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Dosimetric evaluation of whole-breast radiation therapy: Clinical experience
Medical Dosimetry ] (2015) ]]]–]]]
Medical Dosimetry journal homepage: www.meddos.org
Dosimetric evaluation of whole-breast radiation therapy: clinical experience Ernest Osei, Ph.D.,*†‡ Johnson Darko, Ph.D.,*† Andre Fleck, M.Sc.,* Jana White, B.Sc.,M.R.T.T.,§ Alexander Kiciak ,† Rachel Redekop ,† and Darin Gopaul, M.D.║ Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada; †Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada; ‡Department of Systems Design, University of Waterloo, Waterloo, Ontario, Canada; §Department of Radiation Therapy, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada; and ║Department of Radiation Oncology, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada
*
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 November 2014 Received in revised form 15 April 2015 Accepted 9 May 2015
Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of earlystage breast cancer following breast conservation surgery. To improve patient standard of care, there is a need to define a consistent and transparent treatment path for all patients that reduces significance variations in the acceptability of treatment plans. There is lack of consistency among institutions or individuals about what is considered an acceptable treatment plan: target coverage vis-à-vis dose to organs at risk (OAR). Clinical trials usually resolve these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. We developed an institutional criterion for accepting breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed plan acceptability criteria and any possible changes necessary to further improve patient care. The mean patient age is 61.6 years (range: 25.2 to 93.0 years). The mean breast separation for all the patients is 21.0 cm (range: 12.4 to 34.9 cm), and the mean planning target volume (PTV_eval) (breast volume for evaluation) is 884.0 cm3 (range: 73.6 to 3684.6 cm3). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. A total of 147 (23.6%) patients were treated using the deep inspiration breath-hold (DIBH) technique. The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose (PD) are more than 99% and 97%, respectively, for all patients. The mean normalized PTV_eval receiving at least 105% (V105% PD) of the PD is less than 1% for all groups. The mean homogeneity index (HI), uniformity index (UI), and conformity index (CI) for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. Our data confirm the significant advantage of using DIBH to reduce heart dose when compared with the free-breathing technique. The p values analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart comparing DIBH and free-breathing techniques are well less than 0.05 (i.e., p o 0.05). However, similar analyses for the lung give values greater than 0.05 (i.e., p 4 0.05), indicating that there is no significant difference in lung dose comparing the 2 treatment techniques. & 2015 American Association of Medical Dosimetrists.
Keywords: Dose-volume histogram Breast treatment Breath-hold technique Free-breathing technique Hybrid treatment Radiation therapy
Introduction Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of early-stage breast cancer
Reprint requests to Ernest Osei, Ph.D., Department of Medical Physics, Grand River Cancer Center, 835 King Street West, Kitchner, Ontario, Canada N2G1G3. E-mail: [email protected] http://dx.doi.org/10.1016/j.meddos.2015.05.001 0958-3947/Copyright Ó 2015 American Association of Medical Dosimetrists
following breast conservation surgery. To improve patient standard of care, we have developed an evaluation process to define a consistent and transparent treatment path for all patients that reduces significant variations in the acceptability of treatment plans. Over the past few years, many studies have investigated the dosimetric differences between traditional treatment planning techniques using wedges and more recently developed methods such as the field-in-field (FnF), irregular surface compensation,
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hybrid technique, and inverse planned intensity-modulated radiation therapy (IMRT).1-28 Target coverage and dose uniformity parameters such as the planning target volume (PTV) doses, V95, V100, V105, and V107 (PTV volume receiving 95%, 100%, 105%, and 107% of the prescribed dose, respectively) as well as doses to the organs at risk (OAR) such as the ipsilateral lung, heart, and contralateral breast have been compared.1-4,24 A number of studies have reported significantly better dose distributions with FnF2,4,7 and significant dose reduction to the OAR.3,7,24 Gursel et al.3 attributed these improvements to the fact that the FnF technique reduces both the scatter and treatment time. On the contrary, Sun et al.5 reported that the use of the FnF technique is not superior to the physical wedges technique, as it does not improve the dosimetric results. They found that although the number of monitor units delivered was lower and the uniformity index (UI) was higher for the FnF technique, the physical wedges technique had a decreased homogeneity index
(HI) and maximum dose to the OAR, along with an increased conformity index (CI).5 The effect of respiratory motion on breast radiotherapy treatment has also been investigated.6,9 Tanaka et al.9 conducted an investigation to determine whether the FnF technique was more susceptible to respiratory motion than the physical wedges technique. By comparing data from the free-breathing and the deep inspiration breath-hold (DIBH) methods, they concluded that the FnF technique is less affected by respiratory motion when compared with the physical wedges technique.9 The dose-volume histogram (DVH) data showed that the difference in the volume of PTV receiving 90%, 95%, and 107% of the prescribed dose between the free-breathing and the DIBH techniques was less pronounced for the FnF technique than for the physical wedges technique.9 The dosimetric aspect involved in the use of an irregular surface compensator has been compared with treatment plans involving physical wedges.11 The use of the irregular surface
Fig. 1. Structure segmentation showing PTV_eval, lung, and heart volumes. The 50% isodose line is converted to a structure known as the treated volume. The breast contour is created by removing the lung and heart (where applicable) overlap from the treated volume contour. The PTV_eval contour is a contraction of 5 mm (in all directions) of the breast contour. (A) A transverse slice through the isocenter and digitally reconstructed radiograph (DRR) showing the projected (B) medial field and (C) lateral field and showing the PTV_eval, lung, and heart volumes. (Color version of figure is available online.)
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]] Table 1 Summary of the statistical analysis of the homogeneity Index, the uniformity Index, and the conformity index for the PTV_eval for all the patients studied
Age (years) Homogeneity index Uniformity index Conformity index
Minimum
Maximum
Mean
Standard deviation
25.20 0.05 0.46 0.92
93.0 0.15 1.11 1.00
61.56 0.09 1.07 0.98
11.49 0.01 0.03 0.01
compensator technique has been found to result in a decrease in the HI, maximum dose, lung dose, heart dose, and PTV V105 while keeping the number of monitor units delivered constant.11 According to Gursel et al,3 the use of the irregular surface compensator
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algorithm in Eclipse treatment planning system (TPS) is a promising solution for patients with a larger breast size, where the use of the FnF technique or IMRT alone may be less favorable.3 Other researchers have investigated the use of IMRT and hybrid (“open” beams plus optimized beams) techniques for the treatment of breast cancer.12-19,22-28 The hybrid treatment planning uses “open” and optimized beams to produce a homogeneous dose distribution, and to decrease the effect of respiratory motion, the “open” beams are usually assigned weights that are as high as possible, and the tangential posterior field edges are matched to spare lung dose.20,21 There is a lack of consistency among institutions or individuals on what is considered an acceptable treatment plan: target coverage vis-à-vis dose to OAR. Clinical trials usually resolve some of
Fig. 2. Plot of (A) the PTV_eval volumes, (B) breast separation, and (C) a plot of PTV_eval against separation for all patients.
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]]
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Table 2 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) All prescriptions
Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
Small (o 20 cm, n ¼ 229) Mean 17.98 Standard 1.52 deviation Maximum 19.99 Minimum 12.40
All patients (n ¼ 623) Mean 20.99 Standard 3.04 deviation Maximum 34.91 Minimum 12.4
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
551.33 271.6
99.95 0.08
99.76 0.29
98.33 1.15
76.84 10.28
0.24 0.75
– –
– –
– –
1557.78 73.60
100 99.6
100 98.23
100 92.98
92.89 29.47
4.95 –
0.02 –
– –
– –
99.87 0.34
99.58 0.55
98.0 1.38
76.73 7.66
0.48 0.93
– –
– –
– –
100 94.92
100 94.67
99.99 92.14
95.93 45.33
4.81 –
0.02 –
– –
– –
1659.69 493.03
99.59 0.32
98.95 0.50
96.28 0.99
73.03 8.15
1.06 1.43
0.06 0.28
0.03 0.13
– –
3684.61 1017.97
99.98 98.74
99.81 97.7
98.13 94.32
86.35 51.53
4.94 –
1.71 –
0.83 –
0.01 –
884.0 458.07
99.87 0.29
99.59 0.51
97.98 1.38
76.46 8.80
0.44 0.95
0.01 0.08
– 0.04
– –
3684.61 73.6
100 94.92
100 94.67
100 92.14
95.93 29.47
4.95 –
1.71 –
0.83 –
0.01 –
Medium (Z 20 cm and r 25 cm, n ¼ 342) Mean 22.09 988.82 Standard 1.37 346.36 deviation Maximum 24.93 2456.60 Minimum 20.00 129.13 Large (4 25 cm, n ¼ 52) Mean 27.03 Standard 2.03 deviation Maximum 34.91 Minimum 25.04
PD
PD
“–” Indicates that values are less than 0.01%.
