tbuckley/cabot-search huggingface dataset:
Anti-HER2 CD4 T helper type 1 response in breast cancer: Is there a role for immunorestoration?
Authors: Jashodeep Datta, Rachel L Yang, Andrew M Brod, Rosemarie Mick, Erik Berk, Elizabeth Fitzpatrick, Shuwen Xu, Kevin R. Fox, Rachel R Kelz, Brian J. Czerniecki
Journal: Journal of Clinical Oncology (2014)

636 Background: Tumor microenvironment infiltration of IFNγ-producing CD4 T helper 1 (Th1) cells is linked to improved prognosis in invasive breast cancer (IBC). We investigated circulating anti-HER2 CD4 Th1 response (Th1resp) involved in breast tumorigenesis, and compared Th1resp prior to after chemotherapy/trastuzumab (C/T) treatment or dendritic cell vaccination in HER2+ IBC pts. Methods: Th1resp were compared in healthy donors (HD; n=21) and pts with benign breast biopsy (BD; n=9), HER2neg IBC (n=11), HER2+ DCIS (n=31), and HER2+ IBC (n=14). Th1resp of pts enrolled in neoadjuvant immunization trials for HER2+ DCIS and found to have Stage I IBC at surgery (n=11) were analyzed pre/postimmunization, and compared with HER2+ IBC pts after C/T (n=34). Th1resp were generated from PBMC pulsed with 6 HER2 MHC class II peptides, by measuring IFNγ via ELISPOT. Th1resp metrics were (1) anti-HER2 response rate, (2) # of reactive peptides (repertoire), (3) cumulative response across 6 peptides (SFC/106 cells). Contribution of regulatory T cells (Treg) to immune profiles was assessed by IL-10 production via ELISPOT. Results: Stepwise decrements in response rate (100% vs 100% vs 100% vs 84% vs 21%; p<0.0001), repertoire (5.2 vs 4.6 vs 3.9 vs 2.0 vs 0.4; p<0.0001), and cumulative response (259.9 vs 218.7 vs 191.2 vs 125.2 vs 33.0 SFC/106, p<0.0001) were observed among HD, BD, HER2neg IBC, HER2+ DCIS, and HER2+ IBC cohorts respectively. HER2+ DCIS and -IBC pts differed in response rate (p<0.001), repertoire (p=0.001), and cumulative response (p<0.001). HD, BD, and HER2neg groups did not vary significantly. After immunizing HER2+ IBC pts, improvements were seen in response rate (91% vs 18%, p=0.004), repertoire (3.7 vs 0.3, p<0.0001), and cumulative response (162.8 vs 29.7 SFC/106, p<0.0001). C/T treated and untreated IBC patients did not differ significantly. IL-10 production, as well as CD4+Foxp3+ cell (Treg) proportions by flow cytometry, was similar between HD, HER2+IBC, and C/T treated pts. Conclusions: Anti-HER2 Th1resp is progressively lost in breast tumorigenesis, and is Treg-independent. Vaccination – but not targeted therapies – restores Th1resp in IBC, providing rationale for immunization to prevent subsequent breast events.
Lux-Lung 8: A Randomized, Open-Label, Phase III Trial of Afatinib vs. Erlotinib in Patients with Advanced Squamous Cell Carcinoma of the Lung as Second-Line Therapy Following First-Line Platinum-Based Chemotherapy
Authors: G. Goss, S. Lu, E. Felip, A. Ardizzoni, V. Georgoulias, S. Gadgeel, V. Chand, Y. Gu, Y.S. Olivo, J. Soria
Journal: Annals of Oncology (2012)
Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemia
Authors: Je-Hwan Lee, Hawk Kim, Young-Don Joo, Won-Sik Lee, Sung Hwa Bae, Dae Young Zang, Jihyun Kwon, Min Kyoung Kim, Junglim Lee, Gyeong Won Lee, Jung-Hee Lee, Yunsuk Choi, Dae-Young Kim, Eun-Hye Hur, Sung-Nam Lim, Sang-Min Lee, Hun Mo Ryoo, Hyo Jung Kim, Myung Soo Hyun, Kyoo-Hyung Lee
Journal: Journal of Clinical Oncology (2017)

