Citations

ABSTRACTBioinformatics tools are imperative for the in depth analysis of heterogeneous high‐throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community‐driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines.

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.

10 Background: Our objective was to evaluate the cost-utility of 3 lymphadenectomy (LND) strategies in the treatment of low-risk endometrial cancer (EC). Methods: A decision analysis model compared 3 LND strategies in women undergoing minimally invasive surgery (MIS) for EC: 1) routine LND in all pts; 2) selective LND based on intraoperative frozen section, in which 60% of pts undergo LND; and 3) sentinel lymph node mapping (SLN) based on a published algorithm, in which 15% of pts map unilaterally (requiring a contralateral LND) and 5% don’t map (requiring bilateral LND). Costs and outcomes were obtained from published literature and Medicare reimbursement rates. Costs categories consisted of hospital, physician, operating room, pathology, and lymphedema treatment. Effectiveness was defined as 3-year disease-specific survival adjusted for the impact of lymphedema (utility = 0.8) on quality of life. Incremental cost-effectiveness ratios (ICERs) per quality-adjusted life years (QALYs) gained were calculated. QALYs and costs were discounted at an annual 3% rate. Results: For the estimated 40,000 women undergoing surgery for low-risk EC each year in the US, the annual cost of routine LND, selective LND, and SLN is $722 million, $681 million, and $656 million respectively. In the base case scenario, routine LND had a cost of $18,041 and an effectiveness of 2.79 QALYs. Selective LND had a cost of $17,036 and an effectiveness of 2.81 QALYs, while SLN had a cost of $16,401 and an effectiveness of 2.87 QALYs. With a difference of $1,005 and 0.02 QALYs, selective LND was both less costly and more effective than routine LND, dominating it. However, with the lowest cost and highest effectiveness, SLN dominated the other modalities and was the most cost-effective strategy. No ICER could be determined. These findings were robust to multiple one- and two-way sensitivity analyses varying the rates of lymphedema and LND, surgical approach (open or MIS), lymphedema utility, and costs. Conclusions: Compared to routine and selective LND, SLN had the lowest cost and highest quality-adjusted survival, making it the most cost-effective strategy in the management of low-risk EC.

Simultaneous positron emission tomography and MRI (PET/MRI) is a technology that combines the anatomic and quantitative strengths of MR imaging with physiologic information obtained from PET. PET and computed tomography (PET/CT) performed in a single scanning session is an established technology already in widespread and accepted use worldwide. Given the higher cost and complexity of operating and interpreting the studies obtained on a PET/MRI system, there has been question as to which patients would benefit most from imaging with PET/MRI versus PET/CT. In this article, we compare PET/MRI with PET/CT, detail the applications for which PET/MRI has shown promise and discuss impediments to future adoption. It is our hope that future work will prove the benefit of PET/MRI to specific groups of patients, initially those in which PET/CT and MRI are already performed, leveraging simultaneity and allowing for greater degrees of multiparametric evaluation.Level of Evidence: 5Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2017;46:1247–1262.

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.

AbstractBackgroundWe sought to determine whether adolescents with metastatic alveolar rhabdomyosarcoma (ARMS) or embryonal RMS (ERMS) had a different event‐free survival (EFS) compared with younger patients, and to identify treatment‐related factors (adverse events, AEs) that may be associated with differences in outcome.MethodsThe prevalence of AEs in adolescents older than 13 years was compared with that in patients less than or equal to 13 years of age (Fisher exact test) in patients enrolled onto ARST0431. EFS by age and histology was compared by log–rank test.ResultsOf 109 patients, 60 (55%) were older than 13 years; they were more likely to have nausea (17 vs. 4%, P = 0.06) and pain (20 vs. 6%, P = 0.05) compared with younger patients. Adolescents were less likely to complete therapy (63 vs. 76%) and more likely to have unplanned dose modifications outside of protocol guidelines (23 vs. 2.7%). The 3‐year EFS was 26% (95% confidence interval [CI]: 15–38) for adolescents compared with 46% (95% CI: 32–60) for those less than or equal to 13 years (P = 0.011). Forty‐two (59%) adolescents with ARMS had a 3‐year EFS of 13% (95% CI: 2–23) compared with 30% (95% CI: 10–51) for those less than or equal to 13 years (P = 0.032). EFS was comparable between older and younger patients with ERMS (64 vs. 55%, P = 0.53).ConclusionsAlthough there was a significant difference in EFS and protocol compliance by age, the differences in age‐related toxicity are unlikely to account for this. Observed differences in pain and nausea by age could be real or be dependent on patient reporting of symptoms. Future studies in RMS should include patient‐reported outcomes to better evaluate health‐related quality of life.

184 Background: While evidence of the challenges of cancer caregiving has been growing, scant research addresses the experience of partners of young adults with cancer. These individuals and their relationships may be particularly vulnerable to stress, especially when managing the complexity of cancer care and survivorship with their partner. We sought to evaluate psychosocial concerns and mental health in the partners of young survivors of early stage breast cancer (BC). Methods: We invited partners of young women w/BC diagnosed at age ≤ 40 yrs enrolled in a prospective cohort study to participate in a one-time survey evaluating psychosocial concerns including quality of life, coping, social support, financial insecurity, partnership concerns, parenting concerns, anxiety and depression. Logistic regression was used to explore predictors of anxiety (score > 8 on Hospital Anxiety and Depression Scale (HADS)). Results: Most respondents (284/289) were male, with median age 43 yrs (range 27-65). The median time of survey completion was 62 months (range 16 -114) after their partner’s dx. Respondents were mostly white (93%), working full time (94%), and college educated (78%); 29% reported some financial stress, 74% were parenting children < 18 yrs, and 32% reported at least a fair amount of relationship concern. 42% (106/250) had anxiety (39/289 respondents (13%) had incomplete/missing HADS). In univariable analyses, lower education, working full time, parenting concerns, insufficient social support and maladaptive coping were associated (p < .05) with anxiety. In the multivariable model, only maladaptive coping remained significantly associated with anxiety (p < .01, OR = 2.32 (95% CI: 1.22, 4.39)). Conclusions: Partners of young BC survivors who used less constructive/more maladaptive coping strategies experience negative mental health outcomes after tx has ended. Caregivers’ anxiety may have implications for both their own and survivors’ health and QOL. Future interventions might focus on the development of constructive coping strategies to enhance adjustment and role effectiveness in dealing with the impact of cancer.