tbuckley/cabot-search huggingface dataset:
Analysis of early distant metastases of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer.
Authors: Sara Lonardi, Luca Cionini, Francesca Di Fabio, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Katia Bencardino, Angiolo Tagliagambe, Michela Frisinghelli, Francesca Bergamo, Paola Rosetti, Andrea Bonetti, Maria Emanuela Negru, Maria Chiara Tronconi, Gabriele Luppi, Germana Chiaulon, Cristina Granetto, Rita Niespolo, Luca Boni, Carlo Aschele
Journal: Journal of Clinical Oncology (2016)

e15149 Background: Despite standard preoperative pelvic chemoradiation (CRT) and optimal surgery with total mesorectal excision (TME) leading to local recurrence rates below 5% in locally advanced rectal cancer (LARC), distant recurrences remain an issue in 20-30% of patients (pts). STAR-01 investigated the effect on overall survival (OS) of adding oxaliplatin (OXA) to preoperative (preop) CRT; the rate of pathological complete response was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904) (Aschele et al, J Clin Oncol, 2011). Methods: Pts with locally advanced (cT3-4 and/or cN1-2) resectable rectal adenocarcinoma within 12 cm from the anal verge were randomized to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused FU (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with OXA (60 mg/m(2) weekly × 6; arm B, n = 368), at 41 participating Institutions. Surgery was scheduled 6-8 weeks after completing CRT and 4 months of FU adjuvant monotherapy were advised in both arms. OS was the primary endpoint. An analysis of early distant progressions (eDR), defined as within 6 months from randomization, is the object of this report. Results: From November 2003 to August 2008, 739 eligible pts were randomized (arm A: 377, arm B: 362). Ninety-six percent versus 95% of pts underwent radical resection of their primary tumors.. A significant difference in the rate of eDR was observed with 23 events (6,1%) in arm A vs 7 (0,3%) in arm B (p =0.0046, Fisher's exact test). Five pts progressed before surgery, 16 had metastatic disease detected intraoperatively while 2 relapsed at distant sites immediately after surgery in arm A, compared to 1, 2 and 4 pts respectively in arm B. Grade 3 to 4 adverse events during preop treatment were more frequent with OXA plus FU and radiation than with radiation and FU alone (24% v 8% of treated patients; P < .001). Conclusions: Adding oxaliplatin to FU-based preoperative chemoradiotherapy significantly reduces early development of distant metastases in LARC, still this finding should be interpreted in the context of long term outcome (ASCO submitted).
Molecular and immune predictors of response and toxicity to combined CTLA-4 and PD-1 blockade in metastatic melanoma (MM) patients (pts).
Authors: Wei-Shen Chen, Miles Cameron Andrews, Christine Spencer, Hussein Abdul-Hassan Tawbi, Alexander Lazar, Michael T. Tetzlaff, Sapna Pradyuman Patel, Patrick Hwu, Wen-Jen Hwu, Adi Diab, Isabella Claudia Glitza, Rodabe Navroze Amaria, Elizabeth M. Burton, Scott Eric Woodman, Michael A. Davies, Jeffrey E. Gershenwald, Padmanee Sharma, James Patrick Allison, Andrew Futreal, Jennifer Ann Wargo
Journal: Journal of Clinical Oncology (2017)

