Performance of the galactomannan test for the diagnosis of invasive pulmonary aspergillosis using non-invasive proximal airway samples.

OBJECTIVE: To diagnose invasive pulmonary aspergillosis (IPA), galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (BALF) is widely used. However, the utility of proximal airway GM test (from induced sputum or tracheal aspirate) has not been well elucidated. METHODS: In this retrospective cohort study, we evaluated the diagnostic performance of proximal airway GM in diagnosis of IPA including COVID-19 associated pulmonary aspergillosis (CAPA). Between January 2022 and January 2023, patients who had been tested for GM with clinical suspicion or for surveillance from any specimen (serum, induced sputum, tracheal aspirate, and BALF) were screened. IPA was diagnosed using EORTC/MSGERC criteria, and CAPA was diagnosed following the 2020 ECMM/ISHAM consensus criteria. RESULTS: Of 624 patients with GM results, 70 met the criteria for proven/probable IPA and 427 had no IPA. The others included possible IPA and chronic form of aspergillosis. The sensitivities and specificities of serum, proximal airway, and BALF GM for proven/probable IPA versus no IPA were 78.9% and 70.6%, 93.1% and 78.7%, and 78.6% and 91.0%, respectively. Areas under the receiver operating characteristic curve (AUCs) were 0.742 for serum GM, 0.935 for proximal airway GM, and 0.849 for BALF GM (serum GM vs proximal airway GM, p = 0.014; proximal airway GM vs BALF GM, p = 0.334; serum GM vs BALF GM, p = 0.286). CONCLUSION: This study demonstrates that the performance of GM test from non-invasive proximal airway samples is comparable or even better than those from serum and distal airway sample (BALF).

Prevalence of pre-existing lung diseases and their association with income level among patients with lung cancer: a nationwide population-based case-control study in South Korea.

BACKGROUND: This study aimed to estimate the prevalence of pre-existing lung diseases in patients with lung cancer compared to people without lung cancer and examine the association between income levels and pre-existing lung diseases. METHODS: Data on patients with lung cancer (case) and the general population without lung cancer (non-cancer controls) matched by age, sex and region were obtained from the Korea National Health Insurance Service-National Health Information Database (n=51 586). Insurance premiums were divided into quintiles and medicaid patients. Conditional logistic regression models were used to examine the association between pre-existing lung diseases and the risk of lung cancer. The relationship between income level and the prevalence of pre-existing lung disease among patients with lung cancer was analysed using logistic regression models. RESULTS: The prevalence of asthma (17.3%), chronic obstructive lung disease (COPD) (9.3%), pneumonia (9.1%) and pulmonary tuberculosis (1.6%) in patients with lung cancer were approximately 1.6-3.2 times higher compared with the general population without lung cancer. A significantly higher risk for lung cancer was observed in individuals with pre-existing lung diseases (asthma: OR=1.36, 95% CI 1.29 to 1.44; COPD: 2.11, 95% CI 1.94 to 2.31; pneumonia: 1.49, 95% CI 1.38 to 1.61; pulmonary tuberculosis: 2.16, 95% CI 1.75 to 2.66). Patients with lung cancer enrolled in medicaid exhibited higher odds of having pre-existing lung diseases compared with those in the top 20% income level (asthma: OR=1.75, 95% CI 1.56 to 1.96; COPD: 1.91, 95% CI 1.65 to 2.21; pneumonia: 1.73, 95% CI 1.50 to 2.01; pulmonary tuberculosis: 2.45, 95% CI 1.78 to 3.36). CONCLUSIONS: Pre-existing lung diseases were substantially higher in patients with lung cancer than in the general population. The high prevalence odds of pre-existing lung diseases in medicaid patients suggests the health disparity arising from the lowest income group, underscoring a need for specialised lung cancer surveillance.

Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? STUDY DESIGN AND METHODS: For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021). RESULTS: The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration. INTERPRETATION: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02991924; URL: www. CLINICALTRIALS: gov.

