PURPOSE Approximately 10% of patients with epidermal growth factor receptor (EGFR) mutation–positive non–small-cell lung cancer (NSCLC) harbor uncommon mutations. Here, we report the efficacy and safety of osimertinib in patients with NSCLC harboring uncommon EGFR mutations. PATIENT AND METHODS This was a multicenter, single-arm, open-label, phase II study in Korea. Patients with histologically confirmed metastatic or recurrent NSCLC harboring EGFR mutations other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion were eligible for the study. The primary end point of objective response rate was assessed every 6 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary end points were progression-free survival, overall survival, duration of response, and safety. RESULTS Between March 2016 and October 2017, 37 patients were enrolled. All were evaluable except one patient who withdrew consent after starting treatment. Median age was 60 years, and 22 (61%) were male. Among patients, 61% received osimertinib as first-line therapy. The mutations identified were G719X (n = 19; 53%), followed by L861Q (n = 9; 25%), S768I (n = 8; 22%), and others (n = 4; 11%). Objective response rate was 50% (18 of 36 patients; 95% CI, 33% to 67%). Median progression-free survival was 8.2 months (95% CI, 5.9 to 10.5 months), and median overall survival was not reached. Median duration of response was 11.2 months (95% CI, 7.7 to 14.7 months). Adverse events of any grade were rash (n = 11; 31%), pruritus (n = 9; 25%), decreased appetite (n = 9; 25%), diarrhea (n = 8; 22%), and dyspnea (n = 8; 22%), but all adverse events were manageable. CONCLUSION Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.

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BackgroundThe breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis.MethodsWe retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009.ResultsMedian age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0.001).ConclusionsOur results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

The results from this study suggest it to be an effective and feasible treatment method for chronic aphasia, although follow-up studies with more subjects and a control group are needed for a more thorough assessment.

This mobile game-based VR rehabilitation program appears to be feasible and effective for promoting upper limb recovery after ischemic stroke.

Rosiglitazone (RGTZ) has protective effect against various types of injury. This study was performed to evaluate the effect of RGTZ on pancreatic and renal injury caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered alone and together to the rats for 28 days. The effect of RGTZ on CsAinduced pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT), plasma insulin concentrations and pancreatic b -cell morphology. The effect of RGTZ on CsA-induced renal injury was evaluated by assessing renal function and pathology; mediators of inflammation and fibrosis such as angiotensin II (AngII), osteopontin (OPN) and transforming growth factor-beta1 (TGF-b 1) and apoptotic cell death. Four weeks of CsA treatment caused diabetes, renal dysfunction, typical pathologic lesions (arteriolopathy, interstitial fibrosis and inflammatory cells infiltration) and apoptotic cell death. RGTZ treatment decreased blood glucose concentration, increased plasma insulin concentration and preserved pancreatic b islet mass. RGTZ treatment improved renal function and histopathology. Pro-inflammatory and pro-fibrotic molecules such as AngII, OPN and TGF-b 1, and apoptotic cell death also decreased with RGTZ treatment. These data suggest that RGTZ has a protective effect against CsA-induced pancreatic and renal injury.

Stroke rehabilitation requires repetitive, intensive, goal-oriented therapy. Virtual reality (VR) has the potential to satisfy these requirements. Game-based therapy can promote patients' engagement in rehabilitation therapy as a more interesting and a motivating tool. Mobile devices such as smartphones and tablet PCs can provide personalized home-based therapy with interactive communication between patients and clinicians. In this study, a mobile VR upper extremity rehabilitation program using game applications was developed. The findings from the study show that the mobile game-based VR program effectively promotes upper extremity recovery in patients with stroke. In addition, patients completed two weeks of treatment using the program without adverse effects and were generally satisfied with the program. This mobile game-based VR upper extremity rehabilitation program can substitute for some parts of the conventional therapy that are delivered one-on-one by an occupational therapist. This time-efficient, easy to implement, and clinically effective program would be a good candidate tool for tele-rehabilitation for upper extremity recovery in patients with stroke. Patients and therapists can collaborate remotely through these e-health rehabilitation programs while reducing economic and social costs.

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