tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis using a Markov model assessing the addition of bevacizumab to paclitaxel in HER2-negative metastatic breast cancer patients.
Authors: Tamer Refaat, Mehee Choi, Germaine Gaber, William Small, Krystyna D. Kiel
Journal: Journal of Clinical Oncology (2012)

1069 Background: Metastatic breast cancer (MBC) remains an incurable disease despite advances in treatment modalities. In 2008, Eastern Cooperative Oncology Group 2100 trial (E2100) results led to FDA approval for bevacizumab with paclitaxel in the initial treatment of HER2-negative MBC. The addition of bevacizumab to paclitaxel led to a gain of around 2.5 months of progression-free survival (PFS), no significant benefit on overall survival (OS), and increased toxicity. In November 2011, the FDA officially revoked approval of bevacizumab for HER2-negative MBC. However, both the European Medicines Agency (EMEA) and NCCN still endorse bevacizumab for this indication. One of the greatest challenges facing healthcare worldwide is reconciling incremental clinical benefits with exponentially rising costs. This study aimed to assess the cost-effectiveness of bevacizumab with paclitaxel for HER2-negative MBC. Methods: A Markov decision tree using Data 3.5 (TreeAge Software, Inc.) was created to do decision and cost-effectiveness analyses of using bevacizumab in combination with paclitaxel versus paclitaxel alone as first-line chemotherapy in HER2-negative MBC using efficacy and toxicity data from the E2100 study. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule. The model was designed from the patient and payer perspectives and sensitivity analyses were run. Results: The marginal cost between paclitaxel alone versus bevacizumab and paclitaxel was 86K with a marginal efficacy of 0.369 quality-adjusted life-years and marginal cost effectiveness of 232,720.72 USD. The expected outcome value was 1.86 for bevacizumab and paclitaxel and 1.67 for paclitaxel alone. However, the combination was not cost effective and only a marginal survival advantage that was not significant was observed. Conclusions: This study demonstrates that, despite a significant PFS advantage, the addition of bevacizumab to paclitaxel is not cost-effective for patients with HER2-negative MBC. Such data could be informative to policymakers who consider the health economics and incremental cost-effectiveness of medical therapies.
Final result of phase II study of irinotecan (CPT-11) plus oral S-1 for previously treated advanced NSCLC patients.
Authors: Daisuke Arai, Kenzo Soejima, Katsuhiko Naoki, Shinnosuke Ikemura, Hideki Terai, Takashi Sato, Ryousuke Satomi, Souhei Nakayama, Satoshi Yoda, Kouta Ishioka, Keiko Ohgino, Jun Miyata, Hiroki Kabata, Masaki Miyazaki, Tomoko Betsuyaku
Journal: Journal of Clinical Oncology (2012)

e18058 Background: Both CPT-11 and S-1, which contains a prodrug of 5-FU, have moderate activity against NSCLC as a single agent and the combination of these agents have been reported to possess marked synergistic effects and tolerability in several gastrointestinal cancers. So the combination of CPT-11 and S-1 will be a promising alternative for the second line treatment of NSCLC patients. We have previously reported the phase I study of this combination and determined the recommended doses of these agents. This study was conducted as a phase II trial to evaluate the efficacy and safety of CPT-11 and S-1 for NSCLC patients who had previously treated. Methods: :This trial was open-label, multicenter study. NSCLC patients who had received one prior chemotherapy with performance status 0-1 were enrolled. Primary endopoint was response rate and secondary endpoints were progression free survival, overall survival, 1-year survival rate and adverse events. CPT-11 (60mg/m 2 on days1, 8) and oral S-1 (80mg/m 2 /day on days1-14) was administered on every 21 days, maximally 6 cycles. Results: By October 2011, 31 patients were enrolled. Nineteen were adenocarcinoma and 12 were non-adenocarcinoma. The median age was 60 y/o (range 35-74) and the median number of treatment cycles was 4 (range 1-6). The objective response rates were PR 7.7%, SD 61.5% and PD 30.8%. Median PFS, median OS and 1-year survival rate were 2.8 month, 12.6 month and 55%, respectively. Grade 3-4 hematologic toxicities comprised neutropenia (15%), anemia (11%) and thrombocytopenia (3%). Other grade 3-4 non-hematologic toxicities comprised pneumonitis (7%), diarrhea (3%), anorexia (3%), liver dysfunction (3%) and mucosal disability (3%). No treatment related death was observed. Conclusions: Combination of CPT-11 and oral S-1 was moderately effective with acceptable toxicities as a second line treatment for advanced NSCLC patients.
Combination of a second generation genetically modified herpes simplex virus 1 (HSV1) with paclitaxel in the treatment of breast cancer <i>in vitro</i>
Authors: J. C. Hu, G. Hallden, C. Shorrock, G. Simpson, R. Coffin, T. Kamalati, C. Coombes
Journal: Journal of Clinical Oncology (2004)

