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Implications of a high-definition multileaf collimator (HD-MLC) on treatment planning techniques for stereotactic body radiation therapy (SBRT): a planning study

Implications of a high-definition multileaf collimator (HD-MLC) on treatment planning techniques... Purpose: To assess the impact of two multileaf collimator (MLC) systems (2.5 and 5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and dynamic conformal arc techniques for stereotactic body radiation therapy (SBRT) of liver and lung lesions. Methods: Twenty-nine SBRT plans of primary liver (n = 11) and lung (n = 18) tumors were the basis of this study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based plans served as reference, and were designed using static conformal beams (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal arcs (DCA). Reference plans were either re-optimized or recomputed, with identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high- definition (HD120) MLC system. Dose computation was based on the anisotropic analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity taken into account. Each plan was normalized such that 100% of the prescription dose covered 95% of the planning target volume (PTV). Isodose distributions and dose-volume histograms (DVHs) were computed and plans were evaluated with respect to target coverage criteria, normal tissue sparing criteria, as well as treatment efficiency. Results: Dosimetric differences achieved using M120 and the HD120 MLC planning were generally small. Dose conformality improved in 51.7%, 62.1% and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves demonstrated a decreased volume of normal tissue irradiated to the lower (90%, 50% and 25%) isodose levels with the HD120 MLC. Conclusion: Data derived from the present comparative assessment suggest dosimetric merit of the high definition MLC system over the millennium MLC system. However, the clinical significance of these results warrants further investigation in order to determine whether the observed dosimetric advantages translate into outcome improvements. Page 1 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 lation grid of 2.5 mm . Tissue heterogeneity was taken Background Stereotactic body radiation therapy (SBRT) is a modern into account. All treatments were planned for five fraction precision radiation therapy delivery concept characterized delivery (10 Gy/fraction for liver tumors, and 12 Gy/frac- by one to five fraction delivery of focal high-dose radia- tion for lung lesions). All plans were computed such that tion [1,2]. SBRT has become an established treatment the prescribed dose (PD) encompassed 95% of the PTV, technique for lung [3-5], liver [6-8], and spinal lesions [9- with a heterogeneous dose distribution and a desired plan 11]. Conceptually derived from cranial stereotactic radio- maximum of 150% of PD. surgery, the planning and delivery of SBRT is characterized by highly target-conformal dose distributions with steep Comparative plans were generated from corresponding dose gradients towards normal tissues, which allow the reference IMRT plans by re-optimization for the Novalis administration of potent tumor-ablative radiation doses. TX treatment platform (Varian Medical Systems), equipped with a high-definition MLC (HD120 MLC) sys- Beam shaping for linear accelerator-based SBRT planning tem with thirty-two 2.5-mm central leaf-pairs and twenty- and delivery is mostly afforded by multileaf collimator eight 5-mm peripheral leaf-pairs. To assure valid data gen- (MLC) systems. Over the last 15 years, MLCs have evolved eration, all reference plans were carefully selected from a in terms of both field size and width of the individual larger library of SBRT plans to ensure that PTVs were con- tungsten leafs, and it is intuitive to assume that target dose formed by the central 5 mm leafs of the Varian Trilogy conformity and/or the steepness of the dose gradient can platform, and correspondingly, only the central 2.5 mm be influenced by decreasing MLC leaf width [12-23]. The leafs of the Novalis TX platform for the comparative plans. current work seeks to assess if a novel high-definition 2.5- mm leaf MLC system (HD-MLC) integrated into a dedi- In addition to the influence of the respective MLC system cated stereotactic linear accelerator system (BrainLAB/Var- on IMRT-based SBRT dose distributions, the impact of ian Novalis TX) provides dosimetric advantages compared MLC system was also investigated for commonly utilized with a clinically widely utilized 5 mm leaf system for SBRT static three-dimensional conformal radiation therapy of lung and liver lesions, and if potential gains realized (3DCRT), and dynamic conformal arc (DCA) planning may be clinically meaningful. techniques. Hence, besides the available M120 MLC IMRT reference plan, the following five alternative treatment plans were generated for each patient: (1) HD120 MLC Materials and methods Patients and treatment protocol IMRT, (2) M120 MLC 3DCRT, (3) HD120 MLC 3DCRT, The present study is based on 29 patients that had under- (4) M120 MLC DCA, and (5) HD120 MLC DCA. Nine to gone a course of SBRT at Oregon Health & Science Univer- twelve beams were used to generate the IMRT and 3DCRT sity in Portland, Oregon, USA between July 2007 and May plans. Beam angles were arranged in a practical manner 2008. The patient population included 18 primary early according to tumor and critical organ location for the pur- stage lung tumors and 11 hepatocellular carcinoma pose of achieving maximal target coverage and optimal (HCC). Clinical treatment planning simulation imaging dose distribution conformity while keeping doses to OAR and SBRT delivery were performed with patients immobi- (including the contralateral