e20655 Background: ICOGEN was a randomized Phase III clinical trial comparing two EGFR tyrosine kinase inhibitors (TKI), icotinib (I) and gefitinib (G), in EGFR gene mutation status unknown non-small-cell lung cancer (NSCLC) patients previously treated with platinum doublet chemotherapy. Plasma samples from study patients were retrospectively analyzed with a commercially-available blood-based proteomic test which has been shown to have prognostic and predictive properties in NSCLC. This study represents an updated analysis of ICOGEN to evaluate the ability of the test to predict outcome based on therapeutic regimen. Methods: Available pre-treatment plasma samples from ICOGEN were retrospectively analyzed with the proteomic test which classifies subjects as Good or Poor. Progression free survival (PFS ) and over-all survival (OS) were analyzed within treatment (TX) arms and test classification. Results: 352 subjects were evaluated, with 277(78.7%) classified as Good and 75(21.3%) classified as Poor. Among all patients evaluated with the proteomic test, the median PFS was 4.9 mo. and 2.3 mo. (HR [95% CI] 0.61 [0.46 – 0.81]; p = 0.0004) and median OS was 16.6 mo. and 5.5 mo. (HR [95% CI] 0.39 [0.29 – 0.50]; p < 0.0001) for the Good and Poor sub-groups, respectively. Association between test result and PFS was significant in patients treated with I (6.0 mo vs. 1.9 mo, HR = 0.43, p < 0.0001), but not significant in patients treated with G (3.7 mo vs. 2.5 mo, HR = 0.85, p = 0.429). Further evaluation demonstrated that the proteomic test predicted differential therapeutic benefit between icotinib and gefitinib for PFS (pint = 0.036). In OS, a significant association between test result and outcome was shown in both the I (16.3 mo vs. 4.0 mo, HR [95% CI] 0.27[0.19-0.39]; p < 0.0001) and G (16.6 mo vs. 7.0 mo, HR [95% CI] 0.51[0.35-0.76; p = 0.0008) arms, which trended towards prediction of differential therapeutic benefit between icotinib and gefitinib for OS (pint = 0.086). Conclusions: For ICOGEN’s primary study endpoint, the proteomic test was predictive of differential therapeutic benefit between icotinib and gefitinib in EGFR mutations status unknown NSCLC patients.

e20626 Background: VeriStrat, a blood-based MALDI-TOF mass spectrometry serum protein test has been shown to have both prognostic and predictive utility for EGFR targeted therapies in NSCLC.1In an analysis of an all Chinese patient population, VeriStrat was used to classify subjects from the ICOGEN2 clinical trial which compared icotinib,an EGFR-TKI available in China, with gefitinib on NSCLC patients who have had one or two prior chemotherapies. Methods: Pre-treatment plasma samples from the ICOGEN clinical trial were analyzed with VeriStrat which classified subjects with respect to predefined reference groups VS-G and VS-P. Clinical outcomes were analyzed as a function of both treatment arm and VeriStrat status. Results: From the ICOGEN trial, 357 subjects were classified (VS-G: 283; VS-P: 74) with VeriStrat. In the cumulative patient population stratified by VeriStrat but inclusive of both treatmentarms the median OS was 16.5 mo. and 5.75 mo. (HR [95% CI] 0.47 [0.25 – 0.49]; p < 0.001) and median PFS was 5.25 mo. and 2.5 mo. (HR [95% CI] 0.62 [0.40 – 0.73]; p < 0.001) in the VS-G and VS-P groups respectively.Results were similar within the icotinib arm where the median OS was 16.5 mo. and 4.25 mo. (HR [95% CI] 0.35 [0.11–0.39]; p < 0.001) and median PFS was 7.0 mo. and 2.0 mo. (HR [95% CI] 0.46 [0.19 – 0.48]; p < 0.001) in the VS-G and VS-P groups respectively. Conclusions: The blood-based test VeriStrat provides a rapid method for determining the likely response of patients to an EGFR TKI therapy in the second line. Specifically, in this all Chinese cohort, patients classified as VS-G performed significantly better in PFS and OS than those classified VS-P.

Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson's disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50-60(sic) inclusive of taxes. In our own hospital (tertiary level), it is nearly 30(sic) per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6(sic). Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000(sic) more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.

BACKGROUND:Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. METHODS:Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. RESULTS:From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). CONCLUSIONS:In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. TRIAL REGISTRATION:ClinicalTrials.gov NCT02486354.

