The Geometrical And Dose Accuracy Of The Cyberknife System In The .

decision. However, there are some challenges regarding the diagnosis of CCA. The misleadingfactors such as atypical imaging features in some patients, missing the tumor when developed inthe background of predisposing disease, benign and malignant lesions that have similar imagingfeatures as CCA. Therefore, a suitable imaging module with careful image analysis is necessaryfor the proper diagnosis of CCA [16,17].3.2 STENTIn our study, we are using a self-expanding metallic stent (SEMS) with BT and with EBRT. Thestent is a hollow tube that is implanted into anatomical locations, typically in vessels and urologicalor digestive tracts. The stent is made of plastic or metal. Mostly, plastic stents are made ofpolyethylene, Teflon, or polyurethane. All biliary SEMSs are constructed with metal alloys; eithermaking mesh by cutting from a metal cylinder or metal wires are braided [18]. Plastic stents andSEMS efficiency are similar in the short-term result in case of clinical success, morbidity,mortality, and improvement in the quality of life. Whereas in long-term efficacy, SEMS have alower risk of biliary obstruction in comparison to the single plastic stent [19]. In cases of latecomplication, the complication occurs mostly by stent dysfunction, which is approximately twiceas frequent with the plastic stent in comparison to SEMS [19]. Plastic stents are potentiallyretrieval, inexpensive and repositioning is possible as many times as required. However, migrationand interference with mucociliary clearance is the prime problem. Placement of a plastic stentusually requires rigid bronchoscopy and general anesthesia [20]. On the other hand, the metallicstent is technically easier to insert, has comparatively less problem with migration, and has a morefavorable internal to external diameter. Another aspect of the metallic stent is that it often embedsin the mucosa, which makes it difficult to remove [20].3.3 BRACHYTHERAPYBT is a type of internal beam radiotherapy in which a radiation source is placed inside or near tovolume of interest (tumor). The placement of radioactive sources can be done permanently ortemporarily depending upon the radiation source activity, half-life, decay process, photon energyreleased, treatment area, and treatment requirement. Some of the radioisotopes used in BT with10

their half-life, decay process, and photon energy are shown in Table 1.1. Permanent implant BTcan be applied using isotopes such as cesium-131 (131Cs), Iodine-125 (125I), or palladium-103(103Pd) that emit low-energy photons when they decay and can be placed permanently withoutcreating radiation hazard for medical staff or the general public. The temporary implant usesisotopes that release high energy photons such as cesium-137 (137Cs), iridium-192 (192Ir), andcobalt-60 (60Co). The process is implemented in an environment with adequate shielding andsafety measures for staff and the general public. A temporary implant can be a low dose rate(LDR), pulsed dose rate (PDR), or high dose rate (HDR) [21].IsotopeHalf-LifeDecay ProcessPhoton Energy (KeV2261,600 yearsα8305.26 yearsβ1250Ra60Co125I59.4 dayse-capture35103Pd17 dayse-capture21131Cs9.7 dayse-capture30137Cs30 yearsβ662192Ir74.3 daysβ380Table 1.1: General characteristics of radioisotopes used in BT [21].In BT, the dose is better localized to the target volume of interest but can be performed only in thewell localized and relatively small tumors which accounts for about 10-20% of the radiotherapypatients in a typical radiotherapy department [22].3.3.1 Brachytherapy dosimetry formalismOlder calculation formalism for BT dosimetry was based on apparent activity (Aapp), equivalentmass of radium, exposure-rate constants, and tissue-attenuation coefficient which did notaccommodate the factors such as source-to-source differences in encapsulation or internalconstruction. The American Association of Physicists in Medicine (AAPM) Task Group No. 43gave a protocol (TG-43) for the dose calculation in BT in 1995 and was updated in 2004. Theintroduction of TG-43 has resulted in the standardization of dose calculation and dose-ratedistribution. The general formalism for the two-dimensional (2D) dose-rate equation given by TG43 is given below with the descriptions of parameters in the formalism [23].11

