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Background: Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility.Methods: The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk.Discussion: With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time. [ABSTRACT FROM AUTHOR]

Background: Investigating dynamic changes in blood-parameters and weight in patients with locally advanced non-small cell lung cancer (NSCLC) receiving durvalumab maintenance therapy after chemoradiotherapy (cCRT). Laboratory outcomes were determined based on the number of durvalumab administrations received.Methods: Twenty-two patients completed platinum-based cCRT followed by maintenance treatment with durvalumab. Different parameters such as hemoglobin (Hb), leukocytes, Lactate dehydrogenase (LDH), C-reactive protein (CRP), body weight and albumin were analyzed before cCRT, after cCRT, 3, 6, 9 and 12 months after starting durvalumab maintenance.Results: Sixteen (72.7%) patients were male; twelve (54.5%) and fifteen (68.2%) patients had non-squamous histology and Union for International Cancer Control (UICC) stage IIIB-C disease, respectively. Median follow-up time was 24.4 months; 12- and 18-months- progression-free and overall-survival rates were 55.0% and 45.0 as well as 90.2 and 85.0%, respectively. During maintenance treatment Hb increased by 1.93 mg/dl (17.53%) after 9 months (p < 0.001) and 2.02 mg/dl (18.46%) after 12 months compared to the start of durvalumab (p < 0.001). LDH decreased by 29.86 U/l (- 11.74%) after 3 months (p = 0.022). Receipt of at least 12 cycles of durvalumab was beneficial in terms of Hb-recovery (Hb 6 months: 12.64 vs. 10.86 [mg/dl]; Hb 9 months: 13.33 vs 11.74 [mg/dl]; (p = 0.03)). Median weight change [kilogram (kg)] was + 6.06% (range: - 8.89 - + 18.75%) after 12 months. The number of durvalumab cycles significantly correlated with total weight gain [kg] (Spearman-Rho-correlation: r = 0.502*).Conclusion: In the investigated cohort, no severe hematologic toxicity occurred by laboratory blood tests within 1 year of durvalumab maintenance therapy after cCRT for unresectable stage III NSCLC. Receiving at least 12 cycles of durvalumab appears to have a significant effect on recovery of hemoglobin levels and body weight. [ABSTRACT FROM AUTHOR]

Background: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial.Methods: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale.Discussion: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life.Trial Registration: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213. [ABSTRACT FROM AUTHOR]

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included. [ABSTRACT FROM AUTHOR]

To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin's lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan–Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95% CI 72–102 months). Median single dose per fraction was 2.0 Gy (range 1.5–2 Gy) and median total dose was 30.6 Gy (range 16–45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95% CI 8.3–19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan–Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0 Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I–II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I–II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I–II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy. Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19–137). [ABSTRACT FROM AUTHOR]

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Purpose: Spatial distortions in magnetic resonance imaging (MRI) are mainly caused by inhomogeneities of the static magnetic field, nonlinearities in the applied gradients, and tissue‐specific magnetic susceptibility variations. These factors may significantly alter the geometrical accuracy of the reconstructed MR image, thus questioning the reliability of MRI for guidance in image‐guided radiation therapy. In this work, we quantified MRI spatial distortions and created a quantitative model where different sources of distortions can be separated. The generated model was then integrated into a four‐dimensional (4D) computational phantom for simulation studies in MRI‐guided radiation therapy at extra‐cranial sites. Methods: A geometrical spatial distortion phantom was designed in four modules embedding laser‐cut PMMA grids, providing 3520 landmarks in a field of view of (345 × 260 × 480) mm3. The construction accuracy of the phantom was verified experimentally. Two fast MRI sequences for extra‐cranial imaging at 1.5 T were investigated, considering axial slices acquired with online distortion correction, in order to mimic practical use in MRI‐guided radiotherapy. Distortions were separated into their sources by acquisition of images with gradient polarity reversal and dedicated susceptibility calculations. Such a separation yielded a quantitative spatial distortion model to be used for MR imaging simulations. Finally, the obtained spatial distortion model was embedded into an anthropomorphic 4D computational phantom, providing registered virtual CT/MR images where spatial distortions in MRI acquisition can be simulated. Results: The manufacturing accuracy of the geometrical distortion phantom was quantified to be within 0.2 mm in the grid planes and 0.5 mm in depth, including thickness variations and bending effects of individual grids. Residual spatial distortions after MRI distortion correction were strongly influenced by the applied correction mode, with larger effects in the trans‐axial direction. In the axial plane, gradient nonlinearities caused the main distortions, with values up to 3 mm in a 1.5 T magnet, whereas static field and susceptibility effects were below 1 mm. The integration in the 4D anthropomorphic computational phantom highlighted that deformations can be severe in the region of the thoracic diaphragm, especially when using axial imaging with 2D distortion correction. Adaptation of the phantom based on patient‐specific measurements was also verified, aiming at increased realism in the simulation. Conclusions: The implemented framework provides an integrated approach for MRI spatial distortion modeling, where different sources of distortion can be quantified in time‐dependent geometries. The computational phantom represents a valuable platform to study motion management strategies in extra‐cranial MRI‐guided radiotherapy, where the effects of spatial distortions can be modeled on synthetic images in a virtual environment. [ABSTRACT FROM AUTHOR]

