Evaluation of scatter distribution through segmented intensity modulated radiation therapy (IMRT) fields in treatment of head and neck cancer

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1 The University of Toledo The University of Toledo Digital Repository Master s and Doctoral Projects Evaluation of scatter distribution through segmented intensity modulated radiation therapy (IMRT) fields in treatment of head and neck cancer Bishwa K. Aryal Medical University of Ohio Follow this and additional works at: This Scholarly Project is brought to you for free and open access by The University of Toledo Digital Repository. It has been accepted for inclusion in Master s and Doctoral Projects by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's About page.

2 FINAL APPROVAL OF SCHOLARLY PROJECT Master of Science in Biomedical Sciences Evaluation of Scatter Distribution Through Segmented IMRT Fields in Treatment of Head and Neck Cancer Submitted by Bishwa K. Aryal In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences Date of Defense: August 19, 2005 Major Advisor E. Ishmael Parsai, Ph.D. Academic Advisory Committee John Feldmeier, D.O. Dan Schifter, M.S. Dean, College of Graduate Studies Keith K. Schlender, Ph.D.

3 Evaluation of Scatter Distribution through Segmented Intensity Modulated Radiation Therapy (IMRT) Fields in Treatment of Head and Neck Cancer A Scholarly Project Report Submitted to Department of Radiation Oncology in Partial Fulfillment of the requirement of degree of Master of Science in Biomedical Science in Medical Physics By Bishwa K. Aryal November, 2005

4 ACKNOWLEDGEMENTS I would like to thank my major advisor Dr. E. I. Parsai, Ph. D., chief of physics for his continuous guidance and encouragement throughout this project. I am thankful to Mr. Dan Schiftor, M.S.,Assistant Professor for his valuable suggestion. I would like to express my deep appreciation to Dr. J.J. Feldmeier, D.O, Chairman of Radiation Oncology Department for his encouragement. I am thankful to my colleagues for their suggestions. At last, I am very grateful to my husband Mr. Kalyan Adhikary for his continuous encouragement throughout this project.

5 TABLE OF CONTENT ABSTRACT INTRODUCTION AND OBJECTIVES 1.1 Introduction 1.2 Objective LITERATURE STUDY 2.1 Definition 2.2 Planning Process 2.3 Dose verification MATERIALS AND METHODOLOGY 3.1 Materials 3.2 Method RESULTS DISCUSSION CONCLUSION

6 LIST OF TABLES Table 1: Objectives used for head and neck IMRT plans Table 2: Mean, Minimum and Maximum Target and PTV Dose as Average Value of all Patients in Different Beam Arrangement of IMRT. Table 3: Mean and Maximum Dose of Organ at Risk as Average of all Patients Table 4: The mean, maximum and minimum dose of target and PTV for coplanar and non coplanar plan as average of five patients Table 5: Mean and maximum dose of critical structures for coplanar and non coplanar plan for an individual patient Table 6: Point Dose Measurement Using Ionization Chamber Table 7: Measured and Calculated Dose Difference in Vertical and Horizontal Profiles Table 8: Dose difference taken from difference histogram plot Table 9: The Gamma Index of Dose Difference Table 10: Fluence Comparison of IMRT and 3D plans

7 LIST OF FIGURES Figure 1: Beam Arrangement for 5 field IMRT Figure 2: Beam Arrangement for 7 field IMRT Figure 3: Beam Arrangement for 9 field IMRT Figure 4: Optimization process of IMRT Figure5: The Conversion Window in Inverse Planning. Figure 6: Isodose distribution generated by 5 field IMRT technique Figure 7: Isodose distribution generated by 7 field IMRT technique Figure 8: Isodose distribution generated by 9 field IMRT technique Figure 9: Dose volume histogram of a patient for 5 field, 7 field and 9 field regarding the PTV, cord and parotid gland. Figure 10: DVH of PTV (light blue), cord (blue), right parotid (yellow) and left parotid (purple) for 9 field (no dashed line), 7 field (dashed in grey scale), 5 field (dashed line in inverse grey scale). Figure 11: a. Isodose distribution of coplanar plan. b. Isodose distribution of non coplanar plan. Figure 12: Dose volume histogram for coplanar and non coplanar plan. Figure 13: Isodose overlay of planned and measured dose. Black line represents isodose of planned dose and color lines represent isodose of measured dose from film. Figure 14: Figure showing the vertical profile of measured and planned dose Figure 15: Figure showing the horizontal profile of measured and planned dose Figure 16: Figure showing the histogram plot of analysis (low gradient- high dose) Figure 17: Plot of dose difference histogram Figure 18: Plot showing the gamma index. Y-axis shows the number of pixel Figure 19: Plot of gamma index pass/fail image Fig 20: Fluence at plane of different depth from 3D conformal and IMRT plans. Fig 21: Horizontal and vertical profile at plane of different depth

8 ABSTRACT The main aim of this study was to evaluate scatter dose in IMRT of head and neck cancer. All together seven head and neck patients were included. IMRT plans were generated using 5, 7 and 9 beams in each case. IMRT QA was performed to verify the dose calculated from treatment plan. For each case, 3D conformal plans were generated to compare the fluence at different depth. Five cases of brain tumor were used to generate the plan using coplanar and non coplanar technique. The mean target and PTV dose increased with the increase in number of beams. However, the increase is not significant between 5 fields and 7 fields IMRT. There was significant difference in mean dose between 7 and 9 field. There was only slight improvement in dose coverage. The maximum cord dose was slightly decreased with the increase in number of beams. The target dose homogeneity was found to be similar for 5 fields and 7 fields. However, PTV dose homogeneity was best for 7 fields IMRT. Dose verification using point dose measurement showed that the discrepancy between planned and measured dose was below 2.24 %. Film dosimetry showed good agreement between planned and measured dose. The fluence map comparison between IMRT and 3D didn t show any specific trend at different depth. However, qualitative comparison of fluence showed some indication of higher dose at superficial depth in IMRT fields. Based on the dose coverage and homogeneity, 7 field IMRT is suitable number of beams in the treatment of head and neck cancer. RIT system may not be the suitable method for the evaluation of scatter dose. This need to be done by measurement in different plane in phantom.

9 CHAPTER-ONE 1.1 Introduction INTRODUCTION AND OBJECTIVES Head and neck cancer is the major cause of morbidity throughout the world. Approximately 56,520 new cases were diagnosed and 14,500 persons died of head and neck cancer in United States in Radiation therapy for head and neck cancer is difficult task because several critical structures are usually in close proximity to the tumor. The range of dose that can be received by critical structure without complication lie in the range of Gy but tumor control dose is higher than 60 Gy. It is believed that IMRT is able to conform dose to target even in concave tumor and spare critical structures 2. IMRT has been used in the treatment of cancers of the prostate, head and neck, breast, thyroid and lung, gynecologic, liver and brain tumors and lymphomas and sarcomas. IMRT is also beneficial for treating pediatric malignancies. In head and neck, the tumor often curves around the spinal cord or brainstem and other important structures. IMRT is suitable for head and neck cancer as organ motion is minimal. However, every head and neck patient doesn t benefit from IMRT because it is very complex and time consuming process. Patients with paranasal sinus cancer, patients with tumor that encompass most of the salivary glands and patients with tumor that is close to brain stem and spinal cord benefit from IMRT 3. To get an optimal IMRT treatment, it is necessary to choose right number of beams and their orientation. One aspect of this study is the comparison of 5 field, 7 field and 9 field beam arrangements in IMRT of head and neck cancer

10 IMRT is a sophisticated task for treatment planning. The complexity of IMRT dose patterns makes the verification of the match between planned and delivered doses more difficult than for conventional technique. A reliable quality assurance (QA) of the dose distribution within the patient is very important. The dose calculated by treatment planning system will be verified. The goal of radiotherapy is to deliver required dose to the target and minimizing the doses to adjacent organs at risk and other normal tissues. Three-dimensional conformal radiation therapy is an efficient technique for achieving this goal in most cases. There are many critical structures involved in the treatment of brain. With beam apertures conformed to the target, it is possible to spare organ at risk. Coplanar and non coplanar beam arrangements in 3D conformal planning of brain tumor will be compared in terms of dose coverage to the target and dose to the critical structures. Even though IMRT is suitable for the treatment of many cases, it is not always useful. Despite some advantages, there are some disadvantages of IMRT which include dose inhomogeneity within the target, increased volume of normal tissue exposure, requires enormous amount of output or monitor units, and requires prolonged treatment time 4. The total monitor units required for a segmented MLC-IMRT treatment are higher than that of corresponding non intensity modulated treatment. Highly irregularly shaped MLC segment fields pose challenges to dose and MU calculation 5. MLC based IMRT techniques shown some drawbacks in clinical application. Due to high monitor units that need to be delivered with multiple segments secondary radiation from leakage and scatter is increased. Each beamlet contributes scatter dose. In head and neck, the desired intensity profiles produced by the optimization module tend to be highly complex. A large number of small segments are included in the leaf sequences. In these cases head scatter will have significant influence on incidence fluence 6. It is assumed that the scatter dose is higher in shallow

11 depth. The fluence in different depth will be generated for IMRT and 3D-conformal plan and compared. The following objectives have been undertaken to work in this study. 1.2 Objectives i. Comparison of different beam arrangements (5 field, 7 field and 9 field) in IMRT treatment of head and neck. Dose uniformity and sparing of critical structures will be discussed. ii. Qualitative and quantitative comparison of planned vs. measured dose for IMRT plans using film dosimetry and ionization chamber measurements iii. Comparison coplanar vs. non coplanar beam arrangements in 3D conformal treatment planning of brain tumor. The target and critical structure dose will be evaluated. iv. Comparison of conformal 3D optimized plan vs. IMRT plan in terms of quantitative fluence. Will examine changes in fluence mapping at midplane (target central plane), midway towards the surface and at 0.5 cm depth in tissue. Analysis of scatter dose contribution to shallow tissue from IMRT plans as a result of large MU and small segmented field sizes.

