tbuckley/cabot-search huggingface dataset:
Association of immune contexture, age, and tumor stage in peripheral neuroblastic tumors (PNT).
Authors: Salvatore Lorenzo Renne, Chiara Camisaschi, Rosalin Dolores Spagnuolo, Marta Giorgia Podda, Marta Barisella, Chiara Castelli, Roberto Luksch, Paola Collini
Journal: Journal of Clinical Oncology (2017)

e22006 Background: PNTs, a family of tumors arising in the embryonal remnants of the sympathetic nervous system, account for 7-10% of all tumors in children. NMYC status, stage, and age are the most important prognostic factors. The association of patient age and prognosis could be influenced by the maturity of immune system. The aims of this study were to describe the immune contexture in PNTs and to investigate its relationships with patient age and tumor stage. Methods: A cohort of 45 consecutive children with PNT diagnosed and treated at a single centre (2008-2014) with available primary tumor specimen at disease diagnosis and no prior chemotherapy was investigated. Immunohistochemistry for CD45, CD3, CD20, CD14, CD163, CD68, PDL1(P142), and FOXP3 was performed. Presence and status of immune infiltration were scored as follow: the presence of aggregates was assessed at 2.5X scanning magnification and recorded as "high" if present or "low" if no aggregates were visible. Patient age was categorized according to London WB et al (2005) using a 460 days cut-off and INSS tumor stage was considered. Results: Patient age ranged between 8 days and 14 years. Tumor infiltrating CD45 and CD3 scores were lower in INSS tumor stage 4 compared to other INSS tumor stages (CD45: OR=12.37, 95%CI 1.38 -171.00, P=0.01; CD3: OR=9.86, 95%CI 1.52-114.13; P&lt;0.01). Similarly, the monocytes and macrophages markers CD163 and CD14 were associated with tumor INSS stage. The expression of these markers was significantly higher in patient older than 460 days (CD163: OR=4.41, 95%CI 0.77-32.12, P=0.03; CD14: OR=6.94, 95%CI 0.79-335.33, P&lt;0.01). Interestingly, PD-L1 was detected only on immune cells but not on neuroblastic cells. Finally, Treg(FOXP3+) score was low in all but one case. Conclusions: Immune contexture in PNT significantly varies across patient age and tumor stage suggesting a role for maturity of immune system in these patients. [Table: see text]
TCT-358 Reducing stroke while increasing transcatheter aortic valve replacements: case-control analysis of 1,658 procedures over 6 years
Authors: Dominique Monlezun, Adam Whigham, Patrick Byrnes, Abhijeet Dhoble, Richard Smalling, Pranav Loyalka, Biswajit Kar, Tom Nguyen, Anthony Estrera, Prakash Balan
Journal: Journal of the American College of Cardiology (2018)
Abstract 152: Dispatching Emergency Life-Saving Technician Improves Neurological Outcome 1-Month After Out-of-Hospital Cardiac Arrest Independently of Their Advanced Life Support Procedures
Authors: Hiroko Miyauchi, Takahiro Uechi, Takehiro Tsukada, Kyoko Hoshida, Shigeki Shibata, Kazuhiko Ohira, Takanori Ikeda, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao, Takeaki Matsuda, Hideki Nomura
Journal: Circulation (2013)

Background: In Japan, Emergency Life-Saving Technicians (ELSTs) are permitted to place peripheral intravenous catheters, advanced airway devices (esophageal obturator airways, laryngeal mask), and ...
Yellow fever cases in French Guiana, evidence of an active circulation in the Guiana Shield, 2017 and 2018
Authors: Alice Sanna, Audrey Andrieu, Luisiane Carvalho, Claire Mayence, Philippe Tabard, Marina Hachouf, Claire-Marie Cazaux, Antoine Enfissi, Dominique Rousset, Hatem Kallel
Journal: Eurosurveillance (2018)

French Guiana (FG) is a French overseas region bordering Brazil and Suriname that is considered endemic for yellow fever (YF); vaccination is compulsory for residents and travellers. In August 2017 and 2018, two sporadic YF cases were notified 1 year apart, confirming that sylvatic YF virus circulation is active in the region. YF vaccination coverage should be closely monitored and improved in FG and neighbouring territories and clinicians should be aware of the risk.
Association of clinical and biological resistance with a novel mutation in MAP2K1 in a patient with Langerhans cell histiocytosis.
Authors: David Azorsa, David W Lee, Ranjan Bista, Michael Henry, Robert John Arceci
Journal: Journal of Clinical Oncology (2016)

