Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer.

BACKGROUND: The early-generation ROS1 tyrosine kinase inhibitors (TKIs) that are approved for the treatment of ROS1 fusion-positive non-small-cell lung cancer (NSCLC) have antitumor activity, but resistance develops in tumors, and intracranial activity is suboptimal. Repotrectinib is a next-generation ROS1 TKI with preclinical activity against ROS1 fusion-positive cancers, including those with resistance mutations such as ROS1 G2032R. METHODS: In this registrational phase 1-2 trial, we assessed the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1 fusion-positive NSCLC. The primary efficacy end point in the phase 2 trial was confirmed objective response; efficacy analyses included patients from phase 1 and phase 2. Duration of response, progression-free survival, and safety were secondary end points in phase 2. RESULTS: On the basis of results from the phase 1 trial, the recommended phase 2 dose of repotrectinib was 160 mg daily for 14 days, followed by 160 mg twice daily. Response occurred in 56 of the 71 patients (79%; 95% confidence interval [CI], 68 to 88) with ROS1 fusion-positive NSCLC who had not previously received a ROS1 TKI; the median duration of response was 34.1 months (95% CI, 25.6 to could not be estimated), and median progression-free survival was 35.7 months (95% CI, 27.4 to could not be estimated). Response occurred in 21 of the 56 patients (38%; 95% CI, 25 to 52) with ROS1 fusion-positive NSCLC who had previously received one ROS1 TKI and had never received chemotherapy; the median duration of response was 14.8 months (95% CI, 7.6 to could not be estimated), and median progression-free survival was 9.0 months (95% CI, 6.8 to 19.6). Ten of the 17 patients (59%; 95% CI, 33 to 82) with the ROS1 G2032R mutation had a response. A total of 426 patients received the phase 2 dose; the most common treatment-related adverse events were dizziness (in 58% of the patients), dysgeusia (in 50%), and paresthesia (in 30%), and 3% discontinued repotrectinib owing to treatment-related adverse events. CONCLUSIONS: Repotrectinib had durable clinical activity in patients with ROS1 fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.).

Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events. CONCLUSIONS: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).

Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial.

BACKGROUND: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRASG12C. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation who had been previously treated with other anticancer drugs. METHODS: We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries. We recruited patients aged at least 18 years with KRASG12C-mutated advanced NSCLC, who progressed after previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Key exclusion criteria included new or progressing untreated brain lesions or symptomatic brain lesions, previously identified oncogenic driver mutation other than KRASG12C for which an approved therapy is available (eg EGFR or ALK), previous treatment with docetaxel (neoadjuvant or adjuvant docetaxel was allowed if the tumour did not progress within 6 months after the therapy was terminated), previous treatment with a direct KRASG12C inhibitor, systemic anticancer therapy within 28 days of study day 1, and therapeutic or palliative radiation therapy within 2 weeks of treatment initiation. We randomly assigned (1:1) patients to oral sotorasib (960 mg once daily) or intravenous docetaxel (75 mg/m2 once every 3 weeks) in an open-label manner using interactive response technology. Randomisation was stratified by number of previous lines of therapy in advanced disease (1 vs 2 vs >2), ethnicity (Asian vs non-Asian), and history of CNS metastases (present or absent). Treatment continued until an independent central confirmation of disease progression, intolerance, initiation of another anticancer therapy, withdrawal of consent, or death, whichever occurred first. The primary endpoint was progression-free survival, which was assessed by a blinded, independent central review in the intention-to-treat population. Safety was assessed in all treated patients. This trial is registered at ClinicalTrials.gov, NCT04303780, and is active but no longer recruiting. FINDINGS: Between June 4, 2020, and April 26, 2021, 345 patients were randomly assigned to receive sotorasib (n=171 [50%]) or docetaxel (n=174 [50%]). 169 (99%) patients in the sotorasib group and 151 (87%) in the docetaxel group received at least one dose. After a median follow-up of 17·7 months (IQR 16·4-20·1), the study met its primary endpoint of a statistically significant increase in the progression-free survival for sotorasib, compared with docetaxel (median progression-free survival 5·6 months [95% CI 4·3-7·8] vs 4·5 months [3·0-5·7]; hazard ratio 0·66 [0·51-0·86]; p=0·0017). Sotorasib was well tolerated, with fewer grade 3 or worse (n=56 [33%] vs n=61 [40%]) and serious treatment-related adverse events compared with docetaxel (n=18 [11%] vs n=34 [23%]). For sotorasib, the most common treatment-related adverse events of grade 3 or worse were diarrhoea (n= 20 [12%]), alanine aminotransferase increase (n=13 [8%]), and aspartate aminotransferase increase (n=9 [5%]). For docetaxel, the most common treatment-related adverse events of grade 3 or worse were neutropenia (n=13 [9%]), fatigue (n=9 [6%]), and febrile neutropenia (n=8 [5%]). INTERPRETATION: Sotorasib significantly increased progression-free survival and had a more favourable safety profile, compared with docetaxel, in patients with advanced NSCLC with the KRASG12C mutation and who had been previously treated with other anticancer drugs. FUNDING: Amgen.

Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a study called CodeBreaK 100. The CodeBreaK 100 study included patients with non-small-cell lung cancer that had spread outside the lung (advanced). Lung cancer is one of the most common forms of cancer. CodeBreaK 100 specifically looked at patients with a particular change(mutation) in the KRAS gene resulting in the mutated protein called KRAS G12C. The KRAS G12C mutation can lead to development and growth of lung cancer. Patients received a treatment called sotorasib, which has accelerated approval or full approval in over 50 countries for patients with non-small-cell lung cancer with the KRAS G12C mutation. The CodeBreaK 100 study looked at whether sotorasib is a safe and effective treatment for advanced non-small-cell lung cancer. Sotorasib is designed to specifically target and lock the mutated KRAS protein in the inactive state to treat non-small-cell lung cancer. WHAT WERE THE RESULTS?: In total, 174 adults were treated with sotorasib. Treatment-related side effects were seen in 70% of patients and were severe in 21% of patients. The most common side effects included diarrhea, increased liver enzymes, nausea and tiredness. 70 (41%) patients responded to sotorasib and 144 (84%) patients had tumors that either remained stable or shrunk in size. 29 (41%) patients who responded to sotorasib responded for over 12 months. After 2 years, 9 patients with a response remained on sotorasib; there were no notable increases in tumor size or development of new tumors over this time. There were 5patients who received sotorasib for more than 2 years and continued to respond. Long-term benefit was seen for some patients. Patients also benefitted from treatment when the tumor expressed different amounts of a protein called PD-L1.In total, 33% of patients were still alive after 2 years. WHAT DO THE RESULTS MEAN?: Results show the long-term benefit of sotorasib therapy for people with advanced KRAS G12C-mutated non-small-cell lung cancer. Clinical Trial Registration: NCT03600883 (CodeBreaK 100) (ClinicalTrials.gov).

World Association for Bronchology and Interventional Pulmonology (WABIP) guidelines on airway stenting for malignant central airway obstruction.

Malignant Central Airway Obstruction (MCAO) encompasses significant and symptomatic narrowing of the central airways that can occur due to primary lung cancer or metastatic disease. Therapeutic bronchoscopy is associated with high technical success and symptomatic relief and includes a wide range of airway interventions including airway stents. Published literature suggests that stenting practices vary significantly across the world primarily due to lack of guidance. This document aims to address this knowledge gap by addressing relevant questions related to airway stenting in MCAO. An international group of 17 experts from 17 institutions across 11 countries with experience in using airway stenting for MCAO was convened as part of this guideline statement through the World Association for Bronchology and Interventional Pulmonology (WABIP). We performed a literature and internet search for reports addressing six clinically relevant questions. This guideline statement, consisting of recommendations addressing these six PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with expert experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique.

Pan-Cancer Detection and Typing by Mining Patterns in Large Genome-Wide Cell-Free DNA Sequencing Datasets.

BACKGROUND: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. METHODS: By applying unsupervised clustering and supervised machine learning on large cfDNA shallow whole-genome sequencing datasets from healthy individuals (n = 367) and patients with different hematological (n = 238) and solid malignancies (n = 320), we identified cfDNA signatures that enabled cancer detection and typing. RESULTS: Unsupervised clustering revealed cancer type-specific sub-grouping. Classification using a supervised machine learning model yielded accuracies of 96% and 65% in discriminating hematological and solid malignancies from healthy controls, respectively. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. The potential utility of managing a specific cancer was demonstrated by classifying benign from invasive and borderline adnexal masses with an area under the curve of 0.87 and 0.74, respectively. CONCLUSIONS: This approach provides a generic analytical strategy for non-invasive pan-cancer detection and cancer type prediction.

INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance.

MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).

Osimertinib is used to treat a type of lung cancer that has specific changes (mutations) in a gene called EGFR. Although tumors will usually shrink (respond) during treatment with osimertinib, they can stop responding, or become resistant, to osimertinib. A common cause of resistance is 'MET amplification', which describes when extra copies of a gene called MET are present. Lung cancer that is resistant to osimertinib due to MET amplification could be treated by combining osimertinib with a treatment that blocks MET, such as tepotinib. INSIGHT 2 is an ongoing study that is designed to learn about the effects and safety of tepotinib combined with osimertinib, in patients with lung cancer that has stopped responding to osimertinib because of MET amplification. A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1406.

Direct EBUS-guided transtracheal lymphosclerosis for plastic bronchitis after Fontan.

We report on a new puncture technique with direct transtracheal mediastinal lymphatic access to treat plastic bronchitis after Fontan repair. High resolution contrast-enhanced spiral CT identified enlarged lymph nodes in the paratracheal region. Inguinal intranodal Gadolinium Dynamic Contrast-enhanced Magnetic Resonance lymphangiography (DCMRL) confirmed the pathologic centrifugal lymph flow passing through these lymph nodes before leaking into the bronchial tree. The abnormal hypertrophic paratracheal, subcarinal, and hilar lymph nodes were punctured with a 22G needle through an endobronchial ultrasound bronchoscope. Occlusion of the lymph vessels was obtained by injecting a mixture of lipiodol/NBCA N-butyl cyanoacrylate (Histoacryl) 5/1 under fluoroscopic control. There was a total remission of PB with now 10 months of follow-up.

Real-time symptom management in the context of a remote symptom-monitoring system: prospective process evaluation and cross-sectional survey to explore clinical relevance.

PURPOSE: Electronic systems for remotely monitoring symptoms during systemic anticancer treatment are increasingly being used. Some of these systems have features triggering alerts to healthcare professionals for worsening and/or severe symptoms, enabling real-time symptom management. This study aimed at exploring the characteristics and process of real-time alert management as well as its clinical relevance as perceived by healthcare professionals. METHODS: From January until September 2019, a prospective process evaluation was set up to collect data on all alerts and their management. Also, an online survey presenting a selected number of cases was set up to explore oncologists' and oncology nurses' perceived clinical relevance of the real-time management of the alerts. RESULTS: The overall incidence rate of alerts was 1.4%. Of 253 alerts, pain, fever, dyspnea, and nausea were the most prevalent symptoms triggering an alert. The majority of alerts was managed by a nursing telephone consult alone. In 25.3% of cases, clinical examination was deemed necessary to manage the alert. In 148 of the ratings, oncologists and oncology nurses (totally) agreed with the clinical relevance of the real-time management (95.1%). The mean relevance score attached to the cases was 4.51 (±0.80). CONCLUSIONS: The majority of alerts triggered by a mobile tool for remote symptom monitoring during cancer treatment can be managed by a telephone nursing consult and real-time management is evaluated as (very) relevant by the majority of clinicians.

COVID-19 in lung transplant patients: A case series.

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome.

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial.

BACKGROUND: About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR). METHODS: This investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed. DISCUSSION: The combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023. TRIAL REGISTRATION: ImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018-002583-11; Clinicaltrials.gov: NCT03705403; ISRCTN ID: ISRCTN49817477; Date of registration: 03-April-2019.

Systematic and combined endosonographic staging of lung cancer (SCORE study).

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal staging versus the current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone.A prospective, multicentre, international study (NCT02014324) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard.229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63-81%; negative predictive value (NPV) 81%, 95% CI 74-87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67-84%; NPV 84%, 95% CI 76-89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72-88%; NPV 87%, 95% CI 80-91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%).Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.