723 Background: A genetically modified oncolytic HSV1 JS1/ICP34.5-/ICP47- encoding GM-CSF is in a Phase I clinical trial in a number of solid tumours. Preliminary results are encouraging and a Phase II clinical trial in combination with chemotherapy in breast cancer is planned. The aim of the work is to assess the effects of combining the virus and paclitaxel in breast cancer cell lines and to study the mechanism of action of the virus in combination with paclitaxel. Methods: Breast cancer cell lines MDA-MB-231 and MCF-7 were treated with virus, paclitaxel or in combination at different ratios. Cell viability was determined by MTS assays, dose response curves generated and IC50 values estimated and analysed using isobolograms. Cell cycle analysis was performed after propidium iodide (PI) staining using FACS. Apoptosis was assessed with annexin V and PI staining. Effects on viral replication were assessed by plaque assay. Results: The effects of combining JS1/ICP34.5-/ICP47- given prior to, with, or after paclitaxel were either synergistic or additive. For example, for MDA-MB-231, a combination IC50 value was 2x10-4pfu/ml (virus) with 5nM of paclitaxel, but 5x10-5pfu/ml and 20nM respectively alone. This indicated synergism at this ratio. Other ratios indicated at least additive effects.Work to elucidate the mechanisms of this additivity/synergy demonstrated that: - the virus blocks the cell cycle of MCF-7 cells at G1/S and causes some apoptosis; - paclitaxel blocks the cycle at G2/M and causes significant apoptosis; - apoptosis appears not to be enhanced by the combination of drug and virus; - paclitaxel does not affect virus replication. Conclusions: The combination of JS1/ICP34.5/ICP47- with paclitaxel may be beneficial in the treatment of breast cancer as isobolograms show either additivity or synergy. However, synergy did not appear to result from an augmentation of virus replication and was not the result of an increase in the number of cells undergoing apoptosis. Further studies are underway to elucidate the molecular events underlying these findings. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioVex Limited; Hammersmith Hospital BioVex Ltd.
AUMENTO DE LA DETECCIÓN DE ADENOMAS SERRADOS CON EL USO DE ENDOSCOPIOS DE ALTA DEFINICIÓN + I-SCAN DURANTE LA COLONOSCOPIA DE CRIBADO EN PACIENTES DE RIESGO MEDIO
Authors: A Rodriguez-D'jesus, E Saperas
Journal: Endoscopy (2015)

Introducción: La utilidad de la alta definición+i-SCAN (HDIS) durante la colonoscopia de cribado no se ha evaluado de forma exhaustiva. La tasa de detección de adenomas (ADR), serrados (ASDR) y el número de adenomas/colonoscopias (APC) han sido reconocidas como parámetros de la calidad colonoscopia.
Outcome of operable breast cancer with triple negative phenotype
Authors: Y. Izarzugaza, P. Khosravi-Shahi, A. Soria Lovelle, G. Pérez Manga
Journal: Journal of Clinical Oncology (2009)

