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BACKGROUND EGFR tyrosine kinase inhibitors (TKIs) have shifted the treatment paradigm in advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, patients who are treated with TKIs inevitably develop acquired resistance by mechanisms that are not fully understood. The purpose of this study was to investigate the mechanism of acquired resistance after treatment with third-generation EGFR TKIs. METHODS Advanced EGFR-mutant NSCLC patients treated with olmutinib or osimertinib who underwent a rebiopsy before treatment or after progression were analyzed retrospectively. Targeted sequencing was performed on 113 specimens (77 pretreatment and 36 posttreatment, including 15 paired samples) obtained via tissue biopsy. RESULTS A total of 98 patients were included, 53 (54%) of whom were treated with osimertinib and 45 (46%) of whom were treated with olmutinib. Of the 36 patients with posttreatment biopsies, EGFR-dependent mechanisms, including C797S and L718Q mutations, were observed in 10 (28%) patients 29% (5/17) in the osimertinib group and 26% (5/19) in the olmutinib group. EGFR-independent mechanisms were detected in 21 patients (21/36, 58%) 65% (11/17) in the osimertinib group and 53% (10/19) in the olmutinib group. The disappearance of EGFR T790M was detected in 14 patients (39%); of these patients, 59% (10/17) were treated with osimertinib and 21% (4/19) were treated with olmutinib. Patients who lost the T790M mutation were more inclined to show EGFR-independent pathways as a secondary resistance mechanism. CONCLUSION Resistance acquired after third-generation EGFR TKIs is associated with diverse pathways; however, treatment with osimertinib is primarily associated with a loss of EGFR T790M and the subsequent emergence of EGFR-independent resistance mechanisms. © 2020 American Cancer Society.BACKGROUND Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry. METHODS Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database. RESULTS There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59&nbsp;years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25% was observed, whereas TNBC prevalences of 21% and 10% were observed in NHBs and NHWs, respectively. CONCLUSIONS The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was ~2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally. © 2020 American Cancer Society.BACKGROUND AND OBJECTIVE While osseointegration following various dental implant placement protocols has been extensively investigated, the neurohistological integration has received little attention. The primary aim of this study was to compare the myelinated nerve fibers density in peri-implant bone tissue following various implant placement protocols. The secondary aim assessed the effect of follow-up on peri-implant nerve fibers density. METHODS Ten beagle dogs randomly received 68 commercially pure titanium implants in the mandibular premolar or molar region&nbsp;bilaterally following extraction utilizing&nbsp;one of the six treatment protocols (a) immediate implant placement (IIP) and immediate loading (IL); (b) IIP and delayed loading (DL); (c) IIP and left unloaded (UL); (d) delayed implant placement (DIP) and IL; (e) DIP and DL; and (f) DIP and UL. Histomorphometric analysis of the peri-implant myelinated nerve fibers was performed in a 300&nbsp;μm peri-implant zone at the cervical, middle, and apical level followiy in the apical region. A longer loading time had no influence on the peri-implant nerve density. © 2020 The Authors. Journal of Periodontal Research published by John Wiley &amp; Sons Ltd.BACKGROUND Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). METHODS Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). RESULTS Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. [https://www.selleckchem.com/peptide/angiotensin-ii-human-acetate.html Selleck Angiotensin II human] Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). CONCLUSIONS The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM. © 2020 American Cancer Society.