tbuckley/cabot-search huggingface dataset:
CDK 4/6 inhibitors plus endocrine therapy in ER positive metastatic breast cancer (MBC): Systematic review and meta-analysis of randomized clinical trials
Authors: F. D’Avanzo, C. Saggia, V. Rossi, G. Siffredi, F. Barone Adesi, A. Gennari
Journal: Annals of Oncology (2019)

Background: CDK 4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have been rencently introduced in the clinical management of ER positive metastatic breast cancer (MBC) patients, based on significant improvements in terms of progression free survival (PFS); however, no improvent in overall survival (OS) has been demonstrated in individual trials so far. The purpose of this analysis was to assess, across trials, the effect on progression free (PFS) and overall survival (OS) of the combination of endocrine therapy and CDK 4/6 inhibitors. Methods: We searched literature databases to identify randomized controlled trials that compared endocrine therapy (ET) with ET plus CDK4/6 inhibitors in ER positive MBC. The main outcome measures for this analysis were OS and PFS. Log hazard ratios (HRs) for OS and PFS were pooled across the studies by inverse variance weighting. Primary analyses were done with a fixed effects model, since no heterogeneity was found among studies. Results: We found 7 randomised clinical trials including 3854 patients. Of these, 4 included only first line therapy and 3 allowed prior treatments for MBC. Overall, the addition of CDK4/6 inhibitors to ET was associated with a significant improvement in PFS (HR = 0.54, 95% CI, 0.49 to 0.59; P 0.001), without any remarkable heterogeneity (I2 = 0). In trials of first line therapy, the HR was 0.56 (95% CI, 0.49 to 0.63, P < 0.001); in trials including pretreated MBC the HR was 0.52 (95% CI 0.46 to 0.60, P < 0.001). OS data were reported by 3 out of 7studies (1354 patients); a statistically significant improvement in OS was detected (HR 0.79; 95% CI, 0.66 to 0.96; P 0.015). There were no differences in effects on PFS among subgroups defined by age, metastatic site and Disease Free Interval. Conclusions: The addition of CDK 4/6 inhibitors to endocrine therapy in ER positive MBC was consistently associated with a 50% reduction in the rate of progression both in first and subsequent lines of treatment and this effect appears to be independent of age, site of metastasis and DFI. Overall survival data are available in 3 studies, showing that the PFS advantage translates into a clinically meaningful and statistically significant survival advantage. Legal entity responsible for the study: Alessandra Gennari. Funding: Has not received any funding. Disclosure: A. Gennari: Advisory board: Novartis, Roche, Pfizer, MSD, Lilly. All other authors have declared no conflicts of interest.
RISK SCORE FOR EARLY PREDICTION OF INVASIVE CANCER OF BD-IPMNACCORDING TO MORPHOLOGICAL CHARACTERIZATION IN EUS IN PATIENTS WHO UNDERWENT TO PANCREATIC SURGERY
Authors: L Uribarri Gonzalez, E Perez-Cuadrado Robles, S López López, J Lariño Noia, E Martinez Moneo, J Iglesias Garcia, I Fernandez-Urien Sanz, J Carrascosa Gil, PH Deprez, J Vila Costas
Journal: Endoscopy (2019)

To develop a risk score for early prediction of invasive cancer of BD-IPMN according to morphological characterization in EUS, using the surgical specimens as gold standard.
A NOVEL EX VIVO PORCINE SIMULATOR FOR PERORAL ENDOSCOPIC MYOTOMY TRAINING (POMOD)
Authors: F Azzolini, R Sassatelli, P Cecinato, GF Bonura, D Esposito, F Calabrese, G Dell'Anna, V Iori, R Tomba, G Sereni, M Cavina, L Fanti, E Viale, PA Testoni
Journal: Endoscopy (2019)

