tbuckley/cabot-search huggingface dataset:
P01.121 Optune treatment does not affect quality of life in treatment of high grade glioma compared to chemo-radiotherapy alone
Authors: J Onken, U Goerling, M Heinrich, S Guenes, D Krex, P Vajkoczy, M Misch
Journal: Neuro-Oncology (2018)

Tumor treating fields (optune) significantly prolong progression-free and overall survival in patients with newly diagnosed glioblastoma (GBM). Critics claim optune significantly lowers patients’ quality of life (QOL) due to side effects and average daily time on therapy. However, very limited data exist on how QOL is rated by patients under optune treatment in GBM therapy. 27 patients with primary GBM (n=13) or recurrent high grade glioma (rHGG, n=14) have been treated with optune. QOL was assessed using EORTC questionnaires QLQ-C30, BN20, FA13 (fatigue), and SSUK-8 (social support) plus a device-specific questionnaire. Results were compared to 27 patients under primary GBM therapy without optune. Analysis was carried out accordding to the EORTC manual. Optune treated patients did not rate their QOL worse than control. Emotional functioning was clinically relevant better in the optune group. In symptom scales optune patients did not fare worse than control but experienced significantly less fatigue and received more positive social support. Device alarms occured 3.56 times per 24h, 2.29 during night. Alarms were rare (2–3 per week) in 29.6% and often (more than 3x week) in 37% of patients. Moderate or no alarm discomfort numbered 62.9% and severe in 29.6%. Weight (44.4%) and size (33.3%) of the device were seen as compliance barriers a few times per week or more often. 55.5% were annoyed by array change rate. Average time for array changes was 49.92 minutes (n = 25; median 30 minutes) and caused severe discomfort in 25.9%. Therapy was willingly paused during daytime in 66.7% and in 11.1% at night. Daily time on therapy restricted daily routine life moderately in 48.1% and severely in 25.9% of patients. Hair shaving was no issue in >85%. A total of 74% felt moderate or no discomfort by therapy side effects. Working life, hobbys, mobility were affected moderately (<25% of users), sexual life was significantly affected in nearly half of the patients (48.1%). However, therapy motivation was high and social life was stable (,,no” or,,minor” obstacles in 66.6%). QOL generally dropped in the 1st month under therapy and then recovered after an,,adjusting phase”. 74.1 % of patients would recommend optune therapy to others, 18 without restrictions. 66.7% would do optune therapy again, 4 patients would not repeat treatment. In general, the addition of optune treatment did not worsen quality of life in comparison to other patients under first line glioblastoma therapy. Although optune treatment frequently affects daily life in all aspects, most patients did not rate these events as severely discomforting. This may be explained by a repeated and honest consultation strategy before treatment start. Improval of some aspects of therapy (carrying the device, battery life, temperature alarms) may further increase acceptance, compliance and patient satisfaction.
Association of pre-allogeneic hematopoietic stem cell transplant 25-hydroxy-vitamin D level and development of acute skin graft-versus-host-disease: A retrospective analysis of 154 patients.
Authors: Ranjit Joseph, Seema Jabbar, Manasa Reddy, Damon Eugene Houghton, Trull Yun, Xainming Tan, Ibrahim Hashim
Journal: Journal of Clinical Oncology (2017)

