tbuckley/cabot-search huggingface dataset:
Prolonged treatment of patients with cancer associated thromboembolism (CAT). mapping of treatment landscape based on a German statutory health insurance (SHI) claims data analysis [CERTIFICAT].
Authors: Albrecht Kretzschmar, Melanie May, Andreas Heinken, Hanno Riess
Journal: Journal of Clinical Oncology (2018)

e18855 Background: CAT is a common complication of cancer and its therapy with impact on overall prognosis. Since 2003 (CLOT, NEJM) low molecular weight heparin (LMWH) instead of vitamin K antagonists (VKA) became recommended treatment according to guidelines. Recently, the use of direct oral anticoagulant drugs (DOAC) was investigated in patients with CAT. No reliable data is available concerning the incidence and the current treatment situation in Germany. The goal of the CERTIFICAT study was to map the epidemiology and treatment of CAT with real world data. Methods: Data on medications and coding of diagnosis for all continuously insured members of SHI (MSHI) were available. A anonymized health claims database (2011-2016) of German SHI was used for a retrospective analysis of patients (pts) with CAT divided by risk: a) normal risk group (NRG) with metachronous occurrence defined as prevalent cancer with initial VTE diagnoses and anticoagulation during the quarter in which VTE occurred; b) High-risk group (HRG) cancer and VTE occurred simultaneously. Results: The sample of > 4 million MSHI identified 322,600 tumor pts and 13,131 (4%) pts with initial VTE diagnosis. 25% of them had no prescription of any anticoagulant. According to the inclusion criteria 7,313 were CAT: 4,421 (60%) NRG and 2,892 (40%) HRG. CAT pts in the NRG and HRG received LMWH in 53 and 64 %, VKA in 24 and 24 %, and DOAC in 21 and 12%, respectively. During prescription of anticoagulation approx. 20% of all pts with CAT suffered from bleedings with no significant differences between agents (LMWH, DOAC, VKA). Data on individual LMWH type and switch of therapy (e.g LMWH = > DOAK) were analyzed as well. Conclusions: Out of 7,313 CP pts with CAT more than half received secondary prophylaxis of VTE with LMWH in accordance with the German guideline. AE bleeding was comparable in different agents of anticoagulation. As compared to available small market research studies our data set offers more reliable information due to its comprehensive character. A relevant subset of pts with CAT did not receive guideline recommended treatment. This has impact on future guidelines and education.
Antibody-nanoparticle conjugate constructed with trastuzumab and nab-paclitaxel for the targeted therapy of positive human epidermal growth factor receptor 2 gastric cancer.
Authors: Jian Xiong, Haijun Zhang
Journal: Journal of Clinical Oncology (2017)

e15506 Background: Gastric cancer is the most lethal malignancies in the digestive system. This study was to investigate antibody-nanoparticle conjugate (ANC) constructed with Herceptin ® and Abraxane ® (Herceptin ® /Abraxane ® ) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer. Methods: Firstly, we fabricated the ANC with Herceptin and Abraxane by a “one-step” synthesis using EDC/NHS. In vitro study, the cell viability, apoptosis and cell cycle of the positive HER2 gastric cancer NCI-N87 cells were measured and compared in four groups of PBS, paclitaxel (Taxol), nano- paclitaxel (Abraxane) and ANC (Herceptin/ Abraxane). In addition, we constructed gastric cancer xenograft model in nude mice to evaluate the targeted antitumor effect in vivo. Furthermore, we chose the NIR797 to locate on the ANC and use the NIR imaging to demonstrate that the ANC could more precise target and delayed release of paclitaxel. Results: ANC of Herceptin/Abraxane was spherical in shape and in a suitable size (289.18 nm±102.6 nm). In vitro, the half-maximal inhibitory concentration (IC50), defined as the concentration of Taxol equivalent needed to kill 50% of cells, was found to be 0.24, 0.13 and 0.048 μg/ml for Taxol , Abraxane and ANC of Herceptin/Abraxane respectively for NCI-N87 cells with an excellent dose-effect relationship. Compared with Taxol and Abraxane, ANC of Herceptin/Abraxane could induce significant G2/M arrest. In vivo, at 4 weeks after treatment, mice treated by ANC of Herceptin/Abraxane had a mean tumor volume of 233±24 mm 3 , Abraxane of 559±97 mm 3 , Taxol of 871±94 mm 3 and PBS as control of 1576±190 mm 3 . Obviously, the ANC could surpasses Abraxane and Taxol in reducing tumor volume with lesser side effects. Furthermore, NIRF imaging indicated a better targeting and sustained release of paclitaxel with ANC than that with Abraxane and Taxol. Conclusions: Antibody-nanoparticle conjugate of Herceptin/Abraxane could mediate targeted therapy and enhance antitumor activity, which could represent a novel targeted therapeutic agent for positive HER2 gastric cancer.
Use of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with cytology proven axillary node-positive breast cancer at diagnosis.
Authors: Hee Jun Choi, Emad Alsharif, Jai Min Ryu, Isaac Kim, Seok Jin Nam, Yeon Hee Park, Seok Won Kim, Jonghan Yu, Jeong Eon Lee
Journal: Journal of Clinical Oncology (2018)

