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Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: a dosimetric comparison with 3D technique

Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and... Purpose: Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion. However dose distributions can be quite different from standard 3D therapy. This study quantifies those differences, with focus on VMAT plans using unflattened photon beams. Methods: A total of 15 lung cancer patients previously treated with 3D or VMAT SBRT were randomly selected. For each patient, non-coplanar 3D, coplanar and non-coplanar VMAT and flattening filter free VMAT (FFF-VMAT) plans were generated to meet the same objectives with 50 Gy covering 95% of the PTV. Two dynamic arcs were used in each VMAT plan. The couch was set at ± 5° to the 0° straight position for the two non-coplanar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, Fitchburg WI) treatment planning system with VMAT capabilities was used. We analyzed the conformity index (CI), which is the ratio of the total volume receiving at least the prescription dose to the target volume receiving at least the prescription dose; the conformity number (CN) which is the ratio of the target coverage to CI; and the gradient index (GI) which is the ratio of the volume of 50% of the prescription isodose to the volume of the prescription isodose; as well as the V20, V5, and mean lung dose (MLD). Paired non-parametric analysis of variance tests with post-tests were performed to examine the statistical significance of the differences of the dosimetric indices. Results: Dosimetric indices CI, CN and MLD all show statistically significant improvement for all studied VMAT techniques compared with 3D plans (p < 0.05). V5 and V20 show statistically significant improvement for the FFF- VMAT plans compared with 3D (p < 0.001). GI is improved for the FFF-VMAT and the non-coplanar VMAT plans (p < 0.01 and p < 0.05 respectively) while the coplanar VMAT plans do not show significant difference compared to 3D plans. Dose to the target is typically more homogeneous in FFF-VMAT plans. FFF-VMAT plans require more monitor units than 3D or non-coplanar VMAT ones. Conclusion: Besides the advantage of faster delivery times, VMAT plans demonstrated better conformity to target, sharper dose fall-off in normal tissues and lower dose to normal lung than the 3D plans for lung SBRT. More monitor units are often required for FFF-VMAT plans. * Correspondence: geoffrey.zhang@moffitt.org Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA Full list of author information is available at the end of the article © 2011 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Zhang et al. Radiation Oncology 2011, 6:152 Page 2 of 6 http://www.ro-journal.com/content/6/1/152 beam entrance through the uninvolved lung was allowed. Introduction Thus no full rotation arcs were used. The same beam Studies have shown encouraging results when treating entrance strategy was also used in the 3D plans, with 9-11 medically inoperable early stage lung cancer using stereo- beams, of which 4-9 were non-coplanar. A 1 cm wide tactic body radiotherapy (SBRT) [1-3]. Conventionally, avoidance ring structure was used in plan optimization to lung cancer SBRT has been delivered using three-dimen- facilitate rapid dose fall-off away from the PTV. The Pinna- sional (3D) non-coplanar beams [4] or IMRT. Recently, cle’s direct machine parameters optimization (DMPO) fea- volumetric modulated arc therapy (VMAT) was intro- ture was used in the beam weighting optimization by duced to treat various disease sites [5-7], including lung allowing one segment per beam for the 3D plans. Inhomo- SBRT [8,9]. The major advantages of the VMAT SBRT geneity correction was used in all the plans. plans compared to the conventional 3D ones include faster delivery, which reduces the risk of intrafractional motion, Conformity index while simultaneously improving target dose conformity The conformity index (CI) is defined as the ratio of the [8,9]. VMAT plans lead to a smaller percentage of lung total volume receiving at least the prescription dose, V , volume exceeding 5 Gy, (V5), and 20 Gy, (V20) [10]. to the target volume receiving at least the prescription Recently, a flattening-filter-free (FFF) linear accelerator dose, Vt :[12] was installed in our clinic. As part of critical evaluation of this new technology, we included FFF-VMAT into com- CI = V /Vt (1) prehensive comparisons of the dosimetric parameters for 100 100 different lung SBRT treatment techniques. We studied the The value of CI is always greater than unity. A value dose conformity to the target volume, the dose fall-off in that is closer to unity represents a better target confor- normal tissues, and the V20, V5, mean lung dose (MLD), mity of radiation dose in the treatment plan. mean PTV dose, as well as total monitor units (MU) for VMAT, FFF-VMAT and 3D conformal SBRT plans. In the Conformity number present paper, we statistically compare these techniques. The target coverage (TC) is defined as the ratio of the target volume receiving at least the prescription dose, Materials and methods Vt , to the total target volume, Vt: Treatment planning 100 This retrospective study was approved by the institutional TC = Vt /Vt (2) IRB. A total of 15 early stage lung cancer patients with var- ious tumor sizes previously treated with 3D or VMAT The value of CI varies with the value of TC. Poor target SBRT were randomly selected. Four-dimensional (4D) CT coverage may give a better CI. To include the effect of TC was used for each patient to determine the internal gross on conformity, the conformity number (CN) is introduced tumor volume (IGTV) to account for the respiratory and defined as the ratio of the TC to CI [13]: motion. Abdominal compression was applied to thirteen CN = TC/CI = Vt / V · Vt (3) patients to minimize respiratory excursion of the dia- ( ) phragm. For two patients, no abdominal compression was The value of CN is always smaller than unity. A value applied, at the discretion of the treating radiation oncolo- closer to unity represents a better conformity and target gist. A superior/inferior margin of 0.7 cm and axial margin coverage. of 0.5 cm was added to the IGTV to generate the planning target volume (PTV). The average PTV was 61.0 cm Gradient index (range 16.8-160.8 cm ). For each patient, we generated a The gradient index (GI) is defined as the ratio of the non-coplanar 3D plan, both coplanar and a non-coplanar volume covered by at least a given percentage of the pre- conventional VMAT plans, and a non-coplanar FFF- scription dose to the volume covered by the full prescrip- VMAT plan. The same dose objectives were used for each tion dose [14]. For this lung SBRT dosimetric study, the plan. They were designed to deliver 50 Gy in 5 fractions to given percentage is set at 50% of the prescription dose. 95%ofthePTV.Two dynamicarcswereusedinall Mathematically, GI in this study is expressed as: VMAT plans. The couch was offset ± 5° for the non-copla- nar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, GI = V /V (4) 50 100 Fitchburg WI) was used to plan for a 6 MV or 6MV-FFF where V is the volume covered by at least 50% of beams from a TrueBeam linear accelerator (Varian Medical 50 the prescription dose. System Inc. Palo Alto, CA). SmartArc was used for the The value of GI is greater than unity. A value that is VMAT planning [11]. All plans were designed to spare the contralateral lung as much as possible. To that end, no arc closer to unity represents a faster dose fall-off in normal Zhang et al. Radiation Oncology 2011, 6:152 Page 3 of 6 http://www.ro-journal.com/content/6/1/152 tissue in the treatment plan, which may imply a lower Results dose to critical structures. Table 1 lists the statistical data of the dosimetric indices for all the studied cases. Overall, VMAT plans demon- V20, V5, and Mean Lung Dose strate better indices than the 3D plans. The non-coplanar The percentage of normal lung volume exceeding 20 Gy VMAT plans yield slightly better indices than the coplanar of dose, V20, is a key parameter in risk assessment of ones. The GI values for the FFF-VMAT plans were slightly radiation pneumonitis [15], and is often used in thoracic lower than those for conventional plans. VMAT required cancer treatment plan evaluation [1,16]. Other studies higher total MUs than 3D. The FFF-VMAT plans tended also found close correlation between high percentage to use the highest number of MU. normal lung volume exceeding 5 Gy of dose (V5) and Due to the large differences in PTV size as well as indivi- pneumonitis [17,18]. Normal lung volume was defined as dual patient anatomical variations, the standard deviations the total lung volume minus GTV. Our treatment plan- in Table 1 are quite high. This large spread somewhat ning objectives required a V20 < 10%. The mean lung obscures the dosimetric differences between the plans. To dose (MLD) is another important index in radiation better illuminate the differences, all the plans were com- pneumonitis risk assessment [19]. The values of V20, V5 pared with the corresponding 3D plans taken as a refer- and MLD were compared between the planning methods ence. The numbers of cases out of the 15 cases studied for each case. The generalized equivalent uniform dose that dosimetrically favor the VMAT or FFF-VMAT plans (gEUD) [20,21] was calculated for normal lung volume are presented in Table 2. Except for the total MUs, more and compared between all the plans. cases favor the VMAT and FFF-VMAT plans for all other dosimetric indices. Total monitor units At distances beyond a few cm from the field edge, periph- Conformity index (CI) eral dose is dominated by accelerator head leakage and is The overall Friedman test demonstrated highly significant therefore proportional to total MU. Monitor units in each difference between the techniques (p < 0.0001) for the CI. plan were compared as a risk index for potential radiation- Individual comparisons (Dunn’s post-test) for the CI indi- induced secondary malignancies [22]. The accelerators are cate statistically significant difference between the 3D and calibrated to deliver 1 cGy/MU to muscle at a depth of all VMAT techniques: p < 0.05 between the 3D and the maximum dose (1.5 cm) for a 10 × 10 field at source-to- coplanar VMAT plans, p < 0.01 between 3D and the non- surface distance of 100 cm. coplanar VMAT plans and p < 0.001 between 3D and the FFF-VMAT plans,. The differences were not significant Mean dose in PTV (p > 0.05) between different VMAT plans. VMAT offers The mean target dose (MTD) was used to quantify dose statistically significant improvement in CI over 3D. homogeneityinsidethe PTV. With thesame prescribed dose and target coverage, higher MTD implies a more het- Conformity number (CN) erogeneous dose distribution within the PTV. Addition- Similar to CI, the Friedman test indicated overall signifi- ally, the gEUD was calculated for the PTV based on the cant difference in CN (p < 0.0001). The