THE EFFECTIVE APPLICATION OF DYNAMIC ARC RADIOTHERAPY A thesis submitted to The University of Manchester for the degree of PhD In the Faculty of Medical and Human Sciences 2013 CHRISTOPHER JAMES BOYLAN SCHOOL OF MEDICINE (page intentionally blank) 2 TABLE OF CONTENTS 1. INTRODUCTION...............................................................................................................................13 1.1. Radiotherapy for the treatment of cancer.....................................................................13 1.2. From IMRT to VMAT.............................................................................................................17 1.2.2. Inverse planning.............................................................................................................19 1.2.3. Implementation of IMRT............................................................................................21 1.2.4. Clinical argument for IMRT......................................................................................23 1.3. Principles of VMAT.................................................................................................................25 1.4. VMAT research and context for thesis...........................................................................29 1.4.1. Treatment Planning.......................................................................................................30 1.4.2. Delivery and Quality Control..................................................................................33 1.4.3. Imaging...............................................................................................................................38 1.5. Hypothesis and Aims.............................................................................................................41 1.6. Structure of Thesis....................................................................................................................42 2. PUBLICATIONS..................................................................................................................................45 2.1. Publication 1................................................................................................................................45 2.2. Publication 2................................................................................................................................47 2.3. Publication 3................................................................................................................................49 2.4. Publication 4................................................................................................................................50 2.5. Publication 5................................................................................................................................51 2.6. Publication 6................................................................................................................................53 3. DISCUSSION AND FURTHER WORK...................................................................................54 3.1. VMAT plan creation from static IMRT segments.....................................................54 3.2. Automated plan comparison study.................................................................................55 3.3. VMAT delivery emulator.....................................................................................................57 3.4. Investigation into CVDR delivery....................................................................................58 3.5. Monte Carlo VMAT verification system.......................................................................59 3.6. Investigation into simultaneous cone beam imaging during VMAT..............62 REFERENCES..................................................................................................................................................65 APPENDIX 1....................................................................................................................................................73 Word count: 53,000 approx. 3 LIST OF FIGURES Introduction and discussion sections Figure 1. Demonstration of (a) the cell killing effect of fractionated 14 radiotherapy on normal and tumour tissue, (b) the principle of normal tissue complication probability and tumour control probability for a given prescription. Figure 2. Example dose distribution for a head and neck (oropharynx) 16 radiotherapy patient. Figure 3. The principle of (a) conformal radiotherapy, in which only the 17 aperture shapes are modulated, and (b) intensity modulated radiotherapy, where the in‐plane fluence is also modulated. Figure 4. The two techniques for MLC‐based IMRT delivery – (a) step and 18 shoot, and (b) dynamic MLC (‘sliding window’). Figure 5. Geometry of a cone beam CT system for a typical linear accelerator. 22 Figure 6. The principle of VMAT delivery, whereby MLC shapes are 25 changed while the gantry rotates. Figure 7. The influence of the static sampling of control points on VMAT 28 dose calculation accuracy, at distances far from the isocentre. Figure 8. Overview of the different planning techniques for VMAT. 31 Figure 9. Schematic of linac motion between control points. 