12 CHAPTER-TWO LITERATURE STUDY 2.1 Definition of IMRT The treatment technique that uses beams of varying intensities that conforms high dose to the target and spares normal tissue structures is called intensity modulated radiation therapy. The radiation dose is designed to conform to the three-dimensional (3-D) shape of the tumor by modulating or controlling the intensity of the radiation beam to focus a higher radiation dose to the tumor while minimizing radiation exposure to surrounding normal tissues. In IMRT, a series of individual beamlets, each consisting of a narrow incident photon beam produces dose distribution. It involves the optimal distribution of fluence by treatment planning system and dose delivery through a multileaf collimator with several segments per beam in the step and shoot approach. The most common techniques for delivering IMRT treatments use multileaf collimator (MLC). During the treatment, the MLC leaves moves automatically to form the intensity modulation Planning Process Treatment planning is performed using 3-D computed tomography (CT) images of the patient in conjunction with computerized dose calculations to determine the dose intensity pattern that will best conform to the tumor shape. Combinations of several intensity-modulated fields coming from different beam directions radiation maximizes tumor dose while also protecting adjacent normal tissues. Two important steps are involved in an IMRT planning process including the generation of fluence map by the optimization module and conversion of desired intensity maps to MLC leaf sequence as a function of monitor units. In segmented MLC system, the gantry stays fixed while

13 the leaves move during a beam off segment to the next appropriated shape. Calculation of optimum intensity profiles are based on inverse planning and can be divided into two methods 1. Analytical method is a mathematical technique in which the desired dose distribution is inverted by using a back projection algorithm and it is reverse of reconstruction algorithm. It is the process of deconvolution a dose kernel from the desired distribution and the fluence distribution or kernel density can be obtained in the patient 7 2. Iterative method is the optimization process in which beamlet weights for a given number of beams are iteratively adjusted to minimize the deviation from desired goal Dose Verification The dose verification may be done by two methods: point dose measurement by ionization chamber and by radiographic film dosimetry. Measurement of fluence distributions by means of film dosimetry is done in water equivalent slab phantom with the beam direction perpendicular to the film. Quantitative evaluation methods compare the measured and calculated dose distribution values. Quality assurance procedure described by Van Dyke et al 8 includes the dose distribution comparisons into regions of high and low dose gradients. In low gradient regions, the doses are compared directly with an acceptance tolerance placed on the difference between the measured and calculated doses. The regions where the calculated dose distributions disagree with the measurements can be calculated. In high dose gradient regions, the concept of a distance to agreement (DTA) distribution is used to determine the acceptability of the dose calculation 9. DTA is the distance between a measured data point and the nearest point in the calculated dose distribution

14 that exhibits the same dose. Three percent in dose and 3 mm in distance are accepted value for agreement. 10 Another criterion for the comparison between planned and measured dose is gamma index, which is calculated by quadratic addition of the contribution from both spatial and dosimetric disagreements and expressed as percent of reference value as d = 3 mm and D = 0.03 Dcal 11. Good agreement should have gamma index of lower than 1.

15 CHAPTER-THREE METHODOLOGY 3-1. Materials ADAC pinnacle treatment planning system, IMPAC record and verifying system, RIT113Dosimetry System Version 4.1, SL-25 and SL-15 Elekta linear accelerators, Microchamber ionization chamber- A14P Extradin ( SN:XN020911),Ready pack EDR2 film (KODAK), IMRT QA plastic phantom, and Electrometer (CNMC instruments Inc, Model 206 ) Method Seven patients, who visited from April 05 to July 2005 to the Department of Radiation Oncology at Medical University of Ohio with head and neck cancer were included in this study. IMRT plans were generated with 6 MV photon in inverse planning system of ADAC Pinnacle(Version 6.2, Philips Medical System). During the planning process, different region of interest were contoured. Half a centimeter margin was given to gross target volume (GTV) and named as planning target volume (PTV). The GTV includes the primary tumor and any clinically involved lymph nodes. The ring of 0.3 cm was generated around the PTV. Other critical structures that were in treatment fields were also contoured. These structures include brain stem, optic chiasm, optic nerves, eye glove, lens, cord and parotid gland. Mainly involved critical structures were cord and parotid gland. Beam s eye view displays were used to select the individual beams and field sizes. All beams were coplanar beams. For 5 field technique beam angle used were 0 0,72 0,144 0, 216 0, The beam angles for 7 field technique were 0 0, 50 0, 102 0, 154 0, 206 0, 258 0, and 21 0, 65 0, 109 0, 151 0, 208 0, 248 0, 278 0, and for 9 beam technique

16 Figure 1: Beam Arrangement for 5 field IMRT Figure 2: Beam Arrangement for 7 field IMRT

17 Figure 3: Beam Arrangement for 9 field IMRT Beams were equally weighted before optimization. In inverse planning process certain objectives were assigned. The treatment goal was to deliver 6600 cgy to the target and at least 95 % of the dose to the planning target volume (PTV). The maximum point doses to the spinal cord and the brain stem were to be less than 4500 cgy and 5400 cgy respectively. The maximum point doses to the optic chiasm and optic nerve were to be less than 5000 cgy. The mean dose to either parotid gland was to be less than 2600 cgy. List of objectives are shown in the table no. 1 Table 1: Objectives used for head and neck IMRT plans ROI Objectives PTV* 95 % of the PTV receives prescription dose Uniform dose = RadRx= 6600 cgy Max dose = 105 % No more than 20 % of the PTV can receive >110 % of the prescription dose Cord with no margin Max dose cgy

18 Cord expanded (0.5 mm) Brain stem Optic nerve Optic chiasm Retina- posterior 2/3 of globe Lens- anterior 1/3 of globe Parotid, each gland with no margin Unspecified(soft) tissue *PTV = target cm margin Max dose 4600 cgy Max dose < 5400 cgy Max dose < 5000 cgy Max dose < 5000 cgy Max dose < 4500 cgy Max dose < 500 cgy Max DVH % volume Max DVH % volume Max DVH % volume Or Mean Dose < 2600 cgy 50 % volume < 3000 cgy < 110 % of prescribed dose After setting up the objectives in inverse planning, optimization was performed using iterations. Figure 4: Optimization process of IMRT

19 After optimization, the plan was converted to segments. The type of ODM converter was K-means clustering and jaw setting was selected as conform to segment. The error tolerance was 3 % and the minimum segment area was chosen as 2 cm 2. The minimum monitor unit per segment was 2. Figure5: The Conversion Window in Inverse Planning.

20 Minimum, maximum and mean target doses as well as maximum and mean PTV doses were evaluated. Maximum and mean dose to critical structures such as spinal cord, parotid gland and brain stem and optic chiasm were also evaluated. A detail dose histogram was used for the evaluation. Comparison of dose homogeneity of the target and sparing of critical structures was made among three different techniques of IMRT such as 5 field, 7 field, and 9 field. Paired t test for mean was used to compare the dose coverage to target in IMRT plans Each optimized plan was copied to QA phantom. All beam directions were changed to 0 degree and point dose was calculated to phantom isocenter. In case of half beam, chamber was shifted 6 cm superior from isocenter. The plan was exported to IMPAC record and verifying system to deliver dose in QA phantom. Point dose measurement was performed using micro ionization chamber (Extradin A14 SN:XN020911) and electrometer (CNMC instruments INC, Model 206 ). The placement of chamber was at 4.5 cm depth. The SSD setup was 95.5 centimeter. KODAK EDR2 film was used for film dosimetry. The film was placed at 3 cm depth at perpendicular direction. The dose was delivered from each beam. The films were developed after 1 hour and scanned using VIDAR scan and data were analyzed by RIT software in MATLAB environment. For fluence comparison between 3D conformal plan and IMRT plans, 3D conformal plans were generated using 5 beams. For the computation of fluence, one lateral beam was added to each plan. The fluence was calculated on midplane in between the midplane and at 0.5 cm depth. The midplane was determined at the target plane. The pixel size was 0.1x 0.1 cm and the dimension was 200x 200 pixels. These fluences were exported to RIT dosimetry system. The fluences generated with IMRT plans were used as reference image and the

21 fluences generated with 3D conformal plans were target images. These images were coregistered by utilizing appropriate template. The quantitative dose differences were calculated in terms of vertical profile, horizontal profile, difference histogram dose analysis and distance to agreement. For 3D conformal plan of brain, 5 patients were included. All critical structures that are proximal to the brain were contoured. One and half a centimeter margin was given to the target for blocks. Beam s eye views were used for the selection of gantry angles. For each patient, coplanar and non-coplanar plans were generated using 6 MV photon. The prescribed dose was 6000 cgy for 30 fractions.

