tbuckley/cabot-search huggingface dataset:
Randomized phase II trial of cisplatin and radiotherapy with or without erlotinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Renato Martins, Upendra Parvathaneni, Anand K. Sharma, Luis E. Raez, Michael A. Papagikos, Furhan Yunus, Julie E. Bauman, Keith D. Eaton, Jay Justin Liao, Eduardo Mendez, Neal Futran, Brenda F Kurland, David X. Wang, Shawn Xiaoyu, Sarah G. Wallace, David N. Hayes
Journal: Journal of Clinical Oncology (2012)

5503 Background: The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced SCCHN. Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating EGFR as a target. Erlotinib, a small molecule inhibitor of EGFR, has activity in recurrent/metastatic disease. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. Methods: Patients with locally advanced SCCHN were randomized to receive cisplatin 100mg/m 2 on days 1,22 and 43 combined with 70Gy of radiotherapy (arm A) or the same chemoradiotherapy combined with erlotinib 150mg/day, starting one week prior to radiotherapy and continued to its completion (arm B). Randomizing 204 patients had 80% power to compare a 60% complete response rate (CRR) to a 40% null rate. Available tumors were tested for p16, ERCC1 and EGFR FISH. Results: Between June 2006 and October 2011, 204 patients were randomized. Results presented are based on intention to treat. There were more females on arm A however no other differences in patient characteristics, including p16 positivity. Patients on arm B had more rash and gastrointestinal adverse events, but treatment arms did not differ for rates of other grade III/IV toxicities or serious adverse events (SAEs). Arm A had a CRR of 61% and arm B had a CRR of 68% (p=0.3). With a median follow-up of 23 months, there were only 29 events in the overall survival analysis and 46 in the progression-free survival (PFS) analysis. The 2 and 3 year PFS were 71% and 63% for arm A and 78% and 73% for arm B (p=0.61). Conclusions: The addition of erlotinib did not increase the rate of SAEs but failed to significantly increase CRR. As seen in other recent trials, our results in both arms are superior to historical comparisons. Updated PFS data will be presented. Supported by a grant from the investigator-initiated trial program of Genentech/OSI.
Referrals to Psychiatrists in a General Hospital — Comparison of Two Methods of Liaison Psychiatry: Preliminary Communication
Authors: Tom Sensky, Tim Cundy, Steven Greer, Keith Pettingale
Journal: Journal of the Royal Society of Medicine (1985)

Patients on a general medical ward were offered a liaison psychiatric service with 'unlimited' access, in which referrals were accepted from nurses, other paramedical staff and junior doctors in addition to senior medical staff. This new service (method II) was compared with the usual liaison service (method I, referrals initiated or approved by senior medical staff only) which was continued in parallel on a comparable general medical ward. Method II resulted in a threefold increase in referral rate and led to a significant alteration in the types of problem attracting referral. Despite the much higher rate of method II referrals, however, similar percentages of referrals by both methods were offered psychiatric follow up. The results do not support the commonly held belief that it is the failure of ward staff to recognize psychiatric morbidity which accounts for the low rate of referrals to many psychiatric liaison services.
Dose-escalating study of continuative low dose of oral vinorelbine in patients with advanced breast cancer
Authors: A. Felici, M. Russillo, S. Di Segni, A. Fabi, G. Ferretti, P. Carlini, M. Contestabile, B. Nuvoli, I. Sperduti, F. Cognetti, P. Papaldo
Journal: Journal of Clinical Oncology (2009)