lung, liver, spinal cord, lized in a double vacuum whole-body immobilization esophagus, bowel, and ipsilateral kidney) below institu- system (BodyFix; Medical Intelligence, Schwabmuenchen, tional dose limits. Germany). The basis for SBRT was thin slice CT scans acquired on a dedicated 16 slice big-bore CT simulator Evaluation parameters (Philips Medical Systems, Cleveland, OH, USA). The All study cases were categorized into five groups according imaging data was electronically transferred to the Eclipse to ITVs: category O; all ITVs, category I; 1 ≤ ITV < 8 cm , radiation therapy planning system (Varian Medical Sys- category II; 8 ≤ ITV < 27 cm , category III; 27 ≤ ITV < 64 3 3 tems, Palo Alto, CA, USA). Based on both free-breathing cm , and category IV; ITV ≥ 64 cm . Categories I though IV and respiration resolved 4DCT scans, the internal target were selected because they each equaled the volumes of volume (ITV) was delineated and expanded into a plan- cubes with side length of 1, 2, 3, and 4 cm, respectively ning target volume (PTV) by adding isotropic 5 mm mar- [19]. gins. All clinical SBRT plans (reference plans) were computed using a multiple static field sliding-window Each treatment plan was evaluated with respect to target IMRT technique for delivery on the Varian Trilogy plat- coverage criteria, normal tissue sparing criteria, as well as form (Varian Medical Systems, Palo Alto, CA) equipped treatment efficiency. In terms of target coverage criteria, with a 120-leaf Millennium MLC (M120 MLC) system, PTV dose-volume histogram (DVH) parameters including with forty 5-mm central leaf-pairs and twenty 10-mm mean dose (or D , defined in this study as the sum of mean peripheral leaf-pairs. The anisotropic analytical algorithm the product of dose value and percent volume in each (AAA) was used for dose computation with a dose calcu- dose bin), minimum dose (or D , defined in this study min Page 2 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 as dose to 99% of the PTV) and maximum dose (or D , Also, target dose heterogeneity was assessed using a heter- max defined in this study as dose received by the "hottest" 3% ogeneity index (HI) define below: volume of the PTV) were computed and recorded. The conformity of each treatment plan was quantified using a D -D max min HI = . (2) robust conformity index (CI) based on formulations by mean Paddick [24] and Nakamura et al. [25] By considering normal tissue outside the PTV but in the dose volume space as a virtual structure, dose-spillage vol- V ´V PTV PIS CI = , (1) umes [26] were computed to assess normal tissue sparing PTV [] PIS effect of the MLC systems. The following dose spillage vol- where PIS is the prescription isodose surface, V is the umes were assessed: 1) V or high-dose spillage volume PTV HS magnitude of the planning target volume, V is the vol- taking into account normal tissue receiving an ablative PIS ume encompassed by the prescription isodose surface, dose; that is, ≥ 90% of the prescription dose in the current and PTV is the planning target volume encompassed study, 2) V or intermediate-dose spillage volume taking PIS IS within the prescription isodose surface. Since all plans in into account normal tissue receiving a significant fraction the current study were normalized such that 95% of the of the prescription dose; that is, ≥ 50% of the prescription planning target volume was conformally covered by the dose, and 3) V or low-dose spillage volume taking into LS prescription isodose surface, the PTV is 95% of the V . PIS PTV Isodose distr Figure 1 ibutions and DVHs for a lung lesion generated from three different planning techniques and two MLC systems Isodose distributions and DVHs for a lung lesion generated from three different planning techniques and two MLC systems. A1 through A6 are axial isodose distribution corresponding to M120 MLC IMRT, M120 MLC 3DCRT, M120 MLC DCA, HD120 MLC IMRT, HD120 MLC 3DCRT, and HD120 MLC DCA plans, respectively. Page 3 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 account normal tissue receiving low doses of radiation; of the conformity index between the different MLC plans that is, ≥ 25% of the prescription dose. were greater than 0.05. Finally, the efficiency of each treatment plan was com- Additional file 3 summarizes the median dose to OAR puted as a ratio of the cumulative sum of monitor units (including the spinal cord, esophagus, ipsilateral kidney, (MUs) per fraction to the dose per fraction. A paired t-test ipsilateral lung, and liver). For the spinal cord and the with two-tailed distribution, and a p-value < 0.05 defining esophagus, the magnitude of the range of values was statistical significance, was used to assess whether differ- determined by the proximity of the OAR to the PTV. The ences between the MLC systems were statistically signifi- volume of normal tissue irradiated to ≥ 90%, ≥ 50% and cant. ≥ 25% of the prescription dose, normalized to the plan- ning target volume, is summarized in Table 1, along with p-values of paired t-tests comparing corresponding plan- Results Target dose-volume parameters ning techniques of the MLC systems under consideration. The median ITV and PTV for all 29 cases in the current The results indicate an overall lower dose spillage from 3 3 [range: 1.03–91.53 cm ] and 26.33 study were 7.58 cm the HD120 MLC compared with the M120 MLC. The 3 3 cm [range: 13.95–167.44 cm ], respectively. The DVHs number and percentage of patient plans with improved and corresponding isodose distributions for all involved performance of the HD120 MLC over the M120 MLC are treatment planning techniques are shown for a represent- shown in Table 2, while Table 3 summarizes the mean ative lung cancer case in Figure 1. Additional file 1 sum- and maximum absolute percent improvement. marizes the median