tbuckley/cabot-search huggingface dataset:
Evaluation of severe neutropenia and diarrhea in Asian cancer patients receiving <i>UGT1A1</i> genotype-guided irinotecan dosing.
Authors: Natalia Sutiman, Saminathan Ramasamy, Chau Hsien Matthew Ng, SuPin Choo, Rachel Lim Wenrui, Clarinda Chua Wei Ling, John Chia Whay Kuang, Iain B. Tan, Balram Chowbay
Journal: Journal of Clinical Oncology (2015)

e13572 Background: Inactivation of SN-38, the active metabolite of irinotecan, occurs mainly via glucuronidation mediated by UDP glucuronosyltransferase (UGT) 1A1. The role of UGT1A1*6 and *28 polymorphisms in altering SN-38 disposition and increasing the risks of neutropenia and diarrhea has been reported in Asian cancer patients receiving standard-dose irinotecan. This study aimed to evaluate the incidence of severe neutropenia and diarrhea in Asian cancer patients treated with UGT1A1 genotype-guided doses of irinotecan. Methods: High Resolution Melting analysis was performed for the detection of UGT1A1*6 and *28 in 61 patients with advanced solid tumours prior to the initiation of irinotecan-based regimens. Irinotecan dose was administered according to their UGT1A1 genotypes and chemotherapy regimens. Incidence and severity of neutropenia and diarrhea were retrospectively evaluated over the entire duration of irinotecan therapy according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0. Results: Median age of the patients was 64 (range: 29 - 80). Majority of the patients were Chinese (77.0%), followed by Malays (14.8%) and Indians (8.2%). Of the 15 patients receiving single-agent irinotecan, only one (6.67%) developed grade 3/4 neutropenia and diarrhea. Two of the 19 patients (10.5%) treated with weekly XELIRI developed grade 3/4 neutropenia and none developed severe diarrhea. One of the 9 patients (11.1%) treated with three-weekly XELIRI developed grade 3/4 diarrhea and none developed grade 3/4 neutropenia. Three of the 10 patients (30.0%) treated with FOLFIRI had grade 3/4 neutropenia and one (10%) developed grade 3 diarrhea. Of the 6 patients treated with irinotecan and cisplatin, two patients (33.3%) developed grade 3/4 neutropenia and one patient (16.7%) developed grade 3/4 diarrhea. Both patients receiving irinotecan and 5-fluorouracil did not experience neutropenia and diarrhea. Conclusions: UGT1A1*6 and *28 genotype-guided dosing of irinotecan markedly reduced the incidence of grade 3/4 neutropenia and diarrhea in Asian cancer patients.
Chemotherapy-related cognitive impairment (CRCI), and neurotransmitter signaling, longevity, and inflammation pathways in 366 breast cancer (BC) patients and 366 age-matched cancer-free controls: A prospective, nationwide, longitudinal URCC NCORP study.
Authors: Michelle Christine Janelsins, Song Yao, Karen Michelle Mustian, Luke Joseph Peppone, Charles E. Heckler, Benjamin Esparaz, Jeffrey K. Giguere, Robert Irwin, Barbara Neilan, Tim Ahles, Christine B. Ambrosone, Gary R. Morrow
Journal: Journal of Clinical Oncology (2015)

9503 Background: CRCI is a burdensome clinical problem for many BC patients. Large studies are needed to definitively assess CRCI and elucidate its’ biological underpinnings. We conducted the largest longitudinal, observational study to date assessing CRCI in BC patients and controls, and assessed whether neurotransmitter signaling, longevity, and inflammation pathways are involved in CRCI. Methods: We recruited non-metastatic BC patients (n = 366) without previous chemotherapy (CT) and age-matched controls (n = 366). Cognitive function was assessed within 1 wk pre-CT and within 4 wks post-CT using the FACT-Cog to assess self-reported function and neuropsychological assessment (computerized CANTAB Verbal Memory (VM), paper-based Controlled Oral Word Association (COWA), phone-based word recall (RAVLT) and backward counting) to assess executive function. Controls were assessed at the same time intervals as patients. SNPs involved in neurotransmitter signaling (COMT) and longevity (FOXO3), and pre- and post-CT cytokines (IL-1β, MCP-1, sTNFR1) were measured in patients. Results: BC patients (89% white, mean age = 53) reported more CRCI on the FACT-Cog (total score and all 4 domains) from pre- to post-CT and performed worse on all 4 executive function tests over time via t-tests (all p < 0.05).Using ANCOVA, adjusting for age, education, WRAT-4 reading, anxiety (STAI), and pre-CT cognitive score, BC patients performed worse on all measures post-CT compared to controls: FACT-Cog Effect Size (ES) = 0.74, VM ES = 0.27, COWA ES = 0.33, RAVLT ES = 0.27, Backward Count ES = 0.19; all p < 0.05. FOXO3 and COMT SNPs predicted level of CRCI on the FACT-Cog (both p = 0.07). Decreases in executive function were associated with increases in IL-1β, MCP-1 (both p < 0.05) and sTNFR1 (p = 0.08). Conclusions: This is the largest longitudinal study showing significant CRCI amongBC patients receiving CT compared to cancer-free controls. CRCI in BC patients is influenced by neurotransmitter signaling and longevity genes and leads to increased inflammation. NCI UG1CA18996, K07CA168886.
Sublingual vaccination with self-adjuvanting virus-like particles against Group A streptococcus elicit protective immunity in systemic and mucosal sites: implication for allergen-specific immunotherapy
Authors: I Kong, A. Seth, J-Y Yang, S-H Lee, Y-S Lee, Y. Kim, A. Middelberg, N. Wibowo, L. Lua, M-N Kweon
Journal: Allergy (2016)
Efficacy of Daratumumab, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma Among Patients with 1 to 3 Prior Lines of Therapy Based on Previous Treatment Exposure: Updated Analysis of Pollux
Authors: Philippe Moreau, Jonathan L. Kaufman, Heather J. Sutherland, Marc Lalancette, Hila Magen, Shinsuke Iida, Jin Seok Kim, Miles Prince, Tara Cochrane, Nushmia Z Khokhar, Mary Guckert, Xiang Qin, Albert Oriol
Journal: Blood (2016)
Multimodal therapeutic approach in anaplastic thyroid cancer
Authors: Y. Lee, J. Jung, G. Hwang, H. Park, Y. Im
Journal: Journal of Clinical Oncology (2006)

15533 Background: Anaplastic thyroid cancer (ATC) is a rare but highly aggressive neoplasm with a dismal prognosis. However, a few patients survive for a long time after treatment. We tried to identify prognostic factors of this disease and analyzed treatment outcomes in patients with ATC. Methods: We reviewed the medical records of 15 patients diagnosed with ATC in our institution between 1988 and 2003. The survival was compared by the Kaplan-Meier log-rank test. Results: The female-to-male ratio was 1.5:1 (9 women and 6 men), and the mean age at diagnosis was 63.9 years (range, 44–91). The mean tumor size was 6.3cm (range, 4–10 cm). Extrathyroidal invasion was present in 12 cases and distant metastasis at diagnosis was present in 6 cases. Surgery was performed in 8 cases. Radiotherapy was used for 10 cases and chemotherapy for 5 cases. The mean overall survival time of the 15 patients was 237 days (range, 28–717 days). The 6-, 12-, 18- and 24-month survival rates were 33%, 26%, 13% and 0%. No association was found between survival and presenting symptoms, age, gender, tumor size, previous goiter history, extrathyroidal invasion, distant metastasis, surgery, radiotherapy or chemotherapy. A significantly better outcome was observed in patients received triple modality treatment (surgery, radiotherapy and chemotherapy) than in those received single or dual modality treatment (P = 0.05). Conclusions: Although most patients with ATC had a poor prognosis, a multimodal approach including surgery, radiotherapy and chemotherapy, might improve survival. No significant financial relationships to disclose.
INCIDENCE AND PREDICTORS OF TARGET LESION FAILURE IN A MULTI-ETHNIC ASIAN POPULATION RECEIVING THE SYNERGY CORONARY STENT: A PROSPECTIVE ALL-COMERS REGISTRY
Authors: Joshua Ping Yun Loh, Rajiv Ananthakrishna, William Kristanto, Liu Li, Siew Pang Chan, Poay Huan Loh, Edgar Tay, Mark Chan, Koo Chan, Ronald C.H. Lee, Adrian Low, Huay-Cheem Tan
Journal: Journal of the American College of Cardiology (2017)
EFFECT OF OBESITY AND UNDERWEIGHT STATUS ON PERIOPERATIVE OUTCOMES IN PATIENTS WITH CONGENITAL HEART DISEASE: AN ANALYSIS OF DATA FROM THE SOCIETY OF THORACIC SURGEONS CONGENITAL HEART SURGERY DATABASE
Authors: Michael L. O'Byrne, Sunghee Kim, Christoph Hornik, Babatunde Yerokun, Roland Matsouaka, Jeffrey Jacobs, Marshall Jacobs, Richard Jonas
Journal: Journal of the American College of Cardiology (2017)
Minitransplant Using Repeated Unrelated Donor Lymphocyte Infusions as a Treatment of Immunodeficiency in Complete DiGeorge Syndrome.