Health Outcomes for Definite Concurrent Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: In patients with locally advanced lung cancer treated with concurrent chemoradiation, outcome measurements have been mostly limited to survival. OBJECTIVES: We aimed to measure outcomes that matter to these patients beyond survival in a general clinical practice. METHODS: In a prospective single-centre study, consecutive patients with locally advanced non-small cell lung cancer reported their own outcomes using the EORTC Quality of Life Questionnaire Core 30 at baseline, during therapy, at therapy stop and till 1 year after therapy end every 3 months. Survival, complications, quality of death and case-mix variables were measured. RESULTS: There were 32 consecutive patients included prospectively from June 2013 until September 2016. Median overall survival was 24.3 months (95% CI 12.7-35.9). Severe toxicity (grade III-IV) was frequent (haematologic toxicity III-IV in 59%). Patient-reported outcomes (PROs) documented the burden on global health status and on functional domains (physical, role, social, emotional and cognitive functioning). Deterioration was pronounced during and after treatment with drops over 20 up to 40% points from baseline for physical, role and social functioning. Clinically meaningful negative effects did persist up to 6 and 9 months for physical and role functioning. Fifty-six percent of the deceased patients died in hospital. CONCLUSIONS: The assault on health-related quality of life during concurrent chemoradiation for locally advanced lung cancer is considerable. Loss of physical and role functioning persists up to 6 and 9 months after therapy end, respectively. Measuring PROs can help to identify issues for improvement of the value of care delivered.

Lung cancer staging: a concise update.

Diagnosis and clinical staging of lung cancer are fundamental to planning therapy. The techniques for clinical staging, i.e anatomic and metabolic imaging, endoscopies and minimally invasive surgical procedures, should be performed sequentially and with an increasing degree of invasiveness. Intraoperative staging, assessing the magnitude of the primary tumour, the involved structures, and the loco-regional lymphatic spread by means of systematic nodal dissection, is essential in order to achieve a complete resection. In resected tumours, pathological staging, with the systematic study of the resected specimens, is the strongest prognostic indicator and is essential to make further decisions on therapy. In the present decade, the guidelines on lung cancer staging of the American College of Chest Physicians and the European Society of Thoracic Surgeons are based on the best available evidence and are widely followed. Recent advances in the classification of the adenocarcinoma of the lung, with the definition of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma, and the publication of the eighth edition of the tumour, node and metastasis classification of lung cancer, have to be integrated into the staging process. The present review complements the latest guidelines on lung cancer staging by providing an update of all these issues.

Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single-centre experience.

BACKGROUND AND OBJECTIVE: Malignant pleurisy is associated with advanced oncological disease and dyspnoea is the most common presenting symptom. Pleurodesis is the preferred palliative and supportive treatment option, targeting symptom relief. The identification of clinical and endoscopic features that determine the success of talc pleurodesis in malignant pleurisy could guide clinical decision-making. METHODS: All symptomatic patients with malignant pleurisy subjected to talc pleurodesis through medical thoracoscopy between January 2012 and December 2015 were included. Univariate and multivariate analyses were performed to identify factors associated with successful pleurodesis. RESULTS: Of the 155 patients, 122 (78%) were classified as having a successful pleurodesis based on clinical and radiological criteria. Factors associated with unsuccessful pleurodesis (univariate analysis) were the presence of pleural adhesions (odds ratio (OR): 0.43 (95% CI: 0.19-0.96); P = 0.04), extensive spread of pleural lesions (OR: 0.17 (95% CI: 0.05-0.59); P = 0.001), the use of systemic corticosteroids (OR: 0.28 (95% CI: 0.10-0.83); P = 0.02) and a prolonged time period between the clinical diagnosis of the pleural effusion and the moment of pleurodesis (OR: 0.14 (95% CI: 0.06-0.32); P < 0.0001). The latter being associated with failure of pleurodesis in a multivariate analysis (OR: 0.08 (95% CI: 0.01-0.25); P < 0.0001). Chest ultrasound prior to pleurodesis showed a sensitivity of 91% and a specificity of 88% in predicting the success of pleurodesis. CONCLUSION: The success rate of pleurodesis in malignant pleurisy could potentially be enhanced by correct patient selection and early referral for pleurodesis. Ultrasonic assessment of pleural adhesions and potential lung expansion prior to pleurodesis is useful in clinical decision-making.

A Randomized Clinical Trial of Flex 19G Needles versus 22G Needles for Endobronchial Ultrasonography in Suspected Lung Cancer.

BACKGROUND: A flexible 19-gauge (Flex 19G) needle has been developed for endobronchial ultrasonography. OBJECTIVES: We aimed to evaluate quantitative and qualitative specimen characteristics of Flex 19G in a randomized controlled setting for patients with suspected lung cancer. METHODS: We undertook a single-center, randomized, controlled trial. A computer-generated randomization assigned all enrolled patients 1: 1 to undergo endobronchial ultrasonography using a Flex 19G or a 22-gauge (22G) needle for lymph node tissue sampling. Pathologists were blinded to the group assignment. The primary end point was histological tissue core procurement. The secondary end points were diagnostic yield, specimen bloodiness and overall quality, tissue surface area and performance for next-generation sequencing (NGS), and procedure-related complications. RESULTS: Between June 2016 and February 2017, we randomly allocated a total of 78 patients: 39 patients to Flex 19G and 39 patients to 22G. No superiority in tissue core procurement was observed for Flex 19G compared to 22G (67 vs. 72%, p = 0.81). No significant difference was observed in diagnostic yield and overall specimen quality, but transbronchial needle aspiration specimens by Flex 19G were bloodier and had a larger tissue surface area. NGS was successful for clinically relevant genes in 96% and for all 26 genes tested in 81% of the samples. There was no difference in clinically relevant complications. CONCLUSIONS: No superiority is observed for Flex 19G in histological tissue core procurement rate. The Flex 19G needle could be considered when a larger tissue surface is of special interest.

Current Practice of Airway Stenting in the Adult Population in Europe: A Survey of the European Association of Bronchology and Interventional Pulmonology (EABIP).

BACKGROUND: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. OBJECTIVES: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. METHODS: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. RESULTS: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. CONCLUSION: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.

Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer: a prospective multicentre study.

A quarter of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography-computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). In a prospective study, endosonography alone had an unsatisfactory sensitivity (38%) in detecting N2 disease. The current prospective multicentre trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) or VAM-lymphadenectomy (VAMLA).Consecutive patients with operable and resectable (suspected) NSCLC and cN1 after PET-CT imaging underwent VAM(LA). The primary study outcome was sensitivity to detect N2 disease. Secondary endpoints were the prevalence of N2 disease, negative predictive value (NPV) and accuracy of VAM(LA).Out of 105 patients with cN1 on imaging, 26% eventually developed N2 disease. Invasive mediastinal staging with VAM(LA) had a sensitivity of 73% to detect N2 disease. The NPV was 92% and accuracy 93%. Median number of assessed lymph node stations during VAM(LA) was 4 (IQR 3-5), and in 96%, at least three stations were assessed.VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1 lung cancer, and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with a one in four chance of occult-positive mediastinal nodes after negative PET-CT.

Is there a different dose-effect relation between the primary tumor and involved lymph nodes in locally advanced non-small-cell lung cancer? A hypothesis-generating study.

PURPOSE: It is unknown whether the dose-response relation of the primary tumor in NSCLC is different from that of the involved lymph nodes (LN). As the recurrence rate is much lower in LN, we hypothesized that LN need a lower radiation dose. MATERIAL AND METHODS: A retrospective analysis of prospective data was performed on patients with locally advanced NSCLC treated with (chemo)radiotherapy. The impact of EQD2,T prescription dose on relapse was analyzed using Cox regression modeling correcting for baseline diameter. RESULTS: From 2006 to 2010, 75 consecutive patients were included, resulting in 142 lymph nodes in the analysis. Any relapse (locoregional/distant) occurred in 58 patients (77%), while involved nodal relapse (INR) was observed in 13% of patients. No dose-response relationship was observed for INR (p = .22). Primary tumor progression was seen in 40% of patients together with a significant dose-response relationship (p = .033). Baseline nodal diameter was not associated with INR (p = .76), while primary tumor diameter was a highly significant predictor for relapse (p = .0031). CONCLUSIONS: These results suggest that LN control may be achieved at lower radiation doses than needed for the primary tumor. Prospective dose de-escalation studies on LN are warranted to decrease the incidence of severe esophagitis without compromising local tumor control.