tbuckley/cabot-search huggingface dataset:
Zoledronate for early-stage, untreated myeloma: An interim report of a randomized study
Authors: P. Musto, A. Falcone, G. Sanpaolo, C. Bodenizza, A. La Sala, A. M. Carella
Journal: Journal of Clinical Oncology (2004)

6680 Background: We have recently demonstrated that “prophylactic” administration of pamidronate is not useful to prevent or delay disease progression in patients with untreated, early-stage myeloma, although this treatment may reduce the number of cases developing skeletal events, thus possibly changing the clinical manifestations of the disease at progression (Musto et al, Leuk Lymphoma 2003; 44: 1545 and J Clin Oncol 2003; 21: 3177). No data are available about the effect of zoledronate (ZOL), a third generation bisphosphonate, in this specific setting of patients. Methods: Starting on June, 2001, all our patients with asymptomatic monoclonal gammopathy, fulfilling the diagnostic criteria of stage IA, IIA or “smouldering” myeloma, are invited to participate into an on-going clinical, randomized trial comparing one-year administration of ZOL alone vs simple observation. The aim of this study was to establish whether ZOL may modify the natural history of the disease, in terms of rate, time and type of progression, in these otherwise untreated patients. As of December, 2003, sixty-two patients, out of a planned accrual of 120 patients, have been randomized (thrity-one per arm) to receive or not ZOL (Zometa, Novartis Pharmaceuticals. Origgio, Italy) for one year or until progression, on an out-patient basis, at the dose of 4 mg as 15' i.v. single monthly infusion. Results: No significant adverse events have been so far recorded. In the observational arm two patients were lost at follow-up after six and twenty months, respectively. Asymptomatc hypocalcemia occurred in four of ZOL-treated patiens. After a median follow-up of 17 months there have been three (9.6%) progressions requiring treatment in the ZOL group and five (17.2%) within the controls (p.n.s.). Median time-to-progression was 17 and 14.3 months, respectively (p.n.s.). Bone lesions and/or hypercalcemia at the time of progression were observed in 4/5 of controls, and in 1/3 of ZOL-treated patients. Conclusions: In this interim analysis, a moderate trend in favour of ZOL-arm was seen. The final evaluation of our trial, including a larger number of patients with prolonged follow-up, is required to clarify whether the use of ZOL may be clinically useful in initial stages of myeloma. No significant financial relationships to disclose.
A randomized placebo-controlled phase III study of intercalated erlotinib with gemcitabine/platinum in first-line advanced non-small cell lung cancer (NSCLC): FASTACT-II.
Authors: Tony Mok, Yi Long Wu, Sumitra Thongprasert, Chong-Jen Yu, Li Zhang, Guia Elena Ladrera, Vichien Srimuninnimit, Virote Sriuranpong, Jennifer Sandoval-Tan, Yunzhong Zhu, Meilin Liao, Caicun Zhou, Hongming Pan, Victor Lee, Yuh-Min Chen, Yan Sun, Benjamin Margono, Kate Jin, Matt Truman, Jin Soo Lee
Journal: Journal of Clinical Oncology (2012)

7519^ Background: FASTACT, a randomized, phase 2 study in advanced NSCLC, found that intercalated erlotinib with 1st-line platinum-based chemotherapy (CT) significantly prolongs progression-free survival (PFS) (HR 0.47, p=0.0002) versus CT alone (Mok et al. JCO 2009). FASTACT-II is a confirmatory, randomized, phase 3, placebo-controlled, double-blind study in a large patient population Methods: Patients with untreated stage IIIB/IV NSCLC and ECOG PS 0/1 were randomized (1:1) to receive up to 6 cycles of gemcitabine (1,250 mg/m 2 on d1 and 8) plus platinum (carboplatin 5×AUC or cisplatin 75 mg/m 2 on d1) q4w, with either intercalated erlotinib (150 mg/day on d15–28) or placebo. Non-progressing patients received maintenance erlotinib or placebo until progression, unacceptable toxicity or death. Stratification was by disease stage, histology, smoking status and CT regimen. Primary endpoint was PFS; secondary endpoints included overall response rate (ORR), overall survival (OS), safety, QoL and biomarker analyses. Results: From Apr 2009 to Sep 2010, 451 patients were randomized to receive erlotinib (n=226) or placebo (n=225). Baseline demographics were well balanced across the arms; overall, 49% were never smokers, 40% were female and 76% had adenocarcinoma. PFS was significantly prolonged with erlotinib vs placebo: median 7.6 vs 6.0 months, respectively; HR 0.57 (95% CI 0.46–0.70); p&lt;0.0001. ORR was significantly improved with erlotinib vs placebo: 42.9% vs 17.8%; p&lt;0.0001. A non-significant trend towards longer OS was seen with erlotinib vs placebo (median 18.3 vs 14.9 months; HR 0.78 [95% CI 0.60–1.02]; p=0.069); 73% of placebo patients received a 2nd-line EGFR TKI. Except for skin rash with erlotinib, there was no clinically significant difference in toxicity between arms. A total of 283 patients (62.7%) provided samples for biomarker analyses, including EGFR mutation status, results of which will be presented. Conclusions: Intercalation of erlotinib with CT significantly prolonged PFS in 1st-line advanced NSCLC. Biomarker analysis will determine the significance of this regimen in patients with or without activating EGFR mutations.
Initial experience with biodegradable tracheal stents in children
Authors: Juan L. Anton-Pacheco, Carmen Luna-Paredes, Gloria García-Hernández, María López, Rocio Morante, M. Isabel Benavent
Journal: European Respiratory Journal (2014)

