tbuckley/cabot-search huggingface dataset:
Measurement of person-centered care delivery of adult oncology in Ontario, Canada.
Authors: Lesley Moody, Erica Bridge, Suman Dhanju, Brett Nicholls, Simron Singh
Journal: Journal of Clinical Oncology (2017)

223 Background: In the Ontario, Canada, cancer system, the provincially endorsed Person Centred Care (PCC) Guideline provides recommendations for healthcare providers to implement PCC in the delivery of adult oncology services. However, it is unknown whether healthcare providers have incorporated these recommendations into their daily practice within the Regional Cancer Programs (RCPs). The purpose of this study was to develop an assessment tool to evaluate the implementation of the PCC Guideline in Ontario RCPs. Methods: Tool development consisted of a 3-step process: 1) literature review to identify relevant measures, 2) Modified Delphi with a panel of experts (n = 8), and 3) focus groups with patient/family advisors (n = 5) and RCP PCC leads (i.e., designated individual responsible for PCC deliverables) (n = 7). Results: Through the literature review, two relevant tools were identified ( i.e., Institute for Patient- and Family-Centered Care’s Hospital Assessment Tool and Accreditation Canada’s Cancer Care Standards), resulting in 187 measures deemed appropriate to include in the assessment tool. In round one of the Modified Delphi, each measure was evaluated independently by a panel of experts using a 5-point Likert Scale (1 = strongly disagree to 5 = strongly agree) to assess both the importance and feasibility of each measure. Sixty-seven measures were rated 4 or above by 70% of the experts. Consistent with Modified Delphi best practice, these measures were discussed during the second round with the panel of experts. An additional 33 measures were removed due to similarities/duplications. Nine measures were added. The 42 measures were presented to patient/family advisors and the RCP PCC Leads during focus groups and evaluated based on importance and feasibility of assessing PCC implementation in the RCPs. Wording recommendations were made and two additional measures were added. The final tool includes 44 measures to evaluate PCC implementation within the RCPs. The assessment tool was disseminated to the 14 RCPs in October 2016. Conclusions: The results of this assessment will provide an understanding of the current state of PCC Guideline implementation in Ontario, in order to identify facilitators and barriers to implementation.
End-of-Life Racial and Ethnic Disparities Among Patients With Ovarian Cancer
Authors: Jolyn S. Taylor, Suja S. Rajan, Ning Zhang, Larissa A. Meyer, Lois M. Ramondetta, Diane C. Bodurka, David R. Lairson, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2017)

Purpose To assess disparities in end-of-life care among patients with ovarian cancer. Patients and Methods Using Texas Cancer Registry-Medicare data, we assessed patients with ovarian cancer deceased in 2000 to 2012 with at least 13 months of continuous Medicare coverage before death. Descriptive statistics and multivariate logistic regressions were conducted to evaluate end-of-life care, including chemotherapy in the final 14 days of life, intensive care unit (ICU) admission in the final 30 days of life, more than one emergency room (ER) or hospital admission in the final 30 days of life, invasive or life-extending procedures in the final 30 days of life, enrollment in hospice, enrollment in hospice during the final 3 days of life, and enrollment in hospice while not hospitalized. Results A total of 3,666 patients were assessed: 2,819 (77%) were white, 553 (15%) Hispanic, 256 (7%) black, and 38 (1%) other. A total of 2,642 (72%) enrolled in hospice before death, but only 2,344 (64%) died while enrolled. The median hospice enrollment duration was 20 days. In the final 30 days of life, 381 (10%) had more than one ER visit, 505 (14%) more than one hospital admission, 593 (16%) ICU admission, 848 (23%) invasive care, and 418 (11%) life-extending care. In the final 14 days of life, 357 (10%) received chemotherapy. Several outcomes differed for minorities compared with white patients. Hispanic and black patients were less likely to enroll and die in hospice (black odds ratio [OR], 0.66; 95% CI, 0.50 to 0.88; P = .004; Hispanic OR, 0.76; 95% CI, 0.61 to 0.94; P = .01). Hispanic patients were more likely to be admitted to an ICU (OR, 1.37; 95% CI, 1.05 to 1.78; P = .02), and black patients were more likely to have more than one ER visit (OR, 2.20; 95% CI, 1.53 to 3.16; P < .001) and receive a life-extending procedure (OR, 2.13; 95% CI, 1.49 to 3.04; P < .001). Conclusion We found being a minority was associated with receiving intensive and invasive end-of-life care among patients with ovarian cancer.
MR-guided radiation therapy: transformative technology and its role in the central nervous system
Authors: Yue Cao, Chia-Lin Tseng, James M. Balter, Feifei Teng, Hemant A. Parmar, Arjun Sahgal
Journal: Neuro-Oncology (2017)

