Automated planning through robust templates and multicriterial optimization for lung VMAT SBRT of lung lesions.

PURPOSE: To develop and validate a robust template for VMAT SBRT of lung lesions, using the multicriterial optimization (MCO) of a commercial treatment planning system. METHODS: The template was established and refined on 10 lung SBRT patients planned for 55 Gy/5 fr. To improve gradient and conformity a ring structure around the planning target volume (PTV) was set in the list of objectives. Ideal fluence optimization was conducted giving priority to organs at risk (OARs) and using the MCO, which further pushes OARs doses. Segmentation was conducted giving priority to PTV coverage. Two different templates were produced with different degrees of modulation, by setting the Fluence Smoothing parameter to Medium (MFS) and High (HFS). Each template was applied on 20 further patients. Automatic and manual plans were compared in terms of dosimetric parameters, delivery time, and complexity. Statistical significance of differences was evaluated using paired two-sided Wilcoxon signed-rank test. RESULTS: No statistically significant differences in PTV coverage and maximum dose were observed, while an improvement was observed in gradient and conformity. A general improvement in dose to OARs was seen, which resulted to be significant for chest wall V30 Gy , total lung V20 Gy , and spinal cord D0.1 cc . MFS plans are characterized by a higher modulation and longer delivery time than manual plans. HFS plans have a modulation and a delivery time comparable to manual plans, but still present an advantage in terms of gradient. CONCLUSION: The automation of the planning process for lung SBRT using robust templates and MCO was demonstrated to be feasible and more efficient.

The Conventional Non-Articulated SACH or a Multiaxial Prosthetic Foot for Hypomobile Transtibial Amputees? A Clinical Comparison on Mobility, Balance, and Quality of Life.

The effects of a non-articulated SACH and a multiaxial foot-ankle mechanism on the performance of low-activity users are of great interest for practitioners in amputee rehabilitation. The aim of this study is to compare these two prosthetic feet and assess possible improvements introduced by the increased degrees of freedom provided by the multiaxial foot. For this purpose, a group of 20 hypomobile transtibial amputees (TTAs) had their usual SACH replaced with a multiaxial foot. Participants' functional mobility, involving ambulatory skills in overground level walking, ramps, and stairs, was evaluated by performing Six-Minute Walking Test (6 MWT), Locomotor Capability Index-5 (LCI-5), Hill Assessment Index (HAI), and Stair Assessment Index (SAI). Balance performances were assessed using Berg Balance Scale (BBS) and analysing upper body accelerations during gait. Moreover, the Prosthesis Evaluation Questionnaire (PEQ) was performed to indicate the prosthesis-related quality of life. Results showed that participants walked faster using the multiaxial foot (p < 0.05) maintaining the same upright gait stability. Significant improvements with the multiaxial foot were also observed in BBS, LCI-5, and SAI times and 4 of 9 subscales of the PEQ. Our findings demonstrate that a multiaxial foot represents a considerable alternative solution with respect to the conventional SACH in the prosthetic prescription for hypomobile TTAs.

[The prosthetic phase: the prosthesis, the prostheses]. / Fase protesica: la protesi, le protesi.

The technological evolution that has characterized the last two decades, both in terms of materials, electronics and automations, has made available new solutions in the field of design and manufacturing of lower limb prostheses allowing to overcome some of the historical limitations of such devices. The aim of this work is to give an overview of the components of a prosthetic device for lower limb amputations, investigating the functional aspects that guide the clinical and technical choices towards the most suitable solutions according to the somatic features, rehabilitation needs and lifestyle of the amputee subject.

Lexicographic optimization-based planning for stereotactic radiosurgery of brain metastases.