Background and Objective :Stenting may be indicated for the maintenance of airway patency in selected cases in children. Metallic and plastic stents are the most frequently used but complications have been reported repeatedly. Herein, we show our experience with a new type of biodegradable polydioxanone stent evaluating its safety and effectiveness in the setting of severe tracheal narrowing in children.   Patients and methods : Seven custom-made polydioxanone stents were implanted in two infants with severe airway narrowing due to an extensive tracheal re-stenosis after a failed slide tracheoplasty in one case (6 stents) , and a persistent tracheomalacia after aortopexy in the other. Stent size ranged from 5-8mm diameter and 15-30mm length. All the devices were inserted bronchoscopically under general anaesthesia.   Results : There were no complications related to stent placement. Tracheal narrowing relief and clinical improvement were achieved in both patients (age, 5 and 8 months). One patient needed repeat stenting after stent absorption, but no stent displacement, perforation, bleeding, or significant granulation tissue were observed during the study. Time of follow-up was 2 years and one month respectively.   Conclusions : Biodegradable stents are a new and attractive alternative to metallic or plastic stents when dealing with severe airway narrowing in children. Although promising, further clinical studies are necessary in order to establish the precise criteria for the use of absorbable stents in children.
Effect of Varying Photoperiods on Mammary Morphology, DNA Synthesis, and Hormone Profile in Female Rats
Authors: Molina C. Mhatre, Prabhaker N. Shah, Harbans S. Juneja
Journal: JNCI Journal of the National Cancer Institute (1984)

A clear positive correlation between circulating levels of prolactin (Prl) and morphologic development as well as DNA synthetic index in the mammary gland was established in young virgin Holtzman rats exposed to constant light from birth. The observed elevated level of circulating Prl by virtue of its morphogenic and mitogenic properties induced changes in mammary epithelium [numerous actively differentiating terminal end buds into alveolar buds (AB)] highly susceptible for the action of 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]. Conversely, substitution treatment with melatonin in such a model caused a significant decrease in both Prl and 17β-estradiol (E2) levels as well as in the morphologic and DNA synthetic pattern of the mammary gland. Administration of 2-bromo-α-ergocryptin in these animals caused a significant decrease in the plasma level of Prl (without affecting the level of E2) and a decrease in the density of AB and in DNA synthesis. These changes impaired the mammary gland responsiveness to DMBA as seen from the significant decrease in the incidence of mammary carcinoma.
The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.
Authors: U Sagman, R Feld, W K Evans, D Warr, F A Shepherd, D Payne, J Pringle, J Yeoh, G DeBoer, A Malkin
Journal: Journal of Clinical Oncology (1991)

