V2 范春嫦 声望 1 动植物检疫 2024-03-03 15:18:55 上传
Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation
Background & Aims Interferon alfa–based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. Methods In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. Results Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%−82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. Conclusions Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.
V1 Bronwen 声望 1 生物安全 2024-02-29 09:38:08 上传
PACMEL: A phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel
Abstract Background We sought to determine the maximal tolerated dose of the MEK inhibitor trametinib with weekly paclitaxel, with a view to exploring the combination’s activity in melanoma lacking a BRAF V600 mutation. Methods In this phase 1 study we used a fixed dose of paclitaxel (80 mg/m2 intravenous (IV) on days 1, 8 and 15 of each 4 week cycle) and escalated the dose of trametinib (to a maximum 2 mg orally (PO) daily), following a 3 + 3 design. Eligible patients had advanced melanoma and could have received up to two previous lines of treatment for metastatic disease. Findings 15 patients were enrolled, all but one of whose melanoma was wild type for BRAF at codon 600. The maximal monotherapy dose of trametinib proved tolerable with weekly paclitaxel. The most frequent adverse events observed were rash and fatigue. Six (40%) partial responses were reported, including four of eight patients with NRAS mutations. Median progression free survival was 5.5 months (95% confidence interval (CI) 1.8–7.8 months) and overall survival, 14.1 months (95% CI 4.6–not reached). Interpretation Trametinib can safely be given with weekly paclitaxel at the full monotherapy dose. In this small group promising progression free and overall survival were observed in patients with melanoma lacking a V600 BRAF mutation.
V2 林江溪 声望 1 化学 2024-02-29 07:51:51 上传
Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study
Purpose Lower serum testosterone levels correlate with improved cause specific survival and longer time to progression in year 1 of continuous androgen deprivation in men with prostate cancer. ICELAND was a large European study demonstrating the efficacy of leuprorelin (Eligard®) during continuous androgen deprivation. In this post hoc analysis we investigated serum testosterone levels within year 1 of continuous androgen deprivation to determine survival and time to progression. Materials and Methods In ICELAND (ClinicalTrials.gov NCT00378690) patients with locally advanced or relapsing nonmetastatic prostate cancer and with prostate specific antigen 1 ng/ml or less following 6-month induction with leuprorelin 3-month depot 22.5 mg (plus bicalutamide 50 mg per day for 1 month) were randomized 1:1 to continuous androgen deprivation (361) or intermittent androgen deprivation (340) with leuprorelin for 36 months. Patients receiving continuous androgen deprivation were stratified by minimum, median and maximum testosterone levels during year 1 of therapy into 20 or less, greater than 20 to 50 and greater than 50 ng/dl subgroups. Cause specific survival and time to prostate specific antigen (castrate resistant prostate cancer) progression were analyzed. Results A total of 90.1%, 83.5% and 74.5% of patients receiving continuous androgen deprivation achieved minimum, median and maximum serum testosterone levels of 20 ng/dl or less, respectively. Cause specific survival rates and time to prostate specific antigen progression did not differ among the testosterone subgroups. Conclusions In patients receiving continuous androgen deprivation cause specific survival and time to prostate specific antigen progression did not differ according to testosterone levels in year 1 of therapy. This finding may in part be due to the induction period and the effectiveness of leuprorelin in lowering testosterone.
V1 欧希文 声望 1 生物安全 2024-02-29 07:08:30 上传
A 17-Gene Genomic Prostate Score Assay Provides Independent Information on Adverse Pathology in the Setting of Combined Multiparametric Magnetic Resonance Imaging Fusion Targeted and Systematic Prostate Biopsy
Purpose Multiparametric magnetic resonance imaging and biopsy based molecular tests such as the 17-gene Oncotype DX® Genomic Prostate Score™ assay are increasingly performed to improve risk stratification in men with clinically localized prostate cancer. The prostate score assay was previously shown to be a significant independent predictor of adverse pathology findings at radical prostatectomy in men diagnosed by systematic biopsies only. Therefore, we investigated the ability of the prostate score assay to predict adverse pathology findings in the setting of magnetic resonance imaging guided prostate biopsy. Materials and Methods We identified men diagnosed with NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate risk prostate cancer who underwent simultaneous multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy with subsequent radical prostatectomy within 6 months. Prostate score assay testing was performed on biopsy tissue with the highest Gleason score. The primary outcome of the study was adverse pathology findings, defined as Gleason score 4 + 3 or greater disease and/or pT3+ at radical prostatectomy. Independent predictors of adverse pathology findings were determined in a multivariable model to adjust for clinical parameters. Results A total of 134 men were eligible for primary analysis. On univariable analysis the UCLA score, magnetic resonance imaging, prostate score assay results and biopsy Gleason score were significant predictors of adverse pathology findings. After multivariable adjustment prostate score assay values remained a significant predictor of adverse pathology results (prostate score assay per 20 U OR 3.28, 95% CI 1.74–6.62, p <0.001). A wide and overlapping distribution of prostate score assay results was seen across PI-RADS® (Prostate Imaging Reporting and Data System) version 2 scores. Conclusions The prostate score assay result is an independent predictor of adverse pathology findings in patients who were diagnosed with very low, low or intermediate risk prostate cancer in the setting of multiparametric magnetic resonance imaging fusion prostate biopsy. This assay can be useful as an independent technology or an adjunct technology to multiparametric magnetic resonance imaging to individualize risk stratification of low and intermediate risk prostate cancer.
