Systematic Endobronchial Ultrasound-guided Mediastinal Staging Versus Positron Emission Tomography for Comprehensive Mediastinal Staging in NSCLC Before Radical Radiotherapy of Non-small Cell Lung Cancer: A Pilot Study

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC.In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy (± systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT.Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1–5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%–51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7–9) versus 12 mm (range 6–21), P = 0.005.A significant proportion of patients considered for definitive radiotherapy (+/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free.     

Quality assessment of robot assisted thoracic surgical resection of non-small cell lung cancer: nodal upstaging and mediastinal recurrence

BackgroundRobot assisted thoracic surgery (RATS) is the minimally invasive surgical technique of choice for treatment of patients with non-small cell lung cancer (NSCLC), at the Isala Hospital. The aim of this study is to compare clinical and pathological staging results and mediastinal recurrence after RATS for anatomical resections of lung cancer as surrogate markers for quality of mediastinal lymph node dissection (MLND).MethodsThis single institute retrospective study was conducted in patients who underwent RATS for NSCLC. Excluded were patients with a history of concurrent malignant disease, with other previous neoplasms, with small cell lung cancer (SCLC) and patients in whom the robotic technique was converted to thoracotomy, prior to lymph node dissection. Data were obtained from the hospital database. The difference between clinical and pathological staging was expressed as upstaging and downstaging. Computed Tomography scanning was used for follow-up, and diagnosis of mediastinal recurrence.ResultsFrom November 2011 to May 2016, 227 patients underwent RATS at Isala Hospital Zwolle, the Netherlands. Of those, 130 (mean age, 69.5±9.3 years) met the eligibility criteria. Preoperative mediastinal lymph node staging was done by endoscopic ultrasound/endobronchial ultrasound, by positron emission tomography (PET) or mediastinoscopy. In 14 patients (10.8%) unforeseen N2 disease was found, 6 patients (4.6%) were upstaged from cN0 to pN2 and 8 patients (6.2%) were upstaged from cN1 to pN2. Mediastinal recurrence was detected in 7 patients (5.4%) during a median follow-up of 54 months (range, 1.5–102 months).ConclusionsIn patients with NSCLC, who underwent anatomical resection by means of RATS, an unforeseen N2 disease rate of 10.8% was demonstrated and a mediastinal recurrence rate of 5.4%. It is concluded that robotic surgery provides an accurate lymph node dissection.     

The impact of pathologic staging of the hilar/mediastinal nodes on outcomes in patients with early-stage NSCLC receiving stereotactic body radiotherapy

BackgroundThe importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging.MethodsIn this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons.ResultsOverall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% vs. 67% (P=0.65) and 3-year freedom from nodal failure was 84% vs. 69% (P=0.1) for those with and without nodal staging, respectively.ConclusionsSimilar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.     

When Should 99mTc Bone Scintigraphy Be Performed in cT1N0 Non-Small Cell Lung Cancer Patients?

The aim of this retrospective study was to investigate the risk factors for bone metastases (BM) in clinical T1N0 non-small cell lung cancer (NSCLC) patients.From January 2010 to June 2012, 739 patients with primary diagnosed cT1N0 NSCLC were eligible for this study. Clinical variables, including sex, smoking history, age at diagnosis, tumor size, pathologic subtype, preoperative serum Carcino embryonie antigen (CEA) level, lesion imaging performance, and skeletal system symptom, were collected.BM were found in 7 patients (0.95%), in whom 6 patients had skeletal system symptom and 1 had silent metastasis. The frequency of BM was significantly high in younger patients (P = 0.007) and in patients with higher preoperative serum CEA level (P = 0.05). In multivariate analysis, age less than 50 years old (OR = 2.23, 95% CI: 1.56–4.21, P = 0.02), presence of clinical symptom (OR = 3.15, 95% CI: 1.98–6.42, P = 0.008), and CEA level over 5 μg/mL (OR = 2.14, 95% CI: 1.37–3.53, P = 0.03) were independently associated with BM in cT1N0 NSCLC patients.Presence of skeletal system symptom is not the unique criteria for performing BS. Younger age at diagnosis and higher preoperative serum CEA level are also risk factors for BM in cT1N0 NSCLC patients. Therefore, the selection of early-stage NSCLC patients being performed BS should be more precise in the future.     

