Medical Dosimetry 39 (2014) 163–168
Medical Dosimetry journal homepage: www.meddos.org
A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes Andrea Michalski, B.App.Sc., M.R.S., R.T. (Hons),n† John Atyeo, Ph.D.,n Jennifer Cox, Ph.D.,n‡ Marianne Rinks, Ph.D.,n§ Marita Morgia, B.Med., F.R.A.N.Z.C.R.,‡ and Gillian Lamoury, B.Med., F.R.A.N.Z.C.R.‡ *Department of Health Science (MRS), The University of Sydney, Lidcombe, New South Wales, Australia; †Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales, Australia; ‡Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; and § Radiation Oncology, Cancer Services, Illawarra Shoalhaven Local Health District, Wollongong, New South Wales, Australia
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 July 2013 Accepted 3 December 2013
Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. All patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D98% 4 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D98% 4 95% and D2% o 107%. Static tomotherapy offered significantly improved (p ¼ 0.006) dose homogeneity to the PTVboost eval (0.079 ⫾ 0.011) and breast minus the SIB volume (BreastSIB) (p o 0.001, 0.15 ⫾ 0.03) compared with the PTVboost eval (0.085 ⫾ 0.008, 0.088 ⫾ 0.12) and BreastSIB (0.22 ⫾ 0.05, 0.23 ⫾ 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p o 0.001) in doses to the ipsilateral lung mean dose of 6.79 ⫾ 2.11 Gy compared with 7.75 ⫾ 2.54 Gy and 8.29 ⫾ 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p o 0.001) reduced heart doses (mean ¼ 2.83 ⫾ 1.26 Gy) compared to both IMRT and 3D-CRT (mean ¼ 3.70 ⫾ 1.44 Gy and 3.91 ⫾ 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung. Crown Copyright & 2014 Published by Elsevier Inc. on behalf of American Association of Medical Dosimetrists.
Keywords: Breast cancer 3D-CRT IMRT Tomotherapy Simultaneous integrated boost
Introduction Radiation therapy to the whole surgery is the standard of care with early-stage breast cancer.1 It additional boost to the tumor
breast after breast-conserving for most women diagnosed has also been shown that an bed further reduces local
Part of this work was presented at the 10th Annual Scientific Meeting of Medical Imaging and Radiation Therapy, Wrest Point, Hobart, Australia, 8 to 10 March 2013. Reprint requests to: John Atyeo, Ph.D., Department of Health Science, Discipline of Medical Imaging and Radiation Sciences, The University of Sydney, 75 East Street, Lidcombe, New South Wales 2141, Australia. E-mail:
[email protected]
recurrence.1,2 Traditionally, whole-breast treatment is given using 2 opposed, wedged, tangential fields, with multileaf collimators (MLCs) to shield the ipsilateral lung and heart.3 The boost dose is given using electrons with beam angle, field shape, and beam energy chosen to cover the tumor bed and avoid any organs at risk (OARs), such as the lung, heart, and contralateral breast. Although this 3 dimensional conformal radiotherapy (3D-CRT) technique is successful at improving local control, there are still concerns about the toxicities associated with irradiation of the OARs. Larger breast volumes when compared with smaller volumes have also demonstrated decreased dose homogeneity, resulting in an increase in hot spots, possibly leading to a poorer cosmetic outcome.4-6
0958-3947/$ – see front matter Crown Copyright Ó 2014 Published by Elsevier Inc. on behalf of American Association of Medical Dosimetrists http://dx.doi.org/10.1016/j.meddos.2013.12.003
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Intensity-modulated radiation therapy (IMRT) refers to a technique in which radiation of a nonuniform fluence is used to optimize the dose distribution. This is achieved by breaking each treatment beam into smaller beam segments.7 This modality has been shown to improve dose homogeneity and reduce doses to OARs compared with 3D-CRT. Improved dose homogeneity through the use of IMRT can reduce the occurrence of moist desquamation and other toxicities, thus improving quality of life for patients.8 IMRT can be planned using forward planning or inverse planning. Forward-planned IMRT is similar to 3D-CRT planning where beam parameters are specified and manually optimized. It involves the manual generation of each beam segment, optimized using MLCs to create a nonuniform fluence. Inverse-planned IMRT uses optimization algorithms to create fluence maps and shape dose distributions. Previous studies have shown that inverse planning is superior to forward planning in dose coverage and reducing doses to OARs and requires less planning time.9,10 For this study, IMRT refers to inversely planned IMRT designed to be delivered on a linear accelerator. Tomotherapy is a relatively new treatment machine that uses IMRT calculation methods and has 2 treatment modalities: helical tomotherapy and static tomotherapy. During helical tomotherapy, the MLCs are in continuous motion while the gantry rotates around the patient, as the patient is translated longitudinally through the gantry bore. This allows for beam entry at any angle, resulting in the delivery of low doses to