Dosimetric assessment of static and helical TomoTherapy in the clinical implementation of breast cancer treatments

Radiotherapy and Oncology 93 (2009) 71–79

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Breast cancer radiotherapy

Dosimetric assessment of static and helical TomoTherapy in the clinical implementation of breast cancer treatments Truus Reynders a,*, Koen Tournel a, Peter De Coninck a, Steve Heymann b, Vincent Vinh-Hung a, Hilde Van Parijs a, Michaël Duchateau a, Nadine Linthout a, Thierry Gevaert a, Dirk Verellen a, Guy Storme a a b

Radiotherapy Department, Oncology Center, UZ Brussel, 1090 Brussels, Belgium Radiotherapy Department, Centre de Lutte Contre le Cancer Paul Strauss, F-67065 Strasbourg Cedex, France

a r t i c l e

i n f o

Article history: Received 18 December 2008 Received in revised form 9 June 2009 Accepted 6 July 2009 Available online 12 August 2009 Keywords: TomoTherapy TomoDirect Breast Dose verification

a b s t r a c t Background and purpose: Investigation of the use of TomoTherapy and TomoDirect versus conventional radiotherapy for the treatment of post-operative breast carcinoma. This study concentrates on the evaluation of the planning protocol for the TomoTherapy and TomoDirect TPS, dose verification and the implementation of in vivo dosimetry. Materials and methods: Eight patients with different breast cancer indications (left/right tumor, axillary nodes involvement (N+)/no nodes (N0), tumorectomy/mastectomy) were enrolled. TomoTherapy, TomoDirect and conventional plans were generated for prone and supine positions leading to six or seven plans per patient. Dose prescription was 42 Gy in 15 fractions over 3 weeks. Dose verification of a TomoTherapy plan is performed using TLDs and EDR2 film inside a home-made wax breast phantom fixed on a randoalderson phantom. In vivo dosimetry was performed with TLDs. Results: It is possible to create clinically acceptable plans with TomoTherapy and TomoDirect. TLD calibration protocol with a water equivalent phantom is accurate. TLD verification with the phantom shows measured over calculated ratios within 2.2% (PTV). An overresponse of the TLDs was observed in the low dose regions (<0.1 Gy). The film measurements show good agreement for high and low dose regions inside the phantom. A sharp gradient can be created to the thoracic wall. In vivo dosimetry with TLDs was clinically feasible. Conclusions: The TomoTherapy and TomoDirect modalities can deliver dose distributions which the radiotherapist judges to be equal to or better than conventional treatment of breast carcinoma according to the organ to be protected. Ó 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 93 (2009) 71–79

Breast cancer is a widespread disease among women. One out of eight women in western countries will develop breast cancer during her lifetime. Surgery, radiotherapy or the combination of both has proven to be the basic approach for the treatment of breast cancer [1,2]. Since the introduction of IMRT (Intensity-Modulated Radiotherapy) [3] in the mid-90s a lot of research has been performed to implement these IM-techniques for the treatment of breast cancer [4]. Although it was shown that better target coverage and OAR sparing could be achieved, the notion has grown that these techniques will only have benefit on patients when a good imaging and patient positioning technique is available, suggesting a combined IMRT–IGRT approach [5,6]. Helical TomoTherapy [7–9] combines helical intensity-modulated delivery with an integrated image guidance system by means of a MV-CT scan-modality and seems a likely candidate to perform IM-breast treatments. How* Corresponding author. Address: Radiotherapy Department, Oncology Center, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. E-mail address: [email protected] (T. Reynders). 0167-8140/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2009.07.005

ever TomoTherapy has to deal with a few disadvantages. In helical TomoTherapy, the gantry continuously rotates around the patient, who is translated through the beam delivery plane. This technique allows beam delivery from any gantry angle. In comparison with whole-breast treatments with standard tangential (non-IMRT) radiation therapy, the use of all gantry angles could result in a delivery of low doses to areas in the body that would normally receive only scatter dose. To prevent dose delivery to a structure of interest, the structure can be designated as a ‘‘blocked structure” during the TomoTherapy planning process. By using such methods, the treatment delivery is constrained to a smaller range of directions and a smaller set of beamlets. However, because the gantry speed is constant and the number of treatment directions decreases, the treatment delivery efficiency decreases. This is not a significant problem for most delivery types, but can be an important consideration for cases such as breast when the desired treatment is constrained to a small number of directions. This will result in an unnecessary long treatment time. To avoid this inefficiency of beam usage, an obvious extension of helical

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Helical TomoTherapy breast cancer treatments

