tbuckley/cabot-search huggingface dataset:
P75 Influence of vitamin D supplementation on outcome in the treatment of chronic hepatitis C
Authors: P Southern, P El-Sayed, L Fenton, K Forrester, S Morrea
Journal: Gut (2010)

Introduction  Vitamin D, acting as an immune modulator, has recently been shown to increase the sustained virological response (SVR) in genotype 1 patients.  Aim  To retrospectively examine the outcome of patients treated in our institution using pegylated interferon and ribavirin, and compare the effects of treatment with a Vitamin D preparation.  Method  All patients in our treatment database who have received treatment for Hepatitis C using Pegylated Interferon were identified. Only those patients who were greater than 6 months post treatment were included. Data collected included genotype, fibrosis score (Ishak) and if they were prescribed Vitamin D preparations, The primary outcome was to attain a SVR, defined as persistently negative HCV PCR status 6 months after cessation of anti viral therapy.  Results  Data were available for 206 patients treated over a 3 year period. Total SVR by genotype was as follows, Genotype 1–39 % (n=44), Genotype 2–71 % (n=8), Genotype 3–72% (n=151) and Genotype 4–100% (n=3).  27.5 % (n=57) of our patients received Vitamin D supplementation with Calcichew D3 Forte (Shire Pharmaceuticals, Hampshire, UK) during the course of treatment, an observed SVR rate of 72 % was seen in those receiving supplementation compared to 64 % in those not supplemented (p=0.281).  When examining patients by genotype, no patients with genotype 1 received Vitamin D therapy. Of Genotype two patients 25 % (n=2) were treated with Vitamin D, achieving a 50 % SVR compared to 83.3% for those not treated with Vitamin D. 34 % of Genotype 3 patients received Vitamin D (n=52) achieving an SVR in 77% of cases, compared to those who did not receive supplementation (n=99) with an SVR of 71% (p=0.414).  From the subset of genotype three patients, the SVR for fibrosis scores   Outcomes were also analysed using fibrosis scores, as expected those with less significant fibrosis achieved SVR more frequently, no significant differences were detected when the data were analysed using treatment with Vitamin D as a variable.  Conclusion  Our data show that Vitamin D supplementation could improve the SVR in Genotype three patients with mild/moderate fibrosis, this has not been reported so far. We suggest routine testing of vitamin D levels prior to combination therapy and replacement during treatment for chronic hepatitis C.
Comparative effectiveness of adjuvant chemotherapy (AC) versus observation in patients with ≥ pT3 and/or pN+ bladder cancer (BCa).
Authors: Matt D. Galsky, Kristian Stensland, Erin L. Moshier, John Sfakianos, Russell Bailey McBride, Che-Kai Tsao, Martin Francis Casey, Simon J Hall, Paolo Boffetta, William K. Oh, Juan P. Wisnivesky
Journal: Journal of Clinical Oncology (2015)

292 Background: Though Level I evidence supports the use of neoadjuvant chemotherapy (NAC) in BCa, the data supporting AC has been mixed. Experience suggests an adequately powered trial to definitively assess the role of AC is unlikely to be completed. Alternative approaches to evidence development are necessary. Methods: Patients who underwent cystectomy for ≥pT3 and/or pN+ M0 BCa were identified from the National Cancer Database. Patients who received NAC and/or diagnosed after 2006 (most recent year with survival data) were excluded. Logistic regression was used to calculate propensity scores representing the predicted probabilities of assignment to AC versus observation based on: age, demographics, year of diagnosis, pT stage, margin status, lymph node density, distance to hospital, hospital cystectomy volume, and hospital type and location. A propensity score-matched cohort of AC versus observation (1:2) patients was created. Stratified Cox proportional hazards regression was used to estimate the hazard ratio (HR) for overall survival for the matched sample while propensity score adjusted and inverse probability of treatment weighted proportional hazards models were used to estimate adjusted HR for the full sample. A sensitivity analysis examined the impact of comorbidities. Results: 3,294 patients undergoing cystectomy alone and 937 patients undergoing cystectomy plus AC met inclusion criteria.Patients receiving AC were significantly more likely to: be younger, have more lymph nodes examined and involved, have higher pT stage, have positive margins, reside in the Northeast and closer to the hospital, and have private insurance. AC was associated with improved overall survival (Table). The results were robust to sensitivity analysis for comorbidities. Conclusions: AC was associated with improved survival in patients with ≥pT3 and/or pN+ BCa in this large comparative effectiveness analysis. [Table: see text]
Erratum to: Dynamics of gene silencing during X inactivation using allele-specific RNA-seq
Authors: Hendrik Marks, Hindrik H. D. Kerstens, Tahsin Stefan Barakat, Erik Splinter, René A. M. Dirks, Guido van Mierlo, Onkar Joshi, Shuang-Yin Wang, Tomas Babak, Cornelis A. Albers, Tüzer Kalkan, Austin Smith, Alice Jouneau, Wouter de Laat, Joost Gribnau, Hendrik G. Stunnenberg
Journal: Genome biology (2016)

