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Purpose The software Dosimetry Check (DC) reconstructs the 3D dose distribution on CT images data set by using EPID measured signal. This study aimed to evaluate DC for stereotactic body radiotherapy (SBRT) with unflattened photon beams (FFF) for dosimetric independent plan verification in pre-treatment modality. Methods DC v.4.1 was configured for Varian TrueBeam STx FFF beams equipped with EPID aS-1200. The DC FFF models were tested using arc open fields (from 1×1 cm2 to 15×15 cm2) and VMAT (Volumetric Modulated Arc Therapy) SBRT plans on phantom and patient CTs. DC dose distributions ( D DC ) were compared with that calculated by Eclipse with Acuros XB algorithm ( D AXB ) and one measured by Octavius 1000 SRS detector ( D OCT ). All differences were quantified in terms of the local 3D gamma passing rate (%GP), DVH and point dose differences. Results DC was configured for FFF VMAT using an appropriate correction procedure. %GP2%2mm (mean±standard deviation) of D OCT - D DC was 96.3±2.7% for open fields whereas it was 90.1±5.9% for plans on homogeneous phantom CT. However, average %GP3%3mm of D AXB - D DC was 95.0±4.1 for treatments on patient CT. The fraction of plans passing the %GP3%3mm DQA tolerance level [10% (50%) of maximum dose threshold] were 20/20 (14/20) and 18/20 (16/20) for OCT on phantom CT and DC on patient CT, respectively. Conclusions DC characterization for FFF beams was performed. For stereotactic VMAT plan verifications DC showed good agreement with TPS whereas underlined discrepancies with Octavius in the high dose regions. A customized tolerance level is required for EPID-based VMAT FFF pre-treatment verification when DC system is applied.

Purpose To investigate the performance of various algorithms for deformable image registration (DIR) for propagating regions of interest (ROIs) using multiple commercial platforms, from computed tomography to cone beam computed tomography (CBCT) and megavoltage computed tomography. Methods and Materials Fourteen institutions participated in the study using 5 commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH), VelocityAI and SmartAdapt (Varian Medical Systems, Palo Alto, CA), and ABAS (Elekta AB, Stockholm, Sweden). Algorithms were tested on synthetic images generated with the ImSimQA (Oncology Systems Limited, Shrewsbury, UK) package by applying 2 specific deformation vector fields (DVF) to real head and neck patient datasets. On-board images from 3 systems were used: megavoltage computed tomography from Tomotherapy and 2 kinds of CBCT from a clinical linear accelerator. Image quality of the system was evaluated. The algorithms’ accuracy was assessed by comparing the DIR-mapped ROIs returned by each center with those of the reference, using the Dice similarity coefficient and mean distance to conformity metrics. Statistical inference on the validation results was carried out to identify the prognostic factors of DIR performance. Results Analyzing 840 DIR-mapped ROIs returned by the centers, it was demonstrated that DVF intensity and image quality were significant prognostic factors of DIR performance. The accuracy of the propagated contours was generally high, and acceptable DIR performance can be obtained with lower-dose CBCT image protocols. Conclusions The performance of the systems proved to be image quality specific, depending on the DVF type and only partially on the platforms. All systems proved to be robust against image artifacts and noise, except the demon-based software.

To quantify inter-institute variability of Knowledge-Based (KB) models for right breast cancer patients treated with tangential fields whole breast irradiation (WBI).Ten institutions set KB models by using RapidPlan (Varian Inc.), following previously shared methodologies. Models were tested on 20 new patients from the same institutes, exporting DVH predictions of heart, ipsilateral lung, contralateral lung, and contralateral breast. Inter-institute variability was quantified by the inter-institute SDThe overall inter-institute variability of DVH/Dmean ipsilateral lung dose prediction, was less than 2% (20%-80% dose range) and 0.55 Gy respectively (1SD) for a 40 Gy in 15 fraction schedule; it was0.2 Gy for other OARs. Institute 6 showed the lowest mean dose prediction value and no overlap between PTV and ipsilateral lung. Once excluded, the predicted ipsilateral lung Dmean was correlated with median PTV D99% (RResults show limited inter-institute variability of plan prediction models translating in high inter-institute interchangeability, except for one of ten institutes. These results encourage future investigations in generating benchmarks for plan prediction incorporating inter-institute variability.