areas of the body that, with conventional treatment, would only receive scattered dose.11 Static tomotherapy uses fixed gantry angles to deliver fan-beam IMRT. During static tomotherapy, each treatment at a particular beam angle is delivered sequentially. The patient is moved through the gantry bore for each static beam angle while the MLC leaves modulate the beam. This option helps to limit the low-dose wash that is observed in helical tomotherapy, and therefore the static tomotherapy modality was used in this planning comparison study. Conventionally, breast radiation therapy of 50 Gy in 25 fractions is prescribed, with up to an additional 16 Gy in 8 fractions to the boost field.2 The boost dose is usually delivered after the whole-breast treatment, but recent studies have investigated a simultaneous integrated boost (SIB) where the boost dose is delivered at the same time as the breast dose. The use of an SIB has been shown to improve dose conformity to the boost volume as well as to decrease doses to heart, lungs, and normal tissue when incorporated with either 3D-CRT or IMRT compared with a sequential boost.12-14 It also has the advantage of reducing the overall number of treatment appointments for the patient. The improved dose homogeneity observed with IMRT has also led to dose hypofractionation, whereby an increase in the daily dose reduces the overall number of treatment fractions. A hypofractionated prescription of 45 Gy in 20 fractions to the breast and 56 Gy in 20 fractions to the tumor bed is an SIB breast treatment
fractionation schedule previously proposed.15 This prescription has a biological equivalent dose of 46 Gy to the whole breast and 14 Gy to the boost. In a study by Freedman et al.,15 this dose was prescribed to 75 women of all breast sizes producing no grade 3 or higher skin toxicities, a resolution of all grade 2 skin toxicities within 6 weeks, and a 5-year local recurrence rate of 1.4%. This demonstrates the feasibility of the fractionation schedule, although longer-term follow-up is required. However, as our study is purely a planning comparison study of different treatment modalities, the fractionation schedule would have no effect in determining the preferred modality to treat left-sided breast cancer with an SIB. The aim of this study was to perform a dosimetric comparison between 3D-CRT, IMRT, and static tomotherapy for women of small and large breast volumes being planned for a whole left breast and SIB technique. The plans created for each modality were compared for dose homogeneity and conformity, mean and maximum doses to the planning target volumes (PTVs), as well as doses to the OARs.
Methods and Materials Patient selection Computed tomography (CT) scans of 20 patients with left-sided breast cancer were included in this planning study. These data sets were randomly selected from patients who had been treated at the Northern Sydney Cancer Centre with radiation therapy to the whole breast and boost volume during 2009 to 2011. CT scans were obtained using a GE LightSpeed RT (General Electric Company, Giles, UK) CT scanner with 2.5-mm slice thickness. Patients were positioned supine with both arms above the head at a 51 inclination on a C-Qual™ Breastboard (CIVCO Medical Solutions, Kalona, IA). The sample consisted of 10 small- and 10 largebreasted women based on breast volume. A breast was considered small if the breast clinical target volume for breast (CTVbreast) was o 500 cm3 and a large breast if the CTVbreast was 4 500 cm3. All 3 modalities were replanned on each data set for the purposes of this research. Definition of target volumes and OARs Contouring of target volumes and OARs was completed on an Eclipse v10 (Varian Oncology, Palo Alto, CA) treatment planning system. All contours, illustrated in Figs. 1 and 2, followed a set of contouring guidelines designed for the purpose of this study. The CTV were delineated by a radiation oncologist, and all other contours were performed by 1 researcher, a medical dosimetrist, to ensure consistency in contouring. A CTVbreast and boost region (CTVboost) was delineated by a radiation oncologist on each CT data set. The CTVboost encompassed the surgical bed, and the CTVbreast was all breast tissue identifiable on the CT scan assisted by wire markers placed around the palpable breast tissue during simulation, limited posteriorly by the pectoralis muscles and retracted 5 mm from the skin. To create the PTVbreast, the CTVbreast was expanded 5 mm, excluding the heart. The PTVbreast was then retracted from the skin by 5 mm and limited posteriorly to no deeper than the anterior ribs to create the PTVbreast eval structure. To create the PTVboost, the CTVboost was expanded by 10 mm in all directions. The PTVboost was then retracted to within the PTVbreast eval to create the PTVboost eval. The PTVbreast eval and PTVboost eval structures were required for dose-volume histogram analysis. A BreastSIB was also generated as the PTVbreast eval minus the PTVboost with a 5-mm
Fig. 1. Target volume contours. (Color version of figure is available online.)