After the publication of this work [1], we noticed there was an error in Fig. 5 where −1,0 and 1 are incorrectly displayed in the y-axis in panel b. Please see the corrected Fig. 5 below. We apologize for this error.



Fig. 5

llele-specific RNA-seq on three NPC lines identifies three distal regions of genes that escape XCI. a Ratio of Xi/Xa (y-axis; for each of the three NPC lines sorted from highest to lowest) for genes showing a log2 ratio of at least −5. We set ...
Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small-cell lung cancer.
Authors: H Choy, W Akerley, H Safran, J Clark, V Rege, A Papa, M Glantz, Y Puthawala, C Soderberg, L Leone
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel administered weekly on an outpatient basis with concurrent thoracic radiation to patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS In this phase I clinical trial, paclitaxel was administered as a 3-hour intravenous (IV) infusion, repeated every week for 6 weeks. The starting dose of paclitaxel was 10 mg/m2. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients if tolerated. Unacceptable toxicity was defined as grade 3 nonhematologic toxicity, excluding nausea and vomiting, and grade 4 hematologic toxicity according to Cancer and Leukemia Group B expanded common toxicity criteria. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS Twenty-seven patients were entered onto this study through seven dose escalations (from 10 mg/m2/wk to 70 mg/m2/wk for 6 weeks). Severe esophagitis occurred at 70 mg/m2 (two patients with grade 4 disease and one patient with grade 2). One of six patients at 60 mg/m2 developed grade 3 esophagitis and three of seven patients had grade 2 esophagitis. One of 27 patients developed a hypersensitivity reaction. One of 27 patients developed grade 3 neutropenia. CONCLUSION Esophagitis is the principle dose-limiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxel at the MTD of 60 mg/m2/wk is underway.
Experiences of establishing a new community based oxygen service
Authors: Denise Williams, Nicola Stevenson, John Corless
Journal: European Respiratory Journal (2011)

The Wirral has a population of 350 000. We have high rates of lung disease. The prevelence of COPD is 2.3% and we diagnose approximately 300 new lung cancers each year. Many individuals are in receipt of home oxygen therapy. Prior to 2009 there was no no local provision for structured assessment or follow up of patients in receipt of oxygen within our area.  In October 2009 we opened a new community based oxygen service for the provision of oxygen. All new community and secondary care initiated oxygen prescriptions are supervised by our service. Primary care precribing data in September 2009 indicated that there were 1079 active oxygen prescriptions. These data contained numerous inaccuracies. We later confirmed that there were 800 adult patients receiving oxygen in our area. The mean age was 74 (range 17-100), 52 were female. Approximately 50% are in receipt of formal long term oxygen therapy and 50% have “short burst” oxygen.  445 scripts were issued by respiratory specialists, 285 by general practitioners, 70 unknown.  To date we have reviewed over 650 of the original 800 patients and see >20 new referrals each month. Our experience is that many historical oxygen prescriptions were not clinically indicated (based on UK guidelines). We have reduced spending on Oxygen from £51 000 per month in Sept 09 to £44 000 per month currently.  We have ongoing concerns about how best to risk assess patient in terms of potential of fire and falls. We are participating in the UK National Lung Improvement Program and are investigating how best to engage with primary care colleague and patients. We are also studying how to deal with patients who refuse to have oxygen withdrawn even when it is clinically indicated.
Evidence Concerning the Clonal Nature of Chemically Induced Tumors: Phosphoglycerate Kinase-1 Isozyme Patterns in Chemically Induced Fibrosarcomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F D Deamant, P M Iannaccone
Journal: JNCI Journal of the National Cancer Institute (1985)

