|Year : 2014 | Volume
| Issue : 3 | Page : 575-582
Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: A dosimetric comparison
Rajesh A Kinhikar1, Amol B Pawar2, Umesh Mahantshetty3, Vedang Murthy3, Deepak D Dheshpande1, Shyam K Shrivastava3
1 Department of Medical Physics, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Radiotherapy, Holi Spirit Hospital, Mumbai, Maharashtra, India
3 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||14-Oct-2014|
Rajesh A Kinhikar
Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Objective: The objective of this study was to investigate the potential role of RapidArc (RA) compared with helical tomotherapy (HT), sliding window intensity modulated radiotherapy (SW IMRT) and three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer.
Materials and Methods: Prescription doses ranged from 60 Gy to planning target volume (PTV) and 66.25 Gy for clinical target volume prostate (CTV-P) over 25-30 fractions. PTV and CTV-P coverage were evaluated by conformity index (CI) and homogeneity index (HI). Organ sparing comparison was done with mean doses to rectum and bladder.
Results: CI 95 were 1.0 ± 0.01 (RA), 0.99 ± 0.01 (HT), 0.97 ± 0.02 (IMRT), 0.98 ± 0.02 (3D CRT) for PTV and 1.0 ± 0.00 (RA, HT, SW IMRT and 3D CRT) for CTV-P. HI was 0.11 ± 0.03 (RA), 0.16 ± 0.08 (HT), 0.12 ± 0.03 (IMRT), 0.06 ± 0.01 (3D CRT) for PTV and 0.03 ± 0.00 (RA), 0.05 ± 0.01 (HT), 0.03 ± 0.01 (SW IMRT and 3D CRT) for CTV-P. Mean dose to bladder were 23.68 ± 13.23 Gy (RA), 24.55 ± 12.51 Gy (HT), 19.82 ± 11.61 Gy (IMRT) and 23.56 ± 12.81 Gy (3D CRT), whereas mean dose to rectum was 36.85 ± 12.92 Gy (RA), 33.18 ± 11.12 Gy (HT, IMRT) and 38.67 ± 12.84 Gy (3D CRT).
Conclusion: All studied intensity-modulated techniques yield treatment plans of significantly improved quality when compared with 3D CRT, with HT providing best organs at risk sparing and RA being the most efficient treatment option, reducing treatment time to 1.45-3.7 min and monitor unit to <400 for a 2 Gy fraction.
Keywords: Prostate cancer, RapidArc and helical tomotherapy, sliding window intensity modulated radiotherapy, three-dimensional conformal radiation therapy
|How to cite this article:|
Kinhikar RA, Pawar AB, Mahantshetty U, Murthy V, Dheshpande DD, Shrivastava SK. Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: A dosimetric comparison. J Can Res Ther 2014;10:575-82
|How to cite this URL:|
Kinhikar RA, Pawar AB, Mahantshetty U, Murthy V, Dheshpande DD, Shrivastava SK. Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: A dosimetric comparison. J Can Res Ther [serial online] 2014 [cited 2019 Jan 22];10:575-82. Available from: http://www.cancerjournal.net/text.asp?2014/10/3/575/138200
| > Introduction|| |
Prostate cancer is the most common malignant disease in men. External beam radiotherapy (EBT) is one of the potential curative treatment options for clinically localized prostate cancer. Over the past few decades radiotherapy techniques have evolved from conventional two dimensional planning in early 1990's to three dimensional (3D) planning in late 1990's. With conventional planning, dose delivered was typically 68-70 Gy with 2 Gy/fraction, which resulted in toxicity of bladder and bowel.  Although the total radiation dose to the prostate is important for disease control, dose escalation has been limited toxicities. ,, With the advent of 3D planning, the reduction in toxicities led to dose escalation. Subsequently, sliding window intensity modulated radiotherapy (SW IMRT) with image guidance and dose escalation is the standard treatment for locally advanced disease and is also a viable treatment option for early stages. , Dose escalated radiotherapy 3D treatment planning, SW IMRT in conjunction with image-guided radiotherapy, has shown promising results both interns of tumor control and sparing of organs at risk (OAR). ,,,, In past few years, there have been significant refinements in SW IMRT technology. Helical tomotherapy (HT) (HT, TomoTherapy Inc., Madison WI, USA) volumetric arc therapy (VMAT) and rotational RapidArc TM (RA, Varian Medical Systems, Palo Alto, USA) planning and delivery has been implemented successfully in clinical practice. Numerous studies describing their advantages for various sites including head and neck, esophageal, brain, cervical cancers, ovarian cancers etc., have been published. A dosimetric comparison of HT and step-and-shoot IMRT for localized prostate cancer has also been reported.  With an aim to evaluate objectively different external beam techniques in treatment of localized prostate cancer, this study was undertaken. This dosimetric study comparing 3D conformal radiation therapy (3D CRT), SW IMRT, RA and HT forms the basis of this report.