22 CHAPTER-FOUR RESULTS To compare different IMRT techniques, isodose distributions, dose statistics and cumulative dose volume histograms (DVH) were evaluated. DVHs were displayed in terms of absolute dose and normalized volume. Table 2: Mean, Minimum and Maximum Target and PTV Dose as Average Value of all Patients in Different Beam Arrangement of IMRT. Target 5 field IMRT Dose in cgy 7 field IMRT Dose in cgy 9 field IMRT Dose in cgy Mean Dose (SD) 6632 (79) 6645 (74) 6712 (75) Maximum Dose Minimum dose Mean PTV dose 6624 (119) 6636 (125) 6697 (123) Max PTV Min PTV Prescribed dose 6600 cgy Table 2 shows mean, maximum and minimum dose of target as average of all patients. The dose was normalized to point dose. Mean target dose was cgy (100.5%) for 5 field, cgy(100.6%) for 7 field and cgy (102 %) for 9 field. The mean target dose difference between 5 field and 7 field was not statistically significant at 0.05 level (p= 0.72). However, there was statistically significant dose difference ( p = 0.01) between 7 field and 9 field IMRT techniques. It was highest for 9 field and lowest for 5 field. The maximum target dose was highest for 9 field (7041cGy) and lowest for 7 field (6959 cgy). The mean PTV dose was cgy for 9 field and cgy for 7 field and 6624 cgy cgy for 5 field.

23 Individual plan was evaluated for the coverage of PTV and target. Out of 7 patients, 3 patients had better coverage with 9 field technique, 7 field and 5 field IMRTs were best for only one patient. Coverage was similar for 7 field and 9 field for one patient. In one patient, the coverage was found to be similar in all three techniques. Figure 6: Isodose distribution generated by 5 field IMRT technique

24 Figure 7: Isodose distribution generated by 7 field IMRT technique Figure 8: Isodose distribution generated by 9 field IMRT technique Figure 6, 7 and 8 show isodose distribution in 5, 7 and 9 field techniques respectively. The purple color is target and skyblue color is PTV, which was 0.5 cm expansion of target. As shown in figures, target was covered by 97 % isodose line in 5 field IMRT technique, and

25 by 98 % line in 7 field and 9 field techniques. However, the PTV was covered by 95 % isodose line in all three techniques. Figure 9: Dose volume histogram of a patient for 5 field, 7 field and 9 field regarding the PTV, cord and parotid gland. Line without dash was for 5 field, dotted line was for 7 field, inverse grey scale (lines with black dots) was for 9 field. Red color was for PTV, green for cord and khaki color was for parotid. As shown in above figure, 5 field had less coverage for PTV. The coverage in 7 field and 9 field was similar. As number of beams increased, cord dose was decreased. However, there was highest parotid gland dose for 9 field.

26 Table 3: Mean and Maximum Dose of Organ at Risk as Average of all Patients Organ at Risk 5 field IMRT dose in cgy 7 field IMRT dose in cgy 9 field IMRT dose in cgy Cord mean (SD) 1240 (1236) 1342 (1235) 1371 (1278) Cord maximum Rt parotid mean (SD) 1414 (760) 1392 (645) 1536 (658) Rt parotid maximum Lt parotid mean (SD) 1334 (781) 1475 (509) 1469 (477) Lt parotid maximum Brain stem mean (SD) 355 (372) 360 (398) 355 (386) Brain stem maximum Optic chiasm mean (SD) 168 (25) 219 (24) 163 (22) Optic chiasm maximum SD = standard deviation It was found that maximum cord dose was decreasing with the increase in number of beams. It was lowest for 9 field (table 3). However, cord mean dose was highest for 9 field technique. Right parotid mean dose was highest for 9 field and lowest for 5 field. Maximum right parotid dose was lowest for 7 field technique. For left parotid maximum dose, it was highest for 5 fields and lowest for 7 fields. Left parotid mean dose was highest for 9 fields. Even though mean dose to brain stem was highest for 7 field technique, it was minimal. Brain stem maximum dose was decreasing with the increase in number of beams.

27 Figure 10: DVH of PTV (light blue), cord (blue), right parotid (yellow) and left parotid (purple) for 9 field (no dashed line), 7 field (dashed in grey scale), 5 field (dashed line in inverse grey scale). Nine field technique shows least dose to critical structures. Homogeneity of Dose Dose homogeneity was calculated by taking the difference between the maximum and minimum doses, dividing that number by the maximum dose and subtracting the result from 100 percent 12 Average target homogeneity was found to be 90 % for 5 field, and 92 % for both 7 field and 9 field techniques. The homogeneity ranged from 84.5 % to 93 % for 5 field. For 7 field the range was 88 % to 94 % and from 90 % to 93 % in 9 field technique. Average PTV homogeneity was 61.5 % for 5 field technique, 64.5 % in 7 field and 63.3 % for 9 field technique. The average PTV homogeneity was the best for 7 field. The average maximum hot spot was 7311 cgy i.e.110% of the prescribed dose in 5 field, 7306 cgy (110 %) in 7 field and 7232 cgy (109 %) in 9 field techniques.