p values of the dose distribution and compared between all the plans. Dunn’s post-test were p < 0.05 between 3D and the copla- nar VMAT plans, p < 0.01 between 3D and the non-copla- Statistical analysis nar VMAT plans and p < 0.001 between 3D and the FFF- The non-parametric Friedman test was applied in the sta- VMAT plans. No significant difference in CN between tistical analysis. The Friedman test compares three or VMAT techniques could be established (p > 0.05) more paired groups. A p value is generated by the Fried- man test. If it is small (< 0.05), the null hypothesis that Gradient index (GI) there is no difference between the column median values The overall p value from the Friedman test was 0.0035 is rejected. The paired test is chosen because the underly- for GI. The Dunn’s test yielded p < 0.05 between 3D and ing physical problem is identical across the planning the non-coplanar VMAT plans and p < 0.01 between 3D techniques for each patient but varies among the and the FFF-VMAT plans. The test demonstrated no sig- patients. nificant GI improvement (p > 0.05) for coplanar VMAT Following the Friedman test, the rank-based multiple compared to 3D, and no significant differences among comparison test, Dunn’s post-test, was performed. It tests the different VMAT techniques. the same null hypothesis for individual pairs of data col- umns. Dunn’s post-test includes a non-parametric V20, V5 and mean lung dose (MLD) equivalent of Bonferroni adjustment for multiple From the overall Friedman test, p < 0.0001 for V20. A comparisons. statistically significant improvement in V20 was found Zhang et al. Radiation Oncology 2011, 6:152 Page 4 of 6 http://www.ro-journal.com/content/6/1/152 Table 1 Dosimetric data of 3D, coplanar, non-coplanar VMAT and FFF-VMAT plans Plan 3D Coplanar VMAT Non-coplanar VMAT Non-coplanar FFF-VMAT CI 1.44 ± 0.21 1.23 ± 0.20 1.22 ± 0.17 1.19 ± 0.13 CN 0.67 ± 0.09 0.79 ± 0.09 0.79 ± 0.08 0.81 ± 0.07 GI 7.12 ± 1.43 6.49 ± 1.90 6.41 ± 1.78 6.23 ± 1.59 V20 (%) 6.8 ± 2.9 5.8 ± 2.4 5.8 ± 2.3 5.6 ± 2.3 V5 (%) 23.5 ± 8.0 20.9 ± 7.4 21.0 ± 7.2 20.4 ± 7.1 MLD (cGy) 497 ± 153 458 ± 144 459 ± 140 449 ± 142 MTD (cGy) 5359 ± 101 5370 ± 116 5361 ± 104 5324 ± 83 MU 1528 ± 136 1708 ± 194 1660 ± 200 1805 ± 258 In the table, CI = conformity index, CN = conformity number, GI = gradient index, V20 is the percentage volume of lung-GTV exceeding 20 Gy, V5 is the percentage volume of lung-GTV exceeding 5 Gy, MLD = mean lung dose, MTD = mean target dose and MU = number of monitor units. for non-coplanar VMAT (p < 0.01) and FFF-VMAT (p < Mean dose in PTV (MTD) 0.001) techniques compared to 3D. No significant differ- The average MTD was lowest in the FFF-VMAT plans. ence in V20 was found between 3D and coplanar The p value from the Friedman test for MTD was 0.0052. VMAT, as well as between different VMAT techniques. The Dunn ’s test only showed significant difference The Friedman test yielded p = 0.0002 for V5 compari- between the coplanar VMAT and FFF-VMAT techniques sons. Individual comparisons showed no statistically sig- (p < 0.01). These are the planning techniques with the highest and lowest average MTD values. The compari- nificant differences, except for the FFF-VMAT plans sons of the PTV gEUD closely followed the MTD indicating improvement in V5 compared to 3D (p < comparisons. 0.001). The Friedman test was significant (p < 0.0001) for MLD comparisons. The Dunn’s post test demonstrated that all Discussion VMAT techniques showed improvement in MLD com- The VMAT advantage in shortening the treatment time pared to 3D with p < 0.05 between 3D and the coplanar compared to 3D non-coplanar plans is well known [9]. VMAT, p < 0.01 between 3D and the non-coplanar The current study also shows that VMAT plans are more VMAT and p < 0.001 between 3D and FFF-VMAT. No likely to give statistically better target conformity and shar- significant difference inMLD wasshown betweenthe per dose fall-off in normal tissues. The average GI value VMAT techniques. The gEUDs for the normal lung clo- for FFF-VMAT plans was lower than that for 3D plans, sely followed the MLD. indicating better dose fall-off in normal tissues in the FFF- VMAT plans. At the same time, V20 and V5 were lower Monitor units (MU) when treating with FFF-VMAT. V20 was also lower in The overall Friedman test p value for the MU was p < non-coplanar VMAT plans than in 3D. 0.0001. The MUs were significantly different between In general, the comparison of V20, V5 and MLD FFF-VMAT and 3D (p < 0.001) and between FFF-VMAT between VMAT and 3D in this study agrees with the and non-coplanar VMAT (p < 0.05). There was also a study by McGrath et al [23], but not with Chan et al [24]. difference between 3D and coplanar VMAT (p < 0.001). In Chan et al, the comparison was made for the treatment The MU in the FFF-VMAT plans was always greater of the locally advanced non-small cell lung cancer. The than in 3D plans. target volume was usually larger than is suitable for SBRT. In their comparison, mean lung dose and V20 were similar between 3D and VMAT, but V5 was significantly higher in VMAT. The comparison of other parameters in Chan Table 2 Compared to 3D plans, number of cases that is et al, such as CI and MU, agree with our study. dosimetrically in favor of the VMAT or FFF plans Due to collision limitations, the angle separation of the Index CI CN GI V5 V20 MLD MTD MU non-coplanar arcs was uniformly set at 10° (± 5° to the Coplanar VMAT 14 14 12 12 13 15 5 0 straight couch position). It is plausible that the dosimetric