Particle therapy treatment planning requires accurate volumetric maps of the relative stopping power, which can directly be acquired using proton computed tomography (pCT). With fluence-modulated pCT (FMpCT) imaging fluence is concentrated in a region-of-interest (ROI), which can be the vicinity of the treatment beam path, and imaging dose is reduced elsewhere. In this work we present a novel optimization algorithm for FMpCT which, for the first time, calculates modulated imaging fluences for joint imaging dose and image variance objectives. Thereby, image quality is maintained in the ROI to ensure accurate calculations of the treatment dose, and imaging dose is minimized outside the ROI with stronger minimization penalties given to imaging organs-at-risk. The optimization requires an initial scan at uniform fluence or a previous x-ray CT scan. We simulated and optimized FMpCT images for three pediatric patients with tumors in the head region. We verified that the target image variance inside the ROI was achieved and demonstrated imaging dose reductions outside of the ROI of 74% on average, reducing the imaging dose from 1.2 to 0.3 mGy. Such dose savings are expected to be relevant compared to the therapeutic dose outside of the treatment field. Treatment doses were re-calculated on the FMpCT images and compared to treatment doses re-recalculated on uniform fluence pCT scans using a 1% criterion. Passing rates were above 98.3% for all patients. Passing rates comparing FMpCT treatment doses to the ground truth treatment dose were above 88.5% for all patients. Evaluation of the proton range with a 1 mm criterion resulted in passing rates above 97.5% (FMpCT/pCT) and 95.3% (FMpCT/ground truth). Jointly optimized fluence-modulated pCT images can be used for proton dose calculation maintaining the full dosimetric accuracy of pCT but reducing the required imaging dose considerably by three quarters. This may allow for daily imaging during particle therapy ensuring a safe and accurate delivery of the therapeutic dose and avoiding excess dose from imaging. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an extremely challenging disease with a high mortality rate and a short overall survival time. The poor prognosis can be explained by aggressive tumor growth, late diagnosis, and therapy resistance. Consistent efforts have been made focusing on early tumor detection and novel drug development. Various strategies aim at increasing target specificity or local enrichment of chemotherapeutics as well as imaging agents in tumor tissue. Aptamers have the potential to provide early detection and permit anti-cancer therapy with significantly reduced side effects. These molecules are in-vitro selected single-stranded oligonucleotides that form stable three-dimensional structures. They are capable of binding to a variety of molecular targets with high affinity and specificity. Several properties such as high binding affinity, the in vitro chemical process of selection, a variety of chemical modifications of molecular platforms for diverse function, non-immunoreactivity, modification of bioavailability, and manipulation of pharmacokinetics make aptamers attractive targets compared to conventional cell-specific ligands. To explore the potential of aptamers for early diagnosis and targeted therapy of PDAC - as single agents and in combination with radiotherapy - we summarize the generation process of aptamers and their application as biosensors, biomarker detection tools, targeted imaging tracers, and drug-delivery carriers. We are furthermore discussing the current implementation aptamers in clinical trials, their limitations and possible future utilization. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an extremely challenging disease with a high mortality rate and a short overall survival time. The poor prognosis can be explained by aggressive tumor growth, late diagnosis, and therapy resistance. Consistent efforts have been made focusing on early tumor detection and novel drug development. Various strategies aim at increasing target specificity or local enrichment of chemotherapeutics as well as imaging agents in tumor tissue. Aptamers have the potential to provide early detection and permit anti-cancer therapy with significantly reduced side effects. These molecules are in-vitro selected single-stranded oligonucleotides that form stable three-dimensional structures. They are capable of binding to a variety of molecular targets with high affinity and specificity. Several properties such as high binding affinity, the in vitro chemical process of selection, a variety of chemical modifications of molecular platforms for diverse function, non-immunoreactivity, modification of bioavailability, and manipulation of pharmacokinetics make aptamers attractive targets compared to conventional cell-specific ligands. To explore the potential of aptamers for early diagnosis and targeted therapy of PDAC - as single agents and in combination with radiotherapy - we summarize the generation process of aptamers and their application as biosensors, biomarker detection tools, targeted imaging tracers, and drug-delivery carriers. We are furthermore discussing the current implementation aptamers in clinical trials, their limitations and possible future utilization. [ABSTRACT FROM AUTHOR]

