British Journal of Radiology 75 (2002),967-973 © 2002 The British Institute of Radiology
Dose-position and dose-volume histogram analysis of standard wedged and intensity modulated treatments in breast radiotherapy
E M Donovan, MSc
1
N J Bleackley, MSc
1
P M Evans, DPhil
1
S F Reise, MSc
1 and
J R Yarnold, MD
2
1 Joint Department of Physics and 2 Department of Radiotherapy, Royal Marsden NHS Trust and Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT, UK
 |
Abstract
|
|---|
The aim of this work was to evaluate the positional distribution of dose in a concise manner and to analyse dose-histogram results in tangential breast radiotherapy in 300 patients, randomized to standard wedged or intensity modulated radiotherapy (IMRT), for future correlation with clinical outcome data. A simple method for analysing the dose-position relationship in the treatment volume was used to compare the spatial distribution of dose in patients. The breast was divided into equal thirds (upper, middle and lower) and dose was assessed using three dose bands; 95–105%, >105–110% and >110% of the prescription dose. The effect of using IMRT on the dosimetry was assessed from dose-volume histogram data using the following parameters: percentage of the target volume receiving a dose less than 95%, greater than 105%, either less than 95% or greater than 105% of that prescribed; the mean dose; and the maximum dose. Doses greater than 105% were predominantly in the upper and lower regions of the breast in the standard wedged treatment. 96% of these patients received doses greater than 105% in the upper region of the breast and 70% received doses greater than 105% in the lower breast. Only 4% of patients allocated IMRT received doses greater than 105% in either region. Analysis of dose-volume histogram data showed that IMRT reduced the volume receiving a dose greater than 105% by a mean of 10.7% (p=<0.001); the mean change in the volume receiving a dose less than 95% was 0.2% (p=0.63). Average mean plan dose was 101.6% for standard treatment and 99.6% for IMRT (p<0.001 for each compared with 100.0% ideal). The mean value of maximum dose was reduced from 111% to 106% in the group of patients randomized to IMRT. A simple method for describing the relationship between dose and position in the breast, which is helpful for the effective correlation of dosimetry and clinical effects, is reported. Further, application of IMRT to the tangential field irradiation of the breast has been demonstrated to reduce high dose regions in both volume and dose level without compromising either minimum dose coverage or mean dose delivered to the breast.
|
Introduction
|
|---|
The efficacy of radiotherapy in reducing breast cancer mortality is now well established [1]. Concern now focuses on improving dosimetry of tangential field irradiation and assessing the impact on long-term adverse effects to the patient [2]. It has been suggested that poor cosmesis, and other late adverse effects, are related to dose inhomogeneity [3, 4]. Dose inhomogeneity associated with tangent pair irradiation of the breast is associated with a number of factors, including the irregular shape and large size of the breast [3, 4, 5]. Variation in breast separation throughout the volume and the wide range of focus-to-source distance over the treated volume are the chief sources of dose variation. Reports suggest methods for improving dose homogeneity by employing intensity modulation via physical compensators or multileaf collimators [6–15]. A portal-imager-based design for intensity modulated radiotherapy (IMRT) in the breast has been used [16] and employed in an ongoing, randomized clinical trial of 300 patients [17, 18], testing whether improved homogeneity delivered by IMRT noticeably improves late adverse side effects. The authors have previously reported the planning study, which verified the method [19]. The limitation of most of these studies is that they report only results from dose-volume histogram (DVH) calculations; they contain no information on the position of specific dose regions in the breast.
One of the requirements of our clinical trial, comparing standard wedge treatments and IMRT, is to correlate dose in the breast with the pain and tenderness mapped by patients. This involves analysing both the summary of the dose distribution obtained from DVH data and the anatomical distribution of dose, in simple, but clinically relevant ways. In the clinical trial, patients are asked to map any breast pain or tenderness on a diagram of the breast split into regions: upper (superior third); middle, lower (inferior third); left; and right. It is not feasible to use the full three-dimensional dose distribution from a treatment planning system to correlate with this patient self-assessment, as these data are not easily comparable. The full dose distribution is an accurate and visual representation of the consequences of a particular plan, but contains too much information to correlate with the pain and tenderness mapping in a simple manner. Whilst DVH data is a useful summary of the volumetric information in a treatment plan, the lack of positional information on dose is a limitation.
