tbuckley/cabot-search huggingface dataset:
A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse
Authors: Ignace Vergote, Deborah Armstrong, Giovanni Scambia, Michael Teneriello, Jalid Sehouli, Charles Schweizer, Susan C. Weil, Aristotelis Bamias, Keiichi Fujiwara, Kazunori Ochiai, Christopher Poole, Vera Gorbunova, Wenquan Wang, Daniel O’Shannessy, Thomas J. Herzog
Journal: Journal of Clinical Oncology (2016)

Purpose Farletuzumab is a humanized monoclonal antibody that binds to folate receptor-α, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer. Patients and Methods Eligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomly assigned test products in a 1:1:1 ratio: farletuzumab 1.25 mg/kg, farletuzumab 2.5 mg/kg, or placebo). The single-agent test product was continued weekly until disease progression. The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors. Additional analyses not outlined in the original protocol were prespecified in the final statistical analysis plan, including a subgroup analysis by baseline CA-125 and farletuzumab exposure levels. Results A total of 1,100 women were randomly assigned to treatment dose or placebo. PFS from the primary analysis was 9.0, 9.5, and 9.7 months for the placebo, farletuzumab 1.25 mg/kg, and farletuzumab 2.5 mg/kg groups, respectively. Neither farletuzumab group was statistically different from the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.81 to 1.21] and 0.86 [95% CI, 0.70 to 1.06] for farletuzumab 1.25 mg/kg and 2.5 mg/kg group v placebo, respectively). In the prespecified subgroup, baseline CA-125 levels not more than three times the upper limit of normal (ULN) correlated with longer PFS (HR, 0.49; P = .0028) and overall survival (OS) (HR, 0.44; P = .0108) for farletuzumab 2.5 mg/kg versus placebo. Subgroup analysis of farletuzumab exposure above the median, regardless of dose, showed significantly better PFS versus placebo. The most common adverse events were those associated with chemotherapy. Conclusion Neither farletuzumab dose met the study’s primary PFS end point. Prespecified subgroup analyses demonstrated that patients with CA-125 levels not more than three times the ULN and patients with higher farletuzumab exposure showed superior PFS and OS compared with placebo.
PWE-392 Need for further surgery after delormes procedure for rectal prolapse in elderly patients
Authors: MI Aslam, E-J Dilley, J Yeung, S Chaudhri, A Scott, A Miller
Journal: Gut (2015)

<h3>Introduction</h3> Rectal prolapse is a profoundly disabling condition, occurring mainly in elderly females. Delormes procedure is often the preferred operative option for high risk elderly patients due to its minimal invasive nature and minimal postoperative morbidity. A recent randomised control trial looking at the different operative procedure for rectal prolapse has quoted rectal prolapse recurrence after Delormes procedure as high as 46% at 5 years. Whether that high recurrence rates correlates with the need of further surgery is not known. We aimed to analyse rectal prolapse recurrence and further surgery rates for patients undergoing Delormes procedure in our institution. <h3>Method</h3> All consecutive adult patients undergoing Delormes procedure between April, 2000 – December, 2014 at the University Hospitals of Leicester NHS Trust were reviewed. This was a retrospective study. Patients were analysed for mode of surgery, 30 day post-operative mortality, post-operative length of hospital stay, clinically detected recurrence and further rectal prolapse surgery. <h3>Results</h3> 109 patients (median age = 79 years, female n = 102, male n = 7) underwent Delormes procedure over the 14 years. Ninety nine (91%) patients had planned surgery and ten (9%) patients had an urgent operation after being admitted via emergency admission route. Median follow up for all the patients was 4 years and 69 patients were alive at the time of analysis. 30 day post-operative mortality was 2.75% and median length of hospital stay after surgery was 4.5 days. 15 (13.7%) patients had a clinically detected rectal prolapse recurrence during the follow up period, 12 (11%) underwent further surgery for their rectal prolapse (redo Delormes n = 4, Altemeier–s procedure n = 5, abdominal rectopexy n = 3) and 3 patients did not undergo further surgery. <h3>Conclusion</h3> Delormes procedure remains safe and an effective procedure to treat rectal prolapse in elderly patients as clinically significant recurrence rates are low. <h3>Disclosure of interest</h3> None Declared.
Re: Laura Evangelista, Alberto Briganti, Stefano Fanti, et al. New Clinical Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature. Eur Urol 2016;70:161–75
Authors: Egesta Lopci, Arturo Chiti, Massimo Lazzeri
Journal: European Urology (2016)
Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects
Authors: Karen E. Wells, Sonia Cajigal, Edward L. Peterson, Brian K. Ahmedani, Rajesh Kumar, David E. Lanfear, Esteban G. Burchard, L. Keoki Williams
Journal: Journal of Allergy and Clinical Immunology (2016)
EGFR mutation, immunohistochemistry (IHC) and chromogenic <i>in situ</i> hybridization (CISH) as predictors of sensitivity to erlotinib and gefitinib in patients (pts) with NSCLC
Authors: V. A. Miller, M. Zakowski, G. J. Riely, W. Pao, S. Hussain, M. Ladanyi, R. T. Heelan, M. G. Kris
Journal: Journal of Clinical Oncology (2005)

