A Prospective,Blinded Comparison of Magnetic Resonance (MR) Imaging–Ultrasound Fusion and Visual Estimation in the Performance of MR-targeted Prostate Biopsy: The PROFUS Trial

Background

Increasing evidence supports the use of magnetic resonance (MR)–targeted prostate biopsy. The optimal method for such biopsy remains undefined, however.

Objective

To prospectively compare targeted biopsy outcomes between MR imaging (MRI)–ultrasound fusion and visual targeting.

Design, setting, and participants

From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences.

Intervention

Two MRI–ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy.

Outcome measurements and statistical analysis

Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression.

Results and limitations

Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum ≥7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting (p = 0.1374, p = 0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual (p = 0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum ≥7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited.

Conclusions

Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.     

Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

Background

Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery.

Objective

To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC).

Design, setting, and participants

This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible.

Intervention

Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy.

Outcome measurements and statistical analysis

The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST).

Results and limitations

A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers.

Conclusions

Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC.

Patient summary

In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use.

Trial registration

This clinical trial was registered with clinicaltrials.gov (NCT01263769).     

Defining the level of evidence for technology adoption in the localized prostate cancer pathway

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes.     

贝伐珠单抗治疗恶性肿瘤相关不良反应回顾性分析

摘 要 目的：探讨贝伐珠单抗治疗恶性肿瘤的相关不良反应（ADR）发生情况及特点,为临床安全使用贝伐珠单抗提供参考。方法：采用回顾性分析方法,收集2016年10月~2018年4月使用贝伐珠单抗治疗而出现ADR的94例恶性肿瘤病例,统计患者年龄、性别、所患疾病,贝伐珠单抗剂量、联合化疗方案,ADR发生时间、症状、严重程度等。 结果：患者原患疾病主要为结直肠癌、非小细胞肺癌（NSSCLC）和乳腺癌,其中化疗一线治疗53例,二线治疗41例。本组患者中贝伐珠单抗所致ADR发生在6个月内,≤3个月者64例,3~5个月者30例,其中导致出血、贫血、高血压比例分别为29.79%,29.79%,25.53%,明显高于其他ADR占比（P<0.05）。高血糖、肠穿孔等特殊ADR比例分别为7.45%,1.06%。结论：贝伐珠单抗严重ADR比例较低,临床使用贝伐珠单抗时,应密切关注发生概率较高及特殊的ADR,做到定期监测、及时处理。     

IL-6/gp130在类风湿性关节炎疾病中的作用：从机制到临床转化进展

白细胞介素-6（IL-6）参与慢性炎症的发生、自身抗体的产生以及血管通透性改变等过程,是类风湿性关节炎发作期间最高表达的炎性介质之一,成为药物治疗的靶点。不同来源的白细胞介素-6可以通过与白细胞介素-6Rα和gp130结合,经经典信号转导或转移信号转导或聚类信号转导模式,介导JAK-STAT、ERK-MAPK和PI3K-AKT 3种途径的细胞内信号转导,引起炎症发生。针对白细胞介素-6/gp130的靶向药物逐步被开发,但是仍然存在着诸多不良反应和副作用,靶向给药途径或局部给药途径治疗类风湿性关节炎被看好。本文总结了以白细胞介素-6及其受体为靶标的类风湿性关节炎治疗药物研发与使用情况,讨论了新型给药系统在类风湿性关节炎治疗研究中的优势,期望能为治疗类风湿性关节炎药物的研发提供新的思路。     

骨盆骨折病人尿路感染的临床护理要点研究

目的:探讨预防骨盆骨折患者尿路感染的临床护理要点.方法:选择2017年4月-2018年12月期间在我院接受治疗的50例骨盆骨折患者,遵照随机原则分为对照组、观察组,术后对照组实施常规护理,观察组在分析尿路感染成因基础上实施针对性护理干预,对比2组护理效果.结果:2组尿路感染发生率依次为4.0%、20.0%,差异显著(P<0.05);Majeed评估结果表明,观察组患者治疗优良率更高于对照组(P<0.05);末次随访时,在QOL-AD量表各维度评分上,观察组均高于对照组,差异均有统计学意义(P<0.05).结论:骨盆骨折患者治疗期间结合尿路感染发病原因实施针对性护理,能降低尿路感染发生的风险,优化疾病治疗效果,改善生活质量,有推广价值.     

An alternative to product-specific pregnancy registries? PRIM; PRegnancy outcomes Intensive Monitoring

Patient safety during pregnancy is an important concern. This article presents a method of using an industry safety database to access prospective pregnancy cases. This method, termed here 'PRegnancy outcomes Intensive Monitoring' (PRIM) was developed for fingolimod (Gilenya ™), a treatment option for multiple sclerosis (MS), due to slow enrollment in the company pregnancy registry. The aim of PRIM was to enhance the process of pregnancy data collection and improve data quality, and in particular to enable estimation of the proportion of major congenital malformation and other pregnancy outcomes. To do this, the spontaneous reports of maternal exposure to fingolimod in pregnancy or in the eight weeks immediately before the last menstrual period of patients not enrolled in the pregnancy registry were identified. Follow up checklists were sent at four time points: initial pregnancy report, end of pregnancy, infant attained 3 and 12 months of age. These focused on core data required for derivation of programmed analyses. From 01 Mar 2014 to 28 Feb 2018, a total of 831 prospective maternal exposures with 843 infants were reported, with fetal outcomes reported in 459/843 (54.4 %) of those infants. This enabled the calculation of proportions of pregnancy cases with the main pregnancy outcomes and of fetal cases with malformation. The number of reported pregnancies was significantly higher in PRIM than in the registry, showing that structured use of pharmacovigilance data enables speedier assessment of risks of maternal drug exposure.     

阿帕替尼联合调强放疗治疗胃癌的临床价值

目的探讨阿帕替尼靶向治疗联合调强放疗治疗胃癌的临床效果.方法66例胃癌患者,随机分为对照组和观察组,每组33例.对照组给予调强放疗,观察组给予阿帕替尼靶向治疗联合调强放疗.对比两组临床疗效、不良反应发生情况、生存时间、无进展生存时间.结果观察组疾病控制率72.73%高于对照组的42.42%,差异有统计学意义(P<0.05).观察组不良反应发生率为24.24%,与对照组的30.30%对比差异无统计学意义(P>0.05).治疗后,观察组生存时间为(1.52±0.33)年,长于对照组的(1.03±0.24)年,差异有统计学意义(t=6.898,P<0.05);观察组无进展生存时间为(0.69±0.14)年,长于对照组的(0.37±0.12)年,差异有统计学意义(t=9.969,P<0.05).结论胃癌患者采用阿帕替尼靶向治疗联合调强放疗能够改善临床疗效,提高患者生活质量.     

Current status and development of anti-PD-1/PD-L1 immunotherapy for lung cancer

Lung cancer is the leading cause of cancer deaths worldwide, mainly because it is usually in the advanced stage at the time of diagnosis. Although great progress has been made in the diagnosis and treatment of lung cancer in the past 25 years, the prognosis of lung cancer patients remains unsatisfactory. Agents targeting immune checkpoints have shown potential to improve therapeutic outcomes in patients with lung cancer. Inhibitors of PD-1/PD-L1 have been approved for the treatment of different types of lung cancer by FDA. Nevertheless, with the increasing number of clinical trails, the adverse events have emerged. Therefore, attention has been paid to finding out the factors influencing the therapeutic effect of anti-PD-1/PD-L1 therapy and reducing the occurrence of adverse events. Combination therapy may be an effective strategy to reduce the adverse events and improve the therapeutic effect. In this review, we summarized the current status and progress of anti-PD1/PD-L1 agents in lung cancer treatment.     

针对性个案护理结合细节护理在首次使用无创呼吸机患者中的应用

目的:探讨针对性个案护理结合细节护理在首次使用无创呼吸机患者中的应用效果。方法:选取2018年6月1日~2019年10月31日收治的80例首次使用无创呼吸机的患者,采用随机数字表法分为对照组和观察组各40例。对照组接受常规护理,观察组在常规护理基础上接受针对性个案护理结合细节护理。比较两组护理前后舒适度、肺功能[包括用力呼气量(FVC)和一秒用力呼气量(FEV₁)]及生活质量,比较两组不良反应发生情况和护理满意度。结果:护理后,两组舒适度评分、生活质量评分高于护理前(P<0.05),且观察组高于对照组(P<0.01);护理后,两组FVC、FEV₁高于护理前(P<0.05),且观察组高于对照组(P<0.01);观察组不良反应发生率低于对照组(P<0.01,P<0.05),护理满意度高于对照组(P<0.01)。结论:对首次使用无创呼吸机的患者实施针对性个性护理结合细节护理,能够有效提升患者舒适度,降低不良反应发生率,提高其护理满意度,改善患者肺功能,提高生活质量,值得临床推广。