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Purpose Smoking cessation intervention is one of the key components of successful lung cancer screening program. We investigated the effectiveness and related factors of smoking cessation services provided to the participants in a population-based lung cancer screening trial. Materials and Methods The Korean Lung Cancer Screening Project (K-LUCAS) is a nationwide, multi-center lung cancer screening trial that evaluates the feasibility of implementing population-based lung cancer screening. All 5,144 current smokers who participated in the K-LUCAS received a mandatory smoking cessation counseling. Changes in smoking status were followed up using a telephone survey in 6 months after lung cancer screening participation. The lung cancer screening's impact on smoking cessation is analyzed by variations in the smoking cessation interventions provided in screening units. Results Among 4,136 survey responders, participant's motivation to quit smoking increased by 9.4% on average after lung cancer screening. After 6 months from the initial screening, 24.3% of participants stopped smoking, and 10.6% of participants had not smoked continuously for at least 6 months after screening. Over 80% of quitters stated that participation in lung cancer screening motivated them to quit smoking. Low-cost public smoking cessation program combined with lung cancer screening increased the abstinence rates. The smokers were three times more likely to quit smoking when the smoking cessation counseling was provided simultaneously with low-dose computed tomography screening results than when provided separately. Conclusion A mandatory smoking cessation intervention integrated with screening result counselling by a physician after participation in lung cancer screening could be effective for increasing smoking cessation attempts. [ABSTRACT FROM AUTHOR]

Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. Materials and Methods This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. Results A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. Conclusion NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes. [ABSTRACT FROM AUTHOR]

Purpose Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. Materials and Methods In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. Results Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). Conclusion Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients. [ABSTRACT FROM AUTHOR]

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. EGFRmutation 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. [ABSTRACT FROM AUTHOR]

Purpose To reduce lung cancer mortality, lung cancer screening was recommended using low-dose computed tomography (LDCT) to high-risk population. A protocol for multicenter lung cancer screening pilot project was developed to evaluate the effectiveness and feasibility of lung cancer screening to implement National Cancer Screening Program in Korea. Materials and Methods Multidisciplinary expert committee was comprised to develop a standardized protocol for Korean Lung Cancer Screening Project (K-LUCAS). K-LUCAS is a population-based single arm trial that targets high-risk population aged 55-74 years with at least 30 pack-year smoking history. LDCT results are reported by Lung-RADS suggested by American Radiology Society. Network-based system using computer-aided detection program is prepared to assist reducing diagnostic errors. Smoking cessation counselling is provided to all currently smoking participants. A small pilot test was conducted to check the feasibility and compliance of the protocols for K-LUCAS. Results In pilot test, 256 were participated. The average age of participants was 63.2 years and only three participants (1.2%) were female. The participants had a smoking history of 40.5 pack-year on average and 53.9% were current smokers. Among them, 86.3% had willing to participate in lung cancer screening again. The average willingness to quit smoking among current smokers was 12.7% higher than before screening. In Lung-RADS reports, 10 (3.9%) were grade 3 and nine (3.5%) were grade 4. One participant was diagnosed as lung cancer. Conclusion The protocol developed by this study is assessed to be feasible to perform K-LUCAS in multicenter nationwide scale. [ABSTRACT FROM AUTHOR]

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 examine whether 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. [ABSTRACT FROM AUTHOR]

Purpose: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. Materials and Methods: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. Results: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CAmutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. Conclusion: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation. [ABSTRACT FROM AUTHOR]

Purpose Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen. Materials and Methods Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m²) and G (1,000 mg/m²) on days 1 and 8 of each cycle of 21 days until disease progression. Results Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia. Conclusion Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer death in many countries, including Korea. The majority of patients are inoperable at the time of diagnosis because symptoms are typically manifested at an advanced stage. A recent large clinical trial demonstrated significant reduction in lung cancer mortality by using low dose computed tomography (LDCT) screening. A Korean multisociety collaborative committee systematically reviewed the evidences regarding the benefits and harms of lung cancer screening, and developed an evidence-based clinical guideline. There is high- level evidence that annual screening with LDCT can reduce lung cancer mortality and all-cause mortality of high-risk individuals. The benefits of LDCT screening are modestly higher than the harms. Annual LDCT screening should be recommended to current smokers and ex-smokers (if less than 15 years have elapsed after smoking cessation) who are aged 55 to 74 years with 30 pack-years or more of smoking-history. LDCT can discover non-calcified lung nodules in 20 to 53% of the screened population, depending on the nodule positivity criteria. Individuals may undergo regular LDCT follow-up or invasive diagnostic procedures that lead to complications. Radiation-associated malignancies associated with repetitive LDCT, as well as overdiagnosis, should be considered the harms of screening. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Education and actions to stop smoking must be offered to current smokers. Chest radiograph, sputum cytology at regular intervals, and serum tumor markers should not be used as screening methods. These guidelines may be amended based on several large ongoing clinical trial results. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness of using transesophageal and transbronchial needle aspiration using a single ultrasound bronchoscope in the mediastinal staging of non-small cell lung cancer. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) identified mediastinal metastasis in 38 out of 143 patients while endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) diagnosed mediastinal metastasis in three more patients. Negative predictive value, diagnostic accuracy and sensitivity are discussed.

