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Evaluating and improving patient-specific QA for IMRT delivery

ProQuest Dissertations and Theses, 2009
Dissertation
Author: Guanghua Yan
Abstract:
Modern radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) and newly-emerging volumetric modulated arc therapy (VMAT) aim to deliver highly conformal radiation dose to the target volume while sparing nearby critical organs as much as possible with the complex motion of multi-leaf collimator (MLC) leaves. Pre-treatment patient specific quality assurance (QA) has become an essential part of IMRT in making sure the delivered dose distributions agree with the planned ones. This dissertation evaluates the performance of current patient-specific QA process and proposes solutions to improve its sensitivity, accuracy and efficiency. In step and shoot IMRT, the study on the sensitivity of patient-specific QA to minor MLC errors reveals tighter criterion such as 2%/2mm must be employed to detect systematic MLC positioning errors of 2 mm. However, such criterion results in low average passing rate which leads to excessive false alarms, mainly due to inadequate treatment planning system (TPS) beam modeling on beam penumbra. An analytical deconvolution approach is proposed to recover true photon beam profiles to obtain a true beam model which significantly improves agreement between calculated and measured dose distributions. Thus a tighter criterion could be employed to enhance the sensitivity of patient-specific QA to minor errors in the delivery system. Measurement based patient-specific IMRT QA is a time-consuming process. A fast and accurate independent planar dose calculation algorithm is proposed to replace measurement based QA. The algorithm analytically models photons coming out from the accelerator and computes dose distribution from first principles. Accuracy of the algorithm is validated against 2D diode array measurements. The algorithm is found to be fast and accurate enough to replace time consuming measurement based QA. Patient-specific QA for VMAT differs significantly from step and shoot IMRT due to the increased use of dynamic components (dynamic gantry and collimator, dynamic MLC and variable dose rate) in VMAT. A novel four dimensional (4D) diode array is developed by Sun Nuclear Corp for patient-specific VMAT QA. This work develops effective calibration procedures for this novel device by accounting for diode sensitivity and angular response dependence. A real time algorithm to derive gantry angle is developed to interpolate corresponding angular correction factors. Clinical applications of the diode array are demonstrated with IMRT as well as VMAT plans. Excellent agreement (>95% passing rate with 1%/2mm criterion) is achieved between diode array measurement and TPS calculation. The 4D diode array is proved to be a valuable tool for both IMRT and VMAT patient specific QA.

TABLE OF CONTENTS

page

ACKNOWLEDGMENTS ...............................................................................................................4 LIST OF TABLES ...........................................................................................................................7 LIST OF FIGURES .........................................................................................................................8 ABSTRACT ...................................................................................................................................10 CHAPTER 1 INTRODUCTION ..................................................................................................................12 General Introduction ...............................................................................................................12 Patient-specific IMRT QA ......................................................................................................15 Study Aims .............................................................................................................................17 2 ON THE SENSITIVITY OF PATIENT-SPECIFIC IMRT QA TO MLC POSITIONING ERRORS ......................................................................................................23 Introduction .............................................................................................................................23 Materials and Methods ...........................................................................................................25 Patient Plan Selection ......................................................................................................25 Leaf Positioning Errors Simulation .................................................................................26 Dose Distribution Measurement ......................................................................................26 Planar Dose Comparison .................................................................................................28 Criteria for Identifying Errors .........................................................................................28 Results .....................................................................................................................................29 Discussion ...............................................................................................................................30 Conclusions .............................................................................................................................33 3 THE EXTRACTION OF TRUE PHOTON BEAM PROFILE FOR TPS COMMISSIONING ................................................................................................................39 Introduction .............................................................................................................................39 Methods and Materials ...........................................................................................................42 Beam Data Measurement ................................................................................................42 Beam Profile Deconvolution ...........................................................................................42 Detector response function .......................................................................................43 Profile deconvolution ...............................................................................................44 TPS Commissioning ........................................................................................................46 Patient Specific IMRT QA Comparison ..........................................................................47 Results .....................................................................................................................................48 Discussion ...............................................................................................................................51 Conclusions .............................................................................................................................54 5