1128 Background: Low and continuative dose of antineoplastic drugs has been shown to have an antiangiogenic activity. The rapid absorption and relatively short half-life of the oral formulation of vinorelbine are favorable pharmacokinetic characteristics to test a continuative low-dose schedule. Methods: Patients with measurable metastatic breast cancer were treated with escalating dose of oral vinorelbine from 50 mg/m2 per week to 90 mg/m2 per week until progressive disease or unacceptable toxicity. These patients were administered one third of the total weekly dose 3 times per week, every other day. A pharmacokinetic analysis was planned at the first 3 weeks of drug assumption. Results: Of twenty-two patients included in the study, 3 were treated at 50 mg/m2/w (level 1), 5 at 60 mg/m2/w (level 2), 3 at 70 mg/m2/w (level 3), 8 at 80 mg/m2/w (level 4), and 3 at 90 mg/m2/w (level 5); we are still enrolling patients at this level. The median age was 59 years (range 23–75). The median number of prior lines of chemotherapy and hormonal therapy was 2 (range 0–4 for CT and 0–5 for OT). Fifteen of 22 patients had visceral metastasis. No dose-limiting toxicities have been observed until now. The main toxicities were: asymptomatic neutropenia grade 4 in two patients (1 in level 4 and 1 in level 5), asthenia grade 3 in 7 patients (1 at level 1, 2 at level 2, 1 at level 3, 3 at level 4), neurotoxicity grade 3 in two patients (one at level 2 and one at level 4). One patient experienced an intestinal sub-occlusion and hospitalization was required with no permanent side effects. One patient had a partial response, five a stable disease, fourteen progressed and two are not evaluated yet. At 1 year, five of the twenty evaluable patients are died by disease. Samples of twenty patients were collected for pharmacokinetic analysis that will be presented at the meeting. Conclusions: The continuative split 3 times per week oral vinorelbine is feasible, and at 90 mg/m2/w we have not reached yet the maximum tolerated dose. No significant financial relationships to disclose.
In resistant hypertension, add-on spironolactone reduced SBP more than placebo, doxazosin, or bisoprolol over 12 wk
Authors: Mark Rosenberg, Elizabeth Stephens
Journal: Annals of Internal Medicine (2016)

Source Citation Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;Sep 18. [Epub ahead of print.] 26414968
Maintenance of interleukin-21 enhancement of T and NK cell effector function in the presence of dexamethasone
Authors: C. M. Krejsa, F. D. Wagener, M. G. Dodds, D. B. Janszen, S. D. Hughes
Journal: Journal of Clinical Oncology (2008)

3070 Background: Interleukin-21 (rIL-21) immunotherapy is being studied in oncology indications. Since cancer patients frequently receive intermittent steroid treatments, the effects of in vitro dexamethasone (DEX) treatment on rIL-21 mediated functional enhancements to T- helper cells (Th), cytotoxic T lymphocytes (CTL) and natural killer (NK) cells were investigated. Methods: Enriched T and NK cell cultures from healthy volunteers were used. In vitro DEX exposures (50 to 250 ng/mL; 24 h) were based on pharmacokinetic modeling of DEX treatments used to control nausea and infusion reactions. Proliferation of T cells stimulated with CD3 ± rIL-21 was quantified by flow cytometry. A fluorimetric assay was used to measure NK cell cytotoxicity (ADCC) against rituximab-coated DOHH2 cells. Statistical significance was determined by ANOVA. Results: As previously reported, CTL proliferation following CD3 stimulation was enhanced by rIL-21 (p<0.02). Concurrent treatment with DEX resulted in modest reductions in CTL proliferation, whereas 24 h pre-treatment with DEX before CD3 plus rIL-21 stimulation did not reduce proliferation. CTL stimulated with CD3 alone were more susceptible to DEX effects. Stimulation with rIL-21 also increased NK cell ADCC activity (p<0.0025), even in cultures treated concurrently or sequentially with DEX at clinically relevant concentrations. Conclusions: Enhancements in T cell proliferation and NK cell ADCC were maintained under conditions of DEX exposure simulating dosing regimens used to control nausea and infusion reactions. Effects of concurrent DEX treatment on rIL-21 stimulated T and NK cells Endpoint Cell Type Stimulation DEX = 0 DEX = 50 DEX = 100 DEX = 250 Proliferation (mean % of cells in daughter generations, n= 3 donors) CTL CD3 71 33 29 28 CTL CD3 + rIL-21 90 77 79 73 Th CD3 43 7 7 14 Th CD3 + rIL-21 59 26 26 21 ADCC (mean lytic units per 1,000 cells, n= 4–5 donors) NK Control 0.64 0.30 0.30 0.17 NK rIL- 21 2.37 1.33 1.25 1.59 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ZymoGenetics, Inc. ZymoGenetics, Inc.
Recurrence score along the continuum of increasing nodal burden in breast cancer.
Authors: Franz Omar Smith, Marie Catherine Lee, Geza Acs, William J. Fulp, Ji-Hyun Lee, Nazanin Khakpour, John Kiluk, Christine Laronga
Journal: Journal of Clinical Oncology (2013)