mean, minimal and maximal PTV doses for each planning technique, separated in terms of Planning efficiency treatment site and MLC system. Overall, there was The mean value of the total number of MUs necessary to demonstrable quantitative difference between corre- deliver the prescribed dose per fraction for all patients and sponding HD120 MLC and M120 MLC PTV doses, respective treatment plan category are presented in although not every perceived difference was statistically Table 4. significant. The mean MU/cGy for the HD120 MLC system was Target dose conformity and normal/critical structure dose slightly higher for IMRT plans. However, there was virtu- The mean values of the conformity and heterogeneity ally no difference between the MLC systems for the indices, along with p-values of paired t-tests comparing 3DCRT and DCA cases. corresponding planning techniques of the MLC systems under consideration, are summarized in Additional file 2 Discussion according to ITV groups. Overall, HD120 MLC plans One of the most compelling studies to assess the impact exhibited better conformity than M120 MLC plans. of MLCs on dose distributions was performed by Bortfeld Unlike the IMRT cases where no clear trend was exhibited et al. [15]. The authors show that the theoretically calcu- for the mean conformity and heterogeneity indices, plans lated optimal leaf width for a 6 MV photon beam is in the of both 3DCRT and DCA showed a decreasing pattern range of 1.5–2 mm. Of all the practical studies that have with increasing ITV. Furthermore, the conformity index been conducted, there is utter agreement that by changing either stayed the same or increased with increasing MLC MLC widths from 10 mm to 5–3 mm the results are both leaf width. However, unlike the conformity index, the het- statistically and clinically significant [12,13,17-21]. Dosi- erogeneity index either stayed the same or decreased with metric improvements reported by such studies, if applied increasing MLC leaf width. Despite these perceived quan- to the SBRT process, may reduce chronic normal/critical titative differences, all but two the p-values of paired t-tests structure injuries as the percentage volume of these struc- Table 1: Mean dose-spillage volume, normalized to PTV.p-values of the paired t-test included to assess difference between MLC systems. Technique V V V HS IS LS M120 HD120 M120 HD120 M120 HD120 IMRT 0.54 ± 0.30 0.50 ± 0.25 3.86 ± 1.38 3.66 ± 1.22 23.69 ± 9.21 23.14 ± 8.75 p = 0.07 p = 0.03 p = 0.08 3DCRT 0.47 ± 0.13 0.44 ± 0.10 4.08 ± 1.34 3.93 ± 1.12 23.64 ± 7.70 23.36 ± 7.70 p = 0.04 p = 0.24 p = 0.01 DCA 0.44 ± 0.13 0.43 ± 0.12 3.26 ± 0.61 3.19 ± 0.60 15.32 ± 4.36 14.76 ± 4.23 p = 0.34 p = 0.06 p = 0.03 Page 4 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 Table 2: Cases where performance of HD120 MLC surpassed that of M120 MLC. Technique CI HI V V V HS IS LS IMRT 15 (51.7%) 22 (75.9%) 19 (65.5%) 24 (82.8%) 22 (75.9%) 3DCRT 18 (62.1%) 15 (51.7%) 21 (72.4%) 21 (72.4%) 25 (86.2%) DCA 16 (55.2%) 16 (55.2%) 20 (69.0%) 23 (79.3%) 23 (79.3%) The values in the table are presented as the number of cases and their corresponding ratio (as a percentage) over the 29 patient cases assessed in the current study. tures receiving all ranges of dose is in effect reduced. Fur- in the current study as ITV ≥ 64 cm ). As indicated in thermore, for the PTV, increased maximum dose and Tables 2 and 3, in 51.7% of the IMRT cases, use of the improved dose conformity may benefit SBRT as an abla- HD120 MLC improved the conformality of the original tive process. Nevertheless, the quantitation of any advan- plans by a mean value of 3.9% and up to a maximum tage obtained by smaller leaf width MLC systems over the value of 18.5%. In 62.1% and 55.2% of the 3DCRT and 5 mm leaf width MLC has remained controversial DCA cases, respectively, use of the HD120 MLC also [13,14,16,19,20,23]. resulted in improved PTV dose conformality. The mean and maximum improvements were 2.5% and 9.5% for In the present study, the potential clinical benefit of a the 3DCRT technique, and 2.4% and of 8.1% for the DCA novel 2.5 mm leaf width MLC system over a clinically technique, respectively. Nevertheless, the conformity available 5 mm leaf width MLC system was explored for index difference between the MLC systems is quite small, different SBRT treatment planning techniques of lung and regardless of the treatment planning technique (see Addi- liver lesions. A variety of target dose parameters were con- tional file 2), attributable in part to the number of beams sidered, including mean, minimum and maximum PTV used for treatment planning. doses; conformity and heterogeneity indices; and normal tissue sparing. Wu et al. [23], in a similar study on a subset Normal tissue sparing effect of the MLC systems was of five liver cancer patients, showed that the HD120 MLC assessed, by considering normal tissue outside the PTV system has no significant impact on D , D , or D but in the dose volume space as a virtual structure. Similar min max mean values relative to the M120 MLC system. These results to findings by Wu et al. [23], a reduction in normal tissue were in agreement with findings in the current study. dose was observed with the HD120 MLC system, with at Nonetheless, unlike results in Additional file 1 of the cur- least 19 of the 29 cases per treatment planning technique rent study, Wu et al. [23] reported significantly reduced having lower volumes exposed to the 90%, 50% and 25% D values for the liver patient subgroup (p < 0.01) with dose levels. To be specific, at least 65.5%, 72.4%, and max use of IMRT and the HD120 MLC system, albeit small 75.9% cases per planning technique had lower normal tis- (<2%) compared with the M120 MLC system. sue volumes exposed to the V , V , and V , respectively HS IS LS (see Table 2). The