TomoTherapy delivery is therefore the use of static gantry positions, combined with simultaneous couch translation and MLC modulation. This option, called TomoDirect previously called TopoTherapy [10], seems particularly well suited for the treatment of the whole breast. If the static gantry angles are identical to the tangential beam angles, this technique is similar to intensity-modulated tangential fields by the use of DMLC sweeping window, the difference being that in the case of TomoDirect, the patient slides through the beam. TomoDirect is not yet clinically available, only a simulation of the planning is available at the time of writing. To perform the clinical implementation of the TomoTherapy breast cancer treatments three issues were investigated. 1. Planning study. At first the feasibility of TomoTherapy in treating breast cancer was investigated by performing a comparative planning study on eight patients in different clinical situations. TomoTherapy patient plans were compared to conventional (non-IMRT) tangential treatments. Further the plans were also calculated using the experimental TomoDirect TPS [11–20]. 2. Dosimetric verification. A dose verification of a TomoTherapy breast plan was performed with TLDs and EDR2 film [21] on a home-made wax breast phantom that was sealed on a randoalderson phantom. 3. In vivo dosimetry. An in vivo protocol and a calibration protocol for TLD measurements were created. Materials and methods Planning study Patient selection Eight adult female patients with a primary unilateral breast cancer referred for post-operative radiotherapy that were treated conventionally at the UZ Brussel with a curative intent were selected for the planning study. There was no limit of age. Inclusion criteria were the presence of one or more of the following factors of cardio-pulmonary toxicity, past medical history of cardiac or pulmonary disease, obesity, breast and chest wall anatomy, left-sided tumors, eligibility for chemotherapy and anti-HER2 therapy. Each patient was presented with a different combination of the following clinical situations: left- or right-sided tumor, axillary lymph nodes involved or not, and tumorectomy or mastectomy. Simulation After informed consent, each patient underwent a double simulation, in supine and prone positions, using dedicated devices. In supine position, the patient’s arms were raised above the head using an arm support in carbon fiber (SinmedÓ, Reeuwijk, The Netherlands). In prone position a specially made carbon-based plate and a high grade polyester pillow (ORFITÓ, Wijnegem, Bel-

gium) were used and the treated breast hangs vertical in a gap beneath the body. Planning CT scans After simulation two planning CTs were performed one in each treatment position (Somatom Emotion, 16-slice, Siemens, Erlangen, Germany) with contrast enhancement, 3-mm slice, starting from mandible to diaphragm. For the TomoTherapy plans it was very important to have the patient completely in the reconstruction circle of the CT scan because TomoTherapy uses a helical treatment and missing anatomical data would render certain directions unusable for treatment planning. However, TomoTherapy also requires a 5-cm space in the image to insert the TomoTherapy table image. For patients in which it was impossible to comply both prerequisites, the priority was given to scanning the patient completely and the incomplete table image was dealt with during planning. Contouring OARs and PTV All contouring of target volumes and normal structures were performed in the Philips PinnacleÒ P3 v5.2g TPS (Philips Medical System, Eindhoven, The Netherlands). The following structures were delineated: CTV(s) (Clinical Target Volume(s)), PTV(s) (Planning Target Volume(s)), ipsilateral and contralateral lungs, heart, contralateral breast, spinal cord, thyroid, oesophagus and sometimes liver. The CTV, PTV(s) and OARs were outlined on all CT slices. The CTV was expanded to a PTV with 5 mm with a constraint reverse expansion of 4 mm to the skin surface to avoid potential skin toxicity [22,23]. The PTV provided a margin around the CTV to compensate for the variability of treatment setup and motion of the breast or chest with breathing (PTV1 for CTV1, PTV chest wall or PTVw for CTVw and PTVn for CTVn). PTV1 was used for the contouring of a breast of a patient that received a tumorectomy. PTVw was used for the contouring of a chest wall of a patient that received a mastectomy. PTVn was used for the contouring of the supraclavicular, infraclavicular and/or axillary lymph node regions [24]. Other structures and planning strategy Specific dose limiting structures were used to better control the TomoTherapy dose distribution. Beside the critical organs and the PTV(s) there were a few other structures contoured. Some additional structures are used to cope with overlap. Blocking structures are used to block incoming and/or exit beams through certain volumes. Working volumes are created to allow the system to optimize without the application of constraints that are unable to be met in practice, e.g. to give the system ‘‘room” to operate (Table 1). Plans were initiated using complete blocks for all blocking structures, and changed when necessary.

Table 1 Overview of additional structures, blocking structures and working volumes. Structure

Reason

Skin_inverse 4 mm

Helpstructure: to cut-off the PTV outside the patient’s skin

PTV_exp_5 cm

Helpstructure: to limit the dose outside the PTV and outside the OARs and to create blocks and working volumes

Block contralateral breast, heart, ipsilateral lung, contralateral lung, liver and spinal cord exp.

