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Advancing proton minibeam radiation therapy: magnetically focussed proton minibeams at a clinical centre.

ABSTRACT: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that has proven to significantly increase dose tolerances and sparing of normal tissue. It uses very narrow proton beams (diameter ?1?mm), roughly one order of magnitude smaller than state-of-the-art pencil beams. The current implementation of pMBRT with mechanical collimators is suboptimal as it is inflexible, decreases efficiency and produces additional secondary neutrons. As a potential solution, we explore in this article minibeam generation through magnetic focussing and investigate possibilities for the integration of such a technique at existing clinical centres. For this, a model of the pencil beam scanning (PBS) nozzle and beam at the Orsay Proton Therapy Centre was established and Monte Carlo simulations were performed to determine its focussing capabilities. Moreover, various modifications of the nozzle geometry were considered. It was found that the PBS nozzle in its current state is not suitable for magnetic minibeam generation. Instead, a new, optimised nozzle design has been proposed and conditions necessary for minibeam generation were benchmarked. In addition, dose simulations in a water phantom were performed which showed improved dose distributions compared to those obtained with mechanical collimators.

SUBMITTER: Schneider T

PROVIDER: S-EPMC6987213 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Advancing proton minibeam radiation therapy: magnetically focussed proton minibeams at a clinical centre.

Schneider Tim T De Marzi Ludovic L Patriarca Annalisa A Prezado Yolanda Y

Scientific reports 20200128 1

Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that has proven to significantly increase dose tolerances and sparing of normal tissue. It uses very narrow proton beams (diameter ≤1 mm), roughly one order of magnitude smaller than state-of-the-art pencil beams. The current implementation of pMBRT with mechanical collimators is suboptimal as it is inflexible, decreases efficiency and produces additional secondary neutrons. As a potential solution, we explore in this arti ...[more]

PMID: 31992757

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Project description:The goal is to compare, in vitro, the efficiency of minibeam radiotherapy (MBRT) and standard RT in inducing clonogenic cell death in glioma cell lines. With this aim, we report on the first in vitro study performed in an X-ray Small Animal Radiation Research Platform (SARRP) modified for minibeam irradiations. F98 rat and U87 human glioma cells were irradiated with either an array of minibeams (MB) or with conventional homogeneous beams (broad beam, BB). A specially designed multislit collimator was used to generate the minibeams with a with of a center-to-center distance of 1465 (±10)??m, and a PVDR value of 12.4 (±2.3) measured at 1?cm depth in a water phantom. Cells were either replated for clonogenic assay directly (immediate plating, IP) or 24?h after irradiation (delayed plating, DP) to assess the effect of potentially lethal damage repair (PLDR) on cell survival. Our hypothesis is that with MBRT, a similar level of clonogenic cell death can be reached compared to standard RT, when using equal mean radiation doses. To prove this, we performed dose escalations to determine the minimum integrated dose needed to reach a similar level of clonogenic cell death for both treatments. We show that this minimum dose can vary per cell line: in F98 cells a dose of 19?Gy was needed to obtain similar levels of clonogenic survival, whereas in U87 cells there was still a slightly increased survival with MB compared to BB 19?Gy treatment. The results suggest also an impairment of DNA damage repair in F98 cells as there is no difference in clonogenic cell survival between immediately and delayed plated cells for each dose and irradiation mode. For U87 cells, a small IP-DP effect was observed in the case of BB irradiation up to a dose of 17?Gy. However, at 19?Gy BB, as well as for the complete dose range of MB irradiation, U87 cells did not show a difference in clonogenic survival between IP and DP. We therefore speculate that MBRT might influence PLDR. The current results show that X-ray MBRT is a promising method for treatment of gliomas: future preclinical and clinical studies should aim at reaching a minimum radiation (valley) dose for effective eradication of gliomas with increased sparing of normal tissues compared to standard RT.

Project description:There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies.To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment.Population-based study using Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer.Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy.Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses (N = 12,976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score-matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy.Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.

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Advancing proton minibeam radiation therapy: magnetically focussed proton minibeams at a clinical centre.

Publications

Advancing proton minibeam radiation therapy: magnetically focussed proton minibeams at a clinical centre.

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