Purpose We compared two induction regimens, idarubicin (12 mg/m 2 /d for 3 days) versus high-dose daunorubicin (90 mg/m 2 /d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m 2 /d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.
PHOCUS: A phase 3 randomized, open-label study comparing the oncolytic immunotherapy Pexa-Vec followed by sorafenib (SOR) vs SOR in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy.
Authors: Ghassan K. Abou-Alfa, Peter R. Galle, Yee Chao, Karen T. Brown, Jeong Heo, Mitesh J. Borad, Angelo Luca, Adina Pelusio, Delphine Agathon, Monika Lusky, Caroline Breitbach, James Burke, Shukui Qin
Journal: Journal of Clinical Oncology (2016)

TPS4146 Background: Pexa-Vec (pexastimogene devacirepvec; JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to selectively replicate in and destroy cancer cells. It causes direct oncolysis accompanied by tumor vascular disruption and anti-tumor immunity mediated by expression of the transgene GM-CSF. SOR, a multi-targeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced HCC. Both preliminary preclinical and clinical data suggest complementary anti-tumor effects of a sequential combination of Pexa-Vec followed by SOR possibly by targeting the tumor vasculature via different mechanisms (Heo et al., Mol Ther 2011). A randomized phase II dose-finding study with 3 Pexa-Vec intratumoral (IT) liver injections in first line advanced HCC patients showed an acceptable safety profile and a significant increase in overall survival (OS) in the highest dose group (109pfu) (Heo et al., Nat Med 2013). Methods: This global, randomized, open-label, phase III study will compare the efficacy and tolerability of Pexa-Vec followed by SOR vs SOR in advanced HCC patients. Eligible patients are Child-Pugh A, ECOG PS 0-1, BCLC B/C, have at least 1 measurable and viable liver tumor (based on radiographic assessment) injectable under imaging guidance, have liver tumor mass < 50% of the total liver volume, no invasion of the inferior vena cava, and had no prior systemic therapy for HCC. 600 patients will be randomized 1:1 to either 3 Pexa-Vec IT injections administered every 2 weeks at a dose of 109pfu (D1, W2, W4) followed by 400 mg BID SOR starting at W6 or to SOR 400 mg BID (from D1). Patients are allocated to treatment arm using minimization by center, HCC etiology, presence of extra-hepatic disease, vascular invasion, PS 0-1, AFP levels. The primary endpoint is OS (1-sided stratified log-rank test; α = 0.025, 86% power, HR 0.83). Secondary endpoints include time to progression, progression-free survival, overall response rate and disease control rate (radiographic evaluation every 6 weeks). In addition, safety, biomarkers and quality of life will be evaluated. Clinical trial information: NCT02562755.
AB0507 Cobalamin (VITAMIN B12) status in patients with antiphospholipid syndrome (APS), its association with atherosclerotic vascular lesions
Authors: I Segeda, S Shevchuk, I Kuvikova, O Shevchuk, I Segeda, S Shevchuk, I Kuvikova, O Shevchuk
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cobalamin (vitamin B12) insufficienty is associated with the development of many diseases. It is known that the growth of clinical and subclinical manifestations of atherosclerotic vascular lesions are often associated with low cobalamin level. Cobalamin status is unknown in patients with antiphospholipid syndrome (APS). There are no data about the role of folic acid in the development of atherosclerotic vascular lesions in patients with APS <h3>Objectives</h3> To evaluate vitamin B12 status in patients with APS and to explore its relationship with atherosclerotic vascular lesion. <h3>Methods</h3> We observed 82 patients with APS and 37 healthy individuals. Content of cobalamin (vitamin B12) in serum were determined by immunochemical detection (ECLIA). Cobalamin level above 200 pg/ml was considered as normal within 200–300 pg/mL - both extremely low, below 200 pg/ml - insufficienty. All patients were underwent detection of endothelial dysfunction - dilatation of brachial artery endothelium, investigation of "intima-media" thickness of common carotid artery (IMT) and the presence of atherosclerotic plaques (AP). <h3>Results</h3> In patients with APS we recorded a significant reduction of cobalamin in the serum (351±14,3 pg/mL (95% CI: 148–562 pg/mL) compared to control group (445±18,1 pg/mL (95% CI: 272–622 pg/mL). Indicators of cobalamin status in patients with secondary APS were significantly worse than patients with primary APS. Thus, in patients with secondary APS cobalamin content was on 26.7% lower (95% CI: 140–559 pg/ml) than in the control group. In patients with primary APS cobalamin content was on 13.0% lower (95% CI: 202–565 pg/ml) than in controls, but 18.7% higher than in patients with secondary APS. Cobalamin (vitamin B12) insufficienty is accompanied by significant thickening of the walls of the common carotid artery. Thus, in patients with cobalamin deficiency IMT was on 17% higher than that in patients with optimal levels of the vitamin. Cobalamin deficiency is also associated with endothelial dysfunction. Thus, in patients with vitamin deficiency dilatation of brachial artery was significantly, by 48.6% less than in people with normal vitamin B12 status. The share of people with the presence of atherosclerotic plaques, transient ischemic attack (TIA), stroke, myocardial infarction (MI) and angina in patients with cobalamin deficiency was also higher. <h3>Conclusions</h3> Thus, in patients with APS low cobalamin status is associated with subclinical manifestations of atherosclerotic vascular lesions. <h3>Disclosure of Interest</h3> None declared
Pilot trial of chidamide, an oral histone deacetylase (HDAC) inhibitor, in combination with exemestane in hormone receptor-positive advanced breast cancer.
Authors: Qingyuan Zhang, Tao Wang, Cuizhi Geng, Yue Zhang, Jinwen Zhang, Zhi-Qiang Ning, Zefei Jiang
Journal: Journal of Clinical Oncology (2017)

