Improving the Quality of Care in Radiation Oncology using Artificial Intelligence.

Radiation therapy is a complex process involving multiple professionals and steps from simulation to treatment planning to delivery, and these procedures are prone to error. Additionally, the imaging and treatment delivery equipment in radiotherapy is highly complex and interconnected and represents another risk point in the quality of care. Numerous quality assurance tasks are carried out to ensure quality and to detect and prevent potential errors in the process of care. Recent developments in artificial intelligence provide potential tools to the radiation oncology community to improve the efficiency and performance of quality assurance efforts. Targets for artificial intelligence enhancement include the quality assurance of treatment plans, target and tissue structure delineation used in the plans, delivery of the plans and the radiotherapy delivery equipment itself. Here we review recent developments of artificial intelligence applications that aim to improve quality assurance processes in radiation therapy and discuss some of the challenges and limitations that require further development work to realise the potential of artificial intelligence for quality assurance.

A Markov decision process approach to temporal modulation of dose fractions in radiation therapy planning.

The current state of the art in cancer treatment by radiation optimizes beam intensity spatially such that tumors receive high dose radiation whereas damage to nearby healthy tissues is minimized. It is common practice to deliver the radiation over several weeks, where the daily dose is a small constant fraction of the total planned. Such a 'fractionation schedule' is based on traditional models of radiobiological response where normal tissue cells possess the ability to repair sublethal damage done by radiation. This capability is significantly less prominent in tumors. Recent advances in quantitative functional imaging and biological markers are providing new opportunities to measure patient response to radiation over the treatment course. This opens the door for designing fractionation schedules that take into account the patient's cumulative response to radiation up to a particular treatment day in determining the fraction on that day. We propose a novel approach that, for the first time, mathematically explores the benefits of such fractionation schemes. This is achieved by building a stylistic Markov decision process (MDP) model, which incorporates some key features of the problem through intuitive choices of state and action spaces, as well as transition probability and reward functions. The structure of optimal policies for this MDP model is explored through several simple numerical examples.

A feasibility study of spatiotemporally integrated radiotherapy using the LQ model.

This paper investigates the feasibility of spatiotemporally modulated radiotherapy (STMRT)-integrated model with explicit constraints on the tumor dose heterogeneity. In particular, we demonstrate the effect of the tumor dose heterogeneity on the tumor biologically effective dose (BED) achievable and optimal fractionation. We propose an STMRT model that simultaneously optimizes the dose distributions and fractionation schedule for each individual case with the maximum and minimum constraints on the tumor BED to explicitly control the level of tumor dose heterogeneity. Sixteen thoracic phantom cases were planned using (1) STMRT and (2) standard fractionation (60 Gy in 30 fractions fixed) IMRT. Constraints on the organs-at-risk (OAR) BED were identical for both plans. BEDs were calculated using the [Formula: see text] ratio of 10 Gy for the tumor and 3 Gy for all OARs. The maximum tumor BED for STMRT plans was constrained to be less than 100%-150% of the maximum tumor BED resulted from the standard fractionation plans. The mean tumor BED from STMRT plans was up to 110.7%, 128.3%, 135.0% and 148.0% of that from the standard fractionation plans when the maximum tumor BED was constrained to be less than 100%, 120%, 130% and 150% of the maximum BED achieved using the standard plans. The optimal number of fractions varied widely for different phantom geometries for the same radiobiological parameter values. The increase in the tumor BED and the range of optimal fractionation was larger with a larger tumor dose heterogeneity allowed. The results have shown the feasibility of personalizing fractionation schedule using an STMRT integrated model to deliver a maximum feasible BED to the tumor for a fixed OAR BED. The potential increase in the tumor BED was positively correlated to the tumor dose heterogeneity allowed.

Stereotactic radiosurgery: a review and comparison of methods.

PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.

Automatic selection of non-coplanar beam directions for three-dimensional conformal radiotherapy.