This paper describes a succinct method for extracting the anatomical distribution of dose in the breast for the 300 treatment plans to be assessed for the trial, presents the dose-volume data and discusses its probable clinical implications.
|
Materials and methods
|
|---|
Treatment planning
For each patient in the trial, standard or IMRT treatment was planned according to randomized allocation. IMRT was delivered using the method described by Evans et al [17]. The method used a set of transverse outlines derived from radiological thickness data to provide a 3D description of the breast. These outlines were used for DVH calculation and provided a means by which comparison could be made between data from the two arms of the trial. All the data discussed in this paper refer to information from the portal-image-generated slice set, rather than from the single physical contour used for calculation of monitor units [17].
The planning target volume (PTV) was defined as 5 mm inside the external contour and 5 mm anterior to the baseline or lung in the transverse plane, and 1.0 cm inside the field edges at the superior and inferior borders (Figure 1
). This created a PTV representative of that defined at simulation and avoided dosimetric effects due to beam penumbra and build-up.
View larger version (12K):
[in this window]
[in a new window]
|
Figure 1. Example of a portal image generated transverse outline for a patient with right-sided disease.
|
|
All plans were normalized to 100% at the isocentre, following recommendations in the International Commission on Radiation Units and Measurements (ICRU) reports 50 and 62 [20, 21]. A dose of 50 Gy in 25 fractions was prescribed to this reference point. All treatment planning was carried out on a GE Target 2 system (IGE medical systems, Slough, UK).
Positional analysis
Two orthogonal planes through the isocentre were used to provide data on the spatial distribution of dose. Each plane was divided into three equal areas, corresponding to the upper (superior third), middle and lower (inferior third) regions of the breast, as indicated by the dotted lines on the outlines in Figure 2, which shows an example of a standard treatment distribution. In Figure 2a the plane is normal to the baseline of the tangent pair through the isocentre and is referred to as the quasisagittal plane; the quasicoronal slice is a plane parallel to the baseline through the isocentre. Dose was divided into three bands: 95–105%; >105–110%; or >110% of prescribed dose, graded 3, 2 and 1, respectively. In Figure 2, anatomical distribution would be summarized as upper=1, middle=2 and lower=1, i.e. the upper breast receives a dose greater than 110%, the middle of the breast receives a maximum dose between 105% and 110%, and the lower breast receives a dose greater than 110% of that prescribed. For a breast region to be graded with respect to dose, the maximum isodose had to cover at least the area of the ICRU 50 definition of maximum dose [20]. This provided a simple means to relate dose to position in the breast, and hence to correlate dose with pain and tenderness.
View larger version (25K):
[in this window]
[in a new window]
|
Figure 2. (a) Quasi-sagittal outline through the isocentre and normal to the baseline of the tangent pair. (b) Quasi-coronal outline through the isocentre and parallel to the baseline of the tangent pair, showing typical isodose distribution. Dotted lines indicate the division of the outlines into three regions to facilitate positioning of dose data. The isodose plots are at the same magnification.
|
|
Dose volume histogram evaluation
The second tool for analysing treatments was DVH data. The DVH algorithm available on the clinical treatment planning system was used. Dose grid resolution in the transverse plane (x, y) was 5 x 5 mm and 10 mm in the z direction, which was the slice separation of the transverse outlines. A test of the system using resolution of 2 x 2 mm in the transverse plane showed no significant difference in the data. The minimum dose bin resolution on this system was 1%. A standard set of dose bins was used: 0–80%, 80–85%, 85–90%, and then 1% bins to the maximum dose in the plan.
Comparisons between standard and IMRT plan data were carried out using the student t-test with a two tailed distribution, and p-values were evaluated. Inhomogeneity (VI) was defined as the percentage volume of the PTV receiving a dose outside 95% and 105% of the prescribed dose. Treatment planning aimed to minimize this quantity; where VI is reduced, homogeneity is improved. We have used V95 and V105 to represent the volume of the PTV receiving under 95% and above 105% of the dose prescribed. Two other quantities of importance were maximum dose and mean dose. Maximum dose was as in ICRU 50 [20].
|
Results
|
|---|
Anatomical distribution of dose
Figure 3 shows data for 150 standard wedged treatments and 150 IMRT treatments, according to randomization, summarizing how dose relates to regions in the breast. In the upper third of the breast, 50% of patients allocated standard wedged fields received doses of 105–110% and 46% received doses above 110% of the prescribed dose. The corresponding figures for patients allocated IMRT were 3% and 1%, respectively. The majority of patients received 95–105% of the reference dose in the central region of the breast for both treatments. In the lower third breast region, 62% of patients in the standard arm received doses above 105–110% and 8% received dose over 110%. For patients in the IMRT arm this is reduced to 3% and 1%, respectively.
View larger version (18K):
[in this window]
[in a new window]
|
Figure 3. Pie charts summarizing the dose-position relationship for 150 patients treated with standard wedged plans and 150 patients with intensity modulated radiotherapy (IMRT) plans.
|
|
Dose volume histogram evaluation
Although DVH data are useful for summarizing average dosimetry for a group, it is not possible to determine the characteristics of an average dose distribution as spatial information is lost (Appendix A). Figure 4 shows a typical differential DVH for standard wedged and IMRT treatments. Individual DVH are skewed towards high dose volumes for standard treatments, whilst DVH data for patients allocated IMRT show reduced width and skew.
Table 1 shows data from each of the plans and the comparison between them using the two-sided student t-test. On average, IMRT improves homogeneity by 10.9% (p<0.001). The reduction in V105 is 10.7% (p<0.001); the mean change in V95 is 0.2% (p=0.63). If we consider whether the inhomogeneity is owing more to underdose than overdose in the treatment volume, this changes from 7.5% i.e. more high dose volume than low dose volume in the standard treatments to -3.0% in the IMRT. This change is significant, with a p-value of <0.001.
View this table:
[in this window]
[in a new window]
|
Table 1. Comparison of standard wedged and intensity modulated radiotherapy (IMRT) treatments delivered, averaged over all patients in each group. Volume (V) indicates the percentage of the target volume receiving the percentage dose specified in parentheses
|
|
Figure 5 summarizes maximum and mean dose data. The mean reduction in maximum dose level comparing standard treatment to IMRT is 5.0% (p<0.001). Mean dose in the standard treatments is 101.6% and that in the IMRT 99.6%. These values are significantly different from the ideal 100.0% (p<0.001 for both).
View larger version (40K):
[in this window]
[in a new window]
|
Figure 5. Bar chart showing the effect of intensity modulated radiotherapy on the maximum and mean doses in the treatment volume. The data are the mean over all 300 plans.
|
|
|
Discussion
|
|---|
Dose volume data are useful for comparing treatment plans, However, it is believed that anatomical distribution of dose is an important determinant of treatment outcome. The clinical trial data set records the location of pain and discomfort in the treated breast. A simple method was required to show, for each patient, the location of significant dose bands in the breast without having to view the whole dose distribution and without losing positional information, as would occur by using DVH data. A specific concern was the position of high dose in the breast, since this aspect of tangential radiotherapy is expected to affect risk and severity of late adverse effects. The simple method used herein fulfils the clinical requirements. It should be noted that the portal-image-based outline set does not discriminate between left and right, as the outline is symmetrical. The central region of the breast is most likely to deviate from a symmetrical shape and Figure 4
shows that there is only a small amount of high dose in this region; the dominant variation is in the upper and lower breast, where shape is more symmetrical.
Results presented in Figure 3 suggest another approach would have been to evaluate DVH for each of the three regions defined in the PTV. Whilst this would have been comprehensive, this added level of complexity would not have been significantly more sensitive to dose differences in the two sets of patients. This view is supported by the data generated by our approach, summarized in Figure 3, which clearly discriminates between trial arms. Obviously, final analysis must include correlation with clinical outcome data, including change in breast size and shape, scored by patients and physicians, and breast pain, tenderness and discomfort, scored by patients.
Cheng and Das [22] considered the loss of spatial information in the DVH and have developed a concept of the z-dependent DVH (zDVH), which they applied to three disease sites, of which the breast was one. For one example breast plan they evaluated hot and cold spots with respect to the CT slice z coordinate and showed that the largest volumes of overdose occurred in the most inferior planes and underdose in the superior planes. This result was not consistent with our findings; both high and low dose definitions were significantly different and their study was for one patient CT data set only.
Published studies that consider IMRT for breast radiotherapy indicate similar results to our analysis, although other analyses of dose-position relationships are restricted. The majority of authors show single sagittal or quasisagittal slices to demonstrate typical distributions, but do not attempt to quantify this further. Carruthers et al [8] used a measure referred to as "superior-inferior dose variation", which succinctly describes the range of dose in the superior–inferior direction, but did not describe the position of specific dose bands. Hong et al [10] described a comparison of standard tangent pair and intensity modulated plans for 10 CT data sets and showed that the dose homogeneity in treatment volume is improved with IMRT. They reported a reduction of 4% in the high dose regions in the breast, with maximum improvement of 8% in the superior and inferior regions of the breast.
The DVH data presented here are comparable with Donovan et al's previously published study [19], as well as with that reported by several other authors [6, 9, 11, 14, 15]. Of the simpler two-segment methods, Lo et al [13] report that dose uniformity in the breast is improved by 7% and Langmack et al [12] demonstrate a reduction in maximum dose in treatment volume from 116% to 106% for their test patient. These are of similar order of improvement to our results from the much larger treated group of 300 patients. Further, our large patient group allows the evaluation of significance values. The maximum dose values in Figure 5 shows that not only does the IMRT significantly reduce the volume of breast receiving a dose greater than 105% of that prescribed, it also significantly reduces highest dose in the breast from a mean of 111% to 106% of the reference value.
The final column of Table 1 gives an indication of the asymmetry of the differential DVH, and how this differs between the two treatment arms, i.e. whether under dose or over dose dominate the inhomogeneity. If IMRT compensated perfectly for dose inhomogeneity in the breast, this measure would be zero for IMRT plans. This is influenced by the choice of prescription in the design of IMRT. The prescription used for the trial equalized the hot spots in the plan, as is done when choosing wedge angles for a plan on a CT slice set. There is no reference to minimum dose in the prescription and for patients with a large chest wall separation, a small low dose region is seen close to the chest wall in the central region of the plan. This is reflected in the DVH data which shows a mean 4% of the treatment volume receiving a dose less than 95% of that prescribed.
Results show that IMRT is effective in reducing the large volumes of breast receiving high dose levels. However, for the purposes of relating this to patient outcome in the current clinical trial, it is important that mean dose is comparable in both trial arms. If mean dose were lower in the IMRT arm, a lower rate of adverse effects might be owing to a lower mean dose rather than to improved dose uniformity. Figure 5 shows this to be the case; the average of the mean plan dose for patients receiving standard treatment was 101.6% and 99.6% for those receiving IMRT treatment, i.e. 50.8 Gy and 49.8 Gy for a prescription of 50 Gy total, which is unlikely to have clinical significance.
|
Conclusion
|
|---|
The authors have developed and applied a simple method to analyse anatomical dose distribution in the breast in a cohort of 300 patients, randomized to standard wedged radiotherapy or IMRT. Significant improvement in spatial distribution is seen using IMRT, both in terms of volume and dose level, without compromising either minimum dose coverage or mean dose delivered to the breast.