e11621 Background: Breast cancer(BC)is the most frequent neoplasm in women. Triple negative phenotype(TNP)is characterized by lack of expression of estrogen receptor(ER),progesterone receptor(PgR) and Her-2, and it is associated with a worse prognosis. Patients and Method: We conducted a retrospective study of consecutive cases of BC with TNP by immunohistochemistry(IHC),treated in our center within the last 5 years,with primary endpoint of analyzing the disease-free-survival (DFS).Second endpoints of the study were overall survival (OS),place of the first recurrence and cause of death. Results: After reviewing 295clinical histories of localized BC(with available ER,PgR and Her-2 by IHC),we found a total of 24 patients(p)with TNP(Prevalence=8.14%[95CI%: 5.3–11.9%].Ps characteristics:median age=50 years(26–74);premenopausal=55%;tumor grade:G3=40%;G2=60%;85.7% had high Ki-67(&gt;40%);63.2% had stageIIB-III;median tumoral size=2.1cm;node positive=80%(25% with 4 or more positive nodes);96% was ductal carcinoma;56.5% was treated with mastectomy;78% with radiotherapy.Eighty-three percent of ps were treated with neoadjuvant and/or adjuvant chemotherapy with anthracyclines and taxanes:34.8% with adjuvant chemotherapy (AC60/600x4–&gt;Paclitaxel-175x4);21.7% with neoadjuvant ATX(doxorubicin, docetaxel and capecitabine);and 26.1% with neoadjuvant AT(doxorubicin and docetaxel), and only 4 ps with adjuvant CMFx6.With a median follow-up of 36 months(m),median DSF was 42 m(95%CI: 33–51),and the probability of DSF at 3y was 67%.Median OS was 82m(95%CI: 41–123),with a probability at 5y of 52%.Thirty-eight percent(9/24)of ps had an event(3 recurrences and 6 deaths),and 100%of the deaths were caused by tumoural progression. Deaths according to the chemotherapy:75%(3/4 patients)in CMF group vs 15%(3/20)in anthracycline and taxane group(P=0.040; Fisher test).Mainly localization of the first recurrence was multiple in the 44.4%of the cases, followed by the liver(22.2%),lung(11.11%),bone(11.11%)and brain (11.11%). Conclusions: Our study confirmed the worse prognosis associated with triple negative BC.This subtype of BC must be treated with the most active cytostatic drugs in the adjuvant setting. No significant financial relationships to disclose.
Interleukin-1 and estrogen protect against disseminating dentoalveolar infections
Authors: Hesham Youssef, Philip Stashenko
Journal: International Journal of Oral Science (2017)

Dentoalveolar bacterial infections cause localized tissue and bone destruction, but usually remain well-localized within teeth in immunocompetent hosts. However, in certain cases these infections may invade head and neck tissues, resulting in orofacial abscesses, cellulitis and sepsis, with resultant high morbidity and even mortality. In the present studies, we developed a novel model of spreading dentoalveolar infections in mice by treatment with neutralizing antibodies against both interleukin-1α (IL-1α) and IL-1β. Surprisingly male but not female mice given anti-IL-1 antibodies developed orofacial abscesses, weight loss, splenomegaly and sepsis. Female mice developed abscesses and sepsis comparable to males following ovariectomy (OVX), which was reversed by estrogen supplementation. Anti-IL-1 blockade inhibited IL-12, interferon γ (IFNγ) and IL-6 but not IL-10 expression in infrabony lesions, suggestive of a local anti-inflammatory response. There was greater infiltration of neutrophils and other inflammatory cells into lesions in anti-IL-1-treated animals; however, blood leukocytes had reduced bacterial phagocytic and killing activity ex vivo. Estrogen directly stimulated IL-1 production by macrophages, suggesting that the resistance of females to disseminating dentoalveolar infections may be due to their heightened pro-inflammatory responses following bacterial challenge, leading to enhanced localization of these infections.
A placebo-controlled trial of etanercept, a tumor necrosis factor (TNF) inhibitor, in patients with the cancer anorexia/weight loss syndrome. North Central Cancer Treatment Group (NCCTG) trial N00C1
Authors: A. Jatoi, S. R. Dakhil, J. W. Kugler, K. M. Rowland, J. Keit, J. D. Verdirame, P. J. Novotny, J. A. Sloan, P. L. Nguyen, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2006)