V3 假装 声望 42 2024-02-29 06:09:32 上传
Hodgkin lymphoma: A review and update on recent progress
Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced-intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long-term treatment toxicities.
V4 宋建宇 声望 44 中医 2024-02-29 02:16:17 上传
FGF7 Over Expression is an Independent Prognosticator in Patients with Urothelial Carcinoma of the Upper Urinary Tract and Bladder
Purpose Urothelial carcinoma of the bladder and upper tract is the most common tumor type in the urinary tract but its molecular pathogenesis and survival determinants remain obscure. By data mining a published transcriptomic database of bladder urothelial carcinoma (GSE31684) we identified FGF7 as the most significant gene up-regulated during urothelial carcinoma progression. We then used our well characterized urothelial carcinoma cohort to analyze FGF7 transcript and protein expression, and its clinicopathological significance. Materials and Methods We performed real-time reverse transcriptase-polymerase chain reaction assay to determine the FGF7 transcript level in 30 fresh samples each of upper tract and bladder urothelial carcinoma. Immunohistochemistry evaluated by H-score was used to determine FGF7 protein expression in 340 upper tract and 295 bladder urothelial carcinomas. Transcript and protein expression were correlated with clinicopathological features. We further evaluated the prognostic significance of FGF7 protein expression for disease specific and metastasis-free survival. Results An increased FGF7 transcript level was associated with higher pT stage in upper tract and bladder urothelial carcinoma (p = 0.003 and <0.001, respectively). In the upper tract and bladder carcinoma groups FGF7 protein over expression was also significantly associated with advanced pT status (each p <0.001), lymph node metastasis (p = 0.002 and <0.001), high histological grade (p = 0.019 and <0.001), vascular invasion (each p <0.001), perineural invasion (p = 0.002 and 0.021) and frequent mitoses (p = 0.002 and 0.042, respectively). FGF7 over expression predicted dismal disease specific and metastasis-free survival on univariate and multivariate analysis. Conclusions Our study shows that FGF7 over expression is associated with advanced clinical features in patients with upper tract and bladder urothelial carcinoma, justifying its potential prognostic value for urothelial carcinoma.
V1 罗伯特小恶魔 声望 1 遗传学和遗传工程系 2024-02-28 23:49:20 上传
Honorary and ghost authorship in reports of randomised clinical trials in oncology
Abstract Background The International Committee of Medical Journal Editors (ICMJE) has developed guidelines for responsible and accountable authorship. Few studies have assessed the frequency and nature of ghost and honorary authorship in publications of oncology trials. Materials and methods Reports of randomised clinical trials evaluating systemic cancer therapy published from July 2010 to December 2012 in six high-impact journals were identified systematically. Ghost authorship was determined to be present in any scenario where investigators or statisticians listed in the protocol were not included as authors and not acknowledged in the report of the trial. The list of contributions for authors of published articles was recorded, and we defined an article as having an honorary author if any author did not meet all three criteria established by ICMJE in 1985. Results Two hundred publications were identified. For 61 articles, protocols with listed investigators were available, and 40 (66%) of these articles met our definition of ghost authorship. Medical writers were involved in 89 articles (45%), and assistance was acknowledged only in sponsored trials. Contributions of each author were provided in 195 articles, and 63 (33%) articles met our definition for honorary authorship. Funding source was not a predictor for either honorary or ghost authorship. Journal impact factor was positively associated with honorary authorship (odds ratio = 1.03; 95% confidence interval = 1.004–1.065; P = 0.03), but not with ghost authorship. Conclusion Ghost and honorary authorship are prevalent in articles describing trials for systemic therapy of cancer. Guidelines should be enforced to improve transparency and accountability.