34 Figure 10. Different methods of dosimetric verification for VMAT treatment 38 plans. Figure 11. The impact of MV scatter on simultaneously‐acquired CBCTs of 39 prostate VMAT patients. Figure 12. Overview of different scatter‐correction techniques for 41 simultaneous CBCTs. Figure 13. Differences between continuous and static Monte Carlo simulations 60 of VMAT dose delivery for a prostate patient. Publication 1 45 Figure 1. Control point pairs produced by DAO for a prostate VMAT plan. Figure 2. Example of four consecutive control points for resultant VMAT plans. Figure 3. DVH comparison between IMRT and the in‐house VMAT plans, for one of the five prostate patients assessed. Figure 4. Comparison of CHHIP dosimetric parameters between IMRT and the in‐house VMAT plans. Publication 2 47 Figure 1. Flowchart for the automated planning process. Figure 2. Typical regions of interest for a nasopharynx VMAT patient, showing the dummy structures used for optimization Figure 3. Averaged DVH for the nasopharynx plans, comparing VMAT to the IMRT automated solutions. Figure 4. Example DVH showing the progress of the automated planning methodology. 4 Publication 3 48 Figure 1. Flowchart describing the VMAT linac emulator process. Figure 2. Comparison between emulator predictions of dose rate and gantry positions, and those measured on the linac. Figure 3. The effect of increasing the allowable leaf speed on VMAT prostate plan delivery. Figure 4. The effect of increasing the allowable leaf speed on VMAT head and neck plan delivery. Figure 5. The effect of allowing continuously variable dose rate rather than binned dose rate VMAT delivery. Figure 6. The influence of the number of bins (255 and 1023) on the stability of gantry speed. Publication 4 49 Figure 1. MLC leaf positions identified on a portal image during VMAT delivery Figure 2. Principle of flatness monitoring using the integrated portal image during VMAT. Figure 3. Dose rate variation for CVDR and BDR for a head and neck VMAT plan. Figure 4. Deviation of the GT beam profiles for CVDR and BDR over a head and neck delivery. Figure 5. Mean deviation of profiles for BDR and CVDR deliveries. Figure 6. Delta4 gamma histograms for a head and neck delivery, indicating good dosimetric agreement. Figure 7. Plot of mean MLC deviations over an arc for one of the prostate patients. Publication 5 50 Figure 1. Schematic of the modelled Monte Carlo linac head, showing the main components. Figure 2. Demonstration of how the acceleration of the linac head is accounted for using the delivery emulator by distributing the monitor units non‐uniformly between control points. Figure 3. Flowchart for the automated pre‐treatment QA system. Figure 4. Results of the static beam modelling, showing depth dose curves, profiles, output factors and the MLC bar test. Figure 5. Gamma comparison between Monte Carlo and the Marvin phantom. Figure 6. Output of the automated QA system for a prostate VMAT patient. Figure 7. Output of the automated QA system for a head and neck VMAT patient. Figure 8. The effect of increasing the number of steps between control points for the continuous calculation of dose. 5 Publication 6 52 Figure 1. The image quality phantoms used for assessment of the scatter correction technique. Figure 2. Schematic of the correction strategies investigated. Figure 3. An MV‐only scatter frame from a VMAT delivery. Figure 4. Mean image signal pre and post correction for the simultaneous imaging. Figure 5. Comparison of the signal to noise ratios for the different correction methodologies. Figure 6. A single CBCT slice from one of the clinical SCART patients, showing how the scatter correction methods recover image quality. 6 LIST OF TABLES Introduction and discussion sections Table 1. The SCART image quality scoring system for prostate CBCT scans. 62 Publication 1 45 Table 1. CHHIP trial parameters used for prostate IMRT and VMAT plan evaluation. Publication 2 47 Table 1. Nasopharynx plan objectives for the automated planning system. Table 2. Plan parameters used for IMRT and VMAT optimization. Table 3. Dosimetric results for IMRT and VMAT using the automated planning technique. Table 4. Lowest achievable parotid doses using the automated planning methodology. Table 5. Highest achievable prescription doses using the automated planning methodology. Publication 3 48 Table 1. Dynamic modelling parameters for the VMAT delivery emulator. Table 2. Emulator versus measured delivery times for a cohort of prostate and head and neck VMAT plans. Table 3. Required ‘ideal’ linac parameters to ensure 60s delivery time. Publication 4 49 Table 1. Delivery times for BDR and CVDR deliveries. Table 2. Delta4 verification results for plans delivered with BDR and CVDR. Table 3. Leaf positioning errors from BDR and CVDR deliveries. Publication 5 50 Table 1. Gamma analysis results between Delta4 and the Monte Carlo VMAT model for prostate patients. Table 2. Gamma analysis results between the MARVIN phantom and the Monte Carlo VMAT model for head and neck patients. Publication 6 52 Table 1. Standard CBCT imaging parameters used for prostate patients. Table 2. Prostate CBCT image quality scoring scheme. Table 3. Averaged image quality scores for the different variants of the scatter correction. 