mean dose reduction attributable to the Regarding dose distribution conformity, results in Addi- HD120 MLC was between 1 – 4% for the 3DCRT and tional file 2 demonstrated an improvement in conformity DCA techniques, and between 2 – 6% for the IMRT tech- index with target volume for all assessed planning tech- nique. Thus, in terms of dose reduction, the IMRT plans niques. The IMRT technique showed the best PTV cover- were apparently better than either 3DCRT or DCA plans. age of either MLC system, except for large targets (defined However, the quantitative normal tissue volumes exposed to the 90%, 50% and 25% dose levels were smallest for Table 3: Mean (top) and max (bottom) percent improvement or the DCA technique, irrespective of MLC system. worsening of HD120 MLC plans over M120 MLC plans. Regarding treatment planning efficiency, while the Technique Improvement (%) Worsening (%) 3DCRT and DCA techniques showed little difference in CI V V V CI V V V treatment monitor units between MLC systems, results in HS IS LS HS IS LS the current study indicated an increase in monitor units, IMRT 3.9 4.6 5.5 3.5 2.1 3.1 8.5 5.1 albeit statistically insignificant, with the HD120 MLC sys- 3DCRT 2.5 2.5 4.6 1.8 2.2 2.0 5.8 2.6 tem for the IMRT technique. This was attributable to an DCA 2.4 2.2 3.0 3.3 2.7 2.7 4.0 5.1 increase in the number of MLC segments needed to deliver the prescribed dose [12,20]. IMRT 18.5 20.4 26.5 22.7 10.4 17.7 27.6 14.0 3DCRT 9.5 9.8 39.4 3.7 13.2 8.7 25.9 3.7 On a final note, the current work is purely a treatment DCA 8.1 6.4 9.4 9.6 13.2 9.8 12.1 34.3 planning study on a single treatment planning platform Page 5 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 Table 4: Mean number of monitor units (within one standard deviation) necessary to deliver one centigray of prescribed dose for different treatment plan categories. Technique IMRT 3DCRT DCA M120 HD120 M120 HD120 M120 HD120 MU/cGy 3.45 ± 1.06 3.63 ± 1.36 2.25 ± 0.54 2.26 ± 0.54 2.24 ± 0.54 2.28 ± 0.56 (μ ± σ) p = 0.17 p = 0.80 P = 0.18 with no dosimetric verification. The dosimetric differ- Additional material ences reported here are believed to be solely due to the dif- ferent leaf widths used in the treatment planning, since Additional file 1 our comparisons were performed on the same treatment Supplementary table. Median value and range of target dose parameters, planning system for two treatment platforms with similar expressed as a percent of the prescription dose. open-field beam characteristics, using the same beam con- Click here for file figurations, optimization parameters (for IMRT), and [http://www.biomedcentral.com/content/supplementary/1748- 717X-4-22-S1.doc] dose constraints. Nevertheless, it should be pointed out that leaf-width is not the only parameter that is different Additional file 2 between these MLC systems. Factors such as the leaf trans- Supplementary table. Group-based analyses of mean conformity and het- mission and leakage (a function of leaf height, material erogeneity indices for each MLC plan. constituent, and tongue-and-groove), source-to-MLC dis- Click here for file tance, are also different and affect dosimetric parameters. [http://www.biomedcentral.com/content/supplementary/1748- Therefore, the current planning study is not a simple com- 717X-4-22-S2.doc] parison for different MLC leaf-widths, but rather a com- Additional file 3 plex comparison of two dose delivery systems with Supplementary table. Median value and range of organ-at-risk (OAR) different leaf-width MLCs [19]. dose as a percent of the prescription dose. Click here for file Conclusion [http://www.biomedcentral.com/content/supplementary/1748- Data derived from the present comparative assessment 717X-4-22-S3.doc] suggest dosimetric merit of the high definition MLC sys- tem over the millennium MLC system. However, the clin- ical significance of these results warrants further investigation in order to determine whether the observed Acknowledgements dosimetric advantages translate into outcome improve- The authors wish to thank Ms. Maureen Dooley-Dahlgren for the prepara- ments. tion of this manuscript. References Competing interests 1. Potters L, Steinberg M, Rose C, Timmerman R, Ryu S, Hevezi JM, MF: Varian Medical Systems, Palo Alto, CA; Research sup- Welsh J, Mehta M, Larson DA, Janjan DA: American Society for port, Consultant, Speaker. Therapeutic Radiology and Oncology and American College of Radiology practice guideline for the performance of ster- eotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004, Authors' contributions 60:1026-1032. JAT participated in the conception and design of the 2. Papiez L, Timmerman R, DesRosiers C, Randall M: Extracranial stereotactic radioablation: Physical principles. 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Wu QJ, Wang Z, Kirkpatrick JP, Chang Z, Meyer JJ, Lu M, Huntzinger Your research papers will be: C, Yin FF: Impact of collimator leaf width and treatment tech- available free of charge to the entire biomedical community nique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions. Radiat Oncol 2009, 4:3. peer reviewed and published immediately upon acceptance 24. Paddick I: A simple scoring ratio to index the conformity of cited in PubMed and archived on PubMed Central radiosurgical treatment plans: Technical note. J Neurosurg 2000, 93:219-222. yours — you keep the copyright 25. Nakamura JL, Verhey LJ, Smith V, Petti PL, Lamborn KR, Larson DA, BioMedcentral Wara WM, McDermott MW, Sneed PK: Dose conformity of Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 7 of 7 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Implications of a high-definition multileaf collimator (HD-MLC) on treatment planning techniques for stereotactic body radiation therapy (SBRT): a planning study