Purpose: Approximately 40–70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). Methods: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. Results: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04–47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03–18.30). After a median follow-up of 16 months (1–57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. Conclusion: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months. [ABSTRACT FROM AUTHOR]

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Background: The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. 18F-GE-180, a novel TSPO ligand, has shown improved binding affinity and a high target-to-background contrast in patients with glioblastoma. However, the association of uptake characteristics on TSPO PET using 18F-GE-180 with the histological WHO grade and molecular genetic features so far remains unknown and was evaluated in the current study. Methods: Fifty-eight patients with histologically validated glioma at initial diagnosis or recurrence were included. All patients underwent 18F-GE-180 PET, and the maximal and mean tumour-to-background ratios (TBRmax, TBRmean) as well as the PET volume were assessed. On MRI, presence/absence of contrast enhancement was evaluated. Imaging characteristics were correlated with neuropathological parameters (i.e. WHO grade, isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and telomerase reverse transcriptase (TERT) promoter mutation). Results: Six of 58 patients presented with WHO grade II, 16/58 grade III and 36/58 grade IV gliomas. An (IDH) mutation was found in 19/58 cases, and 39/58 were classified as IDH-wild type. High 18F-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of 18F-GE-180-uptake and WHO grades was seen: WHO grade IV gliomas showed the highest uptake intensity compared with grades III and II gliomas (median TBRmax 5.15 (2.59–8.95) vs. 3.63 (1.85–7.64) vs. 1.63 (1.50–3.43), p < 0.001); this association with WHO grades persisted within the IDH-wild-type and IDH-mutant subgroup analyses (p < 0.05). Uptake intensity was also associated with the IDH mutational status with a trend towards higher 18F-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBRmax 4.67 (1.56–8.95) vs. 3.60 (1.50–7.64), p = 0.083); however, within each WHO grade, no differences were found (e.g. median TBRmax in WHO grade III glioma 4.05 (1.85–5.39) vs. 3.36 (2.32–7.64), p = 1.000). No association was found between uptake intensity and MGMT or TERT (p > 0.05 each). Conclusion: Uptake characteristics on 18F-GE-180 PET are highly associated with the histological WHO grades, with the highest 18F-GE-180 uptake in WHO grade IV glioblastomas and a PET-positive rate of 100% among the investigated high-grade gliomas. Conversely, all TSPO-negative cases were WHO grade II gliomas. The observed association of 18F-GE-180 uptake and the IDH mutational status seems to be related to the high inter-correlation of the IDH mutational status and the WHO grades. [ABSTRACT FROM AUTHOR]