Clinicopathological significance and prognostic value of E-cadherin expression in non-small cell lung cancer: A protocol for systematic review and meta-analysis

Background:E-cadherin, a calcium-dependent cell adhesion molecule, as an important mediator of adhesion and signaling pathway, plays a key role in maintaining tissue integrity. However, the association of E-cadherin expression with clinicopathological features and prognostic value in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the purpose of the study is to explore the clinicopathological features and prognostic value of E-cadherin expression in non-small cell lung cancer by meta-analysis.Methods:PubMed, EMBASE, Cochrane Library, and Web of Science were searched to collect the studies about expression of E-cadherin and clinicopathological features and prognosis of non-small cell lung cancer. The last search time was May 2020. Stata 15.0 software was used for statistical analysis.Results:A total of 35 studies were included, of which the results showed that high expression of E-cadherin compared with its low expression, for overall survival, HR = 0.68 (95% CI:0.64–0.73, P < .05); for disease-free survival or progression-free survival, HR = 0.54 (95% CI: 0.44–0.67); low differentiation of lung cancer compared with moderate and high differentiation, OR = 0.40 (95% CI: 0.27–0.58, P < .05); Advanced lung cancer compared with early stage, OR = 0.54 (95% CI: 0.44–0.66, P < .05); lymph node metastasis compared with non-lymph node metastasis, OR = 0.49 (95% CI: 0.31∼0.77).Conclusion:Low expression of E-cadherin is closely related to poor prognosis of patients with NSCLC, promoting tumor staging and lymph node metastasis, inhibiting tumor differentiation as well.     

Positron emission tomography/computed tomography and endobronchial ultrasound-guided transbronchial needle aspiration to evaluate the status of N2 in preoperative non-small cell lung cancer: a diagnostic test

BackgroundAs a minimally invasive method, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was more accurate than non-invasive methods such as positron emission tomography (PET) and computed tomography (CT) to evaluate the lymph nodes in preoperative non-small cell lung cancer (NSCLC). PET/CT has more anatomical advantages than PET scanning and is more accurate in lung cancer staging. However, no relevant studies have comparatively evaluated PET/CT and EBUS-TBNA for NSCLC patients.MethodsA total of 112 patients were included in this retrospective analysis. The golden diagnosis of N2 status was postoperative pathological results. In EBUS-TBNA puncture specimens, if clear malignant tumor cells could be seen, the results were taken as positive. In PET/CT image analysis, the CT values, short diameter, and maximum standardized uptake value (SUVmax) of each lymph node were recorded to evaluate N2 status. The results of PET/CT and EBUS-TBNA were compared with the final pathological results, and respective sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. - Then, the patients were divided into adenocarcinoma group and squamous cell carcinoma group -and the results were calculated and compared with the above method.ResultsThe results showed that EBUS-TBNA had a higher diagnostic value for mediastinal lymph nodes than PET/CT, and the difference was statistically significant (P<0.001). In NSCLC patients, the results showed that the sensitivity (P=0.013), specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.954 and 0.636, respectively). In adenocarcinoma cases, specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.957 and 0.596, respectively).In cases with squamous cell carcinoma, specificity (P=0.003), PPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than PET/CT (AUC =0.952 and 0.657, respectively).ConclusionsFor preoperative diagnosis of mediastinal lymph node metastases in NSCLC, EBUS-TBNA is more accurate than PET/CT. For those patients with suspected mediastinal lymph node metastasis, EBUS-TBNA should be preferred method to evaluate the status of mediastinal lymph nodes.     

PET-CT limitations in early stage non-small cell lung cancer: to whom more aggressive approach in radiotherapy and surgery should be directed?

This editorial comments on the study by Paravati et al., which reported on the incidence of occult regional lymph node metastases in PET-CT T1T2N0 non-small cell lung cancer (NSCLC) patients. A central location and the size of the tumor were shown to be the strongest predictors of the risk of occult nodal disease. Authors comment that in view of limitations of modern imaging, as well as the reported negative predictive value (NPV) of invasive staging methods, the choice of therapeutic options as the extent of surgery (lobectomy or sublobar resection) or radiotherapy [stereotactic body radiation therapy (SBRT) or conformal radiotherapy (RT) with some forms of elective nodal irradiation (ENI)] should consider tumor’s characteristics and not be based only on imaging and invasive staging modalities.     