AIM: To validate a fully-automated lexicographic optimization-planning system (mCycle, Elekta) for single-(SL) and multiple-(ML, up to 4 metastases) lesions in intracranial stereotactic radiosurgery (SRS, 21 Gy, single fraction). METHODS: A pre-determined priority list, Wish-List (WL), represents a dialogue between planner and clinician, establishing strict constraints and pursuing objectives. In order to satisfy the clinical protocol without manual intervention, four patients were required to tweak and fine-tune each WL (SLp, MLp) for coplanar arcs. Thirty-five testing plans (20 SLp, 15 MLp) were automatically re-planned (mCP). Automatic and manual plans were compared including dose constraints, conformality, modulation complexity score (MCS), delivery time, and local gamma analysis (2%/2 mm). To ensure plan clinical acceptability, two radiation oncologists conducted an independent blind plan choice. RESULTS: Each WL-tuning took 3 days. Estimated median manual plans and mCP calculation time were 8 and 3 h, respectively. Significant increases in SLp and MLp target coverage and conformity were registered. mCP showed a not significant and clinically acceptable higher median brain V12Gy. SLp registered a -5.8% MU decrease with comparable median delivery time (MP 2.0 min, mCP 1.9 min) while MLp showed a +9.8% MU increase and longer delivery time (MP 3.5 min, mCP 4.4 min). mCP MCS resulted significantly higher without affecting gamma passing rates. At blind choice, mCP were preferred in the majority of cases. CONCLUSIONS: Lexicographic optimization produced acceptable SRS plans with coplanar arcs significantly reducing the overall planning time in cases with up to 4 brain metastases. These planning improvements suggest further investigations by setting high-quality non-coplanar arc plans as a reference.

A finite element analysis of load distribution during donning and orthostatic posture in the ITOP hybrid subischial socket.

INTRODUCTION: Pressure and shear stresses applied to the stump of a transfemoral amputee wearing a newly designed prosthetic socket have been analyzed by a finite element modeling approach. METHODS: The new socket was developed by the Istituto Tecnico Ortopedico Preneste, and it was named the "hybrid subischial socket." This work aimed at understanding the loads' distribution on the stump surface in 2 operative conditions: at the end of the wearing phase and during the orthostatic posture. The model of the stump was composed of 4 different materials: the femoral bone, the muscle tissue, the fat, and the skin layers. Except for the bone (rigid), the biological tissues were modeled as Neo-Hookean, and their mechanical properties were taken from the literature. The socket was composed of a containment frame, made of carbon fiber composite material, a shell made of flexible silicone, and a liner made of hyperelastic silicone. RESULTS: The results of our simulation show that the main support areas are located in a proper position, in agreement with the ideal principles of this prosthetic design, and the maximum pressures are well below the pain threshold reported in the literature for the same contact areas. CONCLUSIONS: We can conclude that although the upper rim of the socket is well below the ischiatic area, the new socket design allows for a safe and comfortable support of the body weight. This is in agreement with the evidence of a good functionality and acceptance of this prosthetics gathered in the many real applications.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT.

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments.

Experimental and in silico evaluations of the possible molecular interaction between airborne particulate matter and SARS-CoV-2.

During the early stage of the COVID-19 pandemic (winter 2020), the northern part of Italy has been significantly affected by viral infection compared to the rest of the country leading the scientific community to hypothesize that airborne particulate matter (PM) could act as a carrier for the SARS-CoV-2. To address this controversial issue, we first verified and demonstrated the presence of SARS-CoV-2 RNA genome on PM2.5 samples, collected in the city of Bologna (Northern Italy) in winter 2021. Then, we employed classical molecular dynamics (MD) simulations to investigate the possible recognition mechanism(s) between a newly modelled PM2.5 fragment and the SARS-CoV-2 Spike protein. The potential molecular interaction highlighted by MD simulations suggests that the glycans covering the upper Spike protein regions would mediate the direct contact with the PM2.5 carbon core surface, while a cloud of organic and inorganic PM2.5 components surround the glycoprotein with a network of non-bonded interactions resulting in up to 4769 total contacts. Moreover, a binding free energy of -207.2 ± 3.9 kcal/mol was calculated for the PM-Spike interface through the MM/GBSA method, and structural analyses also suggested that PM attachment does not alter the protein conformational dynamics. Although the association between the PM and SARS-CoV-2 appears plausible, this simulation does not assess whether these established interactions are sufficiently stable to carry the virus in the atmosphere, or whether the virion retains its infectiousness after the transport. While these key aspects should be verified by further experimental analyses, for the first time, this pioneering study gains insights into the molecular interactions between PM and SARS-CoV-2 Spike protein and will support further research aiming at clarifying the possible relationship between PM abundance and the airborne diffusion of viruses.

Updating approach for lexicographic optimization-based planning to improve cervical cancer plan quality.

