tbuckley/cabot-search huggingface dataset:
Oncology guidelines usage in a low and middle-income country.
Authors: Nofisat Ismaila, Omolola Salako, Adebayo Oladeji
Journal: Journal of Clinical Oncology (2017)

e18211 Background: Healthcare providers often rely on clinical practice guidelines to help inform and optimize patient care. However, most of these guidelines are from reputable organizations that are based in developed countries. There is a paucity of data about the status of guidelines in low and middle-income countries (LMIC), specifically in terms of their availability, usage and quality. Objective: To determine utilization of oncology guideline and potential barriers to usage in a LMIC among clinical and radiation oncologist (RADONCS) Methods: A cross-sectional survey was conducted with the use of an online questionnaire that was administered to practicing RADONCS in Nigeria via the Association’s email and social media database. In addition, paper questionnaires were administered in person at regional clinical meetings. Results: Survey response rate was 53.4% in a sample of 101 RADONCS from the database. Sixty-nine percent of respondents were consultants and 30% were residents. About 17% had greater than ten years’ experience managing cancer patients, while 43% had less than five years’ experience. All of the respondents are involved in the chemotherapy administration while only about half are involved in the screening and diagnosis of cancer patients. Ninety-three percent report using guidelines in managing patients and the top 3 guidelines used were National Comprehensive Cancer Network (90%), American Society of Clinical Oncology (50%) and European Society of Medical Oncology (46%). The major three barriers to guideline utilization were inadequate facilities for proper guideline implementation, the guideline is not applicable to setting and information in guideline is overwhelming. Potential facilitators include providing adequate facilities, developing local guidelines and increase awareness on the use of guidelines. Almost all respondents are in favour of using guidelines that are adapted to their practice setting. Conclusions: Our study shows that clinicians involved in the management of cancer patients in a LMIC are aware of cancer treatment guidelines. However, issues like inadequate facilities, inapplicability of guideline to local setting and complexity of information in guidelines hinder their usage.
Abstract 18784: Identification of Long Non Coding RNAs Associated to Mesendoderm Differentiation and Cardiovascular Commitment of Early Precursors Generated by Naïve Mouse Embryonic Stem Cells
Authors: Chiara Cencioni, Francesco Spallotta, Matteo Savoia, Carsten Kuenne, Stefan Guenther, Agnese Re, Susanne Wingert, Maike Rehage, Duran Sürün, Johanna Heid, Frank Schnütgen, Harald von Melchner, Michael A Rieger, Fabio Martelli, Antonella Farsetti, Thomas Braun, Andreas M Zeiher, Carlo Gaetano
Journal: Circulation (2016)

Introduction: Nitric oxide (NO) negatively regulates the zinc-finger E-box binding homeobox 1 and 2 (Zeb1, 2) factors via upregulation of miR-200 family members. Although Zeb1, 2 are well known ind...
SM88 in non-metastatic rising PSA-recurrent prostate cancer.
Authors: Giuseppe Del Priore, Gerald H. Sokol, Wen-Tien Chen, Che-Kai Tsao, Steve Hoffman
Journal: Journal of Clinical Oncology (2017)

e16567 Background: SM88 is a novel combination of substituted amino acid ( AA) and repurposed agents with non-toxic activity in a variety of cancers including prostate (PC). Non-metastatic biochemically recurrent PC (nmPC) is ideal for such a well-tolerated, non-androgen based treatment. We present biomarker activity including CTCs (circulating tumor cells) after completion of the Ib dose escalating pharmacokinetic portion of the SM88 development plan. Methods: Planned analysis of an ongoing prospective Phase Ib/II open label study of nmPC (PCWG3 definition). Subject 1 received the 1 st dose level of AA, and others received 2x dose. All subjects also received a combination of low dose re-purposed CYP3a4 inducer, oxidative stress catalyst, and mTOR inhibitor. Results: Four subjects completed at least 1 cycle (28d) with all PK sampling as prespecified. Median age was 73(70-80); all had prior ADT that was discontinued 3-6 yrs earlier, and either had curative intent prostatectomy (n = 2) or RT (n = 2); Testosterone level was castrate in one after prior RT. CTCs fell (p &lt; 0.01) to undetectable (n = 1) or by &gt; 25% (n = 3) (see table) while PSA remained stable (PCWG3 criteria). Preliminary LDH, neutrophil/lymphocyte ratio (N:L), urinary NTx, bone specific AlkPhos (bAP) trends are in the table below. There were no drug related serious adverse events (2 grade: 1- pigmentation, 1- vasomotor). EORTC-QLQ30 and PR25 scores were either improved or stable. Conclusions: Treatment with SM88 in patients with nmPC in the completed phase Ib cohort was associated with CTC reduction, and stable biomarker trends including PSA and LDH. There was no significant toxicity or adverse patient reported outcomes. Based on these results, the dose escalation was stopped at the second level and a cohort expansion phase II initiated. A phase III RCT is planned for confirmation of these results. Clinical trial information: NCT02796898. [Table: see text]
Feasibility of a self-administered geriatric assessment (GA) tool for Spanish-speaking older adults with breast cancer (BC).
Authors: Enrique Soto Perez De Celis, Jessica Vazquez, Heeyoung Kim, Can-Lan Sun, George Somlo, Yuan Yuan, James Ross Waisman, Joanne E. Mortimer, Laura Kruper, Lesley Taylor, Niki Himat Patel, Jeanine Moreno, Kemeberly Charles, Elsa Roberts, Carolina Uranga, Abrahm Levi, Vani Katheria, Irene Paredero Pérez, Dale Mitani, Arti Hurria
Journal: Journal of Clinical Oncology (2018)

e18672 Background: By 2060, nearly a quarter of older adults in the US will identify themselves as Hispanic/Latino. We have previously developed a self-administered GA tool which can be used to identify functional, psychological, social and cognitive vulnerabilities in older adults with cancer. Among English-speaking older adults, answering this tool using a tablet or paper/pencil takes a median of 15-21 minutes (min), and < 10% need assistance to complete it (Hurria, JOP 2016). However, this tool has not been tested in Spanish-speaking older adults. We assessed the feasibility of administering a translated and validated Spanish version of our GA tool for older Hispanic patients with BC, and identified their preferred format (tablet or paper/pencil). Methods: Spanish-speaking women with BC aged ≥ 65 years (y) completed the GA twice on the same day. Patients were randomized into 3 groups: tablet twice; tablet and paper/pencil in random order; and paper/pencil twice. We assessed the proportion of patients requiring assistance to complete the GA, the time needed to complete it, and the proportion of patients who thought it was difficult/very difficult. Results: 143 patients were approached, of which 121 agreed to participate and 117 completed the GA at least once. Median age was 69 y (range 65-95), 57% had ≤ 8th grade education, and 72% were born in Mexico. 38% (n = 45) were unable to complete the GA on their own; median time to complete the GA was 30 min (range 8-90); and 27% (n = 32) thought the GA was difficult/very difficult. The most common reasons for needing assistance were difficulty understanding questions (38%) and visual problems (36%). Patients with ≤ 8th grade education took longer to complete the GA (median 34 vs 24 min, p = 0.01), and needed more assistance (51% vs 21%, p = 0.001) than those with ≥9th grade education. 55% preferred using a tablet to answer the GA, while 45% preferred paper/pencil. Conclusions: A significant proportion of Spanish-speaking older women needed assistance to complete the self-administered GA tool, which may be attributable to low educational levels. In order to increase access to care in multicultural environments, assessments need to be tailored for diverse populations.
Validation of activated molecular pathways in non-T cell-inflamed urothelial bladder cancer (UBC).
Authors: Randy F. Sweis, Riyue Bao, Stefani Spranger, Gladell Paner, Walter Michael Stadler, Gary D. Steinberg, Thomas Gajewski
Journal: Journal of Clinical Oncology (2016)