7031 Background: Erlotinib and gefitinib produce dramatic responses in a subset of pts with NSCLC. Mutations in the EGFR tyrosine kinase (TK), EGFR amplification or polysomy and EGFR overexpression on IHC have all been associated with sensitivity and benefit. This study was undertaken to compare the ability of each of these characteristics to predict clinical benefit. Methods: We studied 44 pts with advanced NSCLC treated with erlotinib (n=24) or gefitinib (n=20) in whom adequate tissue, radiographic and clinical follow-up were available. Sequencing of EGFR exons 19 and 21 was performed as previously described (Pao, et al PNAS, 2004). EGFR copy number was studied by CISH (Zymed). EGFR signals in 30 tumor cells were counted. Detection of ≥6 signals per cell was considered evidence of amplified copy number. EGFR IHC was performed using a DAKO test and scored as 0 vs + (membrane staining in >10% of cells). Fisher’s exact test was used to study the association of each feature in pts with partial response (18) or no partial response (26). Analysis of non-responders was performed using time on drug as a surrogate for biologic effect (< vs ≥ 3 months). Results: Presence of an EGFR mutation in 15/18 tumors that responded was a powerful predictor of response (p <10-4). EGFR by IHC was scored as + in 10/18 responders and 7/26 non-responders (p=0.07). In 3/3 pts with partial response but no EGFR mutation, IHC was + but CISH was < 6. EGFR amplification by CISH was present in 3/18 responders and 6/26 non-responders (p=0.72). No difference in EGFR expression (p=0.66) was observed between pts without partial response who were on drug for < 3 mos (n=14) and ≥ 3 mos (n=12) while CISH was > 6 in 9/14 (< 3 mos) versus 1/12 (≥3 mos) (p=0.17). Conclusions: The presence of an EGFR TK mutation is the strongest predictor of sensitivity to gefitinib or erlotinib. EGFR IHC may correlate with radiographic regressions; this observation is consistent with that seen in BR21. Gene amplification was seen in 9/44 (20%) but did not correlate with mutation status or radiographic regression. Further efforts are needed to refine the molecular features of pts without EGFR-TK mutations who benefit from these agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Genentech AstraZeneca, Genentech AstraZeneca
Analysis of racial variations in disease characteristics, treatment patterns, and outcomes of patients with chronic lymphocytic leukemia
Authors: Chadi Nabhan, Kari G. Chaffee, Susan L. Slager, Natalie Galanina, Sara J. Achenbach, Susan M. Schwager, Neil E. Kay, Tait D. Shanafelt
Journal: American Journal of Hematology (2016)

