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The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation–positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non–small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI. Among 56 enrolled patients, 37 individuals underwent molecular analysis at rebiopsy. Of these 37 patients, 16 individuals (43.2%) had acquired T790M, including 11/21 patients (52.4%) with an exon 19 deletion of EGFR and 5/13 patients (38.5%) with L858R. None of three patients with an uncommon EGFR mutation harbored T790M. T790M was detected in 14/29 patients (48.3%) with a partial response to afatinib, 1/4 patients (25%) with stable disease, and 1/4 patients (25%) with progressive disease as the best response. Median progression-free survival after initiation of afatinib treatment was significantly (P = 0.043) longer in patients who acquired T790M (11.9 months; 95% confidence interval, 8.7–15.1) than in those who did not (4.5 months; 95% confidence interval, 2.0–7.0). Together, our results show that EGFR-mutated NSCLC patients treated with afatinib as first-line EGFR-TKI acquire T790M at the time of progression at a frequency similar to that for patients treated with gefitinib or erlotinib. They further underline the importance of rebiopsy for detection of T790M in afatinib-treated patients.

The authors examined the efficacy of Prolonged Exposure (PE) therapy in Japanese patients with posttraumatic stress disorder (PTSD). Twenty-four patients (21 women, 3 men) with PTSD due to mixed trauma were randomly assigned to the PE group (PE with or without treatment as usual [TAU]) or the control group (TAU) only. The control group received PE after a 10-week period. Intention-to-treat analysis showed the PE group achieved significantly greater reduction than the control group at posttreatment in either PTSD or depressive symptoms. The control group had significantly decreased symptom severity after PE treatment. Symptom levels of 19 PE completers in the both groups remained low in 12-month follow-up assessments. The study's findings will promote the future dissemination and implementation of evidence-based treatment for PTSD in non-Western settings.

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AimsTo investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE).Methods and resultsWe examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3–12 years.ConclusionsInterstitial inflammation or acute lung injury may be an initial step in the development of PPFE.

The expression of GST-Pi in NSCLC patients was significantly related to response to cisplatin-based chemotherapy, and may be a useful predictor of chemotherapy response.

This pilot study aimed to refine a treatment approach for traumatic grief due to violent loss. Our Traumatic Grief Treatment Program, a modification of Shear's complicated grief treatment (Shear et al., 2005), comprises psychoeducation, in vivo exposure, imaginal exposure, discussion of memories about and imaginal conversation with the deceased. Thirteen of 15 Japanese women suffering from posttraumatic stress disorder (PTSD) due to traumatic grief completed 12 to 16 weekly individual sessions based on their therapists' recommendations. Assessment scales included the Inventory of Complicated Grief, the Impact of Event Scale-Revised, and the Center for Epidemiologic Studies Depression Scale. There was significant reduction in symptom severity at treatment end, and symptom levels remained low throughout the 12-month follow-up period. Based on Jacobson's Reliable Change Index, 46% showed change on all 3 measures. These findings suggest that our treatment model may be feasible for treating traumatic grief with PTSD in non-Western settings.