9579 Background: Combined treatment with ipilimumab and nivolumab (Ipi/Nivo) achieves clinical responses in &gt; 50% of mm pts. However, responses are not universal and toxicity may be limiting, thus biomarkers of response and toxicity are needed to optimize and personalize this therapy. Methods: Tumor biopsies were collected before (n = 29) and on treatment (n = 7) from mm pts (n = 40) treated with Ipi/Nivo. Whole exome sequencing (WES), gene expression profiling, TCR sequencing, and immunohistochemistry (IHC) were performed to define molecular and immune features of the tumors. Radiographic responses in patients were assessed via RECIST 1.1criteria, and patients were classified as responders (R) deriving clinical benefit (with SD, PR, CR) and non-responders (NR) not deriving clinical benefit (PD). Toxicity was also scored, with patients dichotomized into low toxicity ( &lt; grade 2) versus high toxicity ( &gt; grade 3) re: immune-related (IR) toxicities. Results: In this cohort, the response rate was 80%, with 53% of patients experiencing &gt; grade 3 toxicity. There was no significant difference in baseline mutational load in responders (R) vs non-responders (NR) to Ipi/Nivo, but NR had a higher burden of copy number alterations (CNA; p = 0.013), with frequent alterations detected in PTEN, JAK2, and B2M. There were no significant differences in baseline CD8+ T cell density, expression of immune-related genes, or T cell clonality for R vs NR pts. Ipi/Nivo treatment increased intratumoral T cell clonality, but this did not correlate with response. A more diverse peripheral T cell repertoire at baseline was detected in pts who developed IR toxicity (p &lt; 0.05). Conclusions: This data suggests that responses to Ipi/Nivo in mm may occur in the absence of high mutational load or brisk immune infiltrate at baseline. Putative mechanisms of resistance to Ipi/Nivo include high burden of CNA and alterations in PTEN, JAK2, and B2M. Together these studies identify candidate biomarkers of resistance and toxicity for Ipi/Nivo, though they need to be tested in larger cohorts and across cancer types.
TCT-849 Safety of Transradial Access compared to Transfemoral Access with Hemostatic Devices (Vessel Plugs, Suture Devices &amp; Vascular Clips) after Percutaneous Coronary Interventions: A systematic review and meta analysis
Authors: Yashasvi Chugh, Chirag Bavishi, Robert Faillace, Jacqueline Tamis-Holland, Mamas Mamas, None Sanjay Chugh
Journal: Journal of the American College of Cardiology (2018)
Transferrin receptor 2 is a potential novel therapeutic target for β-thalassemia: evidence from a murine model
Authors: Irene Artuso, Maria Rosa Lidonnici, Sandro Altamura, Giacomo Mandelli, Mariateresa Pettinato, Martina U. Muckenthaler, Laura Silvestri, Giuliana Ferrari, Clara Camaschella, Antonella Nai
Journal: Blood (2018)
Comprehensive molecular and immunohistochemical analysis of advanced renal cell carcinoma patients treated with mTOR inhibitors.
Authors: JesÃºs GarcÃa-Donas, Jose Maria Roldan, Nuria Lainez, Daniel E. Castellano, Emilio Esteban González, Miguel A. Climent, Javier Puente, Juan Francisco Rodriguez-Moreno, Teresa Alonso Gordoa, Aranzazu Gonzalez del Alba, Jose Angel Arranz, Maria Santos, Susana Hernando Polo, Montserrat Domenech, Laura Rodriguez, Alejandro Herrador, M Isabel Sáez, Enrique Gallardo Díaz, Ana Maria Gutierrez, Cristina Rodríguez-Antona
Journal: Journal of Clinical Oncology (2018)

4559 Background: The development of new combinations with mTOR inhibitors and the description of meaningful responses in cases with mutations in the mTOR pathway have raised the interest on these compounds. Predictive biomarkers of activity are crucial to ensure patients likely to benefit are properly treated. Methods: Through an observational prospective study by the Spanish Oncology Genitourinary Group (SOGUG), FFPE tumor samples were collected from 77 RCC patients treated with temsirolimus or everolimus. Patients with partial response (by RECIST), or stable disease for at least 6 months were classified as responders. Immunositochemistry (IHC) was performed in 64 patients for p-S6, p-S6K1, p-AKT, p21, BAP1 and PBRM1. Mutational analysis of key genes in mTOR pathway was performed through Next Generation Sequencing in tumor DNA. The association between expression of the proteins and response to mTOR inhibitors was analyzed through logistic regression. Results: The 77 patients studied had been treated with everolimus (79%) or temsirolimus (21%); 87% had ccRCC histology, 60% had intermediate, 39% good prognosis, and 1% poor prognosis (MSKCC); 29 patients were responders, 47 non-responders and 1 could not be classified. Among the five cases with mTOR pathway activating mutations (1 TSC1 (p.P333HfsTer5), 1 TSC2 (p.L826M); and 3 MTOR mutations (p.S2215_L2216delinsF, p.Y1974H, p.E773D)), three were responder patients and two non-responders. Regarding p-S6 staining, two responder patients and one non-responder had positive staining, while one responder had negative staining and one non-responder was not evaluable. In the full series, negative IHC expression for BAP1 and PBRM1 was associated with better mTOR inhibitor response (OR = 4.0, 95%CI = 1.4-11.9, P = 0.011 and OR = 3.9, 95%CI = 1.2-12.8, P = 0.025, respectively, multivariable analysis). However, no association between for p-S6, p-S6K1, p-AKT and p21 staining and mTOR inhibitor response was observed. Conclusions: TSC1, TSC2 and MTOR mutations only partially correlated with response. Lack of BAP1 and PBRM1 expression was associated with improved response to mTOR inhibitors.
Cognitive declines in relationship with severe hypogonadism in long-term testicular germ cell tumor survivors: A prospective survivorship study.
Authors: Michal Chovanec, Lucia Vasilkova, Lucia Petrikova, Jana Obertova, Patrik Palacka, Katarina Rejlekova, Zuzana Sycova-Mila, Katarina Kalavska, Daniela Svetlovska, Beata Mladosievicova, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2018)