these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. Any plan fulfilling the criteria is considered acceptable, whereas any plan not fulfilling all the criteria may be considered unacceptable. In such cases, there is relatively less stress on treatment planners, as
they can present treatment plans to radiation oncologists, which are less likely to be rejected. This more likely improves confidence in planners, reduces variation in treatment plans, and improves workflow and patient care. Despite these benefits, some institutions have still not developed local institutional criteria for
Table 3 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients receiving 42.5-Gy dose in 16 fractions. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) 42.5 Gy/16 Prescription
Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
Small (o 20 cm, n ¼ 212) Mean 16.2 Standard deviation 1.52 Maximum 19.99 Minimum 12.4
PD
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
550.93 272.72 1557.78 108.57
99.95 0.08 100 99.6
99.77 0.28 100 98.23
98.36 1.12 100 92.98
76.89 10.32 92.89 29.47
0.23 0.74 4.95 –
– – 0.02 –
– – – –
– – – –
970.58 331.5 231.20 129.13
99.87 0.34 100 94.92
99.59 0.54 100 94.67
98.05 1.35 99.99 93.1
76.85 7.50 95.93 45.33
0.47 0.91 4.81 –
– – 0.02 –
– – – –
– – – –
Large (4 25 cm, n ¼ 38) Mean 26.77 Standard deviation 1.61 Maximum 32.60 Minimum 25.28
1468.37 299.51 2313.34 1017.97
99.59 0.32 99.98 98.74
98.95 0.51 99.81 97.7
96.31 0.92 97.91 94.34
73.22 7.19 83.68 53.65
0.86 1.34 4.75 –
– 0.01 0.09 –
– – – –
– – – –
Total (n ¼ 570) Mean Standard deviation Maximum Minimum
847.69 402.56 2313.34 108.57
99.88 0.28 100 94.92
99.62 0.49 100 94.67
98.05 1.34 100 92.98
76.62 8.68 95.93 29.47
0.41 0.90 4.95 –
– – 0.09 –
– – – –
– – – –
Medium (Z 20 cm and r 25 cm, n ¼ 320) Mean 22.09 Standard deviation 1.37 Maximum 24.93 Minimum 20.00
20.88 2.89 32.60 12.4
“–” Indicates that values are less than 0.01%.
PD
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]]
accepting treatment plans. It was for these reasons that we developed an institutional criterion for accepting volume-based breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed breast plan acceptability criteria and any possible changes necessary to further improve patient care.
Methods and Materials We reviewed the treatment plans of 623 randomly selected patients with breast cancer who were treated at our cancer center from January 2013 to June 2014. Based on staging criteria, patients are treated with either a prescription dose of 50 Gy in 25 fractions or a prescription dose of 42.5 Gy in 16 fractions. For the data reviewed, 53 (8.5%) patients were treated with a prescription dose of 50 Gy in 25 fractions and 570 (91.5%) were treated with a prescription dose of 42.5 Gy in 16 fractions. Based on patient suitability and tolerance, 147 (23.6%) patients were treated using the DIBH technique and 476 (76.4%) were treated with free-breathing technique.
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same level 1.0 cm posterior to palpable breast tissue, and a third BB is placed on the contralateral side at this same level. A wire is placed to delineate the scar, and another wire is placed around the entire breast to delineate the edge of palpable breast tissue. The patient is scanned using the center's “breast” CT scan protocol, with a slice thickness of 0.3 cm. The scan extends superiorly from just below the mandible to inferiorly to include lungs and breast tissue. The scan data are exported to the virtual simulator, where the laser origin is marked at the location of the BBs. If the BB location is acceptable for breast tissue coverage and lung volume, then this point is used for marking. If the BB position is not acceptable, then a new tattoo point is created and placed as appropriate. This point is then marked on the patient. The patient is tattooed at the anterior, right lateral, and left lateral setup points. Additional tattoos can be placed inferiorly for leveling if the patient's anatomy requires a more stable setup point. Marks are also placed on the Vac-Lok for straightening (a mark in line with the AP tattoo and lateral marks).
Field borders placement The superior field border is set at the level of the second intercostal space but may be adjusted to clinically cover the entire breast tissue. The inferior border is set at 1.5 cm inferior to the inframammary fold. The medial border is set at midline and the lateral border is set at the midaxillary line, or 1.0 cm posterior to palpable breast tissue.