e18554 Background: Langerhans cell histiocytosis (LCH) is a rare disease that is characterized by a clonal proliferation of pathologic histiocytes. While the V600E mutation of the BRAF gene is present in about 50% of patients with LCH, activating mutations in the MAP2K1/MEK1 gene occur in about 25% of patients. We evaluated a patient with treatment refractory LCH for mutations in the RAS-BRAF-MEK-ERK pathway and identified a novel mutation in the MAP2K1 gene (c.293_310del; p.L98-I103del;K104Q) predicted to be auto-activating. During treatment with the MEK1 inhibitor Trametinib the patient’s disease showed significant progression. In this study, we characterized the effect of the novel MAP2K1mutation on activation of the ERK pathway and drug response. Methods: Plasmids were constructed for the expression of wild type (WT) and mutant (MUT) MAP2K1 cDNAs. The plasmids were transiently transfected into HEK-293A cells and treated with MEK inhibitors Trametinib or U0126. Inhibition of ERK protein phosphorylation was determined by western blot and AlphaLisa techniques. Stably transfected cells were also generated and subjected to the same analyses. Results: Cells transiently transfected with MUT MAP2K1 showed a 5-7 fold increase in p-ERK activation and a 2-3 fold increase in p-MEK1 relative to WT-transiently transfected cells. Treatment of the cells with 100 nM Trametinib completely inhibited p-ERK activation in WT-transfected cells but had minimal effect on MUT-transfected cells. Treatment of the cells with 30 µM U0126 also showed similar results. Studies done using the stably expressing WT- and MUT-cell lines using identical treatments showed that Trametinib was similarly ineffective on p-ERK activation in the MUT-cells. Conclusions: The newly identified MAP2K1 c.293_310del mutation auto-activates p-MEK1, which leads to p-ERK activation. These in vitro studies are consistent with the clinical results showing the MAP2K1 c.293_310del mutation to be non-responsive to Trametinib. These results emphasize the importance of functional assessment of genomic data in assigning treatment for patients with cancer as well as provide evidence for choice of inhibitor in patients with this mutation.
Compliance with high-risk screening of unaffected <i>BRCA1</i> and <i>BRCA2</i> pathogenic variant carriers.
Authors: Wendy Salinas Brouwer, Ashley Henriksen Woodson, Grace Tran, Banu Arun
Journal: Journal of Clinical Oncology (2018)

e13528 Background: Facing an increased lifetime risk of breast and ovarian cancer, unaffected BRCA1 and BRCA2 mutation carriers receive genetic counseling regarding National Comprehensive Cancer Network (NCCN) high-risk screenings and prophylactic surgical options (NCCN, 2018). Once diagnosed, high-risk screening referrals are made according to the identified mutation and family history. From this point forward, all follow-up is patient driven. Little is known regarding the compliance of these recommendations. Methods: Retrospective Analysis Results: A total of 52 unaffected BRCA1 and BRCA2 patients were identified from 2015 to 2017 including 15 males and 37 females. The average age of men was 49 (26 – 73) and 38 (18 – 68) for women. Of the 9 men who qualified for clinical assessments, 15 (68%) of the 22 available evaluations were completed. Thirty-five women were eligible for approximately 113 clinical examinations though only 72 (64%) were obtained. Fifty screening mammograms were available for 28 qualified women however, 42 (84%) were achieved. Of the 28 females eligible for a single mammogram, 21 (75%) adhered to the recommendation. Conversely, 18 women qualified for 2-mammograms during the 3-year period, and 12 (67%) received them. Additionally, 28 women were eligible for 45 breast MRI screening opportunities and 29 (62%) completed them. Of the 37 women, 10 (27%) chose prophylactic bilateral mastectomies at an average of 6.8 months post genetic counseling; 9 (16%) acquired prophylactic bilateral oophorectomies at approximately 6 months post genetic testing; and a total of 4 women (11%) obtained both within 6 months of each surgery. The data suggests that there is opportunity to improve the rate of compliance in this population. Conclusions: Literature on the compliance of NCCN recommended cancer screening for unaffected BRCA1 and BRCA2 mutation carriers is sparse with a focus primarily on the occurrence of prophylactic surgeries rather than high-risk screenings. Thus, the reported high-risk screening adherence rates of this population is not truly known. In conclusion, understanding high-risk surveillance trends becomes of paramount importance for early cancer detection.
P01.076 Experience with tumor treating fields (TTFields, Optune®) in Israel - patient compliance and adverse effects
Authors: T Siegal, F Bokstein, D T Blumenthal, L Zach, A Leibovici, S Yust-Katz, A Lossos, T Tzuk-Shina, A Lokiec, Z Ram
Journal: Neuro-Oncology (2018)

