Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC.

INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.

Crucial aspects of smoking in wound healing after breast reduction surgery.

BACKGROUND: The aim of this study was to investigate the influence of cigarette smoking on wound-healing in patients undergoing breast reduction. METHODS: In our prospective study, 50 patients (25 smokers, 25 nonsmokers) scheduled for breast reduction have been evaluated. Urine cotinine levels were measured to analyse perioperative smoking habits. Urine samples were taken preoperatively and on the fourth postoperative day. Cotinine as a metabolite of nicotine allows precise evaluation of nicotine exposure. To assess the progress of woundhealing we classified secreting, instable, inflamed or necrotic wound conditions, which required a dressing after the tenth postoperative day as impaired wound healing. For statistical analysis non-parametrical tests for independent and dependent data were used. RESULTS: Ten of 25 smokers presented impaired wound healing compared to 4 of 25 nonsmokers. The median cotinine level of smokers was 1964 (783/3963)ng/cc preoperatively and 432 (148/1695)ng/cc postoperatively. Nonsmokers had a preoperative cotinine level of 18 (7/37)ng/cc and 15 (4/34)ng/cc postoperatively. Smokers who developed impaired wound-healing showed higher levels of cotinine pre- (2117 ng/cc) and especially postoperatively (485 ng/cc) compared to smokers with regular woundhealing (1614 ng/cc and 389 ng/cc). Both differences in cotinine levels were statistically significant (p=0.03 and p=0.02). CONCLUSIONS: The data of the present study confirm the negative effect of smoking on wound healing in patients undergoing breast reduction.