7 LIST OF ABBREVIATIONS VMAT – volumetric modulated arc therapy IMAT – intensity modulated arc therapy IMRT – intensity modulated radiation therapy CBCT – cone‐beam computed tomography TCP – tumour control probability NTCP – normal tissue complication probability OAR – organ at risk PTV – planning target volume CTV – clinical target volume GTV – gross tumour volume ROI – region of interest BDR – binned dose rate CVDR – continuously‐variable dose rate IGRT – image‐guided radiation therapy MLC – multi‐leaf collimator LINAC – linear accelerator DAO – direct aperture optimisation BEV – beam’s eye view dMLC – dynamic multi‐leaf collimator DVH – dose‐volume histogram SIB – simultaneous integrated boost NPC – nasopharyngeal carcinoma PRV – planning reference volume 8 ALTERNATIVE FORMAT Permission has been obtained to submit this thesis in the ‘alternative format’, whereby sections are included in the form of scientific publications. The rationale for submission in alternative format is given in the introduction (section 1.6). The published and submitted papers are given below. LIST OF PUBLICATIONS 1. A VMAT planning solution for prostate patients using a commercial treatment planning system Published in Physics in Medicine and Biology, 2010, vol. 55, pp. N395‐N404 2. A bias‐free, automated planning tool for technique comparison in radiotherapy – application to nasopharyngeal carcinoma treatments Accepted by Journal of Applied Clinical Medical Physics, July 2013 3. The use of a realistic VMAT delivery emulator to optimize dynamic machine parameters for improved treatment efficiency Published in Physics in Medicine and Biology, 2011, vol. 56, pp. 4119‐4133 4. The impact of continuously‐variable dose rate VMAT on beam stability, MLC positioning and overall plan dosimetry Published in Journal of Applied Clinical Medical Physics, 2012, vol. 13, pp. 254‐266 5. Pre‐treatment independent plan verification for VMAT using a treatment delivery emulator and Monte Carlo dose model Accepted by Radiotherapy and Oncology, September 2013 6. A megavoltage scatter correction technique for cone‐beam CT images acquired during VMAT delivery Published in Physics in Medicine and Biology, 2012, vol. 57, pp. 3727‐3739 9 ABSTRACT Volumetric modulated arc therapy (VMAT) is a technique for the delivery of intensity modulated radiotherapy (IMRT) whereby the linear accelerator (linac) delivers dose continuously while rotating around the patient. VMAT has gained attention due to its ability to produce complex dose distributions, deliverable in a much shorter treatment time than IMRT. The purpose of this thesis was to investigate the clinical application of VMAT, and to identify any benefits over IMRT in the areas of treatment planning, delivery, and imaging. A VMAT planning strategy was developed which demonstrates that complex dynamic arc deliveries can be sequenced from static, IMRT‐based control points. For prostate patients, the VMAT solution demonstrated superior sparing of critical structures compared to IMRT plans. A further comparison of VMAT and IMRT was performed with the development of an automated planning methodology, which aimed to reduce the impact of planner bias. Applied over a series of nasopharynx patients, the technique showed that VMAT achieved an improvement in parotid sparing compared to IMRT. To investigate the limitations on the delivery of VMAT plans, a software emulator was produced to accurately simulate linac motion. The emulator was used to determine ʹidealʹ linac parameters for a range of VMAT plans. Leaf speed was found to be a limiting factor for the achievable plan complexity, along with the availability of continuous variable dose rate (CVDR). For a commercial CVDR system, experiments confirmed the improved delivery efficiency, and an improvement in dosimetric accuracy compared to the binned dose rate (BDR) system. An independent dose calculation methodology was developed for VMAT, such that accurate pre‐treatment plan QC can be performed. It was found that the accuracy of a Monte Carlo simulation was improved when accounting for the effects of realistic linac motion. Finally, the impact of MV scatter on simultaneously‐acquired cone beam CT images was investigated, and a scatter correction methodology was developed and validated. This thesis shows that VMAT can offer an alternative to static‐field IMRT, provided that knowledge of the limitations of dynamic linac motion are accounted for within planning. Results suggest that modern linac designs (i.e. faster MLC speed, and a higher, continuously‐variable dose rate) are required to achieve robust delivery of complex plans. The workflow benefits of VMAT can also be optimised through the use of independent dose calculations incorporating delivery characteristics, and through the use of image guidance from CBCT scans acquired during treatment. Christopher James Boylan The University of Manchester Doctor of Philosophy ‘The effective application of dynamic arc radiotherapy’ June 2013 10
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