TTFields are low intensity, intermediate frequency alternating electric fields, delivered through a portable, non-invasive device (Optune, NovocureTM). The EF-14 phase III trial showed significant prolongation of both progression-free and overall survival in newly diagnosed glioblastoma (GBM) patients. This is the first report on clinical experience with 110 patients treated with TTFields in Israel, focusing on safety and patient acceptance in our country. Patients received Optune-prescription in 6 neuro-oncology centers in Israel and used the device for at least one month. The cohort included both newly diagnosed (n=53) and recurrent GBM (n=57) patients. The male/female ratio was 74/36 with a median age of 58.0 (18–82) years at start of treatment. Of patients with recurrent GBM, 51% were treated at first progression. Our data shows a high acceptance, with a compliance rate (monthly usage of the device) within the first 3 months of 80% for newly diagnosed GBM and 66% for recurrent GBM. Median treatment compliance was independent of age, sex and stage of disease. In addition, our data indicates that the compliance is not negatively correlated with time on treatment, as the median compliance for newly diagnosed GBM patients was still at 79% within the first 6 months. With regards to device-related side effects, data shows that in total 30 patients (27%) experienced mild-moderate skin irritations that were usually manageable with local steroid creams and did not cause significant treatment breaks despite the warm climate in Israel. Other side effects related to the device were heat sensation in 10 patients (9%) and electric sensation in 9 patients (8%) that did not cause significant treatment interruption. The accumulating clinical experience shows that TTFields are well-tolerated by patients in Israel without any major deviation from reported treatment-related side effects. Treatment compliance remains stable during a 6-month period.
Cytokine levels in persistent skin lesions of adult-onset Still disease
Authors: Elina Zuelgaray, Maxime Battistella, Marie-Dominique Vignon-Pennamen, Sophie Ly Ka So, Michel Rybojad, Antoine Petit, Florence Cordoliani, David Boccara, Maurice Mimoun, Dan Lipsker, François Chasset, Armand Bensussan, Martine Bagot, Jean-David Bouaziz, Laurence Michel
Journal: Journal of the American Academy of Dermatology (2018)
A single arm, phase 2, multicenter, international trial of tisotumab vedotin (HuMax-TF-ADC) in previously treated, recurrent or metastatic cervical cancer.
Authors: Robert L. Coleman, Nicole Concin, Thomas J. Herzog, Linn Lena Woelber, Mansoor Raza Mirza, Bradley J. Monk, David Cibula, Domenica Lorusso, Antonio González-Martín, Kristian Windfeld, Jeroen Lammerts van Bueren, Signe Diness Vindeloev, Reshma A. Rangwala, Ignace Vergote
Journal: Journal of Clinical Oncology (2018)

TPS5601 Background: Cervical cancer treatment options are limited for patients with recurrent and/or metastatic cervical cancer. Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) composed of a human antibody targeted to tissue factor (TF), a protease-cleavable linker and the potent microtubule-disrupting agent monomethyl auristatin E (MMAE). The phase 1/2 GEN701 trial (NCT02001623) initially enrolled 34 patients with recurrent or metastatic cervical cancer in the cervical expansion cohort. Treatment with intravenous TV at 2 mg/kg every 3 weeks resulted in an overall response rate of 32% (confirmed and unconfirmed responses) by investigator review per RECIST v1.1 as a part of preliminary analysis. Furthermore, TV was safe and tolerable with a safety profile generally consistent with other MMAE-based ADCs Methods: This is an international, multicenter, open-label, non-randomized phase 2 trial evaluating efficacy of TV in approximately 100 patients with recurrent and/or metastatic cervical cancer who have progressed on a standard 1st line therapy and who have not received more than 2 prior systemic treatment regimens for recurrent or metastatic disease. Response will be assessed every 6 weeks for the first 30 weeks, and then every 12 weeks thereafter. The primary objective is to assess the confirmed objective response rate (ORR) by an independent review committee (IRC) using RECIST v1.1. Secondary efficacy endpoints include: duration of response (DOR), ORR by investigator review, time to response (TTR), progression free survival (PFS), overall survival (OS), and safety and tolerability. For the ORR analyses, a 2-sided 95% exact confidence interval will be calculated using the Clopper-Pearson method. PFA and OS will be analyzed using the Kaplan-Meier method. Adverse events (AEs) will be monitored and graded using CTCAE v5.0.
The TLR7/8/9 Antagonist IMO-8503 Inhibits Cancer-Induced Cachexia
Authors: Federica Calore, Priya Londhe, Paolo Fadda, Giovanni Nigita, Lucia Casadei, Gioacchino Paolo Marceca, Matteo Fassan, Francesca Lovat, Pierluigi Gasparini, Lara Rizzotto, Nicola Zanesi, Devine Jackson, Svasti Mehta, Patrick Nana-Sinkam, Deepa Sampath, Raphael E. Pollock, Denis C. Guttridge, Carlo M. Croce
Journal: Cancer Research (2018)