The use of Monte Carlo methods for the set up of Treatment Planning Systems (TPS) in radiotherapy applications is a current standard. The most advanced modeling techniques aim at directly link the output of CT scans to a patient-specific model build up instead of standard phantoms and look-up tables. This link represents a critical step since even the most accurate segmentation and organ volume definition must be translated into a suitable input for the Monte Carlo code. During that step, the segmented volume is usually mapped on a regular geometrical lattice (voxels). A more sophisticated option appears to be a volume description based on an Unstructured Mesh (UM) geometry typical of current finite element codes. In this paper, we compared the two approaches analyzing the bias induced by the different choices. Starting from anonymous patient DICOM files coming from a CT scan, suitable segmentation and volume definition have been carried out and voxel and UM-based equivalent models for the Monte Carlo code MCNP6 have been built. Some computational phantoms, covering some significant portion of the human body (head and lower limb), have been used as a benchmark of the dose distribution obtained from X-ray sources commonly used in orthovoltage applications. The specific clinical application has been chosen because, despite being used on a growing number of patients and with multi-Gy doses, treatment planning is still based on poorly characterized dose mapping systems such as look-up tables or low-resolution computational phantoms for MC codes. Also, experimental measurements on phantom slabs irradiated by an X-ray source were carried out preliminarily to validate the simulated radiation source. As shown in the results, the UM computational phantoms (built through the Simpleware SCAN-IP™ tool) can reduce the bias induced by the regularity of the classical cubic voxel geometry, give a more accurate description of volumes and complex surfaces and, thanks to an optimized discretization of the volumes, are also able to reduce the computational work. For the same UM models, various comparisons with different voxel sizes have been produced to investigate the dose distributions and evaluate the voxelization effects. The comparison shows a convergence pattern of the voxel model to the UM one. It has been possible to verify that the most significant bias occurs where the dose gradient is higher, along the beam borders and at tissue interfaces. The simulations showed that the UM can be really effective and reliable to compute the dose distributions within computational anthropomorphic phantoms obtained from the patient’s CT scans.

Purpose The complexity of the modern Stereotactic Body Radiation Therapy (SBRT) techniques requires comprehensive quality assurance programs, to ensure the right treatment to the patient. Dosimetry of small radiation fields is a challenge especially for radiotherapy centres starting to work on this issue. The matter to be discussed here concerns the need of detailed measurement procedures and cross checks to be paired to the usual recommendations on detectors and correction factors. Materials and Methods The presented work involved 24 Italian radiotheraphy centres, with the specific purpose to minimize systematic errors in output factor measurements over different radiotherapy centres. Using the unshielded silicon diode IBA Razor, reference curves for the relative signal ratio (RSR) as a function of beam size were created for each Linac family. Results With this study we have demonstrated consistency of small field dosimetry on all the centres involved, moreover all radiotherapy centres using Razor are allowed to compare measurements amongst each other and centres with values deviating more than 5% from the reference curve are advised to repeat their measurements. With this procedure, some critical issues were detected from two centres in RSR measurements, that, if implemented into the own treatment planning system, would induce an unwanted overdosage larger than 5%. Conclusions The proposed approach could allow one to envision high-skilled therapy centres providing support to those featuring minor experience and could represent an important strategy for the clinical implementation of emerging technologies at high quality levels. The methodology adopted exploits crowd knowledge methods which could be applied in others areas of radiation dosimetry.

A nationwide survey was conducted in adult patients with psoriasis (PsO) across Italy to obtain their real-world perspective of the impact of PsO on their wellbeing. Patients completed a 26-question survey (based on the patient benefit index; PBI, The Dermatology Life Quality Index; DLQI and the World Health Organization-five; WHO-5 wellbeing index) and workshop discussion sessions were undertaken by dermatologists to interpret results from the survey. 392 patients with PsO completed the survey. Analysis of results was restricted to patients who had moderate-to-severe plaque psoriasis (assessed by patients; n = 252; 64.3%). Dermatologists (n = 32) completed one question from the survey related to wellbeing and rated social, physical and mental domains as contributing to a similar extent, with comparable scores also observed by patients. For treatment, biologics yielded higher scores on average, whereas little difference was observed between topical and conventional systemic treatments. Only 23.8% of patients felt that their dermatologist was taking into consideration their wellbeing and 32.6% of the patients considered their therapy as inadequate in improving signs and symptoms of the disease. This survey identified key factors contributing to barriers impacting on patient wellbeing. Simple, but comprehensive questionnaires can provide important insight to patients’ needs that may significantly increase clinician awareness during visits leading to tailored treatment.

