RADIANCE-A planning software for intra-operative radiation therapy

In the last decades accumulated clinical evidence has proven that intra-operative radiation therapy (IORT) is a very valuable technique. In spite of that, planning technology has not evolved since its conception, being outdated in comparison to current state of the art in other radiotherapy techniques and therefore slowing down the adoption of IORT. RADIANCE is an IORT planning system, CE and FDA certified, developed by a consortium of companies, hospitals and universities to overcome such technological backwardness. RADIANCE provides all basic radiotherapy planning tools which are specifically adapted to IORT. These include, but are not limited to image visualization, contouring, dose calculation algorithms-Pencil Beam (PB) and Monte Carlo (MC), DVH calculation and reporting. Other new tools, such as surgical simulation tools have been developed to deal with specific conditions of the technique. Planning with preoperative images (preplanning) has been evaluated and the validity of the system being proven in terms of documentation, treatment preparation, learning as well as improvement of surgeons/radiation oncologists (ROs) communication process. Preliminary studies on Navigation systems envisage benefits on how the specialist to accurately/safely apply the pre-plan into the treatment, updating the plan as needed. Improvements on the usability of this kind of systems and workflow are needed to make them more practical. Preliminary studies on Intraoperative imaging could provide an improved anatomy for the dose computation, comparing it with the previous pre-plan, although not all devices in the market provide good characteristics to do so. DICOM.RT standard, for radiotherapy information exchange, has been updated to cover IORT particularities and enabling the possibility of dose summation with external radiotherapy. The effect of this planning technology on the global risk of the IORT technique has been assessed and documented as part of a failure mode and effect analysis (FMEA). Having these technological innovations and their clinical evaluation (including risk analysis) we consider that RADIANCE is a very valuable tool to the specialist covering the demands from professional societies (AAPM, ICRU, EURATOM) for current radiotherapy procedures.

Evaluating Patient Education Materials about Radiation Therapy

Targeted treatment education for cancer patients has the potential to promote adjustment through assisting patients to participate in treatment decision making, comply with treatment regimens and cope more effectively with treatment side effects. A quasi-experimental longitudinal pre-test post-test and follow-up design was used to assess the effect of a patient education video about radiation therapy on patients' psychological distress, knowledge about radiation therapy, self-efficacy about coping with treatment and physical symptoms. Patients with head and neck (n = 26) and breast cancer (n = 66) were recruited into the study and allocated into control and intervention groups. No significant differences were found between the control and intervention groups on any of the outcome variables. However, patients in the intervention group reported high levels of satisfaction with the video and all reported that they would recommend the video to other patients preparing for radiation therapy. As well, 90% of patients in the intervention group reported that some or all of the information in the video was new to them. Education materials that have excellent face validity and that are well received by patients may fail to produce significant change using standard controlled study designs. Future research in this area may need to consider alternative paradigms for evaluating the helpfulness of such materials. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Biomechanical modeling of parotid glands morphing in head & neck radiation therapy treatments