: Muscle wasting is a feature of the cachexia syndrome, which contributes significantly to the mortality of patients with cancer. We have previously demonstrated that miR-21 is secreted through extracellular vesicles (EV) by lung and pancreatic cancer cells and promotes JNK-dependent cell death through its binding to the TLR7 receptor in murine myoblasts. Here, we evaluate the ability of IMO-8503, a TLR7, 8, and 9 antagonist, to inhibit cancer-induced cachexia. Using EVs isolated from lung and pancreatic cancer cells and from patient plasma samples, we demonstrate that IMO-8503 inhibits cell death induced by circulating miRNAs with no significant toxicity. Intraperitoneal administration of the antagonist in a murine model for Lewis lung carcinoma (LLC-induced cachexia) strongly impaired several cachexia-related features, such as the expression of Pax7 as well as caspase-3 and PARP cleavage in skeletal muscles, and significantly prevented the loss of lean mass in tumor-bearing mice. IMO-8503 also impaired circulating miRNA-induced cell death in human primary myoblasts. Taken together, our findings strongly indicate that IMO-8503 serves as a potential therapy for the treatment of cancer cachexia. SIGNIFICANCE: Cancer-associated cachexia is a significant problem for patients with cancer that remain poorly understood, understudied, and inadequately treated; these findings report a potential new therapeutic for the treatment of TLR7-mediated cancer cachexia.
Malnutrition and overall survival in older patients with cancer.
Authors: Xiaotao Zhang, Ming Sun, Yunlong Geng, Colin P.N. Dinney, Uday R. Popat, Richard E. Champlin, Vicente Valero, Debu Tripathy, Ann-Marie Hedberg, John R Stroehlein, Beatrice Jara-Almonte Edwards
Journal: Journal of Clinical Oncology (2018)

e22015 Background: A growing number of patients with cancer are 65 years of age and older, and undergo age-related and cancer therapy-related changes. Malnutrition is common among cancer patients, and we assessed its prevalence and its association with overall survival. Methods: This is a single site, retrospective cohort study. Patients 65 years of age and older in cancer care underwent a comprehensive geriatric assessment via referrals. Geriatric assessment included cognitive, functional, nutritional, physical, and comorbidity measurement. Malnutrition status was derived from the Mini nutritional assessment and clinical interviews. Patients received recommendations for nutritional supplementation, and when necessary, appetite stimulants. Patients were followed for 3 years. Analysis: Descriptive statistics, and univariate and multivariable survival analysis (Cox regression model) were used. Results: We enrolled 456 patients with complete data that were included for final analysis. Patients had hematologic, gastrointestinal, urologic, breast, lung and gynecologic cancers. The mean age was 77.7 ± 6.9 years, males and females were equally represented. Forty-one percent (n = 190), presented malnutrition, 33% died during the 3-year follow-up. In univariate Cox regression analysis malnutrition was associated with all-cause mortality in all cancers (HR = 1.46, 95% CI = 1.06, 2.01). In multivariate Cox regression analysis, malnutrition was associated with all-cause mortality (HR = 2.38, 95% CI = 1.14, 4.97) in patients with solid tumors. This was not observed in hematologic malignancies. Conclusions: Malnutrition is commonly identified in older cancer patients. Despite nutritional recommendations for increased dietary intake, malnutrition at the time of initial visit remained a risk factor for mortality in older cancer patients, and an independent risk factor for mortality in patients with solid tumors. Prospective interventional studies are recommended.
Association of early specialist-delivered palliative care with less aggressive chemotherapy in patients with advanced lung cancr.
Authors: Austin J. Lammers, Donald Richard Sullivan
Journal: Journal of Clinical Oncology (2017)