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The IMRT plans included inversely optimized tangentials weighted 80% and open tangent fields weighted 20%. A base plan was initially calculated with 2 parallel opposing 6-MV photon, open tangential fields with MLC leaves shielding lung and heart. The beam weightings were adjusted to create a point maximum of 105%. The 50% isodose line was created into a contour, adjusted to exclude the heart and the lung, retracted 5 mm from skin and from the boost with a 5-mm margin. This new structure was used during optimization to assist the optimizer to achieve a uniform dose distribution to the PTVbreast. The beam weightings were then adjusted to 20% of their current weighting. A second plan was created using fields with the same tangent angles as the base plan. Two additional fields were added at optimal angles to cover the PTVboost and were optimized using the inverse planning optimizer. Once the optimization was complete, the open tangent fields from the base plan were copied into the IMRT plan and calculated.
Static tomotherapy planning technique
Fig. 2. Organs-at-risk contours. (Color version of figure is available online.) margin; this allowed for analysis of doses to the breast outside of the boost region. Figure 1 illustrates the target volume contours described. The OARs contoured were the spinal cord, ipsilateral and contralateral lungs, heart, contralateral breast, and esophagus and are illustrated in Fig. 2. A normal tissue structure was created to encompass all normal tissue not included in the PTVs. A normal tissue ring with a 35-mm expansion of the PTVbreast eval inside the body was created to limit doses outside the PTVs during IMRT optimization.
IMRT static tomotherapy planning was completed using TomoTherapy v4.03 (Accuray, Madison, WI) demonstration planning software that employs a leastsquares minimization-optimization algorithm and a nonvoxel broad-beam dose calculation algorithm. Static tomotherapy planning parameters consisted of a 25mm (displayed as 2.5 cm on the tomotherapy planning software) field width, 0.215 pitch,19 and 2.4 modulation factor calculated on a fine dose grid. These values were kept constant throughout the planning process. Parallel opposed tangential fields using 6 MV were chosen to cover the PTVbreast and PTVboost with overshoot, with 1 or 2 additional fields at optimal angles to cover the PTVboost. An inverse planning optimization was performed for both the PTVbreast and PTVboost with a prescription of 95% of the PTVboost eval to receive 56 Gy. During SIB planning using the tomotherapy software, prescribing to the PTVboost eval instead of the PTVbreast has previously been shown to offer superior dose coverage.20
Dose prescription and constraints Statistical analysis
All patients were prescribed a dose of 45 Gy in 20 fractions to the whole breast, with an SIB of 56 Gy in 20 fractions. The plans were normalized such that 95% of the prescription dose (42.75 Gy and 53.2 Gy) was delivered to at least 98% of the PTVbreast eval and PTVboost eval with a maximum dose to the boost of 107% (59.92 Gy). Therefore, if 1 planning technique demonstrates lower normal tissue doses, this will not be because of poorer coverage of the PTVs. This allows direct comparisons to be made between the 3 modalities under investigation. Planning techniques were also optimized in an attempt to reduce the OARs dose to the dose limits listed in Table 1. All maximum doses reported are to a volume of 2% (International Commission on Radiation Units [ICRU] Report 83).
Dose information was collected to evaluate PTV coverage and doses to OARs. Mean dose (Dmean), maximum dose (Dmax), dose homogeneity index (HI), dose conformation number (CN) and V105% (47.25 Gy) were reported for PTV coverage comparisons. Dmean, Dmax, and volumes receiving specific doses were calculated for the OARs. A repeated measures 3-way difference analysis of variance and repeated measures t-tests were used for statistical analysis. Differences between the 3 modalities were considered significant if p o 0.05. HI was calculated using the formula recommended in ICRU Report 83, with a result closer to zero indicating greater homogeneity.21 CN was calculated using the following equation as described by van't Riet et al,22 which takes into account both the irradiation of the target volume and irradiation of healthy tissue:
3D-CRT planning technique 3D-CRT breast planning was completed using an Eclipse v10 (Varian Oncology, Palo Alto, CA) treatment planning system that employs an anisotropic analytical algorithm for photon-beam calculation and a generalized gaussian pencil-beam algorithm for electron-beam calculation, both with a grid size of 2.5 mm. Planning consisted of 2 opposed tangential fields with nondiverging posterior field edges using 6-MV photons or 18-MV photons, or both. Wedges, MLC leaves, beam weightings, and energy were adjusted to optimize the plan to ensure adequate PTV dose coverage. An electron beam was used to cover the PTVboost. Electron energies ranged from 6 to 20 MeV and were chosen based on the depth of the PTVboost. The plan summation of tangents and electron boost plans was used to ensure adequate PTV dose coverage and to report on doses to the OARs.
