Mixed- and multi-relative biological effectiveness model simultaneous optimization in carbon ion radiotherapy: A proof-of-concept.

Background And Purpose: In carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (D). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between D prescriptions.

Second Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

We comment on the reply by Shiraishito our comments regarding their recently published study 'Modeling for Predicting Survival Fraction of Cells after Ultra-High Dose Rate Irradiation'. While we appreciate the effort of the authors to consider our comments, we see ourselves compelled to add another short comment as we believe that some of our suggestions have been misrepresented. This may have resulted in a misguiding re-evaluation of the model.

Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.

Paediatric medulloblastomas with chromothripsis are characterised by high genomic instability and are among the tumours with the worst prognosis. However, the molecular makeup and the determinants of the aggressiveness of chromothriptic medulloblastoma are not well understood. Here, we apply spatial transcriptomics to profile a cohort of 13 chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup.

Oxygen consumption measurements at ultra-high dose rate over a wide LET range.

Background: The role of radiolytic oxygen consumption for the in-vitro "Ultra-High Dose Rate" (UHDR) sparing and in-vivo FLASH effect is subject to active debate, but data on key dependencies such as the radiation quality are lacking.

Purpose: The influence of "dose-averaged Linear Energy Transfer" (LETd) and dose rate on radiolytic oxygen consumption was investigated by monitoring the oxygen concentration during irradiation with electrons, protons, helium, carbon, and oxygen ions at UHDR and "Standard Dose Rates" (SDR).

Methods: Sealed "Bovine Serum Albumin" (BSA) 5% samples were exposed to 15 Gy of electrons and protons, and for the first time helium, carbon, and oxygen ions with LETd values of 1, 5.

Development and verification of an electron Monte Carlo engine for applications in intraoperative radiation therapy.

Background: In preparation of future clinical trials employing the Mobetron electron linear accelerator to deliver FLASH Intraoperative Radiation Therapy (IORT), the development of a Monte Carlo (MC)-based framework for dose calculation was required.

Purpose: To extend and validate the in-house developed fast MC dose engine MonteRay (MR) for future clinical applications in IORT.

Methods: MR is a CPU MC dose calculation engine written in C++ that is capable of simulating therapeutic proton, helium, and carbon ion beams.

Towards precise LET measurements based on energy deposition of therapeutic ions in Timepix3 detectors.

There is an increasing interest in calculating and measuring linear energy transfer (LET) spectra in particle therapy in order to assess their impact in biological terms. As such, the accuracy of the particle fluence energy spectra becomes paramount. This study focuses on quantifying energy depositions of distinct proton, helium, carbon, and oxygen ion beams using a silicon pixel detector developed at CERN to determine LET spectra in silicon.

Graph machine learning for integrated multi-omics analysis.

Multi-omics experiments at bulk or single-cell resolution facilitate the discovery of hypothesis-generating biomarkers for predicting response to therapy, as well as aid in uncovering mechanistic insights into cellular and microenvironmental processes. Many methods for data integration have been developed for the identification of key elements that explain or predict disease risk or other biological outcomes. The heterogeneous graph representation of multi-omics data provides an advantage for discerning patterns suitable for predictive/exploratory analysis, thus permitting the modeling of complex relationships.

Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

We comment on the recently published study 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' by Shiraishi. While the general approach of the study may be appropriate, we wish to comment on its limitations and point out issues concerning their choice of the benchmarking and fitting data. The approach by the authors could become viable in an extended form once more comprehensive data is available.

Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro.

Background: Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome the radioresistant nature of pancreatic cancer because of its biological and physical characteristics.

Dosimetric study for breathing-induced motion effects in an abdominal pancreas phantom for carbon ion mini-beam radiotherapy.

Background: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation.

Purpose: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer.

Robustness of carbon-ion radiotherapy against DNA damage repair associated radiosensitivity variation based on a biophysical model.

Background: Interpatient variation of tumor radiosensitivity is rarely considered during the treatment planning process despite its known significance for the therapeutic outcome.

Purpose: To apply our mechanistic biophysical model to investigate the biological robustness of carbon ion radiotherapy (CIRT) against DNA damage repair interference (DDRi) associated patient-to-patient variability in radiosensitivity and its potential clinical advantages against conventional radiotherapy approaches.

Methods And Materials: The "UNIfied and VERSatile bio response Engine" (UNIVERSE) was extended by carbon ions and its predictions were compared to a panel of in vitro and in vivo data including various endpoints and DDRi settings within clinically relevant dose and linear energy transfer (LET) ranges.

Clinical Workflow of Cone Beam Computer Tomography-Based Daily Online Adaptive Radiotherapy with Offline Magnetic Resonance Guidance: The Modular Adaptive Radiotherapy System (MARS).

Purpose: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance.

Understanding Relative Biological Effectiveness and Clinical Outcome of Prostate Cancer Therapy Using Particle Irradiation: Analysis of Tumor Control Probability With the Modified Microdosimetric Kinetic Model.

Purpose: Recent experimental studies and clinical trial results might indicate that-at least for some indications-continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy.

Methods And Materials: Treatment plans of 91 patients with prostate tumors (proton: 46, carbon ions: 45) applying 66 GyRBE [RBE = 1.

A Monte Carlo study on the secondary neutron generation by oxygen ion beams for radiotherapy and its comparison to lighter ions.

To study the secondary neutrons generated by primary oxygen beams for cancer treatment and compare the results to those from primary protons, helium, and carbon ions. This information can provide useful insight into the positioning of neutron detectors in phantom for future experimental dose assessments.Mono-energetic oxygen beams and spread-out Bragg peaks were simulated using the Monte Carlo particle transport codes, tool for particle simulation, and Monte Carlo N-Particle, with energies within the therapeutic range.

A phantom to simulate organ motion and its effect on dose distribution in carbon ion therapy for pancreatic cancer.

. Carbon ion radiotherapy is a promising radiation technique for malignancies like pancreatic cancer. However, organs' motion imposes challenges for achieving homogeneous dose delivery.

Development and benchmarking of a dose rate engine for raster-scanned FLASH helium ions.

Background: Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so-called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity.

Development and validation of MonteRay, a fast Monte Carlo dose engine for carbon ion beam radiotherapy.

Background: Monte Carlo (MC) simulations are considered the gold-standard for accuracy in radiotherapy dose calculation; so far however, no commercial treatment planning system (TPS) provides a fast MC for supporting clinical practice in carbon ion therapy.

Purpose: To extend and validate the in-house developed fast MC dose engine MonteRay for carbon ion therapy, including physical and biological dose calculation.

Methods: MonteRay is a CPU MC dose calculation engine written in C++ that is capable of simulating therapeutic proton, helium and carbon ion beams.

Diamond detectors for dose and instantaneous dose-rate measurements for ultra-high dose-rate scanned helium ion beams.

Background: The possible emergence of the FLASH effect-the sparing of normal tissue while maintaining tumor control-after irradiations at dose-rates exceeding several tens of Gy per second, has recently spurred a surge of studies attempting to characterize and rationalize the phenomenon. Investigating and reporting the dose and instantaneous dose-rate of ultra-high dose-rate (UHDR) particle radiotherapy beams is crucial for understanding and assessing the FLASH effect, towards pre-clinical application and quality assurance programs.

Purpose: The purpose of the present work is to investigate a novel diamond-based detector system for dose and instantaneous dose-rate measurements in UHDR particle beams.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy.

. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP)..

DNA-Methylome-Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy.

Purpose: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.