Blocking structures: directional or complete blocks were necessary to avoid exit and/or entrance dose through a structure. The blocking structures were based on both lungs, the heart, the liver and the contralateral breast, all minus the PTV, expanded with 5 cm in all directions

Contralateral breast, heart, ipsilateral lung, contralateral lung and liver working

Helpstructure: the working volumes were based on both lungs, the heart, the liver and the contralateral breast minus the blocking structures

T. Reynders et al. / Radiotherapy and Oncology 93 (2009) 71–79

Dose prescription The TomoTherapy dose prescription is specified in terms of percentage volume and absolute dose (e.g. the percentage volume of the primary PTV that receives at least the prescribed dose). A prescription dose of 42 Gy was defined for the 95% isodoses of the PTV (similar for conventional plan and TomoDirect plan), in 15 fractions of 2.8 Gy daily. The PTV volume (95%) should be covered within 95–110% of the prescribed dose (39.9–46.2 Gy). To evaluate the dose constraints for normal tissues we used the NSABP B-39/ RTOG 0413 protocol [25] corrected for hypofractionation [26–28], e.g. V25 Gy < 10% indicates that at least 10% of the volume of the structure should achieve less than 25 Gy. To allow for comparison the same dose prescription was used for all plans. The dose constraints for organs at risk are  Ipsilateral lung with supraclavicular irradiation: V25 Gy < 10%, V17 Gy < 15%, V8 Gy < 20%.  Ipsilateral lung without supraclavicular irradiation: V25 Gy < 5%, V17 Gy < 8%, V8 Gy < 10%.  Contralateral lung: V2.5 Gy < 15%.  Heart: V17 Gy < 5%, V8 Gy < 10%.  Contralateral breast: Dose max <3% of the prescribed dose, mean dose as low as possible.  Thyroid: V20 Gy < 30% in case of supraclavicular irradiation.

Conventional planning To assess the feasibility of planning breast carcinoma with the TomoTherapy and TomoDirect unit a comparison has been made between the conventional technique, TomoTherapy and TomoDirect. In total 52 plans were created, 6 or 7 plans per patient (Tomo supine, Tomo prone, TomoDirect supine, TomoDirect prone, TomoDirect supine with 6 gantry angles, conventional supine and conventional prone). For the conventional technique a virtual simulation of two opposed tangential fields was used for the PTVw or PTV1 and an anterior beam (0° for supine and 180° for prone) for axillo-supraclavicular field for PTVn. Weighted beams and wedges were used. Additional segments using Multileaf Collimator (MLC) leaves (Elekta SL15, ElektaÓ, Crawley, UK) (one per field maximum) were allowed to improve dose homogeneity or heart sparing. Final dose calculation used the collapsed cone convolution method. The energy used was 6 MV or 10 MV according to the best indication. The planning system used was Philips PinnacleÒ P3 v5.2g (Philips Medical System, Eindhoven, The Netherlands). TomoTherapy planning The TomoTherapy Hi-ART system used for the treatment planning, uses a different set of factors to control the dose delivery than Pinnacle. The different parameters that should be set before the beamlet calculation are a pitch, a field width, a modulation factor and a calculation grid [29]. For treatment, only ‘‘tight” pitch factors between 0.25 and 0.30 are applied. The primary collimation jaws were set to a field width of 2.45 cm at isocenter to determine the fan beam width. A modulation factor of 2.0 was used for all plans. The dose calculation grid size was set to ‘‘normal”. TomoDirect planning The TomoDirect plans were generated using prototype software (TomoTherapy Planning Station Version Alpha6 6.1.0.5) from TomoTherapy. A 2.45-cm field width and a modulation factor of 2.0 were used. Because the gantry was stationary, the pitch lost its meaning and is replaced by a cm per projection. The value refers to how much the couch travels per set of leaf projections. A value of 0.15 cm was used, meaning that a new set of leaf opening times was generated for each 0.15 cm of couch travel [10,20]. With TomoDirect, the same structures, block structures and working

