Probing the therapeutic window of proton minibeam radiotherapy using dose-response curves in a mouse model.

Purpose: Proton minibeam radiotherapy (pMBRT) has been observed in preclinical studies to spare normal tissues through its spatially fractionated dose profile. Translating pMBRT to clinical application requires quantification of its therapeutic gain, compared to conventional proton therapy. We compare pMBRT to conventional proton therapy in vivo, focusing on reducing damage to non-target tissues while ensuring the same uniform target dose to achieve equal tumor control.

Thermoacoustic range verification during conventional dose rate delivery by a synchrocyclotron.

Background: Minimization of range uncertainties is critical for precise and effective proton therapy. Thermoacoustic range verification is a promising non-invasive technique for pinpointing the Bragg peak location in proton therapy.

Purpose: Verification of a prototype device for thermoacoustic range verification with minimal disruption to a clinical workflow for proton therapy delivered by a synchrocyclotron.

Integration of microdosimetry into treatment planning systems using look-up tables (LUT): A proof-of-concept.

Introduction: Microdosimetry provides a statistical, measurable description of energy deposition at the sub-cellular level, directly linked to biological effectiveness. In recent years its application to proton therapy has shown promising improvements in the accuracy of radiobiological modelling. This paper introduces a novel approach for integrating microdosimetric quantities into the treatment planning process.

Commissioning of a multislit collimator system for experimental pMBRT studies with uniform target dose.

. Proton minibeam radiotherapy (pMBRT) is a novel approach to widen the therapeutic window by balancing tumor control and reducing toxicity to healthy tissues. Among the various ways to generate minibeams, a multislit collimator (MSC) is a convenient approach for integration into existing beamlines.

Verification of dose and dose rate for quality assurance of spread-out-Bragg-peak proton FLASH radiotherapy using machine log files.

Background: Ultra-high dose rate radiotherapy elicits a biological effect (FLASH), which has been shown to reduce toxicity while maintaining tumor control in preclinical radiobiology experiments. FLASH depends on the dose rate, with evidence that higher dose rates drive increased normal tissue sparing. The pattern of dose delivery also has significance for conformal proton FLASH delivered via pencil beam scanning (PBS) given its unique spatio-temporal distribution of dose deposition.

Proton minibeam (pMBRT) radiation therapy: experimental validation of Monte Carlo dose calculation in the RayStation TPS.

Proton minibeam radiation therapy (pMBRT) is a spatially fractionated radiation therapy modality that uses a multi-slit collimator (MSC) to create submillimeter slit openings for spatial dose modulation. The pMBRT dose profile is characterized by highly heterogeneous dose in the plane perpendicular to the beam and rapidly changing depth dose profiles. Dose measurements are typically benchmarked against in-house Monte Carlo (MC) simulation tools.

'Dirty dose'-based proton variable RBE models - performance assessment on in vitro data.

Background: In clinical proton radiotherapy, a constant relative biological effectiveness (RBE) of 1.1 is typically applied. Due to abundant evidence of variable RBE effects from in vitro data, multiple variable RBE models have been suggested, typically by describing the and parameters in the linear quadratic (LQ) model as a function of dose averaged linear energy transfer ( ).

Beyond a constant proton relative biological effectiveness: A survey of clinical and research perspectives among proton institutions in Europe and the United States.

Purpose: Although proton relative biological effectiveness (RBE) depends on factors like linear energy transfer (LET), tissue properties, dose, and biological endpoint, a constant RBE of 1.1 is recommended in clinical practice. This study surveys proton institutions to explore activities using functionalities beyond a constant proton RBE.

Proton ARC based LATTICE radiation therapy: feasibility study, energy layer optimization and LET optimization.

LATTICE, a spatially fractionated radiation therapy (SFRT) modality, is a 3D generalization of GRID and delivers highly modulated peak-valley spatial dose distribution to tumor targets, characterized by peak-to-valley dose ratio (PVDR). Proton LATTICE is highly desirable, because of the potential synergy of the benefit from protons compared to photons, and the benefit from LATTICE compared to GRID. Proton LATTICE using standard proton RT via intensity modulated proton therapy (IMPT) (with a few beam angles) can be problematic with poor target dose coverage and high dose spill to organs-at-risk (OAR).

RayStation/GATE Monte Carlo simulation framework for verification of proton therapy based on theN imaging.

.N, having a half-life of 11 ms, is a highly effective positron emitter that can potentially provide near real-time feedback in proton therapy. There is currently no framework for comparing and validating positron emission imaging ofN.

A novel treatment planning method via scissor beams for uniform-target-dose proton GRID with peak-valley-dose-ratio optimization.

Background: Proton spatially fractionated RT (SFRT) can potentially synergize the unique advantages of using proton Bragg peak and SFRT peak-valley dose ratio (PVDR) to reduce the radiation-induced damage for normal tissues. Uniform-target-dose (UTD) proton GRID is a proton SFRT modality that can be clinically desirable and conveniently adopted since its UTD resembles target dose distribution in conventional proton RT (CONV). However, UTD proton GRID is not used clinically, which is likely due to the lack of an effective treatment planning method.