|
Acknowledgments
|
|---|
The authors would like to thank all members of the Breast Technology Group of the Royal Marsden NHS Trust and the Institute of Cancer Research (both Sutton and Chelsea sites) for their assistance in all aspects of the work and, in particular, would like to acknowledge Helen Convery, Shelley Blane, Colin Nalder and Carole Meehan for their invaluable assistance with the treatment planning and portal imager calibration. The authors are very grateful to Liz Adams for help with the manuscript.
|
Appendix A. Simple illustration of the limitation of dose-volume histogram data and the use of dose-position analysis
|
|---|
Consider two simple, hypothetical dose distributions, which are each specified on a 3 x 1 grid, with one dose calculation point for each of upper, middle and lower as shown at the top left and centre of Figure 6. Distribution 1 has 100% dose to the middle and 50% elsewhere, whereas distribution 2 has 100% dose to the top and 50% dose elsewhere. DVH for the two distributions are shown below each and are identical for each. Therefore the average DVH of both is identical to each individual DVH. Average dose distribution is shown at the top right of Figure 6, with its DVH below. Clearly, DVH of the average dose distribution is different from the average DVH. Similarly, for the example in Figure 7 for 10 sets of patient data, the average DVH does not represent the individual data.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 6. The upper line of the diagram shows three hypothetical dose distributions with the corresponding dose-volume histogram beneath.
|
|
View larger version (17K):
[in this window]
[in a new window]
|
Figure 7. An example of 10 individual dose-volume histogram (DVH) plots and their mean DVH plot. ---, individual DVH; —, mean DVH.
|
|
Whilst averaging DVH data is not useful, it is possible to say for the same distributions that 50% have a dose of 100% in the upper region, 50% have a dose of 100% in the middle region and 100% have a dose of 50% in the lower region. This provides a means of averaging with regard to position and also informs of dose.
|
Footnotes
|
|---|
This work is supported by a Programme Grant from The Cancer Research Campaign [CRC] under grant reference SP2312/0201. The South Thames Regional Health Authority and the Royal Marsden NHS Trust provided financial support. 
Received for publication March 20, 2002.
Revision received June 5, 2002.
Accepted for publication August 1, 2002.
|
References
|
|---|
- Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet 2000;355:1757–70.[Medline]
- Neal AJ, Mayles WPM, Yarnold JR. Invited review: tangential breast irradiation—rationale and methods for improving dosimetry. Br J Radiol 1994;67:1149–54.[Abstract/Free Full Text]
- Neal AJ, Torr M, Helyer S, Yarnold JR. Correlation of breast dose heterogeneity with breast size using 3D CT planning and dose-volume histograms. Radiother Oncol 1995;34:210–8.[Medline]
- Taylor ME, Perez CA, Halverson KJ, et al. Factors influencing cosmetic results after conservation therapy for breast cancer. Int J Radiat Oncol Biol Phys 1995;31:753–64.[Medline]
- Moody AM, Mayles WPM, Bliss JM, et al. The influence of breast size on late radiation effects and correlation with radiotherapy dose inhomogeneity. Radiother Oncol 1994;33:106–12.[Medline]
- Aref A, Thornton D, Youssef E, et al. Dosimetric improvements following 3d planning of tangential breast irradiation. Int J Radiat Oncol Biol Phys 2001;48:1569–74.