POEM is a technically challenging procedure even for experienced endoscopists, thus special training is required.
WHO SHOULD ADMINISTER SEDATION DURING ERCP – ANESTHESIOLOGIST, INTENSIVIST OR ENDOSCOPIST? A COMPARATIVE PROSPECTIVE STUDY
Authors: M Alburquerque, A Vargas García, N Zaragoza Velasco, M Pechkova, J Miñana Calafat, M Figa, R Ballester Clau, M Planella De Robinat, JM Reñe Espinet, F González-Húix Lladó
Journal: Endoscopy (2019)

To compare safety and effectiveness of sedation during ERCP (sERCP) regarding which medical doctor directs it.
Identification of a Novel EML4-ALK, BCL11A-ALK Double-Fusion Variant in Lung Adenocarcinoma Using Next-Generation Sequencing and Response to Crizotinib
Authors: Bao-Dong Qin, Xiao-Dong Jiao, Ke Liu, Ying Wu, Yuan-Sheng Zang
Journal: Journal of Thoracic Oncology (2019)
Management of Preexisting Diabetes in Pregnancy
Authors: Anastasia-Stefania Alexopoulos, Rachel Blair, Anne L. Peters
Journal: JAMA (2019)

<h3>Importance</h3> The presence of preexisting type 1 or type 2 diabetes in pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preeclampsia, cesarean delivery, preterm delivery, macrosomia, and congenital defects. Approximately 0.9% of the 4 million births in the United States annually are complicated by preexisting diabetes. <h3>Observations</h3> Women with diabetes have increased risk for adverse maternal and neonatal outcomes, and similar risks are present with type 1 and type 2 diabetes. Both forms of diabetes require similar intensity of diabetes care. Preconception planning is very important to avoid unintended pregnancies and to minimize risk of congenital defects. Hemoglobin A<sub>1c</sub>goals are less than 6.5% at conception and less than 6.0% during pregnancy. It is also critical to screen for and manage comorbid illnesses, such as retinopathy and nephropathy. Medications known to be unsafe in pregnancy, such as angiotensin-converting enzyme inhibitors and statins, should be discontinued. Women with obesity should be screened for obstructive sleep apnea, which is often undiagnosed and can result in poor outcomes. Blood pressure goals must be considered carefully because lower treatment thresholds may be required for women with nephropathy. During pregnancy, continuous glucose monitoring can improve glycemic control and neonatal outcomes in women with type 1 diabetes. Insulin is first-line therapy for all women with preexisting diabetes; injections and insulin pump therapy are both effective approaches. Rates of severe hypoglycemia are increased during pregnancy; therefore, glucagon should be available to the patient and close contacts should be trained in its use. Low-dose aspirin is recommended soon after 12 weeks’ gestation to minimize the risk of preeclampsia. The importance of discussing long-acting reversible contraception before and after pregnancy, to allow for appropriate preconception planning, cannot be overstated. <h3>Conclusions and Relevance</h3> Preexisting diabetes in pregnancy is complex and is associated with significant maternal and neonatal risk. Optimization of glycemic control, medication regimens, and careful attention to comorbid conditions can help mitigate these risks and ensure quality diabetes care before, during, and after pregnancy.
Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma
Authors: Ajai Chari, Joaquín Martinez-Lopez, María-Victoria Mateos, Joan Bladé, Lotfi Benboubker, Albert Oriol, Bertrand Arnulf, Paula Rodriguez-Otero, Luis Pineiro, Andrzej Jakubowiak, Carla de Boer, Jianping Wang, Pamela L. Clemens, Jon Ukropec, Jordan Schecter, Sagar Lonial, Philippe Moreau
Journal: Blood (2019)
The mutational profile of IBC reveals higher mutational burden, deficiency of homologous recombination and NOTCH signalling
Authors: S.J. Van Laere, P. Finetti, C. Rypens, D. Birnbaum, P. Vermeulen, P. Viens, L.Y. Dirix, F. Bertucci
Journal: Annals of Oncology (2019)

Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with elevated metastatic potential. In the past, we have identified a gene expression profile that characterizes IBC, suggesting that a specific molecular biology underpins this devastating disease. Here, we explore the genomic alterations underlying IBC. Methods: Mutation and copy number variation (CNV) profiles for 756 genes were assembled from 2.920 primary tumor samples (subtype distribution: 63% HR+, 18% HER2+, and 19% TNBC) including 101 profiles from patients with IBC before therapy and 468 profiles from metastatic breast cancer samples. Differences in the frequency of genomic aberrations between patients with and without IBC, stratified per subtype, were investigated. Genomic perturbation differences for pathways and mutational signature (MS) profiles were compared between patients with and without IBC. Results: Seventy-six genes showed evidence of extensive genomic alterations in samples from patients with IBC as compared to those without IBC (i.e. false discovery rate < 10%), whereas only 3 genes reveal the opposite pattern. The 10 top scoring genes according to the odds ratio include: MYC, CYP2D6, VEGFA, CCND1, GNAQ, ZNF703, PTPN11, MCL1, CDK4, and CCDC6. Analysis of MS profiles revealed differences for signature 2, -11, -20, -23 and -24. When comparing to metastatic breast cancer samples, mutations in genes involved in homologuous recombination and in the NOTCH pathway were more prevalent in IBC. Conclusions: These data suggest that IBC is characterized by an extensive mutational burden that results, amongst others in the activation of NOTCH signaling as well as deficient homologuous recombination. The analysis of MS profiles identifies 3 mutational processes in IBC that are associated with transcriptional strand-bias for mutations involving a cytosine (i.e. C>T and C>A), which is indicative for transcription coupled nucleotide excision repair and suggests that mutations involve the complementary guanine base. Legal entity responsible for the study: University Antwerp. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
The final call: how to talk about death
Authors: Alison Shepherd
Journal: BMJ (2019)

Shoppers in south London were disoriented this month by the arrival of an airport departure lounge in the middle of a popular shopping centre.

An often used metaphor for the end of life, the pop-up Departure Lounge in Lewisham was designed to encourage passersby to examine what it means to have a “good death.” …
INJECTION OF CYANOACRYLATE FOR THE TREATMENT OF GASTRIC VARICES BLEEDING
Authors: S Abouelhak, S El mansouri, M Tahiri, F Haddad, W Hliwa, A Bellabah, W Badre
Journal: Endoscopy (2019)

The aim of our study is to evaluate the efficacy and safety of gastric varices injection with cyanoacrylate.
Phase II trial of HER2-PET/CT using 68Ga-anti-HER2 VHH1 for characterization of HER2 presence in brain metastases of breast cancer patients
Authors: M. Keyaerts, C. Xavier, H. Everaert, I. Vaneycken, C. Fontaine, L. Decoster, M. Vanhoeij, V. Caveliers, T. Lahoutte
Journal: Annals of Oncology (2019)