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Springer Journals
Copyright
Copyright © 2009 by Tanyi et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology; Radiotherapy
eISSN
1748-717X
DOI
10.1186/1748-717X-4-22
pmid
19591687
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Abstract

Purpose: To assess the impact of two multileaf collimator (MLC) systems (2.5 and 5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and dynamic conformal arc techniques for stereotactic body radiation therapy (SBRT) of liver and lung lesions. Methods: Twenty-nine SBRT plans of primary liver (n = 11) and lung (n = 18) tumors were the basis of this study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based plans served as reference, and were designed using static conformal beams (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal arcs (DCA). Reference plans were either re-optimized or recomputed, with identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high- definition (HD120) MLC system. Dose computation was based on the anisotropic analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity taken into account. Each plan was normalized such that 100% of the prescription dose covered 95% of the planning target volume (PTV). Isodose distributions and dose-volume histograms (DVHs) were computed and plans were evaluated with respect to target coverage criteria, normal tissue sparing criteria, as well as treatment efficiency. Results: Dosimetric differences achieved using M120 and the HD120 MLC planning were generally small. Dose conformality improved in 51.7%, 62.1% and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves demonstrated a decreased volume of normal tissue irradiated to the lower (90%, 50% and 25%) isodose levels with the HD120 MLC. Conclusion: Data derived from the present comparative assessment suggest dosimetric merit of the high definition MLC system over the millennium MLC system. However, the clinical significance of these results warrants further investigation in order to determine whether the observed dosimetric advantages translate into outcome improvements. Page 1 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 lation grid of 2.5 mm . Tissue heterogeneity was taken Background Stereotactic body radiation therapy (SBRT) is a modern into account. All treatments were planned for five fraction precision radiation therapy delivery concept characterized delivery (10 Gy/fraction for liver tumors, and 12 Gy/frac- by one to five fraction delivery of focal high-dose radia- tion for lung lesions). All plans were computed such that tion [1,2]. SBRT has become an established treatment the prescribed dose (PD) encompassed 95% of the PTV, technique for lung [3-5], liver [6-8], and spinal lesions [9- with a heterogeneous dose distribution and a desired plan 11]. Conceptually derived from cranial stereotactic radio- maximum of 150% of PD. surgery, the planning and delivery of SBRT is characterized by highly target-conformal dose distributions with steep Comparative plans were generated from corresponding dose gradients towards normal tissues, which allow the reference IMRT plans by re-optimization for the Novalis administration of potent tumor-ablative radiation doses. TX treatment platform (Varian Medical Systems), equipped with a high-definition MLC (HD120 MLC) sys- Beam shaping for linear accelerator-based SBRT planning tem with thirty-two 2.5-mm central leaf-pairs and twenty- and delivery is mostly afforded by multileaf collimator eight 5-mm peripheral leaf-pairs. To assure valid data gen- (MLC) systems. Over the last 15 years, MLCs have evolved eration, all reference plans were carefully selected from a in terms of both field size and width of the individual larger library of SBRT plans to ensure that PTVs were con- tungsten leafs, and it is intuitive to assume that target dose formed by the central 5 mm leafs of the Varian Trilogy conformity and/or the steepness of the dose gradient can platform, and correspondingly, only the central 2.5 mm be influenced by decreasing MLC leaf width [12-23]. The leafs of the Novalis TX platform for the comparative plans. current work seeks to assess if a novel high-definition 2.5- mm leaf MLC system (HD-MLC) integrated into a dedi- In addition to the influence of the respective MLC system cated stereotactic linear accelerator system (BrainLAB/Var- on IMRT-based SBRT dose distributions, the impact of ian Novalis TX) provides dosimetric advantages compared MLC system was also investigated for commonly utilized with a clinically widely utilized 5 mm leaf system for SBRT static three-dimensional conformal radiation therapy of lung and liver lesions, and if potential gains realized (3DCRT), and dynamic conformal arc (DCA) planning may be clinically meaningful. techniques. Hence, besides the available M120 MLC IMRT reference plan, the following five alternative treatment plans were generated for each patient: (1) HD120 MLC Materials and methods Patients and treatment protocol IMRT, (2) M120 MLC 3DCRT, (3) HD120 MLC 3DCRT, The present study is based on 29 patients that had under- (4) M120 MLC DCA, and (5) HD120 MLC DCA. Nine to gone a course of SBRT at Oregon Health & Science Univer- twelve beams were used to generate the IMRT and 3DCRT sity in Portland, Oregon, USA between July 2007 and May plans. Beam angles were arranged in a practical manner 2008. The patient population included 18 primary early according to tumor and critical organ location for the pur- stage lung tumors and 11 hepatocellular carcinoma pose of achieving maximal target coverage and optimal (HCC). Clinical treatment planning simulation imaging dose distribution conformity while keeping doses to OAR and SBRT delivery were performed with patients immobi- (including the contralateral lung, liver, spinal cord, lized in a double