V2 先生 声望 10 2024-02-28 21:15:12 上传
Comorbid Disease Burden is Independently Associated with Higher Risk Disease at Prostatectomy in Patients Eligible for Active Surveillance
Purpose Comorbid medical conditions are highly prevalent among patients with prostate cancer and may be associated with more aggressive disease. We investigated the association between comorbidity burden and higher risk disease among men eligible for active surveillance. Materials and Methods Using the National Cancer Data Base we identified 29,447 cases of low risk (Gleason score 6 or less, cT1/T2a, prostate specific antigen less than 10 ng/ml) prostate cancer managed with prostatectomy from 2010 to 2011. The primary outcome was pathological upgrading (Gleason score greater than 6) or up staging (T3-T4/N1). The association between Charlson score and upgrading/up staging was analyzed using multivariate logistic regression. Results The study sample comprised 29,447 men, of which 449 (1.5%) had Charlson scores greater than 1. At prostatectomy 44% of cases were upgraded/up staged. On multivariate analysis Charlson score greater than 1, age 70 years or greater, nonwhite race, higher prostate specific antigen and higher percentage of cores involved with disease were significantly associated with upgrading/up staging. After further adjusting for age, race, prostate specific antigen and core involvement, Charlson score remained a significant predictor of upgrading/up staging for younger white men. Specifically, white men less than 70 years old with Charlson comorbidity index greater than 1 had 1.3-fold higher odds of upgrading/up staging than men with Charlson comorbidity index 1 or less (OR 1.31, 95% CI 1.03–1.67, p=0.029). Conclusions Comorbidity burden is strongly and independently associated with pathological upgrading/up staging in men with clinically low risk prostate cancer. This finding may help improve disease risk assessment and clinical decision making in men with comorbidities considering active surveillance.
V1 许蓓烨 声望 2 动植物检疫 2024-02-28 19:29:39 上传
Survival of elderly patients with multiple myeloma—Effect of upfront autologous stem cell transplantation
Abstract Background The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60–79 years) with myeloma. Methods We analysed relative survival (RS) of patients diagnosed in 1998–2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries). Results Utilisation of ASCT has increased rapidly between 2000–2002 and 2009–2011 (60–64years: 7.0–43.0%; 65–69 years: 6.6–23.7%; 70–79 years: 0.4–4.0%). Comparison of 5-year RS of patients from the general German myeloma population who have survived the first year after diagnosis with 5-year RS of patients treated with ASCT revealed higher survival for transplanted patients among all age groups (60–64: 59.2% versus 66.1%; 65–69: 57.4% versus 61.7%; 70–79: 51.0% versus 56.6%). RS increased strongly between 2003–2005 and 2009–2011 for the general German myeloma population (+8.5%) and for patients treated with ASCT (+11.8%). Differences in RS between these groups increased over time from +1.9% higher age-standardised survival in transplanted patients in 2003–2005 to 5.2% higher survival in 2009–2011. Conclusion We conclude that upfront ASCT might be a major contributor to improved survival for elderly myeloma patients in Germany.
V1 王学峰 声望 1 生物工程 2024-02-28 07:40:41 上传
Influence of Age on Incident Diabetes and Cardiovascular Disease in Prostate Cancer Survivors Receiving Androgen Deprivation Therapy
Purpose Observational data suggest that androgen deprivation therapy increases the risk of diabetes and cardiovascular disease. Using data from the population based PCOS we evaluated whether age at diagnosis and comorbidity impact the association of androgen deprivation therapy with incident diabetes and cardiovascular disease. Materials and Methods We identified men with nonmetastatic prostate cancer diagnosed from 1994 to 1995 who were followed through 2009 to 2010. We used multivariable logistic regression models to assess the relationship of androgen deprivation therapy exposure (2 or fewer years, greater than 2 years or none) with incident diabetes and cardiovascular disease, adjusting for age at diagnosis, race, stage and comorbidity. Results Of 3,526 eligible study participants 2,985 without diabetes and 3,112 without cardiovascular disease comprised the cohorts at risk. Androgen deprivation therapy was not associated with an increased risk of diabetes or cardiovascular disease in men diagnosed with prostate cancer before age 70 years. Prolonged androgen deprivation therapy and increasing age at diagnosis in older men was associated with an increased risk of diabetes (at age 76 years OR 2.1, 95% CI 1.0–4.4) and cardiovascular disease (at age 74 years OR 1.9, 95% CI 1.0–3.5). Men with comorbidities were at greater risk for diabetes (OR 4.3, 95% CI 2.3–7.9) and cardiovascular disease (OR 8.1, 95% CI 4.3–15.5) than men without comorbidities. Conclusions Prolonged androgen deprivation therapy exposure increases the risk of cardiovascular disease and diabetes in men diagnosed with prostate cancer who are older than approximately 75 years, especially those with other comorbidities. Older men who receive prolonged androgen deprivation therapy should be closely monitored for diabetes and cardiovascular disease.

肿瘤学,有些医院分为肿瘤内科和肿瘤外科,肿瘤内科主要从事各种良、恶性肿瘤的内科治疗;肿瘤外科提供以手术为主的综合治疗。专门的肿瘤医院的相关科室会根据不同部位再行细分,例如乳腺外科、头颈外科、胸外科、肿瘤妇科、腹部外科、肿瘤内科等。