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A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT)

A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT) Background/Purpose: Radiotherapy (RT) volumes for anal cancer are large and of moderate complexity when organs at risk (OAR) such as testis, small bowel and bladder are at least partially to be shielded. Volumetric intensity modulated arc therapy (VMAT) might provide OAR-shielding comparable to step-and-shoot intensity modulated radiotherapy (IMRT) for this tumor entity with better treatment efficiency. Materials and methods: Based on treatment planning CTs of 8 patients, we compared dose distributions, comformality index (CI), homogeneity index (HI), number of monitor units (MU) and treatment time (TTT) for plans generated for VMAT, 3D-CRT and step-and-shoot-IMRT (optimized based on Pencil Beam (PB) or Monte Carlo (MC) dose calculation) for typical anal cancer planning target volumes (PTV) including inguinal lymph nodes as usually treated during the first phase (0-36 Gy) of a shrinking field regimen. Results: With values of 1.33 ± 0.21/1.26 ± 0.05/1.3 ± 0.02 and 1.39 ± 0.09, the CI's for IMRT (PB- Corvus/PB-Hyperion/MC-Hyperion) and VMAT are better than for 3D-CRT with 2.00 ± 0.16. The HI's for the prescribed dose (HI36) for 3D-CRT were 1.06 ± 0.01 and 1.11 ± 0.02 for VMAT, respectively and 1.15 ± 0.02/1.10 ± 0.02/1.11 ± 0.08 for IMRT (PB-Corvus/PB-Hyperion/MC- Hyperion). Mean TTT and MU's for 3D-CRT is 220s/225 ± 11MU and for IMRT (PB-Corvus/PB- Hyperion/MC-Hyperion) is 575s/1260 ± 172MU, 570s/477 ± 84MU and 610s748 ± 193MU while TTT and MU for two-arc-VMAT is 290s/268 ± 19MU. Conclusion: VMAT provides treatment plans with high conformity and homogeneity equivalent to step-and-shoot-IMRT for this mono-concave treatment volume. Short treatment delivery time and low primary MU are the most important advantages. Page 1 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 to segment on calculated fluences, VMAT on the other Introduction Coverage of large planning target volumes (PTV) as they hand segments on given structures. Several research are treated during the initial part of the protocols for anal groups developed their own IMAT solutions in order to cancer is difficult because protection of critical organs is study and exploit its potential for the reduction of treat- important for the patient's quality of life (QOL) [1]. Until ment time and MU while increasing the number of inci- recently, the standard approach has been three dimen- dent beam directions [15-19], with large target volumes sional conformal radiotherapy (3D-CRT), typically using such as encountered with whole abdominopelvic radio- a 4-field box technique [2]. The target volume for anal therapy (WAPRT) being particularly in the focus of the cancer is currently actively being discussed and a consen- group from Ghent [20,21]. sus document has recently been published by the RTOG [3]. It is, however, not a consequence of specific clinical Only recently commercial treatment planning systems data but the result of a highly subjective approach (super- (TPS) were released for modulated arc therapy. Otto intro- position of targets drawn by several individuals) and duced a single-arc VMAT approach [22] that formed the issues such as vaginal sparing still require cautious evalu- basis for RapidArc (Varian Medical Systems, USA) that in ation. The PTV therefore still ususally comprises primary its first clinical commercial implementation was then tumor and lower external and internal iliac lymph nodes. evaluated by Cozzi et. al[23] and Palma et. al [16]. Medial inguinal lymph nodes are usually treated up to at ERGO++ (Elekta, Sweden) has been released in parallel as least 30.6-36 Gy [4,5] and in case of involvement higher a commercial VMAT system and was evaluated in this doses are required (50.4-54 Gy). Treating inguinal lymph study. To provide comprehensive data, VMAT was com- nodes and pelvic lymph nodes simultaneously leads to a pared with a complex 3D-CRT technique (6 fields) and mean PTV size of more than 2.750 cm as exemplified in step-and-shoot IMRT including Monte Carlo and Pencil figure 1 and such relatively large PTVs are still considered Beam calculation. Several strategies (single and dual rota- appropriate in recent reviews [6]. Previous studies showed tions) were computed, and analysed with regard to dose- that IMRT provides PTV coverage similar to conventional volume-histograms (DVH), homogeneity, conformity, techniques and at the same time efficiently spares OAR exposure of OAR and treatment efficiency (treatment time [7]. On the downside, however, IMRT resulted in longer and monitor units). treatment time and a higher number of monitor units (MU). While step-and-shoot IMRT has become more effi- Methods and materials cient recently [8-10] rotational modulated therapy may be Patient anatomy another approach to improve these parameters [11,12]. Eight CT datasets of patients treated at our department for Volumetric modulated arc therapy (VMAT) is based on anal cancer were the basis for this study. The PTV was typ- the intensity modulated arc therapy (IMAT) paradigm, ical for the initial treatment series including the primary first described by Yu et. al [13,14]. The basic IMAT idea is tumor, pelvic and inguinal lymph nodes (figure 1). It is to be treated at daily doses of 1.8 Gy to a cumulative dose of 36 Gy. In patients without involved inguinal lymph nodes, the PTV would then be reduced to a typical pelvic PTV without coverage of inguinal lymph nodes. Finally, a boost would be delivered to the primary tumor, its dose depending on tumor size. Since the initial PTV used in all patients was the most complex one, evaluation of VMAT is only done in this context. Bladder, small intestine, gonads and femoral heads were contoured as OAR. A wedge-shaped anterior auxiliary structure was generated to facilitate the planning process. Treatment planning systems 3D-CRT (Masterplan) 3D-CRT-plans were generated with Masterplan 3.1 (Nucletron, The Netherlands). The field geometry con- sisted of 6 fields as suggested by Götz and Kiricuta [24]. A standard 4 field box treated at an energy of 23 MV and A Figure 1 xial CT for 3D-CRT with PTV and 6 beams beam angles of 0/87/180/273 degrees was supplemented Axial CT for 3D-CRT with PTV and 6 beams. by 2 oblique auxiliary fields (energy 6 MV) from 30 and Page 2 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 330 degrees, both with 30 degree wedges (figure 1). These rotation conforming the collimator to the PTV with additional beams cover the inguinal extensions of the PTV shielding of the auxiliary structure when it is in front of in the anterior/lateral direction. Dose is calculated based the PTV ('1RotiFo') and one 360° rotation on the PTV on a pencil beam (PB) algorithm. with full shielding of the auxiliary structure ('1RotALLW'). IMRT Treatment Planning The primary beam setup for the step-and-shoot approach The dual-rotation strategy ('2Rot') used two rotations consisted of 9 isotropic nonopposing coplanar beams, with a starting angle of 181° and a stop angle of 179° both for treatment plans generated with Corvus and each (total of 358°/rotation). These two arcs are subdi- Hyperion. vided into 72 subarcs for each rotation which results in one control point every 5 degrees. The first rotation IMRT (Pencil Beam, Corvus) treated the whole PTV-horns without sparing any OAR Corvus 6.3 (Best Nomos, USA) is