4 INDEPENDENT PLANAR DOSE CALCULATION FOR IMRT QA ................................63 Introduction .............................................................................................................................63 Methods and Materials ...........................................................................................................64 Head Scatter Source Models ...........................................................................................64 Planar Dose Calculation Algorithm .................................................................................67 Comparison for Head Scatter Calculation .......................................................................72 Comparison for IMRT Dose Calculation ........................................................................73 Results .....................................................................................................................................74 Comparison of Head Scatter Factors ...............................................................................74 Comparison of Dose Calculation .....................................................................................75 Computation Time ...........................................................................................................76 Discussion ...............................................................................................................................76 Conclusions .............................................................................................................................80 5 THE CALIBRATION OF A NOVEL 4D DIODE ARRAY ..................................................89 Introduction .............................................................................................................................89 Methods and Materials ...........................................................................................................91 Description of the 4-D Diode Array ................................................................................91 Diode Array Calibration ..................................................................................................92 Diode sensitivity correction factors ..........................................................................93 Diode directional response correction factors ..........................................................94 Independence of Calibration Factors on Field Sizes .......................................................97 Gantry Angle Derivation Algorithm ...............................................................................97 Diode Array Calibration Validation ................................................................................99 Results ...................................................................................................................................100 Discussion .............................................................................................................................102 Conclusions ...........................................................................................................................105 6 CLINICAL APPLICATION OF A NOVEL 4D DIODE ARRAY FOR IMRT AND VMAT QA ............................................................................................................................117 Introduction ...........................................................................................................................117 Materials and Methods .........................................................................................................118 Detector characterization ...............................................................................................118 Clinical Application .......................................................................................................120 Sensitivity to errors ........................................................................................................122 Results ...................................................................................................................................123 Discussion .............................................................................................................................126 Conclusions ...........................................................................................................................129 7 CONCLUSIONS ..................................................................................................................141 LIST OF REFERENCES .............................................................................................................146 BIOGRAPHICAL SKETCH .......................................................................................................155 6

LIST OF TABLES Table page

2-1 P-values from two-tailed Wilcoxon rank-sum test. ...........................................................35 3-1 Best-fit shape parameter σ k of the detector response function. .........................................55 3-2 Average passing rate and standard deviation of the IMRT QA results .............................55 4-1 The comparison of average passing rates. .........................................................................82 5-1 Pseudo algorithm to derive instant beam angle. ..............................................................107 5-2 Beam incident angle derivation for four Step and shoot IMRT beams. ..........................108 6-1 Effect of using averaged directional correction factors. ..................................................131

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LIST OF FIGURES Figure page

1-1 Multi-leaf Collimator and a patient undergoing IMRT. ....................................................21 1-2 Flow chart of the dissertation. ............................................................................................22 2-1 Average passing rates of Gafchromic EBT film measurement with DTA. .......................35 2-2 Average passing rates of Gafchromic EBT film measurement with Gamma. ...................36 2-3 Average passing rates of MapCHECK measurement with DTA. ......................................36 2-4 Average passing rates of MapCHECK measurement with Gamma. .................................37 2-5 Drop of average passing rates with film measurement. .....................................................37 2-6 Drop of average passing rates with MapCHECK measurement. .......................................38 2-7 Average passing rates when comparing error free plans to plans with errors. ..................38 3-1 Comparison of cross beam profiles measured with different dosimeters. .........................56 3-2 Diode measured beam profiles and the corresponding TPS calculated beam profiles. .....57 3-3 Convolution to obtain kernel parameters. ..........................................................................58 3-4 Deconvolution results for small and medium field sizes. ..................................................59 3-5 Deconvolution results for large field size. .........................................................................60 3-6 Deconvolution results for asymmetric MLC field. ............................................................60 3-7 Comparison of the passing rates. .......................................................................................61 3-8 Example of calculated planar dose distributions. ..............................................................62 4-1 Flowchart of the proposed IMRT planar dose calculation algorithm. ...............................82 4-2 Comparison of the calculated fluence. ...............................................................................83 4-3 Comparison between the measured and calculated head scatter factors. ...........................84 4-4 Comparison of head scatter factors with modified three source model. ............................85 4-5 Comparison of head scatter factors with modified single source model. ..........................86 4-6 Comparison between the measured and calculated cross beam profiles. ..........................87 8