| > Materials and Methods|| |
Patient selection and contouring
The planning images of ten patient's diagnosed with localized prostate cancer and treated for prostate only were utilized for a dosimetric comparison between 3D CRT, SW IMRT, RA and HT. Five patients were low-intermediate risk, three patients intermediate risk and two diagnosed as high risk localized prostate cancer. All patients were treated with EBT with either 3D CRT (one patient), HT (one patient), SW IMRT (four patients) or RapidArc TM (four patients).
For dosimetric comparison of different external beam techniques, a 3D CRT, SW IMRT, RA or HT treatment plans for each patient were generated. All patients underwent 3 mm slice thickness axial computed tomography (CT) scans ( GE LightSpeed Xtra, GE Medical Systems, Wisconsin, USA) with defined bladder and rectal filling protocols and without any intravenous contrast. The target volumes for prostate namely clinical target volume prostate (CTV-P) and planning target volume (PTV) and OAR delineation were done on the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, USA, V 8.6.14). The CTV-P was contouring was according to risk stratification with prostate alone for low risk, prostate and base of seminal vesicles for intermediate risk and prostate with whole seminal vesicles for high risk patients. An anisotropic margins of 10 mm margins superior-inferiorly and 7 mm margins in anterio-posterior and bilateral dimensions were grown over CTV-P to generate PTV. Outer walls of rectum, urinary bladder, bilateral head femurii and other tissues outside PTV as normal tissue were contoured as OARs.
3D CRT, SW IMRT and RA plans were generated on Eclipse TPS while planning CT images with approved structures exported to Tomotherapy planning system (v 4.2) for HT based SW IMRT planning. Treatment objectives for individual patients varied depending on the volume and extent of the target volume, but in general, the goals for clinically implemented HT plans were as follows: Dose to both bladder and rectum was kept as low as possible while maintaining optimal target coverage and dose uniformity to the target volumes. During planning for RA, SW IMRT and 3D CRT techniques, we aimed to achieve the same (as in HT plans) sparing of the bladder and rectum quantified by V 35 and V 40 (i.e., volume receiving 35 and 40 Gy respectively) and see how this requirement had impact on other structures, especially the PTV dose. Doses for HT, SW IMRT, 3D CRT and RA plans were prescribed such that 95% of the PTV receives 95% of the prescription dose. For dosimetric comparison, prescription was similar to PTV of 60 Gy in 25# while CTV-P to a dose of 66.25 Gy/25# for all planning techniques. Normalization of plans for direct comparison was done by calculating percent dose of prescription for all dose volume histogram (DVH) parameters.
3D CRT plans
3D CRT plans were created in Eclipse using six coplanar fields with 6 MV X-rays with the gantry angles of 225°, 270°, 315°, 450°, 90° and 135°. Calculation grid of 2.5 mm was used for the calculations.
SW IMRT plans
SW IMRT plans were optimized according to the "conventional" intensity modulation approach with fixed gantry and intensity modulated beams delivering the dose by means of the SW approach. In Eclipse, the optimization engine of SW IMRT computes optimal fluence maps from dose volume constraints derived from the general planning objectives. Optimal fluence maps are then converted by a leaf motion calculator into actual fluence maps which are deliverable using a dynamic multileaf collimator (MLC) according to the SW segmentation algorithm. Plans were individually optimized using five coplanar fields in the axial plane. Optimizations and dose calculations were done with Eclipse. Beam geometry optimization was performed by means of the automatic tool implemented in Eclipse as part of the SW IMRT process. Plans were optimized using the high definition MLC 120. This is characterized by a spatial resolution of 2.5 mm at isocenter for the central 8 cm and of 5 mm in the outer 14 cm, a maximum leaf speed of 2.5 cm/s and a leaf transmission of 1.8%. Dose calculation was performed by means of the Anisotropic Analytical Algorithm (AAA) algorithm with a spatial resolution of 2.5 mm.