e12640 Background: To evaluate the prognostic effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in patients with cytology-proven axillary node metastasis breast cancer patients. Methods: This study is a registered medical record review based on a prospectively collected cohort. We selected patients who were diagnosed with invasive breast cancer and axillary lymph nodes metastasis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2014. We classified patients into three groups: Group A, negative SLN status and no further dissection; Group B, negative SLN status with backup ALND; and Group C, no residual axillary metastasis on pathology with ALND regardless of clinical response. We analyzed and compared outcomes including prognoses and survival among all groups. Results: The median age at the time of surgery was 44.4 years. The median follow-up time was 47.0 months (range: 3-115 months) and the median number of retrieved SLNs was 5.0. The SLN identification rate was 98.3% (234/238 patients), and the false negative rate (FNR) of SLNB after NAC was 7.5% (8/106 patients). There was no significant difference in disease-free survival (DFS, p = 0.578) or overall survival (OS, p = 0.149) among Groups A, B, and C. In the subgroup analysis of breast pathological complete response (pCR) status, there was no significant difference in DFS (p = 0.271) or OS (p = 0.207) among Groups A, B, and C of the breast pCR patients. Conclusions: These results suggest that SLNB can be feasible and oncologically safe after NAC for node-positive breast cancer and could help reduce arm morbidity by avoiding standard axillary lymph node dissection in negative SLN patients.
Cell-free circulating BRAF V600 mutations analysis by biochip-based assay and droplet digital PCR in melanoma patients
Authors: M. Emelyanova, E. Telysheva, K. Orlova, I. Abramov, G. Snigiryova, O. Ryabaya, A. Zasedatelev
Journal: Annals of Oncology (2018)

Background: More than 50% of melanomas harbor BRAF V600 mutations and can be treated with targeted therapy. Circulating tumor DNA (ctDNA) harbors the same genetic alterations as a tumor origin. The analysis of ctDNA provides diagnostic and prognostic information before, during treatment and at progression. For detection mutations in ctDNA droplet digital PCR (ddPCR) most often are used. This method is very analytically sensitive, but expensive and time-consuming. Methods: We developed a biochip for simultaneous detection six somatic BRAF mutations (V600E [c.1799T>A], V600E [c.1799_1800delTGinsAA], V600M, V600K, V600R, V600D) in small amount of ctDNA. For preferable amplification of mutated over WT DNA we used nested LNA clamp PCR. PCR fragments were labeled via incorporation of Cy5-dTTP during the second round of PCR and hybridized with specific oligonucleotides immobilized on a biochip. Method allows detecting 0.05% mutated DNA in a background of WT DNA. We tested 35 ctDNA samples from melanoma patients. The ctDNA was isolated from 2-5 ml of plasma. For 10 patients plasma collected prior to surgical intervention. For 25 patients plasma collected during antitumor therapy. For all patients we knew BRAF status in tumor. Results: All ctDNA samples were tested by biochip assay and droplet digital PCR (in duplicate). For each assay we used 5 μl of ctDNA. The concordance of results was observed in 32/35 samples. In two cases mutations were detected only by biochip assay. These samples were collected prior surgical intervention and tumor DNA from these patients harbored coincident mutations. In one case mutation V600E was detected by biochip assay, but in ddPCR result we detected one positive drop in each repetition, but this isn't enough to consider this sample V600E-positive. In general, ctDNA BRAF status strong correlated with tumor status and disease progression. Conclusions: The biochip assay is a sensitive method for BRAF mutation detection in ctDNA. This method can be useful in diagnosis and treatment monitoring of melanoma patients. In addition, the biochip assay has the potential for multiplex analysis in contrast to ddPCR. It is very important for the study of small amounts of ctDNA. Legal entity responsible for the study: Engelhardt Institute of Molecular Biology. Funding: This work was supported by Grant of the President of the Russian Federation (# MK-2519.2017.4). Disclosure: All authors have declared no conflicts of interest.
Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides
Authors: Laura Hulea, Simon-Pierre Gravel, Masahiro Morita, Marie Cargnello, Oro Uchenunu, Young Kyuen Im, Camille Lehuédé, Eric H. Ma, Matthew Leibovitch, Shannon McLaughlan, Marie-José Blouin, Maxime Parisotto, Vasilios Papavasiliou, Cynthia Lavoie, Ola Larsson, Michael Ohh, Tiago Ferreira, Celia Greenwood, Gaëlle Bridon, Daina Avizonis, Gerardo Ferbeyre, Peter Siegel, Russell G. Jones, William Muller, Josie Ursini-Siegel, Julie St-Pierre, Michael Pollak, Ivan Topisirovic
Journal: Cell Metabolism (2018)
Preference among non-white cancer patients for mobile devices and social media to learn about supportive services.
Authors: Jun J. Mao, Audra Hugo, James Yang, Susan Q Li
Journal: Journal of Clinical Oncology (2016)