An experimental validation of a filtering approach for prompt gamma prediction in a research proton treatment planning system.

Prompt gamma (PG) radiation generated from nuclear reactions between protons and tissue nuclei can be employed for range verification in proton therapy. A typical clinical workflow for PG range verification compares the detected PG profile with a predicted one. Recently, a novel analytical PG prediction algorithm based on the so-called filtering formalism has been proposed and implemented in a research version of RayStation (RaySearch Laboratories AB), which is a widely adopted treatment planning system.

Novel radiation quality metrics accounting for proton energy spectra for RBE proton models.

Background: For proton therapy, a relative biological effectiveness (RBE) of 1.1 is widely applied clinically. However, due to abundant evidence of variable RBE in vitro, and as suggested in studies of patient outcomes, RBE might increase by the end of the proton tracks, as described by several proposed variable RBE models.

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

Background: Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LET) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LET was reported.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application.

Treatment planning of scanned proton beams in RayStation.

The use of scanned proton beams in external beam radiation therapy has seen a rapid development over the past decade. This technique places new demands on treatment planning, as compared to conventional photon-based radiation therapy. In this article, several proton specific functions as implemented in the treatment planning system RayStation are presented.

Plan robustness and RBE influence for proton dose painting by numbers for head and neck cancers.

Purpose: To investigate the feasibility of dose painting by numbers (DPBN) with respect to robustness for proton therapy for head and neck cancers (HNC), and to study the influence of variable RBE on the TCP and OAR dose burden.

Methods And Materials: Data for 19 patients who have been scanned pretreatment with PET-FDG and subsequently treated with photon therapy were used in the study. A dose response model developed for photon therapy was implemented in a TPS, allowing DPBN plans to be created.

The dirty and clean dose concept: Towards creating proton therapy treatment plans with a photon-like dose response.

Background: Applying tolerance doses for organs at risk (OAR) from photon therapy introduces uncertainties in proton therapy when assuming a constant relative biological effectiveness (RBE) of 1.1.

Purpose: This work introduces the novel dirty and clean dose concept, which allows for creating treatment plans with a more photon-like dose response for OAR and, thus, less uncertainties when applying photon-based tolerance doses.

Shoot-through proton FLASH irradiation lowers linear energy transfer in organs at risk for neurological tumors and is robust against density variations.

. The goal of the study was to test the hypothesis that shoot-through FLASH proton beams would lead to lower dose-averaged LET (LET) values in critical organs, while providing at least equal normal tissue sparing as clinical proton therapy plans..

Investigation on the physical dose filtered by linear energy transfer for treatment plan evaluation in carbon ion therapy.

Background: Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT.

3D-conformal very-high energy electron therapy as candidate modality for FLASH-RT: A treatment planning study for glioblastoma and lung cancer.

Background: Pre-clinical ultra-high dose rate (UHDR) electron irradiations on time scales of 100 ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically-used gantries and intensity modulation techniques are too slow to match such time scales, novel very-high energy electron (VHEE, 50-250 MeV) radiotherapy (RT) devices using 3D-conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements.

Purpose: To assess the dosimetric plan quality obtained using VHEE-based 3D-conformal RT (3D-CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard-of-care intensity modulated photon RT (IMRT) techniques.

Detectability of Anatomical Changes With Prompt-Gamma Imaging: First Systematic Evaluation of Clinical Application During Prostate-Cancer Proton Therapy.

Purpose: The development of online-adaptive proton therapy (PT) is essential to overcome limitations encountered by day-to-day variations of the patient's anatomy. Range verification could play an essential role in an online feedback loop for the detection of treatment deviations such as anatomical changes. Here, we present the results of the first systematic patient study regarding the detectability of anatomical changes by a prompt-gamma imaging (PGI) slit-camera system.

Modelling tissue specific RBE for different radiation qualities based on a multiscale characterization of energy deposition.

Purpose: We present the nanoCluE model, which uses nano- and microdosimetric quantities to model RBE for protons and carbon ions. Under the hypothesis that nano- and microdosimetric quantities correlates with the generation of complex DNA double strand breakes, we wish to investigate whether an improved accuracy in predicting LQ parameters may be achieved, compared to some of the published RBE models.

Methods: The model is based on experimental LQ data for protons and carbon ions.

Technical note: In silico benchmarking of the linear energy transfer-based functionalities for carbon ion beams in a commercial treatment planning system.

Background: The increasing number of studies dealing with linear energy transfer (LET)-based evaluation and optimization in the field of carbon ion radiotherapy (CIRT) indicates the rising demand for LET implementation in commercial treatment planning systems (TPS). Benchmarking studies could play a key role in detecting (and thus preventing) computation errors prior implementing such functionalities in a TPS.

Purpose: This in silico study was conducted to benchmark the following two LET-related functionalities in a commercial TPS against Monte Carlo simulations: (1) dose averaged LET (LET ) scoring and (2) physical dose filtration based on LET for future LET-based treatment plan evaluation and optimization studies.