Second and later-line erlotinib use in non-small cell lung cancer: real world outcomes and practice patterns overtime in Canada

BackgroundIn Canada, epidermal growth factor receptor (EGFR) inhibitor therapies in advanced non-small cell lung cancer (NSCLC) were initially approved regardless of EGFR status. The purpose of this study is to characterise the use of second or later-line erlotinib therapy in Ontario, Canada from 2007–2016, as well as evaluate the impact of erlotinib therapy on survival and emergency department (ED) visits in a real-world population.MethodsThis is a retrospective cohort study derived at ICES (formerly known as the Institute for Clinical and Evaluative Sciences) of advanced NSCLC patients diagnosed from 2007–2016 in Ontario, Canada, over the age of 65, who received at least one dose of first-line chemotherapy. The exposure of interest was receipt of second or later-line erlotinib. The primary outcome was the hazard ratio for mortality evaluated using a Cox proportional hazards model, and the secondary outcome, ED visits, was evaluated using a Poisson model.ResultsFirst-line chemotherapy was administered in 30.4% of stage IV NSCLC patients. Of these patients, 19.7% received second or later-line erlotinib. The proportion of patients prescribed second or later-line erlotinib decreased over the course of the study (P<0.0001). Unadjusted median overall survival in the entire cohort was 325 days (95% CI: 314–337 days), 513 days (95% CI: 485–539 days) in the erlotinib cohort, and 282 days (95% CI: 270–291 days) in the non-erlotinib cohort. Despite this, the adjusted hazard ratio for death was 1.89 (95% CI: 1.73–2.07, P<0.0001) for patients on erlotinib. Patients receiving erlotinib also had a marginally higher relative rates of ED visits with an adjusted relative risk of 1.10 (95% CI: 1.02–1.19, P=0.013).ConclusionsThis study highlights the importance of using EGFR targeted treatments in NSCLC patients with a predictive biomarker, and suggests that treatment with erlotinib therapy is unlikely to benefit unselected patients with advanced NSCLC.     

Clinical adjustability of radiological tools in patients with surgically resected cT1N0-staged non-small-cell lung cancer from the long-term survival evaluation

BackgroundVarious radiological tools have been introduced to determine the malignancy or prognosis of lung carcinomas. We retrospectively summarized the clinical outcomes to evaluate whether radiological tools such as consolidation-to-tumor ratio (CTR), tumor disappearance ratio (TDR), and mediastinal diameter (MD) are suitable for surgically resected non-small-cell lung cancer (NSCLC).MethodsThis retrospective study included 260 patients (128 men and 132 women; median age, 64 years) with cT1N0-staged NSCLC who underwent thoracotomy. Disease-free survival (DFS) and overall survival (OS) outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards model.ResultsWhen the adjusted hazard ratios (HRs) with reference to cT1a/1 mi were calculated, significant differences were observed in cT1b and cT1c for DFS (P=0.04 and P<0.01, respectively) and in cT1c for OS (P=0.01). For HRs with reference to CTR (≤0.5), a significant difference was only observed in CTR (>0.5) for DFS (P=0.01). For HRs with reference to TDR (≤25%), significant differences were observed in TDR (>75%) for DFS (P=0.02) and OS (P=0.02). For HRs with reference to MD (≤5 mm), significant differences were observed in 6–20 mm (P=0.04) and >20 mm (P=0.02) for DFS and in >20 mm (P=0.02) for OS.ConclusionsAll radiological tools revealed significant correlations with prognosis in the patients with cT1N0-staged NSCLCs. We recommend the use of MD in a clinical context. However, further investigation of this issue is needed.     

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis

Background:There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods:Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I²-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results:Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76–6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01–1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01–1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22–2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20–1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32–4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the “Publication year”, “Country”, “Sample size”, and “Cutoff value” might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.     

Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear.The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients.Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies.According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%–0.99%), 2.33% (95% CI: 1.47%–3.66%), 2.24% (95% CI: 1.34%–3.72%), and 1.43% (95% CI: 0.98%–2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46–6.52; P = 0.42), 0.99 (95% CI: 0.66–1.49; P = 0.95), 4.70 (95% CI: 1.48–14.95; P = 0.0087), and 2.64 (95% CI: 1.22–5.69; P = 0.01), respectively.Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug.     

Risk factors for cardiac rupture after acute ST-segment elevation myocardial infarction during the percutaneous coronary intervention era: a retrospective case-control study

BackgroundIn percutaneous coronary intervention (PCI) era, more clinically valuable risk factors are still needed to determine the occurrence of cardiac rupture (CR). Therefore, we aimed to provide evidence for the early identification of CR in ST-segment elevation myocardial infarction (STEMI).MethodsA total of 22,016 consecutive patients with STEMI admitted to Cangzhou Central Hospital and Tianjin Chest Hospital from January 2013 to July 2021 were retrospectively included, among which 195 patients with CR were included as CR group. From the rest 21,820 STEMI patients without CR, 390 patients at a ratio of 1:2 were included as the control group. A total of 66 patients accepted PCI in the CR group, and 132 patients who accepted PCI in the control group at a ratio of 1:2 were included. The status of first medical contact, laboratory examinations, and PCI characteristics were recorded. Multivariate logistic regression analysis was used to investigate the risk factors related to CR.ResultsThere was a higher proportion of patients with myocardial infarction (MI) in the high lateral wall in the CR group (23.6% vs. 8.2%, P<0.001). The proportion of single lesions was lower in the CR group (24.2% vs. 45.5%, P=0.004). Female (OR =2.318, 95% CI: 1.431–3.754, P=0.001), age (OR =1.066, 95% CI: 1.041–1.093, P<0.001), smoking (OR =1.750, 95% CI: 1.086–2.820, P=0.022), total chest pain time (OR =1.017, 95% CI: 1.000–1.035, P=0.049), recurrent acute chest pain (OR =2.750, 95% CI: 1.535–4.927, P=0.001), acute myocardial infarction (AMI) in the high lateral wall indicated by ECG (OR =5.527, 95% CI: 2.798–10.918, P<0.001), acute heart failure (OR =3.585, 95% CI: 2.074–6.195, P<0.001), and NT-proBNP level (OR =1.000, 95% CI: 1.000–1.000, P=0.023) were risk factors for CR in all patients. In patients who accepted PCI, single lesion (OR =0.421, 95% CI: 0.204–0.867, P=0.019), preoperative thrombolysis in myocardial infarction (TIMI) grade (OR =0.358, 95% CI: 0.169–0.760, P=0.007), and postoperative TIMI grade (OR =0.222, 95% CI: 0.090–0.546, P=0.001) were risk factors for CR.ConclusionsNon-single lesions and preoperative and postoperative TIMI grades were risk factors for CR in patients who accepted PCI. In addition to previously reported indicators, we found that AMI in the high lateral wall maybe helpful in early and accurate identification and prevention of possible CR.     

Minimally-invasive versus transcatheter aortic valve implantation: systematic review with meta-analysis of propensity-matched studies

BackgroundMinimally invasive aortic valve replacement (MiAVR) and transcatheter aortic valve implantation (TAVI) provide aortic valve replacement (AVR) by less invasive methods than conventional surgical AVR, by avoiding complete sternotomy. This study directly compares and analyses the available evidence for early outcomes between these two AVR methods.MethodsElectronic databases were searched from inception until August 2019 for studies comparing MiAVR to TAVI, according to predefined search criteria. Propensity-matched studies with sufficient data were included in a meta-analysis.ResultsEight studies with 9,744 patients were included in the quantitative analysis. Analysis of risk-matched patients showed no difference in early mortality (RR 0.76, 95% CI, 0.37–1.54, P=0.44). MiAVR had a signal towards lower rate of postoperative stroke, although this did not reach statistical significance (OR 0.42, 95% CI, 0.13–1.29, P=0.13). MiAVR had significantly lower rates of new pacemaker (PPM) requirement (OR 0.29, 95% CI, 0.16–0.52, P<0.0001) and postoperative aortic insufficiency (AI) or paravalvular leak (PVL) (OR 0.05, 95% CI, 0.01–0.20, P<0.0001) compared to TAVI, (OR 0.42, 95% CI, 0.13–1.29, P=0.13), while acute kidney injury (AKI) was higher in MiAVR compared to TAVI (11.1% vs. 5.2%, OR 2.28, 95% CI, 1.25–4.16, P=0.007).ConclusionsIn patients of equivalent surgical risk scores, MiAVR may be performed with lower rates of postoperative PPM requirement and AI/PVL, higher rates of AKI and no statistical difference in postoperative stroke or short-term mortality, compared to TAVI. Further prospective trials are needed to validate these results.     

