strategy.

Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected (R1) early stage Non-Small Cell Lung Cancer (NSCLC): A European survey conducted by the European Society for Medical Oncology (ESMO) Young Oncologists Committee

BackgroundEarly stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy (CT) for completely resected stage II–III NSCLC. There is limited evidence for the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1) early stage NSCLC. Materials and methodsA European survey of thoracic oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected NSCLC and to identify factors influencing treatment decisions. Demographics and information on clinical stage, regimens, cycles planned, radiotherapy sites, multidisciplinary management and discussion about inconclusive evidence with the patient were collected. Univariate and multivariate analyses were performed. Results768 surveys were collected from 41 European countries. 82.9% of participants were medical oncologists; 49.3% ESMO members; 37.1% based in University Hospitals; 32.6% practicing oncology for over 15 years and 81.4% active in research. 91.4% of participants prescribed adjuvant CT and mostly cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed limited clinical evidence with the patient. In the univariate analysis, a statistically significant association with CT prescription was found for medical oncology specialty (p<0.001), ESMO membership (p<0.001), activity in clinical research (p=0.002) and increased frequency of ESMO guidelines consultation (p for trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription were associated with radiation oncology specialty (p<0.001), not being an ESMO member (p<0.001), years practicing specialty (p for trend=0.001), workload of lung cancer patients (p for trend=0.027) and decreased frequency in consulting ESMO guidelines (p<0.001). In the multivariate analysis, medical oncology and radiation oncology were the best discriminator for prescription of adjuvant CT and RT, respectively. ConclusionThis survey demonstrates that adjuvant CT and RT are commonly used in clinical practice for R1-resected NSCLC despite limited evidence. Prospective trials are necessary to clarify optimal management in this setting.

Patterns of survival and recurrence after surgical treatment of early stage non–small cell lung carcinoma in the ACOSOG Z0030 (ALLIANCE) trial

Surgical resection has been the mainstay of curative treatment of early stage lung cancer in selected patients. We evaluated survival and patterns of recurrence after surgical resection for early stage lung cancer from the American College of Surgeons Oncology Group Z0030/Alliance trial. One thousand eighteen patients enrolled in the Z0030 trial were analyzed according to clinical T stage. Differences between groups were compared using the 2-sample rank test or χ(2) test. Log rank test and Cox proportional hazards regression were used to compare survival and recurrence. To compare patients who underwent open versus video-assisted thoracoscopic surgery (VATS) resections, propensity-score matched analysis was performed. Seven hundred fifty-two patients (66 undergoing VATS and 686 undergoing open surgery) were classified into 5 equal-sized propensity-score groups. Proportional hazards regression was used to compare these outcomes. There were 578 patients with cT1 tumors and 440 patients with cT2 tumors. Median follow-up was 6.7 years. Median overall survival was 9.1 years (stage T1) and 6.5 years (stage T2). Overall survival at 5 years was 72% (stage T1) and 55% (stage T2). Local recurrence-free survival at 5 years was 95% (stage T1) and 91% (stage T2) (P = .015). Among patients with stage T1 cancer, 4.2% (23 out of 542) had local recurrences, whereas 7.3% (30 out of 409) of those with stage T2 tumors had local failure. There was no difference in the development of new primary tumors between stage T1 and stage T2 groups. In the propensity-score matched analysis of VATS versus open lobectomy patients, there was no difference in overall survival, disease-free survival, and freedom from development of a new primary tumor. Results of patients with resected early stage non-small cell carcinoma from a large-scale, multicenter trial serve as benchmarks against which to compare nonsurgical therapies for early stage lung cancer. Propensity-score matched analysis shows no difference in survival between patients undergoing VATS and open lobectomy.

Adjuvant chemotherapy of completely resected early stage non-small cell lung cancer (NSCLC).

Surgery is regarded as the primary treatment modality for early stage non-small cell lung cancer (NSCLC), but even after complete resection, a substantial percentage of these patients eventually develop local recurrence or distant metastases. Therefore more effective treatment strategies to reduce lung cancer mortality and recurrence rate are needed. Only recently has the use of adjuvant chemotherapy become standard in early stage NSCLC, at least for stage II and resected IIIA NSCLC. Controversies remain about the benefit for stage I patients. Five-year survival improvements of 5% to 10% have been reported with cisplatin-based adjuvant chemotherapy from multiple large randomized phase III clinical trials and meta-analyses. Questions remain as to which patients benefit and which regimens are best. In this paper, important clinical research in the field of adjuvant chemotherapy of NSCLC is reviewed.

Platypnea-orthodeoxia syndrome following left pneumonectomy for early stage non-small cell lung cancer

Abstract Introduction Lobectomy or pneumonectomy represents the treatment of choice for resectable early stage non-small cell lung cancer (NSCLC). The location of heart and great vessels, liver and spleen changes considerably following pneumonectomy as a consequence of mediastinal shift and elevation of the hemidiaphragm. Presentation of case A 70 years old gentleman developed acute shortness of breath two months after undergoing a left pneumonectomy for a pT2pN1M0 NSCLC, squamous cell carcinoma. His dyspnea and oxygen saturation worsened when sitting upright and immediately improved when he assumed the supine position, consistent with platypnea-orthodeoxia syndrome, and suggesting a potential inter-atrial right-to-left shunt. The presence of a patent foramen ovale (PFO) was documented by transoesophageal echocardiography. The patient underwent percutaneous closure of the PFO which markedly reduced the shunt, and led to resolution of symptoms. Discussion PFO is a common anomaly, found in approximately 25% of adults. Its presence is associated with increased risk of stroke from paradoxical emboli. Inter-atrial shunting after major thoracic surgery is a rare but clinically significant event. The case here reported was diagnosed following left pneumonectomy and to our knowledge, only two other single cases of PFO after left pneumonectomy have been reported in the literature so far. Conclusion A PFO should always be considered in the differentials for patients presenting with platypnea-orthodeoxia syndrome after lung surgery. Given the high risk of embolic stroke and high success rate of transcatheter percutaneous closure, these patients should be promptly referred for cardiac investigations and appropriate management.

Metformin Usage and Not Diabetes Influences the Long Term Survival of Resected Early Stage Non-small Cell Lung Cancer Patients

Metformin Usage and Not Diabetes Influences the Long Term Survival of Resected Early Stage Non-small Cell Lung Cancer Patients