tbuckley/cabot-search huggingface dataset:
NHL and rituximab biosimilar: How have prescribing behaviours changed in EU5 in 15 months?
Authors: Alessandra Franceschetti
Journal: Journal of Clinical Oncology (2019)

e19054 Background: 15 months after EMA approval of the first rituximab biosimilar to treat NHL – and 12 months on from our presentation on its initial impact at the Biosimilars Special Clinical Symposium of ASCO 2018 – this study tracks the real world impact of official endorsement on prescribing behaviour and biosimilar adoption for NHL. Methods: The Ipsos Global Oncology Monitor – an online multi-country, multi-centre medical chart review of NHL patients, where 138 geographically representative physicians provided de-identified data on 3,239 patients treated with anti-cancer drugs in France (565), Germany (379), Italy (622), Spain (684) and UK (989) from July 2017 to Sept 2018. Physicians provided diagnosis date, current and historic treatment and reasons for prescribing treatment. Data on patients treated with and without a rituximab biosimilar were compared using descriptive statistics. Results: While prescribing of the rituximab molecule was stable over the study period, prescribing of rituximab biosimilars significantly increased – from 7% to 35% (p &lt; 0.01), most notably in Germany and UK. By Q3 2018, for those patients treated with a rituximab-including regimen (N = 483), prescribing of any EMA-approved rituximab biosimilar was 72% in Germany and 63% in UK; France, Italy and Spain reported 47%, 32% and 30%, respectively. Physicians were significantly more likely to state “Well tolerated” and “Proven efficacy” as reasons for prescribing rituximab biosimilars in Q3 2018 vs Q3 2017 (p &lt; 0.01). Prescribing of branded rituximab in the SC formulation significantly increased, from 21% to 33% (p &lt; 0.01). Rituxan prescribing may be partially driven by availability of the SC mode of administration (MoA) not available for biosimilars. Conclusions: Over time, prescribing of rituximab biosimilars has significantly increased in the EU5, mainly in Germany and UK. Growth is less evident in Italy and Spain, perhaps as Southern physicians are historically more averse to ‘generic’ versions. Physicians’ ongoing experience of mAb biosimilars has resulted in higher associations with “Well tolerated” and “Proven efficacy”. The rise in prescribing Rituxan with the SC MoA has likely contained an even higher prescribing of rituximab biosimilars.
Unique racial patterns in rare T-cell lymphomas: A National Cancer Registry analysis from 2001 to 2015.
Authors: Nishi Shah, Diego Adrianzen Herrera, Urvi Shah, Bhaskar Chandu Kolla, Gurbakhash Kaur, Roberto Alejandro Sica, Aditi Shastri, Ioannis Mantzaris, Amit Verma, Murali Janakiram
Journal: Journal of Clinical Oncology (2019)

e19070 Background: Peripheral T-cell lymphomas (PTCL) are a rare heterogenous group of lymphomas and modern studies on incidence patterns of PTCL are lacking. Methods: Using the National Program of Cancer registries (NPCR) database, which covers 99% of the US population, we aim to evaluate the incidence of PTCL according to age, race-ethnicity, and gender; and examine trends over time. We identified PTCL using ICD-O-3 codes and evaluated incidence trends from 2001 to 2015. Results: A total of 78722 PTCL cases were identified, the most common were Mycoses fungoides/Sezary syndrome (MF-SS), PTCL Not Otherwise Specified (NOS), and ALK+ Anaplastic Large Cell Lymphoma (ALK+ ALCL). The age-adjusted incidence rate was 2.1 per 100,000. Incidence of PTCL increased with age (6.7/100,000 in 80+years). PTCL was more common in males than females (incidence rate ratio [IRR] of 0.6, p&lt;0.05). Most PTCL were more common in Non-Hispanic Blacks (NHB). Incidence rates of MF-SS, PTCL NOS, Hepatosplenic TCL (HSL) in NHB were 0.8, 0.8, and 0.02 per 100,000 [IRR 1.7, 1.8, 2.2, p&lt;0.05] respectively which is approximately twice that of Non-Hispanic whites (NHW). Viral related PTCL like Adult T-cell Leukemia Lymphoma (HTLV), Angio-Immunoblastic T-cell Lymphoma [AITL] (EBV), Extranodal NK-TCL nasal type [ENK TCL] (EBV), NK cell leukemia (EBV) are higher in groups at highest predisposition such as NHB and Non-Hispanic Asian Pacific Islanders (NHAPI). Primary cutaneous (PC) gamma-delta TCL occurs exclusively in NHW at an incidence rate of 0.03 per 100,000. There was no increase in overall yearly incidence of PTCL over the study period (0.1%, p=NS) but the incidence increased in NHB (Annual Percent Change [APC] 1.4%, p &lt;0.05). Incidence of ENK TCL and AITL increased in NHAPI (2.2% and 3.7%, respectively [p &lt;0.05]). The incidence of ALK + ALCL, PC CD30+ TCL decreased (APC -4.2%, -2% [p≤0.05] respectively). Conclusions: This is the first study to show unique incidence patterns of PTCL namely higher incidence in males, African Americans (esp. MF, PTCL-NOS and HSL unaccounted for viral etiologies) and exclusivity of primary cutaneous gamma delta TCL in NHW. Further research is needed to understand these differences.
Abstract 14873: Mouse Model of Takotsubo Cardiomyopathy: The Role of Coronary Metabolic Blood Flow Regulation in Apical Ballooning
Authors: Vahagn A Ohanyan, Jordan Luli, Liya Yin, Molly Enrick, Kelly Stevanov, Christopher L Kolz, Suzanna Logan, William M Chilian
Journal: Circulation (2013)

Takotsubo cardiomyopathy, also known as “transient apical ballooning” mimics acute coronary syndrome and is characterized by transient systolic ballooning of the apex in the absence of significant ...
Abstract LB-060: Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model
Authors: Patrick Fadden, Thi Bui, David Hurtado, Kelli Davis, Ian Belle, Kathrine Krontz, Jacob Hauser, Na Li, Kyle Takayama, Cristina Sokolowski, Edgar Wood
Journal: Cancer Research (2019)

Abstract Immune focused interventions remain a high priority for many drug discovery efforts, spurred on by the success of immune checkpoint therapies such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 inhibitory antibodies. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors. We endeavored to characterize the immune response to checkpoint inhibitors in MC38 tumors using flow cytometry, gene expression analysis, and immunohistochemistry (IHC). Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene overrepresentation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymph structures. These finding suggests that MC38 may provide a good model system for evaluating therapies that can modulate or impact tumor infiltrating B cell populations. Citation Format: Patrick Fadden, Thi Bui, David Hurtado, Kelli Davis, Ian Belle, Kathrine Krontz, Jacob Hauser, Na Li, Kyle Takayama, Cristina Sokolowski, Edgar Wood. Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-060.
Somatic and germline genetic variants of gastric cancer in Russian patients identified by NGS
Authors: A. Kalinkin, A. Tanas, E. Kuznetsova, E. Alekseeva, I. Bykov, T. Kchorobryh, K. Kirillova, D. Zaletaev, V. Strelnikov, M. Nemtsova
Journal: Annals of Oncology (2019)
Abstract 4602: Abi1 promotes breast cancer progression by regulating cell-matrix adhesion
Authors: Xiang Li, Angelina Regua, Gennady Bratslavsky, Vladimir A. Kuznetsov, Leszek Kotula
Journal: Cancer Research (2019)