vacuum whole-body immobilization esophagus, bowel, and ipsilateral kidney) below institu- system (BodyFix; Medical Intelligence, Schwabmuenchen, tional dose limits. Germany). The basis for SBRT was thin slice CT scans acquired on a dedicated 16 slice big-bore CT simulator Evaluation parameters (Philips Medical Systems, Cleveland, OH, USA). The All study cases were categorized into five groups according imaging data was electronically transferred to the Eclipse to ITVs: category O; all ITVs, category I; 1 ≤ ITV < 8 cm , radiation therapy planning system (Varian Medical Sys- category II; 8 ≤ ITV < 27 cm , category III; 27 ≤ ITV < 64 3 3 tems, Palo Alto, CA, USA). Based on both free-breathing cm , and category IV; ITV ≥ 64 cm . Categories I though IV and respiration resolved 4DCT scans, the internal target were selected because they each equaled the volumes of volume (ITV) was delineated and expanded into a plan- cubes with side length of 1, 2, 3, and 4 cm, respectively ning target volume (PTV) by adding isotropic 5 mm mar- [19]. gins. All clinical SBRT plans (reference plans) were computed using a multiple static field sliding-window Each treatment plan was evaluated with respect to target IMRT technique for delivery on the Varian Trilogy plat- coverage criteria, normal tissue sparing criteria, as well as form (Varian Medical Systems, Palo Alto, CA) equipped treatment efficiency. In terms of target coverage criteria, with a 120-leaf Millennium MLC (M120 MLC) system, PTV dose-volume histogram (DVH) parameters including with forty 5-mm central leaf-pairs and twenty 10-mm mean dose (or D , defined in this study as the sum of mean peripheral leaf-pairs. The anisotropic analytical algorithm the product of dose value and percent volume in each (AAA) was used for dose computation with a dose calcu- dose bin), minimum dose (or D , defined in this study min Page 2 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 as dose to 99% of the PTV) and maximum dose (or D , Also, target dose heterogeneity was assessed using a heter- max defined in this study as dose received by the "hottest" 3% ogeneity index (HI) define below: volume of the PTV) were computed and recorded. The conformity of each treatment plan was quantified using a D -D max min HI = . (2) robust conformity index (CI) based on formulations by mean Paddick [24] and Nakamura et al. [25] By considering normal tissue outside the PTV but in the dose volume space as a virtual structure, dose-spillage vol- V ´V PTV PIS CI = , (1) umes [26] were computed to assess normal tissue sparing PTV [] PIS effect of the MLC systems. The following dose spillage vol- where PIS is the prescription isodose surface, V is the umes were assessed: 1) V or high-dose spillage volume PTV HS magnitude of the planning target volume, V is the vol- taking into account normal tissue receiving an ablative PIS ume encompassed by the prescription isodose surface, dose; that is, ≥ 90% of the prescription dose in the current and PTV is the planning target volume encompassed study, 2) V or intermediate-dose spillage volume taking PIS IS within the prescription isodose surface. Since all plans in into account normal tissue receiving a significant fraction the current study were normalized such that 95% of the of the prescription dose; that is, ≥ 50% of the prescription planning target volume was conformally covered by the dose, and 3) V or low-dose spillage volume taking into LS prescription isodose surface, the PTV is 95% of the V . PIS PTV Isodose distr Figure 1 ibutions and DVHs for a lung lesion generated from three different planning techniques and two MLC systems Isodose distributions and DVHs for a lung lesion generated from three different planning techniques and two MLC systems. A1 through A6 are axial isodose distribution corresponding to M120 MLC IMRT, M120 MLC 3DCRT, M120 MLC DCA, HD120 MLC IMRT, HD120 MLC 3DCRT, and HD120 MLC DCA plans, respectively. Page 3 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 account normal tissue receiving low doses of radiation; of the conformity index between the different MLC plans that is, ≥ 25% of the prescription dose. were greater than 0.05. Finally, the efficiency of each treatment plan was com- Additional file 3 summarizes the median dose to OAR puted as a ratio of the cumulative sum of monitor units (including the spinal cord, esophagus, ipsilateral kidney, (MUs) per fraction to the dose per fraction. A paired t-test ipsilateral lung, and liver). For the spinal cord and the with two-tailed distribution, and a p-value < 0.05 defining esophagus, the magnitude of the range of values was statistical significance, was used to assess whether differ- determined by the proximity of the OAR to the PTV. The ences between the MLC systems were statistically signifi- volume of normal tissue irradiated to ≥ 90%, ≥ 50% and cant. ≥ 25% of the prescription dose, normalized to the plan- ning target volume, is summarized in Table 1, along with p-values of paired t-tests comparing corresponding plan- Results Target dose-volume parameters ning techniques of the MLC systems under consideration. The median ITV and PTV for all 29 cases in the current The results indicate an overall lower dose spillage from 3 3 [range: 1.03–91.53 cm ] and 26.33 study were 7.58 cm the HD120 MLC compared with the M120 MLC. The 3 3 cm [range: 13.95–167.44 cm ], respectively. The DVHs number and percentage of patient plans with improved and corresponding isodose distributions for all involved performance of the HD120 MLC over the M120 MLC are treatment planning techniques are shown for a represent- shown in Table 2, while Table 3 summarizes the mean ative lung cancer case in Figure 1. Additional file 1 sum- and maximum absolute percent improvement. marizes the median mean, minimal and maximal PTV doses for