a fully inverse treatment (figure 2). The second rotation around the patient treated planning system that uses a simulated annealing algo- the PTV with permanent shielding of the auxiliary struc- rithm for the beamlet optimization process [25]. Dose cal- ture located between the anterior/lateral PTV-bulges (fig- culation is based on a PB algorithm. ure 3) with a margin of 5 mm between the PTV projection and the leaf edges. After this initial evaluation step, the IMRT (Pencil Beam/Monte Carlo, Hyperion) approach with the best overall plan quality (the dual-rota- Hyperion (University of Tuebingen, Germany [26]) has tion strategy) was evaluated for all 8 treatment planning two major innovative features: evidence-based biological CTs. modelling and X-ray voxel-based Monte Carlo (XVMC) dose computation including multiple photon transport, Treatment devices electron history repetition and continuous boundary IMRT, VMAT and 3D-CRT plans were compted for and crossing used during optimization and final calculation delivered with an Elekta Synergy linear accelerator with [27,28]. The system therefore represents several recent an energy of 6 MV and a dose rate of 600 MU per minute advances in IMRT planning. To evaluate the effect of MC (MU/min). 3D-CRT, step-and-shoot IMRT plans and dose calculation and optimization we generated plans VMAT plans were delivered through the MOSAIQ record- both based on the PB as well as on the MC algorithm. and-verify (R&V) system V1.5 (IMPAC Medical Systems Inc./Elekta) with VMAT plans delivered through the most VMAT (ERGO++) recent release of the console software desktop (V7.0.1). ERGO++ 1.7.1 (3D Line Medical Systems/Elekta) uses a PB algorithm for dose calculation. ERGO++ offers the pos- Plan comparison sibility to adapt the multi-leaf-collimator (MLC) dynami- We compared the calculated dose distributions of all four cally to the target structure during the rotation. Dose rate, planning systems for sagittal, coronal and lateral planes. gantry speed and the collimator angle can be modified The selected patient cases from our database including all during the rotation. For our analysis, however, we used a contours for OAR and PTV were identical for every plan- fixed collimator angle since preliminary studies did not ning system. Specifically, DVH parameters such as mini- suggest an additional gain of optimized collimator angle mal, mean and maximal dose in the PTV and the OAR's as for the PTV geometry studied. The starting point of the well as fractional exposure of non-PTV normal tissue was planning/optimization process is the definition of differ- evaluated. Treatment efficiency was quantified by measur- ent arrangements of the static control points which divide ing/calculating total treatment time (TTT) and MU (beam- the arcs into subarcs and the initial manual MLC adapta- on-time plus time for necessary gantry movements). tion to the target volume. The arc modulation optimiza- Finally, we calculated the homogeneity index (HI) and a tion algorithm AMOA computes the weighting of each modified conformity index (CI) which are objective val- subarc, depending on dose constraints for PTV and each ues to describe how well the dose distribution conforms OAR, and consequently defines the dose rate/MU-number to the shape of a radiosurgical target [29]. The CI was for each subarc. Afterwards the sequencer converts the modified to accommodate the fact, that we prescribed control points into optimized arcs by using predefined dose to the median dose level in the PTV, thus invalidat- rules. ing the classical definition of CI. We therefore defined CI as follows: First we analysed different single-rotation paradigms and a dual-rotation approach on the basis of a typical patient/ VD99% (1) CI = PTV geometry. The single-arc strategies were: one 360° VPTV Page 3 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Two discrete steps during Figure 2 the first rotation without shielding of OAR Two discrete steps during the first rotation without shielding of OAR. with V describing the total volume in cm which Results D99% receives the effective minimal target dose (Dose encom- Evaluation of different VMAT strategies being the target volume Figure 4 shows axial, sagittal and coronal dose distribu- passing 99% of the PTV) and V PTV in cm . This definition of CI has the advantage that the tions (DD) for one selected patient generated by the three value for the minimal dose applied to the target character- different VMAT strategies. The DD differ with regard to izes CI which is in the spirit of the original definition by OAR sparing between the anterior inguinal PTV-exten- RTOG. HI is defined according to the RTOG guidelines as sions, the dose gradient in non-PTV normal tissue, as well follows [30]: as in conformity and homogeneity (figure 4). The '2Rot' strategy provides the best conformity and homogeneity but also the highest dose exposure to the region between Dmax (2) HI = the inguinal PTV extensions (maximum of 28.8 Gy) and Dpresc requires the longest treatment time by using 2 rotations. In contrast, '1RotALLW' creates a steeper dose gradient in with D being the maximum dose in the treatment plan max the normal tissue encompassed by the PTV and thus better and D being the prescription dose. prese Th Figure 3 ree discrete steps during the second rotation with shielding Three discrete steps during the second rotation with shielding. Page 4 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 2Rot 1RotiFo 1RotALLW Dose distributions for differ Figure 4 ent VMAT strategies Dose distributions for different VMAT strategies. Best homogeneity for 2Rot and best conformity and dose sparing in normal tissue for 1RotALLW. protects the anterior OARs (maximum of only 18 Gy). It be expected also with the 2-rotation approach. Since this also exposes non-PTV tissue to lower integral doses and technique provided the best conformity and homogeneity TTT is significantly shorter. Overall conformity and we chose it as the benchmark for the following compari- homogeneity, however, are somewhat inferior due to less son of VMAT with 3D-CRT and fixed beam IMRT. modulation during just one rotation. The third strategy, Comparison of VMAT and other techniques '1RotiFo', represents a mixed solution with intermediate conformity, using only one rotation but providing dose Figure 6 shows the dose display for all treatment modali- homogeneity similar to what is achieved with the '2Rot' ties for a typical patient with the PTV delineated in trans- approach, less dose to the OARs but the highest integral parent red. The VMAT DD's were already shown in figure dose to non-PTV tissue. 4. For all treatment techniques the IRCU50 prescription guidelines (homogeneity -5% and +7% prescription dose DVH analysis (figure 5) showed best PTV coverage for PD) were aimed for but minor deviations had to be '2Rot' with the highest D and the smallest volume accepted as it is usually the case with modulated RT when 99% exposed to high doses. '1RotALLW' was inferior regarding a realistic treatment plan complexity (number of seg- PTV coverage and homogeneity while '1RotiFo' showed ments/rotations) for a treatment plan efficiency that is PTV coverage similar to dual-rotation VMAT. clinically applicable is used. Using our specific treatmtent plan normalization to 50% volume and 50% PD [31], These differences as parametrized by using CI and HI and minor compromises were made on the side of both cover- in addition the differences in dose exposure to fractional age and homogeneity, as reported in table 1. The DD for volumes are displayed in table 1. 