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.

Detecting perturbations of a radiation field inside a head-sized phantom exposed to therapeutic carbon-ion beams through charged-fragment tracking.

Purpose: Noninvasive methods to monitor carbon-ion beams in patients are desired to fully exploit the advantages of carbon-ion radiotherapy. Prompt secondary ions produced in nuclear fragmentations of carbon ions are of particular interest for monitoring purposes as they can escape the patient and thus be detected and tracked to measure the radiation field in the irradiated object. This study aims to evaluate the performance of secondary-ion tracking to detect, visualize, and localize an internal air cavity used to mimic inter-fractional changes in the patient anatomy at different depths along the beam axis.

Quality assurance for on-table adaptive magnetic resonance guided radiation therapy: A software tool to complement secondary dose calculation and failure modes discovered in clinical routine.

Online adaption of treatment plans on a magnetic resonance (MR)-Linac enables the daily creation of new (adapted) treatment plans using current anatomical information of the patient as seen on MR images. Plan quality assurance (QA) relies on a secondary dose calculation (SDC) that is required because a pretreatment measurement is impossible during the adaptive workflow. However, failure mode and effect analysis of the adaptive planning process shows a large number of error sources, and not all of them are covered by SDC.

Radiation induced contrast enhancement after proton beam therapy in patients with low grade glioma - How safe are protons?

Purpose: The optimal treatment strategy for low-grade glioma (LGG) is still a matter of controversy. Considering that the prognosis is typically favorable, the prevention of late sequelae is of particular importance. Proton beam therapy (PRT) has the potential to further reduce the burden of treatment related side effects.

Assessment of Normal Tissue Radiosensitivity by Evaluating DNA Damage and Repair Kinetics in Human Brain Organoids.

DNA-double strand break (DSB), detected by immunostaining of key proteins orchestrating repair, like γH2AX and 53BP1, is well established as a surrogate for tissue radiosensitivity. We hypothesized that the generation of normal brain 3D organoids ("mini-brains") from human induced pluripotent stem cells (hiPSC) combined with detection of DNA damage repair (DDR) may hold the promise towards developing personalized models for the determination of normal tissue radiosensitivity. In this study, cerebral organoids, an in vitro model that stands in its complexity between 2D cellular system and an organ, have been used.

Assessment of secondary neutrons in particle therapy by Monte Carlo simulations.

. The purpose of this study is to estimate the energy and angular distribution of secondary neutrons inside a phantom in hadron therapy, which will support decisions on detector choice and experimental setup design for in-phantom secondary neutron measurements..

C-MORE: A high-content single-cell morphology recognition methodology for liquid biopsies toward personalized cardiovascular medicine.

Cellular morphology has the capacity to serve as a surrogate for cellular state and functionality. However, primary cardiomyocytes, the standard model in cardiovascular research, are highly heterogeneous cells and therefore impose methodological challenges to analysis. Hence, we aimed to devise a robust methodology to deconvolute cardiomyocyte morphology on a single-cell level: C-MORE (cellular morphology recognition) is a workflow from bench to data analysis tailored for heterogeneous primary cells using our R package cmoRe.

Definitive radiotherapy for squamous cell carcinoma of the oral cavity: a single-institution experience.

Background: Surgery is standard of care for oral cavity cancer (OCC). We provide a single-institution experience using definitive radiotherapy (RT) with or without concurrent systemic therapy for primary unresectable OCC.

Patients And Methods: We retrospectively examined 49 patients with non-metastatic primary unresectable OCC treated with definitive RT between 2000 and 2019.

Dual-layer spectral CT for proton, helium, and carbon ion beam therapy planning of brain tumors.

Pretreatment computed tomography (CT) imaging is an essential component of the particle therapy treatment planning chain. Treatment planning and optimization with charged particles require accurate and precise estimations of ion beam range in tissues, characterized by the stopping power ratio (SPR). Reduction of range uncertainties arising from conventional CT-number-to-SPR conversion based on single-energy CT (SECT) imaging is of importance for improving clinical practice.

Combined DNA Damage Repair Interference and Ion Beam Therapy: Development, Benchmark, and Clinical Implications of a Mechanistic Biological Model.

Purpose: Our purpose was to develop a mechanistic model that describes and predicts radiation response after combined DNA damage repair interference (DDRi) and particle radiation therapy.

Methods And Materials: The heterogeneous dose distributions of protons and He ions were implemented into the "UNIfied and VERSatile bio-response Engine" (UNIVERSE). Predictions for monoenergetic and mixed fields over clinically relevant dose and linear energy transfer range were compared with experimental in vitro survival data measured in this work as well as data available in the literature, including different cell lines and DDR interferences.

High-Complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance.