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volumes as for TomoTherapy are used for optimization. For all plans two gantry angles were selected. Afterwards patients in supine position without axillary lymph nodes involvement were replanned with six gantry angles (three to each side) to avoid hotspots outside the PTV [12], and to improve dose conformality and dose homogeneity. To plan the breast (PTV1 or PTVw) tangent-like angles were selected initially. Directly opposed beam entries were avoided. For the six-field plans two more sets of gantry angles were selected at 10–20° from the initial tangent fields. Because of the use of complete blocks for contralateral breast, contralateral lung, part of the heart and a part of the ipsilateral lung, angles could be selected without fear of giving an excessive dose to these organs at risk. To plan the axillo-supraclavicular nodes (PTVn), angles near 0° and 180° were selected. To rank the plans, a point system was used giving the plan which achieved the lowest dose according to our dose constraints the highest score, i.e. four points to the best plan per patient, three points to the second and the third best plan, two points to the fourth and fifth plan and one point to the two worst plans. Points for all patients are counted per critical organ or PTV. Dosimetric verification To assess the ability of the TomoTherapy planning system to correctly calculate the dose given to the patient, a dosimetric verification of a breast plan was performed on an anthropomorphic selfmade wax breast phantom with TLDs and EDR2 films. Wax was used because it has almost the same density as a human breast. The thermoluminescent dosimeters (TLDs) used for the absolute dosimetry are LiF: 700 pellets (Vinten Instruments, Surrey, UK) with 0.50 cm diameter and 0.08 cm thickness. The TLDs were calibrated on the TomoTherapy Hi-ART unit for doses of 2 Gy (SD 1.3%). The TLDs were calibrated with a rotational beam with a construction of solid water equivalent blocks [21,30]. The cube solid water phantom (Gammex Inc., Middleton, USA) has a dimension of 19.5 cm  19.5 cm  10.6 cm. The dose in the phantom was very homogeneous (Mean 2.017 Gy, SD 0.070 Gy, Min 1.992 Gy, Max 2.033 Gy). Film measurements were performed using Kodak EDR2 film calibrated against ionization chamber (Exradin A1SL, Standard Imaging, WI) for the dose range from 5 to 250 cGy. TomoTherapy does not use a flattening filter so a flat field was created using intensity modulation. For the film calibration only the center part of the static beam was used, where the profile is relatively flat (<1–2%) [21,31]. All films originated from the same batch and the background signal was evaluated by developing an unirradiated film from the same batch. The breast phantom was irradiated twice with two different films, to compare the films. To do the dosimetric verification, the phantom was scanned on a CT scan using slices of 3 mm (Somatom Emotion, 16-slice, Siemens, Erlangen, Germany). A PTV breast, all the organs at risk and other planning volumes were contoured on the CT images as described before. Afterwards the phantom was transferred to the planning system and planned using the new planning protocol, a 2.45-cm field width, pitch between 0.25 and 0.30 and modulation factor of 2.0. The plan was optimized as to give a homogeneous dose of 2 Gy per fraction to the right wax breast. To verify the dose at, in and below the breasts and in the lungs of the rando-alderson phantom the film and the TLDs were used. Nineteen TLDs were placed at different locations at or below the breasts and in the phantom lungs. The locations were indicated with letters from A to S (Fig. 1). On each location, the TLDs were placed randomly. Places O, P, Q and S are inside the lungs of the rando-alderson phantom. Before the treatment a MV-CT scan was performed. To identify the location of the TLDs on the MV-CT scan, radio-opaque external markers were placed on the TLDs where possible. To

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identify the location of the TLDs inside the lungs and below the breasts, little lead markers were placed on the TLDs so that they were visible on the MV-CT scan. The radio-opaque external markers were removed before the start of the treatment, after the MVCT scan. The lead markers stayed in or on the phantom. TLD measurements were performed 5 times with the TLDs randomly distributed to all predefined locations A to S. To verify the dose inside the wax breasts and inside the randoalderson phantom, the wax breasts were cut into two parts to insert a film. The film (in envelope) was placed in an axial plane between the two breast parts and inside the rando-alderson phantom partially covering the lung to allow the lung dose to be checked. The breast phantom was irradiated twice with two different films, to compare measurements and to have a backup. A comparison is made between the calculated dose of the TomoTherapy TPS and the measured dose on the two films. To evaluate the calculated dose and the measured dose, the software OmniProTM IMRT (Scanditronix Wellhöfer, Sweden) was used. In vivo dosimetry Finally, a verification of the dose at the skin was performed in vivo with TLDs on TomoTherapy. Fourteen clinical patients treated with a fraction dose of 2 Gy or 2.8 Gy were randomly selected from our breast patients on TomoTherapy (65 TLD measurements). The TLDs were calibrated with a rotational beam method. Four, five or six TLDs were placed on the patient skin by a radiotherapist. Upon each TLD a radio-opaque external marker was placed to allow the determination of the location of the TLD, using registration between MV-CT and planning images. After the scan, markers were removed as not to interfere with the irradiation, and the TLDs were irradiated without build-up material [21]. After treatment the TLDs were read out and compared with the calculated dose on planning.