3D-CRT shows good homogeneity (no hot or cold spots) but the largest region of non-PTV tissue exposed to high Although treatment time for the 2-rotation strategy was doses. The IMRT Hyperion DD are highly conformal but almost double that of the single-rotation approaches in less homogeneous than 3D-CRT or VMAT "2Rot". Hyper- this example, further preliminary studies showed that this ion provides the option to perform PB as well as MC particular case marked the upper limit of the treatment based optimization/calculation. In PB-based calculations, times and that on average shorter treatment times could lateral scattering and linear attenuation of x-rays in the Page 5 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 VMAT PTV 2 Rot 1 Rot iFo 1 Rot ALLW Small intestine Bladder 0 20406080 100 Dose [% prescribed dose] VMAT VMAT Gonades Left femoral neck Right femoral 40 40 k Tissue - PTV 0 2040 6080 100 0 20 406080 100 Dose [% prescribed dose] Dose [% prescribed dose] OAR and Figure 5 PTV DVH's of the VMAT strategies OAR and PTV DVH's of the VMAT strategies. The VMAT '2Rot' (dotted line, best homogeneity), VMAT '1RotiFo' (solid line) and VMAT '1RotALLW' (dashed line, best dose sparing in OAR and tissue-PTV). patient are not modelled correctly. As consequence, the ity. Best anterior OAR sparing is performed by IMRT PB dose distributions look much smoother and subjec- Hyperion. tively better than MCPB based calculation showing more homogeneous dose distributions than MC. While MC- For DVH generation and comparison (figure 7), all treat- based plans are more precisely reflecting true absorbed ment plans were normalized to 36 Gy to the median dose dose, PB was calculated to provide comparison data on level in the PTV. The highest minimal dose and the lowest the same calculation basis as for the other systems. IMRT maximal dose for the PTV was achieved by 3D-CRT, fol- Corvus DD has the worst homogeneity and less conform- lowed by VMAT "2Rot", IMRT Hyperion and finally IMRT Table 1: DVH parameters for the different VMAT techniques 2Rot 1Rot iFo 1RotALLW HI 1.1 1.1 1.15 CI 1.46 1.54 1.49 MU 287 293 348 TT 370s 185s 188s 3 3 3 V 13414 cm ≡ 38.98% 13643 cm ≡ 39.6% 12456 cm ≡ 36.2% Tissue 10% PD 3 3 3 V 10345 cm ≡ 30.1% 10635 cm ≡ 30.9% 8741 cm ≡ 25.4% Tissue 30% PD 3 3 3 V 7571 cm ≡ 22.0% 8157 cm ≡ 23.7% 5321 cm ≡ 15.5% Tissue 50% PD 3 3 3 V 4089 cm ≡ 11.9% 4735 cm ≡ 13.8% 2727 cm ≡ 7.9% Tissue 70% PD 3 3 3 V 430 cm ≡ 1.2% 370 cm ≡ 1.1% 0 cm ≡ 0% Tissue 95% PD D 33.84 Gy ≡ 94% 33.48 Gy ≡ 93% 32.4 Gy ≡ 90% 95% Vol PTV D 0.75 Gy ≡ 2.09% 0.8 Gy ≡ 2.22% 0.02 Gy ≡ 0.06% 95% Vol Tissue Page 6 of 11 (page number not for citation purposes) Vo lu m e [%] Volume [%] Volume [%] Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Axi with PB (top to bottom) Figure 6 al, coronal and sagittal dose distribution for OTP (3D-CRT), IMRT Hyperion with MC, IMRT Hyperion with PB and Corvus Axial, coronal and sagittal dose distribution for OTP (3D-CRT), IMRT Hyperion with MC, IMRT Hyperion with PB and Corvus with PB (top to bottom). Corvus. The best non-PTV tissue sparing was performed Figure 8 and table 2 indicate the best HI but the worst CI by IMRT Hyperion, the worst by 3D-CRT. Analysing the for 3D-CRT. VMAT and IMRT are similar regarding CI and DVH for bladder, the lowest dose exposure to bladder was HI, consistently for all individual plans. With values of acheived by IMRT Hyperion, followed by VMAT "2Rot" 1.07 to 1.15 for HI (table 2) all planning systems are and almost no sparing with 3D-CRT. The DVH's for small within the RTOG recommendations [30]. intestine show no big differenes. Page 7 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Mod PTV Tissue - PTV 80 80 3D-RT 3D-RT IMRT PB Corvus IMRT PB Corvus IMRT MC Hyperion IMRT MC Hyperion VMAT 40 VMAT IMRT PB Hyperion IMRT PB Hyperion 20 20 0 20406080 100 120 0 2040 6080 100 Dose (% prescri bed dose) Do se (% p r e scr ib e d d o se ) Smal l In tes ti n e Mean Bladder 3D-RT 60 3D-RT IMRT MC Hyperion IMRT MC Hyperion VMAT VMAT 40 IMRT PB Hyperion IMRT PB Hyperion 0 20406080 100 0 20 406080 100 Dose (% prescribed dose) Dose (% prescribed dose) D Figure 7 VH comparison of VMAT '2 Rot', IMRT and 3D-CRT DVH comparison of VMAT '2 Rot', IMRT and 3D-CRT. As parametrized by MU-number and TTT (table 2), 3D- lysed by Milano et al [34]. The group could reduce the CRT and VMAT "2Rot" are the fastest/most efficient tech- radiation dose to normal structures with IMRT and niques. TTT is 50% shorter than for IMRT and mean MU- reported a reduction of acute and late toxicities. On the number is reduced by more than 70%. other hand, the increased delivery time allows the repair of sublethal damage (SLD) in tumour cells and might reduce the biological effect [37,38]. Though the relevance Discussion VMAT combines the advantages of conventional 3D-radi- of this issue is unclear with TTT having been reduced since otherapy (3D-CRT) with its fast delivery and low number the introduction of IMRT and initial reports on dose-pro- of monitor units (MU) and the advantages of IMRT with traction effects [39-41], shortening treatment times to ~5 the conformal dose distribution (DD) and the reduced min will completely obviate this discussion. dose to critical OAR in when target volumes are irradiated according to recently published recommendations [6]. Since we studied a PTV paradigm with a moderate cranial extension we did not explicitly evaluate bone marrow The benefit of IMRT over 3D-CRT regarding high dose sparing in the iliac crest, which is in line with the data of conformity and OAR sparing for pelvic tumors and specif- Menkarios et al., who had extensively discussed the merit ically anal cancer was shown earlier [2,7,32-36]. Chen et of modulated treatment for anal cancer [2]. They had al. compared IMRT and 3D-CRT (AP-PA photons with en- stressed the technical feasibility and potential benefit of face electrons) for anal cancer and they could show that IMRT with regard to bone marrow sparing for PTVs with a while PTV coverage of IMRT and 3D-CRT were compara- high upper limit. Their data, however also shows that for ble, surrounding OAR received less dose exposure with targets with a low upper limit, such as ours, there is no rel- IMRT [7]. Mundt et al and Roeske et al. analysed whole evant exposure of the iliac crest with any of the studied pelvic radiation for gynecologic malignancies and con- techniques. cluded that IMRT reduces the volume of normal tissue receiving high doses [32] resulting in fewer small bowel In our evaluation, VMAT, IMRT and 3D-CRT provide complications [35] while retaining PTV coverage. Toxicity almost the same dose coverage in the target but 3D-CRT and clinical outcome of IMRT for anal cancer was ana- exposes the surrounding tissue and consequently the OAR Page 8 of 11 (page number not for citation purposes) Volume (%) Vol um e (%) Vo lu me (%) Volume (%) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 CI 2.00 1.50 VMAT IMRT PB Corvus 1.00 3D-RT IMRT MC Hyperion IMRT PB Hyperion 0.50 0.00 Patient I Patient II Patient III Patient IV Patient V Patient VI Patient VII Patient VIII HI 1.5 VMAT IMRT PB Corvus 3D-RT IMRT MC Hyperion IMRT PB Hyperion 0.5 Patient I Patient II Patient III Patient IV Patient V Patient VI Patient VII Patient VIII H Figure 8 I and CI for all individual patients HI and CI for all individual patients. to