Authors: Renata Formankova, Katerina Zdrahalova, Petr Sedlacek, Petra Keslova, Ondrej Hrusak, Ester Mejstrikova, Tomas Kalina, Hana Zizkova, Anna Sediva, Jirina Bartunkova, Karel Dlask, Jan Stary
Journal: Blood (2005)
QUALITY OF LIFE MEASURED WITH EUROQOL-5D QUESTIONNAIRE PREDICTS LONG TERM MORTALITY AND ECHOCARDIOGRAPHIC RESPONSE IN CRT PATIENTS
Authors: Klaudia Vivien Nagy, Gábor Széplaki, András M. Boros, Péter Perge, Astrid Apor, Annamária Kosztin, Levente Molnár, László Gellér, Bela Merkely
Journal: Journal of the American College of Cardiology (2017)
Gpr124 is essential for blood–brain barrier integrity in central nervous system disease
Authors: Junlei Chang, Michael R Mancuso, Carolina Maier, Xibin Liang, Kanako Yuki, Lu Yang, Jeffrey W Kwong, Jing Wang, Varsha Rao, Mario Vallon, Cynthia Kosinski, J J Haijing Zhang, Amanda T Mah, Lijun Xu, Le Li, Sharareh Gholamin, Teresa F Reyes, Rui Li, Frank Kuhnert, Xiaoyuan Han, Jenny Yuan, Shin-Heng Chiou, Ari D Brettman, Lauren Daly, David C Corney, Samuel H Cheshier, Linda D Shortliffe, Xiwei Wu, Michael Snyder, Pak Chan, Rona G Giffard, Howard Y Chang, Katrin Andreasson, Calvin J Kuo
Journal: Nature Medicine (2017)
Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue
Authors: Prashanth Vallabhajosyula, Laxminarayana Korutla, Andreas Habertheuer, Ming Yu, Susan Rostami, Chao-Xing Yuan, Sanjana Reddy, Chengyang Liu, Varun Korutla, Brigitte Koeberlein, Jennifer Trofe-Clark, Michael R. Rickels, Ali Naji
Journal: Journal of Clinical Investigation (2017)

In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, we quantified islet transplant exosomes in recipient blood over long-term follow-up using anti-HLA antibody, which was detectable only in xenoislet recipients of human islets. Transplant islet exosomes were purified using anti-HLA antibody-conjugated beads, and their cargoes contained the islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to a marked decrease in transplant islet exosome signal along with distinct changes in exosomal microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet and renal transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up periods of up to 5 years. Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a noninvasive window into the conditional state of transplant tissue.
Intratumor heterogeneity (ITH) of lung adenocarcinomas defined by multiregion whole exome sequencing (WES).
Authors: Jianjun Zhang, Junya Fujimoto, Jianhua Zhang, Yu Cao, Chi-Wan Chow, Kathryn A. Gold, Curtis Gumbs, John Heymach, Neda Kalhor, Cesar Moran, Alexei Protopopov, Sahil Seth, Xingzhi Song, Stephen Swisher, Jiabin Tang, William Nassib William, Xifeng Wu, Waun Ki Hong, Ignacio Ivan Wistuba, Andrew Futreal
Journal: Journal of Clinical Oncology (2014)

11032 Background: Individual cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed ITH. ITH may have profound impacts on biopsy strategy, characterization of actionable targets, treatment planning, and drug resistance. The extent and architecture of ITH of lung cancers are largely unknown. Methods: We performed multi-region WES of 48 samples from 11 surgically resected lung adenocarcinomas and their matched peripheral blood leukocytes to an average of 267-fold sequencing depth. All tumor samples were analyzed for point mutations, insertions/deletions, and copy number alterations. All somatic variations were validated with targeted capture ultra-deep sequencing to an average of 869-fold sequencing depth. Sub-clonal analysis based on a Bayesian statistics approach process was performed in each tumor sample. Phylogenetic trees of these 11 tumors were constructed after clonal ordering. Results: 17,572 somatic point mutations, insertions, and deletions were identified and validated. The numbers of somatic alterations varied significantly among different patients and among different samples within the same tumor suggesting significant inter- and intra-tumor heterogeneity. Sub-clonal analysis suggested presence of multiple related populations in each sample with the distribution allele frequencies varying substantially across regions of the same tumor. The majority of known driver mutations (e.g., EGFR, KRAS) were present in all regions of the sampled tumors. There was no correlation with extent/structure of ITH and age, gender, tumor size, lymph node status, or smoking status. With a median follow-up of 2.5 years, 2 patients recurred. Of potential interest, these 2 patients had the most complex ITH architectures in their primary tumors. Conclusions: Different lung adenocarcinomas may have distinct ITH architectures. Although the sample size is very small, the fact that both patients who relapsed had complex ITH architectures suggests that complex ITH architectures may lead to unfavorable clinical outcomes. Studies on larger cohorts are needed to elucidate the clinical impacts of ITH.