CN ¼
TVRI TVRI TV VRI
where, CN ¼ conformation number, TVRI ¼ target volume covered by the reference isodose (95%) in cm3, TV ¼ target volume in cm3, and VRI ¼ volume of the reference isodose (95%) in cm3. This value ranges from zero to 1, where 1 is the ideal value and a result closer to zero indicates either total absence of conformity or a very large volume of healthy tissue being irradiated compared with the target volume.
Results Target coverage
IMRT planning technique The IMRT planning technique employed in our study was a hybrid IMRT technique as is commonly used in breast IMRT.17,18 A hybrid technique uses open and inversely optimized tangent fields. IMRT breast planning was completed using an Eclipse v10 (Varian Oncology, Palo Alto, CA) treatment planning system that employs an anisotropic analytical algorithm with a 2.5-mm grid size.
Table 2 shows the doses to the PTVs for the 3D-CRT, IMRT, and static tomotherapy planning techniques. All plans met the target constraint that 98% of the PTVboost eval and PTVbreast eval must receive at least 95% of the prescription dose. Results are reported as average ⫾ standard deviation.
Table 1 Dose limits for the OARs during breast radiation therapy planning Organ
Dose limits
Ipsilateral lung16 Contralateral lung Combined lung16 Heart7 Contralateral breast7 Spinal cord Esophagus
V10 Gy o 28% V5 Gy o 5% V10 Gy o 15% V20 Gy o 5% Dmean o 2.5 Gy Dmax o 3 Gy Dmax o 10 Gy
n
Danish Breast Cancer Cooperative, accessed June 2012, www.dbcg.dk.
V20 Gy o 22%
V30 Gy o 17%
Dmean o 10 Gy
V20 Gy o 11% V10 Gy o 30% Dmax o 3 Gy
V30 Gy o 8.7% Dmean o 4 Gy
Dmean o 8 Gy Dmax o 40 Gy*
Dmean o 5 Gy
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Table 2 Between techniques analysis for 3D-CRT, IMRT, and static tomotherapy planning techniques Overall 3D-CRT mean ⫾ SD
PTVboost eval V95% (%) Dmax (Gy) Dmean (Gy) HI CN
98.51 58.38 56.35 0.088 0.49
PTVbreast eval V95% (%) CN
99.09 ⫾ 0.55 0.52 ⫾ 0.07
BreastSIB Dmax (Gy) V105% (%) Dmean (Gy) HI
53.91 41.53 47.23 0.23
⫾ ⫾ ⫾ ⫾ ⫾
⫾ ⫾ ⫾ ⫾
0.47 0.64 0.42 0.12 0.09
1.24 10.24 0.5 0.03
Overall IMRT mean ⫾ SD
98.27 58.12 56.38 0.085 0.66
⫾ ⫾ ⫾ ⫾ ⫾
0.26 0.4 0.23 0.008 0.12*
98.22 ⫾ 0.21 0.56 ⫾ 0.08* 52.61 24.65 46.59 0.22
⫾ ⫾ ⫾ ⫾
2.29* 5.86* 0.28* 0.05
Overall static tomotherapy mean ⫾ SD
98.9 58.21 56.65 0.079 0.64
⫾ ⫾ ⫾ ⫾ ⫾
0.63 0.49 0.43 0.011*† 0.09*
98.57 ⫾ 0.40 0.54 ⫾ 0.08 49.63 11.32 45.87 0.15
⫾ ⫾ ⫾ ⫾
1.21*† 5.76*† 0.35*† 0.03*†
SD ¼ standard deviation; Vx% ¼ volume receiving x% of prescription dose; Dmax ¼ maximum dose to a volume of 2%; Dmean ¼ mean dose; CN ¼ conformity number. n
†
Significantly improved over 3D-CRT. Significantly improved over IMRT.