much higher doses. Sparing of bladder and possibly Both single- and multiple-arc approaches are currently small bowel between the inguinal lymph nodes included being established clinically for VMAT, showing similar in the PTV, however, is not adequately achieved by 3D- potential for reducing treatment time when plans of equal CRT. quality are generated [40]. Clinical implementation of these techniques has also prompted reports on appropri- So far, commercial planning systems for IMAT/VMAT are ate QA paradigms [41,42]. a not widely spread and initial data were collected with investigational systems, such as those of the groups from A single-arc therapy approach was devised by Wang et al Beamount Hospital, Ghent and Vancouver. These initial The group used a commercial planning system to opti- reports suggested that VMAT may improve the effiency of mize the intensity profiles of a treatment plan with 36 modulated radiation therapy. Duthoy et al. reported on equi-spaced static beam angles and exported these profiles the feasability of whole abdominopelvic RT using IMAT to an investigational sequencing algorithm to generate a with a low number of MU's (444 MU) [20] and also single-arc plan, recalculated with a MC algorithm that was reported short treatment times (6.3 minutes) for the treat- also developed in-house. They investigated multiple tar- ment of rectal cancer [21]. get locations and found that their arc-modulation-radia- Table 2: Mean TT, MU-number, CI and HI for the three planning systems 3D-CRT VMAT '2Rot' IMRT (MC Hyperion) IMRT (PB Hyperion) IMRT (PB Corvus) HI 1.06 ± 0.02 1.11 ± 0.02 1.11 ± 0.08 1.10 ± 0.02 1.15 ± 0.03 CI 2.00 ± 0.16 1.39 ± 0.09 1.30 ± 0.02 1.26 ± 0.05 1.33 ± 0.21 MU 225 ± 11 268 ± 19 748 ± 193 477 ± 84 1260 ± 172 TT 220s 290s 610s 570s 575s 3 3 3 3 3 V 10739 cm ≡ 48.8% 10463 cm ≡ 47.6% 10806 cm ≡ 48.1% 10347 cm ≡ 46.0% 10591 cm ≡ 47.5% Tissue 10% PD 3 3 3 3 3 V 8187 cm ≡ 37.3% 7674 cm ≡ 34.9% 7593 cm ≡ 33.8% 7199 cm ≡ 32.0% 7874 cm ≡ 35.3% Tissue 30% PD 3 3 3 3 3 V 6052 cm ≡ 27.6% 5089 cm ≡ 23.1% 4203 cm ≡ 18.7% 3971 cm ≡ 17.7% 5186 cm ≡ 23.2% Tissue 50% PD 3 3 3 3 3 V 3428 cm ≡ 15.6% 2734 cm ≡ 12.4% 1939 cm ≡ 8.6% 1933 cm ≡ 8.6% 2612 cm ≡ 11.7% Tissue 70% PD 3 3 3 3 3 V 982 cm ≡ 4.5% 208 cm ≡ 0.9% 14 cm ≡ 0.0% 0 cm ≡ 0.0% 53 cm ≡ 0.2% Tissue 95% PD D 1.97 Gy ≡ 5.46% 0.75 Gy ≡ 2.09% 0.35 Gy ≡ 0.98% 0.31 Gy ≡ 0.85% 0.52 Gy ≡ 1.45% 95% Vol Tissue D 34.09 Gy ≡ 94.7% 33.84 Gy ≡ 94% 33.05 Gy ≡ 91.8% 32.95 Gy ≡ 91.54% 32.33 Gy ≡ 89.8% 95% Vol PTV Page 9 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 tion-therapy (AMRT) paradigm is capable of creating reached a level at which any further discussion about det- conformal treatment plans, comparable to other IMRT rimental effects of treatment protraction [37,38,41] or sec- techniques. A reduction of treatment time by ~50% was ondary tumors due to the higher primary number of MU observed with slightly lower number of MU's for AMRT necessary for modulated therapy [22,43] is futile. [42]. Conclusion Finally, Otto introduced a single arc rotation paradigm VMAT is an efficient treatment modality for large and increasing treatment efficiency by reducing delivery time moderately complex pelvic targets already in its initial to 1.5-3 min which is in the range of what we report in this developmental implementation. While in this situation evaluation. The report was focused on the theoretical dose homogeneity and high dose conformity approach basis and technical details of the approach [22] but for a that of highly modulated fixed beam IMRT, treatment single head-and-neck patient case discussed in his manu- times and MU are further reduced. Further investigations script he reported a treatment time of 107s for VMAT vs. will show how efficient VMAT can handle other target vol- 426s for IMRT with identical dose rate settings. umes and evaluate the delivery accuracy of this complex treatment technique with multiple dynamical changes Palma et al. compared an early prototype of Varian's Rap- during rotation. idArc (Varian Medical Systems, Palo Alto, CA) technique with 3D-CRT and fixed field dynamic IMRT for prostate Competing interests cancer. On a predominantly spherical target, they The authors declare that they have no competing interests. reported, similar to our results, a higher treatment effi- ciency for VMAT (491 MU constant dose rate/454 MU var- Authors' contributions iable dose rate) vs. 789 with IMRT as well shorter FS conceived the experiment design, carried out the exper- treatment times [16], though the absolute level of MU was imental work of the study and drafted the manuscript. higher in their series than in our comparison, reflecting an DW participated in conceiving the study and helped to earlier development stage of both modalities. IMRT and draft the manuscript. VS, FLo and YAM have been VMAT provided better dose distributions than 3D-CRT. A involved in data interpretation. FL and FW have been comparison of non-PTV tissue was not performed and can involved in data interpretation and drafting the manu- therefore not be assessed. script. SM participated in conceiving the study and helped drafting the manuscript. All authors read and approved The most recent report was provided by Cozzi et al. using the final manuscript. an improved version of the RapidArc prototype but with focus on a larger PTV (cervix uteri). They reported a simi- Acknowledgements We gratefully acknowledge the help of Dr. Markus Alber with the imple- lar PTV coverage of VMAT (single rotation, variable dose mentation of Hyperion. We are also indebted to Roberto Pellegrini, rate: up to 600 MU/Min) and IMRT (sliding window, 5 Manuela Duglio, Yvette Bellingham and Nick Linton of 3D-Line/Elekta and beams, fixed dose rate: 300 MU/min) with improved Alison Metcalf/Kevin Brown of Elekta for the close collaboration during the homogeneity, better conformity and a major reduction of implementation and initial evaluation of ERGO++ and VMAT. This work OAR irradiation. Our results showed identical homogene- was supported within the framework of a Research Cooperation Agree- ity for IMRT and VMAT but higher conformity of the IMRT ment between the Department of Radiation Oncology, Mannheim Univer- approach. Although a detailed comparative analysis of the sity Medical Center and Elekta. two series is not possible, this difference is most likely a consequence of the higher number of incident beams - References 1. Tournier-Rangeard L, Mercier M, Peiffert D, Gerard JP, Romestaing P, and possibly more modulation - used in our comparison. Lemanski C, Mirabel X, Pommier P, Denis B: Radiochemotherapy The different geometry of the PTV might also factor in of locally advanced anal canal carcinoma: prospective assess- (PTV encompassing pelvic nodes only in their series vs. ment of early impact on the quality of life (randomized trial ACCORD 03). Radiother Oncol 2008, 87(3):391-7. pelvic and inguinal nodes in ours). Cozzi et al. reported 2. 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Dobler B, Lorenz F, Wertz H, Polednik M, Wolff D, Steil V, Lohr F, Your research papers will be: Wenz F: Intensity-modulated radiation therapy (IMRT) with available free of charge to the entire biomedical community different combinations of treatment-planning systems and linacs: issues and how to detect them. Strahlenther Onkol 2006, peer reviewed and published immediately upon acceptance 182(8):481-8. cited in PubMed and archived on PubMed Central 26. Alber M, Birkner M, Laub W, Nüsslin F: Hyperion: an integrated IMRT planning tool. Proceedings of the XIII Conference on yours — you keep the copyright the use of computers in radiation therapy. Springer, Heidel- BioMedcentral berg; 2000:46-48. Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 11 of 11 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT)

