tbuckley/cabot-search huggingface dataset:
Trends in time to referral to palliative care (PC) at a tertiary care center in Mexico City.
Authors: Andrea Castro-Sanchez, Pier Anyelo Ramos-Elias, Enrique Soto Perez De Celis, Cynthia Mayte Villarreal-Garza, Eucario Leon Rodriguez, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2014)

e20539 Background: A timely referral to PC improves both the quality of life and the survival of cancer patients. Unfortunately, most referrals to PC teams occur within days of death. Additionally, a lack of resources and training in PC delay the care of patients in the final stages of disease. We aimed to evaluate trends in time to referral to PC at our hospital in three different time periods. Methods: Data were collected from death certificates of cancer patients who died at our hospital in 2000, 2005 and 2010. Only those with a diagnosis of advanced-stage disease were included. We used the Kruskal-Wallis test for comparing the groups. Results: A total of 94 patients were included (19 from 2000, 31 from 2005 and 44 from 2010). Median age at death was 60.5 (28-96). 69% were married, 26.6% had graduate education and 77.4% had an average monthly income of US$460 or less. Most died from gastrointestinal cancer (63.8%) and 42% received palliative chemotherapy (15.8% in 2000, 51.6% in 2005 and 47.7% in 2010; p=0.003). 17% received chemotherapy in the 2 weeks before death. 63% had symptoms at the time of PC referral, with pain present in 58.5% of cases. Opioids were prescribed in only 25% of cases, with a significant rise between 2000 and 2010 (5.3 to 41%; p=0.017). The main cause of death was infection (41%), followed by progression of disease (33%). In 2000, only 15.8% of patients were referred to PC, with a significant increase in PC referral in 2005 (51.6%) and 2010 (54.5%) (p=0.003). Median time from first PC visit to death was 2 weeks. There was no difference in time to referral to PC between periods. Conclusions: To our knowledge, this is the first report on time to referral to PC among advanced-stage cancer patients in Latin America. Even though our institution is a tertiary care center with a PC program, almost half of patients with advanced cancer are never referred to PC. While there has been a significant rise in referrals between 2000 and 2010, the time from PC referral to death is short and has not changed over time. A better understanding of the benefits of PC is needed among oncologists in Latin America in order to improve the care of cancer patients at the end of life.
Phase 1 Trial of Cobomarsen, an Inhibitor of Mir-155, in Cutaneous T Cell Lymphoma
Authors: Christiane Querfeld, Francine M. Foss, Youn H. Kim, Lauren Pinter-Brown, Basem M. William, Pierluigi Porcu, Theresa Pacheco, Bradley M. Haverkos, Jennifer DeSimone, Joan Guitart, Ahmad S Halwani, Herbert A. Eradat, Auris Huen, Kristin Schroeder, Linda A. Pestano, Paul J. Williams, Ioanna Cheronis, Gilad S. Gordon, Diana Escolar, Paul Rubin, William S. Marshall
Journal: Blood (2018)
Dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and motor neuron loss in the spinal cord of ALS mouse model
Authors: Jingjing Zhang, Yufei Liu, Xinyao Liu, Song Li, Cheng Cheng, Sheng Chen, Weidong Le
Journal: Translational Neurodegeneration (2018)

Neuron-microglia communication plays a crucial role in the motor neurons (MNs) death in amyotrophic lateral sclerosis (ALS). Neurons can express chemokine (C-X3-C motif) ligand 1 (CX3CL1), which mediates microglial activation via interacting with its sole receptor CX3CR1 in microglia. In the present study, we aimed to investigate the dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and MNs loss in SOD1G93A mouse model of ALS. qPCR, western blot and immunofluorescent staining were used to examine the mRNA and protein levels and localization of CX3CL1/CX3CR1 in the anterior horn region of spinal cord in both SOD1G93A mice and their age-matched wild type (WT) littermates at 40, 60, 90 and 120 days of age. The M1/M2 microglial activation in the spinal cord tissues of SOD1G93A mice and WT mice were evaluated by immunofluorescent staining of M1/M2 markers and further confirmed by qPCR analysis of M1/M2-related cytokines. The immunofluorescent staining revealed that CX3CL1 was predominately expressed in MNs, while CX3CR1 was highly expressed in microglia in the anterior horn region of spinal cord. Compared with age-matched WT mice, CX3CL1 mRNA level was elevated at 40 days but decreased at 90 and 120 days in the anterior horn region of spinal cords in ALS mice. Consistently, CX3CR1 mRNA level was increased at 90 and 120 days. Western blot assay further confirmed the dynamic changes of CX3CL1/CX3CR1 axis in ALS mice. Additionally, the levels of M1/M2 markers of microglia and their related cytokines in the anterior horn region of spinal cord in ALS mice were increased at 90 and 120 days. Moreover, while M1-related cytokines in ALS mice were persistently increased at 120 days, the upregulated M2-related cytokines started to decline at 120 days, suggesting an altered microglial activation. Our data revealed the dynamic changes of CX3CL1/CX3CR1 axis and an imbalanced M1/M2 microglial activation during ALS pathological progression. These findings may help identify potential molecular targets for ALS therapy.
Effect of fluorescence-guided surgery followed by UVC on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) in nude mice.
Authors: Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2014)

