Abstract LB-346: Case study: Non-uniform response to therapy in multiple metastatic is predicted using CANscriptTM, a live tissue, ex - vivo , platform

Abstract Background: It is now clear that the tumor microenvironment drives response or resistance to therapy. More specifically, the stroma, vasculature and immune compartment shape tumor response to therapy. In addition, heterogeneity within a tumor and between metastatic sites will invariably affect the outcome of treatment. Due in large part to these biological complexities, predicting how treatment response varies among multiple metastatic sites may impact overall outcome remains poorly established. Methods: Here, we interrogated the genomic and transcriptomic profile of three metastatic lesions from a patient diagnosed with relapsed head and neck squamous cell carcinoma (HNSCC), refractory to second-line Pembrolizumab (PD-1 checkpoint blockade). In addition, we employed CANscript™, a patient-derived ex-vivo model, which uses live tissue to recapitulate the native 3D tumor microenvironment coupled with an algorithm-driven strategy to predict clinical response in the form of an S-Score (Majumder et al., Nat. Comm., 2015). Using this platform, we tested two combination therapies; carboplatin with gemcitabine, and adriamycin with cyclophosphamide. Moreover, we characterized the tumor microenvironment, following combination treatment, using a multiplexed immunohistochemistry (IHC) panel (Ki67, PanCK, CD3, CD4, CD8, DAPI). Results: We determined that the three metastatic sites displayed distinct transcription and whole exome signatures, prior to CANscriptTM. Based on CANscriptTM predicted responses (S-Score) for the two combinations tested, all three sites responded in a non-uniform manner. Interestingly, each site also displayed distinct patterns of proliferative immune subsets (Ki67 staining) and CD4:CD8 ratios, following treatment with each combination therapy. Conclusion: Together, these findings demonstrate that, due to the underlying genetic and tumor microenvironment heterogeneity, metastatic sites might each confer distinct clinical responses to the same drug regimen, even in immunotherapy-resistant disease. Moreover, we highlight the utility of ex-vivo profiling as a tool to predict therapeutic response - not only at the individual patient level, but also at the level of multiple metastatic sites from a single patient. These findings underscore the importance of characterizing the entire tumor-immune contexture under pressure anticancer drugs. Such information can revise our understanding of personalized cancer care, and may impact rational treatment options. Citation Format: Chukwuemeka Ikpeazu, Munisha Smalley, Baraneedharan Ulaganathan, Allen Thayakumar, Laura Majeiko, Jyothsana Ganesh, Basavaraja Shanthappa, Hans Gertje, Mark Lawson, Sara Lapomarda, Aaron Goldman. Case study: Non-uniform response to therapy in multiple metastatic is predicted using CANscriptTM, a live tissue, ex-vivo, platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-346

The Impact of Streaming on Post-Primary Students' Attitudes to Teachers, Motivation and Learning

This is a study of pupils in a streamed environment to see how their motivation, approaches to learning, and general perceptions of their teachers and school environment, differs according to their stream position. The "Review of the Literature" reveals a continuing debate on the efficacy of this form of ability grouping. Much of the criticism of streaming centres on the negative effects it tends to have on the lower stream pupils, in terms of a lowering of academic performance, and eliciting an anti-school, delinguent subculture. The research methodology involved an Inventory chosen for its diversity of measurement, containing scales describing a wide variety of pupil, teacher and school characteristics. The quantitative study deals with a scientifically selected sample of one hundred and nine Third Year Secondary Boys, living in County Kildare. Our findings did not support current research, with regard to bottom pupils being less positive towards teachers and school than their upper stream counterparts. Indeed, they show a distinct willingness to learn, and display a positiveness towards their teachers, second only to the top stream. Our research did show, however, that the lower stream pupils tend to be less competent in terms of their skill in learning. Yet, the top stream did not report themselves to be overly skilful in this area, either. The "Review of Literature" suggests that the negative effects of streaming may be lessened, should enough resources be focused on the pupils in the lower streams. The uncharacteristically positive attitudes of the lower streams appears to suggest that such is the case in this school. We recommend further study in the side effects of this practice, as, while it appears to be benefiting the lower streams, we found an upper stream to be uniguely negative about teachers and school. We suggest that this hostile upper stream may have been unintentionally neglected as a result of an overconcentration of resources in the lower streams