Abstract Breast cancer is one of the most common diagnosed cancers in the United States. There will be approximately 266,120 new breast cancer cases in the U.S. and over 40,000 patients are predicted to die from the malignant progression of their breast cancer tumors in 2018. Traditional therapeutic methods of the invasive breast cancer include surgery accompanied by chemotherapy. However, following the initial therapy patients often relapse and eventually die from tumor metastasis. Abl interactor 1, or Abi1, is an adaptor protein which regulates actin polymerization through participation in WAVE (Wiscott-Aldrich syndrome protein family verprolin homologous) complex. The WAVE regulatory complex (also called WRC), regulates actin based cellular behavior, such as cellular adhesion and cell migration, by activating Arp2/3 complex and promoting actin polymerization. Previous studies indicated the direct interaction between integrin α4 and Abi1, which suggests a potential role of Abi1 in regulating cell-matrix adhesion signaling by involved in the inside-out integrin signaling pathways. In order to test the above hypothesis, we developed two genetic engineered Abi1 knocked-out breast cell lines from either HER2+ breast cancer cell line SKBR3 or normal breast epithelial cell line MCF10A by using CRISPR-Cas9 technique. After confirming inactivation of Abi1 gene by Western blotting, DNA and RNA sequencing, cells were harvested and analyzed for integrins levels. Western blotting results indicated dysregulation of multiple integrins in the Abi1 knock-out cell lines. The results from subsequent immunofluorescence experiments of the Abi1 knock-out cell lines also suggested changes in cell-matrix adhesion signaling using staining for scaffold protein paxillin and phosphorylated Focal-Adhesion-Kinase (FAK) as readouts. Our findings suggest that Abi1 might functions as a key regulator in breast cancer tumor progression by playing an important role in regulating signal pathways in cell-matrix adhesion. Supported by the Carol Baldwin Foundation of CNY, and in part by NIH-NCI grant No. R01 CA161018. Citation Format: Xiang Li, Angelina Regua, Gennady Bratslavsky, Vladimir A. Kuznetsov, Leszek Kotula. Abi1 promotes breast cancer progression by regulating cell-matrix adhesion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4602.
Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease
Authors: Valerio Nobili, Alessandro Mantovani, Stefano Cianfarani, Anna Alisi, Antonella Mosca, Maria Rita Sartorelli, Claudio Maffeis, Rohit Loomba, Christopher D. Byrne, Giovanni Targher
Journal: Journal of Hepatology (2019)
Abstract 12766: Cardiac Sympathetic Nerve System Activity Evaluated by Cardiac I-123 Metaiodobenzylguanidine Scintigraphy in Heart Failure Patients With Preserved or Reduced Ejection Fraction
Authors: Toshihiko Goto, Kazuaki Wakami, Kento Mori, Tomoyuki Banno, Shohei Kikuchi, Tomonori Sugiura, Hiroshi Fujita, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2016)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure. However, there is no proven therapy for HFpEF. In contrast, significant benefits of beta-blockers that inhibit cardiac nerve system activity have been established in patients with heart failure with reduced ejection fraction (HFrEF). The purpose of this study is to compare cardiac sympathetic nerve system activity in patients with HFpEF versus HFrEF. Methods: The I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to evaluate cardiac sympathetic nerve system activity in 48 heart failure patients (age 77.0±10.6 years; male 52.1%). We compared the early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) in patients with HFpEF (left ventricular ejection fraction; LVEF≥50%, n=20) and HFrEF (LVEF&lt;50%, n=28). Results: There were no differences in age and sex between two groups. LVEF was significantly higher in patients with HFpEF than in those with HFrEF (62.5±11.7 vs 31.7±9.1%, p&lt;0.001). Plasma BNP level was significantly lower in patients with HFpEF than in those with HFrEF (205.1 [IQR, 155.0-430.5] vs 369.0 [IQR, 196.6-662.1] pg/mL, p=0.04). Plasma norepinephrine level was not different between HFpEF patients and HFrEF patients (428.5 [IQR, 210.5-676.3] vs 392.5 [IQR, 307.2-535.8] pg/mL, p=0.93). No significant differences were found in the early H/M ratio (2.17±0.46 vs 2.10±0.32, p=0.53) and in the delayed H/M ratio (1.94±0.53 vs 1.80±0.35, p=0.91) between HFpEF patients and HFrEF patients. The WR was also similar in HFpEF patients and HFrEF patients (37.9±17.0 vs 46.3±16.4%, p=0.09). The use of beta-blockers was significantly lower in patients with HFpEF than in those with HFrEF (35.0 vs 71.4%, p=0.01). Conclusions: Although the use of beta-blockers was lower in patients with HFpEF as compared to in those with HFrEF, cardiac sympathetic nerve system activity was elevated to a similar extent between patients with HFpEF and HFrEF. These findings suggest that cardiac sympathetic nerve system is a promising therapeutic target in patients with HFpEF.
Compliance with follow-up (f.-up) program and outcome of patients (pts) with stage I nonseminomatous germ cell tumors (NSGCT).
Authors: Mikhail Fedyanin, Alexey Tryakin, Elena Denisova, Anatoly Bulanov, Tatiana Zakharova, Vsevolod B. Matveev, Konstantin Figurin, Avgust Garin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2012)