e20621 Background:Advanced stage lung cancer has a poor prognosis with high symptom burden. Early specialist-delivered palliative care (ESDPC) has been shown to improve quality of life (QOL) and may even improve survival, but a minority of patients receive this care. Previous studies have found that &gt; 1 regimen of chemotherapy is associated with reduced QOL near death, but it is unknown how palliative care affects aggressive chemotherapy use. We sought to determine if ESDPC impacted aggressive chemotherapy receipt in patients with advanced lung cancer. Methods: A cohort of Veterans with advanced stage IIIB/IV lung cancer in the national Veterans Health Administration network diagnosed between 2007-2013 were included. Demographic data, cancer characteristics, chemotherapy characteristics and early palliative care consultation (within 90 days of diagnosis) were recorded. Aggressive chemotherapy was defined as receipt of a Bevacizumab/Cetuximab triplet, &gt; / = 2 lines of chemotherapy, and more than 4 cycles of a platinum doublet. Descriptive statistics were used to compare demographic data. Unadjusted p-valves were calculated using two-sample t-test. Results: Among 23,660 patients, mean age 68, 98% male, 71% white, 56% current tobacco users. In total, 45% received chemotherapy and 37% received ESDPC. Mean Charlson comorbidity index (CCI) was 4.5 and functional comorbidity index (FCI) was 3. 89% were stage IV, 82% NSCLC. Patients with ESDPC were notably different in CCI (5.4 vs 4) and stage IV (93 vs 86). Of those receiving ESDPC, patients were less likely to receive triple drug therapy (Bevacizumab or Cetuximab combo), less likely to receive &gt; / = 2 lines of chemotherapy and less likely to receive &gt; / = 4 cycles of platinum doublet (all with p-values &lt; 0.001). Conclusions: Our study found that patients who received ESDPC were less likely to receive aggressive chemotherapy. However, comorbidities, cancer stage, and age may have contributed to this difference. We plan to further analyze this data in an adjusted analysis to determine the association between ESDPC and chemotherapy receipt. Future research should focus on identifying patients that will most benefit from aggressive chemotherapy.
Circulating tumor DNA (ctDNA) as an early marker to monitor clinical benefit of regorafenib and TAS-102 in patients with metastatic colorectal cancer (mCRC).
Authors: Allan Andresson Lima Pereira, Michael Lam, Preeti Kanikarla Marie, Kanwal Pratap Singh Raghav, Van Karlyle Morris, Hiromi Brown, Justin Windham, Dzifa Yawa Duose, Michael J. Overman, Eduardo Vilar Sanchez, Ignacio Ivan Wistuba, Peter Kipp, Filip Janku, Sudhir Sinha, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

3533 Background: Utilization of ctDNA has been rapidly adopted as a predictive diagnostic in advanced Non-Small Cell Lung Cancer and indications in GI cancers may be emerging. We aimed to evaluate ctDNA as an early biomarker of efficacy of new therapies for mCRC. Methods: mCRC patients (pts) who consented to a genomic matching protocol and had started a new line treatment with regorafenib or TAS-102 were eligible. Droplet digital PCR (ddPCR) assays were performed using 3 mL of plasma samples from pts with tumors harboring RAS mutations (BioRad). Serial plasma samples also underwent retrotransposable element (RE) based multiplexed qPCR assay using 300 µL of plasma; a DNA Integrity Index (DII) was calculated using a ratio of long to short DNA fragment size concentrations (Innogenomics). Progressive disease (PD) by ctDNA, defined as any increase in allele frequency (AF) by ddPCR and any decrease in DII by RE-qPCR, was compared to RECIST at first restaging. Results: 40 mCRC pts were included. 16 pts were treated with regorafenib and 31 with TAS-102 (7 pts received both drugs). Therefore, 47 treatment regimens were included in this study with serial monitoring completed in 22 treatments with ≥ 2 serial plasma samples. At baseline, the median AF by ddPCR was 18.1% and the median DII was 0.112. A moderate correlation was seen between baselines CEA and AF by ddPCR (r = 0.43; p = 0.056). The sensitivity and specificity of ddPCR in detecting PD by RECIST was 61.5% (95%CI: 32% - 86%) and 100%, respectively. RE-qPCR had a sensitivity of 47.4% (95%CI: 24% - 71%) and specificity of 100%. Unlike ddPCR which was limited to monitoring patients with common mutations in KRAS and NRAS, the DII was successfully obtained in all patients. There was no false-positive in either assays. Serial change in CEA was more sensitive (77.8%), but less specific (16.8%). Conclusions: Our findings suggest that pts with ctDNA predicted PD may be safely switched to another treatment before radiologic restaging. ctDNA by both ddPCR and RE-qPCR can predict later radiological progression with high specificity, with RE-qPCR providing benefits of a universal assay and limited sample requirements.