4-7 Comparison of MapCHECK-measured and calculated planar dose distributions. ............87 4-8 Example of a calculated planar dose distribution. .............................................................88 4-9 Source intensity distribution. .............................................................................................88 5-1 Prototype of a 4D diode array. .........................................................................................109 5-2 Diagram of a p-n junction diode. .....................................................................................109 5-3 Definition of relative gantry angle and normalized measured beam profile. ..................110 5-4 Field size dependence of diode response. ........................................................................111 5-5 Algorithm for deriving instant beam incident direction. .................................................112 5-6 Convert dose measured in water to dose in acrylic. .........................................................112 5-7 Relative diode response as a function of field size with normal incidence. ....................113 5-8 Relative diode response as a function of field size with oblique incidence. ....................113 5-9 Relative diode sensitivity of all diodes on the diode array. .............................................114 5-10 Directional response as a function of beam incident angle. .............................................115 5-11 Comparison between Pinnacle calculation and diode array measurement. .....................115 5-12 Detector response isotropicity. .........................................................................................116 6-1 Electron pulses and setup to change dose rate by varying source to detector distance. ..132 6-2 Linear detector response as a function of delivered monitor units. .................................133 6-3 Pulse rate and dose rate dependence of diode response. ..................................................134 6-4 Dose profile calculated by Pinnacle and measured by diode rings. .................................136 6-5 Dose profile for conformal arc plan. ................................................................................138 6-6 Average passing rate change of three IMRT beams with gantry rotation errors. ............139 6-7 Average passing rate change of three IMRT beams with MLC errors. ...........................140

9

Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy

EVALUATING AND IMPROVING PATIENT-SPECIFIC QA FOR IMRT DELIVERY

By Guanghua Yan

May 2009

Chair: Chihray Liu Cochair: Jonathan G. Li Major: Nuclear Engineering Sciences

Modern radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) and newly-emerging volumetric modulated arc therapy (VMAT) aim to deliver highly conformal radiation dose to the target volume while sparing nearby critical organs as much as possible with the complex motion of multi-leaf collimator (MLC) leaves. Pre-treatment patient specific quality assurance (QA) has become an essential part of IMRT in making sure the delivered dose distributions agree with the planned ones. This dissertation evaluates the performance of current patient-specific QA process and proposes solutions to improve its sensitivity, accuracy and efficiency. In step and shoot IMRT, the study on the sensitivity of patient-specific QA to minor MLC errors reveals tighter criterion such as 2%/2mm must be employed to detect systematic MLC positioning errors of 2 mm. However, such criterion results in low average passing rate which leads to excessive false alarms, mainly due to inadequate treatment planning system (TPS) beam modeling on beam penumbra. An analytical deconvolution approach is proposed to recover true photon beam profiles to obtain a true beam model which significantly improves agreement 10

11 between calculated and measured dose distributions. Thus a tighter criterion could be employed to enhance the sensitivity of patient-specific QA to minor errors in the delivery system. Measurement based patient-specific IMRT QA is a time-consuming process. A fast and accurate independent planar dose calculation algorithm is proposed to replace measurement based QA. The algorithm analytically models photons coming out from the accelerator and computes dose distribution from first principles. Accuracy of the algorithm is validated against 2D diode array measurements. The algorithm is found to be fast and accurate enough to replace time consuming measurement based QA. Patient-specific QA for VMAT differs significantly from step and shoot IMRT due to the increased use of dynamic components (dynamic gantry and collimator, dynamic MLC and variable dose rate) in VMAT. A novel four dimensional (4D) diode array is developed by Sun Nuclear Corp for patient-specific VMAT QA. This work develops effective calibration procedures for this novel device by accounting for diode sensitivity and angular response dependence. A real time algorithm to derive gantry angle is developed to interpolate corresponding angular correction factors. Clinical applications of the diode array are demonstrated with IMRT as well as VMAT plans. Excellent agreement (>95% passing rate with 1%/2mm criterion) is achieved between diode array measurement and TPS calculation. The 4D diode array is proved to be a valuable tool for both IMRT and VMAT patient specific QA.

CHAPTER 1 INTRODUCTION General Introduction Radiation therapy uses ionizing radiation as part of cancer treatment to control malignant cells. It destroys or kills cancer cells in the targeted area (“tumor”) by damaging their genetic materials and preventing them from growing and dividing. Although radiation can destroy both cancer cells and normal cells, most normal cells will recover from radiation damage due to regrowth process. It is crucial to deliver adequate dose to the tumor cells to achieve cancer killing while avoiding surrounding healthy tissue to minimize side effects. Historically, maximum dose prescribed to the tumor is limited by the sensitivity and limits of nearby organ at risk (OAR) and thus the effectiveness of radiation therapy is reduced. A number of recent refinements and technologies have dramatically increased the effectiveness of external radiation therapy by shaping radiation to the target. Three-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) are among those new technologies. Three dimensional CRT utilizes modern computed tomography (CT) techniques to acquire a 3D image of the patient which allows the physician to delineate the tumor and critical organs precisely. Radiation beams are optimized to conform to the targets with jaws and multi-leaf collimators (MLC). Sufficiently high radiation dose could be delivered to the tumor while surrounding healthy tissues are largely spared. The effectiveness of 3D-CRT is significantly improved compared to traditional two dimensional (2D) treatments where only one or a few axial slices of the patient anatomy were acquired for planning. Three dimensional CRT is a dramatic change from traditional practice in that it utilizes tumor and critical structures delineated on multiple transverse CT images, radiation fields designed in beam’s eye view and volumetric dose calculation and evaluation tools. 1

12

IMRT is a further extension of 3D-CRT in that non-uniform fluences generated by the superposition of multiple MLC segments or dynamic MLC movements are used to improve dose conformity and OAR sparing. The modulated fluences are obtained from inverse planning and computer optimization with the guidance of clinical goals and objectives. It inherits all the new tools and methodologies from 3D-CRT. Previous radiation therapy techniques including 3D- CRT do not provide a method for sparing critical structures that either push into the target or are tightly surrounded by targets. 2 IMRT does allow for highly conformal dose distribution with sharp dose gradient for complex target volumes with concave surfaces. This is accomplished by the complex motion of MLC leaves (Figure 1-1 a) equipped on a medical linear accelerator (LINAC). 3 This advantage has been utilized to escalate dose to the tumor. As a consequence, each IMRT field has many small, irregular and asymmetric subfields defined by MLC leaves and are characterized by high dose gradient. In IMRT delivery, the mechanical components that can be varied are gantry positions, collimator positions, MLC configurations, couch positions and dose rates. IMRT delivery techniques based on MLC can be typically classified into two categories: fixed gantry IMRT and dynamic gantry IMRT. 2 If the gantry remains stationary when radiation beam is on, the delivery is referred to as fixed gantry IMRT. Otherwise, it is referred to as dynamic gantry IMRT. Fixed gantry IMRT includes sliding window techniques and segmental IMRT. Sliding window techniques allow MLC motion when beam is turned on while segmental IMRT turns off the beam when MLC is in motion (so called step and shoot delivery). In both sliding window techniques and segmental IMRT, gantry angles are usually selected manually with the guidance of beam’s-eye-view for optimal target coverage and OAR sparing (Figure 1-1 b). Both techniques in the fixed gantry IMRT category have gained wide application in clinical practice 13

for more than a decade. In the category of dynamic gantry IMRT, a special type called volumetric-modulated arc therapy (VMAT) is rapidly proliferating recently in both academic and community practice due to its shorter treatment time and less monitor units than fixed gantry IMRT. 4 It utilizes all the dynamic components (dynamic gantry and collimator, dynamic MLC and variable dose rate) to achieve these advantages. IMRT represents one of the most exciting technology advancements in radiation therapy since the introduction of CT imaging in radiation treatment planning. 5 It is a new treatment paradigm to deliver high doses of radiation to tumor while providing maximum sparing for nearby OAR. The obvious dosimetric advantage and increased reimbursement have fueled the speed of clinical dissemination of IMRT. 6 A recent survey shows IMRT treatment was used by 73% of the responding radiation oncologists while the number was 32% in 2002. 7 It has been estimated that 30%~60% of the cancer patients in the United States are currently being treated with IMRT. 8 Improved local control and reduced complications as compared with 3D-CRT has been observed for all common anatomical sites with the largest number of applications for prostate and head and neck treatment. 7