8534 Purpose: Tumor necrosis factor (TNF) is a putative mediator of the cancer anorexia/weight loss syndrome. This study was designed to determine if etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton TNF receptor linked to the Fc portion of human IgG1) could palliate this syndrome. Methods: 63 evaluable patients were randomly assigned to etanercept 25 mg SQ twice/week versus a comparably-administered placebo, both of which were to be given for at least 12 weeks. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported weight loss of &gt; 5 pounds over 2 months and/or a daily intake of &lt; 20 calories/kg body weight. The above sample size provided 81% power to detect a 24% difference in the percentage of patients who gained &gt;/= 10% of baseline weight. Results: At baseline, groups were comparable on age, gender, tumor type, and degree of weight loss. Over time, weight gain was minimal in both groups; no patient gained &gt;/= 10% baseline weight. Appetite questionnaires (the NCCTG Anorexia/Cachexia Questionnaire and FACT-AN) revealed negligible improvements in both groups. Median survival was comparable: 175 days versus 148 in etanercept-treated and placebo-exposed patients, respectively (p=0.82). Finally, preliminary data on adverse events showed that etanercept-treated patients had higher rates of neurotoxicity (29% versus 0%) but lower rates of anemia (0% versus 19%) and thrombocytopenia (0% versus 14%). Infection rates were negligible in both groups. Clinical correlative data on TNF genotyping will be available at the time of the meeting. Conclusion: This TNF inhibitor does not appear to palliate the cancer anorexia/weight loss syndrome. The study was supported by CA37404, the American Institute for Cancer Research, and Amgen. No significant financial relationships to disclose.
The prognostic factor of endometrial cancer receiving adjuvant taxane-platinum chemotherapy.
Authors: Fuminori Ito, Naoto Furukawa, Yasuhito Tanase, Seiji Kanayama, Ryuji Kawaguchi, Shozo Yoshida, Hiroshi Kobayashi
Journal: Journal of Clinical Oncology (2014)

e16541 Background: As for the adjuvant chemotherapy of endometrial cancer, a taxane chemotherapy is becoming in use. The aim of the present study is to consider the prognosis of endometrial cancer after receiving adjuvant taxane-platinum chemotherapy from a viewpoint of TOP2A and HER2. Methods: Among endometrial cancer patients receiving first-time medical treatment in our hospital from 2005 to 2010, 56 patients underwent adjuvant taxane-platinum combined chemotherapy. A tissue array was made from paraffin-embedded sections, and immunohistochemistry with TOP2A-HER2 was performed. TOP2A was defined as strong expression more than 3+, and HER2 was defined as expression more than 2+. The log rank test was used to assess the associations between positivity and negativity with overall survival and disease-free survival. Prognostic factors were extracted using Cox proportional hazards. Results: Median age was 61 years (41-77). Median observation period was 49.4 months (17.5-109.5). The histologic type was endometrioid adenocarcinoma G1-G2 in 29, and other in 27. The International Federation of Gynecology and Obstetrics (FIGO) stage was stage±A in 12, stage±B in 23, stage II in 7, stage III in 12, and stage ‡W in 2. Surgery was performed with no lymph node dissection in 7, and with lymph node dissection in 49. Three-year overall survival was 94.1%, and 3-year disease-free survival was 72.4%. Overall survival was significantly shorter in patients positive for HER2 than in those negative for HER2(54.7 months vs. 83.2 months, p= 0.049). Disease-free survival was significantly shorter in those with high expression of HER2 than in those with low expression(56.4 month vs. 100.1 months, and p= 0.020). In multivariate analysis including known prognostic factors, no significant prognostic factor was extracted. Conclusions: TOP2A-positive patients might have a poor prognosis, and combined use with molecular target drugs may be taken into consideration in HER2-positive cases.
Review: α-blockers increase passage of ureteric stones without increasing serious adverse events
Authors: Aaron J. Ruberto, Heather Murray
Journal: Annals of Internal Medicine (2017)