Results Planning study

Fig. 1. Indication of different locations where the TLDs are placed. Upper image: A, B, C, D and E at the surface of irradiated breast; H, I and G at the surface of contralateral breast; F and R at the sternum. Middle image: K, J and L at the thorax wall of irradiated breast; M and N at the contralateral thorax wall. Lower image: P and S inside the phantom lungs (O and Q inside the phantom lungs are not shown).

Six or seven treatment plans for all eight patients were generated, and DVH analysis was performed to compare all planning methods: TomoDirect prone and supine, TomoTherapy prone and supine, and conventional radiotherapy prone and supine (Fig. 2). For patients without PTVn in supine position, an additional plan with six beam directions was created with TomoDirect. Table 2 lists the V95% of PTV1,w and PTVn. The volume of the PTV1,w and PTVn receiving 110% of the dose was always zero. For the ipsilateral lung the V17 Gy and Dmean, for the heart the V17 Gy, Dmean and Dmax and for the contralateral breast Dmax and

Fig. 2. Isodoselines of supine TomoDirect two beams (left), TomoTherapy (middle) and conventional (right) plans for a patient with a right-sided tumor, tumorectomy and negative axillary lymph nodes.

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T. Reynders et al. / Radiotherapy and Oncology 93 (2009) 71–79 Table 2 Plan comparison between conventional radiotherapy, TomoTherapy and TomoDirect. Outside PTV or OAR

PTV1,w

PTVn

Ipsilateral lung

V95%

Dmean

Hotspots (% of 42 Gy)