BACKGROUND: To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy. MATERIAL AND METHODS: Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation. RESULTS: The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6-99.3], mCP01 99.2 [89.7-99.9], mCP02 96.9 [89.4-99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2-47.0], mCP01 40.3 [31.4-45.8], mCP02 32.6 [26.9-42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP. CONCLUSIONS: This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

Fully automated volumetric modulated arc therapy technique for radiation therapy of locally advanced breast cancer.

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed. RESULTS: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V95%) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT. CONCLUSIONS: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.

Breast Volume Is a Predictor of Higher Heart Dose in Whole-Breast Supine Free-Breathing Volumetric-Modulated Arc Therapy Planning.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Comprehensive dosimetric and clinical evaluation of lexicographic optimization-based planning for cervical cancer.

Aim: In this study, a not yet commercially available fully-automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), was validated for cervical cancer. Material and methods: Twenty-four mono-institutional consecutive treatment plans (50 Gy/25 fx) delivered between November 2019 and April 2022 were retrospectively selected. The automatic re-planning was performed by mCycle, implemented in the Monaco TPS research version (v5.59.13), in which the LO and Multicriterial Optimization (MCO) are coupled with Monte Carlo calculation. mCycle optimization follows an a priori assigned priority list, the so-called Wish List (WL), representing a dialogue between the radiation oncologist and the planner, setting hard constraints and following objectives. The WL was tuned on a patient subset according to the institution's clinical protocol to obtain an optimal plan in a single optimization. This robust WL was then used to automatically re-plan the remaining patients. Manual plans (MP) and mCycle plans (mCP) were compared in terms of dose distributions, complexity (modulation complexity score, MCS), and delivery accuracy (perpendicular diode matrices, gamma analysis-passing ratio, PR). Their clinical acceptability was assessed through the blind choice of two radiation oncologists. Finally, a global quality score index (SI) was defined to gather into a single number the plan evaluation process. Results: The WL tuning requested four patients. The 20 automated re-planning tasks took three working days. The median optimization and calculation time can be estimated at 4 h and just over 1 h per MP and mCP, respectively. The dose comparison showed a comparable organ-at-risk spare. The planning target volume coverage increased (V95%: MP 98.0% [95.6-99.3]; mCP 99.2%[89.7-99.9], p >0.05). A significant increase has been registered in MCS (MP 0.29 [0.24-0.34]; mCP 0.26 [0.23-0.30], p <0.05) without affecting delivery accuracy (PR (3%/3mm): MP 97.0% [92.7-99.2]; mCP 97.1% [95.0-98.6], p >0.05). In the blind choice, all mCP results were clinically acceptable and chosen over MP in more than 75% of cases. The median SI score was 0.69 [0.41-0.84] and 0.73 [0.51-0.82] for MP and mCP, respectively (p >0.05). Conclusions: mCycle plans were comparable to clinical manual plans, more complex but accurately deliverable and registering a similar SI. Automated plans outperformed manual plans in blinded clinical choice.

Automated Planning for Prostate Stereotactic Body Radiation Therapy on the 1.5 T MR-Linac.

PURPOSE: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac. METHODS AND MATERIALS: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [Dp]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the Dp to at least 95% of the planning target volume (PTV), V33.2 (PTV) ≥ 95%, a dose less than the Dp to the hottest cubic centimeter (V35 ≤ 1 cm3) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V32 ≤ 5%, V28 ≤ 10%, and V18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans. RESULTS: mCycle plans improved target dose coverage, with V33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans (P < .001), and rectal dose sparing, with significantly reduced V32, V28, and V18 (P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) (P < .001), whereas they were generally faster (-19%) in terms of optimization times (P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) (P = .059) and γ (2 mm, 2%) (P = .432) deliverability metrics. CONCLUSIONS: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task.

Inhibition of colon carcinogenesis by 2-methoxy-5-amino-N-hydroxybenzamide, a novel derivative of mesalamine.

