Juergen debus

Simple Summary This research contributes to the ongoing scientific investigation of the benefits of particle therapy for left-sided breast cancer and presents the potential of the novel application of helium ion therapy. The results obtained reveal a significant improvement in target coverage for both proton and helium ion therapy compared to Volumetric Modulated Arc Therapy (VMAT). Furthermore, particle therapy leads to an increase sparing of surrounding healthy tissues, including the heart, the left anterior descending artery and the ipsilateral lung. Additionally, with the reduction of the low-dose exposure to the right side of the chest, the risk for secondary malignancies with particle therapy is potentially minimized compared to VMAT. Compared to proton therapy, helium could additionally reduce the risk of pneumonitis. Abstract Proton therapy presents a promising modality for treating left-sided breast cancer due to its unique dose distribution. Helium ions provide increased conformality thanks to a reduced lateral scattering. Consequently, the potential clinical benefit of both techniques was explored. An explorative treatment planning study involving ten patients, previously treated with VMAT (Volumetric Modulated Arc Therapy) for 50 Gy in 25 fractions for locally advanced, node-positive breast cancer, was carried out using proton pencil beam therapy with a fixed relative biological effectiveness (RBE) of 1.1 and helium therapy with a variable RBE described by the mMKM (modified microdosimetric kinetic model). Results indicated that target coverage was improved with particle therapy for both the clinical target …

(1) Background: External beam radiotherapy (EBRT) and concurrent chemotherapy, followed by brachytherapy (BT), offer a standard of care for patients with locally advanced cervical carcinoma. Conventionally, large safety margins are required to compensate for organ movement, potentially increasing toxicity. Lately, daily high-quality cone beam CT (CBCT)-guided adaptive radiotherapy, aided by artificial intelligence (AI), became clinically available. Thus, online treatment plans can be adapted to the current position of the tumor and the adjacent organs at risk (OAR), while the patient is lying on the treatment couch. We sought to evaluate the potential of this new technology, including a weekly shuttle-based 3T-MRI scan in various treatment positions for tumor evaluation and for decreasing treatment-related side effects. (2) Methods: This is a prospective one-armed phase-II trial consisting of 40 patients with cervical carcinoma (FIGO IB-IIIC1) with an age ≥ 18 years and a Karnofsky performance score ≥ 70%. EBRT (45–50.4 Gy in 25–28 fractions with 55.0–58.8 Gy simultaneous integrated boosts to lymph node metastases) will be accompanied by weekly shuttle-based MRIs. Concurrent platinum-based chemotherapy will be given, followed by 28 Gy of BT (four fractions). The primary endpoint will be the occurrence of overall early bowel and bladder toxicity CTCAE grade 2 or higher (CTCAE v5.0). Secondary outcomes include clinical feasibility, quality of life, and imaging-based response assessment.

BackgroundThe extended acquisition times required for MRI limit its availability in resource-constrained settings. Consequently, accelerating MRI by undersampling k-space data, which is necessary to reconstruct an image, has been a long-standing but important challenge. We aimed to develop a deep convolutional neural network (dCNN) optimisation method for MRI reconstruction and to reduce scan times and evaluate its effect on image quality and accuracy of oncological imaging biomarkers.MethodsIn this multicentre, retrospective, cohort study, MRI data from patients with glioblastoma treated at Heidelberg University Hospital (775 patients and 775 examinations) and from the phase 2 CORE trial (260 patients, 1083 examinations, and 58 institutions) and the phase 3 CENTRIC trial (505 patients, 3147 examinations, and 139 institutions) were used to develop, train, and test dCNN for reconstructing MRI from …

This article reviews recent and ongoing developments in multiparametric magnetic resonance imaging (mpMRI) of the prostate. Advances in T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopic imaging are described along with advances related to radiofrequency coils and imaging at high magnetic field. As mpMRI is increasingly becoming routine in various aspects of clinical prostate cancer management, its role in detection, localization, staging, assessment of aggressiveness, and active surveillance is discussed. Combined with growing clinical adoption of the techniques already at hand, continual optimization of acquisition techniques and image interpretation schemes will further strengthen the role of mpMRI as an important diagnostic test in prostate cancer management.

BackgroundSolitary fibrous tumors (SFT) of the central nervous system are rare and treatment options are not well established. The aim of this study was to evaluate the clinical outcomes of radiotherapy (RT) and re-radiotherapy (re-RT) for de novo intracranial SFT and recurrent intracranial SFT.MethodsThis retrospective study analyzed efficacy and toxicity of different RT modalities in patients who received radiotherapy (RT) for intracranial SFT at Heidelberg University Hospital between 2000 and 2020 following initial surgery after de novo diagnosis (“primary group”). We further analyzed the patients of this cohort who suffered from tumor recurrence and received re-RT at our institution (“re-irradiation (re-RT) group”). Median follow-up period was 54.0 months (0–282) in the primary group and 20.5 months (0–72) in the re-RT group. RT modalities included 3D-conformal RT (3D-CRT), intensity-modulated RT (IMRT …

Background The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. Purpose In MR‐guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR‐guided particle therapy was developed with minimal ion …

Simple Summary Capsular contracture is one of the substantial complications of breast cancer patients undergoing post-mastectomy radiotherapy (PMRT) following an immediate implant-based breast reconstruction (IBR). Until now, there has been no therapeutic target to directly treat or manage capsular contracture, which emphasizes the importance of its prevention. A further assessment of risk factors and dosimetric characteristics is needed to minimize the risk and choose the optimal therapy approach. Abstract Our study aims to identify the risk factors and dosimetry characteristics associated with capsular contracture. Methods: We retrospectively analyzed 118 women with breast cancer who underwent PMRT following an IBR between 2010 and 2022. Patients were treated with PMRT of 50.0–50.4 Gy in 25–28 fractions. Capsular contracture was categorized according to the Baker Classification for Reconstructed Breasts. Results: After a median follow-up of 22 months, the incidence of clinically relevant capsular contracture (Baker III–IV) was 22.9%. Overall, capsular contracture (Baker I–IV) occurred in 56 patients (47.5%) after a median of 9 months after PMRT. The rate of reconstruction failure/implant loss was 25.4%. In the univariate analysis, postoperative complications (prolonged pain, prolonged wound healing, seroma and swelling) and regional nodal involvement were associated with higher rates of capsular contracture (p = 0.017, OR: 2.5, 95% CI: 1.2–5.3 and p = 0.031, respectively). None of the analyzed dosimetric factors or the implant position were associated with a higher risk for capsular …

PurposeTo assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets.Materials and methodsMice bearing xenografts (n = 59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n = 242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C). Gene expression analysis was conducted using GeneChip Human Transcriptome Arrays. Xenografts were stratified based on their molecular subtypes and previously established gene classifiers. The dose to control 50 % of tumours (TCD50) was compared between these groups. Using differential gene expression …

PurposeNode-positive prostate cancer is a potentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques.MethodsA total of 40 treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34 fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality …

Ion-beam radiotherapy is a growing cancer treatment modality because it offers a superior dose distribution in the patient compared with conventional radiotherapy using X-rays. Thanks to their versatility, application-specific integrated circuits (ASIC) increasingly gain interest for research into ion imaging and ion-beam characterisation. Timepix3 is a hybrid semiconductor pixel detector, which offers nanosecond time binning as well as dead-time-free and noise-free data-driven readout at a pixel pitch of 55 µm × 55 µm. In this work, a novel 4-chip Timepix3 mini-tracker (quad module) was characterised in a therapeutic proton beam. The quad module has two detection layers equipped with two Timepix3 chips each, which are stacked like a particle telescope at a distance of 20.3 mm. In a detection layer, two Timepix3 chips share the same sensitive silicon sensor. The surface area of the silicon sensor is approximately …

Simple Summary Daily adaptation of the radiation plan on the treatment couch has the potential to reduce toxicity to healthy tissue while maintaining the dose or even enabling higher doses applied to cancerous tissue. However, current approaches either require more time and personnel to perform plan adaptation or lack resolution for soft tissue contrast. The Ethos radiotherapy device utilizes artificial intelligence and machine learning to allow rapid plan adaptation based on the daily anatomy. We here outline the first workflow in which we combine the Ethos machine with weekly magnetic resonance imaging, the gold standard for soft tissue resolution. This is facilitated by a shuttle system that allows patients to be transported from one device to the other in treatment position. Abstract Purpose: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance. Methods: From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system …

Background and Purpose After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. Methods In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors.Results Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98 …

While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring. In total, 60 patients with meningiomas and an indication of radiotherapy (RT) and macroscopic tumor on the planning MRI will be enrolled. Blood samples will be obtained before the start, during, and after radiotherapy, as well as during clinical follow-up every 6 months. Extracellular vesicles will be isolated from the …

IntroductionPatient specific quality assurance (QA) in MR-Linacs can be performed with MR-compatible ion chamber arrays. However, the presence of a static magnetic field can alter the angular response of such arrays substantially. This works investigates the suitability of two ion chamber arrays, an air-filled and a liquid-filled array, for patient specific QA at a 0.35 T MR-Linac using a static phantom.MethodsIn order to study the angular response, the two arrays were placed in a static, solid phantom and irradiated with 9.96 × 9.96 cm2 fields every 10° beam angle at a 0.35 T MR-Linac. Measurements were compared to the TPS calculated dose in terms of gamma passing rate and relative dose to the central chamber. 20 patient specific quality assurance plans were measured using the liquid-filled array.ResultsThe air-filled array showed asymmetric angular response changes of central chamber dose of up to 18 …

Background Monte Carlo (MC) simulations are considered the gold‐standard for accuracy in radiotherapy dose calculation; so far however, no commercial treatment planning system (TPS) provides a fast MC for supporting clinical practice in carbon ion therapy. Purpose To extend and validate the in‐house developed fast MC dose engine MonteRay for carbon ion therapy, including physical and biological dose calculation. Methods MonteRay is a CPU MC dose calculation engine written in C++ that is capable of simulating therapeutic proton, helium and carbon ion beams. In this work, development steps taken to include carbon ions in MonteRay are presented. Dose distributions computed with MonteRay are evaluated using a comprehensive validation dataset, including various measurements (pristine Bragg peaks, spread out Bragg peaks in water and behind an anthropomorphic phantom) and simulations of …

Purpose: Recent experimental studies and clinical trial results might indicate that - at least for some indications - continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy.Methods: Treatment plans of 91 prostate tumor patients (proton: 46, carbon ions: 45) applying 66GyRBE [RBE=1.1 for protons and LEM-I, (α/β)x=2.0Gy, for carbon ions] in 20 fractions were recalculated using mMKM ((α/β)x=3.1Gy). Based solely on the response data of photon-irradiated patient groups stratified according to risk and usage of ADT, we derived parameters for an mMKM-based Poisson-TCP model …

PurposeRadiation-induced cerebral contrast enhancements (RICE) are frequent after photon and particularly proton radiation therapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up.Methods and MaterialsWe analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiation therapy (54 Gy relative biological effectiveness) for LGG from 2010 to 2020 who were followed with serial clinical examinations and magnetic resonance imaging for a median 5.6 years.ResultsClassical vascular risk factors including age (≥50 vs <50 years: 1.6-fold; P = .0024), hypertension (2.7-fold; P = .00012), and diabetes (11.7-fold; P …

Simple Summary Pancreatic cancer is one of the most aggressive cancers. New treatment strategies such as particle radiotherapy could offer a way to overcome the limitations in treatment caused by the characteristics of pancreatic cancer. Helium ions represent an attractive therapy option because of their physical and radiobiological features. The aim of this study is to investigate the efficacy of helium ion irradiation in pancreatic cancer cell lines and whether a combination with chemotherapy could increase its efficacy. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment. Abstract Background: Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome …

PurposeAfter radical prostatectomy (RP), adjuvant or salvage radiation treatment in node-positive prostate cancer is offered to prevent systemic disease. Prospective long-term survival and toxicity data on patients with radiation for nodal disease are still scarce. This study evaluates safety and feasibility of salvage radiation therapy to the pelvic lymph nodes in node-positive prostate cancer after RP.Methods and MaterialsBetween 2009 and 2018, 78 patients with lymph node recurrence after RP (PLATIN-4 trial) or after RP and prostate bed radiation therapy (PLATIN-5 trial) were treated with salvage pelvic lymph node radiation therapy with boost to the involved nodes as field abutment (PLATIN-5) and boost to the prostate bed (PLATIN-4). Androgen deprivation therapy was started 2 months before radiation and recommended for 24 months. The primary endpoint was safety and feasibility of the intensity modulated …

Method Consecutive series of four patients with intracochlear schwannomas treated at our institution since 5/2021 by intracochlear spacer insertion through the tumor, definitive radiation therapy, and CI at least one year later.Results All patients underwent standard work-up for CI according to the national guidelines, followed by intracochlear insertion of an MED-ELÒ ANTS (Auditory Nerve Test System) electrode confirming auditory nerve function by E-BERA, followed by insertion of an MED-ELÒ insertion probe as spacer. Four weeks later, all patients received stereotactic radiosurgery (SRS) with a dose 12 Gy to the 80% isodose. All patient underwent clinical and MRI follow-up for at least one year. Two patients received MED-ELÒ Synchrony 2 Flex-28 implants after confirmation of stable auditory nerve function by E-BERA utilizing MED-ELÒ ANTS. Two month after implant activation one patient already has an …

BackgroundApart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer.Materials and methods32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models.ResultsIn 152 …

