Clinical implementations of 4D pencil beam scanned particle therapy: Report on the 4D treatment planning workshop 2016 and 2017.

In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed. This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.

Improving proton therapy by metal-containing nanoparticles: nanoscale insights.

The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/µm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.

Proton Radiography With Timepix Based Time Projection Chambers.

The development of a proton radiography system to improve the imaging of patients in proton beam therapy is described. The system comprises gridpix based time projection chambers, which are based on the Timepix chip designed by the Medipix collaboration, for tracking the protons. This type of detector was chosen to have minimal impact on the actual determination of the proton tracks by the tracking detectors. To determine the residual energy of the protons, a BaF 2 crystal with a photomultiplier tube is used. We present data taken in a feasibility experiment with phantoms that represent tissue equivalent materials found in the human body. The obtained experimental results show a good agreement with the performed simulations.

Challenges of radiotherapy: report on the 4D treatment planning workshop 2013.

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.

Time-of-flight neutron rejection to improve prompt gamma imaging for proton range verification: a simulation study.

Therapeutic proton and heavier ion beams generate prompt gamma photons that may escape from the patient. In principle, this allows for real-time, in situ monitoring of the treatment delivery, in particular, the hadron range within the patient, by imaging the emitted prompt gamma rays. Unfortunately, the neutrons simultaneously created with the prompt photons create a background that may obscure the prompt gamma signal. To enhance the accuracy of proton dose verification by prompt gamma imaging, we therefore propose a time-of-flight (TOF) technique to reject this neutron background, involving a shifting time window to account for the propagation of the protons through the patient. Time-resolved Monte Carlo simulations of the generation and transport of prompt gamma photons and neutrons upon irradiation of a PMMA phantom with 100, 150 and 200 MeV protons were performed using Geant4 (version 9.2.p02) and MCNPX (version 2.7.D). The influence of angular collimation and TOF selection on the prompt gamma and neutron longitudinal profiles is studied. Furthermore, the implications of the proton beam microstructure (characterized by the proton bunch width and repetition period) are investigated. The application of a shifting TOF window having a width of ΔTOF(z) = 1.0 ns appears to reduce the neutron background by more than 99%. Subsequent application of an energy threshold does not appear to sharpen the distal falloff of the prompt gamma profile but reduces the tail that is observed beyond the proton range. Investigations of the influence of the beam time structure show that TOF rejection of the neutron background is expected to be effective for typical therapeutic proton cyclotrons.