However, the advancement in IMRT delivery doesn’t come without a risk. The clinical efficacy of IMRT relies on the ability of the planning system and the delivery system to accurately deliver planned dose to the target. The proximity of critical organ to tumor leads to high dose gradient which puts stringent requirements on modeling radiation beam penumbra as well as radiation dose outside beam opening. The complicated motion of MLC leaves to modulate beam segments makes leaf positioning accuracy more critical than 3D-CRT. 3 Patient delivery quality assurance (QA) has become an integral part of IMRT treatment process. Increased effort has to be made to understand IMRT planning and delivery process and its 14

associated QA procedures compared with 3D-CRT. 3 The AAPM guidance document on IMRT points out that IMRT QA consists of three tasks: commissioning and testing of the treatment planning and delivery systems, routine QA of the delivery system, and patient-specific validation of treatment plans 1 . The first task concerns with the integrity of the planning system in modeling the delivery system. The second task deals with the mechanical and dosimetric accuracy of the delivery system (gantry and collimator rotation, MLC positioning, etc). The third task is to ensure safe and accurate treatment of a patient. In general, IMRT is a complex technique including patient simulation, treatment planning, leaf sequencing, plan transfer, patient positioning, online verification and treatment delivery. Patient specific IMRT QA, as a safe guard and total system check, plays an essential role in making sure IMRT delivery is carried out as prescribed and planned. Patient-specific IMRT QA The clinical efficacy of IMRT treatment depends on the ability of the delivery system to faithfully deliver the planned dose distribution to the desired location. IMRT process as described above has multiple steps with potential errors arising from each step. Patient-specific IMRT QA, as a total system check, provides a unique opportunity to identify these potential sources of errors and plays an essential role in ensuring the safe and accurate delivery of IMRT. Typical patient-specific IMRT QA involves the measurement of a point dose or 2D dose distributions in a homogeneous phantom and compared with the treatment planning system (TPS) calculation. The whole delivery sequence of an IMRT treatment is transferred onto the CT image of the phantom and calculated with TPS. At the same time, the entire delivery sequence is delivered on the phantom and a planar dose at a certain depth is measured with some dosimeters. The measured and calculated planar dose distributions are compared and analyzed with dose difference, distance to agreement 9 or gamma index 10 , etc. The percentage of points, area or 15

volume passing a pre-selected criterion is used to indicate the quality of the whole planning and delivery procedure. IMRT planning and delivery systems are changing rapidly and there have been no well established standards on measuring devices, criteria or acceptance levels for patient-specific IMRT QA. Different dosimeters have been employed or developed for IMRT QA measurement. Ion chamber combined with film is the early popular choice. An ion chamber could be placed in a high dose and low dose gradient region for absolute point dose measurement. Film can be irradiated to measure a relative dose distribution. An absolute planar dose map can be obtained by combining ion chamber and film measurement. Accuracy of the measurement depends on the selection of the measuring point. This is a time consuming process. Film is gradually replaced by online 2D detectors such as diode arrays and ion chamber arrays. Absolute planar dose distribution could be obtained during a single delivery which makes measurement more accurate and efficient. The downside of these online 2D detectors is their limited spatial resolution compared with film. Portal dosimetry based on electronic portal imaging device (EPID) is another alternative for IMRT QA measurement. It has excellent resolution with immediate readout. However, designed as an imaging device, EPID requires a lot of correction factors to achieve accurate dosimetry which may limit its wide application in IMRT QA. Just like there are a lot of different choices of dosimeters for QA measurement, there is no consensus on what criteria one should use in evaluating the agreement between measured and calculated dose distribution. A recent survey shows the majority responding clinical institutions use 3%/3mm criterion in their practice. 11 At the same time, stricter criterion such as 2%/2mm and looser criterion such as 5%/5mm are both used at different institutions. With the same comparison criterion (for example, 3%/3mm), there have been very different achievable agreements (or 16