Objective The field of radiotherapy is highly marked by the lack of datasets even with the availability of public datasets. Our study uses a very limited dataset to provide insights on essential parameters needed to automatically and accurately segment individual bones on planning CT images of head and neck cancer patients. Approach The study was conducted using 30 planning CT images of real patients acquired from 5 different cohorts. 15 cases from 4 cohorts were randomly selected as training and validation datasets while the remaining were used as test datasets. Four experimental sets were formulated to explore parameters such as background patch reduction, class-dependent augmentation and incorporation of a weight map on the loss function. Main results Our best experimental scenario resulted in a mean Dice score of 0.93±0.06 for other bones (skull, mandible, scapulae, clavicles, humeri and hyoid), 0 …

PurposeSurgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks.MethodsPatients receiving surgery for recurrent glioma WHO grade 2–4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed.ResultsBetween 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n= 13; 19%) and …

Background & AimsInoperable hepatocellular carcinoma (HCC) can be treated by Stereotactic Body Radiotherapy. Carbon ion radiotherapy (CIRT) can superiorly spare non-tumorous liver. High linear energy transfer could foster therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Due to different radiobiological models and different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the Local Effect Model (LEM) I.MethodsCIRT was performed every other day in four fractions with Relative Biological Effectiveness (RBE)-weighted fraction doses of 8.1-10.5 Gy (total doses 32.4-42.0 Gy (RBE)). Dose escalation was performed in five dose levels with at least …

Background Interpatient variation of tumor radiosensitivity is rarely considered during the treatment planning process despite its known significance for the therapeutic outcome. Purpose To apply our mechanistic biophysical model to investigate the biological robustness of carbon ion radiotherapy (CIRT) against DNA damage repair interference (DDRi) associated patient‐to‐patient variability in radiosensitivity and its potential clinical advantages against conventional radiotherapy approaches. Methods and Materials The “UNIfied and VERSatile bio response Engine” (UNIVERSE) was extended by carbon ions and its predictions were compared to a panel of in vitro and in vivo data including various endpoints and DDRi settings within clinically relevant dose and linear energy transfer (LET) ranges. The implications of UNIVERSE predictions were then assessed in a clinical patient scenario considering DDRi …

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. The study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). The primary endpoint was the 3-year progression-free survival (PFS), and the secondary endpoints included overall survival, safety and treatment toxicities. Results With a …

BackgroundDue to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial.Materials and methodsA total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and …

Background Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the local failure (LF) risk persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. Methods Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients (two centers); external test cohort: 99 patients (five centers)). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameters previously determined by internal 5-fold cross-validation and tested on the external test set. Results The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. Conclusions A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow …

TPS431Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody …

Simple Summary Around 30% of the patients receiving intracranial particle therapy develop radiogenic reactions of the brain. There are a wide range of symptoms, ranging from asymptomatic blood–brain barrier disorders to life-threatening brain necrosis. The aim of our retrospective study is to assess the patterns of occurrence in patients treated for skull base chordoma and chondrosarcoma with protons or carbon ions. Furthermore, we aimed to develop a prognostic model for the prediction of radiation reactions. Abstract Background: The current study aims to evaluate the occurrence of temporal lobe reactions and identify possible risk factors for patients who underwent particle therapy of the skull base. Methods: 244 patients treated for skull base chordoma (n = 144) or chondrosarcoma (n = 100) at the Heidelberg Ion Beam Therapy Center (HIT) using a raster scan technique, were analyzed. Follow-up MRI-scans were matched with the initial planning images. Radiogenic reactions were contoured and analyzed based on volume and dose of treatment. Results: 51 patients with chordoma (35.4%) and 30 patients (30%) with chondrosarcoma experienced at least one temporal lobe reaction within the follow-up period (median 49 months for chondrosarcoma, 62 months for chordoma). Age, irradiated volume, and dose values were significant risk factors for the development of temporal lobe reactions with the highest significance for the value of DMax-7 being defined as the dose maximum in the temporal lobe minus the 7cc with the highest dose (p = 0.000000000019; OR 1.087). Conclusion: Temporal lobe reactions …

BackgroundTo assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction.MethodsThis multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65–92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated.ResultsThirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by …

Zielsetzung Die auf dem chemischen Austauschsättigungstransfer („chemical exchange saturation transfer “) von Protonen basierende CEST-Bildgebung kann eingesetzt werden, um Peptide und halbfeste Makromoleküle zur Erzeugung von endogenen MRT-Kontrasten zu verwenden. CEST-Kontraste sind jedoch stark von der Feldstärke und den Metriken abhängig, die für die Rekonstruktion der Kontraste aus dem Z-Spektrum verwendet werden. Ziel dieser Studie war daher, den prädiktiven Wert verschiedener CEST-Kontraste des Amid-Protonen-Transfers (APT) und des semisoliden Magnetisierungs-Transfers (ssMT) in einer größeren Kohorte von Patienten mit Gliomen vor Strahlentherapie bei klinischen Feldstärken von 3T zu vergleichen.Material und Methoden Bei 78 Patienten, die wegen eines Glioms biopsiert oder operiert wurden, wurde eine 3T-CEST-MRT des APT und ssMT unmittelbar vor Beginn der …

PurposeRadiation treatment of sinonasal malignancies is a challenging task due to proximity to critical structures of the head and neck and skull base. Local tumor control is highly dose-dependent, but dose application is limited due to accompanying toxicity and dose constraints. To evaluate the toxicity and efficacy of combined radiation treatment with intensity-modulated radiation therapy (IMRT) and carbon ion boost, we conducted a prospective phase 2 IMRT-Heidelberg Ion-Beam Therapy Sinonasal Tumors (HIT–SNT) trial.Methods and MaterialsBetween 2011 and 2019, we treated 35 patients with histologically proven, incompletely resected or inoperable adeno- (51%) or squamous cell carcinoma (49%) of the paranasal sinuses with combined IMRT (50 Gy) and carbon ion boost (24 Gy relative biologic effectiveness) to a total dose of 74 Gy.ResultsAcute mucositis Common Terminology Criteria for Adverse …

PurposeThe European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET.MethodsFor this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients.ResultsThe median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis …

Stopping power ratio (SPR) maps are needed for dose deposition calculations and are typically estimated from single energy CT (SECT) in clinical routine. SECT-based SPR conversion leads to large variability due to the one-to-one relationship assumed by the conversion method. Dual-energy CT (DECT) involving the acquisition of two energy spectra captures both material-specific information and tissue characterization which is essential for an accurate SPR map conversion. The goal of this study is to train a U-Net architecture to generate pseudo-SPR map from MRI (Dixon) using a DECT-converted SPR map. The model performance was validated using Head & Neck cohort of 16 patients with paired MRI and SPR maps. The proposed solution achieved a mean absolute error (MAE) and peak-signal-to-noise-ratio (PSNR) of 19.41 ± 8.67 HU and 58.76 ± 2.17 dB respectively for all test cases. From observation, the …

