Hybrid Immunity Protects against Antibody Fading after SARS-CoV-2mRNA Vaccination in Kidney Transplant Recipients, Dialysis Patients, and Medical Personnel: 9 Months Data from the Prospective, Observational Dia-Vacc Study.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR).

Carbon ion beam dosimetry in magnetic fields using Farmer-type ionization chambers of different radii: measurements and simulations.

To investigate magnetic field effects on the dose distribution and ionization chambers response in carbon ion reference fields and determine magnetic field correction factors for chambers of different volumes.The response of six Farmer-type chambers with varying radii (1-6 mm, termed as R1-R6) was measured in magnetic fields up to 1 T in 0.1 T increments using an experimental electromagnet and compared with Monte Carlo simulations.

Irradiation with Carbon Ions Effectively Counteracts Hypoxia-related Radioresistance in a Rat Prostate Carcinoma.

Purpose: Hypoxia in tumors is associated with increased malignancy and resistance to conventional photon radiation therapy. This study investigated the potential of particle therapy to counteract radioresistance in syngeneic rat prostate carcinoma.

Methods And Materials: Subcutaneously transplanted R3327-HI tumors were irradiated with photons or carbon ions under acute hypoxic conditions, induced by clamping the tumor-supplying artery 10 min before and during irradiation.

Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.

Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the in vivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred.

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions.

Background And Purpose: Ion beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord.

Materials And Methods: The spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses.

Validation of complex radiotherapy techniques using polymer gel dosimetry.

Modern radiotherapy delivers highly conformal dose distributions to irregularly shaped target volumes while sparing the surrounding normal tissue. Due to the complex planning and delivery techniques, dose verification and validation of the whole treatment workflow by end-to-end tests became much more important and polymer gel dosimeters are one of the few possibilities to capture the delivered dose distribution in 3D. The basic principles and formulations of gel dosimetry and its evaluation methods are described and the available studies validating device-specific geometrical parameters as well as the dose delivery by advanced radiotherapy techniques, such as 3D-CRT/IMRT and stereotactic radiosurgery treatments, the treatment of moving targets, online-adaptive magnetic resonance-guided radiotherapy as well as proton and ion beam treatments, are reviewed.

Quality requirements for MRI simulation in cranial stereotactic radiotherapy: a guideline from the German Taskforce "Imaging in Stereotactic Radiotherapy".

Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

Background: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients.

Methods: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively.

Efficacy and toxicity of bimodal radiotherapy in WHO grade 2 meningiomas following subtotal resection with carbon ion boost: Prospective phase 2 MARCIE trial.

Background: Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5).

Methods: A total of 33 patients were enrolled from July 2012 until July 2020.

Multi-parametric optimization of magnetic resonance imaging sequences for magnetic resonance-guided radiotherapy.

Background And Purpose: Magnetic Resonance Imaging (MRI) is widely used in oncology for tumor staging, treatment response assessment, and radiation therapy (RT) planning. This study proposes a framework for automatic optimization of MRI sequences based on pulse sequence parameter sets (SPS) that are directly applied on the scanner, for application in RT planning.

Materials And Methods: A phantom with seven in-house fabricated contrasts was used for measurements.

Monte Carlo simulation for proton dosimetry in magnetic fields: Fano test and magnetic field correction factorsfor Farmer-type ionization chambers.

. In this contribution we present a special Fano test for charged particles in presence of magnetic fields in the MC code TOol for PArticle Simulation (TOPAS), as well as the determination of magnetic field correction factorsfor Farmer-type ionization chambers using proton beams..

Quality assurance and temporal stability of a 1.5 T MRI scanner for MR-guided Photon and Particle Therapy.

Purpose: To describe performance measurements, adaptations and time stability over 20 months of a diagnostic MR scanner for integration into MR-guided photon and particle radiotherapy.

Material And Methods: For realization of MR-guided photon and particle therapy (MRgRT/MRgPT), a 1.5 T MR scanner was installed at the Heidelberg Ion Beam Therapy Center.

Proton beam dosimetry in the presence of magnetic fields using Farmer-type ionization chambers of different radii.

Background: Magnetic resonance-guided proton therapy is promising, as it combines high-contrast imaging of soft tissue with highly conformal dose delivery. However, proton dosimetry in magnetic fields using ionization chambers is challenging since the dose distribution as well as the detector response are perturbed.

Purpose: This work investigates the effect of the magnetic field on the ionization chamber response, and on the polarity and ion recombination correction factors, which are essential for the implementation of a proton beam dosimetry protocol in the presence of magnetic fields.

Strategy for automatic ultrasound (US) probe positioning in robot-assisted ultrasound guided radiation therapy.

. As part of image-guided radiotherapy, ultrasound-guided radiotherapy is currently already in use and under investigation for robot assisted systems Ipsen 2021. It promises a real-time tumor localization during irradiation (intrafractional) without extra dose.