ACP Journal Club21 March 2017Review: α-blockers increase passage of ureteric stones without increasing serious adverse eventsAaron J. Ruberto, MD, Heather Murray, MD, FRCPCAaron J. Ruberto, MDQueen's University, Kingston, Ontario, Canada (A.J.R., H.M.)Search for more papers by this author, Heather Murray, MD, FRCPCQueen's University, Kingston, Ontario, Canada (A.J.R., H.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-166-6-033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHollingsworth JM, Canales BK, Rogers MA, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016;355:i6112. https://pubmed.ncbi.nlm.nih.gov/27908918Clinical Impact RatingsGIM/FP/GP: Emergency Med: Nephrology: References1 Ordon M, Andonian S, Blew B, et al. CUA guideline: Management of ureteral calculi. Can Urol Assoc J. 2015;9:E837-51. [PMID: 26788233] Google Scholar2 Preminger GM, Tiselius HG, Assimos DG, et al; American Urological Association Education and Research, Inc.; European Association of Urology. 2007 guideline for the management of ureteral calculi. Eur Urol. 2007;52:1610-31. [PMID: 18074433] Google Scholar3 Smith-Bindman R, Aubin C, Bailitz J, et al. Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med. 2014;371:1100-10. [PMID: 25229916] Google Scholar4 Melnick ER, Probst MA, Schoenfeld E, et al. Development and testing of shared decision making interventions for use in emergency care: a research agenda. Acad Emerg Med. 2016;23:1346-53. [PMID: 27457137] Google Scholar Author, Article, and Disclosure InformationAffiliations: Queen's University, Kingston, Ontario, Canada (A.J.R., H.M.)This article was published at Annals.org on 7 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 March 2017Volume 166, Issue 6Page: JC33KeywordsComputed axial tomographyHospitalizationsRadiation exposureRisk ratioSafetySerious adverse eventsSurgerySystematic reviewsUltrasound imagingUrology ePublished: 21 March 2017 Issue Published: 21 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of distress on total toxicity burden and activities of daily living among 382 advanced stage cancer patients: A URCC CCOP research base study.
Authors: Marie Anne Flannery, Charles Stewart Kamen, Michelle Christine Janelsins, Charles E. Heckler, Joseph A. Roscoe, Luke Joseph Peppone, Mohamedtaki Abdulaziz Tejani, Anita Roselyn Peoples, Peter Walter Bushunow, Tarit Kumar Banerjee, Min-Chun Chen, Jeffrey K. Giguere, Supriya Gupta Mohile, Gary R. Morrow, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2014)

e20641 Background: Distress is hypothesized to increase morbidity and mortality among cancer patients-possibly through exacerbating toxicities and interfering with activities of daily living (ADL’s). The purpose of this study was to examine the influence of distress on total toxicity burden (TTB) and ADLs, specifically general activity, working, walking, and socializing. Methods: 382 patients (M age=64; 52% female), with mixed cancer diagnosis (62% lung; 85% stage III or IV ) and dyspnea (> grade2) receiving chemotherapy were randomized to receive either Buspirone or placebo as part of a clinical trial. In this secondary analysis we report on data from baseline assessments within 7 days of first chemotherapy treatment. Distress and interference with ADLs were evaluated with the Clinical Symptom Inventory (CSI) using a 10-point NRS scale. TTB was computed as the sum of severity ratings for 8 toxicities on the CSI: fatigue, sleep disturbance, pain, drowsiness, lack of appetite, trouble remembering, nausea, and vomiting (range=0-80). Results: Distress was reported by 81% (N=310; M=4.64; SD=2.66) of patients. Patients with distress (M TTB= 33.12, SD=14.57) reported higher TTB compared to those without distress (MTB=16.28, SD=9.69, p<.01). Distress was correlated with TTB (r= .66; p< .01). 100% of patients with distress reported at least one toxicity, 99% (N=307) reported >4 and 46% (N=143) reported all 8. Patients with distress also reported significantly greater interference with ADLs (general activity M=5.79, SD=2.71; work M=6.26, SD=2.80; walking M=6.04, SD=2.82; socializing M=3.43, SD=2.87) compared to those without distress (general activity M=3.86, SD=2.77; work M=4.25, SD=2.90; walking M=4.33, SD=2.93; socializing M=1.18, SD=2.02; all p<.001). Distress was correlated with interference in all ADLs (general activity r=.48; work r=.44; walking r=.29, socializing r=.48; all p < .01). Conclusions: Distress is significantly associated with increased TTB and interferes with ADLs. These data suggest it is important to screen for, identify, and treat distress among cancer patients, particularly patients with advanced disease and dyspnea. Clinical trial information: NCT 00053846.
Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia
Authors: Surbhi Sidana, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Wilson I. Gonsalves, Ronald S. Go, Yi Lisa Hwa, Nelson Leung, Amie L. Fonder, Miriam A. Hobbs, Steven R. Zeldenrust, Stephen J. Russell, John A. Lust, Robert A. Kyle, Shaji K. Kumar
Journal: American Journal of Hematology (2017)

We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS-39, myeloma-20, lymphoplasmacytic lymphoma-21 and others-14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half.