The average volume (cm3) of the CTVboost for all patients was 17.69 ⫾ 10.01. For small-breasted patients, the average volume (cm3) was 17.14 ⫾ 13.13, and for large-breasted patients, the average volume (cm3) was 18.25 ⫾ 6.18. The HI for the PTVboost eval was significantly better in the tomotherapy plans than the 3D-CRT and IMRT plans (p ¼ 0.006), whereas the CN was significantly better in both the tomotherapy and IMRT plans than the 3D-CRT plans (p o 0.001). There was no difference in doses to the PTVboost eval in relation to patient breast size. The average volume (cm3) of the CTVbreast for all patients was 495.44 ⫾ 267.4. For small-breasted patients, the average volume (cm3) was 300.55 ⫾ 132.9, and for large-breasted patients, it was 690.33 ⫾ 221.12. The CN for the PTVbreast eval was significantly better in the IMRT plans than the 3D-CRT plans (p ¼ 0.009), with no significant difference from the tomotherapy plans. The CN generated for the plans of large-breasted patients was significantly better than for small-breasted patients regardless of modality (p ¼ 0.009). For the BreastSIB, the Dmax, Dmean, and V105% are significantly lower using the IMRT technique over the 3D-CRT technique (p ¼ 0.018, p o 0.001, and p o 0.001, respectively). Tomotherapy is significantly better than both IMRT and conformal for maximum dose (p o 0.001), V105% (p o 0.001), and HI (p o 0.001). There are no significant differences in these measures based on patient breast size. Organs at risk Table 3 shows the doses to the OARs when using 3D-CRT, IMRT, and static tomotherapy planning techniques. For the lungs, there was very little difference in the V5 Gy. Tomotherapy significantly reduced the volumes of the lung receiving between 10 and 30 Gy and the mean ipsilateral and combined lung dose when compared with the 3D-CRT and IMRT plans (p ¼ 0.006). However, tomotherapy produced a significantly higher Dmean than both 3D-CRT and IMRT plans in the contralateral lung (p o 0.001). The IMRT plans had a significantly lower ipsilateral and combined mean dose compared with the 3D-CRT plans (p ¼ 0.006). The heart volumes receiving between 5 and 20 Gy, the Dmean and Dmax are all significantly lower with tomotherapy planning
when compared with both 3D-CRT and IMRT (p ¼ 0.002). The V5 Gy is significantly lower with IMRT than 3D-CRT (p ¼ 0.011), but there were no other significant differences. There were no significant differences between 3D-CRT and IMRT doses to the contralateral breast, the spinal cord, and the esophagus. The Dmean and Dmax to the spinal cord and the esophagus and the Dmean to the contralateral breast were all significantly larger with tomotherapy than 3D-CRT or IMRT planning (p ¼ 0.003). The Dmax to the contralateral breast, however, is significantly reduced with tomotherapy (p o 0.001). When comparing small and large breast volumes, there were no significant differences observed between doses received to the lungs, the heart, the contralateral breast, the spinal cord, or the esophagus, regardless of the modality.
Discussion This study compared 3D-CRT, IMRT, and static tomotherapy for whole-breast radiation therapy with an SIB in patients with small and large breast volumes. Although there have been numerous studies comparing IMRT and tomotherapy with 3D-CRT, there are Table 3 Doses to the OARs for 3D-CRT, IMRT, and static tomotherapy planning techniques Overall 3D-CRT mean ⫾ SD
Ipisilateral lung V5 Gy (%) V10 Gy (%) V20 Gy (%) V30 Gy (%) Dmean (Gy) Contralateral lung V5 Gy (%) Dmean (Gy)
27.54 19.05 14.62 12.91 8.29
⫾ ⫾ ⫾ ⫾ ⫾
9.02 6.89 5.85 5.50 2.76
0.0004 ⫾ 0.001 0.19 ⫾ 0.09‡
Overall IMRT mean ⫾ SD
26.82 18.57 14.79 12.64 7.75
⫾ ⫾ ⫾ ⫾ ⫾
8.27 6.58 6.04 5.66 2.54*
0.046 ⫾ 0.18 0.20 ⫾ 0.17‡
Overall static tomotherapy mean ⫾ SD
28.60 15.95 11.90 9.18 6.79
⫾ ⫾ ⫾ ⫾ ⫾
10.42 5.33*† 4.76*† 4.10*† 2.11*†
0.114 ⫾ 0.510 0.53 ⫾ 0.2
Combined lung V5 Gy (%) V10 Gy (%) V20 Gy (%) V30 Gy (%) Dmean (Gy)
12.51 8.68 6.68 5.89 3.88
⫾ ⫾ ⫾ ⫾ ⫾
4.02 3.19 2.76 2.59 1.29
12.23 8.48 6.76 5.80 3.65
⫾ ⫾ ⫾ ⫾ ⫾
3.79 3.12 2.88 2.68 1.20*
13.02 7.25 5.43 4.19 3.38
⫾ ⫾ ⫾ ⫾ ⫾
4.33 2.45*† 2.22*† 1.90*† 0.95*†
Heart V5 Gy (%) V10 Gy (%) V20 Gy (%) Dmean (Gy) Dmax (Gy)
11.69 7.24 5.65 3.91 36.26
⫾ ⫾ ⫾ ⫾ ⫾
5.22 3.82 3.27 1.58 13.95
10.58 7.42 5.85 3.70 34.44
⫾ ⫾ ⫾ ⫾ ⫾
4.44* 3.73 3.26 1.44 12.30
9.13 5.14 3.51 2.83 25.56