Long-term Survival According to N Stage Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Non-small Cell Lung Cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main procedure for mediastinal staging. However, long-term survival analyses according to clinical nodal stage diagnosed by EBUS-TBNA (eN stage) have not been reported. The value of EBUS-TBNA has not been assessed through an analysis of survival in false-negative EBUS-TBNA cases. RESEARCH QUESTION: What is the prognostic impact of eN stage in non-small cell lung cancer (NSCLC)? What is the survival rate in false-negative EBUS-TBNA cases? STUDY DESIGN AND METHODS: We retrospectively (January 2006 to December 2011) reviewed the medical records of patients with NSCLC who underwent EBUS-TBNA (± transesophageal approach) for initial staging (N = 1,089). Mediastinoscopy was not performed for EBUS-TBNA-negative cases. We performed 5-year survival analyses according to eN stage and treatment modality. Survival in false-negative EBUS-TBNA cases was compared with that in patients with pN0-1, including 941 non-EBUS-TBNA cases, during the same period. RESULTS: Among the 1,089 patients undergoing EBUS-TBNA (eN0-1: n = 681; eN2: n = 314; eN3: n = 94), we observed significant differences in survival between the eN stages (eN0-1 vs eN2: P < .0001; eN2 vs eN3: P = .0118; estimated 5-year overall survival [5YOS] rate: eN0-1 = 57.4%, eN2 = 23.2%, eN3 = 12.8%). Surgery cases had better survival than nonsurgery cases among patients with eN0-1 and eN2 (eN0-1/surgery vs eN0-1/no surgery: P < .0001; eN2/surgery vs eN2/no surgery: P < .0001). Among the patients with eN0-1, there were 55 false-negative cases (eN0-1/pN2-3, pN2: n = 54; pN3: n = 1). The 5YOS rates of patients with pN0, pN1, and eN0-1/pN2-3 were 76.4%, 56.0%, and 56.4%, respectively. Patients with eN0-1/pN2-3 had worse survival than patients with pN0 (P = .0061), whereas there was no significant difference compared with patients with pN1 (P = .9191). INTERPRETATION: Long-term survival significantly differed according to eN stage in NSCLC, highlighting the importance of EBUS-TBNA in NSCLC staging. False-negative EBUS-TBNA cases had favorable survival which was similar to that of patients with pN1, which may provide a rationale for performing surgery after negative EBUS-TBNA results.

Increased Incidence and Associated Risk Factors of Aspergillosis in Patients with Bronchiectasis.

There are insufficient data regarding the relationship between non-cystic fibrosis bronchiectasis and incident aspergillosis. We performed a population-based, matched cohort study using data from the Korean National Health Insurance database between 2003 and 2013. The incidence of aspergillosis was 50/100,000 person-years in the bronchiectasis cohort and 11/100,000 person-years in the matched cohort (subdistribution hazard ratio, 4.53; 95% confidence interval (CI), 3.25-6.32). Among the bronchiectasis cohort, chronic obstructive pulmonary disease (adjusted HR, 1.95; 95% CI, 1.07-3.57), previous pulmonary tuberculosis (adjusted HR, 3.67; 95% CI, 2.03-6.64), and non-tuberculous mycobacterial pulmonary disease (adjusted HR, 11.25; 95% CI, 1.49-85.18) increased the risk of incident aspergillosis. The incidence of aspergillosis in patients with bronchiectasis was approximately 4.5-fold that in those without bronchiectasis. Comorbid pulmonary diseases-chronic obstructive pulmonary disease, previous pulmonary tuberculosis, and non-tuberculous mycobacterial pulmonary disease-significantly increased the risk of aspergillosis in patients with bronchiectasis. Our study indicates that close monitoring is warranted for aspergillosis in patients with bronchiectasis.

Incidence of bronchiectasis concerning tuberculosis epidemiology and other ecological factors: A Korean National Cohort Study.

In South Korea, the estimated incidences of bronchiectasis were 147-229 cases per 100000 with a decreasing trend. It may follow the concurrent decrease in the TB prevalence and incidence, and favourable personal and socioeconomic conditions. https://bit.ly/32UA8xH.

Lung cancer staging: State of the art in the era of ablative therapies and surgical segmentectomy.