e18539 Background: The pathophysiology of acute skin graft versus host disease (asGVHD) is thought to be initiated when donor T cells encounter recipient dendritic cells (DC) and become activated. Studies have shown that vitamin D (VD) inhibits DC maturation, polarizes T cell populations toward Th2 cytokine phenotype, And biases toward tolerating T cell populations. We analyzed pre-SCT serum vitamin D levels and sought to determine an association with development of acute skin GVHD. Methods: 154 patients, with matched SCT at UTSW Medical Center from December 2007 to December 2014, and who had serum samples banked prior to conditioning were included in the analysis. Pertinent data were extracted from the UTSW BMT database and EMR. Serum samples collected 1-3 months prior to SCT were used to detect 25-hydroxyvitamin D (VD) concentrations. Cumulative incidence (CI) of asGVHD grade II-IV were assessed within 100 days post-SCT. A significantl difference (p-value = 0.026, Breslow-Day test) in the associations between Vit D and asGVHD for patients under RIC and ABLgroups was present, so we analyzed the primary endpoint, time to asGVHD since SCT, separately among two these 2 groups. CI functions were constructed with death and relapse as competing risks. Results: Out of 154 patients, 93 were male, mean age was 51, range 20-72 and median VD was 21 ng/ml (range 7.1-63.3). There were 112 patients with VD &lt; 25 ng/mL (VD &lt; 25) and 41 with VD ≥ 25 ng/mL (VD≥25). Age, conditioning regimen, donor type, cell source, ABO compatibility, GVHD prophylaxis were similar in both groups. Overall CI asGVHD was 24%. CI of asGVHD was 23.8% in VD≥25 and 24.1% in VD &lt; 25. Patients were then analyzed separately with respect to type of conditioning regimen they received (Ablative (ABL) vs Reducing intensity (RIC)). Figure 1A shows that in the ABL group the CI of asGVHD appears increased in patient with VitD≥25 (40% vs 27.1%, p = 0.27). In contrast, Figure 1B shows that in RIC group the CI of asGVHD is higher for those with VD &lt; 25 (4.8% vs 24.1% , p = 0.05). Conclusions: After accounting for competing factors, KM analysis in the RIC group showed that patients with VD level &lt; 25 ng/mL were at a higher risk of developing asGVHD. Further studies to clarify the association between VD status and development of asGVHD are warranted.
A breast health (BH) educational program to increase breast cancer awareness among adolescents and their female relatives in low-income communities through intergenerational learning.
Authors: Yanin Chavarri Guerra, David D Smith, Patricia Rojo-Castillo, Arti Hurria, Alba M Pavas-Vivas, Rina Gitler-Weingarten, Martin A Reyes-Bautista, Alejandro Mohar, Edgar Baltazar-Avalos, Max Sirota-Toporek, Mayte Ayala-Gonzalez, Viridiana Chaveste-Ramos, Brenda Cosme-Gonzalez, Sofia N Gallegos-Quintana, Ana FS Martinez-Aviles, Julia A Melendez-Rosas, Andrea Salazar-Moreno, Enrique Soto Perez De Celis
Journal: Journal of Clinical Oncology (2016)

6540 Background: Delays in the diagnosis of breast cancer in developing countries are related to a lack of knowledge on BH, particularly in rural communities with poor access to education. We hypothesized that a school-based BH educational program for adolescents in a Mexican rural community would increase their knowledge and promote intergenerational transmission of information to their female relatives. Methods: Female adolescents enrolled in a public rural middle school were invited to participate in the program. They received age-appropriate, culturally sensitive sessions from educators focused on transmitting BH knowledge in their household. To evaluate both the student’s and the female relatives’ knowledge a pre- and post-intervention validated 8-item questionnaire was administered. Four months after the intervention we evaluated knowledge retention among students and intergenerational transmission of the information to their female relatives using the same instrument. Paired t-test was used to detect changes in knowledge, and a p value of < 0.05 was considered significant. Results: 126 students with a median age of 13.5 years (12 - 16) were enrolled in the program, and 90% (n = 114) completed the 4-month follow-up (FU) tests. The pre-, post- and FU mean proportion of correct answers was 63% (12.5-100%, SD 0.2), 89% (25-100%, SD 0.12) and 82% (37.5-100%) respectively, showing an increase in knowledge of 18.9% (p < 0.001) in the FU test. 182 female relatives (median age 40 years [15 – 89]) completed the pre- and FU tests, showing a 5% increase in the proportion of correct answers (56 to 61%, p < 0.001). Notably, the proportion of students who reported feeling comfortable discussing BH at home increased from 71 to 90% 4 months after the intervention. Conclusions: Implementing a BH educational program for rural adolescents in low-income communities increases their knowledge on BH, and may promote and facilitate intergenerational transmission of such knowledge to their female relatives. Our results warrant further research into intergenerational education as a novel method for cancer education in developing nations.
Epigenetic Modifications in Cardiovascular Aging and Diseases
Authors: Weiqi Zhang, Moshi Song, Jing Qu, Guang-Hui Liu
Journal: Circulation Research (2018)