Risk factors and survival analysis of arrhythmia following lung cancer surgery: a retrospective study

BackgroundSurgical treatment of lung cancer is one of the important treatments for early-stage non-small cell lung cancer (NSCLC). However, arrhythmia, especially atrial fibrillation (AF) and supraventricular arrhythmia, are quite common among patients after surgical treatment of lung cancer. The impact of postoperative arrhythmia (PA) on survival is rarely reported. Our aim was to evaluate the risk factors of PA and its impact on overall survival (OS) after lung cancer surgery.MethodsA total of 344 patients diagnosed with NSCLC who underwent lung cancer surgery were enrolled in this study. These patients were divided into two groups based on the occurrence of PA. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors of PA. The Kaplan-Meier method was applied to show the OS differences between the two groups.ResultsThe incidence of PA was 16% (55/344). Among these 55 patients, 20 had AF, 30 had sinus tachycardia, and 5 had premature beats. A total of 332 patients underwent lung cancer radical resection. Operation type (P<0.001), preoperative abnormal ECG (P=0.032), transfusion (P=0.016), postoperative serum potassium concentration (P=0.001) and clinical stage (P<0.05) were risk factors for PA. PA (HR 2.083, 95% CI, 1.334–3.253; P=0.001), age (HR 1.543, 95% CI, 1.063–2.239; P=0.025) and mediastinal lymph node metastasis (HR 2.655, 95% CI, 1.809–3.897; P<0.001) were independent prognostic risk factors for OS by multivariate cox analysis.ConclusionsWe identified PA as an independent prognostic risk factor to predict poor OS in patients who underwent lung cancer surgery and had risk factors for PA. We therefore provides guidance for PA in improving the prognosis of lung cancer patients.     

¿Cómo clasificamos un tumor central? Resultados de una encuesta multidisciplinaria propuesta desde el área de Oncología Torácica de SEPAR

IntroductionIn patients with non-small cell lung cancer (NSCLC) and normal mediastinal imaging tests, centrally located tumors have greater occult mediastinal involvement. Clinical guidelines, therefore, recommend invasive mediastinal staging in this situation. However, definitions of centrality in the different guidelines are inconsistent. The SEPAR Thoracic Oncology area aimed to evaluate the degree of familiarity with various concepts related to tumor site among professionals who see patients with NSCLC in Spain.MethodsA questionnaire was distributed to members of Spanish medical societies involved in the management of NSCLC, structured according to the 3 aspects to be evaluated: 1) uniformity in the definition of central tumor location; 2) uniformity in the classification of lesions that extend beyond dividing lines; and 3) ability to delineate lesions in the absence of dividing lines.ResultsA total of 430 participants responded. The most voted definition of centrality was «lesions in contact with hilar structures» (49.7%). The lines most often chosen to delimit the hemitorax were concentric hilar lines (89%). Most participants (92.8%) classified tumors according to the side of the dividing line that contained most of their volume. Overall, 78.6% were able to correctly classify a central lesion in the absence of dividing lines.ConclusionsIn our survey, the most widely accepted definition of centrality is not one of the proposals specified in the clinical guidelines. The results reflect wide variability in the classification of tumor lesions.     

