AstraZeneca.

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.

The aims of this cross-sectional study were (i) to compare the overall glucose metabolism between early onset and late onset Alzheimer's disease in a large sample of patients; and (ii) to investigate the pattern of glucose metabolism as a function of dementia severity in early onset versus late onset Alzheimer's disease, using a statistical parametric mapping (SPM) analysis. Subjects consisted of four groups: 74 patients with early onset Alzheimer's disease, 46 patients with late onset of the disease, and two control groups age matched to each patient group. All the subjects underwent 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET under the same scanning conditions. Severity of dementia was rated with the Clincial Dementia Rating (CDR). Voxel-based SPM99 was used for statistical analyses. Overall glucose hypometabolism of early onset Alzheimer's disease patients was much greater in magnitude and extent than that of late onset patients, though both groups were similar in dementia severity: the early onset group showed more severe hypometabolism in parietal, frontal and subcortical (basal ganglia and thalamus) areas. When the decline of glucose metabolism was compared as a function of CDR stage, the slope was steeper in early onset than in late onset Alzheimer's disease. The rapid decline occurred at CDR 0.5-1 in the early onset group, whereas similar changes occurred at CDR 2-3 in the late onset group. The greater hypometabolism in early onset than in late onset patients is required to reach the same severity of dementia, probably reflecting greater functional reserve in younger than in older subjects. Alternatively, the metabolic decline curve suggests that the early onset patients may take a more rapid course in the reduction of glucose metabolism than the late onset patients.

While families strongly agreed that "presence of family" and "not be a burden to family" were important to a good death, the importance of other factors differed between the groups. Health care providers should attempt to discern each patient's view of a good death.

ObjectivesPD-1/PD-L1 and CTLA-4 have been investigated and are thought to play an important role in tumor evasion. This study aimed to investigate expression patterns of immune-related molecules, and their clinical impacts in malignant salivary gland tumors.Patients and methodsWe performed immunohistochemical staining for PD-L1, PD-L2, CTLA-4, PD-1, and CD8+ tumor-infiltrating lymphocytes in 70 malignant salivary gland tumors. Protein expression was assessed by H-score by multiplying the staining intensity by the percentage of cells with positive staining.ResultsThe tumors comprised mucoepidermoid carcinomas (38.6%), adenoid cystic carcinomas (21.4%), salivary duct carcinomas (15.7%), and others. In malignant salivary gland tumors, PD-L2 expression was high, while expression of PD-L1 was relatively low in terms of the percentage of positively stained cells and the staining intensity. In univariate analysis, PD-L2 expression (H-score <1 vs ≥1), PD-1 (H-score <1 vs ≥1), and CD8+ tumor-infiltrating lymphocytes (H-score <1 vs ≥1) were significant prognostic factors. In multivariate analysis, low PD-L2 expression (H-score <1) was independently associated with shorter relapse-free survival (hazard ratio =6.514; 95% confidence interval, 1.2–36.2; P=0.032).ConclusionIn summary, PD-L2 is potentially an important biomarker in malignant salivary gland tumors, especially in regard to relapse.