Ultrasound-stimulated microbubbles to enhance radiotherapy: A scoping review.

INTRODUCTION: Primarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be 'burst' to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound-stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action. METHODS: Primary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action. RESULTS: Overall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action. CONCLUSIONS: USMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to target all three phases of radiation action.

A national education program for rapid genomics in pediatric acute care: Building workforce confidence, competence, and capability.

PURPOSE: To develop and evaluate a scalable national program to build confidence, competence and capability in the use of rapid genomic testing (rGT) in the acute pediatric setting. METHODS: We used theory-informed approaches to design a modular, adaptive program of blended learning aimed at diverse professional groups involved in acute pediatric care. The program comprised 4 online learning modules and an online workshop and was centered on case-based learning. We evaluated the program using the Kirkpatrick 4-level model of training evaluation and report our findings using the Reporting Item Standards for Education and its Evaluation (RISE2) guidelines for genomics education and evaluation. RESULTS: Two hundred and two participants engaged with at least 1 component of the program. Participants self-reported increased confidence in using rGT, (P < .001), and quiz responses objectively demonstrated increased competence (eg, correct responses to a question on pretest counseling increased from 30% to 64%; P < .001). Additionally, their capability in applying genomic principles to simulated clinical cases increased (P < .001), as did their desire to take on more responsibility for performing rGT. The clinical interpretation of more complex test results (such as negative results or variants of uncertain significance) appeared to be more challenging, indicating a need for targeted education in this area. CONCLUSION: The program format was effective in delivering multidisciplinary and wide-scale genomics education in the acute care context. The modular approach we have developed now lends itself to application in other medical specialties or areas of health care.

Two-step offer and return of multiple types of additional genomic findings to families after ultrarapid trio genomic testing in the acute care setting: a study protocol.

INTRODUCTION: As routine genomic testing expands, so too does the opportunity to look for additional health information unrelated to the original reason for testing, termed additional findings (AF). Analysis for many different types of AF may be available, particularly to families undergoing trio genomic testing. The optimal model for service delivery remains to be determined, especially when the original test occurs in the acute care setting. METHODS AND ANALYSIS: Families enrolled in a national study providing ultrarapid genomic testing to critically ill children will be offered analysis for three types of AF on their stored genomic data: paediatric-onset conditions in the child, adult-onset conditions in each parent and reproductive carrier screening for the parents as a couple. The offer will be made 3-6 months after diagnostic testing. Parents will have access to a modified version of the Genetics Adviser web-based decision support tool before attending a genetic counselling appointment to discuss consent for AF. Parental experiences will be evaluated using qualitative and quantitative methods on data collected through surveys, appointment recordings and interviews at multiple time points. Evaluation will focus on parental preferences, uptake, decision support use and understanding of AF. Genetic health professionals' perspectives on acceptability and feasibility of AF will also be captured through surveys and interviews. ETHICS AND DISSEMINATION: This project received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. Findings will be disseminated through peer-review journal articles and at conferences nationally and internationally.

Ultrasound-Stimulated Microbubbles Enhance Radiation-Induced Cell Killing.

Recent in vivo studies using ultrasound-stimulated microbubbles as a localized radiosensitizer have had impressive results. While in vitro studies have also obtained similar results using human umbilical vein endothelial cells (HUVEC), studies using other cell lines have had varying results. This study was aimed at investigating any increases in radiation-induced cell killing in vitro using two carcinoma lines not previously investigated before (metastatic follicular thyroid carcinoma cells [FTC-238] and non-small cell lung carcinoma cells [NCI-H727]), in addition to HUVEC. Cells were treated using a combination of 1.6% (v/v) microbubbles, ∼90 s of 2-MHz ultrasound (mechanical index = 0.8) and 0-6 Gy of kilovolt or MV X-rays. Cell viability assays obtained 72 h post-treatment were normalized to untreated controls, and analysis of variance was used to determine statistical significance. All cells treated with combined ultrasound-stimulated microbubbles and radiation exhibited decreased normalized survival, with statistically significant effects observed for the NCI-H727 cells. No statistically significant differences in effects were observed using kV compared with MV radiation. Further studies using increased microbubble concentrations may be required to achieve statistically significant results for the FTC-238 and HUVEC lines.

Patterns of the use of advanced radiation therapy techniques for the management of bone metastases and the associated factors in Victoria.

INTRODUCTION: To describe the pattern of the use of advanced radiation therapy (RT) techniques, including intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body RT (SBRT) for the management of bone metastases (BM), and the associated factors in Victoria. METHODS: We used a population-based cohort of patients from the state-wide Victorian Radiotherapy Minimum Data Set (VRMDS) who received RT for BM between 2012 and 2017. The primary outcome was proportion of RT courses using advanced RT techniques. The Cochran-Armitage test for trend was used to evaluate temporal trend in advanced RT use. Multinomial logistic regression was used to identify factors associated with advanced RT use. RESULTS: A total of 18,158 courses of RT were delivered to 10,956 patients-16,626 (91.6%) courses were 3D conformal RT, 857 (4.7%) IMRT/VMAT and 675 (3.7%) SBRT. There was a sharp increase in IMRT/VMAT use from <1% in 2012-2015, to 10.1% in 2016 and 16.3% in 2017 (P-trend < 0.001). Increase in SBRT use was more gradual, from 1.2% in 2012 to 4.8% in 2016 and 5.5% in 2017 for SBRT (P-trend<0.001). In multivariate analyses, year of RT was the strongest predictor of IMRT/VMAT use (OR = 41; 95%CI = 25-67; P < 0.001, comparing 2012-2013 and 2016-2017). Primary tumour type (prostate cancer) was the strongest predictor of SBRT use (OR = 6.07; 95% CI = 4.19-8.80; P < 0.001). CONCLUSION: Overall, there was increasing trend in the use of advanced RT techniques for BM in Victoria, with a distinct pattern for IMRT/VMAT compared with SBRT - SBRT uptake was more gradual while IMRT/VMAT uptake was abrupt, occurring contemporaneously with Medicare Benefit Scheme funding changes in 2016.

Practice patterns of radiation therapy technology in Australia: results of a national audit.

INTRODUCTION: This article presents the results of a single-day census of radiation therapy (RT) treatment and technology use in Australia. The primary aim of the study was to ascertain patterns of RT practice and technology in use across Australia. These data were primarily collated to inform curriculum development of academic programs, thereby ensuring that training is matched to workforce patterns of practice. METHODS: The study design was a census method with all 59 RT centres in Australia being invited to provide quantitative summary data relating to patient case mix and technology use on a randomly selected but common date. Anonymous and demographic-free data were analysed using descriptive statistics. RESULTS: Overall data were provided across all six Australian States by 29 centres of a possible 59, yielding a response rate of 49% and representing a total of 2743 patients. Findings from this study indicate the increasing use of emerging intensity-modulated radiotherapy (IMRT), image fusion and image-guided radiation therapy (IGRT) technology in Australian RT planning and delivery phases. IMRT in particular was used for 37% of patients, indicating a high uptake of the technology in Australia when compared to other published data. The results also highlight the resource-intensive nature of benign tumour radiotherapy. CONCLUSIONS: In the absence of routine national data collection, the single-day census method offers a relatively convenient means of measuring and tracking RT resource utilisation. Wider use of this tool has the potential to not only track trends in technology implementation but also inform evidence-based guidelines for referral and resource planning.