Challenges for the Implementation of Primary Standard Dosimetry in Proton Minibeam Radiation Therapy.

: Spatial fractionation of proton fields as sub-millimeter beamlets to treat cancer has shown better sparing of healthy tissue whilst maintaining the same tumor control. It is critical to ensure primary standard dosimetry is accurate and ready to support the modality's clinical implementation. : This work provided a proof-of-concept, using the National Physical Laboratory's Primary Standard Proton Calorimeter (PSPC) to measure average absorbed dose-to-water in a pMBRT field.

Monte Carlo modeling of a commercial machine and experimental setup for FLASH-minibeam irradiations with electrons.

Background: Ultra-high dose rate (UHDR/FLASH) irradiations, along with particle minibeam therapy (PMBT) are both emerging as promising alternatives to current radiotherapy techniques thanks to their improved healthy tissue sparing and similar tumor control.

Purpose: Monte Carlo (MC) modeling of a commercial machine delivering 5-7 MeV electrons at UHDR. This model was used afterward to compare measurements against simulations for an experimental setup combining both FLASH and PMBT modalities.

Implementation and validation of a very-high-energy electron model in the matRad treatment planning system.

Background: While electron beams of up to 20 MeV are commonly used in radiotherapy, the use of very-high-energy electrons (VHEEs) in the range of 100-200 MeV is now becoming a realistic option thanks to the recent advancements in accelerator technology. Indeed, VHEE offers several clinically attractive features and can be delivered using various conformation methods (including scanning, collimation, and focussing) at ultra-high dose rates. To date, there is a lack of research tools for fast simulation of treatment plans using VHEE beams.

A multidisciplinary view of flash irradiation.

The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment.

Proton therapy reduces the effective dose to immune cells in breast cancer patients.

Background: The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC).

Materials And Methods: Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included.

Determinants of radiation dose to immune cells during breast radiotherapy.

Background: The immune system has been identified as an organ at risk in esophageal and lung cancers. However, the dosimetric impact of radiotherapy on immune system exposure in patients treated for breast cancer has never been studied.

Methods: A monocentric retrospective dosimetric study included 163 patients treated at the Institut Curie (Paris, France) between 2010 and 2016 with locoregional helical tomotherapy after conservative surgery or total mastectomy.

Investigating the biochemical response of proton minibeam radiation therapy by means of synchrotron-based infrared microspectroscopy.

The biology underlying proton minibeam radiation therapy (pMBRT) is not fully understood. Here we aim to elucidate the biological effects of pMBRT using Fourier Transform Infrared Microspectroscopy (FTIRM). In vitro (CTX-TNA2 astrocytes and F98 glioma rat cell lines) and in vivo (healthy and F98-bearing Fischer rats) irradiations were conducted, with conventional proton radiotherapy and pMBRT.

Thoracic Proton Minibeam Radiation Therapy: Tissue Preservation and Survival Advantage Over Conventional Proton Therapy.

Purpose: Proton minibeam radiation therapy (pMBRT) is an innovative radiation therapy approach that highly modulates the spatial dimension of the dose delivery using narrow, parallel, and submillimetric proton beamlets. pMBRT has proven its remarkable healthy tissue preservation in the brain and skin. This study assesses the potential advantages of pMBRT for thoracic irradiations compared with conventional radiation therapy in terms of normal tissue toxicity.

Oxygen supplementation in anesthesia can block FLASH effect and anti-tumor immunity in conventional proton therapy.

Background: Radiation-induced neurocognitive dysfunction is a major adverse effect of brain radiation therapy and has specific relevance in pediatric oncology, where serious cognitive deficits have been reported in survivors of pediatric brain tumors. Moreover, many pediatric patients receive proton therapy under general anesthesia or sedation to guarantee precise ballistics with a high oxygen content for safety. The present study addresses the relevant question of the potential effect of supplemental oxygen administered during anesthesia on normal tissue toxicity and investigates the anti-tumor immune response generated following conventional and FLASH proton therapy.

Very high-energy electron dose calculation using the Fermi-Eyges theory of multiple scattering and a simplified pencil beam model.

Background: Very high-energy electrons (VHEE) radiotherapy, in the energy range of 100-200 MeV is currently considered a promising technique for the future of radiation therapy and could benefit from the promises of ultra-high dose rate FLASH therapy. However, to our knowledge, no analytical calculation models have been tested for this type of application and the approximations proposed for multiple scattering with electron beams have not been extensively evaluated at these high energies.

Purpose: In this work, we discuss the derivation of a simple and fast algorithm based on the Fermi-Eyges theory of multiple Coulomb scattering for fast dose calculation for VHEE beams (up to 200 MeV).

Secondary radiation dose modeling in passive scattering and pencil beam scanning very high energy electron (VHEE) radiation therapy.

Background: Electrons with kinetic energy up to a few hundred MeV, also called very high energy electrons (VHEE), are currently considered a promising technique for the future of radiation therapy (RT) and in particular ultra-high dose rate (UHDR) therapy. However, the feasibility of a clinical application is still being debated and VHEE therapy remains an active area of research for which the optimal conformal technique is also yet to be determined.