Subcutaneous fibrosarcomas were induced chemically in mosaic mice heterozygous at the Pgk-1 locus on the X-chromosome. The normal tissues of these animals displayed two electrophoretically distinct isozymes of phosphoglycerate kinase-1-[(PGK-1) EC 2.7.2.3]. The tumors were carefully dissected and analyzed with respect to PGK-1 isozymes. A combination method of multiple sampling of the primary tumor and establishment of tissue culture cell lines from the tumor was utilized. A total of 82 samples was studied from 10 tumors developed in 9 mice. Twenty cell lines were established from 9 tumors; 6 of the tumors were shown to contain neoplastic cells of exclusively PGK-1B activity, 3 of the tumors were shown to contain neoplastic cells of exclusively PGK-1A activity, and 1 tumor contained neoplastic cells with both PGK-1A and PGK-1B activities. The tumor with both A and B activities was hourglass shaped, and the pattern of activity from multiple samples of this tumor suggests that it was formed by the coalescence of a PGK-1A and a PGK-1B tumor. The data presented are concordant with results from chimeric animals and spontaneous tumors in humans and indicate that these tumors display the behavior of clonal growths.
Comparison of histopathologic risk factors in enucleated eyes with retinoblastoma treated with chemoreduction versus no therapy
Authors: N. Tacyildiz, H. Ozdemir, G. Yavuz, E. Unal, H. Ergun, E. Erden, H. Dincaslan, A. Heper, K. Gunduz
Journal: Journal of Clinical Oncology (2008)

10039 Background: There is limited information about the histopathologic findings in the enucleated eyes with retinoblastoma (Rb) following chemoreduction(ChR) therapy to find out risk factors for metastasis and prognosis, although it is well established in Rb patients without ChR. Methods: Re-evaluation of pathologic slides and follow-up records of 53 enucleated patients with Rb that are followed between Jan 1996 - Jan 2007 in Ankara University Department of Pediatric Oncology and ophthalmology have been performed. Twenty nine of 53 patients (54.7 %) had received ChR ( carboplatin, etoposide, vincristine - VEC) between 2–6 cycles before the enucleation. Five out of 29 patients received local therapies and 2 patients have been performed radiotherapy besides ChR. Degree of optic nerve (ON), choroid, and scleral involvement and growth pattern of Rb were performed to analyse their effect on metastasis and prognosis. Results: ON involvement was tend to be lower in ChR group versus no therapy ( 31% versus 40%) Although, 4 retro-laminar ON involvement cases were in no therapy group, 2 ON cut-end positive cases were in ChR group. There was no difference between groups for Choroidal invasion (which was detected in 24 eyes and 73.6% of the cases showed grade-III invasion). Risk of metastasis, relapse and exitus was higher in patients with choroid invasion. ON and choroid invasions have a trend to be higher in undifferentiated and mixed growth pattern of tumor in both groups. Eleven patients showed scleral extension (6 in ChR and 5 in no therapy groups) and they have increased risk of metastasis, relaps and exitus (36.6% versus 3.3% exitus, respectively for scleral invasion positive and negative patients).In addition,2 patients with ON cut-end positivity (they had scleral invasion either) which were in ChR group have died. Conclusions: Undifferentiated, mixed growth pattern of tumor with choroidal, ON and scleral invasion of Rb, are major histopathologic risk factors for metastasis, relaps and exitus of patients with Rb in both ChR and no therapy groups. No significant financial relationships to disclose.
A meta-analysis of taxanes in adjuvant chemotherapy (ACT) of early breast cancer (EBC)
Authors: A. K. Nowak, T. Ferguson, N. R. Wilcken, D. Ghersi
Journal: Journal of Clinical Oncology (2007)