e21686 Background: Disparities in cancer pain management are well-documented. Lack of awareness about supportive care services are key barriers to quality and equitable pain management. Technology, like mobile devices and social media, offer potential solutions; but little is known about the use and preference of communication technologies and social media among cancer patients with pain. We aimed to evaluate information and communication technology use and preferences for cancer patients with pain with a specific focus on racial/ethnic differences. Methods: We conducted a cross-sectional survey study at 1 urban academic medical center and 11 affiliated community hospitals. Patients with a diagnosis of cancer, 18 or older, with a Karnofsky score ≥ 60 who understood written English and reported nonzero pain (0-10 scale) in the last seven days were eligible participants. Participants reported use of communication technology and social media and preference for communicating with healthcare providers about supportive services. We used multivariable logistic regression analyses to determine the relationship between race/ethnicity and use/preference controlling for key social and clinical demographics. Results: Among 662 participants, mean age was 60.4±11.6 (range 23.1-90.4), 65.1% were female, 81.4% white, 13.3% African American, 53.2% were non-metastatic, and 51.5% were seen in community hospitals. Among participants, 27.0% reported mild, 23.8% moderate, and 49.2% severe pain. Of the included technologies, mobile devices were most commonly used (73.8%), followed by email (70.9%), and social media (45.5%). In multivariate analysis, non-white participants expressed a significant preference toward using mobile devices (Adjusted Odds Ratio [A.O.R], 3.19, 2.02-5.05, 95% CI, p < 0.001) and social media (A.O.R 1.94, 1.23-3.07, 95% CI, p = 0.004) to learn about supportive care services. There was no difference in use or preference based on location of treatment. Conclusions: Non-white cancer patients preferred to use mobile devices and social media to learn about supportive care services. Tailoring communication for non-white oncology patients may remove barriers and improve quality pain management.
Abstract 14406: A Novel Population of Neutrophils, Low Density Granulocytes, Are Upregulated in Acute ST Segment Elevation Myocardial Infarction
Authors: Ju H Kim, Heather Teague, Amit K Dey, Aditya A Joshi, Raza Yunus, Joseph B Lerman, Tsion M Aberra, Abhishek Chaturvedi, Qimin Ng, Joanna Silverman, Tarek Aridi, Martin P Playford, Ramesh Mazhari, Nehal Mehta
Journal: Circulation (2016)

Introduction: Neutrophils (PMNs) are known to play a role in atherosclerosis, however, whether they are modulated during STEMI is unknown due to the difficulty in obtaining these cells ex vivo before they activate. Neutrophil extracellular traps (NETs) bearing tissue factor have been implicated in STEMI. Low density granulocytes (LDGs), a subset of pro-inflammatory PMNs first identified in inflammatory diseases such as lupus, have an enhanced ability to form NETs. Whether PMNs are modulated during STEMI and whether LDGs are present during STEMI is unknown. This understanding may augment future therapies targeting these mediators. Methods: A prospective analysis of arterial blood samples obtained from patients presenting with STEMI (n=33) to a single primary percutaneous coronary intervention center was performed. Healthy, age-matched subjects without cardiovascular risk factors were used as controls (n=17). A Ficoll gradient was used to isolate peripheral blood mononuclear cells. LDGs were identified usin...
Cochrane editors hit back at criticisms of HPV vaccine review
Authors: Nigel Hawkes
Journal: BMJ (2018)

An article in a BMJ journal that criticised a Cochrane review on human papillomavirus vaccine made allegations that were not warranted and gave an inaccurate and sensationalised report of the review’s findings, say Cochrane’s two top editors.