QLHLYJHNOCILIT-UHFFFAOYSA-N 4-o-(2, 5-dioxopyrrolidin-1-yl) 1-o-[2-[4-(2, 5-dioxopyrrolidin-1-yl) oxy-4-oxobutanoyl] oxyethyl] butanedioate Chemical compound O= C1CCC (= O) N1OC (= O) CCC (= O) OCCOC (= O) CCC (= O) ON1C (= O) CCC1= O QLHLYJHNOCILIT-UHFFFAOYSA-N 0.000 description 4

Purpose/Objective(s)Radiotherapyof the resection cavity following brain metastasis (BM) resection improves local control. Single-session stereotactic radiosurgery (SRS) can reduce toxicity compared to whole-brain radiotherapy (WBRT). Hypofractionated stereotactic radiotherapy (HFSRT) can deliver a higher biologically effective dose, potentially improving local control over SRS. The ESTRON trial compared HFSRT of the cavity with post-operative WBRT in patients with 1-10 BM.Materials/MethodsEligible patients with 1-10 newly diagnosed BM and following the resection of one BM regardless of histology were randomized 1:1 to receive HFSRT of the cavity and SRS of all unresected lesions or WBRT. A dose of 7 × 5 Gy was delivered to the cavity with a safety margin of 3-4 mm based on highly sensitive and standardized magnetic resonance imaging (MRI). The primary endpoint was intracranial control. Key …

Objective We propose an integration scheme for a biomechanical motion model into a deformable image registration. We demonstrate its accuracy and reproducibility for adaptive radiation therapy in the head and neck region. Approach The novel registration scheme for the bony structures in the head and neck regions is based on a previously developed articulated kinematic skeleton model. The realized iterative single-bone optimization process directly triggers posture changes of the articulated skeleton, exchanging the transformation model within the deformable image registration process. Accuracy in terms of target registration errors in the bones is evaluated for 18 vector fields of three patients between each planning CT and six fraction CT scans distributed along the treatment course. Main results The median of target registration error distribution of the landmark pairs is 1.4±0.3 mm. This is sufficient accuracy …

Objective:Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset.Summary Background Data:IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another.Methods:Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type …

ResultsIn the preliminary analysis we included the first thirteen patients, seven had the tumor in the proximal third of the esophagus, one in the middle and five in the distal third. The analysis showed the smallest mean GTV volume when contoured on MR alone (39.2 cm3) and the largest on PET CT alone (54.9 cm3). We observed the best agreement when contouring on all three imaging modalities (CIgen 0.69), the worst agreement on CT and MR alone, CIgen 0.61 for both (table 1).

ConclusionThe introduction of NIC+ TRI resulted in clinically acceptable dose deviations for all investigated treatment sites. The updated modelling of nuclear interactions and fragment spectra provided more realistic results on energy deposition and LETd maps, particularly in the medium and low dose regions. Further investigation is needed to assess the deviations with respect to the FLUKA MC code.

Simple Summary Retroperitoneal sarcomas represent a very rare entity. The most common pattern of recurrence and cause of death is local recurrence, and the rates of locoregional recurrences are high even at high-volume centers. In contrast to soft-tissue sarcomas of the extremities, the role of radiotherapy in retroperitoneal sarcoma is not fully established. The aim of the study was to report the results of a prospective single-center trial for preoperative dose-escalated intensity-modulated radiotherapy with an intraoperative boost in patients with retroperitoneal sarcoma after all surviving patients had achieved a follow-up of at least 60 months. The primary endpoint of a 5-year local control of 70% was not met; the local control of the cohort was 59.6%. In those patients who received a dose > 50 Gy and the intraoperative boost, the local control was promising at 64.8%. Abstract Background: To report the final results of a prospective, one-armed, single-center phase I/II trial (NCT01566123). Methods: Between 2007 and 2017, 37 patients with primary or recurrent (N = 6) retroperitoneal sarcomas were enrolled. Treatment included preoperative IMRT of 45–50 Gy with a simultaneous integrated boost of 50–56 Gy, surgery and IORT. The primary endpoint was local control (LC) at 5 years. The most common histology was dedifferentiated liposarcoma (51%), followed by leiomyosarcoma (24%) and well-differentiated liposarcoma (14%). The majority of lesions were high-grade (FNCLCC G1: 30%, G2: 38%, G3: 27%, two missing). Five patients were excluded from LC analysis per protocol. Results: The minimum follow-up of …

Since the development of fibroblast activation protein–targeted radiopharmaceuticals, 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has been found to be suitable for detecting primary and metastatic lesions in many types of tumors. However, there is currently a lack of reliable data regarding the clinical impact of this family of probes. To address this gap, the present study aimed to analyze the clinical impact of 68Ga-FAPI PET/CT by examining a large cohort of patients with various tumors. Methods In total, 226 patients (137 male and 89 female) were included in this retrospective analysis. Pancreatic cancer and head and neck cancers were the most common tumor types in this cohort. TNM stage and oncologic management were initially determined with gold standard imaging, and these results were compared with 68Ga-FAPI PET/CT. Changes were classified as major and minor. Results For 42% of all …

Background/PurposeThe present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET).Materials and MethodsThis retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint.ResultsThe median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive …

Background:To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19–197 months). Statistical analysis used Kaplan–Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03.Results:The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P< 0.00005). Patients< 65 years …

Simple Summary Advanced juvenile nasopharyngeal angiofibroma (JNA) can present a considerable therapeutic challenge. Photon radiotherapy has been recognized as an effective treatment approach for recurrent or inoperable advanced JNA in an additive or definitive setting. However, due to the benign nature of JNA and the young age of the affected patients, concerns about long-term radiation-induced morbidity have led to a certain hesitance towards this treatment modality. Proton therapy (PRT) presents a promising alternative for treating benign conditions in young patients, yet there remains a gap in the literature regarding its application to JNA. We retrospectively examined the outcomes of patients with JNA who underwent PRT in our center and evaluated the dosimetric advantages of PRT over conformal radiotherapy. This study is the first report investigating PRT for advanced JNA, highlighting PRT’s safety and effectiveness as a viable therapeutic option. Dosimetric and complication risk evaluations suggest that PRT holds the potential to reduce long-term radiation-induced complications, including the development of secondary neoplasms or decline in neurocognitive function. Abstract Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 …

BackgroundCombined, platinum-based thoracic chemoradiotherapy (TCR) is the current state-of-the-art treatment for patients with limited disease (LD) small-cell lung cancer (SCLC). There is only limited data available regarding the effect of comorbidities on survival following TRC. The purpose of this study is to assess the age-adjusted Charlson comorbidity index (ACCI) as a predictor of overall survival in LD-SCLC patients undergoing TCR.Patients and methodsWe retrospectively analyzed 367 SCLC patients diagnosed with LD-SCLC who received TCR between 2003 and 2017. We evaluated the ACCI (n = 348) as a predictor of overall survival (OS). In this cohort, 322 patients (88%) received platinum-based TCR (either cisplatin or carboplatin), and 37 (10%) patients received vincristine based TCR. Median radiation dose was 60 Gy (range 24–66 Gy). Additionally, 83% of patients (n = 303) received prophylactic …