Background: Brain metastases form a challenge in breast cancer patients, especially in HER2+ patients whose peripheral metastases can often be controlled using standard-of-care HER2 regimens, but with relapse or progression in the brain. This determines survival for such patients. Penetration in brain lesions as well as the therapeutic outcome can be hampered due to the particular tumour microenvironment. The here used anti-HER2 agent is a single-domain antibody or nanobody that targets HER2 with nanomolar affinity but with a size that is ten-fold smaller than conventional antibodies. This could be an important factor in diagnostic and even therapeutic efficacy for nanobody radiopharmaceuticals. The 68Ga-anti-HER2 VHH1 has been successfully tested in phase I trial in 20 breast cancer patients, confirming safety and tolerability, low irradiation burden for PET/CT procedures and high uptake in HER2-positive lesions. The aim of the current study is to test its application potential for PET/CT imaging of breast cancer brain metastases. If favourable, this would support the development therapeutic analogues for targeted radionuclide therapy. Trial design: This is an open label non-randomized monocenter phase II trial in breast cancer patients with brain metastasis, investigating the uptake of the radiopharmaceutical 68Ga-anti-HER2 VHH1 in brain metastasis using PET/CT imaging. To evaluate the specificity of uptake, both HER2-positive and HER2-negative patients are eligible. The tumor targeting potential in brain metastases and other known lesions will be visually scored and quantified by an experienced nuclear medicine physician, unaware of the HER2-status. HER2 amplification will be reassessed on blood-derived cell-free DNA. A total of 30 patients (10 HER2-neg, 20 HER2-pos) will be included. The most important inclusion criteria are (i) presence of at least 1 brain metastasis of at least 8 mm, measured either on CT or MRI; (ii) minimal age 18 years old; (iii) informed consent given. Trial is in progress, with 3 HER2-postive and 1 HER2-negative patients enrolled so far. Clinical trial identification: EudraCT 2015-002328-24, NCT03331601. Legal entity responsible for the study: UZ Brussel. Funding: Scientific fund W. Gepts UZ Brussel, IWT-TBM, Kom Op tegen Kanker (stand up against cancer). Disclosure: M. Keyaerts: Travel and accomodation: Bayer; Research funding: Camel-IDS. C. Xavier: Patents on nanobody imaging and therapy. M. Vanhoeij: Research funding: Etherna. V. Caveliers: Research funding: Camel-IDS, IBA. T. Lahoutte: Co-founder, employee: Camel-IDS; Honoraria: Camel-IDS, IBA, Institut des Radioéléments (IRE). All other authors have declared no conflicts of interest.
Pose de fiduciels par écho-endoscopie pour la radiothérapie stéréotaxique des tumeurs pancréatiques: critères de qualité de la pose et évaluation de son innocuité
Authors: A de Malet, PA Laurent, JM Samson, R Bou-Farah, D Malka, V Boige, M Ducreux, J Durand-Labrunie, P Gustin, P Burtin
Journal: Endoscopy (2019)

Pour le traitement de tumeurs pancréatiques par radiothérapie stéréotaxique, la présence de marqueurs «fiduciels» est essentielle au repérage du volume cible. Les fiduciels peuvent être posés sous guidage écho-endoscopique en respectant des critères de qualité établis initialement pour le traitement des tumeurs hépatiques (distance minimale de 18 mm entre les fiduciels, absence de colinéarité, angulation de 15 °, distance de la cible inférieure à 60 mm). Ces critères sont difficilement applicables aux tumeurs pancréatiques (organe plus petit et davantage soumis au péristaltisme).
Abstract 1628: Increased Circulating Endothelin-1 in Obesity-related Hypertension, but not in Obesity or Hypertension Alone
Authors: Oktavia Lilyasari, Adrianus Kosasih, Lies D Liastuti, Librantoro, I R Gunawan, Idris Idham, Sunu B Raharjo, Ganesja M Harimurti
Journal: Circulation (2007)

Introduction: Hypertension and obesity are two conditions closely linked, although the mechanisms responsible for obesity-related hypertension remain unclear. There are controversies regarding the ...
Growth inhibition of triple-negative breast cancer cells due to the lack of CD73
Authors: N. Petruk, J. Sandholm, J. Tuomela, K. Selander
Journal: Annals of Oncology (2019)