⫾ ⫾ ⫾ ⫾ ⫾
5.78*† 2.91*† 2.41*† 1.26*† 12.04*†
Contralateral breast Dmean (Gy) Dmax (Gy)
0.31 ⫾ 0.11‡ 2.02 ⫾ 0.50
0.38 ⫾ 0.24‡ 2.62 ⫾ 1.29
0.57 ⫾ 0.20 1.85 ⫾ 0.66*†
Spinal cord Dmean (Gy) Dmax (Gy)
0.21 ⫾ 0.09‡ 0.38 ⫾ 0.14‡
0.18 ⫾ 0.08‡ 0.41 ⫾ 0.37‡
0.36 ⫾ 0.22 1.56 ⫾ 1.33
Esophagus Dmean (Gy) Dmax (Gy)
0.48 ⫾ 0.18‡ 0.69 ⫾ 0.28‡
0.48 ⫾ 0.18‡ 1.11 ⫾ 1.12‡
0.79 ⫾ 0.47 2.17 ⫾ 1.63
Normal tissue Dmean (Gy) Dmax (Gy)
2.5 ⫾ 0.48 42.60 ⫾ 4.48
2.55 ⫾ 0.51 41.45 ⫾ 4.60*
2.34 ⫾ 0.54*† 37.32 ⫾ 8.18*†
Normal tissue ring Dmean (Gy) Dmax (Gy)
21.01 ⫾ 2.72 50.18 ⫾ 1.72
21.12 ⫾ 3.07 47.63 ⫾ 1.2*
18.08 ⫾ 3.26*† 47.63 ⫾ 1.27*
SD ¼ standard deviation; Vx Gy ¼ volume receiving x Gy of radiation; Dmax ¼ maximum dose to a volume of 2%; Dmean ¼ mean dose. n
† ‡
Significantly improved over 3D-CRT. Significantly improved over IMRT. Significantly improved over static tomotherapy.
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none that include static tomotherapy and SIB. The aim was to determine which modality provided the best dose distribution while minimizing doses to the OARs. To assess the influence of patient breast size, comparisons of dose distributions were also made in relation to breast volume. CTV contouring was completed by a radiation oncologist, and to minimize interobserver variability in this planning study, all other contouring and treatment planning was completed by 1 researcher, a medical dosimetrist. Initial tomotherapy plans were also reviewed by a tomotherapy application specialist to ensure the quality of the tomotherapy plans. Only patients with left-sided breast cancer were included in this study owing to the importance of minimizing radiation doses to the heart. All other parameters are the same for right-sided patients, so no differences in any other results would be expected. Dosimetry No previous studies have compared 3D-CRT, IMRT, and static tomotherapy for whole breast with an SIB. In our study, all plans achieved the target dose constraint such that 95% of the prescription dose (42.75 Gy and 53.2 Gy) was delivered to at least 98% of the PTVbreast eval and PTVboost eval, with a maximum dose to the boost o 107% (59.92 Gy). Static tomotherapy was the only modality that also kept doses to the OARs below the set dose limits. 3DCRT and IMRT had heart V20 Gy of 5.65% and 5.85%, respectively, slightly above the 5% dose limit. Both the IMRT and static tomotherapy techniques reduced maximum and mean doses to the breast while also lowering mean doses to the OARs compared with 3D-CRT. This is similar to previous studies that have reported improved dose homogeneity and lower doses to OARs using inverse-planned optimization modalities.9,13,23 Static tomotherapy demonstrated further improvements in dose homogeneity and conformity of the target structures and resulted in lower doses to the OARs compared with IMRT. This is consistent with a previous study by Schubert et al.9 who compared treatment modalities to the whole breast without an SIB. In a clinical setting, there can be subjectivity when evaluating any dose plan or technique as each radiation oncology department will have their own guidelines for compromises and trade-offs. Where shorter treatment times might be a priority for some, others might want improved target coverage or reduced doses to the OARs. To reduce this type of subjectivity, the minimum dose to the PTVs in our research study was set at 95% of the prescription dose to 98% of the PTV as recommended in ICRU Report 83.21 Although we have chosen to use this dose, other researchers may have set different dosimetric outcomes. This has resulted in numerous planning parameters and methodologies used in various studies which can affect the plan results making it difficult to compare the plan dosimetry between studies. In 3D-CRT planning, the use of different weightings, wedges, and beam energy will all affect the dosimetric outcome of the plans. However, these options have very little effect on reducing doses to the OARs. For IMRT planning, the creation of different contours, inverse planning parameters, objectives, and priority of structures will also influence the resulting plan dosimetry, including improvements in homogeneity and conformity as well as allowing for superior OAR sparing. For treatments delivered using a linear accelerator, multiple treatment planning software systems and calculation algorithms are available which can also affect the dosimetric result. Different planning and treatment parameters are available with static tomotherapy vs linear accelerator 3D-CRT and IMRT. These include couch translation through the gantry bore during treatment combined with the dynamic micro-MLC leaf motions, which can influence the resulting plan dosimetry and allow for reductions in doses to the OAR. During static tomotherapy planning, increasing the modulation factor can improve