HT is a modality for delivering SW IMRT treatments using a rotating linear accelerator mounted on a continuously moving slip ring gantry in synchrony with the couch motion. This technique delivers highly conformal dose using 6 MV X-ray beams with a 64 leaves binary collimator of a 40 cm wide fan of thicknesses 1.0-5.0 cm to an isocenter 85 cm away from the source. ,, For patients in this study, a field width of 2.5 cm and pitch values of 0.287-0.43 were used. The MLC leaves open 51 times/rotation while closing in between as the gantry moves at a constant speed. All plans were optimized through inverse planning based on least squares optimization method  using the normal (axial matrix 256 × 256) calculation grid. The treatment planning software version used in this study was Hi-ART TomoPlan 3.1.1 (TomoTherapy Inc., Madison, WI, USA).
RA recently released by Varian and is a form of rotational SW IMRT optimization and delivery. The RA treatment technique was investigated by Otto.  The aim of RA was to improve conformal avoidance of treatments and to reduce the treatment time per fraction. Volumetric SW IMRT on a theoretical basis has already been investigated for other clinical cases. ,,, Dose distribution optimization is performed inversely using dose-volume objectives. The optimizer is enabled to continuously vary the instantaneous dose rate, MLC leaf positions, as well as the gantry rotational speed with inter-digitation capability for a single optimized arc around the patient in achieving the desired level of delivery modulation. ,, The (AAA) photon dose calculation algorithm was used for all RA cases in this study on Eclipse TPS (version 8.6.14) Gagne et al.  . have shown that the calculation of the dose distribution can be performed with a clinically acceptable accuracy using the calculation algorithm AAA  using a resolution of 2.5 mm or better.  Ling et al. have shown that the DMLC movement, variable dose rates and gantry speeds can be precisely controlled during RA.  RA plans consisted of a single co-planar arc capable of one rotation during delivery. For single arc plans, collimator angle was set at 45° with a couch angle set to 0° and gantry start angle from 181° to stop angle 179°. Collimator field size and collimator angles were determined automatically through tools within Eclipse to encompass the PTV.
The main focuses of our comparison between the four techniques were plan quality and treatment delivery efficiency. Upon the completion and final approval of all treatment plans, plans for HT, RA, SW IMRT and 3D CRT were compared. Mean doses to rectum and bladder were also estimated and compared. Target dose coverage was evaluated by homogeneity index (HI) as defined by Wu et al. 
HI=(D 2 -D 98 )*100/D p
Where D 2 and D 98 represent the doses to 2% and 98% of the PTV; D P represent the prescription dose. Equation indicates that lower homogeneity values indicate a more homogeneous target dose. The conformity index (CI) described by Feuvret et al.  and van't Riet et al.  was used to assess the target conformity. It is defined as the product of the percentage of PTV encompassed by the 95% isodose volume and the proportion of the 95% isodose volume accounted for by the PTV. The CI ranges from 0 to 1, where 1 is the ideal value.
| > ResultS|| |
The mean volume of the PTV was 138cc (range 65.1-204.3cc) and CTV-P was 45.6cc (range 18.1-71cc). [Table 1] shows in detail the CI and HI indices as mean values ± standard deviation and comparison for different external beam techniques. 3D plans showed better target coverage when compared with the HT, RA and SW IMRT plans (P = 0.1234). HT and RA plans provided better target coverage when compared with the SW IMRT plans (P = 09876). Typical dose distributions for different external beam techniques are as shown in [Figure 1]. CI95 were 1.0 ± 0.01 (RA), 0.99 ± 0.01 (HT), 0.97 ± 0.02 (SW IMRT), 0.98 ± 0.02 (3D CRT) for PTV and 1.0 ± 0.00 (RA, HT, SW IMRT and 3D CRT) for CTV-P. Similarly, the HI was 0.11 ± 0.03 (RA), 0.16 ± 0.08 (HT), 0.12 ± 0.03 (SW IMRT), 0.06 ± 0.01 (3D CRT) for PTV and 0.03 ± 0.00 (RA), 0.05 ± 0.01 (HT), 0.03 ± 0.01 (SW IMRT and 3D CRT) for CTV-P.
|Figure 1: Isodose distribution of 95% of prescribed doses to planning target volume and clinical target volume prostate for (a) helical tomotherapy (b) RapidArc (c) sliding window intensity modulated radiation therapy (d) three-dimensional conformal radiation therapy techniques|
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|Table 1: An overview of all investigated DVH-parameters as mean values±standard deviation (SD)|
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[Figure 2] shows the DVH for (a) bladder, (b) rectum, (c) CTV-P and (d) PTV respectively for different external beam techniques including the 95% confidence limits. 3D CRT by virtue of oblique gantry angles (anterior and posterior) reduced the doses to rectum and bladder. Irradiated normal tissue volume was higher for 3D CRT than for all the other modulated techniques. HT, RA and SW IMRT delivered marginally less dose to OAR and non-target normal tissues. The bladder received a mean dose of 23.68 ± 13.23 Gy (RA), 24.55 ± 12.51 Gy (HT), 19.82 ± 11.61 Gy (SW IMRT) and 23.56 ± 12.81 Gy (3D CRT), while mean dose to rectum was 36.85 ± 12.92 Gy (RA), 33.18 ± 11.12 Gy (HT, SW IMRT) and 38.67 ± 12.84 Gy (3D CRT) respectively.
|Figure 2: Mean dose volume histograms (averaged over the ten patients) with helical tomotherapy, RapidArc, sliding window intensity modulated radiation therapy and three-dimensional conformal radiation therapy techniques for (a) planning target volume (b) clinical target volume (c) bladder and (d) rectum|
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[Figure 3] shows low dose areas of DVH with 30% and 60% isodose distribution for (a) HT (b) RA (c) sliding window intensity modulated radiation therapy (SW IMRT) (d) 3D CRT techniques. As evident from the figure, the 30% and 60% isodose volumes are significantly higher for 3D CRT and SW IMRT when compared to RA and HT with the least volumes seen in HT plans.
|Figure 3: Low isodose distribution of 30% and 60% of prescribed doses for (a) helical tomotherapy (b) RapidArc (c) sliding window intensity modulated radiation therapy (d) Three-dimensional conformal radiation therapy techniques|
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Treatment delivery time: The treatment delivery time for RA, HT, SW IMRT and 3D CRT plans were 1.45 ± 0.14 min, 3.64 ± 0.94 min, 2.36 ± 0.47 min and 1.48 ± 0.16 min respectively. The corresponding monitor units (MUs) were 581 ± 57 MU for RA, 444 ± 49 MU for 3D CRT, 942 ± 188 MU for SW IMRT and 3163 ± 817 MU for HT treatment delivery respectively.
| > Discussion|| |
Dose escalation with newer radiation techniques have been successfully implemented with acceptable late rectal and bladder toxicities in routine practice for localized prostate Cancer (references). However, with the advent of newer technologies in radiation treatment delivery there are many options available in clinical practice. There is no consensus until date on advantages or superiority of one over the other. With an aim to evaluate and compare dosimetrically various newer external beam techniques in radiation treatment of localized prostate cancer we undertook this dosimetric study.
Dose escalation without an increase in late toxicities with the use of newer radiation techniques systematically is a success story in localized prostate cancer. The growing number of publications dealing with the simplification of the SW IMRT planning process and acceleration of the delivery process while maintaining plan quality ,, may be indicative of a convergence of the photon treatment optimization process towards its physical limits, dictated by penumbra and depth dose distribution. Comparisons such as ours will not result in a "best approach overall" but rather provide an impression of the specific strengths and weaknesses. Most advantages for one modality with regard to one parameter are offset when regarding another parameter. Another issue that has to be kept in mind is the use of different dose calculation algorithms, after or even during optimization as in the case of Hyperion. A study by Yang et al. recalculated a data set of 30 prostate patients undergoing an SW IMRT calculated with Corvus. Most investigated parameters for high and low dose regions differed by <3% on average, maximum deviations in the rectum were <4%. 
Synoptically, already at this early stage of the development, all approaches yield treatment plans of similar quality for the paradigm studied in our comparison, with optimal results with HT based and SW IMRT approach (seven incident beams) resulting in improved conformality and OAR sparing that can be expected to be more pronounced with increasing complexity of the PTV, RA moderate modulation produces very good treatment plans at dramatically reduced treatment times. Keeping RA treatment time can be expected to increase with PTV complexity.
Mahantshetty et al.  in their study have reported about comparison of SW IMRT VS RA for whole abdomen radiation therapy (WAR). This study shows that IMRT and RA resulted comparable for target coverage for PTV_WAR and improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA for PTV_WAR. For OAR, small differences were observed between the techniques. RA showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.
