Correction to: “Living with COVID”—implications for immunosuppressed and immunocompromised

Clinical Rheumatology -     

The current status of surgical pilonidal sinus disease therapy in Germany

European Surgery - Treatment of pilonidal sinus disease (PSD) requires a tailored approach. A national guideline was published in 2014. The current status of surgical PSD therapy...     

人脑胶质母细胞瘤miR-4516表达与病人预后的关系

目的 探讨人胶质母细胞瘤（GBM）组织微小核糖核酸-4516（miR-4516）的表达情况及其与病人预后的关系。方法选取 2015年 1月~2019年 5月手术切除的 GBM组织 89例和颅脑损伤内减压术切除的非肿瘤脑组织 35例为对照组，采用 qRT-PCR检测 miR-4516的表达水平，根据 miR-4516表达水平的中位数分为高表达和低表达。GBM病人术后随访 2年，记录生存情况。结果 GBM组织 miR-4516表达水平（[ 5.32±1.75）]明显高于对照组（[ 1.13±0.45）；P<0.01]。术后 2年随访，42例（47.19%）生存，47例 47（52.81%）死亡。多因素 Cox回归分析显示，miR-4516高表达是 GBM生存预后病例的独立危险因素（P<0.05）。生存曲线分析显示 miR-4516高表达组 2年累积生存率（27.45%）明显低于低表达组（73.68%；P<0.001）。结论 GBM组织 miR-4516表达增高，其高表达是病人预后不良的危险因素。     

Mechanisms of defense in clinical ethics consultation

Medicine, Health Care and Philosophy - Clinical ethics consultants respond to a multitude of issues, ranging from the cognitive to the emotional. As such, ethics consultants must be prepared to...     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.