This review article describes advancement of magnetic resonance imaging technologies in radiation therapy planning, guidance, and adaptation of brain tumors. The potential for MR-guided radiation therapy to improve outcomes and the challenges in its adoption are discussed.
Metformin effects on cancer adjacent breast preneoplasia in a randomized pre-surgical trial.
Authors: Andrea De Censi, Matteo Puntoni, Giancarlo Pruneri, Massimiliano Cazzaniga, Andrea Vingiani, Davide Serrano, Aliana Guerrieri-Gonzaga, Oreste Davide Gentilini, Harriet Ann Johansson, Valentina Aristarco, Matteo Lazzeroni, Clara Varricchio, Bernardo Bonanni
Journal: Journal of Clinical Oncology (2013)

1517 Background: Metformin has been associated with a significant reduction in cancer incidence and mortality in diabetic patients, including positive results in breast cancer. In a window-of-opportunity trial in 200 non-diabetic women with breast cancer, we showed a heterogeneous effect of metformin on breast cancer proliferation (Ki-67) depending on insulin resistance, with a trend to a decreased proliferation in women with insulin resistance (HOMA&gt;2.8) and an opposite trend in women with normal insulin sensitivity (Bonanni et al. JCO 2012). Here we determined whether metformin has antiproliferative effects on adjacent lobular or ductal intraepithelial neoplasia (LIN or DIN) and on distant ductal hyperplasia and whether these effects are different according to specific host and tumor characteristics. Methods: Baseline core biopsies of tumor tissue and blood samples were obtained at study entry and before surgery for pre/post-treatment comparisons. Patients were randomly assigned to metformin, 850 mg or placebo once daily on day 1-3 followed by two 850 mg tablets from day 4 to 28. At surgery, three to five specimens of adjacent (≤1 cm from the tumor) and distant (&gt;1 cm from the tumor) grossly normal tissue were obtained to assess systematically the prevalence, grade and proliferation of LIN or DIN and ductal hyperplasia. Results: Overall, the prevalence of LIN, DIN and ductal hyperplasia was 4.5% (9/200), 66.5% (133/200) and 35% (69/200), respectively. Ki-67 was positively associated with DIN grade (p-trend&lt;0.001). The median (and IQ range) Ki-67 LI distribution of LIN+DIN was 12% (8-20) and 10% (6-22) on metformin and placebo, respectively (p=0.6). Compared with placebo, metformin exhibited different effects on Ki-67 according to DIN grade (delta=+4.4% in DIN1 vs -27.9% in DIN3, p-interaction=0.09), cancer HER2 status (median 12% vs. 10% in HER2-ve; 28% vs. 35% in HER2+ve, p=0.03), abdominal circumference (p=0.08), and BMI (p=0.17). Conclusions: Metformin had no overall significant effect on breast preneoplasia proliferation but exhibited heterogeneous effects depending upon host and tumor characteristics. The significant reduction of HER2+ve, DIN3 proliferation under metformin warrants further studies. Clinical trial information: 16493703.
Biohybrids: Multicellular Biohybrid Materials: Probing the Interplay of Cells of Different Types Precisely Positioned and Constrained on 3D Wireframe‐Like Microstructures (Adv. Healthcare Mater. 7/2017)
Authors: Maurizio R. Gullo, Shoji Takeuchi, Oliver Paul
Journal: Advanced Healthcare Materials (2017)

One to trap them, one to guide them and one to rule them all – To ensure the proper functioning of biohybrid microsystems featuring multiple types of cells, a predefined cell arrangement needs to be maintained over time. Article number 1601053 by M. R. Gullo and co-authors presents novel wireframe-like 3D microscaffolds inspired by the extracellular matrix and capable of trapping cells, guiding cell migration and preserving the specific arrangement of multiple cell types.
Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
Authors: Jennifer Ose, Elizabeth M. Poole, Helena Schock, Matti Lehtinen, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Kala Visvanathan, Kathy Helzlsouer, Julie E. Buring, I-Min Lee, Anne Tjønneland, Laure Dossus, Antonia Trichopoulou, Giovanna Masala, N. Charlotte Onland-Moret, Elisabete Weiderpass, Eric J. Duell, Annika Idahl, Ruth C. Travis, Sabina Rinaldi, Melissa A. Merritt, Britton Trabert, Nicolas Wentzensen, Shelley S. Tworoger, Rudolf Kaaks, Renée T. Fortner
Journal: Cancer Research (2017)

Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, OR
Phase IB study of olaparib (AZD2281) plus gefitinib in EGFR-mutant patients (p) with advanced non-small-cell lung cancer (NSCLC) (NCT01513174/GECP-GOAL).
Authors: Rosario García Campelo, Enriqueta Felip, Bartomeu Massuti, Margarita Majem, Enric Carcereny, Felipe Cardenal, Miguel Angel Molina-Vila, Alex Martinez Marti, Juan Luis Marti-Ciriquian, Guillermo Alonso-Jaudenes Curbera, Cinta Pallares, Ramon Palmero, Maria Carmen Gonzalez-Arenas, Clara Mayo-de las Casas, Maria Sanchez-Ronco, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

2581 Background: Progression-free survival (PFS) and response to EGFR tyrosine kinase inhibitors (TKIs) vary in p with NSCLC driven by EGFR mutations. In our experience, high BRCA1 mRNA expression was associated with shorter PFS in EGFR-mutant p treated with erlotinib. We hypothesized that since olaparib downregulates BRCA1 expression, the addition of olaparib to gefitinib could improve PFS in these p. Methods: This is a Phase IB dose escalation study to identify the maximum tolerated dose (MTD), dose limiting toxicity (DLT), pharmacokinetics, and clinical activity of orally administered olaparib in combination with gefitinib in EGFR-mutant advanced NSCLC p. In a standard 3+3 design, p were treated with gefitinib 250mg once daily plus olaparib tablets at escalating doses ranging from 100mg BID to 250mg TDS during a 28-day cycle. Results: 18 p have been included across four dose levels of olaparib: 100mg BID (3), 200mg BID (6), 200mg TDS (3) and 250mg TDS (6). Median age, 69; male, 4; PS 0, 17; EGFR TKI treatment-naïve, 10. Toxicities: anemia (66.6%), leucopenia (33.3%), nausea (33.3%), diarrhea (33.3%), asthenia (27.7%), rash (22.2%) vomiting (11%), decreased appetite (16%), and hyperlipasemia (5.5%). Most toxicities were G1-2; G3 drug-related events included leucopenia (1) and anemia (3). No DLT at dose levels 1, 2, and 3; 1 DLT at dose level 4 (G3 anemia and repeated blood transfusion within 4-6 weeks). Few dose reductions or interruptions were needed. 1 p died due to pulmonary embolism unrelated to treatment. Partial responses (PR) were observed in 7 p (41.1%), all EGFR TKI-naïve; stable disease (SD) in 7 (41.1%), most previously treated; progressive disease (PD) in 3 (17.6%), all previously treated. Durable PR and SD were observed in EGFR TKI-naïve and previously treated p. 8 patients are still on treatment. Enrollment to dose level 4 will be completed in February 2013. Conclusions: This phase IB trial of gefitinib plus olaparib, has confirmed the activity and tolerability of the combination. The final recommended dose of olaparib is expected to be between 200 and 250 mg TDS. A phase II randomized trial in treatment-naïve EGFR-mutant advanced NSCLC will be opened in 2013. Clinical trial information: NCT0151317.
Abstract 19258: Altered Redox State Impairs the Functional Competence of Skeletal Muscle Pericytes in Patients With Complicated Type 2 Diabetes
Authors: Rosa Vono, Cesare Gargioli, Elena Sangalli, Davide Maselli, Ambra Gotti, Sergio Losa, Gaia Spinetti, Paolo Madeddu
Journal: Circulation (2015)

