tbuckley/cabot-search huggingface dataset:
New CT treatment response score for predicting survival in patients with metastatic colorectal carcinoma: A pilot study
Authors: A. Fora, M. Fakih, S. Scheib, T. Hanna, C. Raczyk, A. Hutson, R. Gottlieb
Journal: Journal of Clinical Oncology (2009)

e15026 Background: To develop a methodology that results in an optimized CT Treatment Response Score (CTRS) for prediction of survival using quantified changing lesion features. Methods: We evaluated the overall survival (OS) predictive value of a new methodology to assess CT scan-based responses versus RECIST guidelines in a homogenous metastatic colorectal cancer population. All patients (pts) with MCRC treated with cetuximab and irinotecan (cet &amp; irino) between 2005 and 2008 in our Center after failure of prior oxaliplatin and fluoropyrimidine were included in this analysis. Other inclusion criteria included: at least 6 weeks of cet &amp; irino and serial CT scans on cet &amp; irino including baseline performed in our Center. 38 pts (22 men, 16 women, mean age = 62, range = 28–91 ) were included. CT scans were interpreted by 2 trained physician assistants initially independently with differences resolved by consensus. Parameters evaluated included change in tumor size using standard RECIST and visual based (VB) assessment, VB assessment of enhancement, and interval development of new lesions.VB scoring used Likert-type scales to code reader confidence as to change in an imaging characteristic (size, enhancement) and the presence/absence of a characteristic (new lesions). The most predictive parameters for OS were used to generate the CTRS with an overall range of -2 (definite tumor decrease) to +2 (definite tumor increase). Results: The optimal CTRS resulted from combining VB assessment of change in size of existing lesions and new lesion development. This resulted in prediction of survival with a Cox Hazard Ratio of 1.639 (p = 0.0008). Using a threshold value of 0 to generate good (scores ≤ 0) and poor (scores &gt; 0) response groups resulted in probabilities of survival at 8 months (ms) of 75% (16 pts) and 32% (22 pts), median survival times of 13.3 ms (95% CI = 10.94 ms, 17.81 ms) and 5.06 ms (95% CI = 3.84 ms, 8.77 ms), respectively. CTRS was easier to perform and appeared to be more predictive of OS outcome than RECIST. Conclusions: The methodology results in a single CTRS with transparent for others to test and understandable in terms of predicting survival for pts and caretakers. This methodology needs validation in a larger patient data set and across various tumors and lines of treatment. No significant financial relationships to disclose.
A pilot study using sunitinib malate as therapy in patients with stage IV uveal melanoma
Authors: K. R. Chan, S. Gundala, M. Laudadio, M. Mastrangelo, A. Yamamoto, T. Sato
Journal: Journal of Clinical Oncology (2008)

9047 Background: In contrast to cutaneous melanoma, a significant proportion of uveal melanoma cells express c-kit (CD117). Production of stem cell factor and autocrine stimulation through c-kit receptor is considered to be one of the mechanisms for disease progression. Sunitinib malate is a multi-targeted tyrosine kinase inhibtor against vascular endothelial growth factor receptors, fms-related tyrosine kinase 3 (FLT-3), KIT, and platelet-derived growth factor receptors. Methods: Patients with stage IV uveal melanoma whose tumors have at least 10% CD 117 expression were treated. The initial dose was 37.5 mg daily over a 28 day period cycle. The treatment was continued to disease progression or grade 3 or greater toxicity after dose reduction to 25 mg daily. The primary objectives were assessment of potential clinical efficacy as well as safety of sunitinib in patients with metastatic uveal melanoma. Clinical response using RECIST criteria was evaluated every 8 weeks. Toxicity was assessed every 4 weeks. Further investigation is warranted if clinical benefit, defined as stable or regression of disease, is achieved in 50% of patients. Results: Ten patients aged 29–74 were enrolled. All but one patient failed at least one prior therapy for metastasis. Nine patients had multiple hepatic metastases. There was 1 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The overall clinical benefit rate was 80%. With median follow-up of 5.9 months, the median overall survival was not reached. The median progression free survival was 5.3 months. For patients who achieved PR or SD, median duration of response was 3.9 months. The most common side effect was grade 1–2 fatigue. Grade 3 adverse events included diarrhea (n=1), fatigue (n=2), pneumonia (n=1), leukopenia (n=1), cardiac dysfunction (n=1), and headache (n=1). One patient developed grade 4 thrombocytopenia. While the dose of sunitinib was decreased to 25 mg daily in 6 patients due to toxicity, these patients maintained their best response with the lowered dose. Conclusions: Sunitinib at 37.5 mg daily showed activity in patients with metastatic uveal melanoma. Sunitinib should be tested in a larger cohort of patients with uveal melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.
Authors: M S Mitchell, J Jakowatz, W Harel, G Dean, L Stevenson, W D Boswell, S Groshen
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.
A Phase I/II Study Of Hyper-CVAD Plus Everolimus In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Naval Daver, Hagop M. Kantarjian, Deborah A. Thomas, Michael E. Rytting, Farhad Ravandi, Nitin Jain, Jorge E. Cortes, Rebecca Garris, Mary Ann Richie, Marina Konopleva, Hongbo Hu, Jitesh Kawedia, Kirk Culotta Pharmd, Susan O'Brien, Jordan Basnett, Lianchun Xiao, Xuelin Haung, Linda J. Bendall
Journal: Blood (2013)
P1224 : Next-generation sequencing for the diagnosis of wilson's disease
Authors: D. Németh, J. Pál Kósa, K. Árvai, P. Horváth, B. Tobiás, B. Balla, A. Folhoffer, A. Krolopp, P. András Lakatos, F. Szalay
Journal: Journal of Hepatology (2015)
Skin Tumors in Mice Painted With &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;′-Nitro-&lt;italic&gt;N&lt;/italic&gt;-Nitrosoguanidine and &lt;italic&gt;N&lt;/italic&gt;-Ethyl-&lt;italic&gt;N&lt;/italic&gt;′-Nitro-&lt;italic&gt;N&lt;/italic&gt;-Nitrosoguanidine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Takayama, N Kuwabara, Y Azama, T Sugimura
Journal: JNCI Journal of the National Cancer Institute (1971)

