Development of Research Agenda in Prostate Artery Embolization: Summary of Society of Interventional Radiology Consensus Panel

PurposeTo summarize the Society of Interventional Radiology Foundation’s Research Consensus Panel development of a research agenda on prostate artery embolization (PAE).Materials and MethodsPAE for the treatment of lower urinary tract symptoms has been shown to be safe and effective in decreasing symptoms and prostate size. Lack of randomized controlled trials (RCTs) on PAE in the United States has prevented inclusion in American Urologic Association guideline recommendations for treatment of lower urinary tract symptoms resulting from benign prostatic hyperplasia. Recognizing the need for well-designed trials, the SIR Foundation funded a Research Consensus Panel to prioritize a research agenda. The panel included interventional radiologists, urologists, SIR Foundation leadership, and industry representatives. The goal of the meeting was to discuss weaknesses with current data and study design for development of US trials to report long-term outcomes data.ResultsFinal consensus on a research design could not be made because the group was split on 3 research designs: (i) RCT of PAE versus sham with crossover of the sham group. (ii) RCT of PAE versus simple prostatectomy. (iii) RCT of PAE versus holmium laser enucleation of the prostate/thulium laser enucleation of the prostate. The panel recommended a nonindustry-funded registry to obtain real-world data.ConclusionsLevel 1 data are required to be included in the American Urologic Association guidelines for treatment of benign prostatic hyperplasia. Because of concerns with all 3 study designs, the panel did not reach a consensus. Further meetings are planned with the panel to select among these research designs.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Traversing distance and proximity: the integration of psychodrama and dance movement therapy techniques in supervision

This article explores the potential for intermodal methods in person-centred supervision, focusing on the application of techniques from dance movement therapy (DMT) and psychodrama. The article proposes how specific structures combining psychodrama and DMT allow the supervisee to negotiate between proximity and distance, offering ways to hone in, step out or create alternative perspectives. Somatic congruence is introduced as a person-centred principle that enables the supervisor to understand and/or share somatic reactions in response to the supervisee’s material or the supervisor’s own personal process. Embodying roles and projective techniques are illustrated in the article through examples from the author’s supervisory DMT practice, demonstrating how these interventions may help symbolically crystallise supervisory issues. Caveats to these interventions and cautions to practitioners are presented, contributing to critical analyses of cross-disciplinary work. The article presents a constructive view towards future research and professional development on intermodal, creative supervisory practice.     

New medical treatment options and strategies to assess clinical outcome in soft-tissue sarcoma

Soft-tissue sarcomas (STSs) are a heterogeneous group of rare malignant tumors predominantly arising from the embryonic mesoderm. The mainstay of curative therapy is the complete surgical resection of all tumor manifestations with negative histological margins. However, up to 50% of patients will develop distant metastases during the course of their disease. The prognosis for those patients is grim with a 5-year overall survival of less than 10%. First-line systemic therapy with ifosfamide and doxorubicin results in overall response rates of only 20% by conventional response evaluation criteria in solid tumors (RECIST). However, stabilization of disease can be seen in a greater proportion. Therefore, the role of the RECIST criteria has been questioned and the implementation of new imaging studies (e.g., FDG-PET) has shown promising results in assessing early tumor response to therapy. Furthermore, a broader insight into the molecular pathways of sarcomagenesis has been gained in recent years, revealing intriguing targets for new therapeutic approaches (e.g., VEGF, VEGF receptor, IGF receptor, EGF receptor, mTOR and cyclin-dependent kinases). In addition, a growing body of evidence is linking specific genetic aberrations with clinical outcome (e.g., SYT–SXX translocation in synovial sarcoma). With further insight into the biology of STS and the combination of new treatment options with modern imaging techniques, we will most certainly be able to improve clinical outcome in patients with STS in the upcoming years.     

Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specifc cell-permeable peptide inhibitor

Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identifcation of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efcacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.