Non-coplanar VMAT 14 14 12 13 14 14 8 2 differences between the coplanar and non-coplanar Non-coplanar FFF-VMAT 15 15 13 14 15 14 11 0 VMAT plans were not statistically significant due to this small physical angle separation as opposed to the limited The total number of cases is 15. In the table, CI = conformity index, CN = conformity number, GI = gradient index, V20 is the percentage volume of statistical power. We further postulate that with a larger lung-GTV exceeding 20 Gy, V5 is the percentage volume of lung-GTV angle separation, the differences are expected to increase, exceeding 5 Gy, MLD = mean lung dose, MTD = mean target dose and MU = number of monitor units. favoring the non-coplanar VMAT plans for the CI, GI and Zhang et al. Radiation Oncology 2011, 6:152 Page 5 of 6 http://www.ro-journal.com/content/6/1/152 V20 values. The angular separation can be larger for smal- min vs. 600-1000 MU/min). However, for VMAT plans, ler patients or when the tumor is situated more laterally. the treatment delivery time is largely limited by the gan- The other way to increase the angle separation is to shift try rotation speed, not the dose rate. the isocenter laterally, away from the tumor. We have not The interplay between the dynamic MLC-based delivery explored this option. of VMAT and the respiratory motion of the tumor may Beam arrangements are more restrictive in VMAT plan- degrade target coverage [27]. Since this is not a concern ning compared to 3D conformal planning. First, the couch with 3D technique, we expect a better agreement in target coverage between the plan and delivered treatment for 3D angle range for non-coplanar planning is smaller with the treatment compared to VMAT if there is significant arcs compared to the static beams. Second, the machine limitation prohibiting the gantry from crossing the 180 respiratory tumor motion or if the beam aperture size is degree position often shortens the arc length in VMAT frequently small in a VMAT plan. We are currently planning, as shown in Figure 1. This could affect the qual- exploring the impact of tumor motion on target coverage ity of the VMAT plans. when using IMRT technique. If increased dose heterogeneity is accepted within the target volume, dose fall-off can be sharpened in normal Conclusions tissue [25]. Because FFF-VMAT plans tend to deliver a CI, CN and mean lung dose are highly statistically more homogeneous dose to the target volumes, the GI improved for all studied VMAT techniques compared should be improved if the dose constraints mandate a with 3D plans. GI, V5 and V20 are statistically improved higher mean dose in the targets. The other factor that for FFF-VMAT plans compared with 3D technique. It is affects the dose fall-off in normal tissue is the beam aper- also clear that FFF-VMAT plans require more monitor ture margin. In SmartArc planning, this margin is not units than 3D or non-coplanar VMAT techniques. fixed, but is rather optimized by the software. An option to allow user to use a fixed margin with the arcs would Author details help to improve the dose fall-off in normal tissue. 1 2 Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA. Radiation For off-center PTV volumes, FFF-VMAT typically Oncology, Salem Hospital, Salem, Oregon, USA. School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. requires more MU due to the highly peaked beam profile. This does not automatically translate into higher periph- Authors’ contributions eral doses as there is less head scatter and leakage from GZ: initiated and organized the project; performed the bulk of data collection and analysis; prepared the draft of the manuscript. LK: participated in the an accelerator without a flattening filter [26]. design of the study and the draft of the manuscript. TD: contoured PTVs and The dose rate for the FFF beams can be substantially provided prescriptions; monitored treatment planning; contributed to the draft higher than the conventional beams (1400 or 2400 MU/ of the manuscript. CS: contoured PTVs and provided prescriptions; monitored treatment planning; contributed to the draft of the manuscript. RZ: contributed to the data analysis and the draft of the manuscript. WL: generated most of the treatment plans. VF: supervised the project; contributed to the statistical data analysis and the draft of the manuscript; participated in its design and coordination. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 22 June 2011 Accepted: 9 November 2011 Published: 9 November 2011 References 1. 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McGrath SD, Matuszak MM, Yan D, Kestin LL, Martinez AA, Grills IS: Volumetric modulated arc therapy for delivery of hypofractionated • Thorough peer review stereotactic lung radiotherapy: A dosimetric and treatment efficiency • No space constraints or color figure charges analysis. Radiother Oncol 2010, 95:153-157. • Immediate publication on acceptance 24. Chan OSH, Lee MCH, Hung AWM, Chang ATY, Yeung RMW, Lee AWM: The superiority of hybrid-volumetric arc therapy (VMAT) technique over • Inclusion in PubMed, CAS, Scopus and Google Scholar double arcs VMAT and 3D-conformal technique in the treatment of • Research which is freely available for redistribution locally advanced non-small cell lung cancer-A planning study. Radiother Oncol 2011. Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: a dosimetric comparison with 3D technique

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Copyright © 2011 by Zhang et al; licensee BioMed Central Ltd.