An algorithm is described, based on ray-tracing and the beam's-eye-view, that exhaustively searches all permitted beam directions. The evaluation of the search is based on a general cost function that can be adapted to the clinical objectives by means of parameters and weighting factors. The approach takes into account the constraints of the linear accelerator by discarding beam directions that are not permitted. A sensitivity analysis was carried out to determine appropriate parameters for different sized organs, and a prostate case was used to benchmark the approach. The algorithm was also applied to two clinical cases (brain and sinus) to test the benefits of the approach compared with manual angle selection. The time to perform a beam direction search was approximately 2 min for the coplanar and 12 min for the non-coplanar beam space. The angles obtained for the prostate case compared well with reports in the literature. For the brain case, the mean dose to the right and left optic nerves was reduced by 12% and 50%, respectively, whilst the target dose uniformity was improved. For the sinus case, the mean doses to the right and left parotid glands were reduced by 54% and 46%, respectively, to the right and left optic nerves by 37% and 62%, respectively, and to the optic chiasm by 39%, whilst the target dose uniformity was also improved. For the clinical cases the plans based on optimized beam directions were simpler and resulted in better sparing of critical structures compared with plans based on manual angle selection. The approach provides a practical alternative to elaborate and time consuming beam angle optimization schemes and is suitable for routine clinical usage.

Commissioning an image-guided localization system for radiotherapy.

PURPOSE: To describe the design and commissioning of a system for the treatment of classes of tumors that require highly accurate target localization during a course of fractionated external-beam therapy. This system uses image-guided localization techniques in the linac vault to position patients being treated for cranial tumors using stereotactic radiotherapy, conformal radiotherapy, and intensity-modulated radiation therapy techniques. Design constraints included flexibility in the use of treatment-planning software, accuracy and precision of repeat localization, limits on the time and human resources needed to use the system, and ease of use. METHODS AND MATERIALS: A commercially marketed, stereotactic radiotherapy system, based on a system designed at the University of Florida, Gainesville, was adapted for use at the University of Washington Medical Center. A stereo pair of cameras in the linac vault were used to detect the position and orientation of an array of fiducial markers that are attached to a patient's biteblock. The system was modified to allow the use of either a treatment-planning system designed for stereotactic treatments, or a general, three-dimensional radiation therapy planning program. Measurements of the precision and accuracy of the target localization, dose delivery, and patient positioning were made using a number of different jigs and devices. Procedures were developed for the safe and accurate clinical use of the system. RESULTS: The accuracy of the target localization is comparable to that of other treatment-planning systems. Gantry sag, which cannot be improved, was measured to be 1.7 mm, which had the effect of broadening the dose distribution, as confirmed by a comparison of measurement and calculation. The accuracy of positioning a target point in the radiation field was 1.0 +/- 0.2 mm. The calibration procedure using the room-based lasers had an accuracy of 0.76 mm, and using a floor-based radiosurgery system it was 0.73 mm. Target localization error in a phantom was 0.64 +/- 0.77 mm. Errors in positioning due to couch rotation error were reduced using the system. CONCLUSION: The system described has proven to have acceptable accuracy and precision for the clinical goals for which it was designed. It is robust in detecting errors, and it requires only a nominal increase in setup time and effort. Future work will focus on evaluating its suitability for use in the treatment of head-and-neck cancers not contained within the cranial vault.

Heavy charged-particle stereotactic radiosurgery: cerebral angiography and CT in the treatment of intracranial vascular malformations.

A method is described for stereotactic localization of intracranial arteriovenous malformations (AVM) and for calculating treatment plans for heavy charged-particle Bragg peak radiosurgery. A stereotactic frame and head immobilization system is used to correlate the images of multivessel cerebral angiography and computed tomography. The AVM is imaged by angiography, and the frame provides the stereotactic coordinates for transfer of this target to CT images for the calculation of treatment plans. The CT data are used to calculate the residual ranges and compensation for the charged-particle beam required for each treatment port. Three-dimensional coordinates for the patient positioner are calculated, and stereotactic radiosurgery is performed. Verification of the accuracy of the stereotactic positioning is obtained with computer-generated overlays of the vascular malformation, stereotactic fiducial markers, and bony landmarks on orthogonal radiographs immediately prior to treatment. Using these procedures, the accuracy of the repositioning of the patient at each of a series of imaging and treatment procedures is typically within 1 mm in each of three orthogonal planes.

Stereotactic frame for neuroradiology and charged particle Bragg peak radiosurgery of intracranial disorders.

