MR-guided radiotherapy for liver malignancies

MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology

Anak Krakatau triggers volcanic freezer in the upper troposphere

Volcanic activity occurring in tropical moist atmospheres can promote deep convection and trigger volcanic thunderstorms. These phenomena, however, are rarely observed to last continuously for more than a day and so insights into the dynamics, microphysics and electrification processes are limited. Here we present a multidisciplinary study on an extreme case, where volcanically-triggered deep convection lasted for six days. We show that this unprecedented event was caused and sustained by phreatomagmatic activity at Anak Krakatau volcano, Indonesia during 22-28 December 2018. Our modelling suggests an ice mass flow rate of similar to 5x10(6)kg/s for the initial explosive eruption associated with a flank collapse. Following the flank collapse, a deep convective cloud column formed over the volcano and acted as a 'volcanic freezer' containing similar to 3x10(9)kg of ice on average with maxima reaching similar to 10(10)kg. Our satellite analyses reveal that the convective anvil cloud, reaching 16-18km above sea level, was ice-rich and ash-poor. Cloud-top temperatures hovered around -80 degrees C and ice particles produced in the anvil were notably small (effective radii similar to 20 mu m). Our analyses indicate that vigorous updrafts (>50m/s) and prodigious ice production explain the impressive number of lightning flashes (similar to 100,000) recorded near the volcano from 22 to 28 December 2018. Our results, together with the unique dataset we have compiled, show that lightning flash rates were strongly correlated (R=0.77) with satellite-derived plume heights for this event

Gal-2 increases H3K4me3 and H3K9ac in trophoblasts and preeclampsia

Preeclampsia (PE) is a severe pregnancy disorder with a pathophysiology not yet completely understood and without curative therapy. The histone modifications H3K4me(3) and H3K9ac, as well as galectin-2 (Gal-2), are known to be decreased in PE. To gain a better understanding of the development of PE, the influence of Gal-2 on histone modification in trophoblasts and in syncytialisation was investigated. Immunohistochemical stains of 13 PE and 13 control placentas were correlated, followed by cell culture experiments. An analysis of H3K4me(3) and H3K9ac was conducted, as well as cell fusion staining with E-cadherin and β-catenin—both after incubation with Gal-2. The expression of H3K4me(3) and H3K9ac correlated significantly with the expression of Gal-2. Furthermore, we detected an increase in H3K4me(3) and H3K9ac after the addition of Gal-2 to BeWo/HVT cells. Moreover, there was increased fusion of HVT cells after incubation with Gal-2. Gal-2 is associated with the histone modifications H3K4me(3) and H3K9ac in trophoblasts. Furthermore, syncytialisation increased after incubation with Gal-2. Therefore, we postulate that Gal-2 stimulates syncytialisation, possibly mediated by H3K4me(3) and H3K9ac. Since Gal-2, as well as H3K4me(3) and H3K9ac, are decreased in PE, the induction of Gal-2 might be a promising therapeutic target

Survey on brachytherapy training among radiation oncology residents in the German-speaking regions of Europe.

PURPOSE This survey aimed to determine the perception of brachytherapy training among residents in the DACH region, consisting of Austria, Germany and Switzerland. MATERIAL & METHODS An online questionnaire containing 22 questions related to trainee demographics (n = 5) and to brachytherapy training (n = 17) was sent in two iterations in 11/2019 and 02/2020. The following topics were evaluated: institutional support, barriers to training, extent of training, site-specific training (prostate, gynaecology, breast, gastrointestinal and skin), preferences for further training and outlook on overall development of brachytherapy. The responses were mostly based on a Likert scale of 1 to 5, thereby reflecting strength of opinion. Descriptive statistics were used to describe frequencies. RESULTS Among the 108 respondents, approximately 69% of residents considered the ability to perform brachytherapy independently to be important or somewhat important. However, only 31% of respondents reported to have a dedicated brachytherapy training during residency. The major limitation to achieve independence in performing brachytherapy was seen in a low case load in Austria, in the lack of training in Switzerland and in both of them in Germany. CONCLUSION The interest in brachytherapy training among residents in German-speaking countries was generally high, but there is a perceived lack of sufficient case volumes and partially also in formal training opportunities. Fellowships at departments with a high case load as part of a formalised curriculum and dedicated hands-on workshops at national or international conferences might help to overcome these issues