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Medicine & Public Health; Oncology; Radiotherapy
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1748-717X
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10.1186/1748-717X-6-152
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22070866
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Abstract

Purpose: Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion. However dose distributions can be quite different from standard 3D therapy. This study quantifies those differences, with focus on VMAT plans using unflattened photon beams. Methods: A total of 15 lung cancer patients previously treated with 3D or VMAT SBRT were randomly selected. For each patient, non-coplanar 3D, coplanar and non-coplanar VMAT and flattening filter free VMAT (FFF-VMAT) plans were generated to meet the same objectives with 50 Gy covering 95% of the PTV. Two dynamic arcs were used in each VMAT plan. The couch was set at ± 5° to the 0° straight position for the two non-coplanar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, Fitchburg WI) treatment planning system with VMAT capabilities was used. We analyzed the conformity index (CI), which is the ratio of the total volume receiving at least the prescription dose to the target volume receiving at least the prescription dose; the conformity number (CN) which is the ratio of the target coverage to CI; and the gradient index (GI) which is the ratio of the volume of 50% of the prescription isodose to the volume of the prescription isodose; as well as the V20, V5, and mean lung dose (MLD). Paired non-parametric analysis of variance tests with post-tests were performed to examine the statistical significance of the differences of the dosimetric indices. Results: Dosimetric indices CI, CN and MLD all show statistically significant improvement for all studied VMAT techniques compared with 3D plans (p < 0.05). V5 and V20 show statistically significant improvement for the FFF- VMAT plans compared with 3D (p < 0.001). GI is improved for the FFF-VMAT and the non-coplanar VMAT plans (p < 0.01 and p < 0.05 respectively) while the coplanar VMAT plans do not show significant difference compared to 3D plans. Dose to the target is typically more homogeneous in FFF-VMAT plans. FFF-VMAT plans require more monitor units than 3D or non-coplanar VMAT ones. Conclusion: Besides the advantage of faster delivery times, VMAT plans demonstrated better conformity to target, sharper dose fall-off in normal tissues and lower dose to normal lung than the 3D plans for lung SBRT. More monitor units are often required for FFF-VMAT plans. * Correspondence: geoffrey.zhang@moffitt.org Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA Full list of author information is available at the end of the article © 2011 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Zhang et al. Radiation Oncology 2011, 6:152 Page 2 of 6 http://www.ro-journal.com/content/6/1/152 beam entrance through the uninvolved lung was allowed. Introduction Thus no full rotation arcs were used. The same beam Studies have shown encouraging results when treating entrance strategy was also used in the 3D plans, with 9-11 medically inoperable early stage lung cancer using stereo- beams, of which 4-9 were non-coplanar. A 1 cm wide tactic body radiotherapy (SBRT) [1-3]. Conventionally, avoidance ring structure was used in plan optimization to lung cancer SBRT has been delivered using three-dimen- facilitate rapid dose fall-off away from the PTV. The Pinna- sional (3D) non-coplanar beams [4] or IMRT. Recently, cle’s direct machine parameters optimization (DMPO) fea- volumetric modulated arc therapy (VMAT) was intro- ture was used in the beam weighting optimization by duced to treat various disease sites [5-7], including lung allowing one segment per beam for the 3D plans. Inhomo- SBRT [8,9]. The major advantages of the VMAT SBRT geneity correction was used in all the plans. plans compared to the conventional 3D ones include faster delivery, which reduces the risk of intrafractional motion, Conformity index while simultaneously improving target dose conformity The conformity index (CI) is defined as the ratio of the [8,9]. VMAT plans lead to a smaller percentage of lung total volume receiving at least the prescription dose, V , volume exceeding 5 Gy, (V5), and 20 Gy, (V20) [10]. to the target volume receiving at least the prescription Recently, a flattening-filter-free (FFF) linear accelerator dose, Vt :[12] was installed in our clinic. As part of critical evaluation of this new technology, we included FFF-VMAT into com- CI = V /Vt (1) prehensive comparisons of the dosimetric parameters for 100 100 different lung SBRT treatment techniques. We studied the The value of CI is always greater than unity. A value dose conformity to the target volume, the dose fall-off in that is closer to unity represents a better target confor- normal tissues, and the V20, V5, mean lung dose (MLD), mity of radiation dose in the treatment plan. mean PTV dose, as well as total monitor units (MU) for VMAT, FFF-VMAT and 3D conformal SBRT plans. In the Conformity number present paper, we statistically compare these techniques. The target coverage (TC) is defined as the ratio of the target volume receiving at least the prescription dose, Materials and methods Vt , to the total target volume, Vt: Treatment planning 100 This retrospective study was approved by the institutional TC = Vt /Vt (2) IRB. A total of 15 early stage lung cancer patients with var- ious tumor sizes previously treated with 3D