Purpose/Objective(s) MRT is an approach in radiation therapy that uses highly inhomogeneous radiation fields that are periodically segmented into regions of high dose and low dose. Preclinical studies demonstrated that nonuniform dose distributions spare normal tissue at equal tumor control compared to conventional radiotherapy. We developed a treatment planning and dose calculation engine to investigate various dose delivery strategies. Materials/Methods We employed a hybrid dose calculation algorithm combining an analytical electron convolution approach with the planning tool techniques for photon scattering to calculate multiport treatments with parallel, planar microbeams of 50 µm beam width and 400 µm beam-to-beam spacing. We investigated four different 8-port geometries of 24 microbeams per port with an angular spacing of 45°:1. Superposed: Microbeams are aligned to each other conserving the 50µm/400µm beam pattern in the target.2. Interspersed: Alternating beams were shifted by 200 µm, creating a 50µm/200µm beam pattern in the target.3. Interlaced: Microbeams are shifted by 50 µm from one port to the next, creating an almost homogeneous target dose.4. Cross-fired: planar microbeams are aligned parallel to the rotation axis creating a crossing beam pattern in the target.Moreover, we added tomo and spiral MRT in our comparison, where the target is rotating around an axis perpendicular to the microbeam planes. While in tomo MRT the plane of the beams is maintained, there is a shift of 400 µm in spiral MRT during a 360° rotation. We investigated the dose distribution in a water phantom and a clinical lung tumor case. The target dose was set to 20 Gy. Dose distributions were analyzed using the equivalent uniform dose (EUD) at the planning target volume and organs at risk. Results In the superposed strategy and tomo MRT extremely high peak dose were reached in the target. Interspersed, interlaced and spiral MRT led to the lowest beam entrance doses. Conclusion The alignment of the microbeams plays an important role due to the alternating high- and low-dose micro-fractionated beam pattern. The choice of the field geometry depends on technical and biomedical considerations. The interlaced, interspersed and superposed geometry require a micrometer-precise alignment of the target volume. In contrast, a cross-firing geometry has lower alignment demands. Dosimetric results have shown that spiral MRT of lung cancer had the lowest EUD in the surrounding tissue with the trade-off of distributing the dose over a larger volume. Spiral MRT leads to the lowest dose in organs at risk at equal target dose. However, EUD may not be the only figure of merit and the effect of microbeams may depend on a dose modulation in the target.

PurposeFor women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose-volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort.MethodsRadiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB-IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets.ResultsComparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB.ConclusionThe results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

Background and purpose: Many patients with solid tumors develop brain metastases (BM). With more patients surviving long-term, preservation of neurocognitive function gains importance. In recent years, several methods to delay cognitive deterioration have been tested in clinical trials. However, knowledge on the extent to which these neuroprotective strategies have been implemented in clinical practice is missing. Materials and methods: We performed an online survey regarding treatment patterns of BM in German-speaking countries, focused on the use of neuroprotective approaches. The survey was distributed among radiation oncologists (ROs) registered within the database of the German Society for Radiation Oncology (DEGRO). Results: Physicians of 78 centers participated in the survey. Whole brain radiotherapy (WBRT) is still preferred by 70 % of ROs over stereotactic radiotherapy (SRT) in patients with 6–10 BM. For 4–5 BM WBRT is preferred by 23 % of ROs. The fraction of ROs using hippocampal sparing (HS) in WBRT has increased to 89 %, although the technique is used on a regular basis only by a minority (26 %). The drug memantine is not widely prescribed (14% of ROs). A trend was observed for university hospitals to implement neuroprotective approaches more frequently. Conclusion: There is considerable heterogeneity regarding the treatment of BM in German-speaking countries and a general standard of care is lacking. Neuroprotective strategies are not yet standard approaches in daily clinical routine, although usage is increasing. Further clinical trials, as well as improvement of technical opportunities and reimbursement, might further shift the treatment landscape towards neuroprotective radiation treatments in the future.