545 Background: Taxanes (docetaxel and paclitaxel) are highly active against breast cancer. Recent trials have examined taxanes as ACT for EBC. The objective of this meta-analysis is to compare taxane containing ACT regimens with ACT not containing a taxane in women with operable EBC. Methods: Eligible studies were properly randomized controlled trials in women with operable EBC receiving ACT (neoadjuvant CT was excluded) that compared taxane containing ACT regimens to ACT without a taxane. Studies were identified by a specifically designed search performed of the Cochrane Breast Cancer Group specialized register (to January 2007), Medline (to November 2006), and relevant conference proceedings (to November 2006). The primary outcome measure was overall survival (OS); secondary outcome measures included disease free survival (DFS) and toxicity. Two reviewers independently assessed eligibility, quality, and time-to-event (TTE) outcomes. Hazard ratios were derived for TTE outcomes where possible, and a fixed effect model was used for meta-analysis. Results: 20 studies were identified, 11 (4 abstracts; 7 full publications) with sufficient data published for inclusion (10 for OS, 11 for DFS). The average median follow-up was 54.6 months. All studies fulfilled quality criteria (allocation concealment, outcome measures, balance between arms, follow-up and intention to treat analysis) adequately or well. Amongst 17056 women with 2397 deaths, the HR for OS was 0.81, (95%CI=0.75–0.88, p&lt;0.00001) favoring taxane-containing ACT. 19943 women were included in analysis of DFS with a HR=0.81 (95%CI=0.75- 0.86, p&lt;0.00001) favoring taxane-containing ACT. There was no statistically significant heterogeneity for either OS or DFS. The effects were consistent in studies of node positive or node negative/positive patients, and with the same or longer duration of ACT in the taxane arm. Further analyses of taxane type (docetaxel or paclitaxel), sequential or concurrent taxane-anthracycline, and toxicity will be presented. Conclusions: This is the first meta-analysis quantifying the statistically significant OS and DFS benefit for the use of taxanes as ACT in operable EBC. Additional relevant studies remain unreported. Ongoing studies will define the optimal use of taxanes in EBC. No significant financial relationships to disclose.
Lenalidomide oral monotherapy in relapsed/refractory small lymphocytic non-Hodgkin’s lymphoma
Authors: T. E. Witzig, J. M. Vose, G. Justice, H. G. Kaplan, C. B. Reeder, D. Pietronigro, K. Takeshita, A. Ervin-Haynes, J. B. Zeldis, P. H. Wiernik
Journal: Journal of Clinical Oncology (2008)

8573 Background: Small lymphocytic lymphoma (SLL) is an indolent B-cell neoplasm that is histologically and immunophenotypically identical to chronic lymphocytic leukemia (CLL), but has less peripheral blood involvement. Treatment is similar to other indolent lymphomas. Lenalidomide (Revlimid®) is approved for treatment of patients with transfusion-dependent myelodysplastic syndromes associated with a deletion 5q [31] cytogenetic abnormality in the US and previously treated multiple myeloma in both the US and the EU. The aim of this subgroup analysis was to determine the safety and efficacy of lenalidomide monotherapy in patients with relapsed/refractory (r/r) SLL. Methods: Patients with r/r indolent non-Hodgkin’s lymphoma (NHL) with measurable disease after at least 1 prior treatment regimen were eligible; patients with SLL were included in this analysis. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and disease progression were evaluated using the IWLRC methodology. Results: Eighteen patients with SLL were enrolled. Median age was 65 (55–85) years and 7 were female. Median time from diagnosis to lenalidomide therapy was 4.1 (0.4–15.8) years and median number of prior treatment regimens was 3 (1–15). Four patients (22%) exhibited an objective response (1 unconfirmed complete response and 3 partial responses), 7 had stable disease, 5 had progressive disease and 2 were not evaluated. Progression-free survival is >6.5 months and ongoing. Grade 4 adverse events were neutropenia (28%) and thrombocytopenia (6%). The most common Grade 3 adverse events were neutropenia (33%) and thrombocytopenia (22%). Three patients (14%) experienced Grade 1/2 tumor flare. Conclusions: Lenalidomide oral monotherapy is active with manageable side effects in r/r SLL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation
Failure of Cell-Mediated Effector Mechanisms in Lung Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Feo Figarella, F Morillo, I Blanca, N E Bianco
Journal: JNCI Journal of the National Cancer Institute (1984)