or VMAT The value of CI varies with the value of TC. Poor target SBRT were randomly selected. Four-dimensional (4D) CT coverage may give a better CI. To include the effect of TC was used for each patient to determine the internal gross on conformity, the conformity number (CN) is introduced tumor volume (IGTV) to account for the respiratory and defined as the ratio of the TC to CI [13]: motion. Abdominal compression was applied to thirteen CN = TC/CI = Vt / V · Vt (3) patients to minimize respiratory excursion of the dia- ( ) phragm. For two patients, no abdominal compression was The value of CN is always smaller than unity. A value applied, at the discretion of the treating radiation oncolo- closer to unity represents a better conformity and target gist. A superior/inferior margin of 0.7 cm and axial margin coverage. of 0.5 cm was added to the IGTV to generate the planning target volume (PTV). The average PTV was 61.0 cm Gradient index (range 16.8-160.8 cm ). For each patient, we generated a The gradient index (GI) is defined as the ratio of the non-coplanar 3D plan, both coplanar and a non-coplanar volume covered by at least a given percentage of the pre- conventional VMAT plans, and a non-coplanar FFF- scription dose to the volume covered by the full prescrip- VMAT plan. The same dose objectives were used for each tion dose [14]. For this lung SBRT dosimetric study, the plan. They were designed to deliver 50 Gy in 5 fractions to given percentage is set at 50% of the prescription dose. 95%ofthePTV.Two dynamicarcswereusedinall Mathematically, GI in this study is expressed as: VMAT plans. The couch was offset ± 5° for the non-copla- nar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, GI = V /V (4) 50 100 Fitchburg WI) was used to plan for a 6 MV or 6MV-FFF where V is the volume covered by at least 50% of beams from a TrueBeam linear accelerator (Varian Medical 50 the prescription dose. System Inc. Palo Alto, CA). SmartArc was used for the The value of GI is greater than unity. A value that is VMAT planning [11]. All plans were designed to spare the contralateral lung as much as possible. To that end, no arc closer to unity represents a faster dose fall-off in normal Zhang et al. Radiation Oncology 2011, 6:152 Page 3 of 6 http://www.ro-journal.com/content/6/1/152 tissue in the treatment plan, which may imply a lower Results dose to critical structures. Table 1 lists the statistical data of the dosimetric indices for all the studied cases. Overall, VMAT plans demon- V20, V5, and Mean Lung Dose strate better indices than the 3D plans. The non-coplanar The percentage of normal lung volume exceeding 20 Gy VMAT plans yield slightly better indices than the coplanar of dose, V20, is a key parameter in risk assessment of ones. The GI values for the FFF-VMAT plans were slightly radiation pneumonitis [15], and is often used in thoracic lower than those for conventional plans. VMAT required cancer treatment plan evaluation [1,16]. Other studies higher total MUs than 3D. The FFF-VMAT plans tended also found close correlation between high percentage to use the highest number of MU. normal lung volume exceeding 5 Gy of dose (V5) and Due to the large differences in PTV size as well as indivi- pneumonitis [17,18]. Normal lung volume was defined as dual patient anatomical variations, the standard deviations the total lung volume minus GTV. Our treatment plan- in Table 1 are quite high. This large spread somewhat ning objectives required a V20 < 10%. The mean lung obscures the dosimetric differences between the plans. To dose (MLD) is another important index in radiation better illuminate the differences, all the plans were com- pneumonitis risk assessment [19]. The values of V20, V5 pared with the corresponding 3D plans taken as a refer- and MLD were compared between the planning methods ence. The numbers of cases out of the 15 cases studied for each case. The generalized equivalent uniform dose that dosimetrically favor the VMAT or FFF-VMAT plans (gEUD) [20,21] was calculated for normal lung volume are presented in Table 2. Except for the total MUs, more and compared between all the plans. cases favor the VMAT and FFF-VMAT plans for all other dosimetric indices. Total monitor units At distances beyond a few cm from the field edge, periph- Conformity index (CI) eral dose is dominated by accelerator head leakage and is The overall Friedman test demonstrated highly significant therefore proportional to total MU. Monitor units in each difference between the techniques (p < 0.0001) for the CI. plan were compared as a risk index for potential radiation- Individual comparisons (Dunn’s post-test) for the CI indi- induced secondary malignancies [22]. The accelerators are cate statistically significant difference between the 3D and calibrated to deliver 1 cGy/MU to muscle at a depth of all VMAT techniques: p < 0.05 between the 3D and the maximum dose (1.5 cm) for a 10 × 10 field at source-to- coplanar VMAT plans, p < 0.01 between 3D and the non- surface distance of 100 cm. coplanar VMAT plans and p < 0.001 between 3D and the FFF-VMAT plans,. The differences were not significant Mean dose in PTV (p > 0.05) between different VMAT plans. VMAT offers The mean target dose (MTD) was used to quantify dose statistically significant improvement in CI over 3D. homogeneityinsidethe PTV. With thesame prescribed dose and target coverage, higher MTD implies a more het- Conformity number (CN) erogeneous dose distribution within the PTV. Addition- Similar to CI, the Friedman test indicated overall signifi- ally, the gEUD was calculated for the PTV based on the cant difference in CN (p < 0.0001). The p values of the dose distribution and compared between all the plans. Dunn’s post-test were p < 0.05 between 3D and the copla- nar VMAT plans, p < 0.01 between 3D and the non-copla- Statistical analysis nar VMAT plans and p < 0.001 between 3D and the FFF- The non-parametric Friedman test was applied in the sta- VMAT plans. No significant difference in CN between tistical analysis. The Friedman test compares three or VMAT techniques could be established (p > 0.05) more paired groups. A p value is generated by the Fried- man test. If it is small (< 0.05), the null hypothesis that Gradient index (GI) there is no difference between the column median values The overall p value from the Friedman test was 0.0035 is rejected. The paired test is chosen because the underly- for GI. The Dunn’s test yielded p < 0.05 between 3D and ing physical problem is identical across the planning the non-coplanar VMAT plans and p < 0.01 between 3D techniques for each patient but varies among the and the FFF-VMAT plans. The test demonstrated no sig- patients. nificant GI improvement (p > 0.05) for coplanar VMAT Following the Friedman test, the rank-based multiple compared to 3D, and no significant differences among comparison test, Dunn’s post-test, was performed. It tests the different VMAT techniques. the same null hypothesis for individual pairs of data col- umns. Dunn’s post-test includes a non-parametric V20, V5 and mean lung dose (MLD) equivalent of Bonferroni adjustment for multiple From the overall Friedman test, p < 0.0001 for V20. A comparisons. statistically significant improvement in V20 was found Zhang et al. Radiation Oncology 2011, 6:152 Page 4 of 6 http://www.ro-journal.com/content/6/1/152 Table 1 Dosimetric data of 3D, coplanar, non-coplanar VMAT and FFF-VMAT plans Plan 3D Coplanar VMAT Non-coplanar VMAT Non-coplanar FFF-VMAT CI 1.44 ± 0.21 1.23 ± 0.20 1.22 ± 0.17 1.19 ± 0.13 CN 0.67 ± 0.09 0.79 ± 0.09 0.79 ± 0.08 0.81 ± 0.07 GI 7.12 ± 1.43 6.49 ± 1.90 6.41 ± 1.78 6.23 ± 1.59 V20 (%) 6.8 ± 2.9 5.8 ± 2.4 5.8 ± 2.3 5.6 ± 2.3 V5 (%) 23.5 ± 8.0 20.9 ± 7.4 21.0 ± 7.2 20.4 ± 7.1 MLD (cGy) 497 ± 153 458 ± 144 459 ± 140 449 ± 142 MTD (cGy) 5359 ± 101 5370 ± 116 5361 ± 104 5324 ± 83 MU 1528 ± 136 1708 ± 194 1660 ± 200 1805 ± 258 In the table, CI = conformity index, CN = conformity number, GI = gradient index, V20 is the percentage volume of lung-GTV exceeding 20 Gy, V5 is the percentage volume of lung-GTV exceeding 5 Gy, MLD = mean lung dose, MTD = mean target dose and MU = number of monitor units. for non-coplanar VMAT (p < 0.01) and FFF-VMAT (p < Mean dose in PTV (MTD) 0.001) techniques compared to 3D. No significant differ- The average MTD was lowest in the FFF-VMAT plans. ence in V20 was found between 3D and coplanar The p value from the Friedman test for MTD was 0.0052. VMAT, as well as between different VMAT techniques. The Dunn ’s test only showed significant difference The Friedman test yielded p = 0.0002 for V5 compari- between the coplanar VMAT and FFF-VMAT techniques sons. Individual comparisons showed no statistically sig- (p < 0.01). These are the planning techniques with the highest and lowest average MTD values. The compari- nificant differences, except for the FFF-VMAT plans sons of the PTV gEUD closely followed the MTD indicating improvement in V5 compared to 3D (p < comparisons. 0.001). The Friedman test was significant (p < 0.0001) for MLD comparisons. The Dunn’s post test demonstrated that all Discussion VMAT techniques showed improvement in MLD com- The VMAT advantage in shortening the treatment time pared to 3D with p < 0.05 between 3D and the coplanar compared to 3D non-coplanar plans is well known [9]. VMAT, p < 0.01 between 3D and the non-coplanar The current study also shows that VMAT plans are more VMAT and p < 0.001 between 3D and FFF-VMAT. No likely to give statistically better target conformity and shar- significant difference inMLD wasshown betweenthe per dose fall-off in normal tissues. The average GI value VMAT techniques. The gEUDs for the normal lung clo- for FFF-VMAT plans was lower than that for 3D plans, sely followed the MLD. indicating better dose fall-off in normal tissues in the FFF- VMAT plans. At the same time, V20 and V5 were lower Monitor units (MU) when treating with FFF-VMAT. V20 was also lower in The overall Friedman test p value for the MU was p < non-coplanar VMAT plans than in 3D. 0.0001. The MUs were significantly different between In general, the comparison of V20, V5 and MLD FFF-VMAT and 3D (p < 0.001) and between FFF-VMAT between VMAT and 3D in this study agrees with the and non-coplanar VMAT (p < 0.05). There was also a study by McGrath et al [23], but not with Chan et al [24]. difference between 3D and coplanar VMAT (p < 0.001). In Chan et al, the comparison was made for the treatment The MU in the FFF-VMAT plans was always greater of the locally advanced non-small cell lung cancer. The than in 3D plans. target volume was usually larger than is suitable for SBRT. In their comparison, mean lung dose and V20 were similar between 3D and VMAT, but V5 was significantly higher in VMAT. The comparison of other parameters in Chan Table 2 Compared to 3D plans, number of cases that is et al, such as CI and MU, agree with our study. dosimetrically in favor of the VMAT or FFF plans Due to collision limitations, the angle separation of the Index CI CN GI V5 V20 MLD MTD MU non-coplanar arcs was uniformly set at 10° (± 5° to the Coplanar VMAT 14 14 12 12 13 15 5 0 straight couch position). It