Purpose/Objective(s) The aim of this trial was to investigate the oncological benefit of a re-irradiation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) for patients with recurrent glioblastoma (rGBM) as compared to a re-irradiation based on contrast-enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Materials/Methods GLIAA was a prospective, multicenter, randomized clinical trial (NOA 10/ARO 2013-1, DKTK-a., NCT01252459). Patients with rGBM of 1-6 cm were randomized 1:1 at 14 centers in Germany between a FET-PET-based target volume delineation (experimental arm A) and a T1Gd-MRI-based target volume delineation (control arm B) and received high-precision stereotactic re-irradiation with 39 Gy à 3 Gy, 5x/week. Follow-up was performed by MRI and suspected progression was confirmed by FET-PET or histology, whenever possible. Primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), locally controlled survival (LCS), recurrence patterns, and safety. Results Between November 26, 2013 and September 2, 2021, 200 patients were randomized between FET-PET-based (n = 100) and GdT1-MRI-based (n = 100) target volume delineation, of whom n = 98 and n = 97 patients, respectively, were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI = 3.7-6.0) in the GdT1-MRT arm (one-sided stratified log-rank test P = 0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI = 0.85-1.52], P = 0.39;). Median OS was 9.4 months (95% CI = 7.8-11.1) in the FET-PET arm and 9.0 months (95% CI = 7.6-10.5) in the GdT1-MRI arm (HR 1.01 [95% CI = 0.75-1.37], P = 0.92). Median LCS was 6.3 months (95% CI = 5.1-7.2) in the FET-PET arm and 6.8 months (95% CI = 6.2-7.3) in the GdT1-MRI arm (HR 1.20 [95% CI = 0.88-1.62], P = 0.25). At 12 months, the local control rate was 22% in the FET-PET arm (95% CI = 14%-31%) and 20% in the GdT1-MRI arm (95% CI = 12%-29%). In the PET arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In the MRI arm, 47.4% relapsed in field, 31.6% out of field, and 14.0% marginal. Radiation necrosis was documented in 25.5% of cases in the FET-PET arm and in 21.6% in the GdT1-MRI arm. There were no adverse events related to the application of the FET tracer. Conclusion The GLIAA trial could not identify an oncological benefit of the FET-PET-based rGBM-re-irradiation as compared to the GdT1-MRI-based treatment. Consequently, both imaging modalities remain valid for radiotherapy planning in this case. Both the FET-PET investigation and the re-irradiation were well-tolerated, supporting the safety of this treatment.

High-linear energy transfer (LET) radiation, such as heavy ions is associated with a higher relative biological effectiveness (RBE) than low-LET radiation, such as photons. Irradiation with low- and high-LET particles differ in the interaction with the cellular matter and therefore in the spatial dose distribution. When a single high-LET particle interacts with matter, it results in doses of up to thousands of gray (Gy) locally concentrated around the ion trajectory, whereas the mean dose averaged over the target, such as a cell nucleus is only in the range of a Gy. DNA damage therefore accumulates in this small volume. In contrast, up to hundreds of low-LET particle hits are required to achieve the same mean dose, resulting in a quasi-homogeneous damage distribution throughout the cell nucleus. In this study, we investigated the dependence of RBE from different spatial dose depositions using different focused beam spot sizes of proton radiation with respect to the induction of chromosome aberrations and clonogenic cell survival. Human-hamster hybrid (AL) as well as Chinese hamster ovary cells (CHO-K1) were irradiated with focused low LET protons of 20 MeV (LET = 2.6 keV/µm) beam energy with a mean dose of 1.7 Gy in a quadratic matrix pattern with point spacing of 5.4 × 5.4 µm2 and 117 protons per matrix point at the ion microbeam SNAKE using different beam spot sizes between 0.8 µm and 2.8 µm (full width at half maximum). The dose-response curves of X-ray reference radiation were used to determine the RBE after a 1.7 Gy dose of radiation. The RBE for the induction of dicentric chromosomes and cell inactivation was increased after irradiation with the smallest beam spot diameter (0.8 µm for chromosome aberration experiments and 1.0 µm for cell survival experiments) compared to homogeneous proton radiation but was still below the RBE of a corresponding high LET single ion hit. By increasing the spot size to 1.6-1.8 µm, the RBE decreased but was still higher than for homogeneously distributed protons. By further increasing the spot size to 2.7-2.8 µm, the RBE was no longer different from the homogeneous radiation. Our experiments demonstrate that varying spot size of low-LET radiation gradually modifies the RBE. This underlines that a substantial fraction of enhanced RBE originates from inhomogeneous energy concentrations on the µm scale (mean intertrack distances of low-LET particles below 0.1 µm) and quantifies the link between such energy concentration and RBE. The missing fraction of RBE enhancement when comparing with high-LET ions is attributed to the high inner track energy deposition on the nanometer scale. The results are compared with model results of PARTRAC and LEM for chromosomal aberration and cell survival, respectively, which suggest mechanistic interpretations of the observed radiation effects.

In a next step, we will build the LFxT-2 and aim for first clinical MRT trials at this source. In order to further improve calculated MRT dose distributions, we will implement inverse treatment planning techniques.

Die Bestrahlungsplanung ist ein notwendiger Arbeitsschritt vor Durchführung einer Strahlentherapie. Die Definition von anatomischen Organen, die in direkter Nähe zu der bestrahlten Zielregion liegen, und die Definition des Zielvolumens ist dabei ein zentraler Bestandteil der ärztlichen Tätigkeit einer Strahlentherapeut*In. Die Errungenschaften in der Entwicklung der künstlichen Intelligenz (KI) haben neuronale Netze hervorgebracht, die hocheffektiv zur Segmentierung von medizinischen Bilddaten verwendet werden können. Ziel war die Analyse der Möglichkeiten der KI-basierten Autokonturierung in der Bestrahlungsplanung. Dabei erfolgt die Vorstellung von wissenschaftlichen Arbeiten, die Diskussion klinisch verfügbarer Software und ein Ausblick auf zukünftige innovative Lösungen. Eine Literatursuche (PubMed) wurde durchgeführt, um relevante Literatur zu identifizieren. Erste zugelassene Softwarelösungen ermöglichen die automatisierte Konturierung von anatomischen Organen. Die Segmentierungsgüte erreicht für viele Organe eine hohe Qualität, während bestimmte kleine oder besonders lagevariable Strukturen noch größerer manueller Korrekturen bedürfen. Die Definition von klinischen Zielvolumina, z. B. im Sinne von lokalen Lymphabflusswegen, scheint eine gute Reproduzierbarkeit aufzuweisen. Für verschiedene Tumoren wurde außerdem gezeigt, dass neuronale Netze ebenfalls effektiv und reproduzierbar die Tumorregion definieren können. Weitere Entwicklungen, wie Tumorwachstumsmodelle, könnten außerdem neue individualisierte Definitionswege von Zielvolumina ermöglichen. KI-Modelle zur Autokonturierung haben das Potenzial, die Arbeit von Radioonkolog*Innen durch eine Teilautomatisierung zu beschleunigen, den Personalaufwand zu reduzieren und gleichzeitig eine erhöhte Standardisierung zu erreichen.

HSRT is the most common fractionation form in the treatment of RCs in this multicenter analysis. This approach results in excellent OS and LC outcomes. OS in patients with resected brain metastases is mainly influenced by performance status. In regard to local control, RT of large cavities remain a challenge with significantly worse outcome.

EUD is a superior predictor of in vitro cell survival than other metrics sometimes used in the SFRT literature, including mean dose, maximum dose, and valley dose. The reported studies provide some evidence that SFRT may increase the therapeutic ratio by producing spatial dose distributions that effectively reduce normal-tissue damage with little or no change in biological damage to tumor cells. Additional studies are needed to further extend and generalize our results and to test our conclusions against a larger dose range, low and high linear energy transfer (LET) radiations and additional cell lines.

Background: Target volume definition is a central component of radiation planning in radiation oncology. In addition to anatomical organs that are in close proximity to the irradiated target region, target volume definition is a relevant part of a radiation oncologist's medical practice. Advances in the development of artificial intelligence (AI) have produced neural networks that can be used highly effectively to segment medical image data. Aim: To analyze the potential of AI-based autocontouring in radiation planning. The article presents the body of scientific work, existing software solutions and an outlook on future innovative solutions. Materials and methods: A literature search (PubMed) was performed to identify relevant literature. Results: The first approved software solutions allow automated contouring of anatomical organs. The segmentation quality for many organs is high, while certain positionally variable structures or particularly small organs still requiremore substantial corrections. The definition of clinical target volumes, e.g., in terms of local lymphatic drainage, achieve good reproducibility. For a variety of tumors, it has also been shown that neural networks can effectively and reproducibly define the gross tumor volume. Further developments, such as tumor growthmodels, may provide novel individualized definitions of target volumes. Conclusion: AI models for autocontouring have the potential to accelerate the work of radiation oncologists through partial automation and reducing staff time, while achieving increased standardization.

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Die Bestrahlungsplanung ist ein notwendiger Arbeitsschritt vor Durchführung einer Strahlentherapie. Die Definition von anatomischen Organen, die in direkter Nähe zu der bestrahlten Zielregion liegen, und die Definition des Zielvolumens ist dabei ein zentraler Bestandteil der ärztlichen Tätigkeit einer Strahlentherapeut*In. Die Errungenschaften in der Entwicklung der künstlichen Intelligenz (KI) haben neuronale Netze hervorgebracht, die hocheffektiv zur Segmentierung von medizinischen Bilddaten verwendet werden können. Ziel war die Analyse der Möglichkeiten der KI-basierten Autokonturierung in der Bestrahlungsplanung. Dabei erfolgt die Vorstellung von wissenschaftlichen Arbeiten, die Diskussion klinisch verfügbarer Software und ein Ausblick auf zukünftige innovative Lösungen. Eine Literatursuche (PubMed) wurde durchgeführt, um relevante Literatur zu identifizieren. Erste zugelassene Softwarelösungen ermöglichen die automatisierte Konturierung von anatomischen Organen. Die Segmentierungsgüte erreicht für viele Organe eine hohe Qualität, während bestimmte kleine oder besonders lagevariable Strukturen noch größerer manueller Korrekturen bedürfen. Die Definition von klinischen Zielvolumina, z. B. im Sinne von lokalen Lymphabflusswegen, scheint eine gute Reproduzierbarkeit aufzuweisen. Für verschiedene Tumoren wurde außerdem gezeigt, dass neuronale Netze ebenfalls effektiv und reproduzierbar die Tumorregion definieren können. Weitere Entwicklungen, wie Tumorwachstumsmodelle, könnten außerdem neue individualisierte Definitionswege von Zielvolumina ermöglichen. KI-Modelle zur Autokonturierung haben das Potenzial, die Arbeit von Radioonkolog*Innen durch eine Teilautomatisierung zu beschleunigen, den Personalaufwand zu reduzieren und gleichzeitig eine erhöhte Standardisierung zu erreichen.

Our data show a NaCl induced intensification of intestinal tissue injury following RT. These findings can potentially pave the way for investigating the effect of high salt diet on intestinal radiotoxicity in clinical trials.