Epidermal growth factor receptor mutation and pattern of brain metastasis in patients with non-small cell lung cancer

BACKGROUND/AIMS@#We investigated the time taken for patients with metastatic non-small cell lung cancer (NSCLC) to develop brain metastases (BM), as well as their subsequent overall median survival following diagnosis, considering the epidermal growth factor receptor (EGFR) mutational status.@*METHODS@#We retrospectively investigated the medical records of 259 patients diagnosed with advanced NSCLC from January 2010 to August 2013, who were tested for EGFR mutations. The time from the diagnosis of advanced NSCLC to the development of BM and the overall median survival after BM development (BM-OS) were evaluated and compared by EGFR mutational status.@*RESULTS@#Sixty-seven patients (25.9%) developed BM. Synchronous BM occurred more often in patients with EGFR mutation type (MT) (n = 20, 27.4%) compared with EGFR wild type (WT) (n = 27, 14.5%, p < 0.009). The median BM-OS was significantly longer in patients with EGFR MT than in those with EGFR WT (25.7 months vs. 3.8 months, p < 0.001), and a similar trend was noticed for patients with synchronous BM (25.7 months for EGFR MT vs. 6.8 months for EGFR WT, p < 0.001). However, in patients with metachronous BM development, the difference in BM-OS between patients with EGFR MT (14.6 months) and EGFR WT (2.5 months) did not reach statistical significance (p = 0.230).@*CONCLUSIONS@#Synchronous BM was more common in NSCLC patients with EGFR MT than in those with EGFR WT. However, EGFR mutations were associated with significantly longer median BM-OS, especially when the brain was the first metastatic site.

Effect of a Dose-Escalation Regimen for Improving Adherence to Roflumilast in Patients with Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

BACKGROUND: The adverse effects of the phosphodiesterase-4 inhibitor roflumilast, appear to be more frequent in clinical practice than what was observed in chronic obstructive pulmonary disease (COPD) clinical trials. Thus, we designed this study to determine whether adverse effects could be reduced by starting roflumilast at half the dose, and then increasing a few weeks later to 500 microg daily. METHODS: We retrospectively investigated 85 patients with COPD who had taken either 500 microg roflumilast, or a starting dose of 250 microg and then increased to 500 microg. We analyzed all adverse events and assessed differences between patients who continued taking the drug after dose escalation and those who had stopped. RESULTS: Adverse events were reported by 22 of the 85 patients (25.9%). The most common adverse event was diarrhea (10.6%). Of the 52 patients who had increased from a starting dose of 250 microg roflumilast to 500 microg, 43 (82.7%) successfully maintained the 500 microg roflumilast dose. No difference in factors likely to affect the risk of adverse effects, was detected between the dose-escalated and the discontinued groups. Of the 26 patients who started with the 500 microg roflumilast regimen, seven (26.9%) discontinued because of adverse effects. There was no statistically significant difference in discontinuation rate between the dose-escalated and the control groups (p=0.22). CONCLUSION: Escalating the roflumilast dose may reduce treatment-related adverse effects and improve tolerance to the full dose. This study suggests that the dose-escalated regimen reduced the rate of discontinuation. However, longer-term and larger-scale studies are needed to support the full benefit of a dose escalation strategy.

A Patient with Common Variable Immunodeficiency Followed by Severe Aplastic Anemia Successfully Treated with Allogenic Stem Cell Transplantation

A twenty-year-old male was diagnosed with common variable immunodecifiency (CVID) according to decreased blood level of immunoglobulins along with a history of recurrent sinopulmonary infection since early childhood, no response to prior vaccination, and the absence of all other defined immunodeficiency. Eleven months after the initiation of intravenous immunoglobulin replacement, he presented with petechiae on both lower legs for three weeks. Bone marrow exam was conducted as pancytopenia was not resolved over a month and severe aplastic anemia was diagnosed. Allogenic stem cell transplantation (Allo-SCT) with reduced intensity conditioning (RIC) enabled both a clinical resolution from propensity to infection with an appropriate production of immunoglobulins and a successful rescue of hematopoiesis. This report suggests that Allo-SCT using RIC is a potentially curable option in patients with CVID complicated by SAA if adequate efforts to minimize Allo-SCT-related complications are accompanied.