Low Temperature Plasma : A Novel Focal Therapy for Localized Prostate Cancer?

Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer

Modelling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case

Background: Breast cancer is the most common cancer in women worldwide and is the second most common cause of cancer death in women. Electrochemotherapy (ECT) used in early-phase clinical trials for the treatment of primary breast cancer resulted in a not complete tumor necrosis in most cases. The present study was undertaken to analyze the feasibility to use ECT to treat patients with histologically proven unifocal ductal breast cancer. In particular, results of ECT treatment in a clinical case are compared with the ones of a simplified 3D dosimetric model. Methods: This clinical study was conducted with the pulse generator Cliniporator Vitae (IGEA, Carpi, Italy). ECT procedures were performed according to ESOPE standard operating procedures. Five single needle electrodes were used with one positioned in the center of the tumor, and the other four distributed around the nodule. Histological images of the resected tumor are compared with the maps of the electric field obtained with a simplified 3D model in Comsol Multiphysics v 4.3. Results: The results of the clinical case demonstrated a reduced efficacy of the ECT treatment described. The proposed simple numerical model of the breast tumor located in a low conductive tissue suggests that this is due to the reduced electric field induced inside the tumor with such 5 electrodes placement. However, where the electric field is predicted higher than the reversible electroporation threshold (E > 400 V/cm), also the histological images confirm the necrosis of the target with a good agreement between the modeled and clinical results. Conclusions: The results suggest the dependence of the effectiveness of the treatment on the careful placement of the electrodes. A detailed planned procedure for the tumor analysis after the treatment is also needed in order to better correlate the single electrode positions and the histological images. Simulation models could be used to identify better electrodes configuration in planning the experimental protocol for ECT treatment of breast tumors

Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

PurposeTo determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies.Material and methodsThis retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival.ResultsThe median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities.ConclusionsWe demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC

Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

Health economic aspects to the adoption of MR-HIFU for patients with bone metastases

Bone metastases is a common consequence of advanced cancer that is usually associated with pain, impaired mobility, and reduced overall quality of life. External Beam Radiotherapy (EBRT) is the current standard of care; however, it might take four weeks to induce pain relief. Moreover, 50% of patient recur pain after initial response to EBRT, and reirradiation is limited due to the risk of cumulative doses harming surrounding structures. Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) is an emerging non-invasive procedure that can provide significant and rapid pain palliation for patients with bone metastases with a favorable safety profile. Thus, the FURTHER project aims to evaluate the effectiveness of MR-HIFU to pain palliation of painful bone metastases compared to the EBRT in a randomized controlled trial. In addition to evidence on effectiveness of MR-HIFU, health economic evidence was needed to support adoption of MR-HIFU in Europe. This cumulative dissertation comprises three dissertation subprojects. The first subproject describes a time-driven activity-based costing approach to determine the costs of the MR-HIFU from the hospital perspective. The second subproject consists of an early economic modelling study that aimed to evaluate the cost-effectiveness of MR-HIFU compared to EBRT from the perspective of the German Statutory Health Insurance (SHI). The third subproject consists of a mixed-method participatory research with the objective to investigate contextual factors influencing the adoption of MR-HIFU for treatment of bone metastases in Europe. Based on results of the three subprojects, three main conclusions follow. First, adoption of MR-HIFU would benefit greatly from improvements to the care pathway, which would reduce costs of MR-HIFU, and subsequently impact the cost-effectiveness in relation to EBRT. Second, although still in early phase of implementation, MR-HIFU is potentially cost effective for patients with bone metastases and further research is worthwhile to better inform the decision whether to adopt MR-HIFU as a treatment alternative in the German SHI. Third, to ensure successful adoption of MR-HIFU, several contextual factors have to be addressed strategically, such as hospital referral, logistics and patients’ preferences. MR-HIFU is a promising treatment strategy for patients with painful bone metastases. Although clinical evidence on the effectiveness of MR-HIFU is still needed, the health economic evidence generated in this cumulative dissertation provides strong impetus for the adoption of MR-HIFU in clinical practice

Magnetic resonance thermometry: methodology, pitfalls and practical solutions

Clinically established thermal therapies such as thermoablative approaches or adjuvant hyperthermia treatment rely on accurate thermal dose information for the evaluation and adaptation of the thermal therapy. Intratumoural temperature measurements have been correlated successfully with clinical end points. Magnetic resonance imaging is the most suitable technique for non-invasive thermometry avoiding complications related to invasive temperature measurements. Since the advent of MR thermometry two decades ago, numerous MR thermometry techniques have been developed, continuously increasing accuracy and robustness for in vivo applications. While this progress was primarily focused on relative temperature mapping, current and future efforts will likely close the gap towards quantitative temperature readings. These efforts are essential to benchmark thermal therapy efficiency, to understand temperature-related biophysical and physiological processes and to use these insights to set new landmarks for diagnostic and therapeutic applications. With that in mind, this review summarises and discusses advances in MR thermometry, providing practical considerations, pitfalls and technical obstacles constraining temperature measurement accuracy, spatial and temporal resolution in vivo. Established approaches and current trends in thermal therapy hardware are surveyed with respect to potential benefits for MR thermometry