- Asbury L, Luttrell L, Lake D. Achieving uniform dose with the use of a custom tissue compensator and a leveled beam for tangential breast fields. Med Dosim 1989;14:161–71.[Medline]
- Carruthers LJ, Redpath AT, Kunkler IH. The use of compensators to optimise the three dimensional dose distribution in radiotherapy of the intact breast. Radiother Oncol 1999;50:291–300.[Medline]
- Chang SX, Deschesne KM, Cullip TJ, Parker S, Earnhart J. A comparison of different intensity modulation treatment techniques for tangential breast irradiation. Int J Radiat Oncol Biol Phys 1999;45:1305–14.[Medline]
- Hong L, Hunt M, Chui C, et al. Intensity-modulated tangential beam irradiation of the intact breast. Int J Radiat Oncol Biol Phys 1999;44:1155–64.[Medline]
- Kestin LL, Sharpe MB, Frazier RC, et al. Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience. Int J Radiat Oncol Biol Phys 2000;48:1559–68.[Medline]
- Langmack KA, Hoole A, Routsis D, et al. Practical intensity modulated radiotherapy for improving dose homogeneity in tangent breast irradiation. Br J Radiol 2000;73(Suppl.):41.
- Lo Y-C, Yasuda G, Fitzgerald TJ, Urie MM. Intensity modulation for breast treatment using static multi-leaf collimators. Int J Radiat Oncol Biol Phys 2000;46:187–94.[Medline]
- Van Asselen B, Raaijmakers CPJ, Hofman P, Lagendijk JJW. An improved breast irradiation technique using three-dimensional geometrical information and intensity modulation. Radiother Oncol 2001;58:341–7.[Medline]
- Zachrisson B, Arevarn M, Karlsson M. Optimised MLC-beam arrangements for tangential breast irradiation. Radiother Oncol 2000;54:209–12.[Medline]
- Evans PM, Hansen VN, Mayles WPM, Swindell W, Torr M, Yarnold JR. Design of compensators for breast radiotherapy using electronic portal imaging. Radiother Oncol 1995;37:43–54.[Medline]
- Evans PM, Donovan EM, Fenton N, et al. Practical implementation of compensators in breast radiotherapy. Radiother Oncol 1998;49:255–65.[Medline]
- Evans PM, Donovan EM, Partridge M, et al. The delivery of intensity modulated radiotherapy to the breast using multiple static fields. Radiother Oncol 2000;57:79–89.[Medline]
- Donovan EM, Johnson U, Shentall GS, Evans PM, Neal AJ, Yarnold JR. Evaluation of compensation in breast radiotherapy—a planning study using multiple static fields. Int J Radiat Oncol Biol Phys 2000;46:671–9.[Medline]
- International Commission on Radiation Units and Measurements. Prescribing, recording and reporting photon beam therapy. Report 50. Bethsada, MD: ICRU, 1993.
- International Commission on Radiation Units and Measurements. Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Report 62. Bethsada, MD: ICRU, 1999.
- Cheng C-W, Das IJ. Treatment plan evaluation using dose-volume histogram (DVH) and spatial dose-volume histogram (zDVH). Int J Radiat Oncol Biol Phys 1999;43:1143–50.[Medline]
This article has been cited by other articles:
|
|
|
|
 
P CASTRO PENA, Y M KIROVA, F CAMPANA, R DENDALE, M A BOLLET, N FOURNIER-BIDOZ, and A FOURQUET
Anatomical, clinical and radiological delineation of target volumes in breast cancer radiotherapy planning: individual variability, questions and answers
Br. J. Radiol.,
July 1, 2009;
82(979):
595 - 599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E M DONOVAN, J R YARNOLD, E J ADAMS, A MORGAN, A P J WARRINGTON, and P M EVANS
An investigation into methods of IMRT planning applied to breast radiotherapy
Br. J. Radiol.,
April 1, 2008;
81(964):
311 - 322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J A Violet and C Harmer
Breast cancer: improving outcome following adjuvant radiotherapy
Br. J. Radiol.,
October 1, 2004;
77(922):
811 - 820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M T Guerrero Urbano and C M Nutting
Clinical use of intensity-modulated radiotherapy: part II
Br. J. Radiol.,
March 1, 2004;
77(915):
177 - 182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H V James, C D Scrase, and A J Poynter
Practical experience with intensity-modulated radiotherapy
Br. J. Radiol.,
January 1, 2004;
77(913):
3 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