Purpose/Objective(s)Although SRT is preferred for limited brain metastases from most histologies, WBRT has remained the standard of care for patients with SCLC. It remains unclear whether the benefit of WBRT to SRT for the intracerebral tumor control outweighs the potential neurocognitive risks in SCLC patients.Materials/MethodsThis pilot-trial is a single-center prospective, randomized, two-arm Phase II study. The primary endpoint is neurocognition after cerebral irradiation in SCLC patients treated with WBRT or SRT (radiosurgery (SRS) with 20 Gy or 18 Gy or hypofractionated SRT with 30 Gy in 5 Gy fractions for lesions >3 cm) defined as a drop of at least 5 points from baseline in Hopkins Verbal Learning Test–Revised (HVLT-R) total recall subscale at 3 months after baseline. Eligible patients had histologically confirmed SCLC, MRI-confirmed cerebral metastasis (not resected, maximum number of 10 …

Simple Summary Localized renal cell carcinoma (RCC) has an excellent prognosis. However, once metastatic, patient prognosis declines significantly. There is a rare patient subgroup with localized RCC stage T1 with distant metastasis (M1) and no lymph node involvement (N0). In this study, the survival of patients diagnosed with clear cell RCC (ccRCC) stage T1N0M1 were evaluated in comparison to ccRCC patients stage T1 without metastases (N0M0). As expected, stage T1N0M1 ccRCC patients showed a significantly worse outcome than stage T1N0M0 patients. To further characterize tumor characteristics of stage T1N0M1 ccRCC patients, CD8+ tumor infiltrating lymphocytes (TILs) were analyzed, as it is known that a number of CD8+ TILs is associated with a worse prognosis. It could be shown that tumor specimens from stage T1N0M1 ccRCC patients harbor a substantially higher number of CD8+ TILs than specimens from stage T1N0M0 ccRCC patients, thus resembling advanced stage ccRCC. Nevertheless, long-term survival of stage T1N0M1 ccRCC patients is possible. Abstract Metastatic renal cell carcinoma (RCC) is among the most lethal urological malignancies. However, small, localized RCCs (≤7 cm, stage T1) have an excellent prognosis. There is a rare patient subgroup diagnosed with synchronous distant metastasis (T1N0M1), of which very little is known in terms of survival outcomes and underlying disease biology. Herein, we examined the long-term survival of 27 patients with clear cell RCC (ccRCC) stage T1N0M1 in comparison to 18 patients without metastases (T1N0M0). Tumor tissue …

Objectives To evaluate oral sequelae after head and neck radiotherapy (RT) when using two different types of intraoral appliances. Thermoplastic dental splints (active control) protect against backscattered radiation from dental structures. Semi-individualized, 3D-printed tissue retraction devices (TRDs, study group) additionally spare healthy tissue from irradiation. Materials and Methods A total of 29 patients with head and neck cancer were enrolled in a randomized controlled pilot trial and allocated to receive TRDs (n = 15) or conventional splints (n = 14). Saliva quality and quantity (Saliva-Check, GC), taste perception (Taste strips, Burghart-Messtechnik), and oral disability (JFLS-8, OHIP-14, maximum mouth opening) were recorded before and 3 months after RT start. Radiotherapy target volume, modality, total dose, fractionation, and imaging guidance were case-dependent. To evaluate intra-group developments between baseline and follow-up, nonparametric Wilcoxon tests were performed. Mann-Whitney-U tests were applied for inter-group comparisons. Results At follow-up, taste perception was unimpaired (median difference in the total score; TRDs: 0, control: 0). No significant changes were found regarding oral disability. Saliva quantity (stimulated flow) was significantly reduced with conventional splints (median −4 mL, p = 0.016), while it decreased insignificantly with TRDs (median −2 mL, p = 0.07). Follow-up was attended by 9/15 study group participants (control 13/14). Inter-group comparisons showed no significant differences but a tendency towards a better outcome for disability and saliva quality in the intervention group …

Background/Aim Adjuvant radiotherapy is an integral part of the interdisciplinary curative treatment of breast cancer. We aimed to examine the long-term clinical results of helical tomotherapy in female patients with local restricted, lymph node negative breast cancer after breast-conserving surgery. Patients and Methods In this single-centre analysis, 219 female patients with early-stage breast cancer (T1/2) and no lymph node metastasis (N0) following breast-conserving surgery and sentinel-node biopsy were treated with adjuvant fractionated whole breast radiation therapy using helical tomotherapy. When boost irradiation was indicated, it was administered sequentially or using the simultaneous-integrated boost technique. Local control (LC), metastasis and survival rates, acute toxicity, late toxicity, and secondary malignancy rates were analysed retrospectively. Results The mean follow-up time was 71 months. The …

Materials and MethodsA total of 502 patients were randomized between 2011 and 2015 for the prospective, multicenter, randomized phase-III-trial (NCT 01322854). 5-year results of late toxicity (LENT-SOMA), overall survival, disease-free survival, distant cancerfree survival, cosmesis (Harvard scale) and local control (non-inferiority margin at hazard ratio of 3.5) were analyzed after a median follow-up of 62 months.

ConclusionHypofractionated RT demonstrated promising local PVTT control with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED10= 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

PurposeTo 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 methodsFor 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. To integrate MRI into the treatment process, a flat tabletop and dedicated coil holders for flex coils were used, which prevent deformation of the patient external contour and allow for the use of immobilization tools for reproducible positioning. The signal-to-noise ratio (SNR) was compared for the diagnostic and therapy-specific setup using the flat couch top and flexible coils for the a) head & neck and b) abdominal region as well as for different bandwidths and clinical pulse sequences. Additionally, a quality assurance (QA) protocol with monthly …

Purpose To analyze the dose objectives and constraints applied at the prospective phase II PACK-study at Heidelberg ion therapy center (HIT) for different radiobiological models. Methods Treatment plans of 14 patients from the PACK-study were analyzed and recomputed in terms of physical, biological dose and dose-averaged linear energy transfer (LETd). Both LEM-I (local effect model 1) and the adapted NIRS-MKM (microdosimetric kinetic model), were used for relative biological effectiveness (RBE)-weighted dose calculations (D Bio| HIT and D Bio| NIRS). A new constraint to the gastrointestinal (GI) tract was derived from the National Institute of Radiological Science (NIRS) clinical experience and considered for plan reoptimization (D Bio| NIRS-const_ 48 Gy and D Bio| NIRS-const_ 50. 4 Gy). The Lyman-Kutcher-Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for GI toxicity endpoints …