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Springer Journals
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Copyright © 2009 by Stieler 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-4-48
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19852856
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Abstract

Background/Purpose: Radiotherapy (RT) volumes for anal cancer are large and of moderate complexity when organs at risk (OAR) such as testis, small bowel and bladder are at least partially to be shielded. Volumetric intensity modulated arc therapy (VMAT) might provide OAR-shielding comparable to step-and-shoot intensity modulated radiotherapy (IMRT) for this tumor entity with better treatment efficiency. Materials and methods: Based on treatment planning CTs of 8 patients, we compared dose distributions, comformality index (CI), homogeneity index (HI), number of monitor units (MU) and treatment time (TTT) for plans generated for VMAT, 3D-CRT and step-and-shoot-IMRT (optimized based on Pencil Beam (PB) or Monte Carlo (MC) dose calculation) for typical anal cancer planning target volumes (PTV) including inguinal lymph nodes as usually treated during the first phase (0-36 Gy) of a shrinking field regimen. Results: With values of 1.33 ± 0.21/1.26 ± 0.05/1.3 ± 0.02 and 1.39 ± 0.09, the CI's for IMRT (PB- Corvus/PB-Hyperion/MC-Hyperion) and VMAT are better than for 3D-CRT with 2.00 ± 0.16. The HI's for the prescribed dose (HI36) for 3D-CRT were 1.06 ± 0.01 and 1.11 ± 0.02 for VMAT, respectively and 1.15 ± 0.02/1.10 ± 0.02/1.11 ± 0.08 for IMRT (PB-Corvus/PB-Hyperion/MC- Hyperion). Mean TTT and MU's for 3D-CRT is 220s/225 ± 11MU and for IMRT (PB-Corvus/PB- Hyperion/MC-Hyperion) is 575s/1260 ± 172MU, 570s/477 ± 84MU and 610s748 ± 193MU while TTT and MU for two-arc-VMAT is 290s/268 ± 19MU. Conclusion: VMAT provides treatment plans with high conformity and homogeneity equivalent to step-and-shoot-IMRT for this mono-concave treatment volume. Short treatment delivery time and low primary MU are the most important advantages. Page 1 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 to segment on calculated fluences, VMAT on the other Introduction Coverage of large planning target volumes (PTV) as they hand segments on given structures. Several research are treated during the initial part of the protocols for anal groups developed their own IMAT solutions in order to cancer is difficult because protection of critical organs is study and exploit its potential for the reduction of treat- important for the patient's quality of life (QOL) [1]. Until ment time and MU while increasing the number of inci- recently, the standard approach has been three dimen- dent beam directions [15-19], with large target volumes sional conformal radiotherapy (3D-CRT), typically using such as encountered with whole abdominopelvic radio- a 4-field box technique [2]. The target volume for anal therapy (WAPRT) being particularly in the focus of the cancer is currently actively being discussed and a consen- group from Ghent [20,21]. sus document has recently been published by the RTOG [3]. It is, however, not a consequence of specific clinical Only recently commercial treatment planning systems data but the result of a highly subjective approach (super- (TPS) were released for modulated arc therapy. Otto intro- position of targets drawn by several individuals) and duced a single-arc VMAT approach [22] that formed the issues such as vaginal sparing still require cautious evalu- basis for RapidArc (Varian Medical Systems, USA) that in ation. The PTV therefore still ususally comprises primary its first clinical commercial implementation was then tumor and lower external and internal iliac lymph nodes. evaluated by Cozzi et. al[23] and Palma et. al [16]. Medial inguinal lymph nodes are usually treated up to at ERGO++ (Elekta, Sweden) has been released in parallel as least 30.6-36 Gy [4,5] and in case of involvement higher a commercial VMAT system and was evaluated in this doses are required (50.4-54 Gy). Treating inguinal lymph study. To provide comprehensive data, VMAT was com- nodes and pelvic lymph nodes simultaneously leads to a pared with a complex 3D-CRT technique (6 fields) and mean PTV size of more than 2.750 cm as exemplified in step-and-shoot IMRT including Monte Carlo and Pencil figure 1 and such relatively large PTVs are still considered Beam calculation. Several strategies (single and dual rota- appropriate in recent reviews [6]. Previous studies showed tions) were computed, and analysed with regard to dose- that IMRT provides PTV coverage similar to conventional volume-histograms (DVH), homogeneity, conformity, techniques and at the same time efficiently spares OAR exposure of OAR and treatment efficiency (treatment time [7]. On the downside, however, IMRT resulted in longer and monitor units). treatment time and a higher number of monitor units (MU). While step-and-shoot IMRT has become more effi- Methods and materials cient recently [8-10] rotational modulated therapy may be Patient anatomy another approach to improve these parameters [11,12]. Eight CT datasets of patients treated at our department for Volumetric modulated arc therapy (VMAT) is based on anal cancer were the basis for this study. The PTV was typ- the intensity modulated arc therapy (IMAT) paradigm, ical for the initial treatment series including the primary first described by Yu et. al [13,14]. The basic IMAT idea is tumor, pelvic and inguinal lymph nodes (figure 1). It is to be treated at daily doses of 1.8 Gy to a cumulative dose of 36 Gy. In patients without involved inguinal lymph nodes, the PTV would then be reduced to a typical pelvic PTV without coverage of inguinal lymph nodes. Finally, a boost would be delivered to the primary tumor, its dose depending on tumor size. Since the initial PTV used in all patients was the most complex one, evaluation of VMAT is only done in this context. Bladder, small intestine, gonads and femoral heads were contoured as OAR. A wedge-shaped anterior auxiliary structure was generated to facilitate the planning process. Treatment planning systems 3D-CRT (Masterplan) 3D-CRT-plans were generated with Masterplan 3.1 (Nucletron, The Netherlands). The field geometry con- sisted of 6 fields as suggested by Götz and Kiricuta [24]. A standard 4 field box treated at an energy of 23 MV and A Figure 1 xial CT for 3D-CRT with PTV and 6 beams beam angles of 0/87/180/273 degrees was supplemented Axial CT for 3D-CRT with PTV and 6 beams. by 2 oblique auxiliary fields (energy 6 MV) from 30 and Page 2 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 330 degrees, both with 30 degree wedges (figure 1). These rotation conforming the collimator to the PTV with additional beams cover the inguinal extensions of the PTV shielding of the auxiliary structure when it is in front of in the anterior/lateral direction. Dose is calculated based the PTV ('1RotiFo') and one 360° rotation on the PTV on a pencil beam (PB) algorithm. with full shielding of the auxiliary structure ('1RotALLW'). IMRT Treatment Planning The primary beam setup for the