101 Background: The Oncotype Dx (ODX) Recurrence Score (RS) stratifies breast cancer patients (pts) by risk of recurrence and potential benefit of adjuvant chemotherapy. Pts with early stage, estrogen receptor (ER) positive, lymph node-negative breast cancer were included in the initial validation studies. Limited data exists on the application of ODX in node positive pts. We review our experience with RS along the continuum of nodal burden. Methods: A prospective database of pts with breast cancer for whom ODX RS was obtained for treatment planning was reviewed by final surgical pathology. Patients were grouped into four pathologic categories: negative sentinel lymph node [N0(i-)], isolated tumor cells [N0(i+)], micro-metastasis [N1mic] and macro-macrometastasis [N1, 1-3 + nodes]. P values were calculated using the exact Wilcoxon Rank Sum Test. Results: 637 pts were identified in the study period: 521 (81.8%) pts had negative sentinel lymph nodes; 54 (8.5%) pts had isolated tumor cells (N0(i+)); 29 (4.6%) pts had N1mic, and 33 (5.2%) had N1 disease (Table). Median age overall was 58yrs, median invasive tumor size was 1.5cm; 475 (91.2%) had ductal histology. Median RS for the study pts was 17 (range 0-85), and increasing RS had no correlation to increasing nodal burden (p=0.23). Pathologic factors associated with nodal status were lymphovascular invasion (LVI) and histology. The frequency of LVI was higher with increasing nodal burden (p&lt;0.0001). Ductal histology was significantly associated with abnormal nodal findings. (p = 0.002). Age, mitotic rate, grade and degree of ER-positive staining on IHC were not significantly associated with sentinel lymph node status (p &gt; 0.05). Conclusions: Tumor size, histology and LVI were significant predictors of increased nodal burden. However, ODX RS was neither predictive nor reflective of increasing nodal disease. RS is a potentially useful tool in adjuvant systemic treatment decisions in patients with positive lymph nodes but should not impact decisions regarding local-regional therapy. [Table: see text]
Molecular mechanisms and therapeutic strategies in amyotrophic lateral sclerosis caused by C9orf72 mutations
Authors: Rubika Balendra, Sarah Mizielinska, Thomas Moens, Teresa Niccoli, Charlotte Ridler, Roberto Simone, Nathan Woodling, Gary Parkinson, Stephen Neidle, Rickie Patani, Linda Partridge, Adrian Isaacs
Journal: The Lancet (2016)
Behavioral Screening and Intervention for Improving Lower-Extremity Arthroplasty Outcomes and Controlling Costs—Reply
Authors: Hannah Alphs Jackson, Brian Walsh, Michael Abecassis
Journal: JAMA Surgery (2016)

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Pre-operative chemotherapy in patients with resectable non-small cell lung cancer (NSCLC): First results of the MRC LU22/NVALT/EORTC 08012 multi-centre randomised trial
Authors: M. Nicolson, D. Gilligan, I. Smith, H. Groen, C. Manegold, J. van Meerbeeck, P. Hopwood, M. Nankivell, C. Pugh, R. J. Stephens
Journal: Journal of Clinical Oncology (2007)