Purpose To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms. Methods and materials Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data-sets. Head-and-neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances. Results DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub-voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low-contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free-form intensity based algorithms and resulted robust against intercenter variability. Conclusions The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub-voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm.

Purpose Treatment plans manually generated in clinical routine may suffer from variations and inconsistencies in quality. Using such plans for validating a DVH prediction algorithm might obscure its intrinsic prediction accuracy. In this study we used a recently published large database of Pareto-optimal prostate cancer plans to assess the prediction accuracy of a commercial knowledge-based DVH prediction algorithm, RapidPlan. The database plans were consistently generated with automated planning using an independent optimizer, and can be considered as aground truth of plan quality. Methods Prediction models were generated using training sets with 20, 30, 45, 55 and 114 Pareto-optimal plans. Model-20 and Model-30 were built using 5 groups of randomly selected training patients. For 60 independent Pareto-optimal validation plans, predicted and database DVHs were compared. Results For model-114, differences between predicted and database mean doses of more than ± 10% in rectum, anus and bladder, occurred for 23.3%, 55.0%, and 6.7% of the validation plans, respectively. For rectum V65Gy and V75Gy, differences outside the ±10% range were observed in 21.7% and 70.0% of validation plans, respectively. For 61.7% of validation plans, inaccuracies in predicted rectum DVHs resulted in a deviation in predicted NTCP for rectal bleeding outside ±10%. With smaller training sets the DVH prediction performance deteriorated, showing dependence on the selected training patients. Conclusion Even when analysed with Pareto-optimal plans with highly consistent quality, clinically relevant deviations in DVH predictions were observed. Such deviations could potentially result in suboptimal plans for new patients. Further research on DVH prediction models is warranted.

Purpose Helical Tomotherapy (HT) plans were used to create two RapidPlan knowledge-based (KB) models to generate plans with different techniques and to guide the optimization in a different treatment planning system for prostate plans. Feasibility and performance of these models were evaluated. Material and methods two sets of 35 low risk (LR) and 30 intermediate risk (IR) prostate cancer cases who underwent HT treatments were selected to train RapidPlan models. The KB predicted constraints were used to perform new 20 KB plans using RapidArc technique (KB-RA) (inter-technique validation), and to optimise 20 new HT (KB-HT) plans in the Tomoplan (inter-system validation). For each validation modality, KB plans were benchmarked with the manual plans created by an expert planner (EP). Results RapidPlan was successfully configured using HT plans. The KB-RA plans fulfilled the clinical dose-volume requirements in 100% and 92% of cases for planning target volumes (PTVs) and organs at risk (OARs), respectively. For KB-HT plans these percentages were found to be a bit lower: 90% for PTVs and 86% for OARs. In comparison to EP plans, the KB-RA plans produced higher bladder doses for both LR and IR, and higher rectum doses for LR. KB-HT and EP plans produced similar results. Conclusion RapidPlan can be trained to create models by using plans of a different treatment modality. These models were suitable for generating clinically acceptable plans for inter-technique and inter-system applications. The use of KB models based on plans of consolidated technique could be useful with a new treatment modality.

This study aimed to investigate if a commercial, knowledge-based tool for radiotherapy planning could be used to estimate potential organs at risk (OARs), which would spare the re-planning strategy for adaptive radiotherapy (ART). Sixty-four head and neck (HN) VMAT Pareto plans from our institute's database were used to train a knowledge-based planning (KBP) model. An evaluation set of 10 HN patients was randomly selected. For each patient in the evaluation set, the planning computed tomography (CT) and 2 sets of on-board cone-beam CT (CBCT), corresponding to the 16th and the 26th radiotherapy treatment fraction, were extracted. The original plan was re-calculated on a daily deformed CT (delivered DVH) and compared with the KBP DVH predictions and with the final KBP DVH after optimisation of the plan, which was performed on the same image sets. To evaluate the feasibility of this method, the range of KBP DVH estimation uncertainties were compared with the gains obtained from re-planning. DVH differences and ROC curve analysis were used for this purpose. On average, KBP uncertainties shared the same order of magnitude as the gain in re-planning. However, statistical tests confirmed significant differences between the two groups (p=0.02). There were statistically significant differences between the predicted and true values (after optimisation) (p

Objectives: This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans. Methods: Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm2 to 1 × 1 cm2) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points. Results: The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC‐defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms. Conclusion: The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing. Advances in knowledge: First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.

