Hitting the Target: Developing High-quality Evidence for Proton Beam Therapy Through Randomised Controlled Trials.

The National Health Service strategy for the delivery of proton beam therapy (PBT) in the UK provides a unique opportunity to deliver high-quality evidence for PBT through randomised controlled trials (RCTs). We present a summary of three UK PBT RCTs in progress, including consideration of their key design characteristics and outcome assessments, to inform and support future PBT trial development. The first three UK multicentre phase III PBT RCTs (TORPEdO, PARABLE and APPROACH), will compare PBT with photon radiotherapy for oropharyngeal squamous cell carcinoma, breast cancer and oligodendroglioma, respectively. All three studies were designed by multidisciplinary teams, which combined expertise from clinicians, clinical trialists and scientists with strong patient advocacy and guidance from national radiotherapy research networks and international collaborators. Consistent across all three studies is a focus on the reduction of long-term radiotherapy-related toxicities and an evaluation of patient-reported outcomes and health-related quality of life, which will address key uncertainties regarding the clinical benefits of PBT. Innovative translational components will provide insights into mechanisms of toxicity and help to frame the key future research questions regarding PBT. The UK radiotherapy research community is developing and delivering an internationally impactful PBT research portfolio. The combination of data from RCTs with prospectively collected data from a national PBT outcomes registry will provide an innovative, high-quality repository for PBT research and the platform to design and deliver future trials of PBT.

Subcellular localization of indium-111 in indium-111-labeled platelets.

Human platelets labeled with [111In]oxine have been suggested for use in platelet kinetic studies, thrombus localization, detection of atherosclerotic lesions, and other scintigraphic techniques. To demonstrate the subcellular localization of indium-111 in labeled platelets, we did subcellular fractionation and measured the amount of indium-111 localized in major platelet components. Human platelets were labeled with [111In]oxine and disrupted by nitrogen cavitation. The cellular material was fractionated on sucrose density gradients. When the subcellular fractions were analyzed, more than 70% of the indium-111 was located in the cytoplasmic pool of the platelets. Chromatography on Sephadex G-100 of aliquots of the labeled cytosol material showed that most of the indium-111 was associated with components of approximately 46,000 daltons. This demonstrated that indium-111 in human platelets labeled with [111In]oxine is located predominantly in platelet cytosol and is associated with cytoplasmic components.