each planning technique, separated in terms of Planning efficiency treatment site and MLC system. Overall, there was The mean value of the total number of MUs necessary to demonstrable quantitative difference between corre- deliver the prescribed dose per fraction for all patients and sponding HD120 MLC and M120 MLC PTV doses, respective treatment plan category are presented in although not every perceived difference was statistically Table 4. significant. The mean MU/cGy for the HD120 MLC system was Target dose conformity and normal/critical structure dose slightly higher for IMRT plans. However, there was virtu- The mean values of the conformity and heterogeneity ally no difference between the MLC systems for the indices, along with p-values of paired t-tests comparing 3DCRT and DCA cases. corresponding planning techniques of the MLC systems under consideration, are summarized in Additional file 2 Discussion according to ITV groups. Overall, HD120 MLC plans One of the most compelling studies to assess the impact exhibited better conformity than M120 MLC plans. of MLCs on dose distributions was performed by Bortfeld Unlike the IMRT cases where no clear trend was exhibited et al. [15]. The authors show that the theoretically calcu- for the mean conformity and heterogeneity indices, plans lated optimal leaf width for a 6 MV photon beam is in the of both 3DCRT and DCA showed a decreasing pattern range of 1.5–2 mm. Of all the practical studies that have with increasing ITV. Furthermore, the conformity index been conducted, there is utter agreement that by changing either stayed the same or increased with increasing MLC MLC widths from 10 mm to 5–3 mm the results are both leaf width. However, unlike the conformity index, the het- statistically and clinically significant [12,13,17-21]. Dosi- erogeneity index either stayed the same or decreased with metric improvements reported by such studies, if applied increasing MLC leaf width. Despite these perceived quan- to the SBRT process, may reduce chronic normal/critical titative differences, all but two the p-values of paired t-tests structure injuries as the percentage volume of these struc- Table 1: Mean dose-spillage volume, normalized to PTV.p-values of the paired t-test included to assess difference between MLC systems. Technique V V V HS IS LS M120 HD120 M120 HD120 M120 HD120 IMRT 0.54 ± 0.30 0.50 ± 0.25 3.86 ± 1.38 3.66 ± 1.22 23.69 ± 9.21 23.14 ± 8.75 p = 0.07 p = 0.03 p = 0.08 3DCRT 0.47 ± 0.13 0.44 ± 0.10 4.08 ± 1.34 3.93 ± 1.12 23.64 ± 7.70 23.36 ± 7.70 p = 0.04 p = 0.24 p = 0.01 DCA 0.44 ± 0.13 0.43 ± 0.12 3.26 ± 0.61 3.19 ± 0.60 15.32 ± 4.36 14.76 ± 4.23 p = 0.34 p = 0.06 p = 0.03 Page 4 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 Table 2: Cases where performance of HD120 MLC surpassed that of M120 MLC. Technique CI HI V V V HS IS LS IMRT 15 (51.7%) 22 (75.9%) 19 (65.5%) 24 (82.8%) 22 (75.9%) 3DCRT 18 (62.1%) 15 (51.7%) 21 (72.4%) 21 (72.4%) 25 (86.2%) DCA 16 (55.2%) 16 (55.2%) 20 (69.0%) 23 (79.3%) 23 (79.3%) The values in the table are presented as the number of cases and their corresponding ratio (as a percentage) over the 29 patient cases assessed in the current study. tures receiving all ranges of dose is in effect reduced. Fur- in the current study as ITV ≥ 64 cm ). As indicated in thermore, for the PTV, increased maximum dose and Tables 2 and 3, in 51.7% of the IMRT cases, use of the improved dose conformity may benefit SBRT as an abla- HD120 MLC improved the conformality of the original tive process. Nevertheless, the quantitation of any advan- plans by a mean value of 3.9% and up to a maximum tage obtained by smaller leaf width MLC systems over the value of 18.5%. In 62.1% and 55.2% of the 3DCRT and 5 mm leaf width MLC has remained controversial DCA cases, respectively, use of the HD120 MLC also [13,14,16,19,20,23]. resulted in improved PTV dose conformality. The mean and maximum improvements were 2.5% and 9.5% for In the present study, the potential clinical benefit of a the 3DCRT technique, and 2.4% and of 8.1% for the DCA novel 2.5 mm leaf width MLC system over a clinically technique, respectively. Nevertheless, the conformity available 5 mm leaf width MLC system was explored for index difference between the MLC systems is quite small, different SBRT treatment planning techniques of lung and regardless of the treatment planning technique (see Addi- liver lesions. A variety of target dose parameters were con- tional file 2), attributable in part to the number of beams sidered, including mean, minimum and maximum PTV used for treatment planning. doses; conformity and heterogeneity indices; and normal tissue sparing. Wu et al. [23], in a similar study on a subset Normal tissue sparing effect of the MLC systems was of five liver cancer patients, showed that the HD120 MLC assessed, by considering normal tissue outside the PTV system has no significant impact on D , D , or D but in the dose volume space as a virtual structure. Similar min max mean values relative to the M120 MLC system. These results to findings by Wu et al. [23], a reduction in normal tissue were in agreement with findings in the current study. dose was observed with the HD120 MLC system, with at Nonetheless, unlike results in Additional file 1 of the cur- least 19 of the 29 cases per treatment planning technique rent study, Wu et al. [23] reported significantly reduced having lower volumes exposed to the 90%, 50% and 25% D values for the liver patient subgroup (p < 0.01) with dose levels. To be specific, at least 65.5%, 72.4%, and max use of IMRT and the HD120 MLC system, albeit small 75.9% cases per planning technique had lower normal tis- (<2%) compared with the M120 MLC system. sue volumes exposed to the V , V , and V , respectively HS IS LS (see Table 2). The mean dose reduction attributable