David Tovey, editor in chief, and his deputy, Karla Soares-Weiser, have called on BMJ to review whether the quality assurance processes at BMJ Evidence-Based Medicine were appropriately fulfilled and whether the conclusions of the article were “justified and proportionate.”

The sharp response follows an analysis of the claims made by the three authors—two of them experienced Cochrane researchers—in BMJ Evidence-Based Medicine .1 Lars Jorgensen and Peter Gotzsche, from the Nordic Cochrane Centre in Copenhagen, together with Tom Jefferson of the Centre for Evidence Based Medicine in Oxford, said that the Cochrane HPV vaccine review had omitted relevant trials and was influenced by reporting bias and biased trial designs.

When the …
Esophageal cancer in elderly patients: A population-based study.
Authors: Yuan Zeng, Wenhua Liang, Jianxing He
Journal: Journal of Clinical Oncology (2017)

e15561 Background: As the aging issue and increased elderly esophageal cancer (EC) patients, we sought to study the clinical characteristics, treatment modality and outcomes of EC patients 70 years or older compared with those younger than 70 years old. Methods: The national Surveillance, Epidemiology, and End Results (SEER) database for the period from 1973 to 2013 was analyzed. The patient and treatment characteristics were compared between the age groups. Multivariate Cox proportional hazard regression analyses were also performed to identify independent prognostic factors. Propensity-score matching analyses (PSA) regarding survival after different treatments were also performed in locoregional EC . Results: Of 61,799 eligible patients, 24,046 patients (38.9%) were 70 years or older and 37,753 patients (61.1%) were younger than 70 years. Compared with the younger group, patients 70 years or older were characterized by having a higher proportion of patients with female gender, white race, localized disease, non-ademocarcinoma and without any treatment, as well as inferior overall survival (HR, 1.324) and EC-specific survival (HR, 1.270). In addition, older patients shared same independent prognostic factors with younger patients, including age, histology and race. Specifically, compared with those receiving no intensive treatments, surgery alone (HR, 0.342), both surgery and RT (HR, 0.323) and RT only (HR, 0.525) were favorable among elderly patients, as confirmed by both multivariate adjustment and PSA. Conclusions: Compared to younger EC patients, those 70 years or older showed distinctive clinical characteristics and inferior survival. Despite showing a higher proportion of localized disease, patients 70 years or older were less likely to be subjected to surgery or/and RT. Thus, the role of intensive treatments, which were identified as favorable factors among elderly patients in this study, warrants further investigation.
P01.053 The role of PET- and MRI-derived [18F]FET PET parameters in the discrimination of low- and high-grade gliomas
Authors: S Donche, M Henrotte, S Bonte, J Verhoeven, C van den Broecke, M Acou, I Goethals
Journal: Neuro-Oncology (2018)