action levels) reported in literature. The survey conducted by Nelms et al shows majority of the community employing 3%/3mm criterion for IMRT QA analysis can achieve 90%-95% passing rates between measurement and calculation. 11 Basran et al reported that greater than 95% agreement could be achieved for non-head and neck IMRT with same criterion, while the number for head and neck was only 88%. 12 The AAPM summer school proceedings 13 provide general guidance on IMRT QA, tolerance limits and action levels. However, it doesn’t seem practical to build standards across all institutions with all these diversities in the IMRT practice. It is recommended that each facility offering IMRT should develop its own guidelines and criteria for the acceptance and QA of IMRT planning and delivery. 3 This will inevitably raise the question of how one should evaluate the performance of their own IMRT QA process in making sure the delivered dose distribution agrees with the prescribed and planned dose distribution. In 2008, Radiological Physics Center (RPC) reported that 30% of 250 head and neck IMRT irradiations of an anthropomorphic phantom performed by academic institutions applying for credentialing failed to agree with their own treatment plan to within 7% difference and 4 mm DTA accuracy criteria 14 . In other words, the irradiation of an anthropomorphic phantom demonstrated failings in their own QA procedures usually performed well on homogeneous virtual water phantom with a tighter criterion (such as 3%/3mm). These institutions were those who had confidence in their dosimetry accuracy and expected to pass the credentialing tests. The RPC credentialing test results clearly show the current IMRT QA process in these institutions fail to achieve their goal, i.e., identifying sources of errors in the system. Study Aims This dissertation consists of two parts. The first part evaluates the ability of current IMRT QA practice for fixed gantry IMRT in catching minor errors in the delivery system and proposes solutions to improve its sensitivity to errors and its efficiency. The second part focuses on 17

calibrating a novel four-dimensional dosimeter for dynamic gantry IMRT (VMAT) patient specific QA. Specifically, the first part of this dissertation focuses on these aspects of patient specific QA for fixed gantry IMRT: (1) Sensitivity to errors in delivery system. Patient specific IMRT QA is expected to catch both gross errors and minor errors in the planning and delivery system. Minor MLC positioning errors are of particular interest since MLC positioning reproducibility and accuracy are critical to the success delivery of IMRT. It is not uncommon to observe these errors 15 and they typically lead to large dosimetric impact 16 . Can the current IMRT QA process effectively catch these errors when they are present in the system? Our study shows that with either film or online 2D diode arrays the QA process fails to identify systematical MLC errors of 2 mm using popular 3%/3mm criterion. 17

(2) Accuracy. Our results show that patient-specific IMRT QA with a stricter criterion (such as 2%/2mm) exhibits stronger sensitivity to minor errors in delivery system. 17 However, not all institutions can achieve acceptable passing rate with such strict criterion which leads to large number of false alarms. One of the main reasons causing large discrepancy between calculation and measurement is the inadequate beam modeling by using beam profiles measured with finite-sized ion chambers which suffer from volume averaging effect. 18 In this dissertation, we develop algorithms to extract true photon beam profiles by removing volume averaging effect to improve treatment planning system (TPS) beam modeling. The improved TPS beam model significantly improves dose calculation accuracy. The improved agreement between calculated and measured dose distributions enables the use of stricter criterion in patient specific QA which enhances its sensitivity to minor errors in the delivery system. 18