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conformity but may also increase treatment times. Moreover, increasing the field width from 25 to 50 mm may result in a poorer quality plan but can reduce treatment times.24 Blocking structures can also be created in tomotherapy planning, where structures can be directionally blocked, preventing beams from entering them, or completely blocked, preventing beams from entering or exiting them. Both static tomotherapy and IMRT use photon radiation to treat the boost, whereas 3D-CRT routinely uses electron radiation. The dose profile of electron radiation results in higher skin doses and greater sparing of organs behind the target structure compared with the skin-sparing dose profile of photon radiation. Electron radiation for the breast boost is generally preferred owing to the superficial nature of breast cancer and limiting doses to the heart and the lungs behind the breast. However, SIB techniques with electron radiation are not practical in the clinical environment owing to the extensive time required to set up both the photon whole breast and the electron boost treatment. In addition, breast boost volumes are increasingly situated closer to the chest wall, where electron radiation may not be suitable. Studies investigating 3D-CRT to the whole breast with a 3D conformal photon boost are warranted to ensure differences attributed to planning techniques are not primarily because of the difference in boost radiation modality as well as ensuring clinical feasibility of implementing SIB techniques. Being a dosimetric planning study, there were a number of factors that were not considered in judging the superiority of one modality over another. These include physics resources, cost of new equipment, staff training, adequate patient immobilization, treatment image verification, and treatment times. Factors such as these would need to be further investigated by each radiation oncology department before the implementation of new modalities and planning techniques.
Breast size Previous studies have shown breast size to be an important determinant of breast dose homogeneity and that IMRT can improve dose homogeneity.4-6,25 In this study, we found that breast size had little effect regardless of the modality used. This may be because of the small sample size used in this study or the inclusion of a boost treatment. The location of the boost could affect dose homogeneity and doses to OARs regardless of the patient size. Further studies with larger sample sizes, larger breast volumes, and reporting boost locations might enable more definitive conclusions to be made.
Conclusions This study compared static tomotherapy, IMRT, and 3D-CRT to treat the whole left breast with an SIB, with the aim of determining which modality provided the best target coverage while minimizing doses to the OARs. The influence of patient breast size on dosimetry was also assessed. Of the 3 modalities investigated, the results indicate that static tomotherapy is the best planning technique. Static tomotherapy offered significantly superior doses to the PTVs compared with both 3D-CRT and IMRT while also producing significantly lower doses to the ipsilateral lung, combined lung, and heart. There was very little difference in dosimetry between patients of different breast size regardless of the modality. Where an SIB is to be incorporated and tomotherapy is unavailable, an IMRT modality would be the next preferred treatment option, rather than 3D-CRT. Before clinical implementation, future research in hypofractionation with an SIB as well as
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consideration of other factors including physics resources, daily imaging, and reproducible positioning is warranted.