Gliomas are the most frequent malignant primary brain tumours in adults and can be classified into low-grade gliomas (LGG, WHO grade I-II) and high-grade gliomas (HGG, WHO grade III-IV). Overall survival rate of HGG is poor (months) when compared to LGG (years). Accurate and early diagnosis, for which histopathology is the gold standard, is essential to decide the optimal treatment. Because biopsy and resection bear certain risks, interest is shown in non-invasive diagnostic methods to guide treatment decisions. In this study, different [18F]Fluoro-Ethyl-Tyrosine ([18F]FET) positron emission tomography (PET) parameters were examined for discriminating HGG from LGG. A pre-treatment [18F]FET PET scan and an anatomical MRI were performed in 30 patients. Twenty-four PET-derived parameters, e.g. metabolic tumour volume (MTV), total lesion uptake (TLU) and tumour-to-background ratio (TBR), were calculated using various standardised uptake value (SUV) thresholds. Subsequently, an in-house developed and segmentation algorithm was used to label different tissue categories on both contrast-enhanced T1-weighted and FLAIR MR images: necrosis (N), oedema (OE), non-enhancing tumour (NET) and contrast-enhancing tumour (CET). MR-derived tumour masks were applied on the PET images to calculate 55 PET parameters. PET- and MR-derived FET PET parameters were compared between HGG and LGG. Significantly different parameters were analysed by receiver-operating characteristics (ROC) analysis, yielding area under the curve (AUC) values. Pathological diagnosis served as the reference. Significant differences between HGG and LGG were observed for 13 and 17 for the PET- and MR-derived PET parameters, respectively. The AUC values for significant PET-derived FET PET parameters ranged between 0.78 and 0.85. The lowest AUC value corresponded with TBR1.5 that is defined as the tumour-to-background ratio for the voxels exceeding 1.5 times the mean background SUV. The highest AUC value corresponded with MTV1.5 that is defined as the total volume of voxels with a SUV exceeding 1.5 times the mean background SUV. The AUC values for significant MR-derived FET PET parameters ranged between 0.71 and 0.84. The lowest AUC value corresponded with TLUN+OE+CET+NET that is defined as the total lesion uptake in a volume covering N, OE, CET and NET. The highest AUC value corresponded with TBRmax for all tumour tissue categories (N, OE, CET, NET). TBRmax is defined as the maximal tumour-to-background ratio for N, OE, CET and NET. This study illustrates that various PET- and MR-derived [18F]FET PET parameters differ significantly between HGG and LGG. Hence, PET and MRI of brain tumours may aid the pre-treatment diagnostic classification of gliomas. Further studies in large populations are needed to investigate which parameters may serve as a surrogate for biopsy.
Smoking status and treatment outcome in patients with pancreatic cancer.
Authors: Grzegorz Korpanty, Anna Dodd, Evelyn McGrath, Bethany Pitcher, Ayelet Borgida, Spring Holter, Neesha C. Dhani, David W. Hedley, Steven Gallinger, Sean P. Cleary, Paul D Greig, Ian M McGilvray, Carol-Anne Moulton, Alice Chia-chi Wei, James D. Brierley, Laura A. Dawson, John Kim, Malcolm J. Moore
Journal: Journal of Clinical Oncology (2016)

e15676 Background: Tobacco smoking is a recognized risk factor for pancreatic cancer (PC). The aim of the study was to characterize clinical features, treatment, molecular abnormalities and survival of patients with PC in relation to smoking status. Methods: Data for 299 patients with PC diagnosed and/or treated in the Princess Margaret Cancer Center/University Health Network between 2008-2015 was obtained retrospectively from the electric patient records. Results: There were 141 females (47%), 158 males (53%), median age was 64 years (range: 28-89). Median follow-up was 12.2 months (range: 0.8-82.4). The majority of patients were never smokers (50%) followed by ex- (38%) and current smokers (12%). Of all the patients with known family history, 11% had a history of PC. Among 182 patients with known BRCA status, 14% had germline mutations. Most patients had adenocarcinoma (98%) and presented in stage IV (40%), followed by locally advanced (LO) unresectable (30%) and LO resectable (30%) disease. Smoking did not impact stage at diagnosis. Overall survival (OS) did not differ between never-, ex- and current smokers, with one year OS rates of 51%, 55% and 55%. Smoking pack years was not significantly associated with survival. Smoking was associated with male sex (p = 0.0053), higher body surface area (BSA) (p = 0.00063), and being a BRCA carrier (p = 0.01). Never smokers were more likely to have experienced weight loss at diagnosis (p = 0.027). In multivariable analysis old age ( > 64 vs. < 64; HR = 1.34; 95% CI: 1.01-1.8; p = 0.045) and poor performance status (ECOG 2-3 vs. 0; HR = 1.92; 95% CI: 1.24-3; p = 0.0038)were associated with poorer survival. Metastatic (vs. resectable) disease at diagnosis was associated with poorer survival, however the effect was largest in early follow-up and diminished with time (HR = 6.88, 95% CI: 3.35-14.14; p < .0001, with time HR = 0.95, 95% CI: 0.91-1, p = 0.031).After adjusting for age, BSA, ECOG and stage at diagnosis, smoking status was not significantly associated with survival (HR = 0.89; 95% CI = 0.67-1.18; p = 0.43). Conclusions: Smoking status does not affect treatment outcome in patients with pancreatic adenocarcinoma. Association of germline BRCA and smoking warrants validation studies.