28 Monitor Unit Required The average monitor unit used was 589 MU for 5 field, 661 MU for 7 field and 676 for 9 field per fraction. There was no significance difference in average MU between 7 field and 9 field (p=0.67). The highest monitor unit was 793 for 5 field, 969 for 7 field and 936 MU for 9 field. The lowest monitor unit was 452 for 5 field, 428 for 7 field and 441 for 9 field. Coplanar and Non-coplanar plan Table 4: The mean, maximum and minimum dose of target and PTV for coplanar and non coplanar plan as average of five patients Target Dose from coplanar plan in cgy Dose from non coplanar in cgy Target Mean Dose 6056 (41) 6078 (56) ( SD) Maximum Dose Minimum dose Mean PTV 5835 (451) 5849 (519) dose(sd) Max PTV Prescribed dose As shown in above table there was not much difference in mean dose in coplanar and non coplanar plan. Target and PTV doses were higher in non coplanar plan.

29 Figure 11: a. Isodose distribution of coplanar plan. b. Isodose distribution of non coplanar plan. Table 5: Mean and maximum dose of critical structures for coplanar and non coplanar plan for an individual patient Structure Coplanar dose in cgy Non coplanar-dose in cgy Optic Chiasm Mean 373 (57) 1603 (375) Dose ( SD) Optic Chiasm Maximum Lt optic nerve mean 1945 (1704) 1740 (1189) Lt optic nerve max Rt optic nerve mean 845 (838) 2044 (779) Rt optic nerve max Rt lens mean 237 (165) 259 (54) Rt lens max Lt lens mean 260 (102) 226 (34) Lt lens max The result shown in above table indicates that right and left lens dose was reduced in non coplanar plan.

30 Figure 12: Dose volume histogram for coplanar and non coplanar plan. The corresponding DVH is shown in above figure. Purple color was for target, orange color was for right lens, blue color for optic chiasm, sky blue for left lens and light blue for optic nerve. Lines with no dash is for non coplanar and dotted lines for coplanar plan Dose Verification of IMRT plans Table 6: Point Dose Measurement Using Ionization Chamber Patient ID Prescribed Delivered % Error Dose (cgy) Dose (cgy) 1S C L F B H SC Average The table shows the point dose measurement of individual IMRT plans. The average dose difference between planned and measured dose was %. The highest difference was found to be -4.3 %. Qualitative evaluation of calculated and measured dose was made by superimposing the isodose distribution on RIT

31 Figure 13: Isodose overlay of planned and measured dose. Black line represents isodose of planned dose and color lines represent isodose of measured dose from film. Table 7: Measured and Calculated Dose Difference in Vertical and Horizontal Profiles Patient ID Vertical Profile Horizontal Profile Mean Dose difference (SD) SD of difference Mean dose difference SD of difference 1S C L F B H SC Average The above table shows that average mean dose difference in vertical profile is From horizontal profile the average dose difference was The difference was obtained by subtracting dose from target and reference image. The target image was the fluence taken from planning system and the reference image was from film.

32 Pixels Figure 14: Figure showing the vertical profile of measured and planned dose. Solid line is for target image and dotted line is for reference image. The X-axis shows the no. of pixels and the Y- axis shows the percent dose. In vertical profile shows dotted line and solid line are closely matched which indicates that there is good agreement between plan and measured dose.

33 Pixels Figure 15: Figure showing the horizontal profile of measured and planned dose. The solid line indicates the reference image and dotted line indicates the target image Dose difference Figure 16: Figure showing the histogram plot of analysis (low gradient- high dose)

34 Table 8: Dose difference taken from difference histogram plot Patient ID Mean Difference (%) 1S 3.7 2C L F B 3.9 6H 3.6 7SC -2.1 Average -0.7 The average dose difference was found to be -0.7 %. Out of 7 cases, 6 cases had mean dose difference below 5 %. The highest dose difference was -6.6 % only in one case Dose Difference Figure 17: Plot of dose difference histogram. The figure shows that there is not much difference in dose since the data is centered to zero.

35 Table 9: The Gamma Index of Dose Difference Patient ID Mean Gamma Index Standard deviation 1S C L F B H SC Average The average gamma index was found to be 0.98 as average of all patients. The highest gamma index was Gamma Index Figure 18: Plot showing the gamma index. Y-axis shows the number of pixel

36 Pixels Figure 19: Plot of gamma index pass/fail image. Gamma index exceeding 1 are red and gamma index within 1 are green. Figure 20 a 3D midplane fluence 20 b. IMRT midplane fluence

37 20c.3D fluence at 3 cm depth 20d. IMRT fluence at 3 cm depth 20 e: 3D fluence at 0.5 cm depth 20 f: IMRT fluence at 0.5 cm depth Figure 20: Fluence at plane of different depth from 3D conformal and IMRT plans. The fluence comparison at different depth is shown in above figures. In midplane, the dose is in center in 3D plan. At 0.5 cm depth, the difference seems to be higher in IMRT plan.

