RESUMO
BACKGROUND: Carcinoma of unknown primary (CUP) accounts for 3-5% of all adult solid tumors. An extensive search for the anatomic site of origin is often undertaken in an attempt to tailor systemic treatment, but the latter often has limited efficacy - especially in the setting of an initial treatment failure. Molecularly targeted therapy is an emerging approach that may offer greater efficacy and less toxicity but is most likely to be effective when pairing a tumor harboring a sensitizing genomic alteration with an agent directed at the altered gene product. We report a patient with a CUP harboring a MET amplification with a complete metabolic response to crizotinib despite also harboring a KRAS mutation. METHODS: Ge-nomic profiling was performed using a clinical next-generation-sequencing-based assay, FoundationOne(®), in a CAP-accredited laboratory certified by Clinical Laboratory Improvement Amendments (Foundation Medicine, Cambridge, Mass., USA). RESULTS: The CUP harbored both MET amplification (16 copies) and a KRAS G12V mutation. The patient was treated with crizotinib, a MET inhibitor, and has experienced a complete normalization of tumor metabolic activity for more than 19 months. CONCLUSIONS: Genomic profiling of CUP may reveal clinically meaningful genomic alterations that can guide targeted therapy decision-making. The use of this approach should be studied prospectively as a strategy for the effective treatment of CUP patients and for avoiding resource-intensive workups to identify the tumor site of origin.
RESUMO
PURPOSE: Although bullying is recognized as a serious problem among adolescents, more information is needed regarding bullying within the context of physical education. Grounded in a social-ecological framework, the purpose of this investigation was to discover the perceptions students and teachers have about bullying in physical education and about peer and adult support. METHOD: Data collection included formal and informal interviews with 24 students and 4 teachers and 20 observations of 6th-grade physical education classes in 1 Midwestern school. Data were analyzed using a constant-comparative process. RESULTS: The results indicate that adults acculturate students to support a bullying climate by providing mixed information regarding social interactions, ignoring nonphysical instances of bullying, and promoting inappropriate curricular selections. Participants also report that perceived differences such as appearance, body size, physical ability, and personal attire ignite most episodes of harassment in physical education. Further, students perceive that fear prevents many from (a) reporting instances of bullying to those in authority, (b) assisting bullied friends, and (c) feeling safe in certain physical education locations. Finally, students and teachers report that bullying impacts students' desire to participate in physical education. CONCLUSIONS: Overall, evidence from this investigation suggests that an efficacious support system does not exist for addressing the magnitude of the bullying problem. Although this study provided an initial step toward understanding the social-ecological factors affecting peer harassment in physical education, additional research is warranted.