The association of postoperative radiotherapy with survival in resected N2 non-small cell lung cancer

BackgroundThe current staging system for completely resected pathologic N2 non-small cell lung cancer (NSCLC) treated with chemotherapy is not suitable for distinguishing those patients most likely to benefit from postoperative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized prediction of the net survival benefit of PORT in patients with completely resected N2 NSCLC treated with chemotherapy.MethodsA total of 3,094 cases from between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were included as covariates, and their association with overall survival (OS) with and without PORT was assessed. Data from 602 patients from China were included for external validation.ResultsAge, sex, the number of examined/positive lymph nodes, tumor size, the extent of surgery, and visceral pleural invasion (VPI) were significantly associated with OS (P<0.05). Two nomograms were developed based on clinical variables to estimate individuals’ net survival difference attributable to PORT. The calibration curve showed excellent agreement between the OS predicted by the prediction model and that actually observed. In the training cohort, the C-index for OS was 0.619 [95% confidence interval (CI): 0.598–0.641] in the PORT group and 0.627 (95% CI: 0.605–0.648) in the non-PORT group. Results showed that PORT could improve OS [hazard ratio (HR): 0.861; P=0.044] for patients with a positive PORT net survival difference.ConclusionsOur practical survival prediction model can be used to make an individualized estimate of the net survival benefit of PORT for patients with completely resected N2 NSCLC who have been treated with chemotherapy.     

Differential outcomes of residual disease in surgically-resected non-small cell lung cancer and the importance of guideline-concordant adjuvant therapy

BackgroundPositive mediastinal lymph nodes, a marker for systemic disease, and positive margins, a marker for local disease, following resection of non-small cell lung cancer (NSCLC) are forms of residual disease. The objective of this study is to compare survival of patients with residual disease and to study the effect of receipt of guideline vs. non-guideline concordant care.MethodsThe National Cancer Database (NCDB) was used to identify patients who underwent treatment naïve surgical resection with clinical stage T1-3N0-1M0 NSCLC between 2006–2016 and had pN2 disease, positive surgical margins, or both. Concordant care was determined based on form of chemotherapy and radiation, dosage, volume, modality, and duration. Kaplan-Meier survival curves and log-rank tests were used to compare five-year survival. Multivariable analysis using Cox proportional hazards modeling identified factors that contributed to worse overall survival.ResultsThere were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Five-year survival rates for all patients were pN2 (35.8%), positive margins (33.9%), and both (22.9%) (P<0.0001). On multivariable analysis, positive margins were an independent predictor of better survival relative to pN2 disease (HR =0.729, CI: 0.676, 0.787, P<0.0001). Receipt of non-guideline concordant treatment was an independent predictor of worse survival compared to receipt of guideline-concordant treatment (HR =1.61, CI: 1.504, 1.725, P<0.0001).ConclusionsIn upfront surgical patients, guideline-concordant treatment in the setting of residual disease is associated with better overall survival compared with non-guideline concordant treatment. Pathologic N2 disease is associated with a lower survival rate than positive resection margins, possibly reflecting the systemic nature of pN2 disease.     

Predictability of early changes in derived neutrophil-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors

BackgroundAs association between systemic inflammation and disease progression has been suggested, early changes in neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) may have accurate predictability for prognosis in non-small cell lung cancer (NSCLC) treated with ICI therapy.MethodsComplete blood count (CBC) was measured immediately before the first and second cycles of ICI therapy in patients with advanced NSCLC. Differences in NLR and dNLR were measured. When the increase in NLR was ≥1, the patient was classified into the increased NLR group. Similarly, when the increase in dNLR was ≥1, the patient was classified into the increased dNLR group; otherwise, they were classified into the non-increased NLR or dNLR group.ResultsA total of 89 patients was selected for evaluation. Median progression-free survival (PFS) was significantly shorter in the increased NLR group than in the non-increased NLR group (2.6 vs. 9.5 months, P<0.001). The increased dNLR group showed significantly shorter median PFS than the non-increased dNLR group (4.2 vs. 9.2 months, P=0.001). Association with PFS was analyzed using the Cox regression model. In model 1, increase ≥1 in NLR showed significant association (HR =3.085, 95% CI, 1.657–5.742, P<0.001). In model 2, increase ≥1 in dNLR showed significant association (HR =2.826, 95% CI, 1.436–5.561, P=0.003).ConclusionsEarly changes in dNLR were shown to have prognostic value in patients undergoing immunotherapy. It can be an accurate and a comprehensive biomarker for predicting ICI response.     