V95%

Right breast Tx N0 Tomo su Tomo pr Conv su Conv pr TomoD su TomoD 6 su TomoD pr

109.8 108.8 109.2 111.4 111.5 109.1 170.7

99.8 98.6 97.96 98.7 82.04 91.05 97.29

Tx N+ Tomo su Tomo pr Conv su Conv pr TomoD su TomoD pr

105.1 104.8 107.2 115.3 120 127.9

99.6 92.4 95.7 95.34 97.8 97.3

Mx N0 Tomo su Tomo pr Conv su Conv pr TomoD su TomoD 6 su TomoD pr

105.2 109 109.7 110.4 121.5 106.4 139.8

99.87 99.79 97.68 97.93 97.89 99.92 99.18

Mx N+ Tomo su Tomo pr Conv su Conv pr TomoD su TomoD pr

109.8 113.3 111.1 113.9 107.9 109

95 97.3 98.86 92.2 95.78 94.61

Left breast Tx N0 Tomo su Tomo pr Conv su Conv pr TomoD su TomoD 6 su TomoD pr

105.5 105.2 105.6 110.8 110.2 111.2 122.8

96.76 97.66 96.5 98.7 98.8 94.8 99.25

Tx N+ Tomo su Tomo pr Conv su Conv pr TomoD su TomoD pr

105.2 106.2 110.3 110.1 106.1 108.5

99.05 98.33 98.4 97.1 98.84 97.66

Mx N0 Tomo su Tomo pr Conv su Conv pr TomoD su TomoD 6 su TomoD pr

106.2 108.3 107.9 112 115.2 108.2 148

96.5 95.7 96.06 92.7 99.85 95.75 95.46

Mx N+ Tomo su Tomo pr Conv su Conv pr TomoD su TomoD pr

110.2 108.4 110 113.7 115 121.7

98.56 98.68 98.43 98.37 98.91 98.79

97.15 86.25 36.95 43.34 99.16 97.29

93 84.54 85.12 57.2 98.04 63.02

94.5 90.1 67.5 81.6 89.8 94.8

76.24 33.56 62.6 57.8 99.86 95.28

Heart

Contralateral breast

V17 Gy

Dmax

Dmean

6.87 1.77 4.52 2.67 4.15 7.2 1.18

12.99 1.7 9.2 4.45 7.93 14.62 1.04

3.01 10.44 1.62 40.92 1.94 7.37 2.92

1.09 2.44 0.33 3.4 0.53 0.87 0.71

7.69 4.67 8.74 3.26 5.47 8

16.41 9.08 20.5 6.1 10.61 7.92

4.95 3.97 3.46 2.46 2.05 6.69

4.86 3.31 3.43 3.61 1.94 4.43 1.99

9.58 6.12 6.74 6.27 2.85 8.48 3.1

6.68 6.01 10 7.95 7.33 4.67

V17 Gy

Dmax

Dmean

0 0 0 5.8 0 0 0

1.87 23.47 0.43 38.81 0.62 5.16 30.23

0.33 7.25 0 0.5 0.13 0.23 0.52

0.94 1.01 0.53 0.61 0.51 0.91

0 0 0 0 0 0

2.01 4.87 0.67 39.79 0.82 15.76

0.49 0.87 0.09 1.53 0.27 1.56

1.35 4.64 0.8 2.92 0.71 1.11 1.43

0.48 0.63 0.14 0.23 0.23 0.33 0.4

0 0 0 0 0 0 0

2.45 2.05 0.19 5.4 0.33 0.59 1.21

0.33 0.44 0.06 0.11 0.12 0.18 0.27

13.85 11.17 23.43 20.2 15.43 8.11

5.39 4.33 2.46 6.6 1.86 4.01

0.87 1 0.44 0.7 0.61 0.66

0 0 0 0 0 0

3.02 16.75 9.41 40.65 2.29 18.77

0.48 1.01 0.17 2.6 0.38 0.79

5.6 1.55 4.02 1.67 2.27 1.77 1.3

10.49 0.73 7.3 4.45 3.13 1.28 1

36.55 34.9 41 40.92 39.43 43.49 41.95

4.8 3.2 1.88 3.4 1.99 1.14 1.71

1.51 1.1 1.77 5.8 1.97 0.071 0.94

2.39 38.45 1.01 38.81 5.14 4.26 43.01

0.53 8.58 0.11 0.5 0.36 0.26 0.67

7.59 5.58 9.43 5.09 7.98 4.51

16.2 12 22.8 11.2 18.4 9.5

19.31 36.64 37.6 38.56 34.62 40.35

1.07 1.57 0.74 0.89 0.76 1.15

0.016 0.65 0.25 0.6 0.072 0.175

2.69 5.13 0.35 4.49 1.73 11.81

0.49 0.8 0.11 0.25 0.31 3.19

4.7 9.3 3.49 6.29 3.89 3.57 3.48

9.2 11.4 7.8 14.3 8.4 7.3 6.7

23.44 39.01 41.37 43.2 40.42 43.25 33.15

1.58 6.17 0.95 2.53 2.96 0.94 1.13

0.077 8 1.15 4.6 4.96 0.038 0.091

18.76 25.88 0.73 47.01 44.38 3.79 47.62

3.11 3.85 0.07 6.25 0.62 0.17 4.55

6.99 3.99 7.45 7.47 7.73 6.31

16.1 7.45 21.2 16.05 17.17 13.66

38.99 38.78 40.46 43.15 40.6 41.04

3.37 6.6 3.2 13.29 3.11 7.72

17.35 31.07 6.82 31.57 45.53 50.9

3.56 11.21 0.02 0.51 1.09 3.09

4.6 13.95 5.2 30.9 4.4 16.36

Abbreviations: Tx, tumorectomy; Mx, mastectomy; su, supine; pr, prone; N0, negative axillary lymph nodes; N+, positive axillary lymph nodes; Tomo, TomoTherapy; TomoD, TomoDirect planned for PTV1,w with two tangential beam directions and for PTVn 1 or 2 beam directions; TomoD 6, TomoDirect planned with six tangential beam directions; Conv, conventional radiotherapy; V95%, percentage of target volume receiving 95% of prescription dose; V17 Gy, percentage of volume receiving P17 Gy; Dmax, maximum dose; Dmean, mean dose.

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Dmean have been reported. For the PTV coverage, supine plans were superior in all cases. Conventional plans achieved a bad PTV coverage in comparison with TomoTherapy and TomoDirect plans. Mainly the PTV nodes could not be covered completely with conventional plans. For the ipsilateral lung, prone plans did better than supine plans in 7/8 cases (TomoDirect prone is superior in 4/8 cases), on the other hand supine plans are better for the heart in 7/8 cases (conventional supine is superior in 3/4 cases for a right-sided tumor and TomoTherapy supine is superior in 2/4 cases for a left-sided tumor). For the contralateral lung (not in Table 2), a mean dose could be achieved less than 1 Gy in all cases (average mean dose of 0.55 Gy with TomoTherapy, 0.36 Gy with TomoDirect and 0.17 Gy with conventional radiotherapy). For the contralateral breast, conventional supine plans are the best in 7/8 cases. Hotspots outside the PTV are the highest with TomoDirect but can be avoided by using more than two static angles [12]. So by increasing the number of TomoDirect fields there is an advantage in conformality and homogeneity for the PTV and a low increase of the dose to the ipsilateral lung and the heart (right-sided tumor). Table 3 shows a general ranking of all plans and gives an overview of which plan scores best for which organ or PTV. ‘‘+++” indicates the best plan and ‘‘ ‘‘the worst plan. TomoDirect supine plans received the most ‘‘+”. For a right-sided tumor conventional supine seems to be the best for the heart and the contralateral breast. For a left-sided tumor TomoDirect supine (six beams) can be assumed to be the best option. PTV coverage is the best for TomoTherapy and TomoDirect supine (six beams) plans. Dosimetric verification TLD measurements are performed 5 times with the TLDs each time on random locations as described before. The dose measured with the TLDs and the dose calculated with the TomoTherapy TPS are shown in column bar diagrams (Fig. 3). The measured dose versus the calculated dose for the PTV is within 2.2%. This result is