Background and objective: Although endoscopic ultrasound-guided fine needle aspiration can be helpful when combined with bronchoscopic procedures, endoscopic ultrasound-guided fine needle aspiration is not available as a conjunctive procedure with bronchoscopy at many institutions. This study evaluated the feasibility and the additional role of transoesophageal fine needle aspiration using a convex probe ultrasonic bronchoscope (EUS-B-FNA). Methods: We analysed 84 patients who underwent EUS-B-FNA between Oct 2007 and May 2008. Bronchoscopy and/or endobronchial ultrasound-guided transbronchial needle aspiration was performed on 83 patients prior to EUS-B-FNA. Results: EUS-B-FNA was performed on 89 lesions (1.7 aspirations/lesion) including three lung masses and 86 lymph nodes (nodal stations 1, 3P, 4L, 5, 7, 8, 9 and 10L) without complication. Sample adequacy was 95.4% for each aspiration and 100% for each lesion. Of the 89 lesions, 39 malignant lesions were confirmed by EUS-B-FNA. EUS-B-FNA provided additional diagnostic gain to bronchoscopic procedures in 16 patients (19.0%): 3 lung cancers were upstaged, 11 lung cancers were pathologically confirmed, and 2 patients were diagnosed with mediastinal metastasis from an extrathoracic malignancy. This gain was obtained by the sampling of inaccessible ( n = 4) or difficult lesions by endobronchial ultrasound-guided transbronchial needle aspiration ( n = 2) or when bronchoscopy was difficult due to dyspnoea, cough, brain metastasis or other conditions ( n = 10). Conclusions: EUS-B-FNA is a technically feasible and safe procedure, which may be an alternative to endoscopic ultrasound-guided fine needle aspiration as a procedure that complements bronchoscopy. Additional diagnostic yield can be obtained by combining EUS-B-FNA with bronchoscopic procedures. [ABSTRACT FROM AUTHOR]

The article discusses the study which examines the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) followed by positron emission tomography (PET) computed tomography (CT) scanning in mediastinal staging of non-small cell lung cancer (NSCLC). The study evaluated the diagnostic values of PET/CT scanning with accessible for mediastinal staging. Thus, EBUS-TBNA was an effective invasive method in mediastinal staging of operable NSCLC.

The article investigates the role of amifostine and epoetin-α in the reduction of toxicities in chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC). Results revealed that while amifostine treatment during CCRT was not effective in reducing severe toxicities such as higher febrile neutropenia and nausea, epoetin-α was able to prevent severe anemia during CCRT in LD-SCLC patients.

The article aims to determine the optimal number of aspirations for every lymph node (LN) station during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) to maximize diagnostic yield in the mediastinal staging of non-small cell lung cancer (NSCLC) without rapid and onsite cytopathologic examination.

Background: The current study was performed to compare the nonplatinum-based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer (NSCLC).Methods: Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m(2) plus cisplatin at a dose of 30 mg/m(2) (Arm A) or gemcitabine at a dose of 900 mg/m(2) plus vinorelbine at a dose of 25 mg/m(2) (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first-line therapy followed by crossover at the time of disease progression.Results: A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first-line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second-line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first-line therapy, and 30% vs 13% as second-line therapy) compared with GV. IP also demonstrated a favorable trend in median progression-free survival (4.6 months vs 3.8 months as first-line therapy and 4.5 months vs 2.6 months as second-line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second-line setting.Conclusions: The platinum-based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

This phase II study assessed the efficacy and toxicity profile of a modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic/recurrent esophageal squamous cell carcinoma (SQCC). The eligibility criteria included histologically confirmed esophageal SQCC, no prior chemotherapy, adequate organ functions and written informed consent. Patients received irinotecan 65 mg/m2 plus cisplatin 30 mg/m2 on days 1 and 8, every 3 weeks. Thirty-two patients were assessed for response and toxicity. Ten patients achieved a partial response (31.3%; 95% CI, 16.0–50.0%). With a median follow-up of 19.0 months, median progression-free and overall survival was 4.4 and 9.6 months, respectively, with a 1-year survival rate of 27.4%. Grade (G) 3/4 neutropenia was observed in 50.0% of the patients, which was the most common cause of dose reduction or therapy delay. G3 non-hematologic toxicity included seven (21.9%) asthenias, four (12.5%) diarrheas, and one (3.1%) nausea/vomiting, but no G4 non-hematologic toxicity was observed. This modified weekly irinotecan and cisplatin failed to ameliorate hematologic toxicity and to improve efficacy. However, easy administration and favorable non-hematologic toxicity as well as modest anti-tumor activity against metastatic or recurrent esophageal SQCC can make this regimen a potential treatment option, given the complexity of administration and toxicity of conventional infusional 5-FU and cisplatin. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to several articles in the October 2010 issue on lung cancer staging through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EBUS-FNA) including one by F. J. F. Herth and colleagues on the use of a single bronchoscope, another by B. Hwangbo and colleagues on the use of an ultrasound bronchoscope and one by J. T. Annema and colleagues on the use of endosonography.