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Abstract Background Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. Methods We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). Results Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24–50 Gy, mean BEDα/β10=93), while 41 Gy (range 16–50 Gy, mean BEDα/β10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1–10 Gy) and 3,7 Gy (range 1,6–8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. Conclusions MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Introduction: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM. Materials and methods: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55–50.6 Gy at PTV1 and 45–39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients. Results: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed. Conclusion: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p

Abstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence. Methods Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale. Results From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463). Conclusions MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.

IntroductionPatients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection.Material and methodsA total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP.ResultsGTV centroid motion is

IntroductionContouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment.Materials and methods21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose.ResultsAverage HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively.DiscussionsGIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.

Abstract Background Mesorectal motion (MM) is a source of uncertainty during neoadjuvant chemoradiotherapy (nCRT) delivery for locally advanced rectal cancer (LARC). Previously published experiences using cone-beam computed tomography imaging have already described significant movement. Aim of this analysis is to assess inter-fraction MM using the higher tissue contrast provided by hybrid magnetic resonance imaging (MRI) in LARC patients (pts) treated with MRI guided radiation therapy (MRgRT). Methods The total mesorectum, its superior (Msup), middle (Mmid) and lower (Mlow) regions were contoured on the positioning MRIs acquired on simulation day and on each treatment day. Six PTVs were obtained adding 0.5, 0.7, 1, 1.3, 1.5 and 2 cm margin to the whole mesorectum, starting from the simulation MRI. Margins including 95% of the mesorectal structures during whole treatment in 95% of patients (pts) were considered adequate. Results A total number of 312 fractions of 12 consecutive pts was retrospectively analyzed. The different mesorectum regions show specific motion variability. In particular, Msup shows larger variability in left, right and anterior directions, while the Mlow in caudal and posterior ones. The anterior margin is significantly larger in the Msup than in the other regions. Conclusion Different mesorectal regions move differently throughout the radiotherapy treatment, with the largest MM in the Msup anterior direction. Asymmetrical margins are recommended.

(1) Background: In 90Y-TARE treatments, lung-absorbed doses should be calculated according to the manufacturer’s instructions, using the MIRD-scheme. This scheme is derived from the assumption that 90Y-microspheres deliver the dose in a water-equivalent medium. Since the density of the lungs is quite different from that of the liver, the absorbed dose to the lungs could vary considerably, especially at the liver/lungs interface. The aim of this work is to compare the dosimetric results obtained by two dedicated software packages implementing a water-equivalent dose calculation and a Monte Carlo (MC) simulation, respectively. (2) Methods: An anthropomorphic IEC phantom and a retrospective selection of 24 patients with a diagnosis of HCC were taken into account. In the phantom study, starting from a 90Y-PET/CT acquisition, the liver cavity was manually fixed with a uniform activity concentration on PET series, while the lung compartment was manually expanded on a CT series to simulate a realistic situation in which the liver and lungs are adjacent. These steps were performed by using MIM 90Y SurePlan. Then, a first simulation was carried out with only the liver cavity filled, while a second one was carried out, in which the lung compartment was also manually fixed with a uniform activity concentration corresponding to 10% lung shunt fraction. MIM 90Y SurePlan was used to obtain Voxel S-Value (VSV) approach dose values; instead, Torch was used to obtain MC approach dose values for both the phantom and the patients. (3) Results: In the phantom study, the percentage mean dose differences (∆D%) between VSV and MC in the first and second simulation, respectively were found to be 1.2 and 0.5% (absolute dose variation, ∆D, of 0.7 and 0.3 Gy) for the liver, −56 and 70% (∆D of −0.3 and −16.2 Gy) for the lungs, and −48 and −60% (∆D of −4.3 and −16.5 Gy) for the Liver/Lungs Edge region. The patient study reports similar results with ∆D% between VSV and MC of 7.0%, 4.1% and 6.7% for the whole liver, healthy liver, and tumor, respectively, while the result was −61.2% for the left lung and −61.1% for both the right lung and lungs. (4) Conclusion: Both VSV and MC allowed accurate radiation dose estimation with small differences (50%) were observed for air-equivalent regions in the phantom simulation and the patient study.