7518 Aims: Although surgery offers the best chance of cure for patients with NSCLC, the overall 5-year survival rate is modest, and improvements are urgently required. This intergroup trial was designed to investigate whether, in patients with operable NSCLC of any stage, neo-adjuvant platinum-based chemotherapy prior to surgery would improve outcomes. Methods: Patients were randomised to receive either surgery alone (S), or 3 cycles of platinum-based chemotherapy prior to surgery (CT-S). Results: 519 patients were randomised (261 S, 258 CT-S) from 70 centres in the UK, the Netherlands, Germany and Belgium. The median age of the patients was 63 years, 72% were male, 59% were PS 0, and 50% had squamous cell histology. The majority were clinical stage I (17% Ia, 45% Ib, 3% IIa, 29% IIb, 7% IIIa), and 12% received mitomycin/vinblastine/cisplatin (MVP), 7% mitomycin/ifosfamide/cisplatin (MIC), 45% vinorelbine/cisplatin, 12% carboplatin/docetaxel, and 25% cisplatin/gemcitabine. The trial showed that neo-adjuvant chemotherapy was feasible (76% of patients received all 3 cycles of chemotherapy), resulted in a good response rate (4% CR, 45% PR, and only 2% PD), appeared to cause down-staging in about 20% of patients, and did not affect the type of surgery performed, the post-operative complication rate, or quality of life. However, there was no evidence of a benefit in terms of progression-free survival (282 events, HR 0.98, 95% CI 0.77,1.23) or overall survival (232 deaths, HR 1.04, 95% CI 0.81, 1.35), and more patients were reported as having brain metastases in the CT-S group (30 CT-S vs 11 S patients). Exploratory analyses showed no evidence that any subgroup of patients benefited from the addition of neo-adjuvant chemotherapy. Conclusions: This intergroup trial, which is the largest trial of neo-adjuvant chemotherapy in patients with resectable NSCLC, indicated that the addition of neo-adjuvant platinum-based chemotherapy did not lead to a benefit in overall survival. However, a 19% survival benefit or a 35% detriment cannot be excluded and this result needs to be considered in the context of all other relevant randomised trials of neo-adjuvant chemotherapy for NSCLC. [Table: see text]
Medication adherence and risk of severe exacerbations in asthma- A systematic review
Authors: Marjolein Engelkes, Hettie Janssens, Johan de Jongste, Miriam Sturkenboom, Katia Verhamme
Journal: European Respiratory Journal (2013)

Asthma is a chronic inflammatory disease with a high prevalence worldwide. Asthma therapy includes drugs for asthma control and for quick relief. Especially for controller therapy, adherence is crucial to reduce the risk of exacerbations.

Objective: To systematically review the association between adherence to asthma controller therapy and risk of severe exacerbations in children and adults.

Methods: Systematic literature search of the PUBMED, EMBASE and Web of Knowledge databases from inception until 2013. Studies were included if there were empirical data about adherence, exacerbations and their association. Quality was assessed using a modified version of the Newcastle Ottawa Scale.

Results: The search yielded 2956 unique publications. 33 articles met the inclusion criteria and underwent data extraction and quality scoring. 24 studies used objective measures and 9 used subjective measures to assess adherence. Included studies were published between 1993-2013. Sample sizes ranged from 24 to 97,743 individuals. High levels of heterogeneity across studies in adherence and exacerbation measurements, designs and strategies for evaluating the association, precluded a formal meta-analysis. Although effect measures varied widely and were inconsistent, in high quality studies better adherence tended to be associated with fewer exacerbations.

Conclusions: Based on current literature, it is difficult to make strong statements on adherence to asthma therapy and risk of exacerbations. New, well designed prospective studies, using standardized definitions for adherence and treatment outcomes are needed. This is essential to disentangle their association, and to ultimately increase patient adherence.
Consideration of height-based rather than weight-based dosing as a more appropriate method of treating with radium-223.
Authors: Thomas Andrew Longo, Matthew McDonald, Samuel H. Mehr, Luke T. Nordquist
Journal: Journal of Clinical Oncology (2014)

249 Background: Radium 223 is approved for use in patients with symptomatic bone metastasis from castrate resistant prostate cancer, and no known visceral metastatic disease. It is currently dosed in a weight based fashion, however it is only active in the skeleton, and it is distributed primarily to the bone. A more rational dosing regimen may be based off a patient’s height, and the highest safe dose has yet to be determined. Our study looks at the safety profile of radium 223 in the context of a height based dosing regimen. Methods: This is a retrospective, observational study of all patients receiving radium 223 at the Urology Cancer Center. The patients were dosed at 50 kilobecquerels per kilogram as prescribed in the product insert. The dose each patient received was then recalculated based upon the patient’s height. The medical record was then examined for side effects. Results: As of September 2013 total of 30 discreet patients have received a total of 58 doses at our site since radium 223 was approved. The lowest dose received based on height was 17.39 kBq/cm and the highest dose was 40.7 kBq/cm with an average dose of 27.4 kBq/cm. There were eight grade 1 toxicities. The side effect profile did not show any trends across the different levels of dosing regarding the number or grade of toxicity with a greater number occurring below the median dose. Six of the eight men with significant GI distress have had prior radiation. Conclusions: A height based dosing regimen may be more appropriate for a drug designed to treat only the skeleton. In our population, we administered a wide variety of doses when administered by height. Higher doses appear to be well tolerated, and the optimal dose has yet to be determined. We propose future studies with height-based dosing escalation to look at the safety and efficacy.
Systematic versus on-request patients' access to medical files: Randomized trial—Influence on anxiety, quality of life and treatment satisfaction in cancer patients
Authors: G. Gravis, C. Protiere, F. Eisinger, C. Tarpin, D. Coso, F. Viret, J. Camerlo, M. Cappiello, J. Walz, P. Viens
Journal: Journal of Clinical Oncology (2008)

6524 Background: Most cancer patients (pts) wish to be fully informed about their disease and treatments. The aim of this study was to determine whether giving unlimited and systematic access to the Medical File (MF) for cancer pts could modify their anxiety, quality of life and treatment satisfaction. We conducted a randomized study to investigate the effect of systematic versus on request access to the MF on the pt. Methods: Pts with breast, colon cancer and lymphoma treated by chemotherapy in an outpatient setting were offered to participate in this study, 336 patients were randomly assigned to receive systematically or not a copy of their complete MF. The primary outcome measure was anxiety (state trait anxiety Inventory), secondary were quality of life (QLQ-C30) and pts' satisfaction (specific auto questionnaire). Results: Anxiety levels did not increase for pts who possessed complete MF at study entry and was equivalent for both groups during and at the end of treatment. Global quality of life was not different between the two groups, 90% of the whole were rather or totally satisfied with information. Higher proportion of pts who had systematic access to their MF were sufficiently informed compared to pts who did not have systematic access (65.6% vs 53.5% p=0.066). Of all pts with systematic access to their MF, 81.5% were rather or completely satisfied to possess MF, 76.3% read it and more than 82.2% had understood information provided. Access to MF did not increase anxiety level for 60% and 73.3% did not regret to possess their MF. To the question “do you have some information you had wished to ignore?” 77% answer “not at all” and 70.4% would choose the same option again. Probability of being completely satisfied with treatment information as well as probability to consider being sufficiently informed increased when pts had systematic access to their MF. Conclusions: Full and automatic access to the MF is one way to improve information delivered to pts. Anxiety did not increase when pts had unlimited access to their MF and they would choose this access again after having experienced it. A significant higher proportion of pts were totally satisfied with information delivered when they have had an unlimited access to MF. No significant financial relationships to disclose.