Background: Among breast cancer patients, 10-20 % have triple-negative breast tumors (TNBC) and bear the worst prognosis due to the lack of targetable proteins: ER, PR, and Her2. CD73 is a nucleotidase, which converts AMP to adenosine and involved in many processes, such as promotion of cancer cell proliferation, migration and tumor immunoescape. We and others have shown previously that TNBC patients with low tumor TLR9 expression had significantly worse breast cancer-specific survival, as compared with TNBC patients whose tumors had high TLR9 expression upon diagnosis. TLR9 and CD73 expression have demonstrated mutual regulation in immune cells in certain disease conditions, such as diabetes. However, the mutual relationship of these proteins has not been investigated in cancer. The aim of this study was to investigate whether CD73 and TLR9 have mutual effects in TNBC. Methods: The effect of hypoxia (1% O2) on viability and migration of murine 4T1 control and CD73 shRNA murine tumor cells was analyzed with WST-8 and scratch wound experiments. CD73, four adenosine receptors and TLR9 gene expressions was studied with qPCR. Immunofluorescence was used to study TLR9 localization and actin organization. Additionally, expression of TLR9 and cytoskeletal proteins involved in cell migration, such as paxillin, vimentin and cofilin was determined by Western blotting. Results: In the present study, we show that CD73 suppression induces significant inhibition on cell viability and migration. Lower CD73 gene expression correlated with increased TLR9 mRNA levels in normoxia. On other hand, there was no significant correlation of CD73 and TLR9 on protein level in hypoxic conditions. Cytoskeletal proteins vimentin, cofilin and paxillin had lower protein expression in the CD73 shRNA cells compared to the control shRNA cells in normoxia, but not in hypoxia. Additionally, CD73 shRNA cells showed morphological changes and had less cell protrusions. Conclusions: The data indicate that hypoxia upregulates TLR9 mRNA expression, but does not affect CD73 or cytoskeletal proteins expression. In addition, CD73 might promote migration and viability of cancer cells. Our findings suggest a CD73-TLR9 dependent pathway. Legal entity responsible for the study: University of Turku. Funding: Jane and Aatos Erkko Foundation. Disclosure: All authors have declared no conflicts of interest.
Second malignancies with breast cancer: An audit
Authors: V.K. Srinivasalu, N. Subramaniam, S. K S, A. V, S. Kolathu, V.K. D K, A. Philip, W.M. Jose, B. Kunheri, K. Pavithran
Journal: Annals of Oncology (2019)

Background: Breast cancer survivors are at a higher risk of getting another breast cancer, as well as some other types of cancer. The most common second cancer is another breast cancer either at the same side or on the opposite side. Various factors are implicated in increasing the risk of second primary like hormonal therapy, radiation to the breast and axilla and chemotherapy. We aimed to asses the risk of second cancers in breast cancer survivors. Methods: A retrospective audit was done at amrita institute of medical sciences by including patients with breast cancer treated between 2005 and 2015. Results: A total of 3470 breast cancers were included, 37.9%, 48.1% and 14% were EBC, LABC and MBC at presentation. 49 patients presented with second primary with a incidence of 1.4%. Median age was 51.4 years. The most common second primary was breast cancer 16 (Ipsilateral - 5, contralateral - 11), Ovarian cancer in 6 patients, Gastrointestinal malignancies in 12, endometrial carcinoma in 3, acute myeloid leukemia in 3 and thyroid carcinoma in 3 patients. The survival outcomes in patients with second malignancies were poor with 3 years overall survival of 38%. Majority (74%) of the patients received adjuvant chemotherapy with AC followed by Taxol including radiation (72%) as part of their primary treatment. Median time interval for development of second primary was 543 days. Conclusions: Second primary in patients with breast cancer is not a rarity, these patients need to be on long term follow for early diagnosis and treatment. Genetic testing should be considered in patients with history of familial cancers, as genetic testing is not routinely practised due to logistic issues in our patient population, there is immediate need for diagnostics at a low cost to make it affordable to our patients. Legal entity responsible for the study: Amrita Institute of Medical Sciences. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial
Authors: You-Lin Qiao, Ting Wu, Rong-Cheng Li, Yue-Mei Hu, Li-Hui Wei, Chang-Gui Li, Wen Chen, Shou-Jie Huang, Fang-Hui Zhao, Ming-Qiang Li, Qin-Jing Pan, Xun Zhang, Qing Li, Ying Hong, Chao Zhao, Wen-Hua Zhang, Yan-Ping Li, Kai Chu, Mei Li, Yun-Fei Jiang, Juan Li, Hui Zhao, Zhi-Jie Lin, Xue-Lian Cui, Wen-Yu Liu, Cai-Hong Li, Dong-Ping Guo, Li-Dong Ke, Xin Wu, Jie Tang, Guo-Qi Gao, Ba-Yi Li, Bin Zhao, Feng-Xian Zheng, Cui-Hong Dai, Meng Guo, Jun Zhao, Ying-Ying Su, Jun-Zhi Wang, Feng-Cai Zhu, Shao-Wei Li, Hui-Rong Pan, Yi-Min Li, Jun Zhang, Ning-Shao Xia
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.