BACKGROUNDBecause of the short hospital stay involved in outpatient knee arthroscopy, anesthesiologists should provide an effective and safe anesthesia scheme. Unilateral spinal anesthesia is a conventional choice for outpatient knee arthroscopy, and combined sciatic-femoral nerve block also permits successful results. This study aimed to compare sciatic-femoral nerve block with unilateral spinal anesthesia for outpatient knee arthroscopy.METHODSWe screened randomized controlled trials (RCTs) that compared sciatic-femoral nerve block (SFB) with unilateral spinal anesthesia (USA) from EMBASE, MEDLINE and the Cochrane Library. Ten statistic parameters, such as time-to-readiness for discharge (TRD, minutes), time to first spontaneous urination (minutes), time to perform (PT, minutes), Visual Analogue Scale (VAS) for postoperative (24 hours) pain, patients' satisfaction, and total anesthesia time (TAT, minutes) were considered in this study. RevMan 5.2 and Stata 12.0 softwares were used for data analysis.RESULTThere were 7 RCTs including 402 total patients which met our criteria. Compared with the USA group, in the SFB group TRD (mean difference [MD]=-38.8; 95% CI [-63.7, -14.0]; P=0.002) and time to first spontaneous urination (MD=-78.2; 95% CI [-92.7, -63.7]; P<0.00001) were shorter, TAT (MD=100.2; 95% CI [30.3, 170.1]; P=0.005) and PT (MD=4.0; 95% CI [2.4, 5.6]; P<0.00001; I2=97%) were longer in the SFB group. For the two groups, no statistically significant differences were observed in patients' satisfaction (MD=3.2; 95% CI [0.3, 31.8]; P=0.33).CONCLUSIONSFB provided faster bladder function recovery and faster discharging from hospital, hence it could be a good alternative to USA for outpatient knee arthroscopy.

Pneumothorax can occur in several situations such as; chronic obstructive pulmonary disease (COPD) where emphysema is observed or due to a biopsy for malignancy suspicion. In any case it is a dangerous situation that requires immediate attention and treatment. Pneumothorax can be divided in primary and secondary. Staging of pneumothorax is also very important. In our current editorial we summarize etiology and treatment of pneumothorax from a panel of pulmonary physicians, oncologists and thoracic surgeons.

Mini-interventional procedures are used in the everyday clinical practice by pulmonary physicians and radiologists. Fine needle aspiration and biopsy forceps are the tools mostly used. During these procedures pneumothorax can occur and immediate treatment is necessary. In our current work, we will focus on minimal invasive techniques for biopsy and pneumothorax treatment.

This paper reports a case of endometriosis of the lung in a 29-year-old woman with long-term periodic catamenial hemoptysis. A chest computed tomography image obtained during menstruation revealed a radiographic opaque lesion in the lingular segment of the left superior lobe. During bronchoscopy, bleeding in the mucosa of the distal bronchus of the lingular segment of the left superior lobe was observed. Histopathology subsequent to an exploratory thoracotomy confirmed the diagnosis of endometriosis of the left lung. The 2-year follow-up after lingular lobectomy of the left superior lobe showed no recurrence or complications.

Objective: Existing oncology performance status measurements are used to predict chemotherapy toxicity in all patients with cancer, regardless of age. A new predictive model for grade 3-5 chemotherapy toxicities was developed by Hurria et al. (2011)(1). As the model is from the Cancer and Aging Research Group (CARG), we call it the CARG toxicity tool. We investigated whether this tool can usefully characterize chemotherapy risks for older patients with lung cancer.Methods: Patients from our hospital aged 265 years with lung cancer completed a questionnaire form prior to chemotherapy. We reviewed patients' chemotherapy courses to identify toxicities, and used the toxicity tool to score the patients' outcomes. The sample was divided into three risk strata based on approximate risk score quartiles, with the middle two quartiles combined. Chi-square statistics were used to verify differences among groups.Results: Between September 2011 and September 2012, 120 patients with lung cancer (87 males and 33 females) 265 years of age (mean: 69 years; range: 65-82 years) were enrolled in the study. In our sample, 35% of subjects had >= one grade 3-5 hematologic toxicity; 48% had >= one grade 3-5 nonhematologic toxicity. Toxicity varied significantly among the risk groups (P < 0.001), but the incidence of toxicity did not vary significantly among the KPS-based risk groups (P = 0.322).Conclusion: This new CARG toxicity tool can be used to better distinguish the risks of chemotherapy toxicity than the KPS for older patients with lung cancer, and may change the standards for oncology assessments. (C) 2013 Elsevier Ltd. All rights reserved.

BACKGROUND:Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. METHODS:In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. FINDINGS:400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). INTERPRETATION:Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.

The reform of standardized training for resident physicians in Shanghai will help to train personnel at all levels of clinical medicine and promote the sustainable development of health.The residents participated in training have characteristics of wide range of sources,uneven,bilateral choice,and strong liquidity.The key need to be resolved is how to improve the effect of training.According to the situation of training base,this paper describes how to use a variety of training methods to improve the effects of training in respiratory specialist.

7522 Background: Icotinib is a potent and selective EGFR-TKI. Of 88 kinases profiled, Icotinib (Ic) powerfully inhibited EGFR and its 3 mutants, with no meaningful inhibition of the rest of kinases tested. This study was designed to show that Ic is not inferior to Gefitinib (Ge). Methods: Patients (Pts) with NSCLC progressed after one or two lines of chemotherapies were randomized to receive Ic (150mg Tid) or Ge (250mg Qd). The primary endpoint was PFS. The second endpoints were OS, ORR, TTP, QOL and tolerance. EGFR gene mutational analysis was performed by using DsX Scorpion ARMS. Results: From Feb 2009 to Nov 2010, 399 patients were randomized to receive either Ic (200) or Ge (199). Baseline characteristics were well balanced between the two arms . Ic demonstrated 35 day (d) median PFS extension compared to Ge (Ic vs. Ge: 137 d vs. 102, HR 0.84, 95% CI 0.67-1.05), reaching the primary objective of non-inferiority. With 49.4% maturity, OS was similar between Ic and Ge groups (median OS was 504 d and 531 d, respectively). Furthermore, ORR (Ic vs. Ge: 27.6% vs. 27.2%), DCR (75.4% vs. 74.9%), TTP (156 d vs. 111 d ) and QoL (101.4± 9.6 vs. 103.0± 19.1) were comparable between Ic and Ge groups. Adverse response rate in Ic group was 60.5%, which was significantly lower than that in Ge group (70.4%) (P=0.04). Specifically, 39.5% pts in Ic developed rash compared to 49.2% in Ge; 18.5% pts in Ic had diarrhea compared to 27.6% in Ge (P=0.03); 8.0% pts in Ic had elevated transaminase level compared to 12.6% in Ge. EGFR gene mutational analysis was performed for 132 pts. Mutations were identified in 66 pts (50%), among which 27 (40.9%) were in Ic and 39 (59.1%) were in Ge. The ORR and PFS in both Ic and Ge groups demonstrated significant differences between pts with mutations (M) and pts with the wild type gene (W). In the Ic group, M vs. W was 59.3% (16/27) vs. 5.1% (2/39) for ORR and 198 d vs. 70 d for PFS. In the Ge group it was 52.6% (20/39) vs. 3.7% (1/27) for ORR and 158 d vs. 76 d for PFS. Conclusions: This study demonstrated that Icotinib provides similar efficacy to Gefitinib, but with better tolerability, in NSCLC patients previously treated with one or two chemotherapy agents.

Objective To evaluate the effect and safety of intraluminal stent implantation in the treatment of complete airway obstruction with unilateral pulmonary atelectasis caused by endobronchial tuberculosis(EBTB). Methods 9 cases of pulmonary atelectasis caused by EBTB were treated with high-frequency electricity/microwave,balloon dilation and endobronchial stent implantation. At the time of 1 week and 4-6 months after stenting ,the diameters of stenotic segment were measured. Results All 9 cases with atelectasis of EBTB showed complete re-expansion within 3 days after the stent implantation. The mean diameter of the stenotic segments of 9 EBTB patients increased to 9.17 ± 1.24 mm at 7th day after stent implantation; 3 of 9 EBTB patients occured mild restenosis after implantation of tracheobronchial stents.However,combination therapy of cryotherapy and balloon dilation can effectively prevent the aggravation of restenosis. Conclusion Comparing with traditional surgical treatment,the intraluminal stent implantation for atelectasis caused by EBTB is a new,effective,safe and microtraumatic method with reliable preservation of pulmonary function.(J Intervent Radiol,2007,16: 681-684)

OBJECTIVE:To describe the clinical features and treatment of relapsing polychondritis with involvement of the respiratory tract.METHOD:Thirteen cases (admitted from Aug 2000 to Oct 2006) of relapsing polychondritis with involvement of the respiratory tract treated in our hospital were retrospectively analyzed.RESULTS:There were 9 males and 4 females, with ages ranging from 30 to 61 years (mean 50 years). At early stage of the disease, clinical manifestations included cough, throat pain and hoarseness. Patients in later stage usually complained of chest distress, shortness of breath and dyspnea. Severe complications were repeated lower respiratory tract infections and/or respiratory failure. Bronchoscopic examination revealed an edematous larynx, narrowing of the glottis, tracheobronchial edema, turgescence of bronchial cartilage rings and airway stenosis at early stage. At later stage of the disease, malacia of trachea and bronchi due to disappearance of bronchial cartilage rings, and partly obliteration of the both trachea and main bronchus on expiration were demonstrated. Thoracic CT scan, with three-dimensional reconstruction of the airways, demonstrated a diffusely thickened tracheobronchial wall with tracheobronchial stenosis in earlier period of the disease and showed severe narrowing of both trachea and main bronchi in later period. Lung function measurements showed a moderate obstructive ventilatory disorder in 5 patients. Medical treatment with corticosteroids and immunosuppressive drugs was given in 12 patients. Symptoms were improved in 6 patients in earlier period of the disease, however, 6 patients in later period were not relieved. Twelve self-expanding metallic stents were placed in the airways (trachea and/or main bronchi), and obstruction of the respiratory tract was relieved in 5 patients, but there was no improvement in 1 patient who later was treated with positive airway pressure support. The 13 patients were followed for 1 to 48 months, and 12 patients survived, but one patient died 2 years after diagnosis.CONCLUSIONS:Corticosteroid therapy is effective in improving the symptoms and delaying the progression of relapsing polychondritis with involvement of the respiratory tract at early stage. At later stage of the disease, airway interventional therapy, such as metallic stent placement, tracheostomy or positive airway pressure support, can be used to treat airway obstruction and to improve the survival.