Acknowledgments The authors thank The Royal Brisbane and Women's Hospital Radiation Oncology Department and radiation therapist, Selina Harris, for providing clinical tuition on the TomoTherapy planning system; Regina Bromley from Royal North Shore Hospital for her advice in Eclipse IMRT planning; Accuray and Sue Warren for loan of the TomoTherapy planning demonstration laptop and for all her assistance during the initial project development stage; and Dr Robert Heard, statistician from the University of Sydney, for assisting with the data analysis and results. References 1. Poortmans, P.M.; Collette, L.; Bartelink, H.; et al. The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 “boost versus no boost” trial. Cancer Radiother. 12:565–70; 2008. 2. Bartelink, H.; Horiot, J.C.; Poortmans, P.; et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N. Engl. J. Med. 345:1378–87; 2001. 3. Washington, C.; Leaver, D. Principles and practice of radiation therapy. 2nd ed., St. Louis, Missouri, 2004. 4. Neal, A.J.; Torr, M.; Helyer, S.; et al. Correlation of breast dose heterogeneity with breast size using 3D CT planning and dose-volumes histograms. Radiother. Oncol. 34:210–8; 1995. 5. Ramsey, C.R.; Chase, D.; Scaperoth, D.; et al. Improved dose homogeneity to the intact breast using three-dimensional treatment planning: Technical considerations. Med. Dosim. 25:1–6; 2000. 6. Winfield, E.A.; Deighton, A.; Venables, K.; et al. Survey of tangential field planning and dose distribution in the UK: Background to the introduction of the quality assurance programme for the START trial in early breast cancer. Br. J. Radiol. 76:254–9; 2003. 7. Vicini, F.; Freedman, G.M.; White, J.; et al. A phase III trial of accelerated whole breast irradiation with hypofractionation plus concurrent boost versus standard whole breast irradiation plus sequential boost for early-stage breast cancer: RTOG 1005, Volume 2012; 2011. 8. Pignol, J.-P.; Olivotto, I.; Rakovitch, E.; et al. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J. Clin. Oncol. 26:2085–92; 2008.
9. Schubert, L.; Gondi, V.; Sengbusch, E.; et al. Dosimetric comparison of left-sided whole breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy and topotherapy. Radiother. Oncol. 100:241–6; 2011. 10. Smith, W.; Menon, G.; Wolfe, N.; et al. IMRT for the breast: A comparison of tangential planning techniques. Phys. Med. Biol. 55:1231–41; 2010. 11. O'Donnell, H.; Cooke, K.; Walsh, N.; et al. Early experience of tomotherapybased intensity-modulated radiotherapy for breast cancer treatment. Clin. Oncol. 21:294–301; 2009. 12. Hurkmans, C.W.; Meijer, G.J.; van, V.-V.C.; et al. High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization. Int. J. Radiat. Oncol. 66:923–30; 2006. 13. Singla, R.; King, S.; Albuquerque, K.; et al. Simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT) in the treatment of earlystage left-sided breast carcinoma. Med. Dosim. 31:190–6; 2006. 14. Van der Laan, H.P.; Dolsma, W.V.; Maduro, J.H.; et al. Three-dimensional conformal simultaneously integrated boost technique for breast-conserving radiotherapy. Int. J. Radiat. Oncol. 68:1018–23; 2007. 15. Freedman, G.M.; Anderson, P.R.; Goldstein, L.J.; et al. Four-week course of radiation for breast cancer using hypofractionated intensity modulated radiation therapy with an incorporated boost. Int. J. Radiat. Oncol. 68:347–53; 2007. 16. Teh, A.Y.M.; Park, E.J.H.; Shen, L.; et al. Three-dimensional volumetric analysis of irradiated lung with adjuvant breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 75:1309–15; 2009. 17. Mayo, C.S.; Urie, M.M.; Fitzgerald, T.J. Hybrid IMRT plans—Concurrently treating conventional and IMRT beams for improved breast irradiation and reduced planning time. Int. J. Radiat. Oncol. Biol. Phys. 61:922–32; 2005. 18. van Asselen, B.; Schwarz, M.; van Vliet-Vroegindeweij, C.; et al. Intensitymodulated radiotherapy of breast cancer using direct aperture optimization. Radiother. Oncol. 79:162–9; 2006. 19. Kissick, M.; Fenwick, J.; James, J.; et al. The helical tomotherapy thread effect. Med. Phys. 32:1414–23; 2005. 20. Rong, Y.; Fahner, T.; Welsh, J.S. Hypofractionated breast and chest wall irradiation using simultaneous in-field boost IMRT delivered via helical tomotherapy. Technol. Cancer Res. Treat. 7:433–9; 2008. 21. ICRU Report 83: Prescribing recording and reporting photon beam intensity modulated radiation therapy. J. ICRU 10:1–106; 2010. 22. van't Riet, A.; Mak, A.C.; Moerland, M.A.; et al. A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: Application to the prostate. Int. J. Radiat. Oncol. 37:731–6; 1997. 23. Guerrero, M.; Li, X.A.; Earl, M.A.; et al. Simultaneous integrated boost for breast cancer using IMRT: A radiobiological and treatment planning study. Int. J. Radiat. Oncol. Biol. Phys. 59:1513–22; 2004. 24. Reynders, T.; Tournel, K.; De Coninck, P.; et al. Dosimetric assessment of static and helical tomotherapy in the clinical implementation of breast cancer treatments. Radiother. Oncol. 93:71–9; 2009. 25. Donovan, E.; Bleakley, N.; Denholm, E.; et al. Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother. Oncol. 82:254–64; 2007.