acceptable within the uncertainties for the TLDs. For the low dose regions (<0.1 Gy) in the organs at risk, the measured dose is always higher than the calculated dose. Possible explanations such as overresponse of the TLDs as consequence of the lead markers, an underestimation [32] of the TomoTherapy TPS, leaf leakage or transmittance were investigated separately. To investigate the influence of the scatter from lead markers during irradiation, the TLDs were irradiated (2 Gy) with and without lead markers on TomoTherapy and in addition irradiated at a low dose of 5 cGy also with and without lead markers on a conventional Linac (Elekta Sli Plus). The investigation showed that at low doses (<0.1 Gy) the scatter contribution of the lead markers was 12%. The film measurement shows that TomoTherapy is able to create a high gradient in dose to the thoracic wall (Fig. 4). Both for the high (70%, 90% and 100%) and low (50%, 30% (not on image) and 10% (not on image)) isodoselines inside the phantom, a good agreement can be observed visually between the calculated and the measured doses. In the build-up region and in air outside the phantom, the low doses measured differ from the calculated doses. Discrepancies can be seen at the outer edges of the film that are related to the development and scanning process. For the 2% and 5% isodoselines the low sensitivity of the film results in increased noise that can easily be observed in Fig. 4. In general visual comparison shows that there is a good agreement between the calculated and the measured doses inside the phantom. The two measured films were compared using a commercial software package. All the low isodoselines (5%, 10%, 30% and 50%) inside the phantom are similar for the two films. For the high isodoselines (80%, 95% and 100%) there is a difference of maximum 5%. To determine if the difference between the calculated and the measured doses for the first film measurement is acceptable, a gamma evaluation as defined by Low and Dempsey [33] was applied. The gamma evaluation used is set on a 5% DD (dose difference) and 5 mm DTA (distance-to-agreement) tolerance (Fig. 5). These tolerances

Table 3 Overview of the ranking of the plans for each organ at risk. Conv su PTV1,w PTVn Ipsilateral lung Heart (tumor right) Heart (tumor left) Contralateral breast

Conv pr

Tomo su

Tomo pr

TomoD su

TomoD 6 su

TomoD pr

+++ ++

+

++ +++ + ++ + ++

+++ Not planned

++ + +++ + ++

++ +++ +++

+++ +

+ +++ ++

Fig. 3. Measured (TLDs) versus calculated dose for PTV and organs at risk. Note that the measured dose for the TLDs at locations Q and S (see Fig. 1) is on average 3 times higher than the calculated dose. The measured dose for the TLDs at locations O and P is on average 1.4 times higher than the calculated dose, this can be attributed to the scatter of lead markers.

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Fig. 4. Comparison between TomoTherapy calculated dose distribution and dose measured with film. The place of the film in the phantom is highlighted in yellow, the full lines represent the calculated doses and the dashed lines represent the measured doses.

were given to include: the contribution of errors in phantom positioning, noise at the film (±1%), fluctuations in dose (with TomoTherapy ±1.5%), the junction of the film with the phantom, the uncertainty of the measurement and the matching procedure [21]. This level of evaluation also assures that only major differences will be detected. In vivo dosimetry The results of the TLD measurements were acceptable, 9 out of 65 TLD measurements were not within 5% of the calculated dose after the first measurements. The second and third measurements per patient showed that all measurements were within 5%.

Discussion Comparison of conventional radiotherapy, TomoTherapy and TomoDirect shows an excellent PTV coverage except for the supraclavicular nodes planned with conventional radiotherapy. In history the supraclavicular nodes were never contoured for conventional radiotherapy. When the supraclavicular nodes are contoured and planned conventionally at 3-cm depth we saw that they are not completely covered by the prescription dose. Despite the none 100% coverage of the nodes almost no recurrences were observed. In our daily practice we use no-inclination with the supraclavicular field. As previously studied in our patients, we are aware that this might cause an underdosage notably in the infraclavicular nodal areas [34]. However, in this approach the doses to the pharynx-upper oesophagus and the thyroid are reduced, hence the daily practice in our center has maintained the choice of no-inclination. With TomoTherapy and TomoDirect the supraclavicular nodes are covered completely. Does it mean that

