Evaluating and reporting LET and RBE-weighted dose in proton therapy for glioma - The Dutch approach.

Background And Purpose: With proton therapy, the relative biological effectiveness (RBE) accounts for increased DNA damage caused by higher linear energy transfer (LET) compared to photons. However, the LET and hence the RBE varies along the proton range, particularly at the Bragg peak, introducing challenges in proton treatment planning for brain tumors. The aim of this paper is to standardize evaluating and reporting LET and RBE in proton therapy for patients with grade 2 and 3 IDH mutant gliomas among the Dutch proton therapy centers.

Robust IMPT and follow-up toxicity in skull base chordoma and chondrosarcoma-a single-institution clinical experience.

Background: Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as a definitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands.

A probabilistic evaluation of the Dutch robustness and model-based selection protocols for Head-and-Neck IMPT: A multi-institutional study.

Background And Purpose: In the Netherlands, 2 protocols have been standardized for PT among the 3 proton centers: a robustness evaluation (RE) to ensure adequate CTV dose and a model-based selection (MBS) approach for IMPT patient-selection. This multi-institutional study investigates (i) inter-patient and inter-center variation of target dose from the RE protocol and (ii) the robustness of the MBS protocol against treatment errors for a cohort of head-and-neck cancer (HNC) patients treated in the 3 Dutch proton centers.

Materials And Methods: Clinical treatment plans of 100 HNC patients were evaluated.

Two-dimensional oxygen-diffusion modelling for FLASH proton therapy with pencil beam scanning-Impact of diffusive tissue properties, dose, dose rate and scan patterns.

Oxygen depletion is generally believed to play an important role in the FLASH effect-a differential reduction of the radiosensitivity of healthy tissues, relative to that of the tumour under ultra-high dose-rate (UHDR) irradiation conditions. In proton therapy (PT) with pencil-beam scanning (PBS), the deposition of dose, and, hence, the degree of (radiolytic) oxygen depletion varies both spatially and temporally. Therefore, the resulting oxygen concentration and the healthy-tissue sparing effect through radiation-induced hypoxia varies both spatially and temporally as well.

Cochlear-optimized treatment planning in photon and proton radiosurgery for vestibular schwannoma patients.

Objective: To investigate the potential to reduce the cochlear dose with robotic photon radiosurgery or intensity-modulated proton therapy planning for vestibular schwannomas.

Materials And Methods: Clinically delivered photon radiosurgery treatment plans were compared to five cochlear-optimized plans: one photon and four proton plans (total of 120). A 1x12 Gy dose was prescribed.

Robustness analysis of CTV and OAR dose in clinical PBS-PT of neuro-oncological tumors: prescription-dose calibration and inter-patient variation with the Dutch proton robustness evaluation protocol.

. The Dutch proton robustness evaluation protocol prescribes the dose of the clinical target volume (CTV) to the voxel-wise minimum (VWmin) dose of 28 scenarios. This results in a consistent but conservative near-minimum CTV dose (D).

PTV-based VMAT vs. robust IMPT for head-and-neck cancer: A probabilistic uncertainty analysis of clinical plan evaluation with the Dutch model-based selection.

Background And Purpose: In the Netherlands, head-and-neck cancer (HNC) patients are referred for proton therapy (PT) through model-based selection (MBS). However, treatment errors may compromise adequate CTV dose. Our aims are: (i) to derive probabilistic plan evaluation metrics on the CTV consistent with clinical metrics; (ii) to evaluate plan consistency between photon (VMAT) and proton (IMPT) planning in terms of CTV dose iso-effectiveness and (iii) to assess the robustness of the OAR doses and of the risk toxicities involved in the MBS.

Early and late contrast enhancing lesions after photon radiotherapy for IDH mutated grade 2 diffuse glioma.

Objective: The interpretation of new enhancing lesions after radiotherapy for diffuse glioma remains a clinical challenge. We sought to characterize and classify new contrast enhancing lesions in a historical multicenter cohort of patients with IDH mutated grade 2 diffuse glioma treated with photon therapy.

Methods: We reviewed all follow-up MRI's of all patients treated with radiotherapy for histologically confirmed, IDH mutated diffuse grade 2 glioma between 1-1-2007 and 31-12-2018 in two tertiary referral centers.

Pencil-beam Delivery Pattern Optimization Increases Dose Rate for Stereotactic FLASH Proton Therapy.

Purpose: FLASH dose rates >40 Gy/s are readily available in proton therapy (PT) with cyclotron-accelerated beams and pencil-beam scanning (PBS). The PBS delivery pattern will affect the local dose rate, as quantified by the PBS dose rate (PBS-DR), and therefore needs to be accounted for in FLASH-PT with PBS, but it is not yet clear how. Our aim was to optimize patient-specific scan patterns for stereotactic FLASH-PT of early-stage lung cancer and lung metastases, maximizing the volume irradiated with PBS-DR >40 Gy/s of the organs at risk voxels irradiated to >8 Gy (FLASH coverage).

Accurate assessment of a Dutch practical robustness evaluation protocol in clinical PT with pencil beam scanning for neurological tumors.

Background And Purpose: Scenario-based robust optimization and evaluation are commonly used in proton therapy (PT) with pencil beam scanning (PBS) to ensure adequate dose to the clinical target volume (CTV). However, a statistically accurate assessment of the clinical application of this approach is lacking. In this study, we assess target dose in a clinical cohort of neuro-oncological patients, planned according to the DUPROTON robustness evaluation consensus, using polynomial chaos expansion (PCE).

Practical robustness evaluation in radiotherapy - A photon and proton-proof alternative to PTV-based plan evaluation.

Background And Purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-based treatment plan evaluations.

The TRENDY multi-center randomized trial on hepatocellular carcinoma - Trial QA including automated treatment planning and benchmark-case results.

Background And Purpose: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported.

Materials And Methods: Scans of a single patient were used as a benchmark case.

Pattern phase diagram for two-dimensional arrays of coupled limit-cycle oscillators.

Arrays of coupled limit-cycle oscillators represent a paradigmatic example for studying synchronization and pattern formation. We find that the full dynamical equations for the phase dynamics of a limit-cycle oscillator array go beyond previously studied Kuramoto-type equations. We analyze the evolution of the phase field in a two-dimensional array and obtain a "phase diagram" for the resulting stationary and nonstationary patterns.

Universal description of geometric phases in higher-order optical modes bearing orbital angular momentum.

We study geometric phases that arise from (cyclic) transformations of the transverse spatial structure of paraxial optical modes. Our approach involves bosonic ladder operators that, in the spirit of the quantum-mechanical harmonic oscillator, generate sets of transverse optical modes. It applies to modes of all orders in a very natural way and provides a universal geometric interpretation of the phase shifts acquired by nonastigmatic modes under typical experimental conditions.