e23114 Background: We recently characterized oncogenic pathways linked with non-T cell-inflamed UBC in order to better understand mechanisms of primary immunotherapy resistance. To further investigate the robustness of our findings, we performed a validation analysis on an independent data set and examined human tissue samples by immunohistochemistry (IHC). Methods: Affymetrix microarray files were downloaded from the GEO database (GSE 31684) and preprocessed to generate normalized gene expression values (20,390 genes). Consensus clustering of 93 samples was conducted using 725 genes from our prior analysis of TCGA UBC, a 160 gene set developed across multiple cancer types, or 1,729 genes identified in GSE 31684 using previously described methods (Sweis, et al. ASCO 2015). Three distinct immune subtypes were identified based on gene expression. Differentially expressed genes (DEGs) were filtered by FDR-adjusted P-value < 0.01 and fold change ≥ 1.5. Enriched pathways were identified by Ingenuity Pathway Analysis (IPA). IHC was performed with β-catenin antibody clone CAT-5H1, Life Tech. Results: We first verified the reliability of our methodology by comparing three separate gene lists derived from our T cell gene signature. We found 75% (70/93) of samples clustered into an identical subtype by all three methods. 38% of samples were categorized as non-T cell-inflamed and 22% were T-cell inflamed with concordance across all methods. IPA analysis of DEGs in non-T cell-inflamed tumors confirmed β-catenin and PPARG as top activated regulators (P < 0.0001), with 10 and 6 downstream genes overlapping with our TCGA analysis, respectively. SMARCA4 also emerged as an activated regulator, which is reported to facilitate β-catenin transcriptional activity. Finally, we evaluated β-catenin by IHC and noted 43% of non-T cell-inflamed tumors showed nuclear staining, which was associated with lack of CD8+ T cell infiltration (P = 0.036). Conclusions: We confirm that T cell-inflamed and non-T cell-inflamed UBC can be identified by gene expression with high fidelity. Beta-catenin and PPARG pathways are activated in non-T cell-inflamed UBC across multiple independent data sets, with β-catenin confirmed at the protein level.
Hypomethylation and presence of human endogenous retroviruses –h and –k in the extracellular microvescicles of colon cancer patients.
Authors: Serena del Bue, Maria Dolci, Letizia Tarantini, Valentina Bollati, Chiara Favero, Sonia Villani, Alberto della Valle, Pietro F. Bagnoli, Rosalia Ticozzi, Pasquale Ferrante, Filippo Crivelli, Marco Bregni
Journal: Journal of Clinical Oncology (2018)

e24071 Background: Human Endogenous Retroviruses (HERVs) are remnants of ancient exogenous retroviral infections of the humans, representing 8% of the human genome. Their regulation is based on epigenetic mechanisms, such as methylation of the Long Terminal Repeats (LTRs). Few reports have shown the relationship between the HERVs expression and colorectal cancer (CRC), based on mRNA and/or protein expression profile in normal and cancer tissues, but conclusive evidences are still lacking. Methods: The expressions of the env region of HERV-H, -K, -P, and –R were evaluated in the tumor, in the adjacent normal tissues, in the blood and in the extracellular microvesicles (EV) of 63 CRC patients. All samples were retrieved during routine surgical procedures. RNA was isolated from the clinical specimens, reverse transcripted, and subjected to relative quantitative Real-time PCR. The env expressions were related to the GAPDH gene expression and analyzed by a linear regression model for repeated measures. Methylation status of the HERV LTRs was evaluated by bisulfite-PCR, pyrosequencing and the differences were analyzed using generalized mixed linear models. The correlation between HERVs expression levels and methylation was evaluated by Spearman’s correlation index. Results: No differences were observed in the expression of HERVs env genes in the samples, but HERVs expression levels correlated each other in the tumor tissues (p < 0.001). HERV-H and -K LTRs were significantly (p < 0.0001) hypomethylated in the tumor tissues (56.1% and 54.0% respectively) compared to adjacent tissues (72.5% and 56.6% respectively). The env sequences were present in the EVs of 54% (-H), 38% (-K), 31% (-R), 4% (-P) patients. Conclusions: HERVs expression levels did not significantly differ among the clinical samples. Demethylation of HERV-H and -K LTRs might support the hypothesis of specific liberation of HERV-H and -K LTRs from epigenetic controls in CRC. EV influence tumor microenvironment and support cancer growth and metastasis: HERV-H and -K sequences present in the circulating plasma microvesicles may be transferred from one cell to another, and favour cellular transforming mechanisms.
Abstract 11965: Cardiovascular Risk Factor Reduction Through a Paleolithic Diet
Authors: Connor McKechnie, Madeline McKechnie, Julia McKechnie, Ronald McKechnie, Deepak Talreja
Journal: Circulation (2015)