Implementation of lung cancer screening and improvements in imaging are expected to increase the proportion of lung cancer diagnosed at an early stage. The standard of care has historically been anatomic lobectomy; however, there is now an array of surgical and non-surgical approaches for management of local disease either in active use or under investigation. By their nature, these new modalities offer a theoretical trade-off of reduced morbidity in exchange for reduced efficacy in the setting of advanced disease. It is therefore critical that patients being considered for these approaches (e.g. surgical segmentectomy and SABR) be accurately staged to maximize the potential for definitive treatment. In this article, we will review current approaches to the staging of patients being considered for segmentectomy or ablation. This will serve as a foundation to highlight important questions deserving further investigation.

Pulmonary Tuberculosis is Associated with Elevated Risk of Lung cancer in Korea: The Nationwide Cohort Study.

Objective: Although previous studies suggest that previous pulmonary tuberculosis was associated with increased risk of lung cancer. It remains controversial whether pulmonary tuberculosis is a risk factor for lung cancer. Our study was aimed to examine the association between pulmonary tuberculosis and lung cancer risk in Korean. Methods: The Korean National Health and Nutrition Examination Survey database was linked with the Korean National Cancer Incidence Database to examine the occurrence of pulmonary tuberculosis and lung cancer. The linked databases were also merged with causes of death database of Statistics Korea. The Cox-proportional hazards model was used to estimates the hazard risk of lung cancer for Korean adults aged ≥40 years with pulmonary tuberculosis. Results: Of 20,252 total participants, 2,640 (13.0%) had old pulmonary tuberculosis (a medical history of pulmonary tuberculosis or radiologically inactive tuberculosis). After adjusting for all covariates, the hazard ratio of lung cancer among patients with old pulmonary tuberculosis was 3.24 (95% CI, 1.87‒5.62) compared to the control group. According to smoking status, the hazard ratios of lung cancer for never smokers, ex-smokers, and current smokers among participants with old pulmonary tuberculosis were 3.52 (95% CI, 1.17‒10.63), 2.16 (95% CI, 0.89‒5.24), and 3.71 (95% CI, 1.49‒9.22) compared to the control group, respectively. Conclusions: Korean adults with old pulmonary tuberculosis have a higher risk of lung cancer, compared to general population without pulmonary tuberculosis.

Views on Precision Medicine among Health Professionals in Korea: A Mixed Methods Study.

This study aimed to investigate awareness, attitudes, and perspectives on precision medicine among health professionals in Korea and to identify issues that need to be addressed before implementing precision medicine. Mixed methods research was applied. For qualitative research, a semi-structured focus group interview was conducted with six health professionals. For quantitative research, a self-reported survey was administered. A total of 542 health professionals participated in the survey, and 526 completed the entire questionnaire. Health professionals showed positive attitudes toward precision medicine. About 95-96% of respondents agreed that precision medicine will be effective in treatment and precise diagnosis, and 69.9% reported that they would participate as study subjects. Meanwhile, they expressed concerns regarding educating patients and health professionals in precision medicine and developing research and data sharing infrastructure. Also, they emphasized the importance of developing precision medicine in an equitable way. Despite varying levels of awareness of precision medicine, the health professionals expressed a willingness to engage in precision medicine research, and recommended that health professionals work closely with policymakers to design precision medicine in a way that can be effectively adopted. Health professionals showed had a positive, but cautious, attitude toward precision medicine. The results of this study suggest areas to be addressed before ushering in precision medicine in Korea.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer.

PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for the diagnosis and staging of lung cancer. However, evidence of its usefulness for re-biopsy in treated lung cancer, especially according to the previous treatment, is limited. We evaluated the role of EBUS-TBNA for re-biopsy and its diagnostic values in patients with different treatment histories. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent EBUS-TBNA for re-biopsy of suspicious recurrent or progressive lesions between January 2006 and December 2016 at the National Cancer Center in South Korea. Patients were categorized into three groups based on the previous treatment modalities: surgery, radiation, and palliation. RESULTS: Among the 367 patients (surgery, n=192; radiation, n=40; palliation, n=135) who underwent EBUS-TBNA for re-biopsy, the overall sensitivity, negative predictive value (NPV), and diagnostic accuracy of EBUS-TBNA in detecting malignancy were 95.6%, 82.7%, and 96.3%, respectively. The sensitivity was lower in the radiation group (83.3%) when compared with the surgery (95.7%, p=0.042) and palliation (97.7%, p=0.012) groups. The NPV was lower in the palliation group (50.0%) than in the surgery group (88.5%, p=0.042). The sample adequacy of EBUS-TBNA specimens was lower in the radiation group (80.3%) than in the surgery (95.4%, p < 0.001) or palliation (97.8%, p < 0.001) groups. EGFR mutation analysis was feasible in 94.6% of the 92 cases, in which mutation analysis was requested. There were no major complications. Minor complications were reported in 12 patients (3.3%). CONCLUSION: EBUS-TBNA showed high diagnostic values and high suitability for EGFR mutation analysis with regard to re-biopsy in patients with previously treated lung cancer. The sensitivity was lower in the radiation group and NPV was lower in the palliation group. The complication rate was low.

Effect of Antihypertensive Medications on Sepsis-Related Outcomes: A Population-Based Cohort Study.

OBJECTIVES: Although the effect of antihypertensive agents on sepsis has been studied, evidence for survival benefit was limited in the literature. We investigated differences in sepsis-related outcomes depending on the antihypertensive drugs given prior to sepsis in patients with hypertension. DESIGN: Population-based cohort study. SETTING: Sample cohort Database of the National Health Insurance Service from 2003 to 2013 in South Korea. PATIENTS: Patients over 30 years old who were diagnosed with sepsis after receiving hypertension treatment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes, 30-day and 90-day mortality rates, were analyzed for differences among three representative antihypertensive medications: angiotensin- converting enzyme inhibitors or angiotensin II receptor blockers, calcium channel blockers, and thiazides. In total, 4,549 patients diagnosed with hypertension prior to hospitalization for sepsis were identified. The 30-day mortality was significantly higher among patients who did not receive any medications within 1 month before sepsis (36.8%) than among patients who did (32.0%; p < 0.001). The risk for 90-days mortality was significantly lower in prior angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker users (reference) than in other drug users (odds ratio, 1.27; 95% CI, 1.07-1.52). There was no difference in the risk for 30-day and 90-day mortality depending on whether calcium channel blockers or thiazides were used. Use of calcium channel blockers was associated with a decreased risk for inotropic agent administration, compared with those of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio, 1.23; 95% CI, 1.05-1.44) and thiazides (odds ratio, 1.33; 95% CI, 1.12-1.58). CONCLUSIONS: In patients with sepsis, lower mortality rate was associated with prior use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers not with use of calcium channel blockers or thiazides. The requirement of inotropic agents was significantly lower in prior use of calcium channel blockers, although the survival benefits were not prominent.

WITHDRAWN:The Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer.

Ahead of Print article withdrawn by publisher.

Lung Cancer Screening with Low-Dose CT in Female Never Smokers: Retrospective Cohort Study with Long-term National Data Follow-up.

PURPOSE: Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings. MATERIALS AND METHODS: This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT. RESULTS: After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined. CONCLUSION: Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.

Prognostic Differences in Subgroups of Patients With Surgically Resected T3 Non-Small Cell Lung Cancer.