The application of heavy charged particle Bragg peak radiosurgery for the treatment of intracranial vascular and other disorders requires a system of precise patient immobilization and stereotactic localization of defined intracranial targets. The process of using stereotactic neuroradiological procedures (including cerebral angiography, CT scanning and magnetic resonance imaging) for target definition and localization, and complex treatment planning constrain such a system to be adaptable and reusable. This paper describes a removable stereotactic frame-mask system that is used to immobilize and reposition the patient during stereotactic neuroradiological procedures and charged particle radiosurgery. It consists of four parts--(a) a plastic mask for immobilizing the patient's head; (b) a lucite-graphite mounting frame; (c) a set of fiducial markers; and (d) interfaces between the frame for immobilization and fixation to various diagnostic and therapeutic patient couches. The relationship between each component and the radiosurgical procedure is discussed. This system has proven to be safe, reliable, and noninvasive and it does not require fixation to the bones of the face or skull. When integrated into the radiosurgical treatment planning and localization procedures developed at Lawrence Berkeley Laboratory, it is capable of reliably repositioning the patient to 1 mm in each of three planes and contouring the intracranial target reliably to this accuracy. The application of this stereotactic system in heavy charged particle radiosurgery of intracranial arteriovenous malformations is described in other reports.

Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery.

Recent interest in stereotactic radiosurgery of intracranial lesions, and the development of stereotactic irradiation techniques has led to the need for a systematic and complete comparison of these methods. A method for conducting these comparisons is proposed and is applied to a set of currently-used stereotactic radiosurgical techniques. Three-dimensional treatment planning calculations are used to compare dose distributions for several different radiation types and irradiation geometries. Calculations were performed using charged particles (H, He, C, and Ne ions) and the irradiation geometry currently used at Lawrence Berkeley Laboratory. Photons in the Gamma Knife configuration and the Heidelberg Linac arc method are used. The 3-dimensional dose distributions were evaluated by means of dose-volume histograms and integral doses to the target volume and to normal brain. The effects of target volume, shape and location are studied. The charged particle dose distributions are more favorable than those of the photon methods. The differences between charged particles and photons increase with increasing target volume. The differences between different charged particle species are small, as are the effects of target shape and location.

Image correlation of MRI and CT in treatment planning for radiosurgery of intracranial vascular malformations.

Magnetic resonance imaging (MRI) has been incorporated with stereotactic cerebral angiography and computed tomography (CT) in the treatment planning process of heavy ion radiosurgery of intracranial arteriovenous malformations (AVM's). Correlation of the images of the AVM and normal tissue on each of these neuroradiological imaging modalities is achieved by means of fiducial markers. The computerized transfer of angiographic information to the CT images regarding the size, shape, and location of the abnormal vasculature has been described in an earlier report. A separate computer program calculates a fit between individual fiducial markers on the CT and MR images that enables the transfer of contours between the two imaging modalities. The MR images aid in the determination of the 3-dimensional shape of the AVM, adding to the information derived from the two angiographic projections. Currently, MRI cannot replace cerebral angiography in delineating the entire arterial phase of the AVM. Magnetic resonance imaging is invaluable in the treatment planning of angiographically-occult AVM's, determining the location, size, and shape of the volume to be treated. Correlation of the CT and MRI images allows for the transfer of CT-calculated isodose contours to the MRI images to aid in the determination of optimal treatment plans.

MRI and PET of delayed heavy-ion radiation injury in the rabbit brain.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques were used to obtain in vivo scans of delayed (30 GyE helium ion, 230 MeV/u) radiation injury in rabbit brain. T2-weighted (T2W) MRI scans demonstrated alterations that were restricted primarily to the white matter tracts and the deep perithalamic and thalamic regions. Quantitative measurements of T2 and T1 values demonstrated wide variations in absolute values. However, paired comparisons in hemibrain-irradiated rabbits revealed significant increases in T2 (p less than 0.001) and T1 (p less than 0.01) in irradiated versus unirradiated brain. Gadolinium DTPA (GdDTPA) enhanced MRI and 82Rubidium (82Rb) PET detected focal regions of blood-brain barrier (BBB) disruption restricted to the deep white matter and thalamic regions. Sequential GdDTPA enhanced MRI scans showed the spreading of the tracer from the initial site of contrast enhancement. 18Fluorodeoxyglucose (18FDG) PET studies demonstrated the markedly depressed metabolic profiles of irradiated brain. Histological findings of tissue edema and necrosis correlated well with the in vivo imaging abnormalities. These initial studies demonstrate that the irradiated rabbit brain is a suitable animal model for examining the delayed effects of radiation injury in the brain.