Purpose Small radiation fields (

Purpose A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective. Methods Five CT series were sent to the participants. The dose prescription to PTV was 54 Gy in 3 fractions of 18 Gy. The plans were compared in terms of PTV-gEUD 2 (generalized Equivalent Uniform Dose equivalent to 2 Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD 2 (mean lung dose equivalent to 2 Gy). The data were stratified according to expertise and technology. Results Twenty-six centers equipped with Linacs, 3DCRT (4% – 1 center), static IMRT (8% – 2 centers), VMAT (76% – 20 centers), CyberKnife (4% – 1 center), and Tomotherapy (8% – 2 centers) collaborated. Significant PTV-gEUD 2 differences were observed (range: 105–161 Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8 ± 3.4 Gy, 14.2 ± 10.1%, 0.70 ± 0.15, and 4.9 ± 1.9. Significant correlations for PTV-gEUD 2 versus PTV-HI, and MLD 2 versus PTV-GI, were observed. Conclusions The differences in terms of PTV-gEUD 2 may suggest the inclusion of PTV-gEUD 2 calculation for retrospective data inter-comparison.

Purpose To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. Methods Dose prescription was 75 Gy in 3 fractions, normalised at 67%–95% isodose. Results Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. Conclusions The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

Purpose Glioblastoma Multiforme (GBM) is the most common malignant brain tumor and frequently recurs in the same location after radiotherapy. Intensive treatment targeting localized lesion is required to improve GBM outcome, but dose escalation using conventional methods is limited by healthy tissue tolerance. Helical Tomotherapy (HT) Dose Painting (DP) treatments were simulated to safely deliver high doses in the recurrent regions. Materials and methods Apparent Diffusion Coefficient (ADC) data from five recurrent GBM were retrospectively considered for planning. Hypo-fractionated (25−50 Gy, 5 fractions) voxel-based prescriptions were opportunely converted to personalized structured-based dose maps to create DP plans with a commercial Treatment Planning System. Optimized plans were generated and analyzed in terms of plan conformity to dose prescription (Q 0.90–1.10 ), tolerance of the healthy tissues ( D MAX ), and dosimetry accuracy of the deliverable plans ( γ -index). Results Only three of the five cases could receive a safe retreatment without violating the maximum critical organs dose constraints. The conformity of the simulated plans was between 40.9% and 79.9% (Q 0.90–1.10 ), their delivery time was in the range of 38.3–63.6 min, while the dosimetry showed γ -index of 82.4–92.4%. Conclusions This study proved the ability of our method to simulate personalized, deliverable and dosimetrically accurate DPBN plans. HT hypo-fractionated treatments guided by ADC maps can be realized and applied to deliver high doses in the GBM recurrent regions, although there are some critical issues related to low Q 0.90–1.10 values, to exceeding of healthy-tissue dose constraints for some patients and long delivery times.

Purpose To investigate the accuracy and robustness of commercial algorithms for Deformable Image Registration (DIR) to propagate regions of interest (ROIs), against image quality typical of Cone Beam CT (CBCT) and Megavoltage Cone-beam CT (MVCT) images, using computational phantoms based on real head and neck (HN) patient images. Methods Eleven institutions joined the study with five commercial DIR solutions. Three real patient data-sets from different on board imaging devices (OBI by Varian, XVI by Elekta, and MVCT by Tomotherapy) were used with different image quality. Two specific Deformation Vector Fields (DVF) with realistic level of deformations, were generated with a dedicated software and then applied to each data-set. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Prognostic factors of DIR performances were carried out. Results Based on more than 700 DIR-mapped ROIs the 4-way ANOVA analysis states that DIR algorithm, image quality and organ type are significant predictors of DIR performances. A slightly dependence from applied DVF is detected (p = 0.035) with a post hoc test. Putting together all CI data of all institutions for the first DVF, the mean CI was 0.88 ± 0.05 (1 SD), and the mean MDC is 0.38 ± 0.96 (1 SD); for the second DVF, the mean CI was 0.86 ± 0.11 (1 SD), and the mean MDC is 0.43 ± 1.08 (1 SD). The thyroid, located near the FOV border, was the underperformer organ with large errors (unacceptable). All other organs were mapped with an acceptable accuracy (at voxel size level). One imaging system performs statistically better than the others, and one algorithm produced unsatisfactory results respect all the others. Conclusions This work studies the impact of CBCT and MVCT image quality on DIR performance in a ground truth provided scenario. Clinical issues like Adaptive Radiation Therapy (ART) need accurate and robust DIR software. The reported result highlight that in HN district the image quality and the implemented algorithm are strictly related to DIR performances.