Abstract Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

PurposeThis study aims to assess the quality of a new diffusion-weighted imaging (DWI) sequence implemented on an MR-Linac MRIdian system, evaluating and optimizing the acquisition parameters to explore the possibility of clinically implementing a DWI acquisition protocol in a 0.35-T MR-Linac.Materials and methodsAll the performed analyses have been carried out on two types of phantoms: a homogeneous 24-cm diameter polymethylmethacrylate (PMMA) sphere (SP) and a homemade phantom (HMP) constating in a PMMA cylinder filled with distilled water with empty sockets into which five cylindrical vials filled with five different concentrations of methylcellulose water solutions have been inserted. SP was used to evaluate the dependence of diffusion gradient inhomogeneity artifacts on gantry position. Four diffusion sequences with b-values of 500 s/mm2 and 3 averages have been acquired: three with diffusion gradients in the three main directions (phase direction, read direction, slice direction) and one with the diffusion gradients switched off. The dependence of diffusion image uniformity and SNR on the number of averages in the MR sequences was also investigated to determine the optimal number of averages. Finally, the ADC values of HMP have been computed and then compared between images acquired in the scanners at 0.35 and 1.5 T.ResultsIn order to acquire high-quality artifact-free DWI images, the “slice” gradient direction has been identified to be the optimal one and 0° to be the best gradient angle. Both the SNR ratio and the uniformity increase with the number of averages. A threshold value of 80 for SNR and 85% for uniformity was adopted to choose the best number of averages. By making a compromise between time and quality and limiting the number of b-values, it is possible to reduce the acquisition time to 78 s. The Passing–Bablok test showed that the two methods, with 0.35 and 1.5 T scanners, led to similar results.ConclusionThe quality of the DWI has been accurately evaluated in relation to different sequence parameters, and optimal parameters have been identified to select a clinical protocol for the acquisition of ADC maps sustainable in the workflow of a hybrid radiotherapy system with a 0.35-T MRI scanner.

Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer’s disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force–distance (FD) curves, which allowed us to retrieve the apparent Young’s modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology.

(1) Background: New generation of PET-CT scanners allows performing volumetric dosimetry based on 90Y-activity distribution. The aim of this study was to perform an up-to-date evaluation of the optimal 90Y-PET-CT reconstruction parameters for a Siemens Biograph mCT scanner. (2) Methods: A cylindrical uniform phantom (P1), IEC NEMA Body-phantom (P2) and IEC NEMA Torso-phantom (P3) filled with 90Y were acquired. The matrix size and number of Equivalent Iterations (E.I.) were evaluated through the Recovery Coefficient (RC) and the Coefficient of Variation (CoV). The optimal post-reconstruction Gaussian Filter (GF) was assessed through an analysis of Root Mean Square Error (RMSE) and Full Width at Half Maximum (FWHM) in DVHs. (3) Results: For P1, RC values showed constant trends varying the matrix size (slope m = 1.25 × 10−3) or E.I. (slope m = −2.16 × 10−4). For P2, CoV decreased increasing the matrix size and it grew increasing the E.I. For P3, RMSE and mean dose values showed constant trends varying the Gaussian filter (slope m = 1.51 × 10−2) while FWHM decreased increasing filter. For smaller volumes, RMSE grew increasing the filter (from 34% to 74%) and the use of larger filters resulted in a dose underestimation (from 172 to 133 Gy). (4) Conclusions: The optimal reconstruction parameters for the Siemens Biograph mCT PET/CT scanner are presented, combining old metrics with new ones involving a dosimetric approach.

We report the case of a 38 year-old Caucasian man enrolled in a study aimed at investigating the physical properties of red blood cells (RBCs) using advanced microscopy techniques, including Atomic Force Microscopy (AFM). At the time of his first enrolment in the study, he had normal Fasting Plasma Glucose (FPG) values, a BMI of 24.1, and no other symptoms of diabetes, including fatigue, high triglycerides, low HDL cholesterol, and altered inflammatory and corpuscular RBC indices. The subject reported no family history of diabetes, obesity, and cardiovascular diseases. Despite his apparently healthy conditions, the biomechanics of his RBCs was altered, showing increased values of stiffness and viscosity. More than 1 year after the mechanical measurements, the subject was admitted to the Operational Unit of Diabetology of the Policlinico Gemelli Hospital with high blood glucose and glycosylated hemoglobin (HbA1c) levels and diagnosed with type 1 diabetes (T1DM). Here, we show these data, and we discuss the hypothesis that RBC mechanical properties could be sensitive to changes occurring during the pre-diabetic phase of T1DM.

Many ocular diseases are associated with an alteration of the mechanical and the material properties of the eye. These mechanically-related diseases include macular hole and pucker, two ocular conditions due to the presence of abnormal physical tractions acting on the retina. A complete relief of these tractions can be obtained through a challenging microsurgical procedure, which requires the mechanical peeling of the internal limiting membrane of the retina (ILM). In this paper, we provide the first comparative study of the nanoscale morphological and mechanical properties of the ILM in macular hole and macular pucker. Our nanoscale elastic measurements unveil a different bio-mechanical response of the ILM in the two pathologies, which correlates well to significant differences occurring during microsurgery. The results here presented pave the way to the development of novel dedicated microsurgical protocols based on the material ILM properties in macular hole or pucker. Moreover, they contribute to clarify why, despite a common aetiology, a patient might develop one disease or the other, an issue which is still debated in literature.

Background: Recent studies have highlighted the potentialities of a radiobiological parameter, the early regression index (ERITCP), in the treatment response prediction for rectal cancer patients treated with chemoradiotherapy followed by surgery. The aim of this study is to evaluate the performance of this parameter in predicting pathological complete response (pCR) in the context of low field MR guided radiotherapy (MRgRT) for cervical cancer (CC). Methods: A total of 16 patients affected by CC were enrolled. All patients underwent a MRgRT treatment, with prescription of 50.6 Gy in 22 fractions. A daily MR acquisition was performed at simulation and on each treatment fraction. Gross tumor volume (GTV) was delineated on the MR images acquired at the following biological effective dose (BED) levels: 14, 28, 42, 54 and 62 Gy. The ERITCP was calculated at the different BED levels and its predictive performance was quantified in terms of receiver operating characteristic (ROC) curve. Results: pCR was observed in 11/16 cases. The highest discriminative power of ERITCP was reported when a BED value of 28 Gy is reached, obtaining an area under curve (AUC) of 0.84. Conclusion: This study confirmed ERITCP as a promising response biomarker also for CC, although further studies with larger cohort of patients are recommended.

Atomic force microscopy (AFM) in spectroscopy mode receives a lot of attention because of its potential in distinguishing between healthy and cancer tissues. However, the AFM translational process in clinical practice is hindered by the fact that it is a time-consuming technique in terms of measurement and analysis time. In this paper, we attempt to address both issues. We propose the use of neural networks for pattern recognition to automatically classify AFM force−distance (FD) curves, with the aim of avoiding curve-fitting with the Sneddon model or more complicated ones. We investigated the applicability of this method to the classification of brain cancer tissues. The performance of the classifier was evaluated with receiving operating characteristic (ROC) curves for the approach and retract curves separately and in combination with each other. Although more complex and comprehensive models are required to demonstrate the general applicability of the proposed approach, preliminary evidence is given for the accuracy of the results, and arguments are presented to support the possible applicability of neural networks to the classification of brain cancer tissues. Moreover, we propose a possible strategy to shorten measurement times based on the estimation of the minimum number of FD curves needed to classify a tissue with a confidence level of 0.005. Taken together, these results have the potential to stimulate the design of more effective protocols to reduce AFM measurement times and to get rid of curve-fitting, which is a complex and time-consuming issue that requires experienced staff with a strong data-analysis background.

Pottery is the most common material found in archaeological excavations and is used as the main tool for chronological dating. Due to the geopolitical instability of the Middle East during the latter part of the last century until recent years, Sumerian pottery studies and analyses are limited. The resumption of archaeological excavations in Iraq during the last ten years allows the acquisition of new information and the study of archaeological material excavated through modern stratigraphic methodologies. This paper presents the results of the non-destructive analyses of Abu Tbeirah Sumerian pottery (Iraq) from the 3rd millennium BC and is aimed at analysing the crystallographic composition of ceramic material, therefore contributing to fill a gap in the knowledge of early Southern Mesopotamian pottery production, shedding new light on details of ancient technology and manufacturing techniques. Among the wide range of analytical techniques available, neutron-based ones have been chosen, obtaining detailed analyses in a non-destructive manner. Non-destructive and non-invasive neutron diffraction (ND) was applied in combination with chemometrics such as Principal Component Analysis (PCA) and Cluster Analysis (CA). ND confirms a general uniformity of the raw materials and a local Mesopotamian provenance through a comparison with modern local clay. Moreover, secondary minerals and their marker-temperature formation imply two different ranges of firing temperature that never exceeded 1000 °C, a temperature easily reachable through pit-firing techniques.