Aging is associated with a progressive decline in cardiovascular structure and function. Accumulating evidence links cardiovascular aging to epigenetic alterations encompassing a complex interplay of DNA methylation, histone posttranslational modifications, and dynamic nucleosome occupancy governed by numerous epigenetic factors. Advances in genomics technology have led to a profound understanding of chromatin reorganization in both cardiovascular aging and diseases. This review summarizes recent discoveries in epigenetic mechanisms involved in cardiovascular aging and diseases and discusses potential therapeutic strategies to retard cardiovascular aging and conquer related diseases through the rejuvenation of epigenetic signatures to a young state.
Data Lakes, Clouds, and Commons: A Review of Platforms for Analyzing and Sharing Genomic Data
Authors: Robert L. Grossman
Journal: Trends in Genetics (2019)

HighlightsData commons collate data with cloud computing infrastructure and commonly used software services, tools, and applications to create biomedical resources for the large-scale management, analysis, harmonization, and sharing of biomedical data.Data commons support repeatable, reproducible, and open research.Data lakes provide access to a collection of data objects that can accessed via digital IDs and searched via their metadata.A simple data ecosystem can be built when a data commons exposes an API that can support a collection of third party applications that can access data from the commons. More complex data ecosystems arise when multiple data commons can interoperate and support a collection of third party applications over a common set of core services (framework services), such as services for authentication, authorization, digital IDs, and metadata.AbstractData commons collate data with cloud computing infrastructure and commonly used software services, tools, and applications to create biomedical resources for the large-scale management, analysis, harmonization, and sharing of biomedical data. Over the past few years, data commons have been used to analyze, harmonize, and share large-scale genomics datasets. Data ecosystems can be built by interoperating multiple data commons. It can be quite labor intensive to curate, import, and analyze the data in a data commons. Data lakes provide an alternative to data commons and simply provide access to data, with the data curation and analysis deferred until later and delegated to those that access the data. We review software platforms for managing, analyzing, and sharing genomic data, with an emphasis on data commons, but also cover data ecosystems and data lakes.
<i>PCA3</i> upregulation in prostate cancer: Analysis in a cohort of 497 subjects from TCGA.
Authors: Emmanuel Dias-Neto, Diana N. Nunes, Andrew M. Thomas, Tracey L. Smith, Arpit Rao, Richard C. Lauer, Isan Chen, Wadih Arap, Renata Pasqualini
Journal: Journal of Clinical Oncology (2017)

e16578 Background: Approved by the FDA as a diagnostic test, the long non-coding RNA PCA3 is the most specific human prostate cancer biomarker identified to date. The biological function of PCA3, which involves downregulating the tumor suppressor gene PRUNE2, has important therapeutic implications. Here we investigated RNA expression levels of these genes to better understand the dynamics of this regulatory process during cancer progression and its relevance for tumor aggressiveness. Methods: We downloaded clinical data, as well as PCA3 and PRUNE2 gene expression values (log2 RSEM), from 497 TCGA prostate cancer patients (totaling 550 samples) and their matched normal tissues using the Xena Browser. Expression values for both genes, and their ratios, were evaluated in terms of tumor vs non-tumor tissue, biochemical recurrence, pathologic T stage, Gleason scores and age at diagnosis. All p-values were obtained by the Wilcoxon rank Sum (2 groups) or the Kruskal-Wallis Test (3+ groups). Results: Using 52 malignant/non-malignant tissue pairs from our cohort, we confirmed previous findings that showed simultaneous PCA3 upregulation and PRUNE2 reduction in malignant samples when compared to non-malignant ( p&lt;0.001). Normalized levels of PRUNE2 were informative for advanced tumors (Gleason &gt;7) and in younger subjects (&lt;50 years old), whereas PCA3/ PRUNE2ratios could discriminate all but the age at diagnosis group, and PCA3 levels were informative for all comparison groups. Conclusions: PCA3 appears to be a valuable marker of early stage disease or a less aggressive tumor. This suggests the activation of this oncogene to be an early event in PrCa, which may be later on replaced by other mechanisms that would sustain cancer progression and metastasis. [Table: see text]
P05.23 Local recurrence and leptomeningeal dissemination after resection of brain metastases: a single-institution, retrospective study in the era of individualized treatment
Authors: Y Nakasu, K Mitsuya, S Deguchi, N Hayashi, H Harada, S Nakasu
Journal: Neuro-Oncology (2018)

