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Introduction: Online MR-guided radiotherapy (MRgRT) is a relatively novel advancement in the field of radiation oncology, ensuring superior soft-tissue visualisation, allowing for online plan adaptation to anatomical and functional interfractional changes and improved motion management. Platinum-based chemoradiation followed by durvalumab is the recommended treatment for stage IIB(N1)/III NSCLC. However, this is only the case for patients with favourable risk factors and sufficient pulmonary function and reserve.Methods: Herein, we present a technical report on tumour motion and breathing curve analyses of the first patient with node-positive stage IIB NSCLC and severely compromised pulmonary function and reserve [total lung capacity (TLC) 8.78L/132% predicted, residual volume (RV) 6.35L/271% predicted, vital capacity (VC) max 2.43L/58% predicted, FEV1 1.19L/38% predicted, DLCO-SB corrected for hemoglobin 2.76 mmol/min/kPa/30% predicted] treated in a prospective observational study with moderately hypofractionated MRgRT to a total dose of 48.0 Gy/16 daily fractions on the MRIdian system (Viewray Inc, Oakwood, USA).Results: Radiotherapy was well tolerated with no relevant toxicity. First follow-up imaging at 3 months post-radiotherapy showed a partial remission. The distinctive features of this case are the patient's severely compromised pulmonary function and the first online MR-guided accelerated hypofractionated radiotherapy treatment for primary node-positive NSCLC.Conclusions: This technical report describes the first patient treated in a prospective observational study evaluating the feasibility of this relatively novel technology in stage IIB(N1)/III disease, proposing a clinical pathway for the management of high-risk patients. [ABSTRACT FROM AUTHOR]

Aim: Plantar enthesophyte is a common degenerative disorder. Surgical and medical treatment options are associated with either poor outcome or high percentage of relapse. Observations have indicated a beneficial effect of radiation therapy. We therefore wanted to evaluate pain reduction using orthovolt or cobalt-based radiation treatment for painful plantar enthesophyte and determine long-term response as well as prognostic parameters in this condition. Methods: We identified a total of 102 consecutive patients treated for a total of 117 symptomatic heel spurs. 59 patients were treated with cobalt radiation, 31 patients with orthovolt therapy and 12 patients with both radiation systems. Primary outcome measure was pain reduction being scored using the modified Rowe Score prior therapy, at the end of each treatment series as well as after 6 weeks. Secondary outcome measure was long-term outcome, evaluated in patients with a follow-up period of longer than 3 years. Results: Before radiation therapy, 61 patients (60.4%) had a score of 0, significant strong pain. At the time of completion of radiation treatment, 3 patients (2.7%) were pain-free (score of 30), whereas 8 patients (7.9%) had still severe pain (score 0). 6 weeks after radiation therapy, 33 patients (32.7%) were pain-free and 8 patients (7.9%) had severe pain (score 0), while at the time data of collection, 74 patients (73%) were free of pain and 1 patient (1%) had strong pain (score 0). Duration of pain before the start of radiation treatment was a significant prognostic factor (p = 0.012) for response to treatment. Conclusion: Radiotherapy of painful plantar enthesophyte is a highly effective therapy with little side effects providing long-term therapeutic response. The only significant prognostic parameter for response to treatment is the duration of pre-radiation therapy pain. Early integration of radiation therapy in the treatment seems to result in superior pain reduction. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis.Material and Methods: Ten patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost.Results: MRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities.Conclusion: These early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results. [ABSTRACT FROM AUTHOR]

Purpose: Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology. Methods: The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives' final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives. Results: The strategy retreat's development process resulted in conception of the final vision "Innovative radiation oncology Together – Precise, Personalized, Human." The first term "Innovative radiation oncology" comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term "together" underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. "Precise" mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. "Personalized" emphasizes biology-directed individualization of radiation treatment. Finally, "Human" underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field. Conclusion: The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany. [ABSTRACT FROM AUTHOR]