step-and-shoot approach The dual-rotation strategy ('2Rot') used two rotations consisted of 9 isotropic nonopposing coplanar beams, with a starting angle of 181° and a stop angle of 179° both for treatment plans generated with Corvus and each (total of 358°/rotation). These two arcs are subdi- Hyperion. vided into 72 subarcs for each rotation which results in one control point every 5 degrees. The first rotation IMRT (Pencil Beam, Corvus) treated the whole PTV-horns without sparing any OAR Corvus 6.3 (Best Nomos, USA) is a fully inverse treatment (figure 2). The second rotation around the patient treated planning system that uses a simulated annealing algo- the PTV with permanent shielding of the auxiliary struc- rithm for the beamlet optimization process [25]. Dose cal- ture located between the anterior/lateral PTV-bulges (fig- culation is based on a PB algorithm. ure 3) with a margin of 5 mm between the PTV projection and the leaf edges. After this initial evaluation step, the IMRT (Pencil Beam/Monte Carlo, Hyperion) approach with the best overall plan quality (the dual-rota- Hyperion (University of Tuebingen, Germany [26]) has tion strategy) was evaluated for all 8 treatment planning two major innovative features: evidence-based biological CTs. modelling and X-ray voxel-based Monte Carlo (XVMC) dose computation including multiple photon transport, Treatment devices electron history repetition and continuous boundary IMRT, VMAT and 3D-CRT plans were compted for and crossing used during optimization and final calculation delivered with an Elekta Synergy linear accelerator with [27,28]. The system therefore represents several recent an energy of 6 MV and a dose rate of 600 MU per minute advances in IMRT planning. To evaluate the effect of MC (MU/min). 3D-CRT, step-and-shoot IMRT plans and dose calculation and optimization we generated plans VMAT plans were delivered through the MOSAIQ record- both based on the PB as well as on the MC algorithm. and-verify (R&V) system V1.5 (IMPAC Medical Systems Inc./Elekta) with VMAT plans delivered through the most VMAT (ERGO++) recent release of the console software desktop (V7.0.1). ERGO++ 1.7.1 (3D Line Medical Systems/Elekta) uses a PB algorithm for dose calculation. ERGO++ offers the pos- Plan comparison sibility to adapt the multi-leaf-collimator (MLC) dynami- We compared the calculated dose distributions of all four cally to the target structure during the rotation. Dose rate, planning systems for sagittal, coronal and lateral planes. gantry speed and the collimator angle can be modified The selected patient cases from our database including all during the rotation. For our analysis, however, we used a contours for OAR and PTV were identical for every plan- fixed collimator angle since preliminary studies did not ning system. Specifically, DVH parameters such as mini- suggest an additional gain of optimized collimator angle mal, mean and maximal dose in the PTV and the OAR's as for the PTV geometry studied. The starting point of the well as fractional exposure of non-PTV normal tissue was planning/optimization process is the definition of differ- evaluated. Treatment efficiency was quantified by measur- ent arrangements of the static control points which divide ing/calculating total treatment time (TTT) and MU (beam- the arcs into subarcs and the initial manual MLC adapta- on-time plus time for necessary gantry movements). tion to the target volume. The arc modulation optimiza- Finally, we calculated the homogeneity index (HI) and a tion algorithm AMOA computes the weighting of each modified conformity index (CI) which are objective val- subarc, depending on dose constraints for PTV and each ues to describe how well the dose distribution conforms OAR, and consequently defines the dose rate/MU-number to the shape of a radiosurgical target [29]. The CI was for each subarc. Afterwards the sequencer converts the modified to accommodate the fact, that we prescribed control points into optimized arcs by using predefined dose to the median dose level in the PTV, thus invalidat- rules. ing the classical definition of CI. We therefore defined CI as follows: First we analysed different single-rotation paradigms and a dual-rotation approach on the basis of a typical patient/ VD99% (1) CI = PTV geometry. The single-arc strategies were: one 360° VPTV Page 3 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Two discrete steps during Figure 2 the first rotation without shielding of OAR Two discrete steps during the first rotation without shielding of OAR. with V describing the total volume in cm which Results D99% receives the effective minimal target dose (Dose encom- Evaluation of different VMAT strategies being the target volume Figure 4 shows axial, sagittal and coronal dose distribu- passing 99% of the PTV) and V PTV in cm . This definition of CI has the advantage that the tions (DD) for one selected patient generated by the three value for the minimal dose applied to the target character- different VMAT strategies. The DD differ with regard to izes CI which is in the spirit of the original definition by OAR sparing between the anterior inguinal PTV-exten- RTOG. HI is defined according to the RTOG guidelines as sions, the dose gradient in non-PTV normal tissue, as well follows [30]: as in conformity and homogeneity (figure 4). The '2Rot' strategy provides the best conformity and homogeneity but also the highest dose exposure to the region between Dmax (2) HI = the inguinal PTV extensions (maximum of 28.8 Gy) and Dpresc requires the longest treatment time by using 2 rotations. In contrast, '1RotALLW' creates a steeper dose gradient in with D being the maximum dose in the treatment plan max the normal tissue encompassed by the PTV and thus better and D being the prescription dose. prese Th Figure 3 ree discrete steps during the second rotation with shielding Three discrete steps during the second rotation with shielding. Page 4 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 2Rot 1RotiFo 1RotALLW Dose distributions for differ Figure 4 ent VMAT strategies Dose distributions for different VMAT strategies. Best homogeneity for 2Rot and best conformity and dose sparing in normal tissue for 1RotALLW. protects the anterior OARs (maximum of only 18 Gy). It be expected also with the 2-rotation approach. Since this also exposes non-PTV tissue to lower integral doses and technique provided the best conformity and homogeneity TTT is significantly shorter. Overall conformity and we chose it as the benchmark for the following compari- homogeneity, however, are somewhat inferior due to less son of VMAT with 3D-CRT and fixed beam IMRT. modulation during just one rotation. The third strategy, Comparison of VMAT and other techniques '1RotiFo', represents a mixed solution with intermediate conformity, using only one rotation but providing dose Figure 6 shows the dose display for all treatment modali- homogeneity similar to what is achieved with the '2Rot' ties for a typical patient with the PTV delineated in trans- approach, less dose to the OARs but the highest integral parent red. The VMAT DD's were already shown in figure dose to non-PTV tissue. 