Metastases are the most frequent tumours in the brain, and need to be managed by a multimodality team. Surgical resection of brain metastases contributes to immediate improvement of patients’ performance status. We retrospectively analyzed postoperative local recurrence and leptomeningeal dissemination that influence outcome in patients who underwent resection and adjuvant radiation therapy. One hundred and seventy-three patients who underwent resection surgery for newly diagnosed brain metastases in our institution between 2002 and 2015 were included in this study. Our cancer board determined the individualized indication of treatments for each patient, and supported patient’s decision making. Primary cancers were lung (36.4%), colon (16.2%), breast (11.0%) and others. A majority of patients (88.4%) underwent minimum resection without safety margin around tumour. Surgical procedures caused no permanent morbidities. Eighty-seven percent of patients underwent postoperative adjuvant radiotherapy. The median overall survival time from brain surgery was 9.8 months. Thirty of 173 patients (17.3%) developed local recurrence and 14 (8.1%) developed leptomeningeal carcinomatosis. Male sex (HR: 2.8, 95%CI: 1.0–10.0), colon cancer (HR: 6.5, 95%CI: 2.2–24.2), and no postoperative radiation (HR: 5.6, 95%CI: 2.1–13.7) were identified as risk factors of local recurrence in multivariate analysis. Female sex (HR: 4.4, 95%CI: 1.2–20.9) and recursive partitioning analysis class 3 (HR: 1.0e+9, 95%CI: 1.7-) were identified as risk factors of leptomeingeal dissemination in multivariate analysis. Our retrospective review showed that individualized treatment with surgical resection followed by adjuvant radiation therapy is a safe and feasible method for brain metastases with reasonable local control and infrequent dissemination in the real world.
Impact of denosumab on skeletal-related events in solid tumors.
Authors: Sridevi Rajeeve, Stuthi Perimbeti, Karan Jatwani, Rishi Shrivastav, Vivek Modi
Journal: Journal of Clinical Oncology (2018)

e18754 Background: Skeletal-related events (SRE) are frequent consequences of bone metastases from solid tumours like breast, prostate and lung. In 2010, US FDA approved Denosumab, a monoclonal antibody inhibiting RANK-L, for SRE from metastatic bone tumors. Studies are lacking which compare the trends of SRE before and after the advent of RANK-L inhibitors. Our study aims to examine the trends in hospitalizations and mortality due to SRE in prostate, lung and breast cancer before and after the FDA approval of Denosumab. Methods: We analyzed data using the Nationwide Inpatient Sample (NIS) by extracting the adult admissions with a primary diagnosis of breast, prostate and lung cancer from 2007-2014 using their ICD 9 codes. The admissions were stratified into two groups: Pre-Denosumab era included admissions from 2007 to 2010 and post-Denosumab era from 2011 to 2014. SREs included pathological fracture, hypercalcemia of malignancy and spinal cord compression. We performed Chi-Square analysis to determine frequency of distribution of SRE among different cancers and Cox Proportional Hazard regression to determine the hazard of mortality among patients with and without SREs. Results: N = 54234 ; weighted = 268152 Table 1: SRE in pre and post Denosumab era and Hazard ratios Conclusions: Hospitalizations with SRE have been increasing over the years which can be ascribed to increased cancer survivorship. In prostate cancer, hazard ratio of mortality significantly decreased in post-Denosumab era. The ease of administering Denosumab over other bone conserving agents may contribute to better compliance and persistence of therapy leading to the mortality reduction observed in prostate cancer. Higher levels of compliance and therapy persistence may ensure better clinical results across the other cancers. Cancer 2007-2010 (%) 2011-2014 (%) p-value Prostate 0.30 0.40 0.0163 Lung 4.88 5.67 < 0.0001 Breast 1.50 2.08 < 0.0001 Cancer HR 2007-2010 p-value HR 2011-2014 p-value Prostate 2.22 (1.48-3.32) 0.0001 1.86 (1.17-2.95) 0.0001 Lung 1.22 (1.10-1.35) 0.0002 1.06 (0.96-1.17) 0.256 Breast 1.06 (0.80-1.40) 0.6781 1.15 (0.89-1.49) 0.2839
Abstract A064: Mass spectrometry-based proteomics study makes apolipoprotein E a potential risk factor for prostate cancer
Authors: Juan Bizzotto, Sofia Lage Vickers, Alejandra Paez, Carlos Scorticati, Javier Cotignola, Pia Valacco, Osvaldo Mazza, Elba Vazquez, Geraldine Gueron
Journal: Cancer Research (2018)