Intensity-modulated arc therapy (IMAT) is an arc-based approach to intensity-modulated radiotherapy (IMRT) that can be delivered on a conventional linear accelerator using multiple overlapping arcs. As with other rotational IMRT techniques, IMAT is capable of producing highly conformal dose distributions that are able to compete with the simplest three-dimensional (3D) conformal radiotherapy (CRT) and the most effective static IMRT. Despite its potential, the clinical application of IMAT technique has gone largely unrealized due to the lack of robust and commercially available inverse- planning tools. To overcome this limitation, an in-house forward-planning strategy for planning the IMAT technique, called intensity modulated multiple arcs (IMMA) was developed. This planning approach was implemented for lung and cranial treatments with the aim of generating superior treatment plans compared to the 3D CRT technique. Two treatments plans, on a lung and a cranial tumour respectively, were analyzed as important examples of this new approach. The IMMA plans achieve a similar coverage of the target volumes as well as the 3D CRT technique (coplanar and noncoplanar), but with a better sparing of the critical organs and a delivery efficiency that is superior to that of 3D CRT. This result changes when the comparison is made with the fixed gantry IMRT technique, since the inverse-planned (IP) treatments have a greater flexibility in conforming the dose to the complex targets and in controlling the dose to the critical structures. To improve the IMMA forward-planned procedure, a new IMAT-IP approach has been proposed to obtain treatment plans that approach, in term of tumour dose coverage and dose sparing of the critical organs, the plan quality reached by the IMRT technique.

Background and purpose: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-N, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. Materials and methods: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverseplanning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. Results: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP = 5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. Conclusions: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT. � c 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xx (2008) xxx–xxx.

Dynamic-gantry multi-leaf collimator (MLC)-based, intensity-modulated radiotherapy (IMAT) has been proposed as an alternative to tomotherapy. In contrast to fixed-gantry, MLC-based intensity-modulated radiotherapy (IMRT), where commercial treatment planning systems (TPS) or dosimetric analysis software currently provide many automatic tools enabling two-dimensional (2D) detectors (matrix or electronic portal imaging devices) to be used as measurement systems, for the planning and delivery of IMAT these tools are generally not available. A new dosimetric method is proposed to overcome some of these limitations. By converting the MLC files of IMAT beams from arc to fixed gantry-angle modality, while keeping the leaf trajectories equal, IMAT plans can be both simulated in the TPS and executed as fixed-gantry, sliding-window DMLC treatments. In support of this idea, measurements of six IMAT plans, in their double form of original arcs and converted fixed-gantry DMLC beams (IMAT-SIM), have been compared among themselves and with their corresponding IMAT-SIM TPS calculations. Radiographic films and a 2D matrix ionization chamber detector rigidly attached to the accelerator gantry and set into a cubic plastic phantom have been used for these measurements. Finally, the TPS calculation-algorithm implementations of both conformal dynamic MLC arc (CD-ARC) modalities, used for clinical IMAT calculations, and DMLC modalities (IMAT-SIM), proposed as references for validating IMAT plan dose-distributions, have been compared. The comparisons between IMAT and IMAT-SIM delivered beams have shown very good agreement with similar shapes of the measured dose profiles which can achieve a mean deviation (+/-2sigma) of (0.35+/-0.16) mm and (0.37+/-0.14)%, with maximum deviations of 1.5 mm and 3%. Matching the IMAT measurements with their corresponding IMAT-SIM data calculated by the TPS, these deviations remain in the range of (1.01+/-0.28) mm and (-1.76+/-0.42)%, with maximums of 3 mm and 5%, limits generally accepted for IMRT plan dose validation. Differences in the algorithm implementations have been found, but by correcting CD-ARC calculations for the leaf-end transmission offset (LTO) effect the IMAT and IMAT-SIM simulations agree well in terms of final dose distributions. The differences found between IMAT and the IMAT-SIM beam measurements are due to the different controls of leaf motion (via electron gun delay in the latter) that cannot be used in the former to correct possible speed variations in the rotation of the gantry. As the IMAT delivered beams are identical to what the patient will receive during the treatment, and the IMAT-SIM beam calculations made by the TPS reproduce exactly the treatment plans of that patient, the accuracy of this new dosimetric method is comparable to that which is currently used for static IMRT. This new approach of 2D-detector dosimetry, together with the commissioning, quality-assurance, and preclinical dosimetric procedures currently used for IMRT techniques, can be applied and extended to any kind of dynamic-gantry MLC-based treatment modality either CD-ARC or IMAT.