Introduction: The paleolithic diet consists of grass-fed pasture-raised meats, seafood, vegetables, and also includes fruits, seeds, nuts and eggs. This diet has been shown to contribute to weight loss and mimics the diet our hunter-gatherer ancestors may have consumed. Weight loss is achieved through avoiding refined sugars, starches, dairy and legumes while consumption of protein, carbohydrates, and fat is relatively balanced. Objective: To study the effect of the paleolithic diet on the cardiovascular risk factor profiles of adults in the Hampton Roads area of Virginia. Methods: 35-85 year old non-diabetic adults, with one or more cardiovascular risk factor, were invited to participate. A comprehensive nutritional education program was provided to each participant prior to the 60-day intervention. Baseline weight, blood pressure, fasting glucose, hemoglobin A1c, high-sensitive C-reactive protein, fasting lipid panel and NMR Lipoprofile were assessed through an initial health screen. Each participant maintained daily food logs and met weekly with the multi-disciplinary study team to review their logs. The health screen was repeated after the 60-day intervention and intake logs were evaluated. Results: Weight loss averaged 12 lbs (6.7%, p=0.092). VLDL-particle number (VLDL-P, p=0.045), triglycerides (p=0.003), and HDL-particle number (p=0.011) levels significantly decreased. LDL-particle number (LDL-P) and LDL-cholesterol (LDL-C) did not significantly change, nor did fasting glucose or HbA1c. Blood pressure significantly improved (systolic, p&lt;0.0001; diastolic, p=0.0003). Participants in the lowest tertile for weight loss had higher baseline risk factors including BMI, LDL-P, LDL-C, fasting glucose and HbA1c levels, yet lower baseline VLDL-P, triglycerides and blood pressure. Greater weight loss was associated with greater reductions in VLDL-P, triglycerides and lipoprotein insulin resistance index. Conclusions: The paleolithic diet promoted cardiovascular risk factor modification through weight loss, improved blood pressure, reduced triglyceride, and reduced lipoprotein markers associated with insulin resistance.
The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: A meta-analysis.
Authors: Tengfei Zhang, Ruitai Fan, Ni Shi, Wang Ma
Journal: Journal of Clinical Oncology (2017)

e23075 Background: Immunotherapy based on anti-PD-1 (Programmed death 1)/PD-L1 (PD-1 Ligand 1) antibodies have achieved significant successes from bench to clinic. In this study, we systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. Methods: Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate. Results: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53-2.41, P&lt; 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22-29.75, P= 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46-3.40, P&lt; 0.001), reduced death risk (HR = 0.53; 95% CI: 0.48-0.57; P&lt; 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30-0.80, P= 0.004) compared with other therapies. Conclusions: Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers. PD-L1 expression was associated with better clinical response of anti-PD-1/PD-L1 antibody based immunotherapy.
TCT-368 Feasibility and Outcomes of Endovascular Treatment of Infrapopliteal Peripheral Arterial Disease in Patients with Critical Limb Ischemia: Retrograde Tibiopedal Access Approach
Authors: Apurva Patel, Roosha Parikh, Zoltan Ruzsa, Tak Kwan
Journal: Journal of the American College of Cardiology (2018)
Plasma biomarker for detection of early-stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-A2 isoforms.
Authors: Kazufumi Honda, Michimoto Kobayashi, Takuji Okusaka, Chigusa Morizane, Jo Ann Rinaudo, Ying Huang, Tracey Marsh, Masashi Shimahara, Takaaki Ueno, Akihiko Tsuchida, Naohiro Sata, Tatsuya Ioka, Tomoo Kosuge, Yohichi Yasunami, Masaru Yoshida, Takeshi Azuma, Sudhir Srivastava, Tesshi Yamada
Journal: Journal of Clinical Oncology (2016)

4106 Background: We have previously revealed that circulating levels of apolipoprotein A2 (apoA2) isoforms apoA2-ATQ/AT (C-terminal truncations of apoA2 homo-dimer) are significantly decreased in early-stage pancreatic cancer in comparison with healthy controls on mass spectrometry (MS)-based assays. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measuring apoA2-ATQ/AT and their clinical applicability for the early detection of pancreatic cancer. Methods: Plasma and serum concentrations of apoA2-isoforms were measured in three independent cohorts (two Japanese cohorts and one pancreatic reference set collected by the US National Cancer Institute’s Early Detection Research Network (NCI EDRN), each comprising healthy control subjects and patients with pancreatic cancer or gastroenterological disease (n = 1156). These cohorts included 151 cases of stage-I/II pancreatic cancer. Results: Significant reductions in apoA2-ATQ/AT levels were recognized in patients with pancreatic cancer in comparison with healthy controls in both independent Japanese cohorts (p = 1.34*10-18 and 5.09*10-39). Areas under the receiver operating characteristic curve (AUCs) were > 0.92 for distinguishing patients with stage-I/II pancreatic cancer from healthy controls in the Japanese cohorts. The AUCs of apoA2-ATQ/AT to distinguish patients with pancreatic cancer from healthy controls were higher than those of CA19-9 in both Japanese cohorts. Better discrimination of pancreatic cancer was also observed with apoA2-ATQ/AT than with CA19-9 in the blind test using NCI EDRN data; combining apoA2-ATQ/AT with CA19-9 led to significantly improved AUC compared to CA19-9 alone Conclusions: ELISA for apoA2-isoforms offers a good biomarker for early detection of pancreatic cancer. We have started experimental screening for pancreatic cancer in the Kobe Cancer Screening Network.
What do social media-savvy cancer survivors tell us about the completeness of survivorship care plans?
Authors: Diane Mary Radford, Alicia C. Staley, Jeffrey Landercasper, Leah L. Dietrich, Choua A Vang, Andrew Borgert, Deanna J. Attai
Journal: Journal of Clinical Oncology (2017)

10063 Background: The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of curative treatment. Both the CoC and ASCO have recommended minimum requirements for SCPs, which should include both a treatment summary and follow up care plan. Many cancer patients use social media (SM) as a way to obtain support and information. We have shown previously that the majority of SM savvy cancer survivors (88.2%) do not receive SCPs ( J Clin Oncol 35, 2017 suppl 5S; abstr 104). We sought to determine the contents of the SCPs received. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey from 3/21/2016 to 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Results: A total of 312 patients responded. 63% (194) had completed curative treatment (excluding endocrine therapy). Of these 11.8% (23) reported receiving an SCP at the end of treatment. Of 22 patients who responded, 9/22 (40.9%) found the SCP helpful, 11/22 (50.0%) somewhat helpful, and 2/22 (9.1%) not helpful. The table below shows the components of those SCPs received. Conclusions: Not only did a small percentage of patients receive SCPs but also no patient received a complete SCP per the CoC and ASCO recommendations. Particularly deficient was a description of late/long-term effects of treatment—only 36% received such information. Challenges exist in the delivery of complete SCPs. [Table: see text]