is plausible that the dosimetric Non-coplanar VMAT 14 14 12 13 14 14 8 2 differences between the coplanar and non-coplanar Non-coplanar FFF-VMAT 15 15 13 14 15 14 11 0 VMAT plans were not statistically significant due to this small physical angle separation as opposed to the limited The total number of cases is 15. In the table, CI = conformity index, CN = conformity number, GI = gradient index, V20 is the percentage volume of statistical power. We further postulate that with a larger lung-GTV exceeding 20 Gy, V5 is the percentage volume of lung-GTV angle separation, the differences are expected to increase, exceeding 5 Gy, MLD = mean lung dose, MTD = mean target dose and MU = number of monitor units. favoring the non-coplanar VMAT plans for the CI, GI and Zhang et al. Radiation Oncology 2011, 6:152 Page 5 of 6 http://www.ro-journal.com/content/6/1/152 V20 values. The angular separation can be larger for smal- min vs. 600-1000 MU/min). However, for VMAT plans, ler patients or when the tumor is situated more laterally. the treatment delivery time is largely limited by the gan- The other way to increase the angle separation is to shift try rotation speed, not the dose rate. the isocenter laterally, away from the tumor. We have not The interplay between the dynamic MLC-based delivery explored this option. of VMAT and the respiratory motion of the tumor may Beam arrangements are more restrictive in VMAT plan- degrade target coverage [27]. Since this is not a concern ning compared to 3D conformal planning. First, the couch with 3D technique, we expect a better agreement in target coverage between the plan and delivered treatment for 3D angle range for non-coplanar planning is smaller with the treatment compared to VMAT if there is significant arcs compared to the static beams. Second, the machine limitation prohibiting the gantry from crossing the 180 respiratory tumor motion or if the beam aperture size is degree position often shortens the arc length in VMAT frequently small in a VMAT plan. We are currently planning, as shown in Figure 1. This could affect the qual- exploring the impact of tumor motion on target coverage ity of the VMAT plans. when using IMRT technique. If increased dose heterogeneity is accepted within the target volume, dose fall-off can be sharpened in normal Conclusions tissue [25]. Because FFF-VMAT plans tend to deliver a CI, CN and mean lung dose are highly statistically more homogeneous dose to the target volumes, the GI improved for all studied VMAT techniques compared should be improved if the dose constraints mandate a with 3D plans. GI, V5 and V20 are statistically improved higher mean dose in the targets. The other factor that for FFF-VMAT plans compared with 3D technique. It is affects the dose fall-off in normal tissue is the beam aper- also clear that FFF-VMAT plans require more monitor ture margin. In SmartArc planning, this margin is not units than 3D or non-coplanar VMAT techniques. fixed, but is rather optimized by the software. An option to allow user to use a fixed margin with the arcs would Author details help to improve the dose fall-off in normal tissue. 1 2 Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA. Radiation For off-center PTV volumes, FFF-VMAT typically Oncology, Salem Hospital, Salem, Oregon, USA. School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. requires more MU due to the highly peaked beam profile. This does not automatically translate into higher periph- Authors’ contributions eral doses as there is less head scatter and leakage from GZ: initiated and organized the project; performed the bulk of data collection and analysis; prepared the draft of the manuscript. LK: participated in the an accelerator without a flattening filter [26]. design of the study and the draft of the manuscript. TD: contoured PTVs and The dose rate for the FFF beams can be substantially provided prescriptions; monitored treatment planning; contributed to the draft higher than the conventional beams (1400 or 2400 MU/ of the manuscript. CS: contoured PTVs and provided prescriptions; monitored treatment planning; contributed to the draft of the manuscript. RZ: contributed to the data analysis and the draft of the manuscript. WL: generated most of the treatment plans. VF: supervised the project; contributed to the statistical data analysis and the draft of the manuscript; participated in its design and coordination. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 22 June 2011 Accepted: 9 November 2011 Published: 9 November 2011 References 1. 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McGrath SD, Matuszak MM, Yan D, Kestin LL, Martinez AA, Grills IS: Volumetric modulated arc therapy for delivery of hypofractionated • Thorough peer review stereotactic lung radiotherapy: A dosimetric and treatment efficiency • No space constraints or color figure charges analysis. Radiother Oncol 2010, 95:153-157. • Immediate publication on acceptance 24. Chan OSH, Lee MCH, Hung AWM, Chang ATY, Yeung RMW, Lee AWM: The superiority of hybrid-volumetric arc therapy (VMAT) technique over • Inclusion in PubMed, CAS, Scopus and Google Scholar double arcs VMAT and 3D-conformal technique in the treatment of • Research which is freely available for redistribution locally advanced non-small cell lung cancer-A planning study. Radiother Oncol 2011. Submit your manuscript at www.biomedcentral.com/submit

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Radiation OncologySpringer Journals

Published: Nov 9, 2011

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