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.
Plasma <scp>d</scp>-Dimer Levels in Operable Breast Cancer Patients Correlate With Clinical Stage and Axillary Lymph Node Status
Authors: Kimberly Blackwell, Zishan Haroon, Gloria Broadwater, Donald Berry, Lyndsay Harris, J. Dirk Iglehart, Mark Dewhirst, Charles Greenberg
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the relationship between preoperative plasma d-dimer levels and extent of tumor involvement in operable breast cancer patients. PATIENTS AND METHODS: A total of 140 preoperative plasma specimens were obtained from women scheduled to undergo diagnostic breast biopsies. Ninety-five patients in the initial group went on to undergo axillary lymph node dissection. Of the 140 patients from whom plasma samples were obtained, 102 were subsequently diagnosed with invasive breast carcinoma, nine were subsequently diagnosed with ductal carcinoma-in-situ, and 20 were subsequently diagnosed with benign breast disease. Plasma d-dimer levels were quantitated using a commercially available immunoassay kit (DIMERTEST; American Diagnostica, Greenwich, CT). The relationships between plasma d-dimer and other prognostic variables (tumor size, estrogen receptor, progesterone receptor, nuclear grade, histologic grade, lymphovascular invasion, and clinical stage grouping) were then examined using univariate and multivariate linear and logistic regression analyses. RESULTS: Median plasma d-dimer levels were significantly higher in patients with invasive carcinoma than those patients with either benign breast disease or carcinoma-in-situ (P = .0001). A significant relationship existed between the presence of elevated d-dimer (&gt; 100 ng/mL) and involved axillary lymph nodes (χ 2 test; P = .001). Elevated d-dimer levels predicted positive lymph node involvement in both univariate regression (P = .0035) and multivariate linear regression (P = .012) models. In addition, elevated d-dimer levels predicted the presence of lymphovascular invasion in univariate logistic regression (P = .0025) and multivariate logistic regression analysis (P = .0053). Quantitative d-dimer levels were highly correlated with clinical stage grouping (analysis of variance test; P = .002). CONCLUSION: Plasma d-dimer levels were markers of lymphovascular invasion, clinical stage, and lymph node involvement in operable breast cancer. This correlation suggests that detectable fibrin degradation, as measured by plasma d-dimer, is a clinically important marker for lymphovascular invasion and early tumor metastasis in operable breast cancer.
Late-breaking abstract: The impact of global lung initiative (GLI) implementation in a cohort of patients over the age of 70 years
Authors: Natalie Dean, David Parr, Joanna Shakespeare
Journal: European Respiratory Journal (2014)

The Global Lung Initiative released new All-Age multi-ethnic reference ranges for spirometry in 2012 to replace ESCS/ERS ranges. We evaluated the potential impact of using GLI reference equations on an unselected patient cohort over the age of 70 years attending for screening spirometry.  Data from 251 patients (132 (53%) male) between January and August 2013 were retrospectively analysed and comparison made between GLI and ESCS reference ranges.  GLI reference values were higher than ESCS; 105 and 106 patients had abnormal values, respectively.  These differences could reflect changing population demographics and different selection criteria for the reference populations used. The use of GLI did not appreciably alter clinical interpretation in our patients but the impact of GLI on the definition of physiological normality remains uncertain. Therefore, further studies are needed to quantify the potential for changes in disease prevalence estimates and consequent healthcare costs.
Next-Generation Sequencing and Detection of Minimal Residual Disease in Acute Myeloid Leukemia
Authors: Friederike Pastore, Ross L. Levine
Journal: JAMA (2015)

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Cell division and metabolic activity of naevus cells.
Authors: C. BENTLEY-PHILLIPS, R. MARKS
Journal: British Journal of Dermatology (1976)

Thirty moles have been studied by in vitro techniques employing tritiated precursor compounds in order to demonstrate replicative and metabolic activity in naevus cells. Autoradiographs prepared from the incubated tissue showed that replicative activity occurred at all anatomical levels within the naevi. Synthesis of macro-molecules also occurred throughout the mole., but more actively in the junctional and superficial zones. The term ‘Junctional Activity’ does not appear to have any meaning in cell kinetic terms, and is not associated with any proliferative capacity.
Content and Quality of Currently Published Phase II Cancer Trials
Authors: Luigi Mariani, Ettore Marubini
Journal: Journal of Clinical Oncology (2000)

PURPOSE: A number of statistical methods have been proposed for the design and analysis of phase II studies based on dichotomous outcomes. To investigate to what extent such methods are in current use, we conducted a survey of published studies. Materials and Methods: We identified studies by conducting a computerized literature search of MEDLINE. We considered trials on systemic antineoplastic treatments described as phase II or pilot. The search was limited to articles written in English and published in 1997. RESULTS: Three hundred eight trials were identified. The majority, ie, 295 (95.8%), had been conducted as single-arm studies, with objective tumor response as the primary efficacy end point. An identifiable statistical design was reported for only 58 (19.7%) of these trials. The quality in reporting the statistical design and compliance with the design in carrying out the study or results interpretation were frequently poor. The frequency of reporting the statistical design was not shown to increase over the years of study start and was not associated with sample size or study duration. Instead, a significant association was found with trial results (which were less frequently positive among studies with a statistical design) and with the impact factor of the publishing journal. CONCLUSION: This survey shows that the quality of the statistical component of published phase II cancer trials is generally poor and raises suspicion that low quality is likely to bias study findings. Journals might improve the methodologic standard of published articles through a more vigilant reviewing policy.
A prospective study of Hickman/Broviac catheters and implantable ports in pediatric oncology patients.
Authors: J Mirro, B N Rao, D C Stokes, B A Austin, M Kumar, G V Dahl, M Colten, L Balas, M Rafferty, M Hancock
Journal: Journal of Clinical Oncology (1989)

We prospectively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period (median follow-up, 376 days). Externalized catheters (91 Hickman [H], 113 Broviac [B]) and implantable ports (n = 82) were compared for complications, including infection and thrombosis. The most frequent major complication of all catheters was infection, although the rates of infection varied with the duration of catheter use and were generally lower than reported by others. Overall, when catheter failures (removal) for infection, obstruction, or dislodgement were considered, ports had a significantly longer failure-free duration of use (P = .0024) than did externalized catheters. Likewise, ports had a significantly longer infection-free (P less than .01) duration of use than H and B catheters. However, differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome. In analysis of pairs matched for diagnosis, therapy, and age, ports had lower infection rates than did B catheters after 100 days (P = .053). This difference became significant at 400 days of catheter use (P = .029). Although there was a trend toward lower rates of infections for ports v H catheters, this difference was not significant. In view of our results in matched pairs, selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports. The superiority of ports for long-term use (greater than 100 days) needs to be confirmed in a large randomized clinical trial.
Comparison of lung ventilation volume measurements made with single and separate breath-hold hyperpolarized 3-helium and proton MRI
Authors: Samuel Janoff, Helen Marshall, General Leung, Juan Parra-Robles, Xiaojun Xu, Salman Siddiqui, Chris Brightling, Jim Wild
Journal: European Respiratory Journal (2013)

Overview  Hyperpolarized (HP) gas MRI can be combined with spatially registered proton (1H) images of the lung to calculate percentage lung ventilation (PV). However, any lung inflation difference between separate 1H and 3He breath-holds results in errors.  Aim  To increase PV accuracy using a novel single breath-hold 3He and 1H acquisition.  Methods  10 asthma patients were scanned with 3He MRI. The protocol was repeated at baseline to assess short-term reproducibility. Patients inhaled 1L (35% 3He/65% N2) from FRC. Immediately following this (in the same breath-hold) 1H MRI was acquired. A separate breath-hold set of 1H images were also acquired at FRC+1L.  Ventilated volume (vV), lung volume (LV) and PV(vV/LV) were calculated. PVSingle used 3He and 1H images from the same breath hold. PVSeparate used 1H images from the separate breath hold.  Results  Figure 1 shows how lung inflation variation between separate breath-hold 3He (a) and 1H (b) MRI affects PV (c). Acquisition of 3He and 1H MRI during single breath-hold (a,d) gave a more accurate PV measurement (e).  Mean baseline difference was 2.19±10.1% for PVSingle and 9.79±22.5% for PVSeparate, a significant difference (p  Conclusion  Percentage lung ventilation measurements using single breath-hold 3He and 1H acquisition were more reproducible than measurements using separate breathold 3He and 1H images.  Funding  AIRPROM FP7 and Novartis.
Treatment of Periscaphoid Osteoarthritis by Silastic Scaphoid Implant
Authors: D W Clark, N Blackburn
Journal: Journal of the Royal Society of Medicine (1989)

Periscaphoid osteoarthritis may arise de novo or as a sequel of an established non-union of a scaphoid fracture. The treatment of resultant pain and disability often presents a difficult problem since internal fixation and/or bone grafting of the pseudoarthrosis may fail to relieve the symptoms due to degenerative change. Many methods of alleviating these symptoms have been suggested in the past. We have reviewed the experience of the Windsor Orthopaedic group in the use of Silastic scaphoid implants.
Can Humanized Mice Predict Drug “Behavior” in Humans?
Authors: Dan Xu, Gary Peltz
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Most of what we know about a drug prior to human clinical studies is derived from animal testing. Because animals and humans have substantial differences in their physiology and in their drug metabolism pathways, we do not know very much about the pharmacokinetic and pharmacodynamic behavior of a drug in humans until after it is administered to many people. Hence, drug-induced liver injury has become a significant public health problem, and we have a very inefficient drug development process with a high failure rate. Because the human liver is at the heart of these problems, chimeric mice with humanized livers could be used to address these issues. We examine recent evidence indicating that drug testing in chimeric mice could provide better information about a drug's metabolism, disposition, and toxicity (i.e., its "behavior") in humans and could aid in developing personalized medicine strategies, which would improve drug efficacy and safety.