Abstract Proteomics represents an important tool for the identification of new molecular targets for prostate cancer (PCa) tailored therapy. Innovative high-throughput proteomic platforms are now identifying and quantifying new specific and sensitive biomarkers for PCa detection, stratification, and treatment. Formalin-fixed and paraffin-embedded (FF-PE) sections mounted on microscope slides are hard to achieve given the low peptide yield obtained from the slides. Here we performed an innovative protocol for an in-depth quantitative mass spectrometry-based proteomics analysis of FF-PE PCa and benign prostate hyperplasia (BPH) sections, using phase-transfer surfactant-aided extraction/tryptic digestion of FF-PE proteins. Results yielded a list of 50 differential proteins only expressed in PCa samples. Of note, apolipoprotein E (APOE) was highly present in carcinoma samples. Furthermore, to evaluate the clinical significance of APOE in PCa we performed a bioinformatics analysis using the Oncomine database. We identified 16 publicly available gene expression microarray datasets comparing prostate adenocarcinoma versus normal prostate, which met our eligibility criteria. We carried out meta-analysis combining the data from the independent datasets. APOE was ranked by its P-value for every analysis scoring a gene rank and then we obtained a median rank (median P-value rank across datasets). APOE showed a significant upregulation (fold change &amp;gt;1.5, P&amp;lt;0.05) comparing prostate adenocarcinoma vs. normal prostate gland. Accordingly, when extending the bioinformatics analysis to evaluate whole-exome and RNA-seq data using cBioportal, the most frequent genetic alteration found for APOE was amplification. RNA-seq data also confirmed a significant upregulation for APOE (P&amp;lt;0.05). We thus identify APOE as a key target in PCa, ascertaining it as a potential risk factor for this disease. Citation Format: Juan Bizzotto, Sofia Lage Vickers, Alejandra Paez, Carlos Scorticati, Javier Cotignola, Pia Valacco, Osvaldo Mazza, Elba Vazquez, Geraldine Gueron. Mass spectrometry-based proteomics study makes apolipoprotein E a potential risk factor for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A064.
Conservation of biodiversity in the genomics era
Authors: Megan A. Supple, Beth Shapiro
Journal: Genome biology (2018)

"Conservation genomics" encompasses the idea that genome-scale data will improve the capacity of resource managers to protect species. Although genetic approaches have long been used in conservation research, it has only recently become tractable to generate genome-wide data at a scale that is useful for conservation. In this Review, we discuss how genome-scale data can inform species delineation in the face of admixture, facilitate evolution through the identification of adaptive alleles, and enhance evolutionary rescue based on genomic patterns of inbreeding. As genomic approaches become more widely adopted in conservation, we expect that they will have a positive impact on management and policy decisions.
Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: A 3-year experience.
Authors: Alberto Mendivil, Lisa Nicole Abaid, John V. Brown, Kristina Mori, Katrina Lopez, Bram Goldstein
Journal: Journal of Clinical Oncology (2017)

e17094 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially confers significant survival benefits in the management of ovarian cancer although the long-term data remain scant. We sought to compare the survival rates of advanced stage ovarian cancer patients who were treated with primary induction therapy alone or in conjunction with consolidation HIPEC. Methods: Sixty-nine ovarian cancer patients who underwent surgery and completed their primary induction chemotherapy were treated with consolidation carboplatin (AUC 10) based HIPEC and compared to a historical cohort that received surgery and primary chemotherapy alone (n=69). The demographic and clinical characteristics in which we were primarily interested included: patient age, body mass index, surgery and pathology data, chemotherapy regimen, toxicity, and progression free/overall survival. Results: The two patient groups were similar in terms of tumor characteristics, cyto-reductive status, distribution of neoadjuvant chemotherapy and number of maintenance chemotherapy cycles administered (P&gt; 0.05). Progression free survival was significantly more pronounced in the HIPEC (25.1 months) patients compared to the control group (20 months) (P=0.024) and there was a decreased risk of disease progression accorded to the patients treated with HIPEC (HR, 2.1028; 95% CI: 1.2941 to 3.4167; P=0.0027). However, we did not discern any HIPEC related overall survival advantages (P=0.29). Conclusions: The results from our ovarian cancer study suggest that adjunctive HIPEC proffers a significant progression free survival advantage and a decreased risk for disease progression. There was, however, no overall survival advantage discerned in the HIPEC group. We also recognize that HIPEC remains controversial and thus, randomized studies evaluating HIPEC compared to standard chemotherapy in the management of ovarian cancer are warranted.