Study of the Relationship of Product Infused with Survival in Patients with Hodgkin’s Disease and No Hodgkin’s Lymphoma Undergoing Autologus Stem Cell Transplantation
Authors: Eduardo Salido, Maria Juliana Majado, Alfredo Minguela, Jose Maria Moraleda, Consuelo Gonzalez, Antonio Parrado, Consuelo Funes, Maria Victoria Martinez-Sanchez, Alfonso Morales
Journal: Blood (2008)
PREDICTORS OF PROCEDURAL COMPLICATIONS IN INFRAINGUINAL ENDOVASCULAR INTERVENTIONS
Authors: Barbara Anna Danek, Houman Khalili, Haekyung Jeon-Slaughter, Amutharani Baskar, Ehrin Armstrong, Nicolas Shammas, Andrew Shammas, Ian Cawich, Gerardo Rodriguez, Mazen Abu-Fadel, Anand Prasad, Emmanouil Brilakis, Subhash Banerjee
Journal: Journal of the American College of Cardiology (2017)
Result of APL treatment associated with more experience of centers and more treatment as consolidation.
Authors: Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Mahdi Jalili, Shahrbano Rostami, Seyed Hamidolah Ghaffari, Mohammad Jahani, Seyed Asadollah Mousavi, Babak Bahar, Mohammad Vaezi, Mohsen Esfandbod
Journal: Journal of Clinical Oncology (2013)

7069 Background: The first line therapy strategy remains controversial in acute promyelocytic leukemia (APL) patients. Arsenic trioxide (AS 2 O 3 ) approved in relapsed or resistance patients and recently studies reveals benefits of AS 2 O 3 in first line therapy. Regardless of these, important challenges are early mortality during remission induction and post treatment relapse. Methods: Between 2000 and 2012, patients suffered APL whose was new case and confirmed by t(15;17) translocation with RT-PCR, enrolled in study. Until 2007, patients received 28 days AS 2 O 3 (0.15 mg/kg iv) as induction and after 28 days rest, treatment continued for 2 courses of consolidation therapy with the same dose and after 2007, two additional consolidation courses, one and two year after start treatment, was added for prevent post treatment relapse. At beginning of 2nd and 3th consolidation, consider CSF cytology and RT-PCR for detection of APL cells and weekly CNS prophylaxis by MTX and cytarabine, IT chemotherapy start if needed. Patients received no other treatment. Results: Totally 271 patients enrolled in study. Ninety six patients received 3 dose and 175 patients received 5 dose of AS 2 O 3 . Fifty four (20%) patients died during remission induction before achieve remission. In recent years, early mortality rate reduced below 10% compared with more than 24% in the early years. With median follow-up of 30 months, 170 (78.4%) patients among 217 patients (whose survived after successful induction therapy) were alive (mortality rate: 21.6%) and 2.5-year overall survival and leukemia free survival was 85% and 73% respectively. The cumulative incidence of relapse in group which received three courses of AS 2 O 3 and group which received five courses of AS 2 O 3 was 41.5% and 12.6%, respectively (95%CI: 2.5-9.6, P-value=0.0001). Conclusions: Currently according recent studies, AS 2 O 3 has been considered as first line therapy in APL patients but either early mortality or post treatment relapse remain challengeable factors which affect treatment result. Expedite the referral of patients and improvement of emergencies care can reduce early mortality. The next step might be in order to achieve best treatment strategy for reduce post treatment relapse.
SAFETY AND EFFECT ON HEALTHCARE EXPENSES WITH SAME VERSUS NEXT DAY DISCHARGE AFTER ELECTIVE TRANSRADIAL PERCUTANEOUS CORONARY INTERVENTION
Authors: Gerardo Rodriguez-Araujo, William Rollefson, Mehmet Cilingiroglu, David Mego, Ian Cawich, Vasili Lendel, Andre Paixao, Konstantinos Marmagkiolis, Daniel Sherbet, Patrick Flaherty
Journal: Journal of the American College of Cardiology (2017)
Hot flash placebo responses: Related to baseline hot flash frequency?