The impact of race on outcomes of patients with chronic lymphocytic leukemia (CLL), the most common leukemia in the west, is not well studied. We aimed to understand racial variations in clinical and disease characteristics, treatment patterns, and outcomes in patients with CLL. We utilized the Mayo Clinic CLL database to perform an analysis of these characteristics and natural history of non-white (NW) compared to white (W) CLL patients. Differences by race in median overall survival (OS) and time-to-first-treatment (TTFT) were investigated. Of the 4215 CLL patients, 4114 (97.6%) were W and 101 (2.4%) were NW. NW patients were younger (median age at diagnosis 59.4 vs. 63.4; P = 0.003) and more likely to have an elevated LDH (28.0% vs. 16.2%; P = 0.02). No differences in prognostic parameters were noted. No major differences were observed in treatment selection. OS and TTFT were similar between both groups. In the largest analysis of NW-CLL patients in North America, and contrary to historical retrospective reports, W and NW patients appear to have comparable outcomes when treated similarly. These findings suggest previously noted outcome differences may be due to disparities in access to care and management rather than differences in disease biology. Am. J. Hematol. 91:677-680, 2016. © 2016 Wiley Periodicals, Inc.
Incidence, Clinical Characteristics, and Prognostic Relevance Of Clonal T-Cell Receptor Positive (TCR+) Populations In Patients With Myelodysplastic Syndrome (MDS)
Authors: Preetesh Jain, Hagop Kantarjian, Keyur P. Patel, Elias Jabbour, Naval Daver, Sherry Pierce, Ohad Benjamini, Gautam Borthakur, Courtney D. DiNardo, Stefan H. Faderl, Farhad Ravandi, Jorge E. Cortes, Guillermo Garcia-Manero, Tapan M. Kadia
Journal: Blood (2013)
Abstract 1791: Targeting radiation-inducible cell surface GRP78 using GIRLRG peptide as a novel imaging and therapeutic strategy for tumors
Authors: Vaishali Kapoor, David Dadey, Kim Nguyen, Hua Li, Buck Rogers, Dinesh Thotala, Dennis Hallahan
Journal: Cancer Research (2015)

Abstract Traditional radiation therapy is often associated with significant toxicity to normal cells that could limit the success of cancer therapy. The greater understanding in the molecular differences between cancer cells and normal cells has lead to targeted therapies in cancer treatment. We have discovered novel radiation-inducible antigens in cancer using phage-display peptide libraries. One such inducible-antigen is Glucose regulated protein 78kDa (GRP78) that was shown to bind the hexapeptide GIRLRG. GRP78 is known to regulate cellular stresses, including hypoglycemia, hypoxia and the ER stress response. It is over-expressed in different cancer subtypes and has been correlated to their poor prognosis. In this study, we evaluated the cell surface induction of GRP78 post irradiation (IR) on lung cancer (A549 and LLC), glioma (D54 and GL261) and endothelial (HUVEC and 3B11) cell lines using flow cytometry. Significantly higher surface expression of GRP78 was observed in all cell lines. We determined the specificity of GIRLRG to bind tumors in vivo using nano SPECT technology. GIRLRG was conjugated to a 40KDa PEG (for longer circulation time) and radiolabelled with 111Indium (111In) using diethylene triamine pentaacetic acid (DTPA) as the chelator. The A549 tumor bearing nude mice were irradiated (3Gy x 3 times) or sham irradiated prior to tail vein injections of 111In labeled GIRLRG. The mice were imaged 48h and 96h post injection using nano CT-SPECT imager. The SPECT images revealed that GIRLRG specifically bound to the irradiated A549 tumors while little or no binding was seen in the sham irradiated tumors. The post-SPECT imaging bio-distrubution also revealed maximum uptake in irradiated tumors. We further evaluated tumor binding of GIRLRG in Glioma (D54), esophageal cancer (OE33), cervical cancer (HT3), and pancreatic cancer (BxPC3). The nano-SPECT imaging showed that GIRLRG specifically bound to all the irradiated tumors tested. Phosphor images of the tumor sections showed that GIRLRG specifically bound to the tumors and not to normal tissues. In conclusion, GIRLRG peptide has high affinity to GRP78 in vitro and in vivo. Radiolabeled GIRLRG is a novel tool for imaging tumors and may be developed further as a therapeutic agent to deliver cancer specific drugs or therapeutic radioisotopes. Citation Format: Vaishali Kapoor, David Dadey, Kim Nguyen, Hua Li, Buck Rogers, Dinesh Thotala, Dennis Hallahan. Targeting radiation-inducible cell surface GRP78 using GIRLRG peptide as a novel imaging and therapeutic strategy for tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1791. doi:10.1158/1538-7445.AM2015-1791
Second Primary Cancers Following Treatment of Hodgkin's Disease<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: J F Boivin, G B Hutchison, M Lyden, J Godbold, J Chorosh, D Schottenfeld
Journal: JNCI Journal of the National Cancer Institute (1984)