4. For all treatment techniques the IRCU50 prescription guidelines (homogeneity -5% and +7% prescription dose DVH analysis (figure 5) showed best PTV coverage for PD) were aimed for but minor deviations had to be '2Rot' with the highest D and the smallest volume accepted as it is usually the case with modulated RT when 99% exposed to high doses. '1RotALLW' was inferior regarding a realistic treatment plan complexity (number of seg- PTV coverage and homogeneity while '1RotiFo' showed ments/rotations) for a treatment plan efficiency that is PTV coverage similar to dual-rotation VMAT. clinically applicable is used. Using our specific treatmtent plan normalization to 50% volume and 50% PD [31], These differences as parametrized by using CI and HI and minor compromises were made on the side of both cover- in addition the differences in dose exposure to fractional age and homogeneity, as reported in table 1. The DD for volumes are displayed in table 1. 3D-CRT shows good homogeneity (no hot or cold spots) but the largest region of non-PTV tissue exposed to high Although treatment time for the 2-rotation strategy was doses. The IMRT Hyperion DD are highly conformal but almost double that of the single-rotation approaches in less homogeneous than 3D-CRT or VMAT "2Rot". Hyper- this example, further preliminary studies showed that this ion provides the option to perform PB as well as MC particular case marked the upper limit of the treatment based optimization/calculation. In PB-based calculations, times and that on average shorter treatment times could lateral scattering and linear attenuation of x-rays in the Page 5 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 VMAT PTV 2 Rot 1 Rot iFo 1 Rot ALLW Small intestine Bladder 0 20406080 100 Dose [% prescribed dose] VMAT VMAT Gonades Left femoral neck Right femoral 40 40 k Tissue - PTV 0 2040 6080 100 0 20 406080 100 Dose [% prescribed dose] Dose [% prescribed dose] OAR and Figure 5 PTV DVH's of the VMAT strategies OAR and PTV DVH's of the VMAT strategies. The VMAT '2Rot' (dotted line, best homogeneity), VMAT '1RotiFo' (solid line) and VMAT '1RotALLW' (dashed line, best dose sparing in OAR and tissue-PTV). patient are not modelled correctly. As consequence, the ity. Best anterior OAR sparing is performed by IMRT PB dose distributions look much smoother and subjec- Hyperion. tively better than MCPB based calculation showing more homogeneous dose distributions than MC. While MC- For DVH generation and comparison (figure 7), all treat- based plans are more precisely reflecting true absorbed ment plans were normalized to 36 Gy to the median dose dose, PB was calculated to provide comparison data on level in the PTV. The highest minimal dose and the lowest the same calculation basis as for the other systems. IMRT maximal dose for the PTV was achieved by 3D-CRT, fol- Corvus DD has the worst homogeneity and less conform- lowed by VMAT "2Rot", IMRT Hyperion and finally IMRT Table 1: DVH parameters for the different VMAT techniques 2Rot 1Rot iFo 1RotALLW HI 1.1 1.1 1.15 CI 1.46 1.54 1.49 MU 287 293 348 TT 370s 185s 188s 3 3 3 V 13414 cm ≡ 38.98% 13643 cm ≡ 39.6% 12456 cm ≡ 36.2% Tissue 10% PD 3 3 3 V 10345 cm ≡ 30.1% 10635 cm ≡ 30.9% 8741 cm ≡ 25.4% Tissue 30% PD 3 3 3 V 7571 cm ≡ 22.0% 8157 cm ≡ 23.7% 5321 cm ≡ 15.5% Tissue 50% PD 3 3 3 V 4089 cm ≡ 11.9% 4735 cm ≡ 13.8% 2727 cm ≡ 7.9% Tissue 70% PD 3 3 3 V 430 cm ≡ 1.2% 370 cm ≡ 1.1% 0 cm ≡ 0% Tissue 95% PD D 33.84 Gy ≡ 94% 33.48 Gy ≡ 93% 32.4 Gy ≡ 90% 95% Vol PTV D 0.75 Gy ≡ 2.09% 0.8 Gy ≡ 2.22% 0.02 Gy ≡ 0.06% 95% Vol Tissue Page 6 of 11 (page number not for citation purposes) Vo lu m e [%] Volume [%] Volume [%] Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Axi with PB (top to bottom) Figure 6 al, coronal and sagittal dose distribution for OTP (3D-CRT), IMRT Hyperion with MC, IMRT Hyperion with PB and Corvus Axial, coronal and sagittal dose distribution for OTP (3D-CRT), IMRT Hyperion with MC, IMRT Hyperion with PB and Corvus with PB (top to bottom). Corvus. The best non-PTV tissue sparing was performed Figure 8 and table 2 indicate the best HI but the worst CI by IMRT Hyperion, the worst by 3D-CRT. Analysing the for 3D-CRT. VMAT and IMRT are similar regarding CI and DVH for bladder, the lowest dose exposure to bladder was HI, consistently for all individual plans. With values of acheived by IMRT Hyperion, followed by VMAT "2Rot" 1.07 to 1.15 for HI (table 2) all planning systems are and almost no sparing with 3D-CRT. The DVH's for small within the RTOG recommendations [30]. intestine show no big differenes. Page 7 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 Mod PTV Tissue - PTV 80 80 3D-RT 3D-RT IMRT PB Corvus IMRT PB Corvus IMRT MC Hyperion IMRT MC Hyperion VMAT 40 VMAT IMRT PB Hyperion IMRT PB Hyperion 20 20 0 20406080 100 120 0 2040 6080 100 Dose (% prescri bed dose) Do se (% p r e scr ib e d d o se ) Smal l In tes ti n e Mean Bladder 3D-RT 60 3D-RT IMRT MC Hyperion IMRT MC Hyperion VMAT VMAT 40 IMRT PB Hyperion IMRT PB Hyperion 0 20406080 100 0 20 406080 100 Dose (% prescribed dose) Dose (% prescribed dose) D Figure 7 VH comparison of VMAT '2 Rot', IMRT and 3D-CRT DVH comparison of VMAT '2 Rot', IMRT and 3D-CRT. As parametrized by MU-number and TTT (table 2), 3D- lysed by Milano et al [34]. The group could reduce the CRT and VMAT "2Rot" are the fastest/most efficient tech- radiation dose to normal structures with IMRT and niques. TTT is 50% shorter than for IMRT and mean MU- reported a reduction of acute and late toxicities. On the number is reduced by more than 70%. other hand, the increased delivery time allows the repair of sublethal damage (SLD) in tumour cells and might reduce the biological effect [37,38]. Though the relevance Discussion VMAT combines the advantages of conventional 3D-radi- of this issue is unclear with TTT having been reduced since otherapy (3D-CRT) with its fast delivery and low number the introduction of IMRT and initial reports on dose-pro- of monitor units (MU) and the advantages of IMRT with traction effects [39-41], shortening treatment times to ~5 the conformal dose distribution (DD) and the reduced min will completely obviate this discussion. dose to critical OAR in when target volumes are irradiated according to recently published recommendations [6]. Since we studied a PTV paradigm with a moderate cranial extension we did not explicitly evaluate bone marrow The benefit of IMRT over 3D-CRT regarding high dose sparing in the iliac crest, which is in line with the data of conformity and OAR sparing for pelvic tumors and specif- Menkarios et al., who had extensively discussed the merit ically anal cancer was shown earlier [2,7,32-36]. Chen et of modulated treatment for anal cancer [2]. They had al. compared IMRT and 3D-CRT (AP-PA photons with en- stressed the technical feasibility and potential benefit of face electrons) for anal cancer and they could show that IMRT with regard to bone marrow sparing for PTVs with a while PTV coverage of IMRT and 3D-CRT were compara- high upper limit. Their data, however also shows that for ble, surrounding OAR received less dose exposure with targets with a low upper limit, such as ours, there is no rel- IMRT [7]. Mundt et al and Roeske et al. analysed whole evant exposure of the iliac crest with any of the studied pelvic radiation for gynecologic malignancies and con- techniques. cluded that IMRT reduces the volume of normal tissue receiving high doses [32] resulting in fewer small bowel In our evaluation, VMAT, IMRT and 3D-CRT provide complications [35] while retaining PTV coverage. Toxicity almost the same dose coverage in the target but 3D-CRT and clinical outcome of IMRT for anal cancer was ana- exposes the surrounding tissue and consequently the OAR Page 8 of 11 (page number not for citation purposes) Volume (%) Vol um e (%) Vo lu me (%) Volume (%) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 CI 2.00 1.50 VMAT IMRT PB Corvus 1.00 3D-RT IMRT MC Hyperion IMRT PB Hyperion 0.50 0.00 Patient I Patient II Patient III Patient IV Patient V Patient VI Patient VII Patient VIII HI 1.5 VMAT IMRT PB Corvus 3D-RT IMRT MC Hyperion IMRT PB Hyperion 0.5 Patient I Patient II Patient III Patient IV Patient V Patient VI Patient VII Patient VIII H Figure 8 I and CI for all individual patients HI and CI for all individual patients. to much higher doses. Sparing of bladder and possibly Both single- and multiple-arc approaches are currently small bowel between the inguinal lymph nodes included being established clinically for VMAT, showing similar in the PTV, however, is not adequately achieved by 3D- potential for reducing treatment time when plans of equal CRT. quality are generated [40]. Clinical implementation of these techniques has also prompted reports on appropri- So far, commercial planning systems for IMAT/VMAT are ate QA paradigms [41,42]. a not widely spread and initial data were collected with investigational systems, such as those of the groups from A single-arc therapy approach was devised by Wang et al Beamount Hospital, Ghent and Vancouver. These initial The group used a commercial planning system to opti- reports suggested that VMAT may improve the effiency of mize the intensity profiles of a treatment plan with 36 modulated radiation therapy. Duthoy et al. reported on equi-spaced static beam angles and exported these profiles the feasability of whole abdominopelvic RT using IMAT to an investigational sequencing algorithm to generate a with a low number of MU's (444 MU) [20] and also single-arc plan, recalculated with a MC algorithm that was reported short treatment times (6.3 minutes) for the treat- also developed in-house. They investigated multiple tar- ment of rectal cancer [21]. get locations and found that their arc-modulation-radia- Table 2: Mean TT, MU-number, CI and HI for the three planning systems 3D-CRT VMAT '2Rot' IMRT (MC Hyperion) IMRT (PB Hyperion) IMRT (PB Corvus) HI 1.06 ± 0.02 1.11 ± 0.02 1.11 ± 0.08 1.10 ± 0.02 1.15 ± 0.03 CI 2.00 ± 0.16 1.39 ± 0.09 1.30 ± 0.02 1.26 ± 0.05 1.33 ± 0.21 MU 225 ± 11 268 ± 19 748 ± 193 477 ± 84 1260 ± 172 TT 220s 290s 610s 570s 575s 3 3 3 3 3 V 10739 cm ≡ 48.8% 10463 cm ≡ 47.6% 10806 cm ≡ 48.1% 10347 cm ≡ 46.0% 10591 cm ≡ 47.5% Tissue 10% PD 3 3 3 3 3 V 8187 cm ≡ 37.3% 7674 cm ≡ 34.9% 7593 cm ≡ 33.8% 7199 cm ≡ 32.0% 7874 cm ≡ 35.3% Tissue 30% PD 3 3 3 3 3 V 6052 cm ≡ 27.6% 5089 cm ≡ 23.1% 4203 cm ≡ 18.7% 3971 cm ≡ 17.7% 5186 cm ≡ 23.2% Tissue 50% PD 3 3 3 3 3 V 3428 cm ≡ 15.6% 2734 cm ≡ 12.4% 1939 cm ≡ 8.6% 1933 cm ≡ 8.6% 2612 cm ≡ 11.7% Tissue 70% PD 3 3 3 3 3 V 982 cm ≡ 4.5% 208 cm ≡ 0.9% 14 cm ≡ 0.0% 0 cm ≡ 0.0% 53 cm ≡ 0.2% Tissue 95% PD D 1.97 Gy ≡ 5.46% 0.75 Gy ≡ 2.09% 0.35 Gy ≡ 0.98% 0.31 Gy ≡ 0.85% 0.52 Gy ≡ 1.45% 95% Vol Tissue D 34.09 Gy ≡ 94.7% 33.84 Gy ≡ 94% 33.05 Gy ≡ 91.8% 32.95 Gy ≡ 91.54% 32.33 Gy ≡ 89.8% 95% Vol PTV Page 9 of 11 (page number not for citation purposes) Radiation Oncology 2009, 4:48 http://www.ro-journal.com/content/4/1/48 tion-therapy (AMRT) paradigm is capable of creating reached a level at which any further discussion about det- conformal treatment plans, comparable to other IMRT rimental effects of treatment protraction [37,38,41] or sec- techniques. A reduction of treatment time by ~50% was ondary tumors due to the higher primary number of MU observed with slightly lower number of MU's for AMRT necessary for modulated therapy [22,43] is futile. [42]. Conclusion Finally, Otto introduced a single arc rotation paradigm VMAT is an efficient treatment modality for large and increasing treatment efficiency by reducing delivery time moderately complex pelvic targets already in its initial to 1.5-3 min which is in the range of what we report in this developmental implementation. While in this situation evaluation. The report was focused on the theoretical dose homogeneity and high dose conformity approach basis and technical details of the approach [22] but for a that of highly modulated fixed beam IMRT, treatment single head-and-neck patient case discussed in his manu- times and MU are further reduced. Further investigations script he reported a treatment time of 107s for VMAT vs. will show how efficient VMAT can handle other target vol- 426s for IMRT with identical dose rate settings. umes and evaluate the delivery accuracy of this complex treatment technique with multiple dynamical changes Palma et al. compared an early prototype of Varian's Rap- during rotation. idArc (Varian Medical Systems, Palo Alto, CA) technique with 3D-CRT and fixed field dynamic IMRT for prostate Competing interests cancer. On a predominantly spherical target, they The authors declare that they have no competing interests. reported, similar to our results, a higher treatment effi- ciency for VMAT (491 MU constant dose rate/454 MU var- Authors' contributions iable dose rate) vs. 789 with IMRT as well shorter FS conceived the experiment design, carried out the exper- treatment times [16], though the absolute level of MU was imental work of the study and drafted the manuscript. higher in their series than in our comparison, reflecting an DW participated in conceiving the study and helped to earlier development stage of both modalities. IMRT and draft the manuscript. VS, FLo and YAM have been VMAT provided better dose distributions than 3D-CRT. A involved in data interpretation. FL and FW have been comparison of non-PTV tissue was not performed and can involved in data interpretation and drafting the manu- therefore not be assessed. script. SM participated in conceiving the study and helped drafting the manuscript. All authors read and approved The most recent report was provided by Cozzi et al. using the final manuscript. an improved version of the RapidArc prototype but with focus on a larger PTV (cervix uteri). They reported a simi- Acknowledgements We gratefully acknowledge the help of Dr. Markus Alber with the imple- lar PTV coverage of VMAT (single rotation, variable dose mentation of Hyperion. We are also indebted to Roberto Pellegrini, rate: up to 600 MU/Min) and IMRT (sliding window, 5 Manuela Duglio, Yvette Bellingham and Nick Linton of 3D-Line/Elekta and beams, fixed dose rate: 300 MU/min) with improved Alison Metcalf/Kevin Brown of Elekta for the close collaboration during the homogeneity, better conformity and a major reduction of implementation and initial evaluation of ERGO++ and VMAT. This work OAR irradiation. 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Dobler B, Lorenz F, Wertz H, Polednik M, Wolff D, Steil V, Lohr F, Your research papers will be: Wenz F: Intensity-modulated radiation therapy (IMRT) with available free of charge to the entire biomedical community different combinations of treatment-planning systems and linacs: issues and how to detect them. Strahlenther Onkol 2006, peer reviewed and published immediately upon acceptance 182(8):481-8. cited in PubMed and archived on PubMed Central 26. Alber M, Birkner M, Laub W, Nüsslin F: Hyperion: an integrated IMRT planning tool. Proceedings of the XIII Conference on yours — you keep the copyright the use of computers in radiation therapy. Springer, Heidel- BioMedcentral berg; 2000:46-48. Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 11 of 11 (page number not for citation purposes)

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