(3) Efficiency. IMRT QA with offline detectors (film, gel dosimeter) is extremely time- consuming. With fast online electronic dosimeters (diode or IC arrays), it still takes 30 min on average for each patient QA. It has been pointed out that patient-specific verification could be reduced once confidence in dosimetric accuracy has been accumulated 19 . In this dissertation, we develop a fast and accurate independent planar dose calculation algorithm to replace measurement based patient specific IMRT QA. 20 The independent planar dose calculation is validated against diode array measurement. When performing patient-specific QA, TPS dose calculation is compared with the fast independent dose calculation instead of time-consuming delivery and measurement after clinic hours. The second part of this dissertation deals with the calibration and testing of a novel device for patient-specific QA for the newly emerging VMAT. Patient-specific QA for VMAT differs significantly from IMRT due to its increased use of dynamic components (dynamic gantry and collimator, dynamic MLC and variable dose rate). 21, 22 Ideally, patient-specific QA for VMAT should be performed in arc mode with an isotropic 3D dosimeter to check dosimetric impact of the interplay of these dynamic components. At present, there has been no such isotropic 3D dosimeter available in the market. Sun Nuclear Corp developed the first isotropic 3D dosimeter (ArcCHECK TM ) for patient-specific QA for VMAT. However, effective calibration procedure, dosimetric characterization and clinical application of this device are yet to be established. In this dissertation, we develop calibration procedures for this novel device and demonstrate its clinical application for both IMRT and VMAT patient-specific QA. In summary, this dissertation is organized with five specific aims (Figure 1-2): Specific aim 1: Investigate the sensitivity of current patient-specific IMRT QA to MLC leaf positioning errors (Chapter 2). 19

Specific aim 2: Develop deconvolution algorithms to recover true beam profiles to improve Pinnacle beam modeling and dose calculation accuracy. Tighter criteria could thus be employed in IMRT QA for enhanced sensitivity (Chapter 3). Specific aim 3: Develop independent planar dose calculation algorithms to replace measurement based IMRT QA to improve its efficiency (Chapter 4). Specific aim 4: Develop effective calibration procedure for ArcCHECK for its use in VMAT QA (Chapter 5). Specific aim 5: Study ArcCHECK dosimetric characteristics and validate its clinical application for both IMRT and VMAT QA (Chapter 6).

20

Figure 1-1. (a) Multi-leaf Collimator designed by Varian Medical Systems. Typical MLC leaf has a width of 1 cm and each leaf can be moved independently to modulate the beam. (b) A patient undergoing IMRT. The LINAC can rotate around the patient to shoot the beam from the best angles.

21

22

Figure 1-2. Flow chart of the dissertation. The purpose of this work is to propose solutions for existing issues with patient specific IMRT QA. Major work towards improving QA for fixed gantry IMRT includes the evaluation of its sensitivity (SA 1), development of deconvolution algorithm to extract true photon beam profiles for TPS commissioning (SA 2) and an independent planar dose calculation (SA 3) aiming to replace measurement based IMRT QA. For VMAT, a novel 4D diode array is characterized and calibrated (SA 4). Algorithms for its clinical application in both IMRT and VMAT QA are developed (SA 5).

CHAPTER 2 ON THE SENSITIVITY OF PATIENT-SPECIFIC IMRT QA TO MLC POSITIONING ERRORS Introduction Intensity-modulated radiation therapy (IMRT) has become the treatment technique of choice for many types of cancers receiving radiation therapy. The clinical efficacy of IMRT relies on dose escalation to the tumor while avoiding toxicity to the surrounding critical structures. Accurate multi-leaf collimator (MLC) leaf positioning plays a crucial role in the effective implementation of MLC-based IMRT 13 . Tolerance limits for leaf position accuracy and reproducibility have been suggested for IMRT which are more stringent than for conventional radiation therapy 23 . Several authors have studied the dosimetric effect of leaf positioning errors 16, 24-27 . Luo et al studied the correlation between leaf position errors and dosimetric impact in prostate cancer treatment 24 . They found a linear correlation between the target dose error and the average MLC position error, with 1% target dose change arising from 0.2 mm systematic leaf position errors. LoSasso et al also reported that a 0.2 mm gap variation leads to 1% dose variation with an average gap width of 2 cm with dynamic beam delivery 28 . Mu et al studied the dosimetric effect of leaf position errors on head and neck patients by deliberately introducing random (uniformly sampled from 0 mm, ±1 mm and ±2 mm) and systematic (±0.5 mm or ±1 mm) leaf positioning errors into the plan 26 . They found no significant dosimetric effect (<2% dose change to both target and critical organs) introduced by random leaf position errors up to 2 mm, while significant effects (8% change in D 95% and ~12% in D 0.1cc to critical organs) were observed by 1 mm systematic leaf position errors in complex IMRT plans. Zygmanski et al studied the dosimetric effect of truncated Gaussian (with 0.1 cm standard deviation) shaped random leaf position errors 27 . They found that although the average composite dose to the target of a nine 23