38 Table 10: Fluence Comparison of IMRT and 3D plans Patient ID with fluence at difference depth Vertical profile Mean dose difference (SD) Horizontal profile mean dose difference (SD) Difference histogram (%) (SD) analysis(low gradient-high dose) (SD) B(MP) (16) -3.27(20.5) -3.2(16.22) -2.69(22) 15 DTA ( high gradient- low dose) in mm B ( 2.5 cm ) -7.7(16.9) -9.19(13.5) -6.2(13.5) -13.2(15.9) 9.97 B(0.5 cm) 17.6(34) 2.29(19.26) 0.725(18.47) -0.06(38) F(MP) 0.427(16) (20.8) 0.52(12.8) -2.6(31) F(3.5 cm ) (25.37) -8.67(26.7) (14.9) -9.3(46.96) 14.2 F(0.5 cm) -7.6(17.6) -18.4(14.8) -3.2(17.6) (27.35) - H (MP) 2.9(16) -6.9(17) -4.16(19) 11.89(25) 10 H (3.5 cm) 7.1(13) 8.2(17.38) 5.7(12.26) 11(15) 0.7 H (0.5 cm) 13.7(27) -5.2(42) -3.68(23.57) -6(39.7) 11.7 S (MP) -3(8.8) -3.4(19) -1.14(9.3) -7(23) 20 S(3.5 cm ) -4.67(11) 3.7(25) 0.76(11.9) 8.87(35) 20 S(0.5 cm ) -13(34) 3(42) 0.649(15.6) 1.9(59) 14.2 C ( MP) 9.9(24) 10.79(17.5) 5.8(15.8) 25(29) 14.8 C(3.25 cm) -4.11(8.9) 5.8(21.8) C (0.5 cm ) 21.21(108) 445(773) 58(292) 865(785) 18.6

39 Sc(MP) -3.1(5) -2.26(11) -3.49(8.8) -4.85(8.59) 6.6 Sc (3.25 cm) 3(12) 11.6(18.5) 2.9(13) 5(15.6) 12 Sc (0.5 cm) 1.5(10.2) 7.8(32) -0.69(21) 3.26(28.75) 13.6 L(MP) 1.66(4.65) 4.67(21.8) 0.689(10.86) 8.8(29.4) - L(3 cm) -1.64(14.95) 10(32.6) 0.48(13.7) 11.36(37.55) - L(0.5 cm ) -4.62(22) 0.219(20.59) (10.38) 4.83(29.29) MP = midplane The dose difference is calculated as the subtraction of reference image dose from dose of target image. Target image is fluence of 3D plan and reference image is fluence of IMRT plan. Figure 21 a: Horizontal profile at midplane 21 b: Vertical profile at midplane

40 Fig 21c: Horizontal profile at 3.5 cm depth Fig 21d:Vertical profile at 3.5 cm depth Fig 21 e: Horizontal profile at 0.5 cm depth Fig 21f: Vertical profile at 0.5 cm depth As shown in figures, the profiles show not much difference in planned and measured dose in midplane. The difference is highest at 0.5 cm depth.

41 CHAPTER-FIVE DISCUSSION Number of beam required to meet the treatment objectives depends upon the complexity of target shape and its proximity to the critical structures. Increase in the number of beam has ability to conform dose to target. The mean target dose increased with the increase in number of beams. However, the difference was only 0.19 % between 5 field and 7 field IMRT. There was 1 % increase in mean target dose from 7 field to 9 field, which was statistically significant at 0.05 level. Similarly, there was no significant difference in mean PTV dose between 5 and 7 field (p = 0.7) but the mean dose difference was significant between 7 field and 9 field ( p = 0.04). However, this increase is only 0.9 %. This result indicates that there is slight improvement in dose coverage when we increase the number of beams. This result is in agreement with the result obtained by Zhou J et al 13. They found that increasing the number of beams from 9 to 15 in head and neck IMRT plan increased the dose by only 1 Gy. Nutting CM et al 14 compared 3D conformal radiotherapy (3D- CFRT) with 9 field and 4 field IMRT. They found that for PTV 9F IMRT technique produced similar minimum and maximum doses and dose inhomogeneity to the CFRT technique. There was no improvement in mean lung dose with 9F IMRT compared with CFRT. The mean dose to the PTV the 4F IMRT plans was comparable with the CFRT and 9F IMRT techniques. 4F IMRT technique reduced the volume of lung receiving both high and lower doses of radiation. Soderstrom and Brahme 15 and Stein et al 16 have shown that three or four beams can produce acceptable dose distribution for prostate tumors. Increasing the number of beam may decrease the dose to organ at risk. It was found that maximum cord dose decreased with increase in number beams. However the decrease in dose was only 0.7 % from 5 field to 7 field and only 0.5 % from 7 field to 9 field. The