N-methyl-N′-nitro-N-nitrosoguanidine (MNG) and N-ethyl-N′ -nitro-N-nitrosoguanidine (ENG) were locally carcinogenic when applied to the skin of noninbred ICR mice. Among 28 mice painted with MNG, squamous cell carcinomas developed in 7, fibrosarcomas of the skin in 17, colliding tumors composed of both squamous cell carcinoma and fibrosarcoma in 8, and papillomas in 6. Among 14 mice painted with ENG, squamous cell carcinomas developed in 5, fibrosarcomas in 1, and papillomas in 8. At a concentration of 0.5%, MNG induced malignant tumors in a greater proportion of animals than did ENG at the same concentration. However, this difference could be attributed to the greater frequency of dermal fibrosarcomas in the MNG-painted mice. Amyloidosis was detected in 10 of the 67 effective mice.
Abstract 12671: Growth Differentiation Factor-15 is an Akt1-Regulated Skeletal Muscle-Secreted Factor
Authors: Yasuhiro Izumiya, Satoshi Araki, Shinsuke Hanatani, Taku Rokutanda, Kenneth Walsh, Hisao Ogawa
Journal: Circulation (2012)

Introduction: Wasting is a strong independent risk factor for mortality in patient with heart failure. We have recently demonstrated that increase in lean muscle mass can attenuate pathological car...
Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: an Eastern Cooperative Oncology Group Trial.
Authors: J H Schiller, K Kim, P Hutson, R DeVore, J Glick, J Stewart, D Johnson
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the response rate and survival of chemotherapy-naive patients with extensive-stage small-cell lung cancer (SCLC) treated with topotecan, and to determine the relationship of topotecan pharmacokinetics with response and toxicity. PATIENTS AND METHODS Forty-eight patients with previously untreated, extensive-stage SCLC received 2.0 mg/m2 of topotecan daily for 5 days. The first 13 patients were treated without colony-stimulating factor (CSF) support; the next 35 patients received 5 micrograms/kg of granulocyte-colony-stimulating factor (G-CSF) for 10 to 14 days starting on day 6. Cycles were repeated every 3 weeks for a maximum of four cycles. Patients who had a partial response to topotecan after four cycles, stable disease after two cycles, or progressive disease at any time received salvage chemotherapy with cisplatin and etoposide. Topotecan pharmacokinetics were measured using a four-point sampling scheme. RESULTS Of 48 patients, none had a complete response and 19 had a partial response, for an objective response rate of 39% (95% confidence interval [CI], 25.2% to 53.0%). The median response duration was 4.8 months (95% CI, 3.0 to 7.3). After a median follow-up duration of 18.2 months, the overall median survival time was 10.0 months (95% CI, 8.2 to 12.7); the 1-year survival rate was 39% (95% CI, 25.2% to 53.0%). Eight of 34 patients (24%) who received salvage chemotherapy responded. Four of 17 patients who did not respond to first-line therapy with topotecan responded to cisplatin and etoposide. The most common toxicity was hematologic. Ninety-two percent of patients treated without G-CSF developed grade 3 or 4 neutropenia, compared with 29% who received G-CSF. However, the incidence of neutropenic fevers was similar between the two groups (8% and 11%, respectively), and one patient in each group died of neutropenic fevers. There were no differences in objective tumor response, duration of response, time to treatment failure, or survival between the 13 patients who entered the study before G-CSF administration was mandated and the 35 patients who entered after and received G-CSF. There was poor correlation between the WBC count and absolute neutrophil counts (ANCs) and both the area under the curve (AUC) and maximum concentration++ (Cmx) of total topotecan in plasma. There was no correlation between the tumor response and either AUC or Cmx of total topotecan. CONCLUSION The activity of topotecan in extensive-stage SCLC noted in this study warrants further investigation of this agent in phase III clinical trials.
Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.
Authors: G Bolis, G Favalli, S Danese, F Zanaboni, G Mangili, C Scarabelli, S Tateo, M G Valsecchi, G Scarfone, G Richiardi, L Frigerio, M Melpignano, A Villa, F Parazzini
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.
Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Acute Occupational Pesticide-Related Illness and Injury — United States, 2007–2010
Authors: Geoffrey M. Calvert, John Beckman, Joanne Bonnar Prado, Heidi Bojes, Prakash Mulay, Michelle Lackovic, Justin Waltz, Abby Schwartz, Yvette Mitchell, Stephanie Moraga-McHaley, Kathy Leinenkugel, Sheila Higgins
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Tracking occupational injuries, illnesses, and hazards has been an integral part of the National Institute for Occupational Safety and Health (NIOSH) since its creation by the Occupational Safety and Health Act in 1970.In collaboration with its many partners, NIOSH has established surveillance programs to help describe the magnitude of occupational hazards, diseases, and injuries in the U.S.These surveillance activities have often documented the Nation's progress in reducing the burden of work-related diseases and injuries.They have also identified many old and new problems that require additional research and prevention efforts.Despite these accomplishments, occupational health surveillance in the U.S. remains fragmented, with substantial data gaps.Given these deficiencies, the changes in the workplace over the past 30 years, and the competing demands for resources, NIOSH embarked on a process to assess current surveillance needs and to identify its goals for the next decade.The Surveillance Strategic Plan is the result of this effort.I am grateful for the tremendous cooperation from our partners in developing this plan.I anticipate that it will serve not only as a guide for surveillance within NIOSH, but will provide a framework for occupational safety and health surveillance nationally.I look forward to continued collaboration with our many partners in government, the private sector, labor, academia, and non-governmental organizations in implementing this plan and making its vision and mission a reality.
Comparison of Continuation of HMA Vs Allogeneic Stem Cell Transplant and Its Timing in Myelodysplastic Syndromes: Can It Wait? Results of a Retrospective Study
Authors: Monica Cabrero, Guillermo Garcia-Manero, Koji Sasaki, Naval Daver, Gautam Borthakur, Courtney D. DiNardo, Jorge E. Cortes, Zach Bohannan, Victoria Sukholutsky, Farhad Ravandi, Sherry Pierce, Tapan M. Kadia, Naveen Pemmaraju, Betul Oran, Richard E. Champlin, Hagop Kantarjian, Elias Jabbour
Journal: Blood (2014)
Investigator-Reported Bleeding Versus Post Hoc Adjudication of Bleeding
Authors: Tannas Jatene, Robert A. Harrington, Gregg W. Stone, Ph. Gabriel Steg, C. Michael Gibson, Christian W. Hamm, Matthew J. Price, Jayne Prats, Efthymios N. Deliargyris, Kenneth W. Mahaffey, Harvey D. White, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2016)
High-dose chemotherapy, fractionated total-body irradiation, and allogeneic marrow transplantation for malignant lymphoma.
Authors: G L Phillips, R H Herzig, H M Lazarus, J W Fay, R Griffith, G P Herzig
Journal: Journal of Clinical Oncology (1986)

