Cerebral blood volume and apparent diffusion coefficient - Valuable predictors of non-response to bevacizumab treatment in patients with recurrent glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The core of standard of care for newly diagnosed GBM was established in 2005 and includes maximum feasible surgical resection followed by radiation and temozolomide, with subsequent temozolomide with or without tumor-treating fields. Unfortunately, nearly all patients experience a recurrence. Bevacizumab (BV) is a commonly used second-line agent for such recurrences, but it has not been shown to impact overall survival, and short-term response is variable. METHODS: We collected MRI perfusion and diffusion images from 54 subjects with recurrent GBM treated only with radiation and temozolomide. They were subsequently treated with BV. Using machine learning, we created a model to predict short term response (6 months) and overall survival. We set time thresholds to maximize the separation of responders/survivors versus non-responders/short survivors. RESULTS: We were able to segregate 21 (68%) of 31 subjects into unlikely to respond categories based on Progression Free Survival at 6 months (PFS6) criteria. Twenty-two (69%) of 32 subjects could similarly be identified as unlikely to survive long using the machine learning algorithm. CONCLUSION: With the use of machine learning techniques to evaluate imaging features derived from pre- and post-treatment multimodal MRI, it is possible to identify an important fraction of patients who are either highly unlikely to respond, or highly likely to respond. This can be helpful is selecting patients that either should or should not be treated with BV.

IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?

OBJECTIVES: Molecular screening plays a major role in prognostic categorization and subsequent definition of treatment strategies for acute myeloid leukemia. The possibility of using IDH1/2 mutations as a marker for the monitoring of minimal residual disease (MRD) is still under investigation and remains unclear. METHODS: In this retrospective study, we evaluated 90 patients with de novo AML using Sanger sequencing (exon 4, IDH1 and IDH2). For subsequent MRD monitoring were used both methods, massive parallel sequencing and droplet digital PCR (ddPCR). RESULTS: We identified 22 patients (24%) who harboured mutations in IDH1 or IDH2 genes. Fourteen (64%) of them had other commonly used MRD markers (insertion in NPM1 and partial tandem duplication of MLL, MLL-PTD). Eight of the 22 patients had IDH1 mutations, 13 had IDH2 mutations and 1 had both IDH1 and IDH2 mutations. In our cohort, this IDH1/2 marker responded to the treatment in all of the patients and reflected the onset of the relapse very well. NPM1 mutation based MRD monitoring was more sensitive and predicted relapse earlier but IDH1/2 based monitoring was more sensitive than a method based on MLL-PTD. Both massive parallel sequencing and ddPCR were competent to monitor MRD using IDH1/2. Nevertheless, ddPCR was able to achieve a higher sensitivity in some cases and moreover this method can analyse a single sample without significant price increases. CONCLUSION: Given these data, we conclude that IDH1/2 mutations can be used as a reliable and cost-effective marker for MRD monitoring.

Safety and Efficacy of Endovascular Treatment of Previously Clipped Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: The safety and efficacy of endovascular treatment of previously clipped aneurysms have not been well-established. We conducted a systematic review of the literature to evaluate the outcomes of endovascular treatment of previously clipped aneurysms. METHODS: A systematic search of MEDLINE, Embase, Scopus, and the Web of Science was performed for studies published until October 2017. We included studies with ≥2 patients that described endovascular treatment of previously clipped aneurysms. A random-effects meta-analysis was used to pool the following outcomes: technical success, aneurysm occlusion/recurrence/rebleed, ischemic/thrombotic/thromboembolic events, neurologic/procedure-related morbidity/mortality, and favorable neurologic outcomes. We performed subgroup analyses by aneurysm rupture status on presentation to the endovascular procedure, treatment timing, and by aneurysm location (anterior vs. posterior circulation). RESULTS: In total, 27 studies with 271 patients were included. Overall complete occlusion was 76.1% (95% confidence interval [CI] 0.676-0.836) and technical success was 97.9% (95% CI 0.958-0.993). Combined procedure-related morbidity/mortality was 4.5% (95% CI 0.024-0.073). There were no statistically significant differences in any of the safety and efficacy outcomes by aneurysm location. Overall long-term favorable neurologic outcome was 78.5% (95% CI 0.732-0.834). All included studies are retrospective. CONCLUSIONS: Our meta-analysis demonstrated that endovascular treatment is acceptably safe and effective. It is important to point out that the complication rate of treatment of these aneurysms is not negligible. These findings should be considered when deciding the best therapeutic strategy. Our findings may suggest that endovascular treatment of previously clipped aneurysms should only be considered in circumstances in which conservative management seems to be unsafe.