e15220 Background: Fluorescence-guided surgery (FGS) is a rapidly developing field. However, even with the improvement of FGS in mouse models, there are still problems with microscopic residual disease. The aim of the present study is to eradicate residual disease after FGS using a patient-derived orthotopic xenograft (PDOX) nude mouse models of pancreatic cancer. Methods: Two weeks after orthotopic implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3 treatment groups; BLS-only (n = 8) or FGS-only (n = 8) or FGS-UVC (n = 8). The residual tumors were resected using a hand-held portable imaging system under fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical resection bed was irradiated with 2700 J/m2UVC (254 nm) in the mice treated with FGS-UVC. Results: The average residual tumor area after FGS only (n = 16) was significantly smaller than after BLS only (n = 24) (0.135 ± 0.137 mm2 and 3.338 ± 2.929 mm2, respectively; p = 0.007). The BLS-only treated mice had significantly reduced survival compared to FGS- and FGS-UVC treated mice for both relapse-free survival (RFS) (p < 0.001 and p < 0.001, respectively) and overall survival (OS) (p < 0.001 and p < 0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to FGS-only treated mice (p = 0.008 and p= 0.025, respectively), with RFS lasting at least 150 days indicating the animals were cured. Conclusions: The results of the present study suggest that UVC irradiation, in combination with FGS, eradicates microscopic residual disease resulting in apparent cures of pancreatic cancer in a nude mouse model that closely resembling the patient.
Hypercytokine-Producing Cells and Oligoclonal T-Cell Populations in Lymph Nodes from Castleman Disease Patients
Authors: Anna Wing, Wenzhao Meng, Gerald Wertheim, Dale Frank, Michele Paessler, Megan S. Lim, Eline T. Luning Prak, David C Fajgenbaum, Vinodh Pillai
Journal: Blood (2018)
Bone density in men receiving androgen deprivation therapy for prostate cancer: A randomized comparison between transdermal estrogen and luteinising hormone-releasing hormone agonists.
Authors: Ruth E Langley, Trinh Duong, Gordana Jovic, Fay Cafferty, Lesley Honeyfield, Richard Abel, Michael Stone, Howard Kynaston, Abdulla A Alhasso, Christopher D Scrase, Edgar M Paez, Ben Spittle, Anna Bara, Mahesh M K Parmar, Paul D Abel
Journal: Journal of Clinical Oncology (2014)

