Purpose Limited treatment options exist for patients with thymic epithelial tumor (TET) whose disease progresses after platinum-based chemotherapy. We conducted a phase II study of pembrolizumab in patients with TET to evaluate its efficacy and safety. Methods Patients with histologically confirmed TET whose disease progressed after at least one line of platinum-based chemotherapy were eligible for the study. Patients were excluded if they had an active autoimmune disease requiring systemic treatment within the past year or documented history of clinically severe autoimmune disease. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until tumor progression or unacceptable toxicity. The primary objective of response rate was assessed every 9 weeks by investigators. Results Of 33 patients enrolled, 26 had thymic carcinoma and seven had thymoma. Of seven thymoma, two (28.6%; 95% CI, 8.2% to 64.1%) had partial response, and five (71.6%) had stable disease. Of 26 thymic carcinoma, five (19.2%; 95% CI, 8.5% to 37.9%) had partial response and 14 (53.8%) had stable disease. The median progression-free survival was 6.1 months for both groups. The most common adverse events of any grade included dyspnea (11; 33.3%), chest wall pain (10; 30.3%), anorexia (seven; 21.2%), and fatigue (seven; 21.2%). Five (71.4%) of seven patients with thymoma and four (15.4%) of 26 patients with thymic carcinoma reported grade ≥ 3 immune-related adverse events, including hepatitis (four; 12.1%), myocarditis (three; 9.1%), myasthenia gravis (two; 6.1%), thyroiditis (one; 3.0%), antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis (one; 3.0%), colitis (one; 3.0%), and subacute myoclonus (one; 3.0%). Conclusions Pembrolizumab showed encouraging antitumor activity in patients with advanced TET. Given the high incidence of autoimmunity, additional studies are needed to identify those who can benefit from pembrolizumab without immune-related adverse events.

Purpose: To investigate blood-based dynamic biomarkers that predict responses to anti-programmed cell death protein 1 (PD-1) therapy in solid tumors.Experimental Design: Preplanned biomarker analysis was performed as part of a phase II clinical trial (NCT02607631) in patients with metastatic or refractory thymic epithelial tumors (TETs; n ¼ 31) who received pembrolizumab. The biomarker was further tested in an independent cohort of prospectively recruited patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab (NSCLC cohort 1; n ¼ 33) and validated in an independent cohort of patients with NSCLC (NSCLC cohort 2; n ¼ 46). Peripheral blood samples were obtained immediately before treatment (D0) and 7 days after the first dose (D7) and analyzed using multi-color flow cytometry.Results: A higher fold-change in the percentage of Ki-67 þ cells among PD-1 þ CD8 þ T cells 7 days after the first dose (Ki-67 D7/D0 ) significantly predicted durable clinical benefit (DCB; P < 0.001) and prolonged progression-free survival (PFS; P ¼ 0.027) in patients with TETs. Ki-67 D7/D0 ! 2.8 was also associated with better DCB, PFS, and overall survival (OS) in NSCLC cohort 1 (all P < 0.05). Ki-67 D7/D0 was subsequently validated in NSCLC cohort 2, and Ki-67 D7/D0 ! 2.8 significantly predicted better DCB (P ¼ 0.001), PFS (P ¼ 0.002), and OS (P ¼ 0.037). Ki-67 D7/D0 had a low correlation with tumor PD-L1 expression and combining both factors did not improve the predictive power of Ki-67 D7/D0 .Conclusions: The proliferative response of peripheral blood PD-1 þ CD8 þ T cells, measured as the fold-change in the percentage of Ki-67 þ cells 7 days after treatment (Ki-67 D7/D0 ), may be a useful surrogate biomarker for predicting the response and prognosis to anti-PD-1 therapy in solid tumors.

No abstract

A B S T R A C TThis article explores how an economic ideology-neoliberalism-serves as a covert language policy mechanism pushing the global spread of English. Our analysis builds on a case study of the spread of English as a medium of instruction (MoI) in South Korean higher education. The Asian financial crisis of 1997/98 was the catalyst for a set of socioeconomic transformations that led to the imposition of "competitiveness" as a core value. Competition is heavily structured through a host of testing, assessment, and ranking mechanisms, many of which explicitly privilege English as a terrain where individual and societal worth are established. University rankings are one such mechanism structuring competition and constituting a covert form of language policy. One ranking criterion-internationalization-is particularly easy to manipulate and strongly favors English MoI. We conclude by reflecting on the social costs of elevating competitiveness to a core value enacted on the terrain of language choice. (English as a global language, globalization, higher education, medium of instruction (MoI), neoliberalism, South Korea, university rankings)* This world that appears to them as involved in an inevitable process of globalization, is in reality, and this is the worst of it, the product of a systematic, organized, and orchestrated policy.(Pierre Bourdieu, 2001) 1