Multifocal high-grade glioma radiotherapy safety and efficacy

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

ExacTrac Dynamic workflow evaluation: Combined surface optical/thermal imaging and X‐ray positioning

In modern radiotherapy (RT), especially for stereotactic radiotherapy or stereotactic radiosurgery treatments, image guidance is essential. Recently, the ExacTrac Dynamic (EXTD) system, a new combined surface-guided RT and image-guided RT (IGRT) system for patient positioning, monitoring, and tumor targeting, was introduced in clinical practice. The purpose of this study was to provide more information about the geometric accuracy of EXTD and its workflow in a clinical environment. The surface optical/thermal- and the stereoscopic X-ray imaging positioning systems of EXTD was evaluated and compared to cone-beam computed tomography (CBCT). Additionally, the congruence with the radiation isocenter was tested. A Winston Lutz test was executed several times over 1 year, and repeated end-to-end positioning tests were performed. The magnitude of the displacements between all systems, CBCT, stereoscopic X-ray, optical-surface imaging, and MV portal imaging was within the submillimeter range, suggesting that the image guidance provided by EXTD is accurate at any couch angle. Additionally, results from the evaluation of 14 patients with intracranial tumors treated with open-face masks are reported, and limited differences with a maximum of 0.02 mm between optical/thermal- and stereoscopic X-ray imaging were found. As the optical/thermal positioning system showed a comparable accuracy to other IGRT systems, and due to its constant monitoring capability, it can be an efficient tool for detecting intra-fractional motion and for real-time tracking of the surface position during RT

Role of Radiosurgery/Stereotactic Radiotherapy in Oligometastatic Disease: Brain Oligometastases

During the natural history of oncologic diseases, approximately 20–40% of patients affected by cancer will develop brain metastases. Non-small lung cancer, breast cancer, and melanoma are the primaries that are most likely to metastasize into the brain. To date, the role of Radiosurgery/Stereotactic Radiotherapy (SRS/SRT) without Whole brain irradiation (WBRT) is a well-recognized treatment option for patients with limited intracranial disease (1–4 BMs) and a life-expectancy of more than 3–6 months. In the current review, we focused on randomized studies that evaluate the potential benefit of radiosurgery/stereotactic radiotherapy for brain oligometastases. To date, no difference in overall survival has been observed between SRS/SRT alone compared to WBRT plus SRS. Notably, SRS alone achieved higher local control rates compared to WBRT. A possible strength of SRS adoption is the potential decreased neurocognitive impairment

Simultaneous stereotactic radiosurgery of multiple brain metastases using single-isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

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

Offline and online LSTM networks for respiratory motion prediction in MR-guided radiotherapy

Objective. Gated beam delivery is the current clinical practice for respiratory motion compensation in MR-guided radiotherapy, and further research is ongoing to implement tracking. To manage intra-fractional motion using multileaf collimator tracking the total system latency needs to be accounted for in real-time. In this study, long short-term memory (LSTM) networks were optimized for the prediction of superior–inferior tumor centroid positions extracted from clinically acquired 2D cine MRIs. Approach. We used 88 patients treated at the University Hospital of the LMU Munich for training and validation (70 patients, 13.1 h), and for testing (18 patients, 3.0 h). Three patients treated at Fondazione Policlinico Universitario Agostino Gemelli were used as a second testing set (1.5 h). The performance of the LSTMs in terms of root mean square error (RMSE) was compared to baseline linear regression (LR) models for forecasted time spans of 250 ms, 500 ms and 750 ms. Both the LSTM and the LR were trained with offline (offline LSTM and offline LR) and online schemes (offline+online LSTM and online LR), the latter to allow for continuous adaptation to recent respiratory patterns. Main results. We found the offline+online LSTM to perform best for all investigated forecasts. Specifically, when predicting 500 ms ahead it achieved a mean RMSE of 1.20 mm and 1.00 mm, while the best performing LR model achieved a mean RMSE of 1.42 mm and 1.22 mm for the LMU and Gemelli testing set, respectively. Significance. This indicates that LSTM networks have potential as respiratory motion predictors and that continuous online re-optimization can enhance their performance