field IMRT plan was changed only by 3%, fluence change resulted from each single field was commonly > 10%. Woo et al found that leaf position uncertainty could lead to dose variations of up to 13% when positioning the ion chamber on the field edge 16 . All these studies emphasized the importance of the MLC positioning accuracy and reproducibility. Several authors have reported excellent accuracy of MLC leaf position by analyzing MLC log files for both dynamic MLC and static MLC 24, 27, 28 . For dynamic MLC, Zygmanski et al reported <0.05 cm leaf position error 27 , while LoSasso et al found that the average leaf gap error was much smaller than 0.02 cm 28 . For static MLC, Luo et al reported average leaf position errors of ~0.05 cm based on the analysis of MLC log files 24 . On the other hand, by using a fast video-based electronic portal imaging device, Zeidan et al observed a maximum unplanned leaf movement of 3 mm during static MLC delivery 15 . The same group’s study, based on MLC log file analysis, reported that in approximately 80% of the total segment deliveries, at least one collimator leaf had unplanned movement of at least 1 mm (projected at isocenter) during segment delivery 29 . Significant dosimetric impact could arise from these MLC position errors which suggests that periodic MLC quality assurance (QA) should be performed to ensure the accuracy and reproducibility of MLC leaf positions. It is both challenging and time-consuming to check the position accuracy of every single MLC leaf pair at all possible off axis positions 30-33 . In practice, dedicated MLC QA is conducted bi-weekly, or even less frequently, whereas patient-specific IMRT QA is usually done for every new patient before the start of IMRT treatment. The aim of this work is to assess the sensitivity of patient-specific IMRT QA to leaf position errors. A common method of patient-specific QA is to re-calculate the treatment plan in a QA phantom with all beams at 0 o gantry angle (IEC convention) and normal to the phantom surface. The planar dose distribution is measured under 24

Full document contains 156 pages
Abstract: Modern radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) and newly-emerging volumetric modulated arc therapy (VMAT) aim to deliver highly conformal radiation dose to the target volume while sparing nearby critical organs as much as possible with the complex motion of multi-leaf collimator (MLC) leaves. Pre-treatment patient specific quality assurance (QA) has become an essential part of IMRT in making sure the delivered dose distributions agree with the planned ones. This dissertation evaluates the performance of current patient-specific QA process and proposes solutions to improve its sensitivity, accuracy and efficiency. In step and shoot IMRT, the study on the sensitivity of patient-specific QA to minor MLC errors reveals tighter criterion such as 2%/2mm must be employed to detect systematic MLC positioning errors of 2 mm. However, such criterion results in low average passing rate which leads to excessive false alarms, mainly due to inadequate treatment planning system (TPS) beam modeling on beam penumbra. An analytical deconvolution approach is proposed to recover true photon beam profiles to obtain a true beam model which significantly improves agreement between calculated and measured dose distributions. Thus a tighter criterion could be employed to enhance the sensitivity of patient-specific QA to minor errors in the delivery system. Measurement based patient-specific IMRT QA is a time-consuming process. A fast and accurate independent planar dose calculation algorithm is proposed to replace measurement based QA. The algorithm analytically models photons coming out from the accelerator and computes dose distribution from first principles. Accuracy of the algorithm is validated against 2D diode array measurements. The algorithm is found to be fast and accurate enough to replace time consuming measurement based QA. Patient-specific QA for VMAT differs significantly from step and shoot IMRT due to the increased use of dynamic components (dynamic gantry and collimator, dynamic MLC and variable dose rate) in VMAT. A novel four dimensional (4D) diode array is developed by Sun Nuclear Corp for patient-specific VMAT QA. This work develops effective calibration procedures for this novel device by accounting for diode sensitivity and angular response dependence. A real time algorithm to derive gantry angle is developed to interpolate corresponding angular correction factors. Clinical applications of the diode array are demonstrated with IMRT as well as VMAT plans. Excellent agreement (>95% passing rate with 1%/2mm criterion) is achieved between diode array measurement and TPS calculation. The 4D diode array is proved to be a valuable tool for both IMRT and VMAT patient specific QA.