Purpose In modern radiation therapy accurate dosimetry within small photon fields is a challenge. This study presents a multicenter characterization of MLC-defined small field for the two major linear accelerator manufacturers. Materials and methods The project enrolled 31 Italian centers, 15 equipped with Elekta Linacs and 16 equipped with Varian Linacs. Each center performed TPR, in-plane and cross-plane dose profile of 0.8 × 0.8 cm2 field and OFs measurements for field sizes ranging from 0.6 × 0.6 to 10 × 10 cm2. Set-up conditions were 10 cm depth in water phantom at SSD 90 cm. Measurements were performed using two Exradin W1 plastic scintillator detectors correcting for the Cerenkov effect as proposed by the manufacturer. Results Analysis of the measurements performed by 12 Varian and 13 Elekta centers was performed. TPR measurements showed standard deviations within 0.6%; penumbra values of dose profiles showed standard deviations within 0.5 mm. FWHM measurements showed a greater variability. OF measurements showed standard deviations within 1.5% for field size greater than 2 × 2 cm2; for field size less than 2 × 2 cm2 measurements’ variability increases with decreasing field size. OF values show no dependence from the effective field size. Conclusions Relatively high degree of consistency regarding TPR and penumbra values was registered. FWHM and OF instead show greater variability. Our work confirmed the importance of multicenter dosimetric studies and W1 PSD as a candidate for small field clinical radiation dosimetry in advanced radiation therapy techniques.

A project dedicated to stereotactic body radiotherapy (SBRT) dosimetric aspects started in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. Its main objectives are manifold but sharing the knowledge between different clinics is the one of the most important. More than 30 centres, equipped with Varian, Elekta, Siemens or CyberKnife linac were enrolled. The project was divided in several work-packages, the first one evaluated the relative measurements with detectors routinely used by individual centers and in the following different detectors run in various centre. Each centre in the same work-package performed dose profile of field size ranging from 0.6 × 0.6 cm 2 to 5.0 × 5.0 cm 2 , and relative output factors (ROF) measurements with a diamond or silicon diode or scintillator detector. In workpackage-1 ROF values measured in the first phase were compared with the ones measured with a microdiamond showing a higher inter-center consistency with this dosimeter compared to routine detectors. In workpackage-2 a silicon diode of new generation was used also to develop a mathematical relation from multicentric experimental data, which describes and predicts the ROF as a function of effective field size for TrueBeam Varian and Elekta linacs. Workpackage-3 used a plastic scintillator for TPR20, 10 and ROF; the latter showed a greater variability. Workpackage-4 used diamond and plastic scintillator with Cyberknife beams, to evaluate if microDiamond could be a suitable alternative to silicon diodes for OF determination and to validate the feasibility of using the scintillator as a reference detector in consideration of the CerenkovLightRatio and experimental uncertainties. The results of the study for all the detectors emphasized the usefulness of a multi-center validation over a single center approach.

Computational power and anthropomorphous phantoms advances in the last years have extended greatly the number of potential applications of Monte Carlo methods in the medical field. Aiming at an orthovoltage treatment plan definition, the results of Monte Carlo simulations performed with the MCNP6 code on two different typologies of computational models have been compared: Unstructured Mesh (UM) model and Voxel model. The capability to simulate the particle transport directly on the unstructured mesh model geometry has been recently introduced in the release 6 of MCNP [1] , which has been chosen for this study. These kind of models overcome the insurgence of voxel effects [2] and provide a more accurate description of volumes and complex surfaces. The simulations were performed on anthropomorphous models based on anonymous CT scans. Firstly, the UM model was obtained from the CT scans thanks to the SCAN-IP mesh tools (Simpleware), and secondly the CT was voxelized with different voxel sizes in order to compare and gauge the voxel effects. The radiation source simulates the Orthovoltage X-Ray tube in use at IRCCS-ASMN in Reggio Emilia, tested in different configurations and tube voltages. The computational source has been validated with experimental measures on the real one applied on heterogeneous slab phantoms. The validation showed good agreement of the simulated setups with the experiments, with deviations varying accordingly to the source configuration, but always below 5–6%. The comparison between the two models showed how, with decreasing voxel sizes, the voxel models results partially converge to the UM models values. Furthermore, it was highlighted that the major deviations between the models resulted where the dose gradient is higher, along the field borders and when tissue heterogeneity is more and more considered. The study shows how the UM model can be implemented for evaluating the dose deposition within anthropomorphous phantoms and, in perspective, be used in treatment planning.