Introduction: Type 2 diabetes mellitus (T2D) in association with critical limb ischemia (CLI) is detrimental to skeletal muscle function and metabolism and compromises muscle intrinsic regenerative ability. Hypothesis: Assess whether T2D+CLI negatively impact on muscular regenerative cells such as muscle pericytes (MPs) functional properties. Methods: Skeletal muscle biopsies were obtained under ethical approval at occasion of osteosarcoma diagnosis (H-MPs, n=8 ) or major amputation (T2D+CLI-MPs, n=11). MPs were characterized by flow cytometry (CD90, CD44, and Alkaline Phosphatase-AP), immunofluorescence (PDGFR-β, α-SMA, CD146, and NG2) and immunicytochemistry (AP). MP proliferation (BrdU assay), migration (scratch assay), apoptosis (caspase assay), myogenic differentiation (myosine heavy chain-MyHC staining), HUVECs tubulogenesis (Matrigel) and ROS production (MitoSox-Red) were assessed in vitro in at least n=3 donors per group. Molecular analysis were performed by RT-PCR. Results: Both H-MPs and T2D+CLI-MPs expressed typical pericyte markers, but T2D+CLI-MPs proliferated slowly (0.16±0.06 vs. 1.98±0.46 vs. H-MPs) and differentiated less into MyHC positive fibres (4.78±0.34 vs. 16.15±5.032 vs. H-MPs) while migration and apoptosis were not modified. The addition of T2D+CLI-MPs or their conditioned media to HUVECs impaired endothelial tubulization on Matrigel (respectively 10.40±1.39 vs. 13.73±0.64, and 11.88±1.04 vs. 16±1.4, vs. HUVECs alone). Furthermore ROS content increased in T2D+CLI-MPs (3.70±0.45 vs. 0.57±0.24, vs. H-MPs) and was associated with a down-regulation of SOD-1 (0.53±0.11 vs. 1.03±0.11) and catalase (0.41±0.1 vs. 0.97±0.2 vs. H-MPs) and an up-regulation of p66Shc (2.84±0.6 vs. 0.81±0.02 vs. H-MPs). Antioxidant treatment with N-acetylcysteine reverted altered proliferation (1.55±0.06 vs. 1.21±0.02) and antiangiogenic effect (13.63±1.00 vs. 7.367±0.75) compared to untreated counterparts. For all experiments significance was p&lt;0.05. Conclusions: T2D+CLI hampers MPs biological functions relevant to muscular repair. Reversion of T2D+CLI-MPs alterations by antioxidant treatment suggests possible therapeutic targets for attenuation of peripheral complications.
Phase I study of PS-341 (bortezomib) with 5-fluorouracil/leucovorin (5-FU/LV) in advanced solid tumors: A California Cancer Consortium study
Authors: S. Iqbal, S. Cole, D. Yang, P. N. Lara, P. H. Gumerlock, S. Shibata, T. Synold, J. H. Doroshow, D. Gandara, H. J. Lenz
Journal: Journal of Clinical Oncology (2004)

2057 Background: PS-341 inhibits the proteasome and the degradation of a number of proteins involved in cell cycle regulation, apoptosis and cell adhesion. PS-341 was combined with 5-FU/LV, to find the maximum tolerated dose (MTD) and investigate pharmacodynamics. Previously we reported interim results of this trial (Iqbal et al; Proc ASCO 2002). We are now reporting the final results. Methods: PS-341 was administered IV bolus in escalating doses (0.5 mg/m2, 0.7 mg/m2, 1.0 mg/m2, 1.3 mg/m2) twice weekly, with weekly 5-FU 500 mg/m2/LV 20 mg/m2 for 4 weeks, with 2 weeks rest. Two patients (pts) were entered at each dose level (DL) until moderate toxicity was observed in 2 pts or dose-limiting toxicity (DLT) was observed in 1; thereafter the standard 3+3 design was used. Results: Twenty-one pts were entered: 12 males, 9 females; median age: 58 (range 43–84) years; 15 colorectal primary; 2 unknown; and 1 esophageal, breast, pancreatic and anal. Pts received a median of 3 (range 0 –4) prior chemotherapeutic regimens for advanced disease. Two, 7, 9, and 3 pts entered dose levels 1, 2, 3, and 4, respectively. One pt at DL 2 and 3 pts at DL 3 did not complete Cycle 1 and were inevaluable for toxicity. All DLT's were Grade 3. Two pts at DL 4 experienced DLTs (Pt1: abdominal pain or cramping; Pt2: anorexia, dehydration, diarrhea). DL 3 was then expanded, at which 2 pts experienced DLTs (Pt1: abdominal pain or cramping; Pt2: dehydration, depressed level of consciousness, fatigue, hypoxia, anorexia, dyspnea, nausea). DL 2 was then also expanded, at which only 1 pt experienced DLTs (vomiting, nausea, fatigue, headache, anorexia). The MTD was determined to be DL 2. Interestingly, peripheral neuropathy was not a DLT in this trial. Pts received a median of 2 (range 1–4) cycles of chemotherapy. Nineteen pts were evaluable for response: 1 partial response (esophageal) at DL 4; 8 stable disease (7 colorectal, 1 anal) at DLs 1–4; 10 progressive disease. Conclusions: PS-341 0.7 mg/m2, when given twice weekly with once weekly 5-FU 500 mg/m2/LV 20 mg/m2 for 4 weeks, followed by 2 weeks rest is a safe regimen for Phase II testing. Grant#: U01CA62505 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Millennium; Sanofi Millennium
Exploring the Link between the Germline and Somatic Genome in Cancer
Authors: Paul Geeleher, R. Stephanie Huang
Journal: Cancer Discovery (2017)