e15025 Background: There are limited data about f.-up quality of pts with stage I NSGCT after orchiectomy (OE) management and their survival. A retrospective analysis was performed to find the impact of compliance with schedule of f.-up on outcome of relapsed pts with stage I NSGCT. Methods: We analyzed data of 261 pts with stage I GCT treated in our department from 1994 to 2010. NSGCT was revealed in 128 (49%) pts. Therapeutic options following OE comprised retroperitoneal lymph node dissection (RPLND) – in 4/128 (3%), adjuvant cisplatin-based chemotherapy (CT) - in 75/128 (58%) and surveillance - in 49/128 (39%). The following procedures were performed in our center during the f.-up: ultrasound of the abdomen and pelvis, serum AFP, HCG and LDH – bimonthly in the 1 st year, quarterly in the 2 nd year, biannually in the 3 rd -4 th years and then annually; X-Ray of the chest – thrice-yearly in the 1 st year, biannually on the 2 nd year and then annually. Median f.-up time was 75 (range 16 - 176) months. Results: No pts had relapse after RPLND, 4/75 (5,3%) pts had relapses after CT, 16/49 (32%) pts – in surveillance group. 17/20 (85%) relapses were revealed in the first 2 years of f.-up. During relapses, 17/20 (85%) pts had good, 2/20 (10%) - intermediate and 1 patient - poor IGCCCG prognosis. The mean number of visits in the 1 st year after OE was 3, on the 2 nd year -1,4, in the 3 rd - 4 th years - 1 per year. All relapsed pts received induction CT (EP or BEP regimen). 11/20 (55%) pts were compliant to visits, 9/20 (45%) pts were not. The 5-years overall survival was 90% and 68% (p=0,3); the median size of metastases in RPLN was 2,2 and 5,5 cm (p=0,001), respectively. All pts in intermediate and poor prognosis were in the noncompliant group, whereas all pts, who were compliant were in good prognosis (3/9 (33%) vs 0/11 (0%), p=0,07). Moreover, surgical removal of residual tumor after induction CT was more often performed in the noncompliant group (5/11 (33%) vs 5/9 (71%), р=0.6). Conclusions: Poor compliance with f.-up program in stage I NSGCT results to non significant worse long-term outcome. Also pts, who were compliant had significantly smaller size of metastases in retroperitoneal lymph nodes at relapse and had good IGCCCG prognosis in all case.
Abstract 928: Preventing melanoma from healing itself after therapy-induced immune attack through IPRES blockade
Authors: Marco Piva, Lu Sun, Gatien Moriceau, Zhentao Yang, Antoni Ribas, Willy Hugo, Roger S. Lo
Journal: Cancer Research (2019)