e12543 Background: Chidamide (CHI) is a novel benzamide type of subtype-selective histone deacetylase inhibitor approved in China for refractory and relapsed peripheral T-cell lymphoma with a dosage of 30 mg PO twice a week. A randomized, double blind and placebo-controlled phase 3 clinical trial of CHI plus exemestane (EXE) is currently ongoing in patients (pts) with hormone receptor-positive (HR+) advanced breast cancer (ABC). This abstract reports the results from the pilot study preceded the phase 3 trial. Methods: Eligible pts were postmenopausal women recurrent or progressed to at least one endocrine therapy. In the run-in period for pharmacokinetic (PK) analysis, pts received EXE 25 mg on day (D) 1 and CHI 30 mg on D 2. From D 5 pts started combination treatment having EXE 25 mg daily and CHI 30 mg twice a week until progression of disease (PD) or intolerable toxicities. A treatment cycle was defined as 28 days. Safety, PK parameters and preliminary efficacy were assessed. Results: 20 pts with HR+ and HER-2 negative were enrolled between Jul and Dec, 2015. Median duration of treatment was 5 cycles (range 0-16), with 4 pts still on treatment. 3 pts discontinued due to adverse events (AE). Drug-related AEs ≥ grade 3 in 2 or more pts were neutropenia (35%), thrombocytopenia (30%), and leucopenia (20%). Similar plasma exposure of EXE was observed in the absence and presence of CHI ( 73 ± 27 vs. 80 ± 29 ng·hr/mL). A potential increased plasma exposure of CHI was noted in the presence of EXE compared with CHI alone ( 2232 ± 973 vs 1787 ± 946 ng·hr/mL), apparently related to the inter-patient variations in CHI plasma concentrations. Best response in 18 pts was assessed by RECIST, including 3 pts with partial response, 12 pts with stable disease and 3 pts with PD. Median progression free survival was 7.6 months. Conclusions: The combination of CHI and EXE was generally well tolerated. Most AEs were related to the CHI single-agent treatment that are generally manageable. Encouraging antitumor activity was observed. The overall results from this pilot trial enabled the next-stage clinical development of this combination regimen in HR+ ABC pts. Clinical trial information: NCT02482753.
Most deaths of babies and brain injuries in childbirth are avoidable, says college
Authors: Jacqui Wise
Journal: BMJ (2017)

Three quarters of deaths of babies or injuries to their brain during childbirth could be avoided with better fetal monitoring and neonatal care, a report from the Royal College of Obstetricians and Gynaecologists has concluded.1

An investigative team conducted more than 2500 expert assessments of local reviews into the care of 1136 babies born in the UK in 2015, of whom 126 were stillborn, 156 died within the first seven days of birth, and 854 had severe brain injury.