A study of Duthoy et al.  reported about VMAT for large volumes with four rotations in patients to undergo whole abdominopelvic radiation therapy with a mean treatment time of 13.8 min with only 444 MU for a fraction dose of 1.5 Gy. The same authors reported treatment times of 6.3 min (3-6 arcs and 456 MU) for seven patients with rectal cancer at a prescription dose of 1.8 Gy.  Otto recently described a single arc treatment planning paradigm that also holds the potential to shorten the treatment time for several indications considerably to 1.5-3 min, similar to our data. Patient data were only presented as a case study, however, with promising DVH data, but no comprehensive dose display or systematic analysis on a meaningful number of patient datasets was reported. 
There is a considerable controversy regarding what range of dose exposure to the rectum is clinically most relevant ,, and there may also be a different sensitivity depending on the level (rectum versus anorectal junction).  The disadvantage of modulated radiotherapy is the higher number of MUs and resulting longer treatment times when compared with unmodulated 3D CRT. The influence of more efficient modulated approaches such as RA on secondary cancer risk is not clear to date. Whereas improved treatment efficiency may reduce secondary malignancies due to less scatter dose from reducing MU.
When comparing treatment times, one has, however, to consider that sequential tomotherapy needs distinctly longer treatment time than the helical approach, whereas estimated results in plan quality are due to the same approach being equal. ,, Treatment times for a typical prostate cancer treatment (2 Gy) with sequential tomotherapy with a linac and a dose rate of 200 MU/min were in the range between 15 and 20 min  and can still be expected to be >10 min even with a fast linac. Published treatment times by Ramsey et al. and Cao et al. for the helical approach were in the range of 5 min, thus being clearly faster. [ 18], Palma et al., for the same group, compared 3D CRT versus MLC based SW IMRT versus arc therapy for prostate cancer.
For clinical prostate treatments, Zelefsky et al. reported for a prescribed dose of 1.8 Gy/fraction approximately 700 MU for DMLC-SW IMRT, when compared with 300 MU for conventional 3D CRT.  For 10 samples treatment plans (prostate) Shaffer et al. published with the predecessor of the RA optimizer an average of 949 MU for the VMAT approach and 1814 MU for a conventional nine-field SW IMRT. The prescription dose here was 74 Gy in 37 fractions at 2 Gy to the PTV with an integrated boost to the CTV-P (prostate) to 88.8 Gy (120% of PTV-prescription dose). The relatively high MUs needed for both approaches are in contrast to the earlier publication with a simpler target paradigm and are indicative of the increased need of modulation across the field with increased target complexity.
The most systematic comparison of a VMAT and a static approach, albeit on a larger target paradigm (whole pelvis radiotherapy), was recently provided by Cozzi et al.  This study shown that, RA was investigated for cervix uteri cancer showing significant improvements in OAR and healthy tissue sparing with uncompromised target coverage leading to better conformal avoidance of treatments w.r.t. conventional IMRT. While reporting comparable MU and treatment time requirements for fixed beam IMRT (SW), they could generate VMAT plans with a delivery time of consistently <2 min and <300 MU with, on average, better quality than the benchmark SW IMRT plans. While the new treatment approach has to be evaluated for the major target geometries and the delivery accuracy of this multi-degree-of-freedom paradigm has to be evaluated and constantly monitored, further acceleration of treatment times while providing treatment plans with excellent quality will continue to advance overall treatment precision and help to efficiently use departmental resources. The advantage of RA is its shorter treatment times compared to HT and conventional IMRT. It uses more beam directions than fixed-gantry IMRT, 3D CRT and delivers highly conformal volumetric dose distributions in a single or multiple arcs.
Murthy et al.  in their study have reported their results for tomotherapy plans compared with conventional IMRT. They concluded that HT improves dose homogeneity, target coverage and conformity when compared to step and shoot IMRT, with overall improvement in critical organ sparing.
The resulting plan quality with all the mentioned treatment modalities was evaluated according to various indices of the PTV. The dosimetric feasibility was assessed based on the minimum and maximum dose in the target volume. Our results were in good agreement with the studies mentioned above. However, when compared to 3D CRT, one has to be careful in plan optimization and the doses to OARs. VMAT and Tomotherapy have a great potential for achieving complex dose distributions and sparing the OARs as well.
| > Conclusion|| |
All studied intensity-modulated techniques yield treatment plans of significantly improved quality when compared to 3D-conformal treatments, with HT providing best OAR sparing and RA being the most efficient treatment option for the targets studied in our comparison, reducing treatment time to 1.45-3.7 min and MU to <400 for a 2 Gy fraction.
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[Figure 1], [Figure 2], [Figure 3]