5067 Background: Androgen deprivation therapy (ADT) for prostate cancer with luteinising hormone-releasing hormone agonists (LHRH) reduces bone mineral density (BMD), as testosterone suppression also causes estrogen deficiency in men. Transdermal estrogen is a compelling alternative to LHRH as it achieves similar castrate levels of testosterone but mitigates the cardiovascular toxicity associated with oral estrogen (Langley et al. Lancet Oncology 2013;14:306-16) and may avoid estrogen depletion related toxicities including osteoporosis. Methods: PATCH (Prostate Adenocarcinoma: TransCutaneous Hormones,PR09) is a randomised trial (n=686) comparing estrogen patches (EP; FemSeven 100 µg/24 hr, 4 patches changed twice-weekly reducing to 3 after 4 weeks) versus LHRH for locally advanced or metastatic prostate cancer (allocation ratio 2:1 before 21/2/2011, 1:1 after). In a bone-sub-study, dual-energy x-ray absorptiometry (DXA) scans were performed at baseline, 1 and 2 years. Primary outcome was change in lumbar spine (LS) BMD (mean L1-L4) at 1 year, compared between arms based on intention-to-treat using analysis of covariance, adjusting for baseline values. Results: 85 patients were enrolled from October 2007 to September 2012 from 7 centres (31 LHRH, 54 EP), of whom 8 were excluded (2 withdrew, 6 not eligible as they had osteoporosis on baseline scan). LS BMD data were available for 60 patients (21 LHRH, 39 EP). Median age was 77 years (IQR 73-80), 24 (40%) had bone metastases. At 1 year, mean LS BMD change was -0.03 g/cm3 (95% CI -0.06, -0.003) in LHRH vs 0.08 g/cm3(0.04, 0.11) EP arm (p<0.001); corresponding mean percentage change was -2.11% vs +6.43%, respectively. In patients without bone metastases, the difference was -3.74% LHRH vs +5.04% EP (p=0.001). At 2 years, LS BMD decreased further in LHRH patients (-6.09% from baseline, n=10) while the increase was maintained in those on EP (+4.58%, n=20); p<0.001 comparing arms. Conclusions: Transdermal estrogen, used for achieving androgen deprivation in prostate cancer, protects against bone mineral density loss, confirming the need to continue evaluation of its clinical efficacy. Clinical trial information: ISRCTN70406718.
PROBAST: A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies: Explanation and Elaboration
Authors: Karel G.M. Moons, Robert F. Wolff, Richard D. Riley, Penny F. Whiting, Marie Westwood, Gary S. Collins, Johannes B. Reitsma, Jos Kleijnen, Sue Mallett
Journal: Annals of Internal Medicine (2018)

Prediction models in health care use predictors to estimate for an individual the probability that a condition or disease is already present (diagnostic model) or will occur in the future (prognostic model). Publications on prediction models have become more common in recent years, and competing prediction models frequently exist for the same outcome or target population. Health care providers, guideline developers, and policymakers are often unsure which model to use or recommend, and in which persons or settings. Hence, systematic reviews of these studies are increasingly demanded, required, and performed. A key part of a systematic review of prediction models is examination of risk of bias and applicability to the intended population and setting. To help reviewers with this process, the authors developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) for studies developing, validating, or updating (for example, extending) prediction models, both diagnostic and prognostic. PROBAST was developed through a consensus process involving a group of experts in the field. It includes 20 signaling questions across 4 domains (participants, predictors, outcome, and analysis). This explanation and elaboration document describes the rationale for including each domain and signaling question and guides researchers, reviewers, readers, and guideline developers in how to use them to assess risk of bias and applicability concerns. All concepts are illustrated with published examples across different topics. The latest version of the PROBAST checklist, accompanying documents, and filled-in examples can be downloaded from www.probast.org.
Abstract 11527: Depletion of Pro-angiogenic Progenitor Cells in Bone Marrow of Diabetic Patients Involves the Deregulation of Micro-RNA-155/FOXO3a/p27kip1 Signaling Pathway
Authors: Gaia Spinetti, Daniela Cordella, Orazio Fortunato, Elena Sangalli, Sergio Losa, Ambra Gotti, Franco Carnelli, Francesco Rosa, Fausto Sessa, Antonio P Beltrami, Costanza Emanueli, Paolo Madeddu
Journal: Circulation (2012)

Background:Diabetes mellitus reduces the availability and function of circulating progenitor cells (PCs). This study investigates the effect of diabetes on BM composition, focusing on the microRNA-155 (miR-155)/FOXO3a/p27kip1 signaling pathway as a mechanism underlying the shortage of CD34pos-PCs. Methods:BM was obtained from age-matched non-diabetic (C) and type 2 diabetic (T2D) patients undergoing hip replacement, and from T2D patients undergoing amputation for critical limb ischemia (CLI) (7 to 10 patients/group). BM remodeling was assessed by histomorphometry, immunostaining, and flow cytometry analyses. Apoptotic BM mononuclear cells (MNCs) were identified in situ by TUNEL assay. Expressional studies were performed on MAC-sorted CD34pos-PCs. Results: Diabetes causes a reduction of hematopoietic tissue, fat deposition, and microvascular rarefaction, especially when associated to CLI. Immunofluorescence microscopy documented a decrease of CD34posCD45pos-PCs in BM of both diabetic groups (T2D:-41%, and ...
The shifting landscape of pancreatic cancer research funding.
Authors: Carlyn Rose Co Tan, Rhonda Aizenberg, Lynne Davies, Lynn Matrisian, Xiao Zhang, Richard Tuli, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2014)