Anti-SARS-CoV-2 Revaccination Success in Kidney Transplant Recipients With No Initial Humoral Response Is Linked to Primary Vaccine Type.

Background: While anti-SARS-CoV-2 vaccination success in kidney transplant recipients (KTR) after two doses and 1273-mRNA was associated with higher seroconversion rates compared to BNT162b2-mRNA in our "DIA-Vacc Study" (NCT04799808), it remains unclear whether this may also be the case in non-responding KTR after a third vaccination dose.

Materials And Methods: Non-responding KTR (after two mRNA vaccinations) were investigated 4.5-6 months after study enrollment at first vaccination.

Results of a prospective randomized trial on long-term effectiveness of protons and carbon ions in prostate cancer: LEM I and α/β = 2 Gy overestimates the RBE.

Aim: To analyze the long-term effectiveness of carbon ions relative to protons in the prospective randomized controlled ion prostate irradiation (IPI) trial.

Methods: Effectiveness via PSA assessment in a randomized study on prostate irradiation with 20x3.3 Gy(RBE) protons versus carbon ions was analyzed in 92 patients.

Impact of DNA Repair Kinetics and Dose Rate on RBE Predictions in the UNIVERSE.

Accurate knowledge of the relative biological effectiveness (RBE) and its dependencies is crucial to support modern ion beam therapy and its further development. However, the influence of different dose rates of the reference radiation and ion beam are rarely considered. The ion beam RBE-model within our "UNIfied and VERSatile bio response Engine" (UNIVERSE) is extended by including DNA damage repair kinetics to investigate the impact of dose-rate effects on the predicted RBE.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination.

Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion ( IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR ( = 0·005), respectively.

Roadmap: helium ion therapy.

Helium ion beam therapy for the treatment of cancer was one of several developed and studied particle treatments in the 1950s, leading to clinical trials beginning in 1975 at the Lawrence Berkeley National Laboratory. The trial shutdown was followed by decades of research and clinical silence on the topic while proton and carbon ion therapy made debuts at research facilities and academic hospitals worldwide. The lack of progression in understanding the principle facets of helium ion beam therapy in terms of physics, biological and clinical findings persists today, mainly attributable to its highly limited availability.

Relative biological effectiveness of single and split helium ion doses in the rat spinal cord increases strongly with linear energy transfer.

Background And Purpose: Determination of the relative biological effectiveness (RBE) of helium ions as a function of linear energy transfer (LET) for single and split doses using the rat cervical spinal cord as model system for late-responding normal tissue.

Material And Methods: The rat cervical spinal cord was irradiated at four different positions within a 6 cm spread-out Bragg-peak (SOBP) (LET 2.9, 9.

The history of ion beam therapy in Germany.

The advantageous depth dose profile of ion beams together with state of the art beam delivery and treatment planning systems allow for highly conformal tumor treatments in patients. First treatments date back to 1954 at the Lawrence Berkeley Laboratory (LBL) and in Europe, ion beam therapy started in the mid-1990s at the Paul-Scherrer Institute (PSI) with protons and at the Helmholtz Center for Heavy Ion Research (GSI) with carbon ions, followed by the Heidelberg Ion Therapy Center (HIT) in Heidelberg. This review describes the historical development of ion beam therapy in Germany based on the pioneering work at LBL and in the context of simultaneous developments in other countries as well as recent developments.

An abdominal phantom with anthropomorphic organ motion and multimodal imaging contrast for MR-guided radiotherapy.

. Improvements in image-guided radiotherapy (IGRT) enable accurate and precise treatment of moving tumors in the abdomen while simultaneously sparing healthy tissue. However, the lack of validation tools for newly developed MR-guided radiotherapy hybrid devices such as the MR-Linac is an open issue.

End-to-end test for fractionated online adaptive MR-guided radiotherapy using a deformable anthropomorphic pelvis phantom.

In MR-guided radiotherapy (MRgRT) for prostate cancer treatments inter-fractional anatomy changes such as bladder and rectum fillings may be corrected by an online adaption of the treatment plan. To clinically implement such complex treatment procedures, however, specific end-to-end tests are required that are able to validate the overall accuracy of all treatment steps from pre-treatment imaging to dose delivery.In this study, an end-to-end test of a fractionated and online adapted MRgRT prostate irradiation was performed using the so-called ADAM-PETer phantom.

DCE-MRI detected vascular permeability changes in the rat spinal cord do not explain shorter latency times for paresis after carbon ions relative to photons.

Background And Purpose: Radiation-induced myelopathy, an irreversible complication occurring after a long symptom-free latency time, is preceded by a fixed sequence of magnetic resonance- (MR-) visible morphological alterations. Vascular degradation is assumed the main reason for radiation-induced myelopathy. We used dynamic contrast-enhanced (DCE-) MRI to identify different vascular changes after photon and carbon ion irradiation, which precede or coincide with morphological changes.