Purpose: Helium ions offer intermediate physical and biological properties to the clinically used protons and carbon ions. This work presents the commissioning of the first clinical treatment planning system (TPS) for helium ion therapy with active beam delivery to prepare the first patients’ treatment at the INSTITUTION-XXXMethods: Through collaboration between RaySearch Laboratories and INSTITUTION-XXX, absorbed and relative biological effectiveness (RBE)-weighted calculation methods were integrated for helium ion beam therapy with raster-scanned delivery in the TPS RayStation. At INSTITUTION-XXX, a modified Microdosimetric Kinetic biological Model was chosen as reference biological model. TPS absorbed dose predictions were compared against measurements with several devices, using phantoms of different complexities, from homogeneous to heterogeneous anthropomorphic phantoms. RBE …

PurposeThe purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml.MethodsThe study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed.ResultsThe final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66–70 Gy …

BackgroundParticle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study.MethodA patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0, 45, 90, 180) and imaging (0, 70, 90, 110). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated.ResultsOut of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90 and 110, respectively. The average result for claustrophobia (0= no claustrophobia to 4= extreme claustrophobia) was none to light …

PurposeThe IMRT-MC2 trial was conducted to demonstrate the noninferiority of conventionally fractionated intensity modulated radiation therapy with a simultaneous integrated boost to 3-dimensional conformal radiation therapy with a sequential boost for adjuvant breast radiation therapy.Methods and MaterialsA total of 502 patients were randomized between 2011 and 2015 for the prospective, multicenter, phase III trial (NCT 01322854). Five-year results of late toxicity (late effects normal tissue task force-subjective, objective, management, and analytical), overall survival, disease-free survival, distant disease-free survival, cosmesis (Harvard scale), and local control (noninferiority margin at hazard ratio [HR] of 3.5) were analyzed after a median follow-up of 62 months.ResultsThe 5-year local control rate for the intensity modulated radiation therapy with simultaneous integrated boost arm was non-inferior to the …

Amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) imaging can predict clinical outcomes in patients with glioma. However, the treatment of brain tumors is accompanied by the deposition of blood products within the tumor area in most cases. For this reason, the objective was to assess whether the diagnostic interpretation of the APT and ssMT is affected by methemoglobin (mHb) and hemosiderin (Hs) depositions at the first follow-up MRI 4 to 6 weeks after the completion of radiotherapy. A total of 34 participants underwent APT and ssMT imaging by applying reconstruction methods described by Zhou et al. (APTwasym), Goerke et al. (MTRRexAPT and MTRRexMT) and Mehrabian et al. (MTconst). Contrast-enhancing tumor (CE), whole tumor (WT), mHb and Hs were segmented on contrast-enhanced T1wCE, T2w-FLAIR, T1w and T2*w images. ROC-analysis, Kaplan–Meier analysis and the log rank test were used to test for the association of mean contrast values with therapy response and overall survival (OS) before (WT and CE) and after correcting tumor volumes for mHb and Hs (CEC and WTC). CEC showed higher associations of the MTRRexMT with therapy response (CE: AUC = 0.677, p = 0.081; CEC: AUC = 0.705, p = 0.044) and of the APTwasym with OS (CE: HR = 2.634, p = 0.040; CEC: HR = 2.240, p = 0.095). In contrast, WTC showed a lower association of the APTwasym with survival (WT: HR = 2.304, p = 0.0849; WTC: HR = 2.990, p = 0.020). Overall, a sophisticated correction for blood products did not substantially influence the clinical performance of APT and ssMT imaging in patients with glioma early after …

BackgroundAnnual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial.ObjectiveTo determine DRE diagnostic performance in a screening trial.Design, setting, and participantsThis analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa.Intervention(1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen–driven biopsies (N = 578).Outcome measurements and statistical analysis(1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome …

Background and purpose: Glioblastoma multiforme (GBM) is a stroma rich immune cold tumor with still dismal prognosis of despite multimodal therapy consisting of postoperative surgery and radiochemotherapy. Consequently, all randomized Phase III clinical GBM trials attempting to integrate immune checkpoint blockade (ICB) have failed to demonstrate efficacy. We have recently shown that tumor immune microenvironment (TIME) reprograming via Bintrafusp alpha (Anti-PD-L1/TGF-beta bispecific molecule) combined with conventional photon radiotherapy elicits beneficial effects and prolong survival in experimental models (Lan, Knoll, Moustafa et al. Cancer Cell 2021). Moreover, eradication of radioresistant i.e., stem cell like, invasive and hypoxic tumor subpopulations by high linear energy transfer (LET) carbon ion radiotherapy (CIRT) was shown to generate an immune permissive niche in experimental GBM …

BackgroundStereotactic radiotherapy of ultracentral lung tumors (ULT) is challenging as it may cause overdoses to sensitive mediastinal organs with severe complications. We aimed to describe long-term outcomes after stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) as an innovative treatment of ULT.Patients & methodsWe analyzed 36 patients that received SMART to 40 tumors between 02/2020 – 08/2021 inside prospective databases. ULT were defined by planning target volume (PTV) overlap with the proximal bronchial tree or esophagus. We calculated Kaplan Meier estimates for overall survival (OS) and progression-free survival (PFS), and competing risk estimates for the incidence of tumor progression and treatment-related toxicities. ULT patients (N = 16) were compared to non-ULT patients (N = 20).ResultsBaseline characteristics were similar between ULT and non …

Materials and MethodsDemographic and treatment characteristics (132 features) of patients treated with PBT were used to predict grade≥ 2 pulmonary toxicities from 7 institutions enrolled in the Proton Collaborative Group prospective clinical trial NCT01255748. A total number of 868 patients were evaluated across all centers and individual center enrollment ranged from 65–229 cases. Machine learning algorithms (Logistic Regression and Random Forrest) were trained using cases from each center and tested on intra-cases (from the same center as the training dataset) and inter-case (outside the center of the training dataset). A double 10-fold cross-validation was performed to tune hyperparameters without leak of information. Balanced Accuracy (BA) and Area under the Curve (AUC) were calculated. Confidence intervals were obtained using bootstrap sampling.

Materials and MethodsA cross-sectional questionnaire was disseminated via social media, Facebook, Twitter, Instagram, and LinkedIn between January and March 2022 using Microsoft Forms. Twenty-one questions were selected from a previously published questionnaire to measure the extent of knowledge and misconceptions surrounding RT. Respondents were divided into groups–A-Those who previously received RT/had a cancer diagnosis, B–Those with a family member/close friend who had RT, C–no exposure to RT, D–healthcare worker not working in oncology. Data were analysed using Microsoft Excel; Chi-squared and Student t-tests were used to assess the statistical significance of the results. Ethical approval was obtained from the University College Cork’s Social Research Ethics Committee (SREC).

BackgroundPatients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical …

Background Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs—in light of the diverse selected treatment regimes. Methods A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed. Results Divergent initial histological diagnoses were encountered in 40.7%. There was no …

Catheter ablation of ventricular tachycardia and premature ventricular contractions originating from the left ventricular summit is particularly challenging owing to myocardial wall thickness, epicardial fat, and proximity of coronary arteries. Cardiac stereotactic body radiation therapy (cSBRT) might provide an effective and safe treatment option in refractory cases.

PurposeThe APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women with uterine cervical or endometrial cancer. In this analysis, we report the primary study endpoint of safety and treatment tolerability as well as toxicity rates and progression-free survival (PFS).Methods and Materials25 patients were treated with postoperative proton beam therapy with a total dose of 45 to 50.4 Gy (RBE) in 5 to 6 × 1.8 Gy (RBE) fractions weekly using active raster-scanning intensity modulated proton beam therapy (IMPT). Sequential or simultaneous platinum-based chemotherapy was administered if indicated. The primary endpoint was defined as the lack of any acute ≥grade 3 gastrointestinal (GI) or urogenital (GU) toxicity according to the Common Terminology Criteria for Adverse Events v 4.0 or premature treatment abortion …

Purpose/Objective(s)While the results of prospective studies support the use of postoperative stereotactic radiotherapy (RT) to the resection cavity (RC) as the standard of care after surgery, there are several issues that need to be investigated such as factors for improving local control, risk of leptomeningeal disease and radiation necrosis. Further, the optimal dose and fractionation is still under debate.Materials/MethodsThe working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology (DEGRO) analyzed its multi-institutional database with 661 patients who received postoperative stereotactic RT to the RC. Treatment was performed at 13 centers between 2008 and 2021. Patient characteristics, treatment details, and follow-up data including overall survival (OS), local control (LC) were evaluated. Cox Regression and Kaplan-Meier curves with Log-rank Tests were calculated for selected …

BackgroundMobile health (mhealth) is gaining interest, with mobile devices and apps being ever more available among medical facilities and patients. However, in the field of radiation oncology, the medical benefits of mhealth apps are still underexplored. As an additional approach to patient care during radiotherapy, we designed a mobile treatment surveillance app based on patient-reported outcomes.ObjectiveWe aimed to examine the feasibility of app-based treatment surveillance in patients undergoing radiotherapy (RT). Alongside technical practicability and acceptance, we assessed patient satisfaction and quality of life during treatment.MethodsThis prospective single-center study was performed at Heidelberg University Hospital between August 2018 and January 2020. During RT we measured patients’ quality of life, symptoms, and treatment satisfaction. Respective questionnaires (EORTC QLQ-C30 with …

Purpose Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. Experimental Design A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression–based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results Although hypoxia-GES failed to …

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IntroductionApproximately 40% of non-small-cell lung cancer (NSCLC) patients develop brain metastases (BM). Stereotactic radiosurgery (SRS) instead of whole-brain radiotherapy (WBRT) is increasingly administered as an upfront treatment to patients with a limited number of BM. We present outcomes and validation of prognostic scores for these patients treated with upfront SRS.MethodsWe retrospectively analyzed 199 patients with a total of 268 SRS courses for 539 brain metastases. Median patient age was 63 years. For larger BM, dose reduction to 18 Gy or hypofractionated SRS in 6 fractions was applied. We analyzed the BMV-, the RPA-, the GPA- and the lung-mol GPA score. Cox proportional hazards models with univariate and multivariate analyses were fitted for overall survival (OS) and intracranial progression-free survival (icPFS).ResultsSixty-four patients died, 7 of them of neurological causes. Thirty …

ConclusionThe early results of MR guided SF-SABR delivered in breath-hold reveal high tumor control rates, indicating that the use of automatic beam gating with a 3 mm gating boundary is safe for patients with peripheral lung tumors.

ConclusionThe use of SABR on previously treated lesions by SABR is an option. The treatment is safe and the doses are acceptable. More studies with more patients can be necessary to predict and avoid severe toxicities.

ConclusionThis study presented a proof of concept describing the optimization of aperture positions for HN cancer. Proton plans with multiple AA shapes have longer delivery times, but this is acceptable giving the dosimetric benefit. Forward optimization of AA shapes resulted in clinically relevant NTCP reduction with preserved target coverage.

IntroductionRe-irradiation is frequently performed in the era of precision oncology, but previous doses to organs-at-risk (OAR) must be assessed to avoid cumulative overdoses. Stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) enables highly precise ablation of tumors close to OAR. However, OAR doses may change considerably during adaptive treatment, which complicates potential re-irradiation. We aimed to compare the baseline plan with different dose accumulation techniques to inform re-irradiation.Patients & methodsWe analyzed 18 patients who received SMART to lung or liver tumors inside prospective databases. Cumulative doses were calculated inside the planning target volumes (PTV) and OAR for the adapted plans and theoretical non-adapted plans via (1) cumulative dose volume histograms (DVH sum plan) and (2) deformable image registration (DIR)-based dose …

Introduction Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. Methods Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively …

BackgroundMany automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation.MethodsWe analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers.ResultsThe model based on T1-CE alone …

Carbon-ion radiotherapy (CIRT) is a highly conformal form of radiotherapy that offers precise dose distributions for cancer treatment. On the other hand, CIRT is sensitive to morphological changes in the patient anatomy, such as swelling, tumor size variation, or cavity filling. Our research group at the German Cancer Research Center has been developing a method for monitoring such changes along the course of the treatment by tracking nuclear charged fragments that emerge from irradiated patients. A non-invasive in-vivo detection system with seven mini-trackers composed of 28 Timepix3 pixel detectors was developed. The detection system is used in the ongoing In-Vivo Monitoring (InViMo) clinical trial at the Heidelberg Ion-Beam Therapy Center. FLUKA Monte Carlo (MC) simulations were developed to support the clinical measurements and link specific anatomical changes to observed differences in the …

Purpose The purpose of this study was to compare the potential of asymmetry‐based (APTwasym), Lorentzian‐fit‐based (PeakAreaAPT and MTconst), and relaxation‐compensated (MTRRexAPT and MTRRexMT) CEST contrasts of the amide proton transfer (APT) and semi‐solid magnetization transfer (ssMT) for early response assessment and prediction of progression‐free survival (PFS) in patients with glioma. Methods Seventy‐two study participants underwent CEST‐MRI at 3T from July 2018 to December 2021 in a prospective clinical trial four to 6 wk after the completion of radiotherapy for diffuse glioma. Tumor segmentations were performed on T2w‐FLAIR and contrast‐enhanced T1w images. Therapy response assessment and determination of PFS were performed according to response assessment in neuro oncology (RANO) criteria using clinical follow‐up data with a median observation time of 9.2 mo …

Background and PurposeIn online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs.Materials and MethodsMLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan.ResultsAll positions in the motor step – position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2 ± 0.1 mm for …

Purpose/Objective(s)Stereotactic Radiosurgery (SRS) is increasingly used as an alternative to whole-brain radiotherapy (WBRT) in the treatment of patients with multiple brain metastases (BM) with the aim of reducing toxicity and improving tumor control. The CYBER-SPACE trial evaluated SRS based on highly sensitive magnetic resonance imaging (MRI) for patients with 1-10 BM with the aim of avoiding or delaying WBRT.Materials/MethodsEligible patients with 1-10 newly diagnosed BM regardless of histology were randomized 1:1 to receive SRS of all visible lesions based on either SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or MPRAGE (magnetization-prepared rapid gradient-echo) MRI sequence. If during follow-up new BM occurred, SRS was repeated for those BM. The primary endpoint was ineligibility for further SRS. It was defined as the …