𝐺 (𝑟,𝜃)Ḋ(𝑟, 𝜃) 𝑆𝐾 𝛬 𝐺 𝐿(𝑟𝐿0 ,𝜃0 ) 𝑔𝐿 (𝑟) 𝐹(𝑟, 𝜃) ,(1)where r is the distance from the center of the active source, ro is reference distance and kept as 1cm, θ denotes the polar angle specifying the point of interest P(r, θ), relative to the sourcelongitudinal axis and θ0 is the reference angle which defines the source transverse plane and valueis 90 as shown in Figure 3.2 [23]. The different parameters used in the equation are describedbelow.Figure 3.2: Figure illustrating BT coordinate system for dosimetry calculation [23].Air-kerma strength (SK): Air kerma strength is the air kerma rate (K̇𝛿) in a vacuum where thephoton attenuation and scattering in any medium are not considered. It has a unit of µGym 2 h-1.Mathematically, it can be represented as,𝑆𝐾 𝐾̇𝛿 (𝑑)𝑑2 ,where d is the distance from the center of the source to the point of K̇𝛿 (d) [23]Dose rate constant (𝛬): It is the ratio of dose rate at reference point per air-kerma strength.Mathematically, it can be written as,𝛬 Ḋ(𝑟0 ,𝜃0 )𝑆𝐾,The dose rate constant can be determined using the Monte Carlo calculation method [24].Geometrical function (G): This function is used for inverse square-law correction and does nottake scattering and attenuation into account. It helps to improve the accuracy of the dose rate12

estimation. Following mathematical expression is used for approximation in the point and linesource.𝐺𝑃 (𝑟, 𝜃) 𝑟 2 for point-source approximation,𝛽𝐺𝐿 (𝑟, 𝜃) if 𝜃 0 {𝐿𝑟 sin 𝜃2(𝑟 2 𝐿 /4) 1 if 𝜃 0 for line source approximation.Where β is the angle as shown in Figure 3.2 [23].Radial dose function (𝑔𝑋 (𝑟)): The photon attenuation and scattering during the process cause thefall in the dose level. This parameter in the formalism takes account into those falls in doses onthe transverse plane.Ḋ(𝑟,𝜃0 ) 𝐺𝑋 (𝑟0 𝜃0 )0 ,𝜃0 ) 𝐺𝑋 (𝑟,𝜃0 )𝑔𝑋 (𝑟) Ḋ(𝑟,where X is the radial dose function and geometry function [23].2D Anisotropy Function F (r, θ): It is defined asḊ(𝑟,𝜃) 𝐺𝐿 (𝑟,𝜃0 )0 ) 𝐺𝐿 (𝑟,𝜃)𝐹(𝑟, 𝜃) Ḋ(𝑟,𝜃.It describes the effects of anisotropic photon attenuation as a function of polar angle relative tothe transverse plane [23,24].3.3.2 HDR brachytherapyHDR BT is a widely used mode of BT. It delivers a dose of 12 Gy/hour which makes it possibleto deliver the desired high dose in a short period of time. It is generally performed in the outpatientsetting [25]. The clinical outcome of HDR and LDR BT provides relatively equivalent treatmentin terms of survival in cervical cancer, gastrointestinal and genitourinary toxicity [25,26]. Themajor advantage of HDR is short treatment time which allows outpatient treatment, the radiationexposure to staff and the general public can be reduced near to null, consistency and reproducibleapplicator positioning, and the ability to optimize dosing to normal tissues [25,27]. Usually, HDRis performed using 192Ir isotope which has a half-life of 74 days. The activity of the new 192Ir sourceis generally around 10 Ci and the air kerma strength at the distance of 1 m (reference air kermarate) is 1.1337*10-5 Gy.m2.s-1 [28,29]. 192Ir isotope is a popular radiation source for HDR because13

of its high specific activity and high neutron cross-section [24]. In a year, the 192Ir source has tobe replaced 3 to 4 times to avoid prolonging the treatments [28]. HDR BT for the treatment ofperihilar cholangiocarcinoma has been used widely and has shown a positive impact on thetreatment outcome [5,30,31].3.4 STEREOTACTIC BODY RADIATION THERAPY AND CYBERKNIFEConventional radiotherapy uses 1.8-2 Gy/fraction for the radiotherapy treatments. On the otherhand, SBRT uses a hypofractionated schedule or a single fraction with a high doses [32]. Highradiation doses of SBRT kills the tumor not only by directly damaging DNA but also by affectingthe adventitia, most notably by causing vascular damage which increases the tumor hypoxia andinduces secondary tumor cell death. The effect on vasculature is more dominant with fractionaldoses of 8 to 12 Gy or higher. The direct tumor cell death and indirect tumor cell death due tovascular dysfunction after high dose irradiation cause a large number of tumor antigens and variousimmune factors which eventually elevates anticancer immunity. This radiobiological phenomenonis an important aspect of SBRT [33–35].In SBRT, the steep dose gradient is created by spreading out the radiation dose over a large surfacearea. When incoming photon beams are entering the patient, they are widely spread, and theintensity of the individual radiation beam is relatively low which causes minimal damage to normaltissue distant from the focus point. However, the total intensity in the desired target is high. Withthe development in the imaging and image guidance technology, the precise and accuratelocalization of OARs and target volume can be achieved, and thus the treatment margins can beminimized. The higher doses of radiation can be delivered with small field sizes by applying theprinciples of spreading out the energy, and precise and accurate localization [36]. Small volumesof the healthy organ can tolerate much higher radiation doses without injury than large volumes ofthe same organ which helps operate SBRT [34,35].CK consist of linear accelerator, robotic manipulator, imaging system and treatment couch. Thelinear accelerator mounted on a robotic manipulator is capable of delivering non-isocentric andnon-coplanar treatment beams. High accuracy of treatment beam alignment and delivery isobtained through an X-ray image guidance system, a robotic manipulator, frequent image guidanceand alignment correction throughout each treatment fraction. These features help to minimizeclinical target volume (CTV) to planning target volume (PTV) margin. High dose conformality14