Tumor size as a predictor for prognosis of patients with surgical IIIA-N2 non-small cell lung cancer after surgery

BackgroundThe 8^th edition of the American Joint Committee on Cancer staging system for lung cancer made major revisions to T staging, especially the size division of stage II/III patients. However, the value of tumor size in the postoperative prognosis of IIIA–N2 non-small cell lung cancer (NSCLC) is seldom mentioned, and survival data of such patients should be re-evaluated according to the 8^th edition staging system.MethodsPatients with IIIA-N2 NSCLC after surgery were identified in the Surveillance, Epidemiology, and End Results database (n=4,128). All patients were stratified according to tumor size, 5-year overall survival (OS) was then compared. Cox regression analysis was used to determine the value of size to discriminate patients with prognostic differences and establish a predictive nomogram system. Patients with IIIA-N2 NSCLC from our own institute (n=583) were used to validate the results.ResultsThe prognosis of patients with tumor sizes of 0–2, 2–4 and 4–5 cm differed greatly from each other in the training cohort, with 5-year OS rates of 53.7%, 43.9% and 36.9% respectively (P<0.001), in the validation cohort, the rates were 54.1%, 38.4% and 33.8% respectively. Tumor size >2 cm was considered an independent risk factor compared to the ≤2 cm group in the Cox regression analysis: 2–4 cm (HR =1.25, 1.12–1.39; P<0.001), 4–5 cm (HR =1.51, 1.32–1.39; P<0.001), the validation cohort showed the same trend. The concordance index of the training set was 0.634 (0.622–0.646), while that of the validation set was 0.716 (0.686–0.746). The calibration plot showed optimal consistency between the nomogram predicted survival and observed survival.ConclusionsTumors with different sizes showed significant postoperative survival differences among patients with IIIA-N2 NSCLC. Tumor size should be considered when making surgery decisions in such patients, with tumor size ≤2 cm showing considerably better prognosis.     

Association of marital status with cardiovascular outcome in patients with breast cancer

BackgroundThe influences of marital status on cardiovascular death risk in patients with breast cancer remained unclear. This study aimed to evaluate the associations of different marital status with cardiovascular death risk in patients with breast cancer.MethodsA total of 182,666 female breast cancer patients were enrolled in this study from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2014, and was divided into two groups: married (N=107,043) and unmarried (N=75,623). A 1:1 propensity score matching (PSM) was applied to reduce inter-group bias between the two groups. Competing-risks model was used to assess the associations between different marital status and cardiovascular death risk in patients with breast cancer.ResultsAfter PSM, marital status was an independent predictor for cardiovascular death in patients with breast cancer. Unmarried condition was associated with increased cardiovascular death risk than married condition among breast cancer patients [unadjusted model: hazard ratio (HR) =2.012, 95% confidence interval (CI): 1.835–2.208, P<0.001; Model 1: HR =1.958, 95% CI: 1.785–2.148, P<0.001; Model 2: HR =1.954, 95% CI: 1.781–2.144, P<0.001; Model 3: HR =1.920, 95% CI: 1.748–2.107, P<0.001]. With the exception of separated condition (adjusted HR =0.886, 95% CI: 0.474–1.658, P=0.705), further unmarried subgroups analysis showed that the other three unmarried status were associated with increased cardiovascular death risk as follows: single (adjusted HR =1.623, 95% CI: 1.421–1.853, P<0.001), divorced (adjusted HR =1.394, 95% CI: 1.209–1.608, P<0.001), and widowed (adjusted HR =2.460, 95% CI: 2.227–2.717, P<0.001). In particularly, widowed condition showed the highest cardiovascular death risk in all 4 unmarried subgroups.ConclusionsUnmarried condition (e.g., single, divorced and widowed) was associated with elevated cardiovascular death risk compared with their married counterparts in patients with breast cancer, suggesting that more attention and humanistic care should be paid to unmarried breast cancer patients (especially the widowed patients) in the management of female breast cancer patients.