Purpose: Patients with left-sided breast cancer frequently receive deep inspiration breath-hold (DIBH) radiotherapy to reduce the risk of cardiac side effects. The aim of the present study was to analyze intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice.Material and Methods: Overall, we analyzed 103 patients receiving left-sided breast cancer radiotherapy using a surface-guided DIBH technique. During each treatment session the vertical motion of the patient was continuously measured by a surface guided radiation therapy (SGRT) system and automated gating control (beam on/off) was performed using an audio-visual patient feedback system. Dose delivery was automatically triggered when the tracking point was within a predefined gating window. Intra-breath-hold stability and inter-fraction reproducibility across all fractions of the entire treatment course were analyzed per patient.Results: In the present series, 6013 breath-holds during beam-on time were analyzed. The mean amplitude of the gating window from the baseline breathing curve (maximum expiration during free breathing) was 15.8 mm (95%-confidence interval: [8.5-30.6] mm) and had a width of 3.5 mm (95%-CI: [2-4.3] mm). As a measure of intra-breath-hold stability, the median standard deviation of the breath-hold level during DIBH was 0.3 mm (95%-CI: [0.1-0.9] mm). Similarly, the median absolute intra-breath-hold linear amplitude deviation was 0.4 mm (95%-CI: [0.01-2.1] mm). Reproducibility testing showed good inter-fractional reliability, as the maximum difference in the breathing amplitudes in all patients and all fractions were 1.3 mm on average (95%-CI: [0.5-2.6] mm).Conclusion: The clinical integration of an optical surface scanner enables a stable and reliable DIBH treatment delivery during SGRT for left-sided breast cancer in clinical routine. [ABSTRACT FROM AUTHOR]

Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication. [ABSTRACT FROM AUTHOR]

Background and Purpose: Radiation necrosis is a possible adverse event after cranial radiation therapy and can cause severe symptoms, such as an increased intracranial pressure or neurological deterioration. The vascular endothelial growth factor (VEGF) inhibitor bevacizumab (BEV) has been shown to be a feasible therapeutic option for symptomatic radiation necrosis, either when traditional antiedematous steroid treatment fails, or as an alternative to steroid treatment. However, to the best of our knowledge, only one randomized study with a rather small cohort exists to prove a beneficial effect in this setting. Therefore, further real-life data are needed. This retrospective monocentric case study evaluates patients who received BEV due to radiation necrosis, with a specific focus on the respective clinical course.Methods: Using the internal database for pharmaceutical products, all patients who received BEV in our department were identified. Only patients who received BEV as symptomatic treatment for radiation necrosis were included. Patient characteristics, symptoms before, during, and after treatment, and the use of dexamethasone were evaluated using medical reports and systematic internal documentation. The symptoms were graded using CTCAE version 5.0 for general neurological symptoms. Symptoms were graded directly before each cycle and after the treatment (approximately 6 weeks). Additionally, the daily steroid dose was collected at these timepoints. Patients who either improved in symptoms, received less dexamethasone after treatment, or both were considered to have a benefit from the treatment.Results: Twenty-one patients who received BEV due to radiation necrosis were identified. For 10 patients (47.6%) symptoms improved and 11 patients (52.4%) remained clinically stable during the treatment. In 14 patients (66.7%) the dexamethasone dose could be reduced during therapy, 5 patients (23.8%) received the same dose of dexamethasone before and after the treatment, and 2 patients (9.5%) received a higher dose at the end of the treatment. According to this analysis, overall, 19 patients (90.5%) benefited from the treatment with BEV. No severe adverse effects were reported.Conclusion: BEV might be an effective and safe therapeutic option for patients with radiation necrosis as a complication after cranial radiation therapy. Patients seem to benefit from this treatment by improving symptomatically or through reduction of dexamethasone. [ABSTRACT FROM AUTHOR]

Background: PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as 18F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. 18F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic 18F-FET PET and contrast-enhanced MRI in patients with HGG.Methods: Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent 18F-GE-180 PET, dynamic 18F-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in 18F-GE-180 and 18F-FET PET. Dynamic 18F-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the Sørensen-Dice coefficient.Results: The median TBRmax tended to be higher in 18F-GE-180 PET compared to 18F-FET PET [4.58 (2.33-8.95) vs 3.89 (1.56-7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in 18F-GE-180 PET compared to 18F-FET PET [5.45 (2.56-8.95) vs 4.06 (1.56-4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33-6.81) vs 3.79 (2.01-7.15) p = 1.000]. Only 5/20 cases showed higher TBRmax in 18F-FET PET compared to 18F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in 18F-GE-180 PET correlated with TTPmin (p > 0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4-236.0) ml] compared to BTVFET [19.3 (0.7-150.2) ml; p = 0.062] with a moderate spatial overlap [median Sørensen-Dice coefficient 0.55 (0.07-0.85)]. In MRI, median VOLCE [9.7 (0.1-72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p < 0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01-0.48)] and BTVFET [0.38 (0.01-0.68)].Conclusion: PET with 18F-GE-180 and 18F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients' management. [ABSTRACT FROM AUTHOR]

Objective: The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. Methods: Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent F-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUV), maximal tumour-to-background ratio (TBR) and PET volume using different thresholds (SUV × 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI. Results: All gliomas were positive on F-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUV 0.47 (0.37-0.93), TBR 6.61 (3.88-9.07)). F-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Sørensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58. Conclusion: F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results. [ABSTRACT FROM AUTHOR]

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Background: To report our initial clinical experience with the novel surface imaging system Catalyst? (C-RAD AB, Sweden) in connection with an Elekta Synergy linear accelerator for daily patient positioning in patients undergoing radiation therapy. Methods: We retrospectively analyzed the patient positioning of 154 fractions in 25 patients applied to thoracic, abdominal, and pelvic body regions. Patients were routinely positioned based on skin marks, shifted to the calculated isocenter position and treated after correction via cone beam CT which served as gold standard. Prior to CBCT an additional surface scan by the Catalyst? system was performed and compared to a reference surface image cropped from the planning CT to obtain shift vectors for an optimal surface match. These shift vectors were subtracted from the vectors obtained by CBCT correction to assess the theoretical setup error that would have occurred if the patients had been positioned using solely the Catalyst? system. The mean theoretical set up-error and its standard deviation were calculated for all measured fractions and the results were compared to patient positioning based on skin marks only. Results: Integration of the surface scan into the clinical workflow did not result in a significant time delay. Regarding the entire group, the mean setup error by using skin marks only was 0.0 ± 2.1 mm in lateral, -0.4 ± 2. 4 mm in longitudinal, and 1.1 ± 2.6 mm vertical direction. The mean theoretical setup error that would have occurred using solely the Catalyst? was -0.1 ± 2.1 mm laterally, -1.8 ± 5.4 mm longitudinally, and 1.4 ± 3.2 mm vertically. No significant difference was found in any direction. For thoracic targets the mean setup error based on the Catalyst? was 0.6 ± 2.6 mm laterally, -5.0 ± 7.9 mm longitudinally, and 0.5 ± 3.2 mm vertically. For abdominal targets, the mean setup error was 0.3 ± 2.2 mm laterally, 2.6 ± 1.8 mm longitudinally, and 2.1 ± 5.5 mm vertically. For pelvic targets, the setup error was -0.9 ± 1.5 mm laterally, -1.7 ± 2.8 mm longitudinally, and 1.6 ± 2.2 mm vertically. A significant difference between Catalyst? and skin mark based positioning was only observed in longitudinal direction of pelvic targets. Conclusion: Optical surface scanning using Catalyst? seems potentially useful for daily positioning at least to complement usual imaging modalities in most patients with acceptable accuracy, although a significant improvement compared to skin mark based positioning could not be derived from the evaluated data. However, this effect seemed to be rather caused by the unexpected high accuracy of skin mark based positioning than by inaccuracy using the Catalyst?. Further on, surface registration in longitudinal axis seemed less reliable especially in pelvic localization. Therefore further prospective evaluation based on strictly predefined protocols is needed to determine the optimal scanning approaches and parameters. [ABSTRACT FROM AUTHOR]