Background: Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making. Methods: Patients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients. Results: 20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42–84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm3. Median volume of the PTV was 425.7 cm3 and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2–62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33–79.7) and 40.7 percent (range 14.9–64.1), respectively. Median survival was eight months (95% KI 3.6–12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8–7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy. Conclusion: Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields. [ABSTRACT FROM AUTHOR]

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.Materials and Methods: 20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.Results: The dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.Conclusions: A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected. [ABSTRACT FROM AUTHOR]

Background: Single-isocenter dynamic conformal arc (SIDCA) therapy is a technically efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of linear accelerator (LINAC) based SRS with SIDCA for patients with multiple brain metastases. Methods: All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial were included. The patients were irradiated with a dedicated planning tool for multiple brain metastases using a LINAC with a 5 mm multileaf collimator. Follow-up was performed every 3 months, including clinical and radiological examination with cranial magnetic resonance imaging (MRI). These early data were analyzed using descriptive statistics and the Kaplan–Meier method. Results: A total of 65 patients with 254 lesions (range 2–12) were included in this analysis. Median beam-on time was 23 min. The median follow-up at the time of analysis was 13 months (95% CI 11.1–14.9). Median overall survival and median intracranial progression-free survival was 15 months (95% CI 7.7–22.3) and 7 months (95% CI 3.9–10.0), respectively. Intracranial and local control after 1 year was 64.6 and 97.5%, respectively. During follow-up, CTCAE grade I adverse effects (AE) were experienced by 29 patients (44.6%; 18 of them therapy related, 27.7%), CTCAE grade II AEs by four patients (6.2%; one of them therapy related, 1.5%), and CTCAE grade III by three patients (4.6%; none of them therapy related). Two lesions (0.8%) in two patients (3.1%) were histopathologically proven to be radiation necrosis. Conclusion: Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple brain metastases. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). Methods: Four treatment plans were created (3D-CRT and IMRT –/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. Results: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. Conclusion: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT. [ABSTRACT FROM AUTHOR]

• GANs segment organs-at-risk in pelvic 0.35T MRIs with high accuracy. • Segmented organs: rectum, bladder and femoral heads (left and right) • Our networks generalised well on an external independent dataset. • 3D GAN outperforms its 2D equivalent in both accuracy and generation time. • This is the first attempt of organ auto-segmentation in 0.35T MRI with GANs. Manual recontouring of targets and Organs At Risk (OARs) is a time-consuming and operator-dependent task. We explored the potential of Generative Adversarial Networks (GAN) to auto-segment the rectum, bladder and femoral heads on 0.35T MRIs to accelerate the online MRI-guided-Radiotherapy (MRIgRT) workflow. 3D planning MRIs from 60 prostate cancer patients treated with 0.35T MR-Linac were collected. A 3D GAN architecture and its equivalent 2D version were trained, validated and tested on 40, 10 and 10 patients respectively. The volumetric Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95th) were computed against expert drawn ground-truth delineations. The networks were also validated on an independent external dataset of 16 patients. In the internal test set, the 3D and 2D GANs showed DSC/HD95th of 0.83/9.72 mm and 0.81/10.65 mm for the rectum, 0.92/5.91 mm and 0.85/15.72 mm for the bladder, and 0.94/3.62 mm and 0.90/9.49 mm for the femoral heads. In the external test set, the performance was 0.74/31.13 mm and 0.72/25.07 mm for the rectum, 0.92/9.46 mm and 0.88/11.28 mm for the bladder, and 0.89/7.00 mm and 0.88/10.06 mm for the femoral heads. The 3D and 2D GANs required on average 1.44 s and 6.59 s respectively to generate the OARs' volumetric segmentation for a single patient. The proposed 3D GAN auto-segments pelvic OARs with high accuracy on 0.35T, in both the internal and the external test sets, outperforming its 2D equivalent in both segmentation robustness and volume generation time. [ABSTRACT FROM AUTHOR]

Abstract Introduction MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines. Materials and methods 1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens". Results Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered. Conclusion Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis.