A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT)
© Stieler et al; licensee BioMed Central Ltd. 2009
Received: 15 July 2009
Accepted: 25 October 2009
Published: 25 October 2009
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.
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.
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.
Only recently commercial treatment planning systems (TPS) were released for modulated arc therapy. Otto introduced a single-arc VMAT approach  that formed the basis for RapidArc© (Varian Medical Systems, USA) that in its first clinical commercial implementation was then evaluated by Cozzi et. al and Palma et. al . ERGO++ (Elekta, Sweden) has been released in parallel as a commercial VMAT system and was evaluated in this study. To provide comprehensive data, VMAT was compared with a complex 3D-CRT technique (6 fields) and step-and-shoot IMRT including Monte Carlo and Pencil Beam calculation. Several strategies (single and dual rotations) were computed, and analysed with regard to dose-volume-histograms (DVH), homogeneity, conformity, exposure of OAR and treatment efficiency (treatment time and monitor units).
Methods and materials
Eight CT datasets of patients treated at our department for anal cancer were the basis for this study. The PTV was typical for the initial treatment series including the primary 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-plans were generated with Masterplan 3.1 (Nucletron, The Netherlands). The field geometry consisted of 6 fields as suggested by Götz and Kiricuta . A standard 4 field box treated at an energy of 23 MV and beam angles of 0/87/180/273 degrees was supplemented by 2 oblique auxiliary fields (energy 6 MV) from 30 and 330 degrees, both with 30 degree wedges (figure 1). These additional beams cover the inguinal extensions of the PTV in the anterior/lateral direction. Dose is calculated based on a pencil beam (PB) algorithm.
IMRT Treatment Planning
The primary beam setup for the step-and-shoot approach consisted of 9 isotropic nonopposing coplanar beams, both for treatment plans generated with Corvus and Hyperion.
IMRT (Pencil Beam, Corvus)
Corvus 6.3 (Best Nomos, USA) is a fully inverse treatment planning system that uses a simulated annealing algorithm for the beamlet optimization process . Dose calculation is based on a PB algorithm.
IMRT (Pencil Beam/Monte Carlo, Hyperion)
Hyperion (University of Tuebingen, Germany ) has two major innovative features: evidence-based biological modelling and X-ray voxel-based Monte Carlo (XVMC) dose computation including multiple photon transport, electron history repetition and continuous boundary crossing used during optimization and final calculation [27, 28]. The system therefore represents several recent advances in IMRT planning. To evaluate the effect of MC dose calculation and optimization we generated plans both based on the PB as well as on the MC algorithm.
ERGO++ 1.7.1 (3D Line Medical Systems/Elekta) uses a PB algorithm for dose calculation. ERGO++ offers the possibility to adapt the multi-leaf-collimator (MLC) dynamically to the target structure during the rotation. Dose rate, gantry speed and the collimator angle can be modified during the rotation. For our analysis, however, we used a fixed collimator angle since preliminary studies did not suggest an additional gain of optimized collimator angle for the PTV geometry studied. The starting point of the planning/optimization process is the definition of different arrangements of the static control points which divide the arcs into subarcs and the initial manual MLC adaptation to the target volume. The arc modulation optimization algorithm AMOA computes the weighting of each subarc, depending on dose constraints for PTV and each OAR, and consequently defines the dose rate/MU-number for each subarc. Afterwards the sequencer converts the control points into optimized arcs by using predefined rules.
First we analysed different single-rotation paradigms and a dual-rotation approach on the basis of a typical patient/PTV geometry. The single-arc strategies were: one 360° rotation conforming the collimator to the PTV with shielding of the auxiliary structure when it is in front of the PTV ('1RotiFo') and one 360° rotation on the PTV with full shielding of the auxiliary structure ('1RotALLW').
IMRT, VMAT and 3D-CRT plans were compted for and delivered with an Elekta Synergy® linear accelerator with an energy of 6 MV and a dose rate of 600 MU per minute (MU/min). 3D-CRT, step-and-shoot IMRT plans and VMAT plans were delivered through the MOSAIQ record-and-verify (R&V) system V1.5 (IMPAC Medical Systems Inc./Elekta) with VMAT plans delivered through the most recent release of the console software desktop (V7.0.1).
with Dmax being the maximum dose in the treatment plan and Dprese being the prescription dose.
Evaluation of different VMAT strategies
DVH parameters for the different VMAT techniques
VTissue 10% PD
13414 cm3 ≡ 38.98%
13643 cm3 ≡ 39.6%
12456 cm3 ≡ 36.2%
VTissue 30% PD
10345 cm3 ≡ 30.1%
10635 cm3 ≡ 30.9%
8741 cm3 ≡ 25.4%
VTissue 50% PD
7571 cm3 ≡ 22.0%
8157 cm3 ≡ 23.7%
5321 cm3 ≡ 15.5%
VTissue 70% PD
4089 cm3 ≡ 11.9%
4735 cm3 ≡ 13.8%
2727 cm3 ≡ 7.9%
VTissue 95% PD
430 cm3 ≡ 1.2%
370 cm3 ≡ 1.1%
0 cm3 ≡ 0%
D95% Vol PTV
33.84 Gy ≡ 94%
33.48 Gy ≡ 93%
32.4 Gy ≡ 90%
D95% Vol Tissue
0.75 Gy ≡ 2.09%
0.8 Gy ≡ 2.22%
0.02 Gy ≡ 0.06%
Although treatment time for the 2-rotation strategy was almost double that of the single-rotation approaches in this example, further preliminary studies showed that this particular case marked the upper limit of the treatment times and that on average shorter treatment times could be expected also with the 2-rotation approach. Since this technique provided the best conformity and homogeneity we chose it as the benchmark for the following comparison of VMAT with 3D-CRT and fixed beam IMRT.
Comparison of VMAT and other techniques
Mean TT, MU-number, CI and HI for the three planning systems
IMRT (MC Hyperion)
IMRT (PB Hyperion)
IMRT (PB Corvus)
1.06 ± 0.02
1.11 ± 0.02
1.11 ± 0.08
1.10 ± 0.02
1.15 ± 0.03
2.00 ± 0.16
1.39 ± 0.09
1.30 ± 0.02
1.26 ± 0.05
1.33 ± 0.21
225 ± 11
268 ± 19
748 ± 193
477 ± 84
1260 ± 172
VTissue 10% PD
10739 cm3 ≡ 48.8%
10463 cm3 ≡ 47.6%
10806 cm3 ≡ 48.1%
10347 cm3 ≡ 46.0%
10591 cm3 ≡ 47.5%
VTissue 30% PD
8187 cm3 ≡ 37.3%
7674 cm3 ≡ 34.9%
7593 cm3 ≡ 33.8%
7199 cm3 ≡ 32.0%
7874 cm3 ≡ 35.3%
VTissue 50% PD
6052 cm3 ≡ 27.6%
5089 cm3 ≡ 23.1%
4203 cm3 ≡ 18.7%
3971 cm3 ≡ 17.7%
5186 cm3 ≡ 23.2%
VTissue 70% PD
3428 cm3 ≡ 15.6%
2734 cm3 ≡ 12.4%
1939 cm3 ≡ 8.6%
1933 cm3 ≡ 8.6%
2612 cm3 ≡ 11.7%
VTissue 95% PD
982 cm3 ≡ 4.5%
208 cm3 ≡ 0.9%
14 cm3 ≡ 0.0%
0 cm3 ≡ 0.0%
53 cm3 ≡ 0.2%
D95% Vol Tissue
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%
D95% Vol PTV
34.09 Gy ≡ 94.7%
33.84 Gy ≡ 94%
33.05 Gy ≡ 91.8%
32.95 Gy ≡ 91.54%
32.33 Gy ≡ 89.8%
As parametrized by MU-number and TTT (table 2), 3D-CRT and VMAT "2Rot" are the fastest/most efficient techniques. TTT is 50% shorter than for IMRT and mean MU-number is reduced by more than 70%.
VMAT combines the advantages of conventional 3D-radiotherapy (3D-CRT) with its fast delivery and low number of monitor units (MU) and the advantages of IMRT with the conformal dose distribution (DD) and the reduced dose to critical OAR in when target volumes are irradiated according to recently published recommendations .
The benefit of IMRT over 3D-CRT regarding high dose conformity and OAR sparing for pelvic tumors and specifically anal cancer was shown earlier [2, 7, 32–36]. Chen et al. compared IMRT and 3D-CRT (AP-PA photons with en-face electrons) for anal cancer and they could show that while PTV coverage of IMRT and 3D-CRT were comparable, surrounding OAR received less dose exposure with IMRT . Mundt et al and Roeske et al. analysed whole pelvic radiation for gynecologic malignancies and concluded that IMRT reduces the volume of normal tissue receiving high doses  resulting in fewer small bowel complications  while retaining PTV coverage. Toxicity and clinical outcome of IMRT for anal cancer was analysed by Milano et al . The group could reduce the radiation dose to normal structures with IMRT and reported a reduction of acute and late toxicities. On the 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 of this issue is unclear with TTT having been reduced since the introduction of IMRT and initial reports on dose-protraction effects [39–41], shortening treatment times to ~5 min will completely obviate this discussion.
Since we studied a PTV paradigm with a moderate cranial extension we did not explicitly evaluate bone marrow sparing in the iliac crest, which is in line with the data of Menkarios et al., who had extensively discussed the merit of modulated treatment for anal cancer . They had stressed the technical feasibility and potential benefit of IMRT with regard to bone marrow sparing for PTVs with a high upper limit. Their data, however also shows that for targets with a low upper limit, such as ours, there is no relevant exposure of the iliac crest with any of the studied techniques.
In our evaluation, VMAT, IMRT and 3D-CRT provide almost the same dose coverage in the target but 3D-CRT exposes the surrounding tissue and consequently the OAR to much higher doses. Sparing of bladder and possibly small bowel between the inguinal lymph nodes included in the PTV, however, is not adequately achieved by 3D-CRT.
So far, commercial planning systems for IMAT/VMAT are a not widely spread and initial data were collected with investigational systems, such as those of the groups from Beamount Hospital, Ghent and Vancouver. These initial reports suggested that VMAT may improve the effiency of modulated radiation therapy. Duthoy et al. reported on the feasability of whole abdominopelvic RT using IMAT with a low number of MU's (444 MU)  and also reported short treatment times (6.3 minutes) for the treatment of rectal cancer .
Both single- and multiple-arc approaches are currently being established clinically for VMAT, showing similar potential for reducing treatment time when plans of equal quality are generated . Clinical implementation of these techniques has also prompted reports on appropriate QA paradigms [41, 42].
A single-arc therapy approach was devised by Wang et al The group used a commercial planning system to optimize the intensity profiles of a treatment plan with 36 equi-spaced static beam angles and exported these profiles to an investigational sequencing algorithm to generate a single-arc plan, recalculated with a MC algorithm that was also developed in-house. They investigated multiple target locations and found that their arc-modulation-radiation-therapy (AMRT) paradigm is capable of creating conformal treatment plans, comparable to other IMRT techniques. A reduction of treatment time by ~50% was observed with slightly lower number of MU's for AMRT .
Finally, Otto introduced a single arc rotation paradigm increasing treatment efficiency by reducing delivery time to 1.5-3 min which is in the range of what we report in this evaluation. The report was focused on the theoretical basis and technical details of the approach  but for a single head-and-neck patient case discussed in his manuscript he reported a treatment time of 107s for VMAT vs. 426s for IMRT with identical dose rate settings.
Palma et al. compared an early prototype of Varian's RapidArc (Varian Medical Systems, Palo Alto, CA) technique with 3D-CRT and fixed field dynamic IMRT for prostate cancer. On a predominantly spherical target, they reported, similar to our results, a higher treatment efficiency for VMAT (491 MU constant dose rate/454 MU variable dose rate) vs. 789 with IMRT as well shorter treatment times , though the absolute level of MU was higher in their series than in our comparison, reflecting an earlier development stage of both modalities. IMRT and VMAT provided better dose distributions than 3D-CRT. A comparison of non-PTV tissue was not performed and can therefore not be assessed.
The most recent report was provided by Cozzi et al. using an improved version of the RapidArc prototype but with focus on a larger PTV (cervix uteri). They reported a similar PTV coverage of VMAT (single rotation, variable dose rate: up to 600 MU/Min) and IMRT (sliding window, 5 beams, fixed dose rate: 300 MU/min) with improved homogeneity, better conformity and a major reduction of OAR irradiation. Our results showed identical homogeneity for IMRT and VMAT but higher conformity of the IMRT approach. Although a detailed comparative analysis of the two series is not possible, this difference is most likely a consequence of the higher number of incident beams - and possibly more modulation - used in our comparison. The different geometry of the PTV might also factor in (PTV encompassing pelvic nodes only in their series vs. pelvic and inguinal nodes in ours). Cozzi et al. reported VMAT delivery with less than 2 min delivery time and less than 245 MU/fraction. A direct comparison of IMRT and VMAT to our situation was not possible due to the fact that we used a step-and-shoot IMRT with 9 beams and a dose rate of 600 MU/min.
While the relative merit of the different modulation approaches with regard to PTV coverage and OAR sparing cannot finally be assessed, the constant reduction in treatment time and MU used for all approaches has now reached a level at which any further discussion about detrimental effects of treatment protraction [37, 38, 41] or secondary tumors due to the higher primary number of MU necessary for modulated therapy [22, 43] is futile.
VMAT is an efficient treatment modality for large and moderately complex pelvic targets already in its initial developmental implementation. While in this situation dose homogeneity and high dose conformity approach that of highly modulated fixed beam IMRT, treatment times and MU are further reduced. Further investigations will show how efficient VMAT can handle other target volumes and evaluate the delivery accuracy of this complex treatment technique with multiple dynamical changes during rotation.
We gratefully acknowledge the help of Dr. Markus Alber with the implementation of Hyperion. We are also indebted to Roberto Pellegrini, Manuela Duglio, Yvette Bellingham and Nick Linton of 3D-Line/Elekta and Alison Metcalf/Kevin Brown of Elekta for the close collaboration during the implementation and initial evaluation of ERGO++ and VMAT. This work was supported within the framework of a Research Cooperation Agreement between the Department of Radiation Oncology, Mannheim University Medical Center and Elekta.
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