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Background: There is a potential for adverse cardiovascular effects in long-term breast cancer survivors following adjuvant radiotherapy (RT). For this purpose, the deep inspiration breath-hold technique (DIBH) has been introduced into clinical practice, to maximally reduce the radiation dose to the heart. However, there are a variety of DIBH delivery techniques, patient positioning and visual patient feedback mechanisms. The aim of the present study was to evaluate the application of radiotherapy in DIBH using the CatalystTM/SentinelTM system, with a special emphasis on treatment planning and dosimetric plan comparison in free breathing (FB) and DIBH. Patients and methods: A total of 13 patients with left-sided breast cancer following breast conserving surgery were included in this prospective clinical trial. For treatment application the CatalystTM/SentinelTM system (C-RAD AB, Uppsala, Sweden) was used and gating control was performed by an audio-visual patient feedback system. CT and surface data were acquired in FB and DIBH and dual treatment plans were created using Pencil Beam and Collapsed Cone Convolution. Dosimetric output parameters of organs at risk were compared using Wilcoxon signed-rank test. Central lung distance (CLD) was retrieved from iViewTM portal images during treatment delivery. Results: The system contains a laser surface scanner (SentinelTM) and an optical surface scanner (CatalystTM) interconnected to the LINAC systems via a gating interface and allows for a continuous and touchless surface scanning. Overall, 225 treatment fractions with audio-visual guidance were completed without any substantial difficulties. Following initial patient training and treatment setup, radiotherapy in DIBH with the CatalystTM/ SentinelTM system was time-efficient and reliable. Following dual treatment planning for all patients, nine of 13 patients were treated in DIBH. In these patients, the reduction of the mean heart dose for DIBH compared to FB was 52% (2.73 to 1.31 Gy; p = 0.011). The maximum doses to the heart and LAD were reduced by 59% (47.90 to 19.74 Gy; p = 0.008) and 75% (38.55 to 9.66 Gy; p = 0.008), respectively. In six of the nine patients the heart completely moved out of the treatment field by DIBH. The standard deviation of the CLD varied between 0.12 and 0.29 cm (mean: 0.16 cm). Conclusion: The CatalystTM/SentinelTM system enabled a fast and reliable application and surveillance of DIBH in daily clinical routine. Furthermore, the present data show that using the DIBH technique during RT could significantly reduce high dose areas and mean doses to the heart. [ABSTRACT FROM AUTHOR]

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Purpose: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. Methods: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. Results: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. Conclusions: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa. [ABSTRACT FROM AUTHOR]

Background:The prediction of therapy response in head and neck squamous cell cancer (HNSCC) requires biomarkers, which are also a prerequisite for personalised therapy concepts. The current study aimed to identify therapy-responsive microRNAs (miRNAs) in the circulation that can serve as minimally invasive prognostic markers for HNSCC patients undergoing radiotherapy.Methods:We screened plasma miRNAs in a discovery cohort of HNSCC patients before therapy and after treatment. We further compared the plasma miRNAs of the patients to age- and sex-matched healthy controls. All miRNAs identified as biomarker candidates were then confirmed in an independent validation cohort of HNSCC patients and tested for correlation with the clinical outcome.Results:We identified a signature of eight plasma miRNAs that differentiated significantly (P=0.003) between HNSCC patients and healthy donors. MiR-186-5p demonstrated the highest sensitivity and specificity to classify HNSCC patients and healthy individuals. All therapy-responsive and patient-specific miRNAs in plasma were also detectable in tumour tissues derived from the same patients. High expression of miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p in the plasma correlated with worse prognosis.Conclusions:Circulating miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p represent the most promising markers for prognosis and therapy monitoring in the plasma of HNSCC patients. We found strong evidence that the circulating therapy-responsive miRNAs are tumour related and were able to validate them in an independent cohort of HNSCC patients. [ABSTRACT FROM AUTHOR]

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The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression. [ABSTRACT FROM AUTHOR]

Background: The role of postoperative radiotherapy in breast-conserving therapy is undisputed. However, optimal timing of adjuvant radiotherapy is an issue of ongoing debate. This retrospective clinical cohort study was performed to investigate the impact of a delay in surgery-radiotherapy intervals on local control and overall survival.Patients and Methods: Data from an unselected cohort of 1393 patients treated at a single institution over a 17-year period (1990-2006) were analyzed. Patients were assigned to two groups (CT+/CT-) according to chemotherapy status. A delay in the initiation of radiotherapy was defined as > 7 weeks (CT- group) and > 24 weeks (CT+ group).Results: The 10-year regional recurrence-free survival for the CT- and CT+ groups were 95.6 and 86.0 %, respectively. A significant increase in the median surgery-radiotherapy interval was observed over time (CT- patients: median of 5 weeks in 1990-1992 to a median of 6 weeks in 2005-2006; CT+ patients: median of 5 weeks in 1990-1992 to a median of 21 weeks in 2005-2006). There was no association between a delay in radiotherapy and an increased local recurrence rate (CT- group: p = 0.990 for intervals 0-6 weeks vs. ≥ 7 weeks; CT+ group: p = 0.644 for intervals 0-15 weeks vs. ≥ 24 weeks) or decreased overall survival (CT- group: p = 0.386 for intervals 0-6 weeks vs. ≥ 7 weeks; CT+ group: p = 0.305 for intervals 0-15 weeks vs. ≥ 24 weeks).Conclusion: In the present cohort, a delay of radiotherapy was not associated with decreased local control or overall survival in the two groups (CT-/CT+). However, in the absence of randomized evidence, delays in the initiation of radiotherapy should be avoided. [ABSTRACT FROM AUTHOR]