42 cord mean dose was increased with the increase in number of beams. The standard deviation was very high for the mean cord dose. It was due to the fact that the range of dose for cord was very high. The cord was contoured even in outside the treatment fields. The target dose homogeneity was found to be 92 % for both of the 7F and 9F IMRT and less for 5 F IMRT. There was less homogenous dose in PTV. 7F IMRT had highest percent of homogeneity which was only 64.5 %. A large dose inhomogeneity within the target is common in IMRT. The dose inhomogeneity is significantly larger than the + 5 % which is considered as limit for 3D conformal therapy 17. OH CE et. al 12 found that IMRT technique resulted in the least homogenous dose distribution in PTV as compared to 3D conformal radiotherapy. The hot spot decreased with the increase in number of beams. The maximum hot spot was least for 9 field and it was in PTV. The area that received the maximum dose was minimal. However the percent volume was not calculated. The average MU used was 589 for 5 field, 661 MU for 7 field and 676 for 9 field. The required MU depends on the complexity of plan. Zabel et al 18 used a median of 999 total MU from 7 9 beams. In 3D conformal plan, coplanar and non coplanar techniques were compared. The mean doses to target and PTV were slightly higher in non coplanar plan. Even though there was better coverage of target in non coplanar plan, it involved more normal tissue (figure 11). As far as the reduction in critical structure dose, there was slight improvement only in lens dose. Other structures had higher dose in non-coplanar plan (Table 5 ). The significant reduction of dose to critical structure depends upon the site of tumor. Most cases had tumor close to the brain stem. The non coplanar techniques takes longer time to treat since couch need to be rotated in treatment room. There will be higher uncertainty about the localization because of patient movement.

43 For the dose verification both point dose measurement and film dosimetry were used. EDR2 film was used because of its linearity and high dose range. EDR2 can be used as an absolute dosimeter within an accuracy of about + 3 %. 11 The average deviation for point dose measurement was % (Table 6), which indicates that there is good agreement between planned and measured dose. Qualitative evaluation was performed by overlaying isodose from treatment plan and from measured dose. The isodose lines were closely matched. There was good agreement in vertical and horizontal profile comparison. Another criterion to calculate the dose difference was subtraction method. It performs a pixel by pixel subtraction between the two images. Difference histogram shows subtraction data in histogram plot (figure 17). Gamma index is very important criterion for the comparison of measured and calculated dose. Average gamma index was found to be 0.98 which indicates that there was good agreement between planned and measured dose. The gamma index for only one case had unacceptable value. However, the point dose measurement showed only % deviation in that case. The histogram plot (figure 18 ) of gamma function shows that gamma index were below than 1. The qualitative evaluation of fluence showed that there is difference between IMRT plan and 3D plan in different depth ( figure 20). Different criteria such as vertical profile, horizontal profile, analysis(low gradient-high dose), DTA (high gradient-low dose) were used for the comparison of fluence at different depth. It was expected that there will be more difference in dose between 3D and IMRT plans at shallower depth. The higher difference is due to more scatter because of small segments in IMRT. One of the criterion is analysis in high gradient and low dose area by DTA, which has tolerance of 3 mm. Higher the value of DTA, higher the difference in

44 dose between two different plans. It is assumed that the value of DTA should be highest at 0.5 cm depth and lowest in midplane. It was found only in one case and other cases didn t have any trend of data. This may be due to that analysis on RIT may not give the proper result. It would be better if we could do measurement in different points using ionization chamber and film. Some drawbacks of this study include limited sample size. The percent volume that receive maximum dose was not calculated. One of the error might be in image registration in RIT. Since both target and reference images were from treatment planning, the registration points can t be selected as in film. During registration there may be deviation between two images. Another drawback is that in 3D conformal plan of brain, we couldn t choose the right sample type to be able to see the benefit of noncoplanar technique to spare the normal tissue.

45 CONCLUSION The mean target and PTV doses increased with the increase in number of beams. However, there was only slight improvement in dose coverage. The maximum cord dose was slightly decreased with increase in the number beams. There was no difference in target dose homogeneity between 5 field and 7 field IMRT plans and PTV dose homogeneity was highest for 7 fields IMRT. Non coplanar plan was able to reduce only lens dose. The qualitative and quantitative comparison showed good agreement in planned and measured dose. Even though there was slight improvement in dose coverage and homogeneity in 9 field IMRT, it takes longer time for treatment and there will be more monitor unit delivered. Seven field IMRT was found to be reasonable technique for the treatment of head and neck cases. The fluence map comparison between IMRT and 3D plans didn t show any specific trend at different plane. The comparison need to be performed by measuring at different planes using film and ionization chamber or mapcheck device.

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