British Journal of Radiology 74 (2001),177-182 © 2001 The British Institute of Radiology
Evaluation of the optimal co-planar field arrangement for use in the boost phase of dose escalated conformal radiotherapy for localized prostate cancer
V S Khoo, FRACR, MD1,
J L Bedford, PhD2,
S Webb, PhD, FInstP, FIPEM2 and
D P Dearnaley, FRCR, FRCP, MD1
1 The Academic Unit of Radiotherapy & Oncology
2 The Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK
Correspondence: Dr V S Khoo, The Academic Department of Radiation Oncology, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
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Abstract
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The aim of this study was to determine the optimal co-planar beam arrangement from a variety of three-field (3F), four-field (4F) and six-field (6F) plans for the boost phase of a dose escalated conformal radiotherapy schedule. Three selected plans (3F 0°, 90°, 270° plan, 4F 45°, 90°, 270°, 315° plan and 6F 40°, 90°, 115°, 245°, 270°, 320° plan) were compared with reference plans (3F 0°, 120°, 240° plan, 4F 0°, 90°, 180°, 270° plan, 6F 55°, 90°, 125°, 235°, 270°, 305° plan and 6F 50°, 90°, 130°, 230°, 270°, 310° plan) in 10 patients. Doses of 64 Gy and 74 Gy were prescribed to the isocentre using 6 MV photons. The boost planning target volume comprised the prostate gland alone without a margin. Plans were compared by means of rectal volumes irradiated to >50% (V50), >80% (V80) and >90% (V90) of the prescribed dose. Irradiated volumes were also measured for the bladder (V90) and the femoral heads (V70). All optimal 3F, 4F and 6F plans gave lower irradiated rectal V80 and V90 levels than their corresponding reference plan. The 3F (0°, 90°, 270°) plan consistently provided lower irradiated rectal levels at V50 to V90, with acceptable bladder and femoral head doses compared with the other plans in the study. When the 6F (50°, 90°, 130°, 230°, 270°, 310°) plan used at our institution for the boost phase was compared with the 3F (0°, 90°, 270°) plan, the rectal V50 was reduced from 20.8±5.2% to 12.6±5.1%, the rectal V80 was reduced from 8.7±2.9% to 6.5±3.1% and the rectal V90 was reduced from 5.5±2.1% to 3.9±2.0% (all p<0.001). The bladder V90 and the femoral heads V70 levels were equivalent. For the boost phase when escalating the dose from 64 Gy to 74 Gy, the co-planar plan that allowed optimal rectal sparing was a 3F beam arrangement using gantry angles of 0°, 90° and 270°. This 3F plan provided improved rectal sparing compared with the 6F (50°, 90°, 130°, 230°, 270°, 310°) beam arrangement currently used at our institution, with equivalent and acceptable bladder and femoral head doses.
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Introduction
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Radical radiotherapy is commonly used for the curative treatment of localized prostate cancer. Dearnaley et al [1] recently reported that conformal radiotherapy (CFRT) techniques in the radical treatment of prostate cancer provided significant reduction of late rectal morbidity compared with conventional open field techniques. Using prescribed doses of up to 64 Gy, rectal complications 
grade 2, measured on the Radiation Therapy Oncology Group (RTOG) scale, were reduced from 15% to less than 5% (p=0.01). This provided the foundation for the randomized Medical Research Council (MRC) RT-01 trial of dose escalation for localized prostate cancer. Using CFRT, this on-going trial randomizes the treatment of men with prostate cancer between a dose of 64 Gy or an escalated dose of 74 Gy.
We have demonstrated that the normal tissue complication probability model using the Lyman–Kutcher–Burman scheme [2–4] predicts a significant increase in rectal dose complications if the planning target volume (PTV) or treatment margins are not modified when the dose is escalated from 64 Gy to 74 Gy [5–7]. The MRC RT-01 trial protocol has anticipated these issues by specifying a two-phase approach in which the clinical target volume (CTV) is reduced for the boost phase to a volume that covers the prostate gland only, with no PTV margin. In previous studies [5–7], we have evaluated plans suitable for the first phase of prostate CFRT to 64 Gy using planning margins of 10 mm, but we have not specifically addressed the situation where the PTV is equal to a prostate-only CTV.