e17545 Background: Although pancreatic cancer is the fourth most common cause of cancer death, it only receives approximately 2% of federal dollars distributed by the NCI. Recognizing the need for research support, patient advocacy groups and private institutions are playing a growing role in providing pancreatic cancer research funding to supplement government funds. Methods: The International Cancer Research Partnership (ICRP) is an alliance of governmental and charitable organizations funding regional, national and international cancer research grants and awards which provides key information about ongoing and historical research funding. We interrogated the publicly available ICRP database and corresponding common scientific outline (CSO) codes to review the number of grants for pancreatic cancer (> 80% relevance) awarded from 2008 to 2012. We compared total pancreatic cancer research funding to non-U.S. government funding. Results: The number of awards that include pancreatic cancer decreased by 44% (909 vs 507 awards) from 2008 to 2012. Among awards focused on pancreatic cancer the percentage of funding from non-government entities compared to US government funding increased from 17% to 22% during the same time period. Analy.sis of CSO categories of non-government pancreatic cancer grants over this 5 year period suggests that community-based organizations are predominantly focused on Biology (CSO1), Early diagnosis, detection, and prognosis (CSO4), and Treatment (CSO5). It also demonstrates an increasing emphasis on Etiology (CSO2) and Prevention (CSO3) and decreased activity in Treatment (CSO5). Conclusions: The U.S. government continues to provide a large portion of awards (75 to 80%) in pancreatic cancer research. However, data suggests that the number of government awards in pancreatic research decreased from 2008 to 2012 while the number of awards from non-government entities increased. ICRP data: pancreatic cancer, 2008 - 2012 Non-U.S. governmet ICRP organizations (# awards) CSO CY2008 CY2010 CY2012 CSO 1 biology 44% 44% 48% CSO 2 etiology 3% 5% 9% CSO 3 prevention 1% 3% 6% CSO 4 early detection, diagnosis, prognosis 12% 17% 9% CSO 5 treatment 32% 27% 24% CSO 6 cancer control, survivorship, outcomes research 2% 2% 4% CSO 7 Scientific Model Systems 6% 3% 1%
New paradigm for the treatment of metastatic salivary gland tumors.
Authors: Aron Popovtzer, Michal Sarfaty, Dror Limon, Gideon Marshack, Addie Dvir, Lior Soussan-Gutman, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2014)

e17043 Background: The treatment for metastatic salivary gland adenoid cystic carcinoma (SACC) is not well standardized due to limited clinical evidence. We hypothesized that comprehensive molecular profiling (MP)-guided treatment could individualize treatment and improve clinical outcomes. We compared a cohort of MP-guided treated patients to a historical control cohort treated at the same institute. Methods: All metastatic SACC patients treated at a referral center (2010- 2013) were included. MP was performed using Caris Molecular Intelligence (CMI; Caris Life Sciences); treatment was selected based on the biomarkers identified. The historical controls included all metastatic SACC patients treated at the same institute from 1996 to 2009. Results: The study and historical control cohorts included 14 and 9 patients, respectively. For each study patient, 1-13 biomarkers associated with clinical benefit for specific therapies were identified (most commonly: low/negative TYMS, low ERCC1, high TOPO1). Eleven of the 14 study patients (79%) received MP-guided treatment (2 died prior to treatment initiation, 1 opted not to be treated), whereas 2 (22 %) of the 9 control cohort were treated (1 achieved partial response [PR], 1 progressed). Of the 11 patients receiving MP-guided treatment, 1 experienced complete response, 2 PR, and 5 stable disease; median (range) progression-free survival in the first line of MP-guided treatment was 6.7 (1.4-41.5+) months. Overall survival (from metastatic disease diagnosis) was 25.8 (1.4-70.1+) months in the study cohort vs. 14.0 (1.5-116) months in the control cohort. Conclusions: In this patient population, MP is feasible, expands treatment options, and may improve clinical outcomes. In orphan diseases where prospective randomized trials cannot be performed, MP could become a standard clinical tool.
Modified docetaxel, cisplatin, and 5-fluorouracil combination regimen in advanced gastric cancer: Toxicity and efficacy results.
Authors: Cagatay Arslan, Fatos Dilan Koseoglu
Journal: Journal of Clinical Oncology (2014)

e15036 Background: Platin + fluoropyrimidines ± docetaxel/epirubicin are systemic combination chemotherapy choices for metastatic gastric cancer. Docetaxel+cisplatin+5-fluororacil (TCF) combination is an effective regimen with high rate of toxicity and is not well tolerated especially in patients with poor condition. We aimed to evaluate the efficacy and toxicity of a modified TCF (mTCF) combination regimen in metastatic gastric cancer (MGC). Methods: Data of MGC patients treated with first line mTCF regimen (docetaxel 60 mg/m2 d1 iv, cisplatin 50 mg/m2 d1 iv, 5-fluouracil 400 mg/m2 d1 iv push, 2400 mg/m2; 46 hours iv infusion, leucovorin 400 mg/m2d1 iv push, filgrastim 30/48 MU d4 to d8; sc) were analysed retrospectively. HER-2(+) patients were excluded. Results: Fourty patients were treated and total number of mTCF cycles given was 358. Mean age was 53±11 (min-max:26-75). Dose reduction was made in 11 of 40 patients (27.5%). Total number of cycles dose reduction made was 65 (18.16%). Median number of mTCF cycles given was 9 (min-max: 1-23). There was 1 CR (2.5%) and 18 PRs (45%). Twelve patients had SD, 3 patients had PD and response evaluation could not be made in 6 due to early death of patients. Grade ¾ toxicity was seen in 20 patients (50%) and 35 of the 358 cycles given (9.8%). Hematologic grade ¾ toxicity occurred in 13 patients (32.5%) and 25 of the 358 cycles given (7%). The most frequent grade ¾ toxicities were neutropia (n=11, 27.5%, cycles-n= 12), mucositis (n=9, 22.5%, cycles-n=13). Neutropenic fever was seen in 4 patients (10%, cycles-n=4). Median follow up time was 7.9 months (min-max:0.5-33). Mean TTP was 8.58±1.06 months (95% CI; 6.50-10.66). Mean OS was 8.80 ±1.2 months (95% CI; 3.14-12.40). Conclusions: All grade 3-4 toxicity, neutropenia and neutropenic fever rates were lower in mTCF compared to standard TCF regimen (van Cutsem E, J Clin Oncol 2006) (50% vs 70%, 22.5 vs 81% and 10 vs 29%; respectively). The ORR was higher (47.5 vs 37%), median TTP was longer (8.6 vs 5.6 months) in mTCF compared to V325 study, and OS was similar (8.8 vs 9.2 months) in both studies. Modified TCF is a tolerable and effective chemotherapy regimen for the first line treatment of MGC.
The clinical and pathologic characteristics of 400 gastrointestinal stromal tumor patients from Turkey: The final results of the Turkish Anatolian Society of Medical Oncology Multicenter Registery.
Authors: Alper Sevinc, Mesut Seker, Ramazan Yildiz, Sener Cihan, Mehmet Ali Kaplan, Faysal Dane, Halit Karaca, Ummugul Uyeturk, Ahmet Bilici, Nuriye Ozdemir, Dogan Uncu, Taflan Salepci, Abdurrahman Isikdogan, Mustafa Benekli, Metin Ozkan, Mahmut Gumus, Berna Oksuzoglu
Journal: Journal of Clinical Oncology (2014)

e15176 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. We aimed to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs among the oncology centers in Turkey. Methods: Four hundred patients with GIST from oncology centers in Turkey were retrospectively evaluated on behalf of the Anatolian Society of Medical Oncology registery database. Results: Between January 2001 and March 2013, a total of 400 patients with GISTs were included.The median age was 56 years (range; 22-102 years). Patients were grouped either to R0 resection or to metastatic disease. The median follow-up period is 32 months (range; 12-180 months). There was a statistically significant difference in the tumor site (p< 0.001), tumor size (p=0.04), mitotic index (p< 0.001) and risk categories (p=0.04) between the two groups. The 5-year OS rate for the patients with R0 resection were significantly higher than patients with metastatic diseases (81.7 vs. 74.7% respectively, p=0.04). The 1-, 3- and 5-year overall survival (OS) rates were 97.0%, 86.8% and 76.5%, respectively. All of the metastatic patients received imatinib in the first line and sunitinib in the second line. The third line consists of nilotinib and sorafenib. However, all of the adjuvant patients did not receive imatinib as the drug was re-imbursed in 2008. Conclusions: The study included both resectable, unresectable and metastatic GIST patients in Turkey in a registery database system. Radical surgery is the current treatment of choice with tyrosine kinase inhibitor treatment with novel therapeutics.