<b/> Carter and colleagues propose a systematic analysis of the germline and somatic genome in cancer. They identify interactions that occur between germline and somatic variants. This elucidates the function of the germline genome in the context of cancer risk and development. Cancer Discov; 7(4); 354-5. ©2017 AACRSee related article by Carter et al., p. 410.
Increasing food security and nutrition resilience in response to climate change in east Africa: findings from a multisectoral symposium
Authors: Paula Braitstein, Tenzin Lama, Susan Keino, Branka Gladanac, Faith Yego, Donald Cole, John Simiyu Tabu, Andrea Cortinois, Carren Tarus, Ann Fox
Journal: The Lancet Global Health (2017)

BackgroundThe symposium Kuwa Tayari ("be prepared" in English): finding pathways to nutrition and food security resilience in response to climate change in East Africa was held in Eldoret, Kenya, in May, 2016. The goals of this symposium were to increase awareness, stimulate research ideas and recommendations, catalyse the development of training opportunities, and provide an evidence base for policy and decision-making in these regions in preparation for, and response to, our changing world. Here, we describe the structure, aims, and outcome of the symposium.MethodsThe 2-day symposium was a partnership initiative between University of Toronto Dalla Lana School of Public Health in Toronto, Canada, and Moi University, College of Health Sciences, School of Public Health in Eldoret, Kenya. Target audiences were scientists, students, and educators in public health, environmental studies, agriculture, agroecology, civil society, non-government organisations, and government stakeholders. Symposium organisers did a literature review to develop a background paper that helped inform the selection of five planetary health subthemes of the symposium: (1) agriculture, nutrition, and agro-biodiversity; (2) water security; (3) renewable and sustainable cooking fuels; (4) nutrition and food security issues affecting vulnerable populations; and (5) human rights and sustainable development. The symposium format consisted of keynote and oral abstract presentations, plenary discussions, small group work, poster viewing sessions, and networking opportunities. A final report was produced to highlight key outcomes and recommendations.FindingsThere were 121 attendees at the symposium from 26 institutions in Kenya, Uganda, Canada, USA, and elsewhere; most were from academic and community organisations. Participants' reasons for attending were met: personal growth and development, networking, research, course and training ideas, and potential collaborations. There was consensus on the need to invest in innovative, context-specific, climate-smart agricultural practices that support sustainable livelihoods and development, and improve food security at the household level throughout east Africa.InterpretationMultisectoral, transdisciplinary, community-based, and population health research and interventions are needed to address the complex and interconnected issues of climate change, nutrition, and food security. Within east Africa, participatory initiatives that engage vulnerable populations (such as women, pastoral populations, and the urban poor), and those that integrate indigenous food system practices are crucial. Training priorities should be in the areas of integration of climate change topics into existing public health curriculums, and novel interdisciplinary courses on planetary health.FundingCanadian Institutes of Health Research.
The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival
Authors: Eric M Thompson, Stephen T Keir, Talaignair Venkatraman, Christopher Lascola, Kristen W Yeom, Andrew B Nixon, Yingmiao Liu, Daniel Picard, Marc Remke, Darell D Bigner, Vijay Ramaswamy, Michael D Taylor
Journal: Neuro-Oncology (2017)

Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survival in Group 3 medulloblastoma.VEGFA mRNA expression and survival from several patient cohorts were analyzed. Group 3 xenografts were implanted intracranially in nude rats. Dynamic susceptibility weighted (DSC) MRI and susceptibility weighted imaging (SWI) were obtained. DSC MRI was used to calculate relative cerebral blood volume (rCBV) and flow (rCBF). Tumor vessel density and rat vascular endothelial growth factor alpha (VEGFA) expression were determined.Patient VEGFA mRNA levels were significantly elevated in Group 3 compared with the other subgroups (P < 0.001) and associated with survival. Xenografts D283, D341, and D425 were identified as Group 3 by RNA hierarchical clustering and MYC amplification. The D283 group had the lowest rCBV and rCBF, followed by D341 and D425 (P < 0.05). These values corresponded to histological vessel density (P < 0.05), rat VEGFA expression (P < 0.05), and survival (P = 0.002). Gene set enrichment analysis identified 5 putative genes with expression profiles corresponding with these findings: RNH1, SCG2, VEGFA, AGGF1, and PROK2. SWI identified 3 xenograft-independent categories of intratumoral vascular architecture with distinct survival (P = 0.004): organized, diffuse microvascular, and heterogeneous.Angiogenesis plays an important role in Group 3 medulloblastoma pathogenesis and survival. DSC MRI and SWI are clinically relevant biomarkers for tumor vascularity and overall survival and can be used to direct the use of antivascular therapies for patients with Group 3 medulloblastoma.