we do not need homogeneous doses? Future trials should try to answer this question. According to our scoring system (Table 3), conventional supine seems to be optimal for a right-sided tumor, the heart and the contralateral breast are best spared. TomoDirect supine (six beams) seems to be optimal for a left-sided tumor. The dose to the contralateral breast is found to be higher with the TomoTherapy plans because of the rotational treatment setup. This may be a concern for young patients who experience long survival times and as a result may be at risk of radiation-induced cancer [35]. As a consequence of this ranking it is possible to decide which modality is best suited for a patient based on parameters such as: the laterality of the tumor (left- or right-sided tumor), axillary lymph nodes involved or not, tumorectomy or mastectomy, heart condition, lung functionality, age and general condition. A disadvantage of treating breast carcinoma with TomoDirect is the presence of hotspots between 115% and 120% of the prescribed dose. Those hotspots can be avoided by the use of more than two beams. Another disadvantage of treating breast carcinoma with TomoTherapy and TomoDirect is the long beam-on time. The beam-on times have been calculated for the three treatment techniques. TomoTherapy (1291.5 s SD 207.8 s) has an average beam-on time that is 5.4 times longer than the average beam-on time of a conventional treatment (237.6 s SD 66.3 s). The average beam-on time of a TomoDirect (531.7 s SD 136.5 s) treatment is 2.2 times longer than the average beam-on time of a conventional treatment (data not shown). For the longer beam-on time with TomoTherapy and TomoDirect in contrast with the conventional treatment technique there are two reasons: the inefficient use of the photon beam by the use of virtual blocks and the use of intensity modulation. With IMRT a better target coverage is achievable but often at the cost of an increase in the number of monitor units. This means more scat-

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Helical TomoTherapy breast cancer treatments

tionship between rotation axis and target), the optimal choice of beam directions to plan a breast patient remains difficult with TomoDirect. TomoDirect is a good option to treat breast carcinoma and has shortened the treatment time in comparison with TomoTherapy. Further research of TomoDirect is necessary before the clinical implementation. TLD and film dosimetry on the wax breast phantom fixed on a rando-alderson phantom show good agreement. In vivo TLD measurements are clinically feasible, 13.8% was not within 5% after the first TLD measurement per patient. Uncertainties that influenced the measured doses were positioning of the patient, registration of MV-CT and planning images, TLD calibration, TLD positioning under the radio-opaque external marker, intrafraction motion and the fact that the predicted dose is superimposed on the MVCT (not recalculated). A little movement of the patient during treatment or a little mispositioning of the TLD under the external marker can cause big differences between the calculated and the measured dose because of the high dose gradient at the level of the patient’s skin. Further research with a moving phantom can bring more clarity. The differences of maximum 5% observed between the two films for the high isodoselines can be attributed to a combination of fluctuations in the output of the TomoTherapy unit between the first and the second irradiation, a difference in tightening of the films between the two phantom parts, the reproducibility or setup of the measurement and the inherent uncertainty of the films.

Conclusion

Fig. 5. Upper image: Comparison between TomoTherapy calculated dose (full lines) and measured dose (dashed lines) with film. Note that TomoTherapy is able to create a high gradient in dose to the thoracic wall. Middle image: Relative dose distribution through a vertical section of the dose distribution (see black vertical line on upper image). The vertical line on this figure represents the interface between tissue and air. The dose difference outside the phantom in air can be explained by the absence of a build-up region. Lower image: Relative dose distribution through a horizontal section of the dose distribution (see black horizontal line on upper image). Sharp dose gradients from breast to thoracic wall as created by the TPS are correct. The low dose regions in the thorax are well predicted by the TomoTherapy TPS. The dose difference at the edge of the film can be explained by the absence of a build-up region.

ter is produced and the potential risks of radiation-induced second malignancies will increase. However it is difficult to compare the scattered dose of TomoTherapy and a conventional linac because with TomoTherapy there is no linear relation between the MU delivered and the scattered dose. The scattered dose with TomoTherapy is lower outside the PTV volume because of the special design of the linac (the table translates and there is an especially designed fan beam collimator) [36]. The use of a 5.02-cm field width instead of a 2.45-cm field width for TomoTherapy will reduce the treatment time with approximately 40%. Because neither conventional simulation nor virtual simulation is adapted for TomoTherapy or TomoDirect procedures (e.g. rela-

This study showed that TomoTherapy and TomoDirect can deliver dose distributions which the radiotherapist judges to be equal to or better than conventional treatment of breast carcinoma. The treatment of breast carcinoma with TomoTherapy is feasible according the dose verifications. Further research with a moving phantom can bring more clarity about the uncertainties that influence the TLD measurements during the treatment. In vivo dosimetry with the TLDs was clinically feasible. Before the implementation of TomoDirect in our hospital a dosimetric verification is necessary to start treating patients in clinic. In vivo TLD measurements will continue for each patient. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.radonc.2009.07.005.

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