In this study we are primarily interested in selection of the optimal beam arrangement for delivery of the boost phase from 64 Gy to 74 Gy. We have therefore evaluated a series of three-field (3F), four-field (4F) and six-field (6F) plans for use in the boost phase of dose escalation in prostate CFRT. These selected plans are compared with a series of reference plans, some of which are recommended in the MRC RT-01 trial protocol. The aim is to determine which of the 3F, 4F and 6F plan arrangements provide the best rectal sparing, with acceptable bladder and femoral head doses, for this situation.
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Methods and materials
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Patients
Ten patients with histologically confirmed prostate cancer were retrospectively studied. All patients underwent staging investigations that revealed no clinical evidence of regional nodal disease or distant metastasis. The local tumour stage [8] ranged from T1c to T3c. The median age of these patients was 65 years (range 53–76 years). All patients were previously treated with CFRT techniques in a preliminary dose escalation trial at the Royal Marsden NHS Trust.
For prostate CFRT, all patients were scanned using CT in a supine position with a "comfortably full" bladder. CT scan slices of 5 mm thickness were taken at 5 mm intervals from 10 mm inferior to the level of the ischial tuberosities to the apex of the bladder or to the bottom of the sacroiliac joint, whichever was greater. The CT images were then automatically transferred to a TARGET-2 planning workstation (Prism Microsystems, Elstree, UK) where the CTV and relevant organs-at-risk (OARs) were outlined. As previously mentioned there was no PTV margin used in the boost phase, therefore the CTV, which encompassed the prostate gland alone, equalled the PTV. The CT scans and the outlines of the relevant volumes-of-interest were subsequently transferred to our research three-dimensional (3D) planning workstation (VOXELPLAN, DKFZ, Heidelberg, Germany) and planned using the virtual simulator VIRTUOS [9] that is included within it. The use of VOXELPLAN facilitated full 3D treatment planning and beam weight optimization by simulated annealing [10]. In this manner, individual patient anatomy was taken into account and the main variable assessed was plan geometry.
Beam arrangements
In this study we used previous experience [5–7] in designing co-planar beam arrangements to select 3F, 4F and 6F plans for comparison with reference plans. We selected the best beam arrangement designed for a prostate-only volume with acceptable avoidance of the rectum and femoral heads. For description, the orientation of each sequential beam in the plan configuration was named in a clockwise fashion (e.g. the 4F "box" plan was given the notation 0°, 90°, 180°, 270°). Four reference plans were chosen for comparison. Three of these reference plans (i.e. the 4F and 6F plans) are recommended in the MRC RT-01 protocol. The selected plan arrangements together with the reference plans are schematically illustrated in Figure 1
and are discussed below.
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Figure 1. Schematic representation of the three-field (3F), four-field (4F) and six-field (6F) co-planar plans. The gantry angles for each plan type are noted in parentheses. Note that the presence of a wedge on a particular beam does not necessarily imply that it is used in practice, as the beam weight optimization program may select a low weight for the wedged component of that field.
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The 3F reference plan had gantry angles of 0°, 120° and 240° (3F0,120,240). This 3F0,120,240 plan was the only reference plan not recommended in the MRC RT-01 protocol. The selected 3F plan had gantry angles of 0°, 90° and 270° (3F0,90,270). In a study evaluating a variety of 3F co-planar plans [6], this 3F0,90,270 plan provided optimal high dose rectal sparing because the high dose region was straight posteriorly and spared the rectum, with acceptable bladder and femoral head doses.
The 4F reference plan recommended in the MRC RT-01 protocol had gantry angles of 0°, 90°, 180° and 270° (4F-box). The selected 4F plan consisted of laterally symmetric anterior oblique beams with opposing lateral fields, which were found to provide the optimal dose distribution for phase I volume in our previous study [5]. The lateral beams afforded the best rectal sparing by giving a straight posterior edge to the PTV while the anterior oblique beams were orientated to reduce dose to the femoral heads and to provide only exit dose to the rectum. The anterior oblique angle was assessed every 5° and selected such that the femoral head volume irradiated to >70% of the prescribed dose (V70) was 
10% in all patients. This 4F boost plan had gantry angles of 45°, 90°, 270° and 315° (4F 45/lats).