e22104 Background: Long-term testicular germ cell tumor (GCT) survivors suffer from long-term cognitive function declines. We aimed to evaluate, whether patients with hypogonadism are more vulnerable to cognitive impairment resulting from treatment for GCT. Methods: GCT survivors included in the survivorship study at National Cancer Institute of Slovakia prospectively completed a FACT-Cog questionnaire at a median 10 years of follow up (range 5-32). Four cognitive domains were evaluated and overall cognitive function score was subsequently calculated. Whole peripheral blood was drawn from each survivor at the same day and the testosterone (T) level was determined by Enzyme-Linked Immunosorbent Assay. Severe hypogonadism (SH) was defined as serum T < 100 ng/dL. Results: We evaluated cognitive function in 155 GCT survivors. Median age at evaluation was 41 years (range 21-77). Serum T levels drawn at the day of completing the FACT Cog questionnaires were available from 82 study participants. Compared to survivors with T > 100 ng/dL, SH survivors had higher perceived cognitive impairment (P = 0.054), higher cognitive impairment perceived by others (P = 0.007) and lower perceived cognitive abilities (P = 0.004). Overall cognitive function score was significantly lower in SH compared to T > 100 ng/dL (P = 0.019). SH survivors did not report lower quality of life resulting from their cognitive impairment. Cognitive functioning was independent of age in the multivariable analysis. Conclusions: Severe hypogonadism was associated with cognitive difficulties in three of four FACT-Cog domains and in the overall cognitive function score. We propose hypogonadism as a possible underlying mechanism for long-term cognitive impairment. Further studies are needed to explore mechanistic implications.
Developmental neurotoxicology of endocrine disruptors and pesticides: identification of information gaps and research needs.
Authors: H A Tilson
Journal: Environmental Health Perspectives (1998)

There is increasing evidence that some environmental chemicals can interrupt neurodevelopmental processes during critical periods of development, resulting in effects on sensory, motor, and cognitive function. It is now generally accepted that developing organisms are differentially sensitive to chemical exposure because of toxicokinetic and/or toxicodynamic factors. Regulatory mechanisms have been implemented to protect humans from over- or inappropriate exposures to environmental chemicals. Current regulatory practices, however, may be insufficient because of the possibility that some environmental chemicals interfere with endocrine function at key periods of neurodevelopment. In addition, a recent National Research Council (NRC) report on pesticide contamination in the diets of infants and children concluded that current regulatory practices may not sufficiently protect infants and children from the risk of pesticide exposure. The NRC report indicates that regulatory agencies might underestimate the actual exposure of infants and children to pesticides and rely too heavily on data from adults in the risk assessment of pesticides. Consideration of endocrine-disrupting chemicals and the differential susceptibility of infants and children has led to identification of a number of information gaps and research needs that should be addressed in order to improve future risk assessments for these chemicals.
TCT-622 Comparative safety and effectiveness of polymer-free biolimus-eluting stents versus permanent-polymer everolimus-eluting stents in routine clinical practice
Authors: Arturo Giordano, Paolo Ferraro, Nicola Corcione, Pietro Pieri, Massimo Mancone, Gennaro Sardella, Giuseppe Biondi-Zoccai
Journal: Journal of the American College of Cardiology (2018)
An unexplored intersection of patient care: Analyses of cancer related emergency department utilization.
Authors: Donna Rivera, Jeremy Brown, Benmei Liu, Chun-Ju Hsiao, Nonniekaye Shelburne
Journal: Journal of Clinical Oncology (2016)

6527 Background: An estimated 134 million people visit the Emergency Department (ED) each year. Fourteen million people are living with cancer in the United States. The ED is an accessible care setting for treatment of cancer related complications, yet there is limited prior research. This study provides the first estimates of ED utilization and clinical presentation of adult cancer patients. Methods: ED visit data from adult cancer patients were analyzed from two large, nationally representative surveys, National Hospital Ambulatory Medical Care Survey (NHAMCS 2006-2011) and Nationwide Emergency Department Sample (NEDS 2006-2009). Variable specific algorithms were created to identify cancer-related visits based on ICD-9 diagnoses at the ED visit. Descriptive frequencies using appropriate survey weighting assessed ED utilization by adult cancer patients (age > 18) including demographic, geographic, and clinical characteristics. Results: (NHAMCS) There were 598.5 million weighted ED visits, of which 4 million were identified as cancer-related. Among cancer-related ED visits, 84.5% were associated with patients over age 45 compared to 53.7% for total ED visits. The primary chief compliant was shortness of breath (11.6%). (NEDS) There were 381.8 million weighted ED visits, of which 10.3 million visits (3%) were identified as cancer-related. Cancer-related ED visits with patients over age 65 comprised 57% of the visits compared to 21% for total ED visits. Disposition of cancer-related ED visits differed largely from that of total ED visits, with 54.6% of patients admitted to the hospital compared to 18.6% in the general population. Cancer-related ED visits accounted for 1-3% of all ED visits. Malignant neoplasm of the bronchus and lung was the most commonly reported cancer-specific diagnosis. The most common non-cancer diagnoses were pneumonia, chest pain, abdominal pain and dehydration. Conclusions: The majority of cancer related visits occur in the aging population, indicating the need to manage multiple comorbidities. Further study is needed to better identify a “Cancer-related ED Visit” and areas in which ED physicians and oncologists can work together to improve patient care.
ECLYPS: Multicenter trial of FDG-PET/CT to detect residual nodal disease in locally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after chemoradiotherapy (CRT).
Authors: Tim Van Den Wyngaert, Nils Helsen, Laurens Carp, Remco De Bree, Michel J. Martens, Carl Van Laer, Isabel Hutsebaut, Philip R. Debruyne, Annelies Maes, Joost van Dinther, Sabine Meersschout, Laurence Goethals, Hilde Verstraete, Kristof Deben, Sara Hakim, Pol M. Specenier, Olivier Lenssen, Otto S. Hoekstra, Danielle Van den Weyngaert, Sigrid Stroobants
Journal: Journal of Clinical Oncology (2016)

6021 Background: FDG-PET/CT surveillance after CRT in LAHNSCC results in non-inferior overall survival (OS) compared to routine neck dissection (ND) (Mehanna H, ASCO 2015). However, optimal imaging frequency, interpretation in p16+ patients (pts), and value of image quantification remain uncertain. Methods: Prospective multicenter trial of FDG-PET/CT 12wks after end of CRT in pts with newly diagnosed LAHNSCC (stage IVa/b), with scanner (cross-)calibration, standardized image reconstruction, and blinded central review (Hopkins criteria). Reference standard was histology or > 1y negative clinical follow-up after imaging. The primary end-point was the negative predictive value (NPV) for nodal recurrence (target > 90% with 95% CI excluding 85%). Secondary analyses assessed time-dependency of test characteristics, value of quantitative SUV assessment, and impact of p16 status. Results: Of 152 pts recruited in 7 centers, 125 had adequate primary tumor control after CRT and entered follow-up (median 20.4mos), during which 23 (18.4%) neck recurrences occurred (ND rate 16%; 2y OS 85.9%). Overall NPV of FDG-PET/CT was 92.1% (95% CI 86.9 – 95.3; H0 : NPV = 85% p= 0.012), with sensitivity 65.2% (95% CI 44.9 – 81.2) and specificity 91.2% (95% CI 84.1 – 95.3). Sensitivity was time-dependent, decreasing from 83.3% at 3mos to 59.7% at 12mos after imaging (p= 0.04). Specificity was stable over time. Visual FDG-PET/CT analysis was prognostic for OS (HR 11.27; p< 0.0001) and time to nodal recurrence (SHR 12.36; p< 0.0001), as was p16+ status (HR 0.16 and SHR 0.34; both p= 0.02). Quantitative assessment (SUV70 ) was superior to local read (p= 0.01), but not Hopkins criteria. For neck recurrences < 6mos after imaging, SUV70 in p16+ pts was higher compared to p16- pts, affecting optimal SUV70 cut-off values. Conclusions: FDG-PET/CT can rule out neck disease with high probability 12 wks after CRT in LAHNSCC, but sensitivity was lower for late recurrences, which may warrant an additional surveillance scan. SUV analysis outperformed local visual read, but not Hopkins criteria. Optimal absolute SUV thresholds may depend on p16 status. Clinical trial information: NCT01179360.
Key facilitators to implementing smoking cessation support for cancer patients across Canada.
Authors: Deb Keen, Michelle Halligan, Caitlyn Timmings, Graham W. Warren
Journal: Journal of Clinical Oncology (2018)

e18555 Background: There are little data providing key facilitators to implementing smoking cessation support across cancer care systems. Reported are results from a 15 month project across 7 provinces and 2 territories in Canada developed by the Canadian Partnership Against Cancer (CPAC) to facilitate adoption of smoking cessation support to cancer patients. Methods: Funding, implementation, and evaluation support was provided by CPAC to 9 Canadian jurisdictions over 15 months. Quantitative and qualitative evaluations at 3, 9, and 15 months were obtained for process, system, and patient outcomes. Framework analyses were performed to identify key patient and systems level facilitators and barriers to successful implementation. Results: Successful change related to smoking cessation for cancer patients include: early engagement of leadership, clearly defined roles within project teams, engaging patients and family, embedding cessation support into existing care pathways, leveraging existing cessation support resources, use of electronic medical records, and use of key indicators to measure and track performance. Challenges to integration within cancer systems include: patient stigma, provider attitude and knowledge, lack of perceived clinical skills to provide cessation support, lack of access to pharmacotherapy, competing priorities in oncology care, and cultural norms. A lack of sustained funding threatens maintenance of efforts after adoption. Conclusions: Integration of smoking cessation within cancer systems requires coordination with existing infrastructure and practice environments. Sustained access to financial support appears necessary to facilitate transition from adoption to sustained provision of evidence-based cessation support.
Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones
Authors: Bauke de Boer, Janine Prick, Maurien G. Pruis, Peter Keane, Maria Rosaria Imperato, Jennifer Jaques, Annet Z. Brouwers-Vos, Shanna M. Hogeling, Carolien M. Woolthuis, Marije T. Nijk, Arjan Diepstra, Sebastian Wandinger, Matthias Versele, Ricardo M. Attar, Peter N. Cockerill, Gerwin Huls, Edo Vellenga, André B. Mulder, Constanze Bonifer, Jan Jacob Schuringa
Journal: Cancer Cell (2018)
Utilizing a practical tablet-based modified geriatric assessment in clinic for older adults with multiple myeloma (MM).
Authors: Nitya Nathwani, Arti Hurria, Sandra E. Kurtin, Brea Lipe, Supriya Gupta Mohile, Donna Catamero, Debra Wujcik, Agnes Davis, Kristy Birchard, Carrie Tompkins Stricker, Tanya Marya Wildes
Journal: Journal of Clinical Oncology (2018)

10043 Background: More than 60% of patients diagnosed with MM are > 65 years old and at greater risk for treatment toxicity. Comprehensive geriatric assessment predicts toxicity and survival but is difficult to add to already stressed clinical workflow. We have previously demonstrated feasibility of a tablet-based modified geriatric assessment (mGA). Here, we provide a final report of impact on decision-making and treatment outcomes. Methods: In this multi site study, patients with MM > 65 years old completed a tablet-based mGA in clinic just prior to an oncology visit to discuss a treatment decision. Using the International Myeloma Working Group (IMWG) frailty model, a summary score, along with selected other GA and clinical data, was displayed to oncology providers at the beginning of the clinical visit. Results: 166 patients enrolled. Most were white (76%, n = 127) and male (56%, n = 93); mean age was 72 years (SD6.46; range 61-95). Based on IMWG criteria, patients were fit (39%, n = 64), intermediate fit (33%, n = 55) or frail (28%, n = 47), and 69% of providers agreed/strongly agreed that the mGA influenced the treatment recommendations for the patient. Treatments selected were more intensive for fit patients, while frail patients received lower intensity, with a reduced number of agents or a different route of administration (χ2 = 20.81 (4), p < .0001). There was a significant association between fit status and transplant eligibility, with more fit patients being transplant eligible (χ2 = 20.81 (6), p = .007). Outcome follow-up at 3 months on 144 patients indicated 39% (n = 56) of patients had a dose modification after the initial assessment and 18% (n = 26) discontinued therapy earlier than planned; 19.4% (n = 28) had a CTCAE grade 3-5 hematologic toxicity and 22% (n = 31) had a grade 3-5 non-hematologic toxicity, most commonly fatigue. Rates of toxicity were similar between patients considered fit, intermediate fit and frail. Conclusions: Results of a mGA presented to a provider at the point of care influenced treatment decisions. Most patients continued the prescribed therapy at 3 months, with relatively low rates of grade 3-5 toxicity. Further study is needed to compare outcomes with standard care. Clinical trial information: NCT03068637.