Abstract Over the past few years, therapeutics development for melanoma has led the oncology field, including the development of mutant BRAF-targeted therapies (e.g., BRAF inhibitor (BRAFi)) and immune checkpoint blockade therapies (e.g., anti-PD-1 or aPD-1, aPD-L1, etc). Based on the complementary qualities of aPD-1/L1 immunotherapy (long duration of response) and MAPKi (high rate of initial response), there are currently clinical trials testing the combination of the two. However, despite a more durable tumor suppression, resistance still eventually develops in patients treated by the combination (ref: KEYNOTE-022). My earlier study reported significant intra-patient and intra-tumoral heterogeneity which affect patient-specific responses to therapy. Furthermore, I also observed complex transcriptomic and tumor microenvironment reprogramming associated with resistance to targeted- or immuno-therapies in melanoma. However, the increased immune/stromal cells in the tumor under therapy has prevented us from definitively accounting the source of such reprogramming. To address this need, I utilized the novel single cell transcriptomic analysis to discover therapy-response-associated gene programs across different types of cells within a tumor. In murine mutant BRAF melanoma YUMM1.7, regressing/responding tumors on the 6th day of BRAFi treatment showed significant infiltration of the T cells and other immune cell population and, by the 15th day, the tumor showed activation of IPRES related processes. Combination of BRAFi and aPD-L1 in YUMM1.7 increased the proportion of lymphoid population in the tumor on the 7th day but only incrementally delayed the development of BRAFi resistance. Inhibition of IPRES-related processes (anti-VEGF and/or anti-TGFB) further delayed BRAFi resistance but no complete responses were observed. However, when we employed a UV-mutated subline of the same model, named the YUMMER (Bosenberg lab, Yale), combination of BRAFi, aPD-L1 and IPRES inhibition started to result in durable complete responses in our mouse model. We are now in midst of analyzing the differential response that we observed with this model; our current working hypothesis is that YUMMER induces higher level of antigen-specific antitumor response, which is augmented by the addition of immune checkpoint blockade and IPRES suppression. The results from our study will eventually pave the way to a novel therapeutic combination to overcome melanoma. Citation Format: Marco Piva, Lu Sun, Gatien Moriceau, Zhentao Yang, Antoni Ribas, Willy Hugo, Roger S. Lo. Preventing melanoma from healing itself after therapy-induced immune attack through IPRES blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 928.
Reply to Wang et al.
Authors: Haruhiro Inoue
Journal: Endoscopy (2019)

See also: Peroral endoscopic myotomy and fundoplication: a novel NOTES procedureEndoscopy eFirstDOI: 10.1055/a-0820-2731 See also: Is the endoscopic Dor fundoplication definitely effective?Endoscopy 2019; 51(07): 697-697DOI: 10.1055/a-0880-5344
Abstract 4586: PLAG enhances macrophage mobility for efferocytosis of active neutrophils via membrane redistribution of P2Y2
Authors: Guen Tae Kim, Do Young Lee, Ki-young Sohn, Sun Young Yoon, Jae Wha Kim
Journal: Cancer Research (2019)

Abstract Neutrophil activity is prerequisite during chemotherapy. The DAMP (Damage Associated Molecular Pattern) molecules generated by chemotherapy could be effectively trapped by activated neutrophil called ‘NETosis’. Efferocytosis of macrophages should remove most activated neutrophils including NETosis A timely removal of activated neutrophils is essential for the prevention of abnormal activation of immune response and metastatic activity of cancer cells induced by tumor microenvironment (TME). Particularly, appropriate clearance of the activated neutrophils by efferocytosis should be carried out because activated neutrophils have a detrimental effect on TME. In this research, we investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on efferocytosis and its underlying molecular mechanisms. In a co-culture of activated neutrophils with macrophages, PLAG increased the activity of efferocytosis for elimination of activated neutrophils. PLAG accelerated translocation of P2Y2 from lipid rafts to non-lipid-raft plasma membrane domains in macrophages. This repositioning of P2Y2 enables the polarization of the cytoskeleton by association of the receptor with cytoskeletal proteins such as α-tubulin and actin to improve the mobility of macrophages. Through these protein assemble, PLAG encouraged macrophage mobility toward the activated neutrophils. Formation of micelle including PLAG, chylomicron-like structures, was a prerequisite for induction of this macrophage activity. PLAG effect on this activity was not observed in the absence of GPIHBP1, micelle receptor. Taken together, these data showed that PLAG triggered a prompt clearance of activated neutrophils through enhancement of efferocytosis activity. Subsequently, PLAG could have effects on modulation of TME. PLAG could be utilized as an effective lipid-based TME modulator via the prevention of abnormal activation induced by uncontrolled immune response during chemotherapy. Citation Format: Guen Tae Kim, Do Young Lee, Ki-young Sohn, Sun Young Yoon, Jae Wha Kim. PLAG enhances macrophage mobility for efferocytosis of active neutrophils via membrane redistribution of P2Y2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4586.