A quarter of the local reports were branded inadequate as they were not thorough enough to allow a full assessment. The Each Baby Counts report, the findings of …
Analysis of total tumor load of sentinel lymph node as a prognostic factor in patients with early breast cancer.
Authors: Vicente Peg, Irene Sansano, Begona Vieites, Laia Bernet, Rafael Cano, Alicia Cordoba, Magdalena Sancho, Maria Dolores Martin, Felip Vilardell, Martin Espinosa-Bravo, Jose Manuel Perez-Garcia, Javier Cortes, Isabel T Rubio, Santiago Ramon y Cajal
Journal: Journal of Clinical Oncology (2016)

1042 Background: Axillary staging (pN) is considered one of the main prognostic factors in breast cancer patients. However, the publication of the Z0011 study drastically reduced the number of surgical axillary dissections in a particular group of patients, limiting the prognostic information of axillary involvement only to the sentinel lymph node (SLN). Following the publication of the relationship between SLN total tumor load (TTL) and axillary involvement, this work aims to study a possible relationship between the former and recurrence risk and overall survival of breast cancer patients. Methods: clinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification). Results: TTL (defined as the sum CK19 mRNA copies in all SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL < 2.5E + 04 CK19 mRNA copies/uL) versus another high-risk group ( > 2.5E + 04 CK 19 mRNA copies/uL). The prognostic value of this variable is enhanced if other clinical and pathological criteria (tumor size, lymphovascular invasion, HER2, Ki67), grouped in a nomogram, are added. Conclusions: SLN TTL permits the differentiation between two patient groups in terms of disease-free survival and overall survival, independently of axillary staging (pN), tumor and age characteristics. This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed after sentinel node involvement.
Особливості перебігу та можливості корекції кишкового дисбіозу у хворих на ішемічну хворобу серця
Authors: E.Y. Arkhiy, Ya.S. Derbak, S.E. Derbak
Journal: GASTROENTEROLOGY (2013)

У статті наведено результати обстеження та лікування 107 хворих на ішемічну хворобу серця у поєднанні із дисбіозом кишечника. Показано, що домінуючим симптомом кишкового дисбіозу у хворих на ішемічну хворобу серця є запор. Включення до стандартних схем терапії ішемічної хвороби серця засобів корекції мікробіоценозу кишечника сприяє зменшенню вираженості не тільки дисбіотичних змін, але й клінічних симптомів основного захворювання.
Phase I study of the combination of balixafortide (CXCR4 inhibitor) and eribulin in HER2-negative metastatic breast cancer (MBC) patients (pts).
Authors: Marta Gil-Martin, Patricia Gomez Pardo, Sara Lopez-Tarruella, Luis Manso, Jose Alejandro Perez-Fidalgo, Foluso Olabisi Ademuyiwa, Ingrid A. Mayer, Timothy J. Pluard, Maria Martinez Garcia, Peter A. Kaufman, Linda T. Vahdat, Leon W. Hooftman, Barbara Romagnoli, Cristina Hernando, Katherine N. Weilbaecher, Eva M. Ciruelos, Miguel Martin, Sonia Pernas Simon, Javier Cortes
Journal: Journal of Clinical Oncology (2017)

2555 Background: Balixafortide (POL6326) is a cyclic peptide and a potent, selective antagonist of the chemokine receptor CXCR4. Evidence suggests that CXCR4 inhibition interferes with the tumor-protective microenvironment and sensitizes tumor cells to chemotherapy. The combination of balixafortide (B) and eribulin (E) was safe with early signs of efficacy in the dose escalation part of this study. Methods: The expanded cohort of thisopen label phase I study was designed to assess the anti-tumor activity, safety and pharmacokinetics of the addition of the recommended phase 2 dose (RP2D) of B to E in pts with MBC and with any CXCR4 expression level at the tumor site. Patients received E (1.4 mg/m 2 ) on days 2 and 9, flanked by B (5.5 mg/kg) on days 1-3, and 8-10 of 21-day cycles. Results: 24 pts with relapsed MBC (median age 59 [33-82]) were enrolled in the expanded cohort. Median number of prior chemotherapies for MBC was 2 (range 1-3). 20/24 (83%) pts were ER and/or PR positive; 3/24 (13%) pts had TNBC. Objective response rate (ORR) was 33%. 8/24 (33%) pts achieved a partial response and 4/24 (17%) pts had meaningful (≥ 6 months) stable disease for a Clinical Benefit Ratio of 50%. Median duration of treatment was 15.3 weeks (range 5-40) with 11 pts still on treatment. The most common Gr 3-4 adverse events were neutropenia (9/24, 38%) and leucopenia (3/24, 13%); 2 pts had febrile neutropenia and 1 patient died from sepsis. 15/24 (63%) pts experienced histamine-like infusion reactions related to B that were manageable with anti-histamines. Conclusions: The therapeutic activity of this treatment regimen appears promising with an ORR of 33% in patients with advanced MBC. B (5.5 mg/kg) can be combined safely with E (1.4 mg/m 2 ) and the safety profile resembles E monotherapy as previously reported. This is the first study of the treatment combination of E with B in relapsed MBC pts. Further confirmatory studies are being considered. Clinical trial information: NCT01837095.
Impact of Changes in Consensus Diagnostic Recommendations on the Echocardiographic Prevalence of Diastolic Dysfunction
Authors: Olivier Huttin, Alan G. Fraser, Stefano Coiro, Erwan Bozec, Christine Selton-Suty, Zohra Lamiral, Zied Frikha, Patrick Rossignol, Faiez Zannad, Nicolas Girerd
Journal: Journal of the American College of Cardiology (2017)
Treatment options for oesophageal cancer: The influence of combined synchronous PET-CT
Authors: Z Bell, C McKeown, G Spence, T Lynch, J McGuigan
Journal: Endoscopy (2005)