The status of cell-mediated effector mechanisms was studied in 28 patients with lung cancer (25/28 in stage III). Patients' precultured peripheral blood mononuclear leukocytes, isolated by Ficoll-Hypaque, were tested for lymphocyte proliferation responses to alloantigens in mixed lymphocyte culture (MLC). The influence of autologous patients' sera was studied further on MLC responses from patients and controls. Cell-mediated lympholysis (CML), with the use of allogenic blast cells as targets, and antibody-dependent cell-mediated cytotoxicity (ADCC) against human red blood cells also were tested. Major differences between the cancer patients and controls were not demonstrated by MLC. Inhibition or enhancement of MLC responses by the autologous serum was shown; bimodal influence was significant; 72% of the sera caused inhibition and 28% caused enhancement. CML was depressed in 54% of the patients, and ADCC was depressed in 50%. The decrease in both cytotoxic responses was significant (P less than .005). Thirteen patients died after initiation of the investigative protocol; in 11 of 13, CML or ADCC was diminished. The altered cytotoxic capabilities were more prevalent among the epidermoid type, including the deceased patients. This study provides evidence that a severe impairment of cell-mediated effector mechanisms is frequent in advanced lung cancer and may be associated with poor clinical course and with the histologic type.
A phase II study of NGR-hTNF, a novel vascular targeting agent (VTA), administered as single agent at low dose in pretreated patients (pts) with advanced hepatocellular carcinoma (HCC)
Authors: G. Citterio, A. Santoro, R. Scalamogna, T. Pressiani, V. Gregorc, G. Rossoni, G. Donadoni, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2008)

15544 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13 highly expressed on tumour blood vessels. NGR-hTNF combines activity on tumour vascular permeability and direct anticancer activity. In preclinical models, NGR-hTNF showed antitumor activity either at low doses or at high doses. Methods: Pts with unresectable or metastatic HCC were treated with a low dose of NGR-hTNF given at 0.8 mcg/m2 as 1-hour intravenous infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled in stage 1 and 2, respectively. Progression-free survival (PFS) was the primary end point and tumor reassessment (WHO criteria) was performed q6w. Results: 16 pts with progressive disease following prior loco-regional treatment (63%), systemic therapy (50%), or both (19%), were recruited into the first stage. Pts characteristics were: M/F 13/3; median age 66 years (range, 53 to 79); PS 0/1 11/5; Child-Pugh score A/B: 14/2. To date, 46 cycles (median 2, range: 1–8) have been administered and 5 pts (28%) received ≥4 doses. In the first step of the trial, 5 out of 14 assessable pts (36%) had a stabilization of disease (SD) with a median duration of 4.3 months (range: 2.7–6.2). The median PFS was 2.4 months (95% CI: 1.5–3.1). Neither grade 3–4 treatment-related adverse events nor toxicity-related death were observed. Main grade 1–2 toxicities per patient were infusion-related constitutional symptoms, including chills (59%), and transient blood pressure increase (6%). The study is currently recruiting patients into the second stage and in a subsequent cohort of 12 patients treated with a weekly schedule of administration. Conclusions: NGR-hTNF given at 0.8 mcg/m2 q3w is well tolerated and appears to induce promising disease control in pretreated patients with advanced HCC. The drug will be further explored as single agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MolMed
Cross-trial prediction of treatment outcome in depression: a machine learning approach
Authors: Adam Mourad Chekroud, Ryan Joseph Zotti, Zarrar Shehzad, Ralitza Gueorguieva, Marcia K Johnson, Madhukar H Trivedi, Tyrone D Cannon, John Harrison Krystal, Philip Robert Corlett
Journal: The Lancet Psychiatry (2016)
Older patients with HIV should be offered cancer screening, study recommends
Authors: Jacqui Wise
Journal: BMJ (2015)

People with HIV should be monitored for cancers as they get older, says a study in Annals of Internal Medicine which shows that they are at higher risk for several cancers including lung cancer.1

The cohort study compared time trends in cumulative cancer incidence by age 75 in 86 620 people with HIV and 196 987 …