Bladder replacement after radical cystectomy using detubularized right colonic segment.

Bladder replacement after radical cystectomy offers the cancer patient the possibility of restoration to a functional level not possible with the standard means of urinary diversion. Herein we present our experience using a detubularized right colonic segment to create functional reservoirs in 2 male patients and a continent reservoir in a female patient. Cystometric analysis reveals capacious reservoirs, low basal pressures, and a tendency toward pressure spikes at higher filling volumes. All 3 patients are continent at volumes up to 400 cc with preservation of the upper urinary tracts and the absence of reflux. We believe the simplicity of this technique and the encouraging results will contribute to more widespread application of continent and functional reservoirs.

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury.

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.

Changes in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme.

OBJECTIVE: To examine and evaluate improvements in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status in postmyocardial infarction patients during and after a comprehensive 12 month exercise rehabilitation programme. SUBJECTS: The sample population comprised 124 patients with a clinical diagnosis of myocardial infarction (122 men and two women). INTERVENTIONS: 62 patients were randomly allocated to a regular weekly aerobic training programme, three times a week for 12 months, and compared with 62 matched controls who did not receive any formal exercise training. A five year follow up questionnaire/interview was subsequently conducted on this population to determine selected vocational/lifestyle changes. RESULTS: Significant improvements in cardiorespiratory fitness (p < 0.01-0.001), psychological profiles (p < 0.05-0.001), and quality of life scores (p < 0.001) were recorded in the treatment population when compared with their matched controls. Although there were no significant differences in mortality, a larger percentage of the regular exercisers resumed full time employment and they returned to work earlier than the controls. Controls took lighter jobs, lost more time from work, and suffered more non-fatal reinfarctions (p < 0.05-0.01). CONCLUSIONS: Regularly supervised and prolonged aerobic exercise training improves cardiorespiratory fitness, psychological status, and quality of life. The trained population also had a reduction in morbidity following myocardial infarction, and significant improvement in vocational status over a five year follow up period.

Cerebral blood flow evaluation of arteriovenous malformations with stable xenon CT.

Twenty patients with supratentorial arteriovenous malformations (AVMs) were evaluated with angiography, conventional CT, and stable xenon CT to determine cerebral blood flow. Contralateral and ipsilateral regions of interest relative to the AVM were evaluated from cerebral blood flow maps and correlated with angiography. A significant decrease in cerebral blood flow was observed in the ipsilateral cortical gray matter adjacent to the AVM relative to the corresponding contralateral cortex (mean difference = 9.52 ml/100 g/min, p less than .01). The larger AVMs (greater than 8 cm3) were associated with a more marked decrease with a mean difference of 12.22 ml/100 g/min (p less than .02). Regions of interest were also chosen on the basis of angiographic findings, which suggested areas of decreased flow. Comparison of these areas with analogous contralateral areas also showed a significant decline in cerebral blood flow (mean difference = 8.86 ml/100 g/min); this decline was greater with larger AVMs (volume greater than 8 cm3), which had a mean difference of 11.38 ml/100 g/min (p less than .01). Our correlative study enabled us to pinpoint the regions most likely to have reduced flow from an AVM.

Endovascular treatment of cerebral arteriovenous malformations following radiosurgery.

PURPOSE: Previous reports of embolization of cerebral arteriovenous malformations (AVMs) have evaluated the technique as adjunctive therapy prior to surgery or radiosurgery; our aim is to assess the role of embolization following radiosurgery. PATIENTS: Six patients previously treated with radiosurgery and showing no response as judged by cerebral angiography were embolized 24 to 55 months (mean 34.3 months) after initial radiosurgery. RESULTS: In five of six, a significant volume reduction was achieved ranging from 60%-100% (mean 74%). One patient was treated with embolization alone and the AVM has remained fully thrombosed 2 years after treatment. Three patients underwent surgical resection for cure after embolization, and two patients had repeat radiosurgery to a significantly smaller AVM volume. One patient had an asymptomatic carotid dissection at embolization; however, no clinically apparent complications occurred in the treatment group. CONCLUSION: Embolization can be used after radiosurgery to assist in the management of those AVMs that have not responded to initial treatment.

Dynamic and omni wedge implementation on an Elekta SL linac.

The concommitant use of a multileaf collimator (MLC) and a wedge can result in conflicts in the optimal collimator angle if both MLC and wedge are fixed relative to one another. This is particularly true of linacs in which a single wedge orientation is provided. In this paper, a solution is provided that makes use of two orthogonal universal wedges (omni wedge). Although this technique can be applied regardless of the means by which the wedged fields are implemented, the measurements reported in this paper were performed using a fixed, internal mechanical wedge coupled with a dynamic wedge, formed by the motion of one of the backup jaws. An implementation of a dynamic wedge for the Elekta SL series of linear accelerators is presented. Results of measurements of the dosimetric characteristics of both the particular implementation of the dynamic wedge and of the omni field are presented. For the dynamic wedge, measurements were made of the wedge factor and dose profile as a function of field size and depth. In addition, the effects of variables, such as dynamic delivery technique and direction of diaphragm motion, on the dynamic wedge profiles were studied and discussed. For the omni wedge, measurements were made of the degree to which the mathematical formalism for describing an omni wedge matches the measured isodose distributions. Comparisons between mechanical wedge dose distributions and the omni wedge were also made.

Verification of dynamic intensity-modulated beam deliveries in canine subjects.

Our objective in this work was to assess the precision and degree of accuracy with which intensity modulated radiation therapy (IMRT) can deliver highly localized dose distributions to tumors near critical structures using the dynamic sliding window technique. Measurements of dose distribution were performed both in vivo and in vitro using a combination of dosimeters [thermoluminescent dosimeters (TLD's), films, and diodes]. In vivo measurements were performed in two groups of purpose-bred dogs: one receiving four-field three-dimensional (3D) conformal treatment and the other receiving IMRT. The algorithms used in the inverse planning process included the Macro Pencil Beam (MPB) model and Projections onto Convex Sets (POCS). Single beam measurements were performed in phantoms to verify the accuracy of monitor unit settings required for delivering the desired doses. The composite doses from the delivery of the seven beam intensity modulated plans were measured in phantoms and cadavers, Biological end points (spinal cord toxicity and neurologic deficits due to irradiation) were evaluated at the end of one year to determine the spatial accuracy of the IMRT treatments over a fractionated course in live subjects. Results in single beam measurements were used at first to improve the dose calculation and translation algorithms. Results of the measurements for the delivery of all seven beams in phantoms confirmed that the system was capable of accurate spatial and dosimetric IMRT delivery. The in vivo results showed dramatic differences between control and IMRT-treated dogs, with the IMRT group showing no adverse effects and the control animals showing severe spinal cord injuries due to irradiation. The measurements presented in this paper have helped to verify the successful and accurate delivery of IMRT in a clinically related model using the University of Washington Medical Center (UWMC) system.

Accelerated helium-ion beams for radiotherapy and stereotactic radiosurgery.

A new beam line for radiotherapy and radiosurgery with accelerated helium-ion beams has been set up at the Bevalac. The new treatment room has been equipped with a very precise patient positioner in order to utilize the superior dose localization properties of light-ion beams. The beam spreading and shaping system is described, the trade-offs involved in positioning the beam modifying devices are discussed, and the physical properties of the generated radiation fields are reported. The Bragg peak modulation by axial beam stacking employing a variable range shifter is explained and the control system including beam monitoring and dosimetry is presented.

Effects of irradiation geometry on treatment plan optimization with linac-based radiosurgery.

A comparison was made of different treatment plans to determine the effect on the three-dimensional dose distributions of varying the allowed parameters in linac-based stereotactic radiosurgery with circular collimators; these parameters are arc position, length, and weighting, and collimator diameter. For the class of eccentrically shaped target volumes that are not so irregular as to require several separate isocenters, it was found that superior dose distributions could be achieved by varying arc length, arc position, arc weighting, and collimator diameter. An analysis of the results achieved with an automated planning program indicates that, in general, the variables of arc position and arc length are of greater importance than collimator size or beam weighting. However, there are cases where varying these latter two parameters does result in markedly better dose distributions. A deeper investigation into the effects of multiple collimators on the dose distribution in the area of steepest gradient demonstrated that multiple collimator sizes do not significantly degrade the dose falloff, which is in fact mostly determined by the effects of intersecting arcs.