It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400 000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analyzed. Fractionated IR induced a strong selective pressure for clonal reduction which significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to-clone difference within tumor cell lines.

Human mesenchymal stromal cells maintain their stem cell traits after high-LET particle irradiation - Potential implications for particle radiotherapy and manned space missions.

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton (H), helium (He), carbon (C) and oxygen (O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using γH2AX immunofluorescence and Western blots.

Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy.

Biomarkers with relevance for loco-regional therapy are needed in human papillomavirus negative aka HPV(-) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome-based classifier identifying HPV(-) HNSCC patients at risk for loco-regional recurrence (LR) and all-event progression after postoperative radiochemotherapy (PORT-C). The training cohort consisted of HPV-DNA negative HNSCC patients (n = 128) homogeneously treated with PORT-C in frame of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial.

Dataset for predicting single-spot proton ranges in proton therapy of prostate cancer.

The number of radiotherapy patients treated with protons has increased from less than 60,000 in 2007 to more than 220,000 in 2019. However, the considerable uncertainty in the positioning of the Bragg peak deeper in the patient raised new challenges in the proton therapy of prostate cancer (PCPT). Here, we describe and share a dataset where 43 single-spot anterior beams with defined proton energies were delivered to a prostate phantom with an inserted endorectal balloon (ERB) filled either with water only or with a silicon-water mixture.

Efficient uncertainty quantification for Monte Carlo dose calculations using importance (re-)weighting.

. To present an efficient uncertainty quantification method for range and set-up errors in Monte Carlo (MC) dose calculations. Further, we show that uncertainty induced by interplay and other dynamic influences may be approximated using suitable error correlation models.

Radioresistance and Transcriptional Reprograming of Invasive Glioblastoma Cells.

Purpose: Infiltrative growth pattern is a hallmark of glioblastoma (GBM). Radiation therapy aims to eradicate microscopic residual GBM cells after surgical removal of the visible tumor bulk. However, in-field recurrences remain the major pattern of therapy failure.

How LEM-based RBE and dose-averaged LET affected clinical outcomes of sacral chordoma patients treated with carbon ion radiotherapy.

Purpose/objective: To understand the role of relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET) distributions in the treatment of sacral chordoma (SC) patients with carbon ion radiotherapy (CIRT).

Material/methods: Clinical plans of 50 SC patients consecutively treated before August 2018 with a local effect model-based optimization were recalculated with the modified microdosimetric kinetic RBE model (mMKM). Twenty-six patients were classified as progressive disease and the relapse volume was contoured on the corresponding follow-up diagnostic sequence.

Simultaneous targeting of TGF-β/PD-L1 synergizes with radiotherapy by reprogramming the tumor microenvironment to overcome immune evasion.

Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation of programmed cell death-ligand 1 (PD-L1) and transforming growth factor β (TGF-β).

Quality of life after simultaneously integrated boost with intensity-modulated versus conventional radiotherapy with sequential boost for adjuvant treatment of breast cancer: 2-year results of the multicenter randomized IMRT-MC2 trial.

Background: We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). Here, we report on 2-year quality of life results.

Patients And Methods: 502 patients were enrolled and randomized to IMRT-SIB (50.

Stereotactic body radiotherapy of lymph node metastases under MR-guidance: First clinical results and patient-reported outcomes.

Objective: Stereotactic body radiotherapy (SBRT) is a noninvasive treatment option for lymph node metastases (LNM). Magnetic resonance (MR)-guidance offers superior tissue contrast and enables treatment of targets in close vicinity to radiosensitive organs at risk (OAR). However, literature on MR-guided SBRT of LNM is scarce with no report on outcome parameters.

Carbon ion radiotherapy as definitive treatment in locally recurrent pancreatic cancer.

Purpose: Data on management of locally recurrent pancreatic cancer (LRPC) after primary resection are limited. Recently, surprisingly high overall survival rates were reported after irradiation with carbon ions. Here, we report on our clinical experience using carbon ion radiotherapy as definitive treatment in LRPC at the Heidelberg Ion-Beam Therapy Center (HIT).

FAP imaging in rare cancer entities-first clinical experience in a broad spectrum of malignancies.

Purpose:  Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors.

Material And Methods: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a  Ga-FAPI-PET/CT scan.

GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy.

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity.

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

Purpose: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network.

Material And Methods: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones.

Towards real-time PGS range monitoring in proton therapy of prostate cancer.

Proton therapy of prostate cancer (PCPT) was linked with increased levels of gastrointestinal toxicity in its early use compared to intensity-modulated radiation therapy (IMRT). The higher radiation dose to the rectum by proton beams is mainly due to anatomical variations. Here, we demonstrate an approach to monitor rectal radiation exposure in PCPT based on prompt gamma spectroscopy (PGS).