Two 6F reference plans, which were symmetric around the mid coronal plane, were defined in the MRC RT-01 trial protocol. These two symmetric 6F plans had gantry angles of 55°, 90°, 125°, 235°, 270° and 305° (6F 35/35) and 50°, 90°, 130°, 230°, 270° and 310° (6F 40/40), respectively. For ease of description, the notation ant/post was used to indicate the angles of the oblique fields relative to the mid coronal plane. The 6F 40/40 plan is used routinely at The Royal Marsden for the boost phase. In a recent study [7], the optimum 6F plan for the phase I volume was shown to have asymmetrically arranged beams around the mid coronal plane that provided different entry and exit orientations. Similar to the 4F selection, the oblique beam angles were assessed every 5° and selected such that the femoral head V70 was 10% in all patients. This 6F boost plan had gantry angles of 40°, 90°, 115°, 245°, 270° and 320° (6F 50/25).
Planning parameters
Apart from the anterior and posterior fields, all fields were wedged to overcome the obliquity of the patient contour and to ensure that the target dose was as homogenous as possible. For the case of the 6F 40/40 plan, it was designed without any beam wedges, in accordance with the MRC RT-01 protocol. All wedges were orientated with the thin end of the wedge directed posteriorly, with the exception of the posterior oblique fields where the orientation of the wedge was reversed when the gantry angle of these fields exceeded 20° to the mid coronal plane.
The isocentre was located centrally within the PTV for all plans. Each beam portal was conformally shaped to the beam's eye view of the PTV. A 6 mm margin was added to the PTV to account for the beam penumbra [11]. All beams that required a wedge were comprised of two fields, one wedged and one unwedged. Adjustment of the wedge angle was effected by varying the relative weights of the two fields [12]. In this manner, optimizing the beam weights also had the effect of optimizing the wedge angles.
The beam weights were optimized using the automatic method of Oldham et al [10]. This algorithm and its application to prostate CFRT have previously been described in detail [5–7, 10]. Briefly, this optimization method minimizes an objective function consisting of a series of terms relating to the PTV and OARs, the relative importance of these terms being controlled by importance factors, which, in accord with our previous studies [5–7], were chosen to be PTV 20, rectum 20, bladder 2, femoral heads 8 and body 20. Dose was calculated using a pencil beam convolution algorithm with CT-based equivalent path length inhomogeneity correction [13]. The pencil beam kernels were generated using tissue phantom ratios and output factors for the 6 MV photon beam of an Elekta SL25 linear accelerator with an Elekta multileaf collimator (Elekta Oncology Systems, Crawley, UK).
Coverage of the PTV was designed to be between -5% and +7% of the prescribed (isocentric) dose [14]. However, using a 3D dose cube with full inhomogeneity calculations, on occasions the minimum PTV coverage was slightly lower. When this situation arose, a manual check of the PTV coverage was performed and the minimum PTV dose of 92% was accepted if 1% of the PTV was between 92–95%. The maximum dose within the superficial region of the patient was measured approximately 20–30 mm below the skin surface; this was required to be maintained below 95% of the isocentric dose for a plan to be acceptable.
In the RT-01 trial, the phase I treatment of 64 Gy is given using a PTV with a 10 mm margin around the gross tumour volume (prostate±seminal vesicles). The boost volume is the prostate alone without a margin, which is given a further 10 Gy. We were unable to combine the dose from the two separate phases, therefore biological indices were not considered; furthermore there is a large degree of uncertainty in the parameters used to calculate them. The boost plans were computed to 74 Gy to compare the different beam arrangements. Dose thresholds for the pelvic structures were determined using published tolerances [4, 15]. Rectal dose statistics were used as the primary arbiter because the rectum is considered to be the dose-limiting organ in prostate radiotherapy [16, 17]. The proportions of the rectum receiving greater than 80% (V80) and 90% (V90) of the prescribed isocentric dose were recorded in this study as the main factors influencing the suitability of a plan. The high dose region was also chosen because Benk et al [16] observed that the probability of rectal complications increased with larger volumes irradiated to target dose levels. The proportion of the rectum receiving greater than 50% (V50) of the isocentric dose was also considered as a further measure describing the fraction of the rectum receiving a moderate to high dose.