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was conducted. This report describes 2,591 patients with HD diagnosed in 1940-75 and presents an analysis of follow-up findings through 1978. Seventy-four second primary cancers (excluding basal cell and squamous cell cancers of the skin and in situ carcinomas of the cervix uteri) were observed 1 year or more after diagnosis of HD, including 21 leukemias. Twenty leukemias occurred after chemotherapy. The relative risk (RR) of leukemia after intensive chemotherapy with or without radiotherapy was 136 relative to general population incidence rates. In the subgroup with both intensive chemotherapy and intensive radiotherapy, the RR of leukemia was 125. Both RR estimates differed significantly from unity. The RR of cancers other than leukemia 10 years or more after intensive radiotherapy relative to no intensive therapy was 19.5 (95% confidence limits: 4.8-80).
Pilot trial assessing the efficacy and safety of a supplemental B vitamin complex to reduce the onset and severity of chemotherapy-induced peripheral neuropathy.
Authors: Janet Margaret Schloss, Maree Colosimo, Caroline Airey, Anthony W Linanne, Paul Masci, Luis Vitetta
Journal: Journal of Clinical Oncology (2015)

9604 Background: Chemotherapy induced peripheral neuropathy [CIPN] is a debilitating side effect resulting from the administration of neurotoxic chemotherapy agents. It is estimated that a third of all patients undergoing chemotherapy experience CIPN, with a third of those progressing to a permanent neuropathy. Patients experiencing moderate to severe CIPN report reduced quality of life, chronic discomfort and disruption of physical abilities for general life activities which can be temporary or permanent. Moreover, CIPN can lead to a dose reduction or possible cessation of treatment, which may adversely impact disease outcomes. Methods: In a randomised placebo-controlled trial, newly diagnosed patients undergoing chemotherapy treatment with paclitaxel, oxaliplatin or vincristine were assessed for the safety and efficacy of an oral B group vitamin to reduce the incidence of CIPN. The primary outcome was the TNS and secondary outcomes included B vitamin pathology, EORTC QoL, Brief Pain Inventory and PNQ. Results: A total of 71 subjects were randomised from 121 evaluable patients (B vitamin n = 38; placebo n = 33). Participants between groups were matched for gender, chemotherapy agents, age and BMI. No statistical significance was found for the prevention of CIPN from vitamin B supplementation through total TNS score (p = 0.73). Statistical significance was recorded for sensory peripheral neuropathy in the PNQ (12 weeks p = 0.03; 24 weeks p = 0.005; 36 weeks p = 0.021). The risk estimate for the PNQ was also statistically significant with an OR = 5.78, 95% CI = [1.63-20.5]. Conclusions: B vitamin supplementation throughout chemotherapy administration was not superior to placebo (p > 0.05) for the prevention of CIPN. Patient perception of reduced sensory peripheral neuropathy with B vitamin supplementation over placebo was statistically significant. Although not significant a trend was observed for the prevention of the onset and severity of CIPN throughout chemotherapy with B vitamins supplementation over placebo. Furthermore, patients with moderate to severe CIPN may have a vitamin B12 deficiency that may lead to a worse symptomatic presentation. Clinical trial information: 12611000078954.
Call for urgent actions to ensure access to early diagnosis and care of tuberculosis among refugees
Authors: Masoud Dara, Ivan Solovic, Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Delia Goletti, Raquel Duarte, Stefano Aliberti, Fernando Maria de Benedictis, Graham Bothamley, Tom Schaberg, Ibrahim Abubakar, Brian Ward, Vitor Teixeira, Christina Gratziou, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

Tuberculosis (TB) is a major cause of mortality from an infectious disease, globally affecting 9.6 million cases, with 1.5 million deaths in 2014 [1]. In 2014, there were 273 381 TB cases reported in the World Health Organization (WHO) European region, and an estimated 33 000 deaths [2]. Vulnerable populations ( i.e . individuals affected by discrimination, hostility or economic adversity), which often include migrants and refugees, have an increased risk of suffering from TB disease [1, 3, 4]. If this is not efficiently addressed, the exposure of these groups to Mycobacterium tuberculosis strains may lead to a rise in the number of cases of disease and related deaths, as well as contributing to a further increase in drug-resistant TB cases. ERS and the European Region of The Union call for prioritisation of TB care, prevention and control among refugees <http://ow.ly/YYCL8>
Bladder-sparing regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer
Authors: N. Miyanaga, H. Akaza, N. Sekido, S. Hinotsu, K. Hattori, K. Kawai, T. Shimazui, Y. Akine, M. Hata, K. Tokuue
Journal: Journal of Clinical Oncology (2005)