Durante i trattamenti radioterapici dei pazienti oncologici testa-collo, le ghiandole parotidee (PGs) possono essere indebitamente irradiate a seguito di modificazioni volumetriche-spaziali inter/intra-frazione causate da fattori quali il dimagrimento, l’esposizione a radiazioni ionizzanti ed il morphing anatomico degli organi coinvolti nelle aree d’irraggiamento. Il presente lavoro svolto presso la struttura di Fisica Medica e di Radioterapia Oncologica dell’A.O.U di Modena, quale parte del progetto di ricerca del Ministero della Salute (MoH2010, GR-2010-2318757) “ Dose warping methods for IGRT and Adaptive RT: dose accumulation based on organ motion and anatomical variations of the patients during radiation therapy treatments ”, sviluppa un modello biomeccanico in grado di rappresentare il processo di deformazione delle PGs, considerandone la geometria, le proprietà elastiche e l'evoluzione durante il ciclo terapeutico. Il modello di deformazione d’organo è stato realizzato attraverso l’utilizzo di un software agli elementi finiti (FEM). Molteplici superfici mesh, rappresentanti la geometria e l’evoluzione delle parotidi durante le sedute di trattamento, sono state create a partire dai contorni dell’organo definiti dal medico radioterapista sull’immagine tomografica di pianificazione e generati automaticamente sulle immagini di setup e re-positioning giornaliere mediante algoritmi di registrazione rigida/deformabile. I constraints anatomici e il campo di forze del modello sono stati definiti sulla base di ipotesi semplificative considerando l’alterazione strutturale (perdita di cellule acinari) e le barriere anatomiche dovute a strutture circostanti. L’analisi delle mesh ha consentito di studiare la dinamica della deformazione e di individuare le regioni maggiormente soggette a cambiamento. Le previsioni di morphing prodotte dal modello proposto potrebbero essere integrate in un treatment planning system per metodiche di Adaptive Radiation Therapy.

Development and Optimization of Four-dimensional Magnetic Resonance Imaging (4D-MRI) for Radiation Therapy

A tenet of modern radiotherapy (RT) is to identify the treatment target accurately, following which the high-dose treatment volume may be expanded into the surrounding tissues in order to create the clinical and planning target volumes. Respiratory motion can induce errors in target volume delineation and dose delivery in radiation therapy for thoracic and abdominal cancers. Historically, radiotherapy treatment planning in the thoracic and abdominal regions has used 2D or 3D images acquired under uncoached free-breathing conditions, irrespective of whether the target tumor is moving or not. Once the gross target volume has been delineated, standard margins are commonly added in order to account for motion. However, the generic margins do not usually take the target motion trajectory into consideration. That may lead to under- or over-estimate motion with subsequent risk of missing the target during treatment or irradiating excessive normal tissue. That introduces systematic errors into treatment planning and delivery. In clinical practice, four-dimensional (4D) imaging has been popular in For RT motion management. It provides temporal information about tumor and organ at risk motion, and it permits patient-specific treatment planning. The most common contemporary imaging technique for identifying tumor motion is 4D computed tomography (4D-CT). However, CT has poor soft tissue contrast and it induce ionizing radiation hazard. In the last decade, 4D magnetic resonance imaging (4D-MRI) has become an emerging tool to image respiratory motion, especially in the abdomen, because of the superior soft-tissue contrast. Recently, several 4D-MRI techniques have been proposed, including prospective and retrospective approaches. Nevertheless, 4D-MRI techniques are faced with several challenges: 1) suboptimal and inconsistent tumor contrast with large inter-patient variation; 2) relatively low temporal-spatial resolution; 3) it lacks a reliable respiratory surrogate. In this research work, novel 4D-MRI techniques applying MRI weightings that was not used in existing 4D-MRI techniques, including T2/T1-weighted, T2-weighted and Diffusion-weighted MRI were investigated. A result-driven phase retrospective sorting method was proposed, and it was applied to image space as well as k-space of MR imaging. Novel image-based respiratory surrogates were developed, improved and evaluated.

Advanced Applications of 3D Dosimetry and 3D Printing in Radiation Therapy

As complex radiotherapy techniques become more readily-practiced, comprehensive 3D dosimetry is a growing necessity for advanced quality assurance. However, clinical implementation has been impeded by a wide variety of factors, including the expense of dedicated optical dosimeter readout tools, high operational costs, and the overall difficulty of use. To address these issues, a novel dry-tank optical CT scanner was designed for PRESAGE 3D dosimeter readout, relying on 3D printed components and omitting costly parts from preceding optical scanners. This work details the design, prototyping, and basic commissioning of the Duke Integrated-lens Optical Scanner (DIOS).