BACKGROUND: This study determined the characteristics and prognosis of each descriptor of T3 non-small cell lung cancer (NSCLC). METHODS: A total of 3,241 patients underwent an operation for NSCLC between 2001 and 2013, and this study included 461 patients who received complete anatomic resection of T3 NSCLC. The T3 descriptors were coded as follows: tumor invading main bronchus within 2 cm of the carina (T3-cent), tumor invading beyond visceral pleura (T3-inv), tumor larger than 7 cm (T3-size), separate tumor nodules (T3-sep), or tumor with combined T3 descriptors (T3-comb). RESULTS: The T3 distribution was as follows: T3-cent, 75 patients (16.3%); T3-inv, 157 patients (34.1%); T3-size, 132 patients (28.6%); T3-sep, 34 patients (7.4%); and T3-comb, 63 patients (13.7%). Subgroup analyses revealed a significant survival benefit in the T3-cent group compared with the other groups (all p < 0.05). The 5-year disease-free survival (DFS) values were 55.4%, 36.7%, 40.9%, 30.3%, and 32.0% in the T3-cent, T3-inv, T3-size, T3-sep, and T3-comb subgroups, respectively. Multivariable analyses revealed that age (p = 0.019), N status (p = 0.001), adjuvant chemotherapy (p < 0.001), and T3 descriptors (T3-cent versus others, p < 0.001) were the most important independent prognostic factors for DFS. Additional analyses were performed to evaluate prognostic factors for DFS in the T3-cent group. Multivariable analysis revealed that bronchoplastic procedures (p = 0.004) was an independent prognostic factor for DFS. CONCLUSIONS: Survival for centrally located T3 NSCLC is better than other types of T3 NSCLC. Lung-preserving operations such as bronchoplastic procedures might result in improved survival of these patients.

Comparison of Epidermal Growth Factor Receptor Mutations between Metastatic Lymph Node Diagnosed by EBUS-TBNA and Primary Tumor in Non-Small Cell Lung Cancer.

INTRODUCTION: Although the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasing for epidermal growth factor receptor (EGFR) testing in lung cancer, the discordance rate in EGFR mutations between lymph node (LN) samples obtained by EBUS-TBNA and primary tumor (PT) is not well known. Thus, we compared the EGFR mutation status of LN samples obtained by EBUS-TBNA and PTs to estimate the efficacy of using EBUS-TBNA specimens for EGFR testing in advanced, non-squamous, non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using data of patients from the EBUS-TBNA database (N = 1914) obtained between January 2009 and January 2013, we identified 100 treatment-naïve, advanced, non-squamous NSCLC patients (stage 3 and 4) with matched LN specimens obtained by EBUS-TBNA and PT specimens. Of these, 74 patients with paired specimens were feasible for EGFR mutation analysis, which we performed using a direct sequencing method. RESULTS: Of the 74 cases, at least one major [exon 19 deleted (19del) and L858R] or minor (T790M, exon 20 insertion, and other point mutations) EGFR mutation was detected in 31 cases (41.9%), which included PT (n = 31, 41.9%) and LN (n = 28, 37.8%) specimens. Major mutations were detected in 25 PT (33.8%, 19del = 13, L858R = 12) and 22 LN (29.8%, 19del = 11, L858R = 11) specimens. The discordance rate in major mutations between matched PT and LN specimens was 4.1% (3/74). Among minor mutations, T790M was detected in LN specimen only in 2 cases with L858R in PT and LN. The discordance rate major and minor EGFR mutations combined between matched PT and LN specimens was 12% (9/74). CONCLUSIONS: We observed a high concordance rate of major EGFR mutations between matched LN specimens sampled by EBUS-TBNA and PTs, suggesting that LN samples obtained by EBUS-TBNA from advanced non-squamous NSCLC patients are effective for use in EGFR mutation testing.

A phase II study of nintedanib in patients with relapsed small cell lung cancer.

OBJECTIVES: Nintedanib is an oral triple angiokinase inhibitor. This study was conducted to evaluate the efficacy and safety of nintedanib in patients (pts) with relapsed/refractory small cell lung cancer (SCLC). PATIENTS AND METHODS: Pts with an ECOG PS from 0 to 2 who exhibited progression after one or two prior chemotherapy or chemo/radiotherapy were enrolled. Pts received nintedanib 200mg BID daily in a 4-week cycle until progression or intolerable toxicity. The primary end point was the objective response rate (ORR). A two-stage design was employed. To continue to stage 2, ≥2 responders out of 22 pts were required. RESULTS: From Dec 2011 to June 2014, 24 pts were enrolled. Twenty-two pts completed treatment and were evaluable for response. The median follow-up was 9.7 (0.5-19.8) months. The median age was 64 (46-77) years. Twenty-two pts were male. Six pts had sensitive relapse. Eight pts received one prior chemotherapy. A median of one (range 1-5) cycle was administered. One pt had a partial response, and seven pts exhibited stable disease. The ORR was 5% (95% confidence interval [CI], 0.1-22.8). Median progression-free survival was 1.0 (95% CI, 0.9-1.1) month, and overall survival was 9.8 (95% CI, 8.4-11.2) months. The response criteria to proceed to full accrual were not met. The most frequent drug-related adverse events (AE) included hepatic enzyme elevation (86%), anemia (73%), anorexia (59%), and nausea (50%). Most AEs were mild and manageable. Grade 3 hepatic enzyme elevation occurred in 5 pts (23%). CONCLUSIONS: Nintedanib exhibited only limited activity with a manageable AE profile in relapsed or refractory SCLC (NCT01441297).

Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer.

RATIONALE: Conventional transbronchial needle aspiration (TBNA) and endobronchial ultrasound (EBUS)-TBNA are widely accepted tools for the diagnosis and staging of lung cancer and the initial procedure of choice for staging. Obtaining adequate specimens is key to provide a specific histologic and molecular diagnosis of lung cancer. OBJECTIVES: To develop practice guidelines on the acquisition and preparation of conventional TBNA and EBUS-TBNA specimens for the diagnosis and molecular testing of (suspected) lung cancer. We hope to improve the global unification of procedure standards, maximize the yield and identify areas for research. METHODS: Systematic electronic database searches were conducted to identify relevant studies for inclusion in the guideline [PubMed and the Cochrane Library (including the Cochrane Database of Systematic Reviews)]. MAIN RESULTS: The number of needle aspirations with both conventional TBNA and EBUS-TBNA was found to impact the diagnostic yield, with at least 3 passes needed for optimal performance. Neither needle gauge nor the use of miniforceps, the use of suction or the type of sedation/anesthesia has been found to improve the diagnostic yield for lung cancer. The use of rapid on-site cytology examination does not increase the diagnostic yield. Molecular analysis (i.e. EGFR, KRAS and ALK) can be routinely performed on the majority of cytological samples obtained by EBUS-TBNA and conventional TBNA. There does not appear to be a superior method for specimen preparation (i.e. slide staining, cell blocks or core tissue). It is likely that optimal specimen preparation may vary between institutions depending on the expertise of pathology colleagues.

EBUS-centred versus EUS-centred mediastinal staging in lung cancer: a randomised controlled trial.

BACKGROUND: The impact of procedure sequence and primary procedure has not been studied in the combined application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lung cancer staging. METHODS: In a randomised controlled trial, 160 patients with histologically confirmed or strongly suspected potentially operable non-small cell lung cancer were enrolled (Group A, n=80, EBUS-centred; Group B, n=80, EUS-centred). EBUS-TBNA and EUS-FNA with an ultrasound bronchoscope were used as the first procedures in Groups A and B, respectively, and secondary procedures (EUS-FNA in Group A, EBUS-TBNA in Group B) were added. RESULTS: Diagnostic values were evaluated in 148 patients (74 in each group). In Groups A and B the diagnostic accuracy (93.2% (95% CI 87.5% to 99.0%) vs 97.3% (95% CI 93.6% to 101.0%), p=0.245) and sensitivity (85.3% (95% CI 68.9% to 95.0%) vs 92.0% (95% CI 74.0% to 99.0%), p=0.431) in detecting mediastinal metastasis were not statistically different. In Group A, adding EUS-FNA to EBUS-TBNA did not significantly increase the accuracy (from 91.9% to 93.2%, p=0.754) or sensitivity (from 82.4% to 85.3%, p=0.742). In group B, adding EBUS-TBNA to EUS-FNA increased the accuracy (from 86.5% to 97.3%, p=0.016) and sensitivity (from 60.0% to 92.0%, p=0.008). There were no intergroup differences in procedure time, cardiorespiratory parameters during procedures, complications or patient satisfaction. CONCLUSIONS: Using a combination of EBUS-TBNA and EUS-FNA in mediastinal staging, we found that diagnostic values and patient satisfaction were not different between the EBUS-centred and EUS-centred groups. However, the necessity for EBUS-TBNA following EUS suggests that EBUS-TBNA is a better primary procedure in endoscopic mediastinal staging of potentially operable lung cancer. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT01385111.