4663 Background: First-pass effect of intra-arterial chemotherapy seemed to be a strong tool in bladder sparing therapy for invasive bladder cancer (Miyanaga. et al., Int. J. Urol. 7:41–8, 2000). In this paper, we present the latest result of our study. Methods: Patients with invasive bladder cancer, T2–3, N0, M0 were included in the study. Methotrexate (30mg/m2) and cisplatin (50mg/m2) at 3-week intervals were injected via indwelling catheters in bilateral internal iliac artery. Simultaneously, the patients underwent x-ray irradiation (41.4Gy) of the small pelvic space. When a post-treatment TUR biopsy showed no residual tumor, the tumor site was irradiated by a 33.0 Gy proton beam, and the bladder was preserved. When tumors remained, radical cystectomy was performed. Results: Between 1990 and 2004, 67 patients (Median age: 70 years, range 37 to 89) were treated according to this protocol. Sixty-five patients completed the regimen. Out of them, 55 (85%) showed no residual tumors in post-treatment TUR. The bladder was preserved in 54 patients. After a median follow-up of 59 months (range: 4 to 168 months), 5-year non-recurrence rate and bladder-preserved rate was 60% and 78%, respectively. The pattern of recurrence included 15 superficial bladder tumors, 2 invasive bladder tumors and 3 visceral metastases, however no lymphnode metastasis was observed. Four cancer deaths occurred among the patients who spared the bladder, and 5-year over-all survival rate and cause-specific survival rate was 65% and 88%, respectively. Urodynamic study of the patients revealed no significant deteriorations of the bladder function. Conclusions: Bladder-sparing regimen is realistic in a selected T2–3 locally invasive bladder cancer. No significant financial relationships to disclose.
DKK3 expression in hepatocytes defines susceptibility to liver steatosis and obesity
Authors: Lanfeng Xie, Pi-Xiao Wang, Peng Zhang, Xiao-Jing Zhang, Guang-Nian Zhao, Aibing Wang, Junhong Guo, Xueyong Zhu, Qin Zhang, Hongliang Li
Journal: Journal of Hepatology (2016)
Changing pattern of poisoning in children.
Authors: B N Gaind, M Mohan, S Ghosh
Journal: BMJ (1983)

Changing pattern of poisoning in children SIR,-In relation to the correspondence on the changing pattern of poisoning in children (17 September, p 833) some data from Ireland, where there are no regulations on the use of child resistant containers or packaging, may be relevant.The table shows our experience in 1975 and 1980 in dealing with accidental ingestions at a busy children's casualty department.Comparison of accidental ingestions seen in a children's casualty department in 1975 and in 1980 1975 1980
Small Cell Carcinoma Presenting as an Extrapulmonary Neoplasm: Sites of Origin and Response to Chemotherapy&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R M Levenson, D C Ihde, M J Matthews, M H Cohen, A F Gazdar, P A Bunn, J D Minna
Journal: JNCI Journal of the National Cancer Institute (1981)

Eight (4%) of 203 consecutive prospectively staged and treated patients with small cell carcinoma (SCC) had no evidence of pulmonary or mediastinal tumor on chest roentgenogram or at fiberoptic bronchoscopy at the time of diagnosis. There were two distinct clinical presentations in these SCC patients with exclusively extrapulmonary tumors. Four had discrete localized extrapulmonary neoplasms, presumably originating in these sites. In the other 4 cases with either regional or widely metastatic disease, no obvious primary tumor could be documented in the lungs or elsewhere. One complete and two partial responses to chemotherapy (duration 6 to greater than 11 mo) occurred in 6 evaluable patients. Two remaining patients were inevaluable for response because they received adjuvant chemotherapy after irradiation or excision of the primary tumor and are free of disease at 15 and 28 months. Results document two clinicopathologic entities of extrapulmonary SCC, more firmly establish that it can be responsive to chemotherapy, and encourage systemic therapy as part of initial treatment planning.