The convex scanning geometry was designed in ScanSim, an in-house Monte Carlo optical ray-tracing simulation. ScanSim parameters were used to build a 3D rendering of a convex ‘solid tank’ for optical-CT, which is capable of collimating a point light source into telecentric geometry without significant quantities of refractive-index matched fluid. The model was 3D printed, processed, and converted into a negative mold via rubber casting to produce a transparent polyurethane scanning tank. The DIOS was assembled with the solid tank, a 3W red LED light source, a computer-controlled rotation stage, and a 12-bit CCD camera. Initial optical phantom studies show negligible spatial inaccuracies in 2D projection images and 3D tomographic reconstructions. A PRESAGE 3D dose measurement for a 4-field box treatment plan from Eclipse shows 95% of voxels passing gamma analysis at 3%/3mm criteria. Gamma analysis between tomographic images of the same dosimeter in the DIOS and DLOS systems show 93.1% agreement at 5%/1mm criteria. From this initial study, the DIOS has demonstrated promise as an economically-viable optical-CT scanner. However, further improvements will be necessary to fully develop this system into an accurate and reliable tool for advanced QA.

Pre-clinical animal studies are used as a conventional means of translational research, as a midpoint between in-vitro cell studies and clinical implementation. However, modern small animal radiotherapy platforms are primitive in comparison with conventional linear accelerators. This work also investigates a series of 3D printed tools to expand the treatment capabilities of the X-RAD 225Cx orthovoltage irradiator, and applies them to a feasibility study of hippocampal avoidance in rodent whole-brain radiotherapy.

As an alternative material to lead, a novel 3D-printable tungsten-composite ABS plastic, GMASS, was tested to create precisely-shaped blocks. Film studies show virtually all primary radiation at 225 kVp can be attenuated by GMASS blocks of 0.5cm thickness. A state-of-the-art software, BlockGen, was used to create custom hippocampus-shaped blocks from medical image data, for any possible axial treatment field arrangement. A custom 3D printed bite block was developed to immobilize and position a supine rat for optimal hippocampal conformity. An immobilized rat CT with digitally-inserted blocks was imported into the SmART-Plan Monte-Carlo simulation software to determine the optimal beam arrangement. Protocols with 4 and 7 equally-spaced fields were considered as viable treatment options, featuring improved hippocampal conformity and whole-brain coverage when compared to prior lateral-opposed protocols. Custom rodent-morphic PRESAGE dosimeters were developed to accurately reflect these treatment scenarios, and a 3D dosimetry study was performed to confirm the SmART-Plan simulations. Measured doses indicate significant hippocampal sparing and moderate whole-brain coverage.

The Feasibly of Functionally Guided Intensity Modulated Radiation Therapy Treatment Planning Using Perfluoropropane-Enhanced MRI for Lung Cancer

Radiotherapy is commonly used to treat lung cancer. However, radiation induced damage to lung tissue is a major limiting factor to its use. To minimize normal tissue lung toxicity from conformal radiotherapy treatment planning, we investigated the use of Perfluoropropane(PFP)-enhanced MR imaging to assess and guide the sparing of functioning lung. Fluorine Enhanced MRI using Perfluoropropane(PFP) is a dynamic multi-breath steady state technique enabling quantitative and qualitative assessments of lung function(1).

Imaging data was obtained from studies previously acquired in the Duke Image Analysis Laboratory. All studies were approved by the Duke IRB. The data was de-identified for this project, which was also approved by the Duke IRB. Subjects performed several breath-holds at total lung capacity(TLC) interspersed with multiple tidal breaths(TB) of Perfluoropropane(PFP)/oxygen mixture. Additive wash-in intensity images were created through the summation of the wash-in phase breath-holds. Additionally, model based fitting was utilized to create parametric images of lung function(1).

Varian Eclipse treatment planning software was used for putative treatment planning. For each subject two plans were made, a standard plan, with no regional functional lung information considered other than current standard models. Another was created using functional information to spare functional lung while maintaining dose to the target lesion. Plans were optimized to a prescription dose of 60 Gy to the target over the course of 30 fractions.

A decrease in dose to functioning lung was observed when utilizing this functional information compared to the standard plan for all five subjects. PFP-enhanced MR imaging is a feasible method to assess ventilatory lung function and we have shown how this can be incorporated into treatment planning to potentially decrease the dose to normal tissue.

MRI-Guided Radiation Therapy: Investigating the Accuracy of Treatment Delivery

Purpose: To develop, evaluate and apply a novel high-resolution 3D remote dosimetry protocol for validation of MRI guided radiation therapy treatments (MRIdian® by ViewRay®). We demonstrate the first application of the protocol (including two small but required new correction terms) utilizing radiochromic 3D plastic PRESAGE® with optical-CT readout.

Methods: A detailed study of PRESAGE® dosimeters (2kg) was conducted to investigate the temporal and spatial stability of radiation induced optical density change (ΔOD) over 8 days. Temporal stability was investigated on 3 dosimeters irradiated with four equally-spaced square 6MV fields delivering doses between 10cGy and 300cGy. Doses were imaged (read-out) by optical-CT at multiple intervals. Spatial stability of ΔOD response was investigated on 3 other dosimeters irradiated uniformly with 15MV extended-SSD fields with doses of 15cGy, 30cGy and 60cGy. Temporal and spatial (radial) changes were investigated using CERR and MATLAB’s Curve Fitting Tool-box. A protocol was developed to extrapolate measured ΔOD readings at t=48hr (the typical shipment time in remote dosimetry) to time t=1hr.

Results: All dosimeters were observed to gradually darken with time (<5% per day). Consistent intra-batch sensitivity (0.0930±0.002 ΔOD/cm/Gy) and linearity (R2=0.9996) was observed at t=1hr. A small radial effect (<3%) was observed, attributed to curing thermodynamics during manufacture. The refined remote dosimetry protocol (including polynomial correction terms for temporal and spatial effects, CT and CR) was then applied to independent dosimeters irradiated with MR-IGRT treatments. Excellent line profile agreement and 3D-gamma results for 3%/3mm, 10% threshold were observed, with an average passing rate 96.5%± 3.43%.

Conclusion: A novel 3D remote dosimetry protocol is presented capable of validation of advanced radiation treatments (including MR-IGRT). The protocol uses 2kg radiochromic plastic dosimeters read-out by optical-CT within a week of treatment. The protocol requires small corrections for temporal and spatially-dependent behaviors observed between irradiation and readout.

Effects of radiation therapy on the structure and function of the pelvic floor muscles of patients with cancer in the pelvic area : a systematic review

Purpose Radiation therapy (RT) is often recommended in the treatment of pelvic cancers. Following RT, a high prevalence of pelvic floor dysfunctions (urinary incontinence, dyspareunia, and fecal incontinence) is reported. However, changes in pelvic floor muscles (PFMs) after RT remain unclear. The purpose of this review was to systematically document the effects of RT on the PFM structure and function in patients with cancer in the pelvic area. Methods An electronic literature search using Pubmed Central, CINAHL, Embase, and SCOPUS was performed from date of inception up to June 2014. The following keywords were used: radiotherapy, muscle tissue, and pelvic floor. Two reviewers selected the studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Out of the 369 articles screened, 13 met all eligibility criteria. The methodological quality was assessed using the QualSyst scoring system, and standardized mean differences were calculated. Results Thirteen studies fulfilled all inclusion criteria, from which four were of good methodological quality. One presented strong evidence that RT affects PFM structure in men treated for prostate cancer. Four presented high-level evidence that RT affects PFM function in patients treated for rectal cancer. Meta-analysis was not possible due to heterogeneity and lack of descriptive statistics. Conclusion There is some evidence that RT has detrimental impacts on both PFMs’ structure and function. Implications for cancer survivors A better understanding of muscle damage and dysfunction following RT treatment will improve pelvic floor rehabilitation and, potentially, prevention of its detrimental impacts.