The bladder and femoral heads dose statistics were also measured. In our previous studies we had selected the irradiated femoral head volume (V70) that corresponded to 70% of the prescribed dose as an appropriate level to measure. Emami et al [15] had suggested that a dose of 52 Gy to the entire femoral head may result in a 5% complication probability of necrosis at 5 years (TD5/5=52 Gy). This 52 Gy level corresponded to 70% of 74 Gy. In practice, the dose to the whole femoral head seldom exceeds this 52 Gy threshold. For the bladder, the irradiated bladder volume that was raised to 90% (V90) of the prescribed dose was measured.
The various 3F, 4F and 6F plans were compared using mean dose–volume statistics. A two-tail Student's t-test was used to verify the significance of differences in the mean results of the treatment plans after correlation of quantile–quantile plots had shown the data to be normally distributed.
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Results
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Mean statistics for each of the 3F, 4F and 6F plans assessed are shown in Table 1. Each of the optimized 3F0,90,270 (p=0.001), 4F 45/lats (p=0.01) and 6F 50/25 (p=0.08) plans improved on its companion reference plan(s) in terms of both V80 and V90. When the rectal V50 level was compared with the reference plans, rectal sparing was maintained using the optimized 3F0,90,270 and 4F 45/lats plans (p=0.001). Whilst the 6F 50/25 plan recorded significantly lower rectal V50 than the 6F 40/40 plans (p=0.001), there was no significant difference compared with the 6F 35/35 plan (p=1.0).
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Table 1. Mean (±1 SD) statistics for three-field (3F), four-field (4F) and six-field (6F) plans used in the boost phase of conformal radiotherapy
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The three beam arrangements with the best rectal sparing are compared in Figure 2 with the 6F 40/40 plan currently used for the boost phase at The Royal Marsden. It is clear from Figure 2 that the highest degree of rectal sparing is provided by the 3F0,90,270 plan. When the 3F0,90,270 plan was compared with the 6F 50/25 plan, this 3F plan gave lower irradiated rectal volumes for each of the 50% to 90% dose levels (p<0.001). Compared with the 4F 45/lats plan, the 3F0,90,270 plan gave lower rectal V50 (p=0.001) and V80 (p=0.05), but there was no significant difference in rectal V90 (p=0.6). However, the 3F0,90,270 plan provided the lowest irradiated rectal volume at 50%, and this moderate dose region may become more important when the dose is escalated.
When the irradiated bladder volumes were examined, each of the optimized 3F0,90,270 (p=0.6), 4F 45/lats (p=0.05) and 6F 50/25 (p=0.2) plans improved on its companion reference plan(s). The 3F0,90,270 plan irradiated a higher volume of bladder to 90% than the 4F 45/lats plan (p=0.2) and the 6F 50/25 plan (p=0.2).
When V70 for the femoral head was assessed, both the optimized 3F0,90,270 plan (p=0.1) and the 4F 45/lats plan (p=0.1) recorded higher values compared with their reference plans (Table 1
). The 6F 50/25 plan irradiated a smaller volume of femoral head to 70% than either of the two reference plans (p=0.1). The femoral head V70 using the 3F0,90,270 plan was higher compared with both the 4F 45/lats plan (p=0.7) and the 6F 50/25 plan (p=0.5). However, the femoral head V70 for the 3F0,90,270 plan was similar to that of the currently used 6F 40/40 plan (p=0.9).
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Discussion
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In terms of rectal sparing, the optimized plan arrangements for each of the 3F, 4F and 6F plans improves on its respective reference plan. These three plans are the 3F0,90,270 plan, the 4F 45/lats plan and the 6F 50/25 plan. The higher degree of rectal sparing resulting from the design of these improved beam orientations for the target volume used in the boost phase, is consistent with our previous prostate planning experience using larger target volumes with planning margins [5–7]. Whilst these three plans improve on the 6F 40/40 plan currently used at The Royal Marsden for the boost phase, the 3F0,90,270 plan consistently provides the best rectal sparing at high doses of all the evaluated plans. Furthermore, the 3F0,90,270 plan also gives the best rectal sparing at the rectal V50 level, and this isodose region may become significant as the dose is escalated.
Use of a 6F plan with 35/35 or 40/40 beam orientation, or alternatively the 4F-box plan, has been recommended as the boost plan arrangement in the MRC RT-01 protocol. The 3F0,90,270 plan has demonstrated improved rectal sparing compared with these recommended 4F and 6F boost plans for all the measured irradiated rectal volumes (Table 1). However, the 3F0,90,270 plan bladder V90 values are slightly higher compared with the 6F plans, and lower compared with the 4F-box plan, but these values are not significantly different. Similarly, the femoral head V70 values are higher for the 3F0,90,270 plan compared with the 4F-box plan, and lower compared with the 6F plans, but again the differences are not significant. Therefore, the 3F0,90,270 plan would be an acceptable replacement to the current 6F boost plan arrangement, providing improved rectal sparing with acceptable bladder and femoral head doses. The advantages of the 3F0,90,270 plan are that this beam configuration is relatively simple in set-up, treatment delivery and field verification.
It is anticipated that use of the 3F0,90,270 plan would provide the smallest increase in rectal dose when combined with any phase I plan and is, therefore, likely to produce the least increase in predicted late rectal complications when the dose is escalated from 64 Gy to 74 Gy. We have previously reported that the predicted rectal normal tissue complication probability (NTCP) resulting from the use of the reference beam arrangements treating larger PTVs (i.e. prostate plus seminal vesicles and incorporating a 10 mm CTV–PTV margin) can be reduced by optimizing the beam arrangement [5–7]. This is clearly the case for late rectal complications. The bladder is less important because the predicted bladder NTCPs are <1% at 74 Gy even when treating a PTV that includes the prostate plus seminal vesicles [5–7], since the use of a full bladder for treatment ensures that a large proportion of the bladder remains outside of the high dose region. Therefore, it should be safe to assume that the small increase in bladder dose using the 3F0,90,270 plan for a much smaller PTV used in the boost phase will be unlikely to result in higher late effects. A similar situation exists for the femoral heads.
In this study, beam weights were optimized using an inverse planning algorithm. For the 3F0,90,270 plan arrangement we have shown that a 2:1:1 weighting at the isocentre produces near equivalent results and is practical for "forward" planning methods. Another consideration for the use of a 3F plan in the boost phase is that it avoids irradiating large volumes of the pelvis to low doses. Using a 6F plan, low to medium dose regions are spread around the pelvis. As yet, it is unknown what the value of spreading the dose distribution within the pelvis may be. It has been envisaged that spreading the dose may allow the tolerance of relevant OARs in the pelvis to be maintained. However, it is of some concern that increasing the dose "bath" may result in other late complications in organs that have much lower tolerance thresholds, such as the bone marrow, or result in the development of leukaemia [18].
One aspect that we have not investigated in this study is the potential benefit of non-co-planar planning. Mesina et al [19] compared the use of a conformal non-co-planar 4F boost (two anterior–inferior oblique beams and parallel-opposed lateral fields) and the standard 4F-box co-planar arrangement. It was reported that the non-co-planar 4F plan described allowed a mean reduction in rectal and bladder volume at the high dose region (approximately V90) of 3.4% and 7.0%, respectively. In the present study, the difference between the 3F0,90,270 and the 4F-box plan for rectal V90 values was 1.3%, with the bladder V90 values at 0.3% in favour of the 3F plan (Table 1). The boost volumes used by Mesina et al [19] utilized planning margins of 1.5 cm, which may have benefited from non-co-planar orientations. Non-co-planar treatment planning remains an important issue and we will be exploring the potential of this in future studies.
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Conclusion
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For the boost phase during dose escalation from 64 Gy to 74 Gy, the co-planar plan arrangement that provided the best rectal sparing for all three dose levels (50–90%), with acceptable bladder and femoral head doses, was a 3F plan with gantry angles of 0°, 90° and 270°. This 3F plan also significantly improved on the 6F 40/40 plan currently used for the boost phase at The Royal Marsden. It is anticipated that this 3F plan would also provide the smallest increase in rectal dose when combined with any phase I plan.
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Acknowledgments
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This work was supported in part by the Bob Champion Cancer Trust Fund and the Cancer Research Campaign. This work has been carried out using the VOXELPLAN treatment planning system supplied by the German Cancer Research Centre (DKFZ), Heidelberg. We would like to thank Professor W Schlegel and his group at DKFZ for their continuing support and co-operation on this project.
Received for publication April 6, 2000.
Accepted for publication July 25, 2000.
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References
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Abstract
Introduction
), four-field (X) and six-field (
) plans compared with the current 6F plan (
) used at The Royal Marsden Hospital.