to the Regarding dose distribution conformity, results in Addi- HD120 MLC was between 1 – 4% for the 3DCRT and tional file 2 demonstrated an improvement in conformity DCA techniques, and between 2 – 6% for the IMRT tech- index with target volume for all assessed planning tech- nique. Thus, in terms of dose reduction, the IMRT plans niques. The IMRT technique showed the best PTV cover- were apparently better than either 3DCRT or DCA plans. age of either MLC system, except for large targets (defined However, the quantitative normal tissue volumes exposed to the 90%, 50% and 25% dose levels were smallest for Table 3: Mean (top) and max (bottom) percent improvement or the DCA technique, irrespective of MLC system. worsening of HD120 MLC plans over M120 MLC plans. Regarding treatment planning efficiency, while the Technique Improvement (%) Worsening (%) 3DCRT and DCA techniques showed little difference in CI V V V CI V V V treatment monitor units between MLC systems, results in HS IS LS HS IS LS the current study indicated an increase in monitor units, IMRT 3.9 4.6 5.5 3.5 2.1 3.1 8.5 5.1 albeit statistically insignificant, with the HD120 MLC sys- 3DCRT 2.5 2.5 4.6 1.8 2.2 2.0 5.8 2.6 tem for the IMRT technique. This was attributable to an DCA 2.4 2.2 3.0 3.3 2.7 2.7 4.0 5.1 increase in the number of MLC segments needed to deliver the prescribed dose [12,20]. IMRT 18.5 20.4 26.5 22.7 10.4 17.7 27.6 14.0 3DCRT 9.5 9.8 39.4 3.7 13.2 8.7 25.9 3.7 On a final note, the current work is purely a treatment DCA 8.1 6.4 9.4 9.6 13.2 9.8 12.1 34.3 planning study on a single treatment planning platform Page 5 of 7 (page number not for citation purposes) Radiation Oncology 2009, 4:22 http://www.ro-journal.com/content/4/1/22 Table 4: Mean number of monitor units (within one standard deviation) necessary to deliver one centigray of prescribed dose for different treatment plan categories. Technique IMRT 3DCRT DCA M120 HD120 M120 HD120 M120 HD120 MU/cGy 3.45 ± 1.06 3.63 ± 1.36 2.25 ± 0.54 2.26 ± 0.54 2.24 ± 0.54 2.28 ± 0.56 (μ ± σ) p = 0.17 p = 0.80 P = 0.18 with no dosimetric verification. The dosimetric differ- Additional material ences reported here are believed to be solely due to the dif- ferent leaf widths used in the treatment planning, since Additional file 1 our comparisons were performed on the same treatment Supplementary table. Median value and range of target dose parameters, planning system for two treatment platforms with similar expressed as a percent of the prescription dose. open-field beam characteristics, using the same beam con- Click here for file figurations, optimization parameters (for IMRT), and [http://www.biomedcentral.com/content/supplementary/1748- 717X-4-22-S1.doc] dose constraints. Nevertheless, it should be pointed out that leaf-width is not the only parameter that is different Additional file 2 between these MLC systems. Factors such as the leaf trans- Supplementary table. Group-based analyses of mean conformity and het- mission and leakage (a function of leaf height, material erogeneity indices for each MLC plan. constituent, and tongue-and-groove), source-to-MLC dis- Click here for file tance, are also different and affect dosimetric parameters. [http://www.biomedcentral.com/content/supplementary/1748- Therefore, the current planning study is not a simple com- 717X-4-22-S2.doc] parison for different MLC leaf-widths, but rather a com- Additional file 3 plex comparison of two dose delivery systems with Supplementary table. Median value and range of organ-at-risk (OAR) different leaf-width MLCs [19]. dose as a percent of the prescription dose. Click here for file Conclusion [http://www.biomedcentral.com/content/supplementary/1748- Data derived from the present comparative assessment 717X-4-22-S3.doc] suggest dosimetric merit of the high definition MLC sys- tem over the millennium MLC system. However, the clin- ical significance of these results warrants further investigation in order to determine whether the observed Acknowledgements dosimetric advantages translate into outcome improve- The authors wish to thank Ms. Maureen Dooley-Dahlgren for the prepara- ments. tion of this manuscript. References Competing interests 1. Potters L, Steinberg M, Rose C, Timmerman R, Ryu S, Hevezi JM, MF: Varian Medical Systems, Palo Alto, CA; Research sup- Welsh J, Mehta M, Larson DA, Janjan DA: American Society for port, Consultant, Speaker. Therapeutic Radiology and Oncology and American College of Radiology practice guideline for the performance of ster- eotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004, Authors' contributions 60:1026-1032. JAT participated in the conception and design of the 2. Papiez L, Timmerman R, DesRosiers C, Randall M: Extracranial stereotactic radioablation: Physical principles. 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Wu QJ, Wang Z, Kirkpatrick JP, Chang Z, Meyer JJ, Lu M, Huntzinger Your research papers will be: C, Yin FF: Impact of collimator leaf width and treatment tech- available free of charge to the entire biomedical community nique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions. Radiat Oncol 2009, 4:3. peer reviewed and published immediately upon acceptance 24. Paddick I: A simple scoring ratio to index the conformity of cited in PubMed and archived on PubMed Central radiosurgical treatment plans: Technical note. J Neurosurg 2000, 93:219-222. yours — you keep the copyright 25. Nakamura JL, Verhey LJ, Smith V, Petti PL, Lamborn KR, Larson DA, BioMedcentral Wara WM, McDermott MW, Sneed PK: Dose conformity of Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 7 of 7 (page number not for citation purposes)

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Radiation OncologySpringer Journals

Published: Jul 10, 2009

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