PurposeProton beam radiotherapy (PRT) has been demonstrated to improve neurocognitive sequelae particularly. Nevertheless, following PRT, increased rates of radiation-induced contrast enhancements (RICE) are feared. How safe and effective is PRT for IDH-mutated glioma WHO grade 2 and 3?MethodsWe analyzed 194 patients diagnosed with IDH-mutated WHO grade 2 (n = 128) and WHO grade 3 (n = 66) glioma who were treated with PRT from 2010 to 2020. Serial clinical and imaging follow-up was performed for a median of 5.1 years.ResultsFor WHO grade 2, 61% were astrocytoma and 39% oligodendroglioma while for WHO grade 3, 55% were astrocytoma and 45% oligodendroglioma. Median dose for IDH-mutated glioma was 54 Gy(RBE) [range 50.4–60 Gy(RBE)] for WHO grade 2 and 60 Gy(RBE) [range 54–60 Gy(RBE)] for WHO grade 3. Five year overall survival was 85% in patients with WHO …

Materials and MethodsWe used data extracted from two European radiation oncology clinics to develop a prediction model for near complete response (defined as a residual tumour diameter< 2cm and pT1-2N0M0). The variables included in the model based on availability and expert knowledge were: T, N and M stages, mesorectal fascia involvement, WHO status, tumour volume, distance to the anal junction, treatment, age, and gender. We imputed missing values using multiple imputation with chained equations for the training dataset. We trained a Bayesian network (BN) applying the nonparametric bootstrap using the hill climbing algorithm and the Bayesian Dirichlet equivalent score without sharing data, using federated learning. We asked three radiation oncologists to propose the structure of the BNs and then compared the performance of the BN in terms of area under the ROC curve (AUC) when the …

Materials and MethodsWe investigated pCSI for the cranial junction and for the spinal junction. Treatments plans were generated with our inhouse research treatment planning system TRiP98. The biological effect was estimated by the Local-effect model IV. Figure 1 shows that recalculating a plan for constant RBE with varying RBE leads to a V105> 30%. To regain robustness, two new strategies were developed: for parallel fields, opposing ramps in particle numbers were generated from a single biologically optimized treatment plan, utilizing that particle numbers are additive, while dose gradients are not under variable RBE. The second strategy considered direct robust optimization assuming symmetric shifts in anterior-posterior and lateral direction. Furthermore, asymmetric shifts, where one field was shifted cranially and the other caudally (and vice versa) were included. We investigated the impact of the …

ConclusionWe believe these recommendations will standardise the RT treatment of vulvar cancer in the UK. We also aim to improve compliance with national recommendations such as the treatment of vulvar cancer as category 1 and compensation of gaps during treatment. The national RCR audit will be repeated in 2024 to assess the impact of these recommendations on UK practice.

Simple Summary Stereotactic body radiotherapy (SBRT) using direct magnetic resonance (MR) guidance is a comparably new technology and enables ablative treatment of liver metastases without invasive placement of fiducials. We aimed to evaluate long-term clinical outcome. Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation based on the daily anatomy). The most prevalent fractionation scheme was 50 Gy in five fractions. Estimated local control of the irradiated liver metastases was 75% at 2 years and overall survival was 57% at 2 years. We report the largest patient cohort to date, demonstrating promising long-term clinical results for SBRT of liver metastases applying MR-guidance. Abstract (1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC …

Brain tumor patients are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity, particularly the risk of radionecrosis. We used human cerebral organoids to investigate the mechanisms and nature of postirradiation brain image changes commonly linked to necrosis. Irradiation of cerebral organoids lead to increased formation of ZO1+/AQP1+/CLN3+-choroid plexus (CP) structures. Increased CP formation was triggered by radiation via the NOTCH/WNT signaling pathways and associated with delayed growth and neural stem cell differentiation, but not necrosis. The effect was more pronounced in immature than in mature organoids, reflecting the clinically-observed increased radiosensitivity of the pediatric brain. Protons were more effective than X-rays at the same dose, as also observed in clinical treatments. We conclude that radiation-induced brain image-changes can be …

Radiotherapy is recommended by current EANO guidelines for patients with atypical meningiomas (WHO grade 2) following subtotal resection. While meningiomas are generally considered radioresistant, novel radiotherapeutic modalities using carbon ions present an increased relative biological effectiveness (RBE) compared to photons, while reducing the radiation exposure for adjacent organs at risk by exploiting the Bragg peak. Our prospective phase 2 trial investigated bimodal radiotherapy using a carbon-ion boost in patients with atypical meningiomas following subtotal resection. A total of 33 patients were enrolled from 07/2012 until 07/2020. The study was prematurely terminated in 07/2020 after recruiting 33 of the initially planned 40 patients due to one grade 5 toxicity. Study treatment comprised a carbon ion boost (18 Gy [RBE] in 6 fractions) targeted to the macroscopic tumor in combination with …

Background and purposeOutcome prediction of patients with glioma early after the completion of radiotherapy represents a major clinical challenge. Previously, the prognostic value of chemical exchange saturation transfer (CEST) imaging has been demonstrated in patients with newly diagnosed glioma. The objective of this study was to assess the potential of amide proton transfer (APT)-, relayed nuclear Overhauser effect (rNOE)- and semi-solid magnetization transfer (ssMT)-imaging according to Zhou et al. (APTwasym), Goerke et al. (MTRRexAPT, MTRRexNOE and MTRRexMT) and Mehrabian et al. (PeakAreaAPT, PeakAreaNOE and MTconst) for the prognostication of the overall survival (OS) of patients with glioma at the first follow-up after the completion of radiotherapy.Materials and Methods49 of 72 participants with diffuse glioma, who underwent CEST MRI at 3T between July 2018 and December 2021 4 …

Background/Aim To determine the interaction of gemcitabine in chemoradiotherapy with heavy carbon ions in vitro in a mucoepidermoid carcinoma (MEC) cell line. Materials and Methods The human lymphatic MEC metastasis cell line NCI-H292 was used. The cells were treated with photons, carbon ions, and gemcitabine. Survival fractions (SF), apoptosis, and cell cycle progression were analyzed. A paired two-sided t-test was used. Significance was defined as p<0.05. Results Cell proliferation assays showed a significant reduction in SF for combined photon chemoradiation versus photons only. The linear-quadratic fits of combined therapy with carbon ion dose of 0 to 2.5 Gy led to reductions of mean 15% in SF. The LD50 (lethal radiation dose required to reduce cell survival by 50%) for carbon ions only was 0.7 Gy and for carbon ions with gemcitabine 0.6 Gy. The LD50 for photons (with gemcitabine) was 2.8 Gy …