Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer

Objectives: Detection of activating epidermal growth factor receptor (EGFR) mutation is crucial for individualized treatment of advanced non-small-cell lung cancer (NSCLC). However little is known about how biopsy technique affects the detection rate of EGFR mutations. This retrospective, single center study evaluated the detection rate of EGFR mutations in tissue obtained by bronchoscopic cryobiopsy and compared this to other standard tissue sampling techniques. Materials and methods: We retrospectively analyzed 414 patients with histologically confirmed NSCLC and known EGFR mutation status between 3/2008-7/2014. Tumor specimens obtained by tissue preserving bronchoscopic cryobiopsy were compared to those obtained by other techniques. Results and conclusion: Analysis of bronchoscopic cryobiopsy tissue detected 29 activating EGFR mutations in 27 (21.6 ) out of 125 patients, while analysis of tissue obtained by non-cryobiopsy techniques (bronchoscopic forceps biopsies, fine needle aspiration, imaging guided transthoracical and surgical procedures) detected 42 EGFR mutations in 40 (13.8 ) out of 298 patients (p < 0.05). Cryobiopsy increased detection rate of EGFR mutations in central tumors compared with forceps biopsy (19.6 versus 6.5 , p < 0.05), while an insignificant trend was detected also for peripheral tumors (33.3 versus 26.9 ). Bronchosopic cryobiopsy increases the detection rate of activating EGFR mutations in NSCLC in comparison to other tissue sampling techniques. This will help to optimize individualized treatment of patients with advanced tumors. Because of the retrospective nature of this analysis, a prospective trial is mandatory for final assessment. © 2020 The Author(s

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation

Background. Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. Methods. We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. Results. Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 ± 17) than standard patients (29 ± 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). Conclusion. We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reaction

Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival

Forward and backward diffraction radiation of relativistic electrons in a dielectric targets

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions

A reply to "A modern approach to Advanced Non-Small Cell Lung Cancer: Minimally-invasive procedures and in parallel multiple DNA/RNA high-throughput sequencing".

We would like to thank G. Rossi et al. for their interest and taking the time to comment on our manuscript "Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer”