tbuckley/cabot-search huggingface dataset:
THU-124-Efficacy and safety of glecaprevir/pibrentasvir for the pangenotypic treatment of chronic hepatitis C in former intravenous drug users: Subanalysis from a Spanish real-world cohort (Hepa-C)
Authors: Marc Puigvehí, Agustin Albillos, Ana Viu, Manuel Hernandez-Guerra, Inmaculada Fernández Vázquez, M Prieto, Xavier Torras, Jose Miguel Rosales Zabal, Lourdes Grande Santamaria, Rosa Morillas, Moises Diago, Beatriz de Cuenca Morón, Manuel Delgado, Lucia Bonet, Juan Turnés, Javier Crespo, Carme Baliellas, José Luis Calleja Panero, Esther Badia-Aranda, Juan Manuel Pascasio, Jose María Moreno, Vanesa Bernal Monterde, Isabel Carmona, Miguel Fernandez-Bermejo, Rosa Quiles, Pablo Bellot Garcia, Jesus M Gonzalez-Santiago, Maria Luisa Gutierrez, José Juan Moreno, M Dolores Anton Conejero, Juan De la Vega, Desamparados Escudero-García, Juan Arenas, Jose A. Carrión
Journal: Journal of Hepatology (2019)
Benefits of a brief psychological intervention targeting fear of cancer recurrence in people at high risk of developing another melanoma: 12‐month follow‐up results of a randomized controlled trial
Authors: M. Dieng, R.L. Morton, D.S.J. Costa, P.N. Butow, S.W. Menzies, S. Lo, G.J. Mann, A.E. Cust, N.A. Kasparian
Journal: British Journal of Dermatology (2019)

People with melanoma want and need effective interventions for living with fear of cancer recurrence (FCR). This study reports the 12‐month outcomes of a brief, psychological intervention designed to reduce FCR in people at high risk of developing another primary melanoma compared with usual care. In this two‐arm randomized controlled trial, adults previously diagnosed with stage 0, I or II melanoma were randomly allocated to the intervention (n = 80) or control (usual care) arm (n = 84). The trial was registered with the Australian and New Zealand Clinical Trials Registry on 19 March 2013 (registration: ACTRN12613000304730). The intervention comprised a 76‐page psychoeducational resource and three individually tailored, telephone‐based sessions with a psychologist, scheduled at specific time points around participants' dermatological appointments. The primary outcome was the level of self‐reported fear of new or recurrent melanoma assessed at 12 months postintervention using the severity subscale of the Fear of Cancer Recurrence Inventory. Compared with the control arm, the intervention group reported significantly lower FCR at 12 months postintervention; the between‐group mean difference was −1·41 for FCR severity [95% confidence interval (CI) −2·6 to −0·2; P = 0·02] and −1·32 for FCR triggers (95% CI −2·6 to −0·02; P = 0·04). The odds ratio for FCR severity scores ≥13 (54% intervention, 63% control) was 0·59 (95% CI 0·30–1·14, P = 0·12). There were no differences between groups in secondary outcomes, such as anxiety, depression or health‐related quality of life. The previously reported 6‐month benefits of this brief, patient‐centred psychological intervention in reducing FCR were found to continue 12 months postintervention, with no known adverse effects, supporting implementation as part of routine melanoma care.
Treatment of dermatofibrosarcoma protuberans (DFSP) with fixed Mohs micrographic surgery (f-MMS).
Authors: Jean-Francois Sei, Veronique Chaussade, Arnold Tchakerian, Marc Serra, Ute Zimmermann, Thierry Clerici, Christine Longvert, Philippe Saiag
Journal: Journal of Clinical Oncology (2015)

e20066 Background: DFSP is a rare skin sarcoma with historically a high recurrence rate. In conventional surgery, 3-5 cm margins of normal skin are required. Mohs micrographic surgery (MMS) ensures complete excision of tumors by examination of all margins and minimizes normal tissue loss, but residual DFSP can be difficult to see on the frozen MMS sections. We developed a modified MMS procedure (f-MMS) aiming to reduce recurrence rate and facilitate wound closure. Methods: Non-randomized prospective observational study performed in a single referral center. Since 1998, all consecutive pathology-proven DFSP pts were treated with f-MMS and entered in a database. DFSP was first excised using a lateral margin of 1 cm and a deep margin close to the underlying aponevrosis. A 2-3 mm_thick horizontal layer of the entire surgical bed was then removed, rush-formalin-fixed, paraffin-embedded, tangentially sectioned, stained with hematoxilin-eosin and CD 34 stain. If excision was incomplete, an oriented additional excision was performed a few days later with the same procedure. No other treatment was used, regardless of fibrosarcomatous transformation, Endpoints were recurrence rate and wound-closure procedures. Results: 226 pts (mean age 41.2 y) with DFSP (204 primary, 22 recurrent, median longitudinal axes of 33.8 & 23.1 mm) were treated. Excision was complete at first stage in 207 (91.2%) patients and incomplete (only deeply) in 19. Lateral margins were reduced to 1.3 cm in all pts, facilitating wound closure by direct suture (N = 147), wound healing by secondary intention (N = 42), skin graft (N = 26) or flap (N = 11). After a median delay of 5.31 y. after surgery, only 1 local recurrence was observed 2 y. after surgery, with no death nor regional spread (20% pts lost to follow-up). Conclusions: f-MMS greatly reduced unnecessary normal tissue loss, simplified reconstruction and provided a very small 0.4% (95%CI:0-1.3%) recurrence rate in this large prospective series. Provided our findings are validated, DFSP can be treated efficiently with less-invasive surgical approaches.
Skeletal tumor burden on baseline <sup>18</sup>F-fluoride PET/CT to predict bone marrow failure after radium-223.
Authors: Elba Etchebehere, John C. Araujo, Denai Milton, Patricia S Fox, Nancy Swanston, Homer A. Macapinlac, Eric Rohren
Journal: Journal of Clinical Oncology (2015)

11012 Background: The purpose of this study is to evaluate if skeletal tumor burden on whole-body 18F-sodium fluoride PET/CT (Fluoride PET/CT) is able to predict bone marrow failure Radium-223 therapy (Ra-223). Methods: We retrospectively reviewed 76 histologically confirmed hormone-refractory prostate cancer patients (43-89 y old; mean 71 ± 9 yrs.) with bone metastases who underwent Fluoride PET/CT either prior to, during and/or 3 months after therapy with Ra-223. Bone marrow failure (BMF) was the primary end point. BMF was defined as: (1) the development of hematologic toxicity (WHO Grades 3 or 4) associated with no recovery after 6 weeks, or (2) death due to BMF after the last Ra-223 dose. The following parameters were evaluated: Fluoride PET/CT skeletal tumor burden (TLF10 < 12,000 vs ≥ 12,000), the total number of Ra-223 doses the patients received (RaTot), the use of chemotherapy during and after Ra-223, serum hemoglobin concentration (HBG < 10 vs ≥ 10g/dl), serum alkaline phosphatase (AP < 147 vs ≥ 147UI/L), and serum PSA ( < 10 vs ≥ 10 ng/ml). Results: Forty-one patients underwent a baseline Fluoride PET/CT prior to Ra-223 and were eligible for analysis. The number of Ra-223 administrations ranged from 2 to 6 (mean = 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significant increased risk of developing BMF was observed for patients with TLF10 ≥ 12,000 (OR = 40.0; p = 0.0013), fewer RaTot (OR = 0.51; p = 0.0190), HGB < 10 g/dl (OR = 51.0; p = 0.0137) and AP ≥ 147UI/L (OR = 9.50; p = 0.0025). Chemotherapy used concomitant to or after Ra-223 was not found to increase risk of BMF (OR = 0.79; p = 0.71), nor was PSA (OR = 1.17; p = 0.83). Moreover, in a multivariable analysis including all evaluated parameters, TLF10 was the only independent predictor of BMF (OR = 8.74; p = 0.0450). Conclusions: Bone marrow failure may occur after Ra-223 treatment, and high skeletal tumor burden as quantified by Fluoride PET/CT is a significant risk factor.
FRI-043-Primary biliary cholangitis-Autoimmune hepatitis overlap syndrome: Characteristics and response to obeticholic acid in TARGET-PBC, a diverse, large United States real-world cohort
Authors: Marlyn J. Mayo, Christopher Bowlus, Elizabeth Carey, Ester Little, Karen Deane, Richard Zink, Robert Sandefur, W. Ray Kim, Cynthia Levy
Journal: Journal of Hepatology (2019)
FRI-168-Understanding HDV and HBsAg kinetics during nucleic acid polymer REP 2139 mono-therapy in HBeAg-negative chronic HBV/HDV co-infected patients via mathematical modeling
Authors: Louis Shekhtman, Scott Cotler, Susan Uprichard, Michel Bazinet, Victor Pantea, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Adalbert Krawczyk, Andrew Vaillant, Harel Dahari
Journal: Journal of Hepatology (2019)
THU-320-Evaluation of atherosclerosis and coronary artery stenosis of non-alcoholic fatty liver disease
Authors: Yoshihito Kubotsu, Hirokazu Takahashi, Chika Inadomi, Kenichi Tanaka, Yuka Fujioka, Michiaki Okada, Hiroshi Isoda, Satoshi Ooeda, Takumi Akiyama, Shinji Iwane, Keizo Anzai, Yuichiro Eguchi
Journal: Journal of Hepatology (2019)
Crying is an acceptable way to manage emotional stress
Authors: Isobel Phillips
Journal: BMJ (2019)

Should doctors be able to cry at work?1 The answer is entirely contextual. There is an absolute difference between crying during an emotionally challenging conversation with the family of a dying patient and crying in private because of excessive workloads and pressure. Regardless, doctors are human beings. Professionalism is the bread and butter of medicine, but doctor-patient relationships …
Genetic variation of lymphotoxin beta receptor (LTβR) rs10849448 (A/G) is associated with risk for lung cancer and metastatic spread to adrenals
Authors: F.-I.D. Dimitrakopoulos, A. Antonacopoulou, A. Kottorou, V. Tzelepi, N. Panagopoulos, M. Kalofonou, D. Dougenis, A. Koutras, T. Makatsoris, H. Kalofonos
Journal: Annals of Oncology (2019)

Background: During the last years there is an expansion of our knowledge in lung cancer immunology. In addition, there is a growing number of studies on the role of lymphotoxin beta receptor (LTβR), a member of the tumor necrosis factor (TNF) family, which plays an important role in lymphoid system formation and homeostasis as well as in immune system regulation mainly through NF-κB signaling. The aim of the current study was to investigate the clinical relevance of LTβR single nucleotide polymorphism (SNP) rs10849448 (A/G) with the susceptibility to NSCLC, the clinicopathological parameters, the relapse and the survival rates of NSCLC patients, as well as with the protein expression of LTβR. Methods: LTβR SNP was genotyped in 268 randomly selected NSCLC patients and 279 age- and gender-matched healthy donors. Immunohistochemical analysis for LTβR was performed on 127 NSCLC tumors. The studied cohort was under observation during a five-year period. Results: Genotype frequencies of rs10849448 (AA, AG, and GG) varied between healthy controls and patients, but the difference did not reach statistical significance (p = 0.054). AA homozygotes were found to have lower risk for NSCLC compared to G allele carriers in univariate as well as in multivariate analysis (both p = 0.016). Moreover, rs10849448 was associated with development of metastases with A allele carriers developing less often metastatic disease in adrenals (p = 0.013). Interestingly, rs10849448 was related to membranous LTβR protein expression (p = 0.035) in malignant cells, with AA homozygotes being associated with higher protein levels. Conclusions: The present findings suggest that the investigated SNP rs10849448 may be associated with NSCLC initiation as well as with the development of metastatic disease. More association and functional studies are needed in order to further clarify it's role in NSCLC. Legal entity responsible for the study: H. Kalofonos. Funding: This research was co-funded by the Hellenic Society of Medical Oncology (HeSMO) through a research funding program. Disclosure: All authors have declared no conflicts of interest.
Efficacy and safety of empegfilgrastim, a novel pegylated G-CSF: Results of complete analysis after 4 cycles of myelosuppressive chemotherapy in phase III double-dummy randomized clinical study.
Authors: Olga Filon, Marina Nechaeva, Olga Burdaeva, Vladimir Ivanovich Vladimirov, Igor Lifirenko, Nadezhda Vitalievna Kovalenko, Mikhail V. Kopp, Marina Matrosova, Guzel Mukhametsina, Sergey Panchenko, Pavel Skopin, Daniil Stroyakovskiy, Petr Krivorotko, Julia Shapovalova, Irina Jelvakova, Ludmila Sheveleva, Anastasia Abrosimova, Roman Ivanov, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2015)

e20735 Background: Empegfilgrastim is an innovator drug product of pegylated G-CSF indicated for prophylaxis of neutropenia in patients receiving myelosuppressive chemotherapy. Methods: Objective was to compare safety and efficacy of a single dose of empegfilgrastim and daily dosing of filgrastim in patients receiving docetaxel 75 mg/m2 + doxorubicin 50 mg/m2. 135 patients with breast cancer were randomly assigned at a ratio of 1:1:1 to receive either single s.c. injection of empegfilgrastim at doses of 6 mg or 7.5 mg, or daily s.c. injections of filgrastim at a dose of 5 mcg/kg (until ANC ≥ 10x109/L). Results: At the cycle 1 mean duration of grade 4 neutropenia (primary endpoint) was significantly shorter in both empegfilgrastim groups: 0,905, 0,791 and 1,725 days in 6 mg, 7.5 mg and filgrastim groups, correspondingly. Mean difference in duration of grade 4 neutropenia between filgrastim and 7.5 mg groups was -0,934 d (95% CI -1,504 to -0,364 d) (p < 0,05). During the next 3 cycles duration of grade 4 neutropenia was also significantly shorter in both empegfilgrastim groups: cycle 2 (0.452, 0.326 and 0.925 d), cycle 3 (0.244, 0.310 and 0.641 d), cycle 4 (0.195, 0.475 and 0.892 d) (p < 0.05). Bacterial infections were observed only in 4 patients from filgrastim group, all patients were treated with oral anti-infective drugs. Empegfilgrastim at both doses was as safe and well tolerated as daily filgrastim administration. Most AEs were associated with chemotherapy. Frequency of G-CSF-specific reactions as all other AEs was equivalent in all groups: myalgia (7.14%, 4.65% and 4.65%), arthralgia (14.29%, 6.98% and 6.98%), ossalgia (9.52%, 9.30% and 4.65%), local reactions (7.14%, 2.33% and 2.33%). Conclusions: The results of this study demonstrated therapeutic superiority of empegfilgrastim, especially at a dose of 7.5 mg, compared to filgrastim. Clinical trial information: NCT02104830. Empegfilgrastim 6 mg Empegfilgrastim 7.5 mg Filgrastim p value Febrile neutropenia cycle 1 1 (2.38%) 1 (2.33%) 1 (2.50%) p > 0.05 all cycles 1 (2.38%) 3 (6.98%) 1 (2.50%) p > 0.05 Severe neutropenia cycle 1 31 (73.81%) 29 (67.44%) 35 (87.50%) p > 0.05 all cycles 40 (95.24%) 34 (79.07%) 40 (100.00%) p < 0.05
Descriptive analysis in <i>ALK-</i>positive non-squamous cell lung cancer.
Authors: Natalia Ferrari-Gabilondo, Kelly Wilt, Joseph Won
Journal: Journal of Clinical Oncology (2015)

e19136 Background: EML4-ALK fusion gene is prevalent in about 5% of lung adenocarcinomas. ALK-positive disease responds to targeted therapies. There is little data on the prevalence of ALK gene rearrangements among African Americans. The patterns of care in ALK-positive lung cancer in our patient population are unknown. Methods: We performed a retrospective chart review of patients with ALK-positive lung cancer at Henry Ford and West Bloomfield Hospitals between December 1, 2010 and December 31, 2013. Demographic and clinical variables were obtained for the ALK-positive patients. Results: 388 patients were tested for the ALK fusion protein. Eighteen patients (5%) tested positive for ALK, and 370 patients (95%) tested negative. Five out of 18 (28%) ALK-positive patients were African American. Five out of 66 (7.5%) African Americans tested for ALK resulted positive. 66% of ALK-positive patients were female and 33% were male. There was no statistically significant difference between age, sex and race between ALK-positive and ALK-negative patients. There were significantly more patients who ever smoked in the ALK-negative group (90%) as compared to the ALK-positive group (39%) (p< 0.001). The most common sites of metastases for ALK-positive cancer were: CNS in 6 patients (40%) and bone in 6 patients (40%). The first line treatment for metastatic ALK-positive cancer was crizotinib in 5 patients, chemotherapy in 7 patients and hospice care in 2 patients. Conclusions: The prevalence of ALK-positive lung cancer in African Americans was 7.5% in our sample. The prevalence of ALK-positivity in females doubles that of male patients. There were significantly more patients who ever smoked in the ALK- negative group. We found a high tropism of ALK-positive lung cancers for the central nervous system. Crizotinib was used as a first-line therapy in 5 out of 14 patients. Comparison of response duration with crizotinib vs. chemotherapy for ALK-positive patients was limited due to small sample size, but the absolute numbers show a longer duration of response with crizotinib. This study can serve as data for future studies on the natural history of ALK-positive lung cancer.
Computer simulation and in vitro validation for prediction of therapeutic efficacy and personalized medicine in Waldenstrom macroglobulinemia.
Authors: Pilar de la Puente, Shireen Vali, Ansu Kumar, Ravi Vij, Kareem Azab
Journal: Journal of Clinical Oncology (2015)

e22210 Background: Waldenstrom Macroglobulinemia (WM) is a rare and incurable lymphoma that can be can be managed by a wide number of available chemotherapy agents. In this study, we propose a novel model based on computer simulation and in vitro validation for prediction of therapeutic efficacy and personalized therapy in WM patient. Methods: MWCL-1 is a patient derived WM cell line, which with rigorous genetic testing has confirmed its clonal relationship to the primary WM tumor. Using genomic information of MWCL-1, we created a simulation template and predicted the major dysregulated pathways which converged on proliferation and viability. Through simulation screening of digital drug library, we explored the sensitivity of MWCL-1 cells to various drugs, which were also validated using in vitro proliferation assay. In addition, primary cells from a WM patient were genetically characterized, and simulated using the same template used for the MWCL-1 cell line to predict therapeutic efficacy of drugs used in WM, which were also validated using in vitro proliferation assay. Results: The MWCL-1 simulation showed increased regulation of AKT, ERK, NFkB, HIF1A and AURKA is also up-regulated due to high CNV of ETS1 and FLI. MWCL-1 cells were predicted to be resistant to Bortezomib, Etanercept and Metformin; moderately sensitive to Celecoxib, Zileuton and Rigosertib; and very sensitive to cell cycle inhibitor LEE011. All of these predictions were prospectively validated with a correlation with experimental in vitro data. Furthermore, the in silico simulation predicted that the cells from WM patient will be sensitive to BTK inhibitor (Ibrutinib) and mTOR inhibitor (Sirolimus), and that these will have synergy in WM cells. In vitro proliferation assay recapitulated the in silico simulation results. Conclusions: This demonstrates and validates methodology to design personalized treatments for a rare disease like WM without necessarily targeting one of the driver mutations. The simulation and repurposing approach provides a rapid clinical translation pathway for developing and advancing a new therapy to clinic.
PS-187-Transient elastography is the most reliable non-invasive predictor of advanced liver fibrosis in fontan-associated liver disease: The VALDIG FONLIVER study
Authors: Luis Téllez, Payance Audrey, Valérie Paradis, Enrique Rodríguez-Santiago, Aurélie Plessier, Ana Clemente, Rafael Bañares, Dominique Valla, Agustin Albillos, PE Rautou
Journal: Journal of Hepatology (2019)
Prognostic significance of neutrophil/lymphocyte ratio in patients undergoing treatment with nivolumab for recurrent non-small cell lung cancer
Authors: B.L. Rapoport, D.A. Vorobiof, L. Langenhoven, J.M. Hall, R.I. Van Eeden, T. Smit, S.W. Chan, M.C. Botha, J.I. Raats, M. De Necker, H. Duvenhage
Journal: Annals of Oncology (2019)

Background: Neutrophil-to-lymphocyte ratio (NLR) has prognostic value in several types of cancers. We investigated the influence of NLR in patients undergoing treatment with PD-1 checkpoint inhibitors for recurrent Non-Small Cell Lung Cancer (NSCLC). Methods: Study CA 209-8C3, is a multicenter, non-interventional retrospective data analysis, which include patients who were previously treated for recurrent (unresectable or metastatic) NSCLC. Retrospective data was collected from 5 participating oncology centers. Results: We analyzed data of 56 patients treated with nivolumab, 32 (57%) were male with a median age of 65 (46-86). Thirty-two (57%) had NSCLC specified as adenocarcinoma. Fifty (89%) patients had an ECOG performance status (PS) of 0 or 1, and 6 (11%) had an ECOG PS of 2. A ≥ 4 cut-off value for NLR was calculated using the receiving operating characteristic (ROC) curves. The median OS was 11 months. One and two-year survival was 45% (95% CI 32% - 58%) and 32% (95% CI 20% - 45%) respectively. Median progression-free survival (PFS) was 6 months (95% CI 4 – 8). Univariate analysis found the number of metastatic sites and a higher NLR to be associated with shorter OS. Patients with ≤2 metastatic sites had a median OS of 11.4 months and patients with >2 sites 6.10 months (HR = 3.29 [95% CI 1.23-8.78], p = 0.0174). Patients with NLR ≥4 at 5-weeks post treatment had a median OS of 8.13 months, with median OS not reached for patients with NLR <4 (HR = 4.18, p < 0.001). NLR ≥4 at 9-weeks post treatment were also significantly correlated with shorter OS (HR = 4.15, p = 0.001) with median OS of 7.28 months, median OS for NLR <4 not reached. In a Cox multiple regression model with age, gender, race, ECOG PS, diagnosis, smoking status and NLR at 3-, 5- and 9-weeks, NLR ≥4 at five-weeks post nivolumab was the only factor that retained significance (HR = 5.41 95% p < 0.001). Clinically relevant grade ≥3 toxicities include pneumonitis (n = 5), severe skin rash (n = 1), colitis (n = 1) and other (n = 3). Conclusions: Elevated NLR is associated with a poor outcome in patients with recurrent metastatic NSCLC treated with nivolumab. Legal entity responsible for the study: The authors. Funding: BMS: Study CA 209-8C3. Disclosure: B.L. Rapoport: Contract research, Advisory boards, Speaker: BMS, MSD, Roche South Africa, AstraZeneca; Research grant: BMS, Roche South Africa. All other authors have declared no conflicts of interest.
Nephrology in the Eastern and Central European region: challenges and opportunities
Authors: Goce Spasovski, Merita Rroji, Evgueniy Vazelov, Nikolina Basic Jukic, Vladimir Tesar, Marina Mugosa Ratkovic, Adrian Covic, Radomir Naumovic, Halima Resic, Rumeyza Turan Kazancioglu
Journal: Kidney International (2019)