Authors: J. M. Jones, C. L. Loprinzi, R. Qin, D. L. Barton
Journal: Journal of Clinical Oncology (2009)

9628 Background: As multiple treatments have been studied for the management of hot flashes in randomized, controlled trials, hot flash placebo responses have been quite variable across trials. Based on observations of trial reports, it was hypothesized that the magnitude of placebo effect might correlate with the number of baseline hot flashes in different studies. The current project examines the effect of the baseline hot flash frequency required for study participation and also the actual number of baseline hot flashes observed as these individually relate to the eventual reductions of hot flash frequency observed in patients receiving placebos. Methods: Data were collected from placebo-controlled, double-blinded, randomized trials, identified by a PubMed search, which reported hot flash frequency at baseline, 4–6 weeks and 12 weeks. Trials were excluded if they had less than 20 participants completing the placebo arm. Data gathered, in each study, included the number of hot flashes required to enroll in the study, the average hot flash number during the baseline period, and the hot flash changes in the placebo arms of each study (percent reduction from the baseline period). A simple statistical analysis was conducted in a descriptive fashion since standard deviation was not available in many trials. Scatter plots and Pearson's correlation coefficients demonstrated the relationships between the placebo hot flash percent reduction from baseline and both the minimum required number of hot flashes at baseline, and the mean number of hot flashes at baseline. Results: 45 trials with 49 placebo arms were included in this analysis. A significant positive correlation was seen between the number of hot flashes required to enroll in a study and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p = 0.003). There was also a significant positive correlation between the number of hot flashes at baseline and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p= 0.002) and at 12 weeks (Rho = 0.573, p= 0.003). Conclusions: These data support that higher baseline hot flash enrollment requirements and also higher baseline hot flash frequencies are associated with an increased placebo response. No significant financial relationships to disclose.
A phase III study of pemetrexed (Pem) plus carboplatin (Cb) plus bevacizumab (Bev) followed by maintenance pem plus bev versus paclitaxel (Pac) plus cb plus bev followed by maintenance bev in stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC): Overall and age group results.
Authors: Mark A. Socinski, Jyoti D. Patel, Edward B. Garon, Ramaswamy Govindan, Craig H. Reynolds, David R. Spigel, Mark R. Olsen, Jingyi Liu, Susan C. Guba, Philip Bonomi
Journal: Journal of Clinical Oncology (2013)

8004 Background: This study compared Pem+Cb+Bev followed by Pem+Bev maintenance (Pem arm) to Pac+Cb+Bev followed by Bev maintenance (Pac arm). The primary endpoint of improved overall survival (OS) for the Pem arm was not met. Methods: Advanced NS-NSCLC pts, ECOG PS 0/1, were randomized to 4 cycles of induction Pem+Cb+Bev with folic acid+vitamin B 12 or Pac+Cb+Bev (Pem 500 mg/m 2 or Pac 200 mg/m 2 ; Cb AUC 6; Bev 15 mg/kg) every 3 weeks. Eligible pts received maintenance Pem+Bev or Bev. OS, progression-free survival (PFS), overall response (ORR), and toxicity were evaluated. A hazard ratio (HR) of 0.80 required 676 OS events/900 pts with 2-sided type-I error .05 and at least 80% power for superiority of Pem over Pac arm. Exploratory Cox models estimated treatment HRs with 95% confidence intervals (CIs) for each age subgroup analyzed: ≤ or &gt;65, 70 (prespecified) and ≤ or &gt;75 yrs (not prespecified). Results: 939 pts (median age, 64.7) were randomized. Median (m) OS for ITT pem and pac arms was 12.6 vs 13.4 mos (HR 1.00, p=0.949); mPFS was 6.0 vs 5.6 mos (HR 0.83, p=0.012) Subgroup efficacy is shown in the Table; ≤ or &gt;65 data were similar to ITT. Pem pts had significantly more drug-related grade 3/4 thrombocytopenia, anemia (except &gt;75 yrs) and fatigue (except &gt;70 and &gt;75 yrs). Pac pts had significantly more grade 3/4 neutropenia (except &gt;70 and &gt;75 yrs), sensory neuropathy (except &gt;75 yrs) and grade 1/2 alopecia. Results parallel overall safety data. Conclusions: OS was not significantly different in any of the age subgroups. PFS was significantly longer in Pem arm overall and for pts ≤70, but was similar for pts &gt;70, &gt;75 yrs. Toxicity profiles differed; subgroup safety data paralleled overall data. Clinical trial information: NCT00762034. [Table: see text]