Citations

AbstractBackgroundA recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline.MethodsIn this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment.ResultsThe APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P < .01) and higher amyloid beta (Aβ 1–42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014).ConclusionsPatients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline.

OBJECTIVE Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle–based liquid biopsy targeting nonneoplastic extracellular vesicles. METHODS The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance. RESULTS Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM. CONCLUSIONS Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon’s arsenal in the near future for the treatment and management of GBM patients.

AbstractObjectiveTo evaluate the extent to which the canonical steps of shared decision making (SDM) take place in clinical encounters in practice and across SDM forms.MethodsWe assessed 100 randomly selected video‐recorded primary care encounters, obtained as part of a randomized trial of an SDM intervention in patients with type 2 diabetes. Two coders, working independently, noted each instance of SDM, classified it as one of four problem‐based forms to SDM (weighing alternatives, negotiating conflicting issues, solving problems, or developing existential insight), and noted the occurrence and timing of each of the four canonical SDM steps: fostering choice awareness, providing information, stating preferences, and deciding. Descriptive analyses sought to determine the relative frequency of these steps across each of the four SDM forms within each encounter.ResultsThere were 485 SDM steps noted (mean 4.85 steps per encounter), of which providing information and stating preferences were the most common. There were 2.7 (38 steps in 14 encounters) steps per encounter observed in encounters with no discernible SDM form, 3.4 (105 steps in 31 encounters) with one SDM form, 5.2 (129 steps in 25 encounters) with two SDM forms, and 7.1 (213 steps in 30 encounters) when ≥3 SDM forms were observed within the encounter. The prescribed order of the four SDM steps was observed in, at best, 16 of the 100 encounters. Stating preferences was a common step when weighing alternatives (38%) or negotiating conflicts (59.3%) but less common when solving problems (29.2%). The distribution of SDM steps was similar to usual care with or without the SDM intervention.ConclusionThe normative steps of SDM are infrequently observed in their prescribed order regardless of whether an SDM intervention was used. Some steps are more likely in some SDM forms but no pattern of steps appears to distinguish among SDM forms.Clinical Trial RegistrationClinicalTrial.gov: NCT01293578.