Mycobacterium genavense is a frequently missed agent of disseminated disease in AIDS patients. The increasing frequency with which such organism is being isolated in Italy suggested a comparison of local survey with data reported in literature. Isolates presumed to belong to the species M. genavense were centralized and identified by means of genomic sequencing and/or HPLC analysis of cell wall mycolic acids; clinical data were obtained from relevant patients' record and collected using a proper questionnaire. In 24 cases in which this organism has been isolated in Italy M. genavense was grown, prevalently from blood, in liquid medium after an average of six weeks of incubation. In overwhelming majority, patients were males, presented other opportunistic diseases and were characterized by very low CD4+ counts (average 23/μl); most frequent symptoms were fever, anemia and weight loss. All but two patients, who died before the mycobacterial infection was diagnosed, were treated with at least three drugs; the mean survival was close to one year. A review of literature reports revealed a wide overlapping of clinical and microbiological features.

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs.

Background Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. Methods We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Results Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Conclusion Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient.

Purpose The SBRT working group of Italian Association of Medical Physics (AIFM) performed 4 multicenter planning studies on patients who were candidates for SBRT in the treatments of prostate, liver, lung and spine cancer with the aim of evaluating the dosimetric consistency among the different hospitals. Methods and materials Plans were performed following the dose prescription of 35 Gy in five fractions for the planning target volume (PTV) on prostate, 54 Gy in 3 fractions for liver, 75 Gy in 3 fractions for lung and 3 fractions of 10 Gy for spine. Different techniques were used (3D-CRT, fixed-Field IMRT, VMAT, TomoTherapy, CyberKnife) and plans were compared in terms of dose-volume histogram (DVH) parameters. Results For prostate, important differences were found in terms of the HI. Doses to OARs were heterogeneous. For Liver, no significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. For lung, significant correlations for PTV-gEUD2 versus PTV-HI, and MLD2 versus PTV-GI, were observed. Conclusions Important dosimetric differences with possible clinical implications, in particular related to OARs, were found. Multicenter clinical trials on SBRT should require a preplanning study to standardize the optimization procedure. The differences both in terms of target coverage and OAR sparing suggest inter-comparison of DVH could be a useful tool to standardize treatment planning of stereotactic treatments before starting multicentric clinical trial.

Purpose: Various commercial algorithms for deformable image registration (DIR) were tested to investigate their accuracy and robustness, against image noise and artifacts. Methods: Ten institutions with five available commercial solutions provided data to assess the agreement of DIR-propagated ROIs with automatically drawn ROIs considered as ground-truth for the comparison. The DIR algorithms were tested on real patient data (pelvis). A Deformation was applied to the reference data set (CTref) using the ImSimQA software, a (CTeval) and seven CBCT images with increasing level of noise and capping artifacts were simulated. Every center performed DIR between CTref, and the deformed datasets. The noise was defined as standard deviation normalized to signal in an homogeneous medium, artefacts as the difference of mean HU values between the central and peripheral region of an homogeneous medium. To investigate the relationship between image quality parameters and the DIR results a three way ANOVA was performed on logit function of DICE index. Results: Based on 480 DIR-mapped ROIs the ANOVA test states that centers, ROIs and Image Quality are significant predictors of DIR performances. DIR conducted on CBCT simulated images is significant worst of the ones obtained on the original images. Increasing noise and artefacts didn't affect significantly DIR performances. Considering a limit for Dice Index of 0.75 one center underperform this level. DIR resulted significantly more accurate in rectal contours propagation. Conclusion: This work illustrates the effect of image noise to DIR performances in a ground truth provided scenario. Clinical issues like ART or Dose Accumulation need accurate and robust DIR software using CBCT images. For the range of artefacts and noise explored in this experiment the commercial software appeared to be robust. One centre didn't satisfy the minimum accuracy requirement showing that QA is mandatory to implement clinically DIR for ROI propagation.