Aims: Accurate staging of oesophageal cancer is essential for optimal treatment planning. This study evaluated the clinical utility of combined positron emission tomography – computed tomography (PET-CT) scanning in selecting the appropriate therapeutic approach for patients.
Traitement endoscopique palliatif des sténoses malignes du duodénum par insertion de prothèses métalliques
Authors: I Graber, J Dumas, B Filoche, J Boyer, D Coumaros, H Lamouliatte, JL Legoux, B Napoléon, T Ponchon
Journal: Endoscopy (2005)

Les sténoses néoplasiques duodénales symptomatiques sont habituellement traitées par gastroentéroanastomose chirurgicale associée ou non à une dérivation biliaire. Depuis quelques années a été développée une prothèse duodénale endoscopique métallique expansive. Le but de cet essai prospectif, multicentrique, de phase II a été d'évaluer l'efficacité immédiate et tardive du traitement endoscopique et sa morbidité.
Transformation in Pre-Treatment Presentations of Gaucher Disease during the First Two Decades of Imiglucerase Enzyme Replacement Therapy: A Report from the International Collaborative Gaucher Group Gaucher Registry
Authors: Pramod Mistry, Neal J. Weinreb, Julie Batista, Hans C. Andersson, Manisha Balwani, Thomas Andrew Burrow, Joel Charrow, Paige Kaplan, Aneal Khan, Priya S. Kishnani, Edwin H. Kolodny, Barry E. Rosenbloom, C. Ronald Scott
Journal: Blood (2016)
A GP’s experience of the Grenfell Tower fire
Authors: Ahmed Kazmi
Journal: BMJ (2017)

Wednesday 14 June was a tragic day for so many and a very atypical day in our surgery. My clinic is less than 800 m from Grenfell Tower, and several of our patients were residents there. We spent the day trying to compile a list of our patients who had been dispossessed. We made comfort calls to those affected (especially the vulnerable ones), offered walk-in appointments to those who found themselves without their medication, and tried to offer some comfort. It is difficult, though. What do you say to someone who has just lost their home and everything they own? “I am …
Evaluation de l'intérêt clinique de la “Patency Capsule M2A“ chez des patients suspects de sténose intestinale avant un examen par la capsule vidéo-endoscopique
Authors: G Gay, E Ben Soussan, V Laurent, E Lerebours, M Delvaux
Journal: Endoscopy (2005)

Le seul risque de complication reconnu de la capsule endoscopique (VCE – Pill Cam™) est le blocage de sa progression par une sténose digestive. La “patency capsule“ (Given Imaging, Yoqneam, Israel) est un dispositif constitué d'une capsule auto-soluble et d'un détecteur de métaux permettant de la localiser au niveau de l'abdomen. La patency capsule permet donc de calibrer la lumière digestive; lorsque sa progression est arrêtée par une sténose, elle se dissout 40 à 80 heures après l'ingestion et ne devrait donc pas entraîner d'occlusion intestinale. Le but de cette étude était d'évaluer l'utilité de ce dispositif chez des patients suspects de sténose digestive et ayant une indication d'examen par la VCE.