30 years of ocular proton therapy,the Nice view

PurposeRadiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization.Materaial and methodsMEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991–2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (～95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract).ResultsAlthough demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice.ConclusionsSome of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.     

Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations

BackgroundAdjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews.ObjectiveTo assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process.MethodsFour electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs.ResultsWe included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n = 9), joint posture procedures (JPPs, n = 11), and active ATs (n = 14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score = 7 [6–8]) but moderate (n = 2) or poor (n = 2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (> 3 months after botulinum toxin injections), particularly when performed at a high-intensity (> 3 h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended.ConclusionsJPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life.Review RegistrationPROSPERO (CRD42018105856).     

物理治疗翻转课堂教学应用效果的系统综述

目的 系统评价翻转课堂教学模式在物理治疗学教学中的应用效果。方法 计算机检索CENTRAL、MEDLINE、EMBASE、CINAHL Plus、Academic Search Premier、Teacher Reference Center、ERIC以及Education Research,纳入翻转课堂教学模式应用于物理治疗学教学的原始研究。检索时限为建库至2021年6月。由2名研究人员独立完成文献筛选、数据提取、质量评价,对翻转课堂教学模式对比传统教学模式在物理治疗学教学中的效果进行综述。结果与结论 共检索文献1 307篇,最终纳入7篇,包括至少770名学生。发表时间集中在2013年至2019年,研究对象为物理治疗学专业学生,主要结局指标为考试成绩。翻转课堂教学模式总体说来可提高学生的笔试成绩,增强高阶思维能力,得到了学生和教师的积极评价。     

多功能套针浮刺疗法治疗神经根型颈椎病——一项随机对照观察研究＊

目的 评价多功能套针浮刺疗法对神经根型颈椎病的临床疗效。方法 选取256例神经根型颈椎病患者，按随机数字表法分为观察组与对照组各128例。观察组应用多功能套针浮刺疗法进行干预，对照组为常规针刺治疗。两组患者均治疗7天。分别于治疗前后观察两组患者的简化McGill疼痛问卷（SF-MPQ）、国际标准颈椎功能障碍指数（NDI）和田中靖久颈椎病症状20分法量表评分，并于治疗结束后3个月观察复发率。结果 两组患者治疗后的SF-MPQ量表评分、NDI量表评分及田中靖久颈椎病症状20分法评分与治疗前相比均有改善（P<0.05），且观察组优于对照组（P<0.05）；两组患者于治疗后3个月随访，SF-MPQ量表评分与治疗后相比均有改善，且观察组优于对照组（P<0.05）；观察组临床疗效总有效率为96.88%，愈显率为81.25%；对照组总有效率为78.13%，愈显率为46.88%，观察组优于对照组（P<0.05）。结论 应用多功能套针浮刺疗法治疗神经根型颈椎病临床疗效显著，见效较快，可有效降低其复发率，且作用稳定，效果持久，值得临床推广应用。     

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.