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Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. [ABSTRACT FROM AUTHOR]

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Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The phagocytic clearance of apoptotic cells is essential to prevent chronic inflammation and autoimmunity. The phosphatidylserine-binding protein milk fat globule-EGF factor 8 (MFG-E8) is a major opsonin for apoptotic cells, and MFG-E8−/− mice spontaneously develop a lupus-like disease. Similar to human systemic lupus erythematosus (SLE), the murine disease is associated with an impaired clearance of apoptotic cells. SLE is routinely treated with glucocorticoids (GCs), whose anti-inflammatory effects are consentaneously attributed to the transrepression of pro-inflammatory cytokines. Here, we show that the GC-mediated transactivation of MFG-E8 expression and the concomitantly enhanced elimination of apoptotic cells constitute a novel aspect in this context. Patients with chronic inflammation receiving high-dose prednisone therapy displayed substantially increased MFG-E8 mRNA levels in circulating monocytes. MFG-E8 induction was dependent on the GC receptor and several GC response elements within the MFG-E8 promoter. Most intriguingly, the inhibition of MFG-E8 induction by RNA interference or genetic knockout strongly reduced or completely abolished the phagocytosis-enhancing effect of GCs in vitro and in vivo. Thus, MFG-E8-dependent promotion of apoptotic cell clearance is a novel anti-inflammatory facet of GC treatment and renders MFG-E8 a prospective target for future therapeutic interventions in SLE. [ABSTRACT FROM AUTHOR]

Background Existential behavioural therapy (EBT) was developed to support informal caregivers of palliative patients in the last stage of life and during bereavement as a manualised group psychotherapy comprising six sessions. We tested the effectiveness of EBT on mental stress and quality of life (QOL). Methods Informal caregivers were randomly assigned (1:1) to EBT or a treatment-as-usual control group using computer-generated numbers in blocks of 10. Primary outcomes were assessed with the Brief Symptom Inventory (subscales somatisation, anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at baseline, pre-treatment, post-treatment and follow-ups after 3 and 12 months. Treatment effects were assessed with a multivariate analysis of covariance. Results Out of 160 relatives, 81 were assigned to EBT and 79 to the control group. Participants were 54.5 ± 13.2 years old; 69.9% were female. The multivariate model was significant for the pre-/post-comparison ( p = 0.005) and the pre-/12-month comparison ( p = 0.05) but not for the pre-/3-month comparison. Medium to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12-month follow-up. No adverse effects of the intervention were observed. Conclusion Existential behavioural therapy appears to exert beneficial effects on distress and QOL of informal caregivers of palliative patients. Further longitudinal evidence is needed to confirm these findings. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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The purpose of this paper is to understand intrafraction movement as a stochastic process driven by random external forces. The hypothetically proposed three-dimensional random walk model has significant impact on optimal PTV margins and offers a quantitatively correct explanation of experimental findings. Properties of the random walk are calculated from first principles, in particular fraction-average population density distributions for displacements along the principal axes. When substituted into the established optimal margin recipes these fraction-average distributions yield safety margins about 30% smaller as compared to the suggested values from end-of-fraction Gaussian fits. Stylized facts of a random walk are identified in clinical data, such as the increase of the standard deviation of displacements with the square root of time. Least squares errors in the comparison to experimental results are reduced by about 50% when accounting for non-Gaussian corrections from the random walk model. [ABSTRACT FROM AUTHOR]

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