Seventeen patients with malignant lymphoma, including 13 with progressive disease and four in remission following primary chemotherapy, received high-dose chemotherapy, fractionated total-body irradiation (TBI), and allogeneic marrow transplants. Eleven of the 13 (85%) patients in relapse who received transplants achieved remission, and three remain disease free 41, 21, and 17 months later; one patient in second remission who received a transplant is disease free at 11 months. Thirteen patients are dead: four because of progressive lymphoma, seven because of interstitial pneumonitis, and two because of complications of severe acute graft-v-host disease. These results are similar to those noted in marrow transplantation series for advanced acute leukemia; since transplantation during remission has decreased relapse and improved survival in leukemia, earlier transplantation may produce improved results in lymphoma patients as well. However, the effectiveness of conventional therapy regimens for most lymphomas and the high incidence of severe transplant-related complications usually limit allogeneic transplantation to lymphoma patients in situations other than consolidation of first remission. Initial partial remission, early relapse from an initial remission, and perhaps second remission are situations in which conventional therapy is often ineffective, but the adverse features of very advanced lymphoma are not present; marrow transplantation may be considered in eligible patients. Transplant recipients with more advanced disease are anticipated to have poorer survivals.
Slowly adapting strtech receptors upregulate mixed cough responses in the rabbit
Authors: Chayra Abdou, Sissi On, Bruno Demoulin, Odile Ruckebusch, Anne-Laure Leblanc, Noelle Bertin, François Marchal, Silvia Varechova
Journal: European Respiratory Journal (2012)

Rationale . Inhibition of slowly adapting stretch receptors (SARS) inhibits the cough reflex (CR), but it is not clear whether SARS stimulation facilitates CR and/or expiration reflex (ER). The issue is relevant to the long term understanding of chronic cough because those mechanisms that regulate cough are poorly understood.

The aim of the study was to demonstrate whether SARS stimulation by continuous positive airway pressure (CPAP) alters CR and/or ER in the rabbit.

Methods : 5 rabbits were anesthetized and tracheostomized. The trachea was exoposed to punctuate mechanical stimuli at control and with 4-5 hPa CPAP. 24 stimulations were aimed in each condition in each animal. CR and ER were identified from airflow and volume signals, diaphragmatic and abdominal muscle electrical activity. The reflexes were defined as a forced expiratory effort preceded (CR) or not (ER) by an augmented inspiration. Mixed responses were differentiated from the pattern of the first breath as ER/CR and CR/ER.

Results: 241 stimulations, evenly distributed in inspiration and expiration, were obtained at control (n = 121) and on CPAP (n = 120). The overall incidence of positive responses significantly increased from 66% at control to 85% on CPAP (p = 0.0005). Incidence of ER, CR or CR/ER was not significantly altered. In contrast the mixed ER/CR response significantly increased from 14% at control to 38% on CPAP (p = 0.0005).

Conclusions . SARS stimulation up regulates airway defensive reflexes, namely ER/CR. Thus SARS appear to sensitize preferentially those ER-facilitated coughs. It is speculated that a proper identification of airway defensive responses in patients may be relevant to a better understanding of chronic cough.
Correlation of Met expression in TCC of the bladder with stage and grade.
Authors: M. Sorbellini, B. McNeil, H. Simpson, A. Giubellino, T. Hsieh, R. H. Getzenberg, M. Schoenberg, C. Gagani, D. P. Bottaro
Journal: Journal of Clinical Oncology (2010)

e15110 Background: Bladder cancer has the highest cost per patient in the US compared to all other cancers, reflecting the complexity and prevalence of this disease. Current methods of bladder cancer detection and staging need improvement: cystoscopy misses small tumors and CIS; and cytology is at best 80% sensitive and 90-95% specific. Oncogenic signaling via Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), is associated with multiple neoplastic processes, including bladder cancer. The goal of this study was to investigate whether Met expression could differentiate grade and stage in well-established models of bladder TCC. Methods: Commercially available cell-lines derived from bladder TCC were grown: RT4: papillary, low grade (LG), HT1376: pT2, high grade (HG), T24: pT3, HG, TCC-SUP pT4, HG, +metastasis. Cells were serum-deprived for 24-hours prior to performing a sensitive and quantitative electrochemiluminescence immunoassay. Additionally, soluble-Met levels were assessed in patients with and without known Bladder TCC. Statistical analysis (t-test, unpaired, double-tail test) was performed in GraphPad. Results: Met expression levels correlated directly with pathologic stage (Ta vs T2/T3 vs T4, p=0.0002 and p=0.0297) and grade (low grade vs. high grade, p=0.0001) in TCC of the bladder. HGF levels and steady-state Met activation levels were undetectable in all cell-lines tested, ruling out the possibility of an autocrine loop. Met phosphorylation was readily detectable upon stimulation with exogenous HGF. In urine samples, Met levels differentiated between patients with and without bladder TCC and between different grades and stages. Conclusions: A sensitive, quantitative, high throughput method was used to determine Met protein levels in cultured cell models of bladder TCC as well as soluble-Met in urine samples. Met expression correlated directly with pathologic stage and grade, suggesting that Met expression may serve as a marker of disease status and progression in TCC of the bladder and potentially as a molecular target for pharmacological intervention. No significant financial relationships to disclose.