BACKGROUND & AIMS: Mesalamine has been reported to protect against inflammatory bowel disease-related colorectal cancer (CRC), but several drug-related issues have limited its use in chemopreventive programs. We evaluated the antineoplastic properties of mesalamine derivatives using in vitro and in vivo models of CRC. METHODS: CRC cell proliferation and cell-cycle progression were evaluated by flow cytometry after exposure to mesalamine or mesalamine derivatives. Cyclins, cyclin-dependent kinases, and endoplasmic reticulum stress-related molecules were examined by immunoblotting. The in vivo antineoplastic effect of 2-methoxy-5-amino-N-hydroxybenzamide (2-14) was evaluated in a syngenic, CT26-derived xenograft mouse model of CRC and in the azoxymethane/dextran sulfate sodium-induced mouse model of colitis-associated CRC. RESULTS: The mesalamine derivative 2-14 was 10-fold more potent than mesalamine in inhibiting CRC cell proliferation. After exposure to 2-14, cyclin D1 expression was reduced and G0/G1 phase cells accumulated. These events were preceded by activation of eukaryotic translation initiation factor 2-alpha kinase 3 (pancreatic endoplasmic reticulum eIF2alpha kinase), phosphorylation of eukaryotic translation initiation factor 2alpha, induction of activating transcription factor 4, and splicing of X-box binding protein 1 messenger RNA, events that define endoplasmic reticulum stress. Silencing of PERK restored cyclin D1 levels, allowing cells to overcome the cell-cycle block induced by 2-14. Mice injected with 2-14 developed fewer CRC xenograft-derived tumors. Moreover, 2-14 injection reduced the development of neoplastic lesions induced by azoxymethane and dextran sulfate sodium in mice. CONCLUSIONS: The mesalamine derivative 2-14 inhibited CRC cell proliferation in vitro and prevented CRC progression in mouse models.

MRI only in a patient with prostate cancer with bilateral metal hip prostheses: case study.

OBJECTIVE: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts. CASE DESCRIPTION: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists. CONCLUSIONS: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time.

PURPOSE: Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. MATERIAL AND METHODS: For twenty PC patients treated by 35 Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95% ≥ 95%Dp to PTV, and D1cc ≤ Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. RESULTS: For each patient, CTV coverage resulted in D95% > 95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was < Dp for rectum, urethral-PRV, and penile bulb, whereas < 103.5%Dp for the bladder. Significant correlations resulted between metrics computed by Dsum and as ifa by Drec, by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis. CONCLUSIONS: Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5 T MR-linac, and the consistency between dose-volume metrics computed by Drec and Dsum.

Quality assurance of volumetric modulated arc therapy using Elekta Synergy.

PURPOSE. Recently, Elekta has supplied volumetric modulated arc therapy (VMAT) in which multi-leaf collimator (MLC) shape, jaw position, collimator angle, and gantry speed vary continuously during gantry rotation. A quality assurance procedure for VMAT delivery is described. METHODS AND MATERIALS. A single-arc VMAT plan with 73 control points (CPs) and 5-degree gantry angle spacing for a prostate cancer patient has been created by ERGO + + treatment planning system (TPS), where MLC shapes are given by anatomic relationship between a target and organs at risk and the monitor unit for each CP is optimized based on given dose prescriptions. Actual leaf and jaw positions, gantry angles and dose rates during prostate VMAT delivery were recorded in every 0.25 seconds, and the errors between planned and actual values were evaluated. The dose re-calculation using these recorded data has been performed and compared with the original TPS plan using the gamma index. RESULTS. Typical peak errors of gantry angles, leaf positions, and jaw positions were 3 degrees, 0.6 mm, and 1 mm, respectively. The dose distribution obtained by the TPS plan and the recalculated one agreed well under 2%-2 mm gamma index criteria. CONCLUSIONS. Quality assurance for prostate VMAT delivery has been performed with a satisfied result.

Molecular basis of the potential of mesalazine to prevent colorectal cancer.

Patients with ulcerative colitis (UC) and Crohn's disease (CD) are at increased risk for developing colorectal cancer (CRC), and this is believed to be a result of chronic inflammation. Although conclusive evidence is still missing, both epidemiological and experimental observations suggest that certain drugs used to treat inflammation, such as mesalazine, can reduce the incidence of colitis-associated CRC. Therefore, in recent years, several studies have been conducted to dissect the mechanisms by which mesalazine interferes with CRC cell growth and survival. This review summarizes the current information on the molecular mechanisms that underlie the antineoplastic action of mesalazine.

Fully automated, multi-criterial planning for Volumetric Modulated Arc Therapy - An international multi-center validation for prostate cancer.

