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.

Fractionated stereotactic radiotherapy of brainstem metastases - Clinical outcome and prognostic factors.

Introduction: Brain metastases (BM) are the most common malignancy in the central nervous system (CNS) and observed in approximately 30% of cancer patients. Brainstem metastases (BSM) are challenging because of their location and the associated neurological risks. There are still no general therapeutic recommendations in this setting.

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.

Prompt gamma emission prediction using a long short-term memory network.

: To present a long short-term memory (LSTM)-based prompt gamma (PG) emission prediction method for proton therapy.: Computed tomography (CT) scans of 33 patients with a prostate tumor were included in the dataset. A set of 10histories proton pencil beam (PB)s was generated for Monte Carlo (MC) dose and PG simulation.

Proton dose calculation with LSTM networks in presence of a magnetic field.

To present a long short-term memory (LSTM) network-based dose calculation method for magnetic resonance (MR)-guided proton therapy.35 planning computed tomography (CT) images of prostate cancer patients were collected for Monte Carlo (MC) dose calculation under a perpendicular 1.5 T magnetic field.

Intrafraction organ movement in adaptive MR-guided radiotherapy of abdominal lesions - dosimetric impact and how to detect its extent in advance.

Introduction: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes.

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.

Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases - Clinical outcome and prognostic factors.

Background And Purpose: After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity.

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.

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.

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.

Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk-benefit analysis.

Purpose: Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks.

Methods: Patients receiving surgery for recurrent glioma WHO grade 2-4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively.

Evaluation of 2D ion chamber arrays for patient specific quality assurance using a static phantom at a 0.35 T MR-Linac.

Introduction: Patient specific quality assurance (QA) in MR-Linacs can be performed with MR-compatible ion chamber arrays. However, the presence of a static magnetic field can alter the angular response of such arrays substantially. This works investigates the suitability of two ion chamber arrays, an air-filled and a liquid-filled array, for patient specific QA at a 0.

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.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

Background: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation.

Methods: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers.

Leaf-individual calibration for a double stack multileaf collimator in photon radiotherapy.

Background And Purpose: In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs.

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)..

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

Background: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR).