RESUMEN
The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma-extracellular signal-regulated kinase-MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been successful in treating many adult cancers. Despite advances in other cancer types, the morbidity and survival outcomes of patients with glioma have remained relatively stagnant. Recently, there has been recognition that MAPK dysregulation is almost universally present in paediatric and adult gliomas. These findings, accompanying broad molecular characterization of gliomas, has aided prognostication and offered opportunities for clinical trials testing targeted agents. The use of targeted therapies in this disease represents a paradigm shift, although the biochemical complexities has resulted in unexpected challenges in the development of effective BRAF inhibitors. Despite these challenges, there are promising data to support the use of BRAF inhibitors alone and in combination with MEK inhibitors for patients with both low-grade and high-grade glioma across age groups. Safety and efficacy data demonstrate that many of the toxicities of these targeted agents are tolerable while offering objective responses. Newer clinical trials will examine the use of these therapies in the upfront setting. Appropriate duration of therapy and durability of response remains unclear in the glioma patient cohort. Longitudinal efficacy and toxicity data are needed. Furthermore, access to these medications remains challenging outside of clinical trials in Australia and New Zealand. Compassionate access is limited, and advocacy for mechanism of action-based drug approval is ongoing.
RESUMEN
OBJECTIVE: This study compared rural location identified through the National Registration (AHPRA) registry with location obtained through labour-intensive personal contact. DESIGN: Longitudinal cohort study with two methods to identify the work locations of medical graduates from The Rural Clinical School of Western Australia (RCSWA). PARTICIPANTS: Consenting alumni from the University of Western Australia and the University of Notre Dame Fremantle participating in RCSWA between 2002 and 2009 inclusive and available to contact in 2011. MAIN OUTCOME MEASURE: Percentage location matches between two contact methods. RESULTS: There was 80% agreement for principal suburb, 92% agreement for principal city and 94% agreement for principal state between RCSWA personal contact and the AHPRA registry. AHPRA identified nearly two times as many graduate locations. However, there was only 31% agreement for a rural placement location (of any length). In more detail, for year-long rural placement, personal contact was 88% concordant with AHPRA; work six months or more were less concordant (44% agreement); work less than six months were not concordant (4% agreement). CONCLUSIONS: AHPRA data matched RCSWA alumni data only for graduates in full-time rural work. Since medical alumni spend up to 10 years in pre-vocational and vocational training, which includes many rural options, personal contact was able to pick up the myriad of rural choices, whereas the AHPRA database was not sensitive enough to identify them. Until graduates have stably finished training, the optimal method to identify rural work is through personal contact but statistical correction for missing data needs to be considered.