Purpose: In this work, we will apply two existing formalisms based on analytical Gaussian multiple-Coulomb scattering theory and Monte Carlo (MC) simulations to study and compare the electron and bremsstrahlung photon dose distributions arising from two beam delivery systems (passive scattering with or without a collimator or active scanning).

Proton minibeam radiation therapy for treating metastases: A treatment plan study.

Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma-bearing rats compared to conventional proton therapy. Such preclinical results encourage the preparation of clinical trials.

Purpose: In this study, the potential of pMBRT for treating clinical indications candidates for the first clinical trials (i.

First experimental measurements of 2D microdosimetry maps in proton therapy.

Background: Empirical data in proton therapy indicate that relative biological effectiveness (RBE) is not constant, and it is directly related to the linear energy transfer (LET). The experimental assessment of LET with high resolution would be a powerful tool for minimizing the LET hot spots in intensity-modulated proton therapy, RBE- or LET-guided evaluation and optimization to achieve biologically optimized proton plans, verifying the theoretical predictions of variable proton RBE models, and so on. This could impact clinical outcomes by reducing toxicities in organs at risk.

Cardiotoxicity model-based patient selection for Hodgkin lymphoma proton therapy.

Introduction: Hodgkin lymphoma (HL) is a highly curable hematological malignancy. Consolidation radiation therapy techniques have made significant progresses to improve organ-at-risk sparing in order to reduce late radiation-induced toxicity. Recent technical breakthroughs notably include intensity modulated proton therapy (IMPT), which has demonstrated a major dosimetric benefit at the cardiac level for mediastinal HL patients.

Preclinical dosimetry in proton minibeam radiation therapy: Robustness analysis and guidelines.

Purpose: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma-bearing rats compared to conventional proton therapy. The dosimetry of pMBRT is challenging and error prone due to the submillimetric beamlet sizes used. The aim of this study was to perform a robustness analysis on the setup parameters utilized in current preclinical trials and provide guidelines for reproducible dosimetry.

Clinical and technical challenges of cancer reirradiation: Words of wisdom.

Since the development of new radiotherapy techniques that have improved healthy tissue sparing, reirradiation (reRT) has become possible. The selection of patients eligible for reRT is complex given that it can induce severe or even fatal side effects. The first step should therefore be to assess, in the context of multidisciplinary staff meeting, the patient's physical status, the presence of sequelae resulting from the first irradiation and the best treatment option available.

A Comprehensive Analysis of the Relationship Between Dose Rate and Biological Effects in Preclinical and Clinical Studies, From Brachytherapy to Flattening Filter Free Radiation Therapy and FLASH Irradiation.

Purpose: For many years, the effect of dose rate (DR) was considered negligible in external beam radiation therapy (EBRT) until very-high DR (>10 Gy/min) became possible and ultrahigh DR (>40 Gy/s) showed dramatic protection of normal tissues in preclinical experiments. We propose a critical review of preclinical and clinical studies to investigate the biological and clinical effects of DR variation in the range covering brachytherapy to flattening filter free EBRT and FLASH.

Methods And Materials: Preclinical and clinical studies investigating biological and clinical DR effects were reviewed extensively.

Development of Simplified Auto-Segmentable Functional Cardiac Atlas.

Purpose: There is increasing evidence that radiation doses to cardiac substructures are associated with cardiac adverse events. Manual delineation of cardiac substructures is time-consuming, and auto-segmentation of cardiac substructure atlases has consequently been evaluated. However, proper automatic delineation of small substructures, such as the left anterior descending coronary artery, is challenging, and auto-segmentation of cardiac conduction system substructures has never been evaluated, despite multiple reports of radiation-induced arrhythmia after thoracic irradiations.

Proton Minibeam Radiation Therapy and Arc Therapy: Proof of Concept of a Winning Alliance.

(1) Background: Proton Arc Therapy and Proton Minibeam Radiation Therapy are two novel therapeutic approaches with the potential to lower the normal tissue complication probability, widening the therapeutic window for radioresistant tumors. While the benefits of both modalities have been individually evaluated, their combination and its potential advantages are being assessed in this proof-of-concept study for the first time. (2) Methods: Monte Carlo simulations were employed to evaluate the dose and LET distributions in brain tumor irradiations.

Converging Proton Minibeams with Magnetic Fields for Optimized Radiation Therapy: A Proof of Concept.

Proton MiniBeam Radiation Therapy (pMBRT) is a novel strategy that combines the benefits of minibeam radiation therapy with the more precise ballistics of protons to further optimize the dose distribution and reduce radiation side effects. The aim of this study is to investigate possible strategies to couple pMBRT with dipole magnetic fields to generate a converging minibeam pattern and increase the center-to-center distance between minibeams. Magnetic field optimization was performed so as to obtain the same transverse dose profile at the Bragg peak position as in a reference configuration with no magnetic field.