BACKGROUND AND PURPOSE: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. MATERIAL AND METHODS: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. RESULTS: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p < 0.001) in Dmean, 4.0% (p < 0.001) in V60Gy, and 1.5% (p = 0.001) in V75Gy, and for bladder Dmean (0.9 Gy, p < 0.001). Also the clinicians' plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum Dmean and V60Gy of [-4,12] Gy and [-2,15]%, respectively. CONCLUSION: Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

Comparison between SACH foot and a new multiaxial prosthetic foot during walking in hypomobile transtibial amputees: physiological responses and functional assessment.

BACKGROUND: The most prescribed prosthetic foot for hypomobile transtibial amputees (TTAs) is the solid ankle cushion heel (SACH). Recently, the new 1M10 Adjust (Ottobock, Duderstadt, Germany) has been designed for hypomobile TTAs. No studies are available about the physiological responses to walking with 1M10 Adjust or about the related energy cost of walking (ECW). The aim of this study was to assess physiological responses to walking with 1M10 Adjust and with SACH in low-mobility TTAs and their ECW, and to compare 1M10 Adjust and SACH for physiological responses, ECW, relative perceived effort and satisfaction (SATPRO) using the prosthesis. DESIGN: Observational study. SETTING: The study was conducted in the outpatient rehabilitation unit of a rehabilitation center. POPULATION: Twenty hypomobile unilateral TTAs were enrolled. Amputees who ranged K-levels 1 or 2 were defined. METHODS: TTAs performed two over ground walking tests in two separate days, with an interval time in between of 30 days. TTAs performed the first walking test wearing their habitual SACH foot; the second walking test fitting the 1M10 Adjust, after 30 days of its use. During walking tests, TTAs walked back and forth for 6 minutes at self-selected walking speed (SSWS) and physiological data were collected. At the end of each walking test, the relative perceived effort was assessed by Borg scale. Finally, SATPRO questionnaire was administered. RESULTS: Twenty TTAs (17 males) were enrolled (mean age, body mass and height were 66.6±6.7 years, 78.5±13.2 kg, and 168.5±7.5 cm, respectively): 19 had a K-level 2 and one had a K-level 1. Physiological responses using SACH or 1M10 Adjust foot did not show statistical differences. ECW, SSWS and relative perceived effort significantly improved using the 1M10 Adjust. Satisfaction with 1M10 Adjust was significantly greater than with SACH. CONCLUSIONS: TTAs showed a significant improvement in ECW, relative perceived effort and SATPRO with 1M10 Adjust than with SACH. This suggests that 1M10 Adjust foot could be a good choice for hypomobile TTAs. CLINICAL REHABILITATION IMPACT: The better prosthetic performance provided by 1M10 Adjust foot during gait could improve mobility in TTAs with low mobility contributing to prevent comorbidity deriving from sedentary lifestyle. With its long-term benefits, 1M10 Adjust could contribute to a better quality of life.

Feasibility of single-isocenter, multi-arc non-coplanar volumetric modulated arc therapy for multiple brain tumors using a linear accelerator with a 160-leaf multileaf collimator: a phantom study.

The feasibility of single isocenter, multi-arc non-coplanar volumetric modulated arc therapy (VMAT) for multiple brain tumors was studied using an Elekta Synergy linear accelerator with an Agility multileaf collimator and a Monaco treatment planning system. Two VMAT radiosurgery plans consisting of a full arc and three half arcs were created with a prescribed dose of 20 Gy in a single fraction. After dose delivery to a phantom, ionization chambers and radiochromic films were used for dose measurement. The first VMAT radiosurgery plan had nine targets inside the phantom, and the doses were measured by the chambers at two different points and by the films on three sagittal and three coronal planes. The differences between the calculated dose and the dose measured by a Farmer ionization chamber and a pinpoint ionization chamber were <1.00% and <2.30%, respectively, and the average pass rates of gamma indices among the six planes under each of 3%/3 mm and 2%/2 mm criteria were 98.6% and 92.6%, respectively. The second VMAT radiosurgery plan was based on a clinical 14 brain metastases. Differences between calculated and film-measured doses were evaluated on two sagittal planes. The average pass rates of the gamma indices on the planes under each of 3%/3 mm and 2%/2 mm criteria were 97.8% and 88.8%, respectively. It was confirmed that single-isocenter, non-coplanar multi-arc VMAT radiosurgery for multiple brain metastases was feasible using Elekta Synergy with Agility and Monaco treatment planning systems. It was further shown that film dosimetry was accurately performed for a dose of up to nearly 25 Gy.