and steep dose gradients in all directions are acquired through robotic manipulator, variablecollimator, and plan optimization algorithms [37].Radiosurgery treatments require the system to produce high conformality, steep dose gradients,and motion tracking of the treatment area. These conditions are met by different features andinstruments to build in a CK. The robotic manipulator uses multiple numbers of non-isocentric andnon-coplanar beams which are individually targeted at a unique point within the patient withoutthe need to reposition the patient for each beam, The IrisTM Variable Aperture collimator canproduce multiple field sizes which combine with each treatment to create complex dosedistribution from a set of independently targeted and sized beams. Ideal beam weight, beamdirection, and beam sizes are selected through inverse plan optimization. The image guidancesystem frequently tracks the patient, organ, and target movement. Information obtained from itguide the system to automatically correct beam targeting without hindering treatment [37–39]. Thelinear accelerator of the CK produces flattening filter free (FFF) beams. FFF beams help to providehigh dose rate, reduction in out-of-field dose, and decrease head scattering [40–42]. Studies relatedto clinical cases using FFF beams for treatment planning and dose delivery have demonstratedsuitability and superiority over flattening filter (FF) beams [42].15

Figure 3.3: The CyberKnife treatment machine of Kuopio University Hospital.CK (Accuray inc.) is designed for stereotactic radiotherapy treatments (SRT). The accuracy of CKis in sub-millimeter in tracking target and tumor position compared to accuracy of millimeter withconventional linear accelerator [43].3.5 MULTIPLAN: TREATMENT PLANNING SYSTEM OF CYBERKNIFEThe Multiplan treatment planning system (Accuray Inc.) (TPS) of CK in the Kuopio UniversityHospital consists of a Monte Carlo (MC) dose calculation algorithm and ray tracing algorithm.Accuracy of dose calculation is vital in the TPS. The over approximation and under approximationof the calculated dose leads to the decrease and increase in actual irradiation dose, respectively[44,45]. In the homogeneous medium, almost same result is obtained from all the calculationalgorithms. But in case of a tumor is in an inhomogeneous medium, the precise calculation of dosedistribution in the tumor and the surrounding medium is vital, significantly in radiosurgery because16

of the use of hypofractionation schedule [46]. An algorithm such as ray tracing uses an equivalentpath-length algorithm (EPL) which consistently underestimates the penumbra width in low densityregions and overestimates the dose to PTV [47,48]. The EPL based algorithm merely accounts fordecreasing attenuation of the primary photon beams in low density such as lung tissue, whileincreased electron range is not accounted [47].MC dose calculation is the most accurate dose calculation algorithm for radiation therapy treatmentplanning and dosimetry verification [47,49]. The MC method is a stochastic technique that usesrandom numbers and probability statistics to investigate problems. MC methods involve theprocess to get an approximation of the answer to the problem by performing many simulations(histories) using random numbers and probability distribution. It uses random numbers throughoutthe simulation process [50]. The MC technique for the simulation of the transport of electrons andphotons is performed by using knowledge of the probability distributions of the individualinteractions of electrons and photons in materials to simulate the random trajectories of individualparticles. The tracking of physical quantities of interest for a large number of histories is done toprovide the required information about the average quantities [51,52]. When applying this conceptin d

THE GEOMETRICAL AND DOSE ACCURACY OF THE CYBERKNIFE SYSTEM IN THE TREATMENT OF BILE DUCT WITH THE USE OF METALLIC STENT . evaluating PHC was given by the Bismuth-Corlette system [14,15]. In this system, the lesions are . Therefore, a suitable imaging module with careful image analysis is necessary for the proper diagnosis of CCA [16,17].