Patient positioning
Radiation treatment planning
As part of the standard protocol for breast treatment at our institution, the patients were positioned supine, with both the arms raised above the head. A VacLok cushion is used to support the arms, and a kneefix is placed under the knees. This positioning can be modified if required. If the positioning of the patient results in breast tissue falling superiorly to the level of the second intercostal space, a breast board is used at an appropriate inclined angle, and a headrest is placed under the head. In such a case, the ipsilateral arm is raised above the head, the contralateral arm is placed by the patient's side, and a kneefix remains under the knees. In the case where a pendulous breast falls too far laterally, resulting in a large volume of lung being included in the treatment field, a breast sling may be used. A sling may also be used if the breast falls inferiorly and creates a fold.
The CT scan data set and all points are exported into the Eclipse (Version 10: Varian Medical Systems) TPS. The scar is contoured, and the CT value is set to zero Hounsfield units. The isocenter is placed at the International Commission on Radiation Units and Measurements point at midbreast separation, and the gantry, collimator, couch, and jaws/multi-leaf collimator of the medial field are adjusted such that the entire breast is covered and the lung volume included in the field is acceptable. An opposing lateral field is created from the approved medial field, and the lateral gantry angle is adjusted for divergence on the posterior border.
CT simulation Before CT scan, the second intercostal space is palpated, and a wire is placed on the patient's skin, midway along the breast at that level. Another wire is also placed 1.5 cm inferior to the inframammary fold, and a small ball bearing (BB) is placed midline at the level middistance between the 2 wires. A second BB is placed at the
Target volumes and OAR The body and lung contours are created using an automated contouring feature of the TPS. To ensure less cleanup and maintain consistent PTV_eval (breast volume for evaluation) creation, a treated volume (50% isodose line) is first created by reducing the field lengths by 1.0 cm in the superior and inferior directions and calculating the dose distribution. The 50% isodose line is then converted to a structure known as the treated volume. The ipsilateral lung and heart (for left-sided treatment) are contoured. The breast contour is created by removing the lung and
Table 4 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients receiving 50-Gy dose in 25 fractions. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) 50 Gy/25 Prescription Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
PD
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
Small (o 20 cm, n ¼ 17) Mean 17.86 Standard deviation 1.56 Maximum 19.82 Minimum 14.37
556.23 265.12 1010.98 73.60
99.95 0.09 100 99.66
99.71 0.36 100 98.84
98.04 1.46 99.88 94.85
76.22 9.92 91.75 57.32
0.37 0.86 2.97 –
– – – –
– – – –
– – – –
Medium (Z 20 cm and r 25 cm, n ¼ 22) Mean 22.07 Standard deviation 1.37 Maximum 24.78 Minimum 20.32
1254.12 447.09 2456.60 567.45
99.76 0.37 100 98.62
99.34 0.68 99.96 97.37
97.25 1.50 99.18 92.14
74.86 9.64 86.41 56.76
0.66 1.21 4.06 –
– – 0.01 –
– – – –
– – – –
Large (4 25 cm, n ¼ 14) Mean 27.74 Standard 2.82 deviation Maximum 34.91 Minimum 25.04
1713.82 81.70
99.59 0.33
98.94 0.50
96.20 1.20
72.53 10.62
1.60 1.57
0.21 0.53
0.09 0.25
– –
3684.61 1654.20
99.91 98.84
99.58 97.86
98.13 94.32
86.35 51.53
4.94 –
1.71 –
0.83 –
0.01 –
Total (n ¼ 53) Mean Standard deviation Maximum Minimum
1274.58 752.78 3684.61 73.60
99.77 0.32 100 98.62
99.36 0.62 100 97.37
97.23 1.56 99.88 92.14
74.68 9.90 91.75 51.53
0.81 1.30 4.94 –
0.06 0.28 1.71 –
0.02 0.13 0.83 –
– – 0.01 –
22.21 4.23 34.91 14.37
“–” Indicates that values are less than 0.01%.
PD
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heart (where applicable) overlap from the treated volume contour. The PTV_eval contour is a contraction of 5 mm (in all directions) of the breast contour (Fig. 1).
Hybrid IMRT technique The hybrid IMRT technique uses both “open” and optimized beams for generating the treatment plans of the patients with breast cancer. This technique has the potential to produce a homogeneous dose distribution. To decrease the effect of respiratory motion, the “open” beams are usually assigned weights that are as high as possible. The superior and inferior field borders of the “open fields” are
now reset to their original positions, and the dose distribution is recalculated using the desired energy. The prescription of this “open-field” plan is set to 70% of the prescription dose (i.e., 3000c-Gy dose for a prescription dose of 4250 Gy in 16 fractions or 3530c-Gy dose for a prescription dose of 5000c Gy in 25 fractions). The plan is normalized to the isocenter or a normalization point (if required). The “open-field” plan is copied to create a plan for optimization. We usually use lowenergy beams for the optimized field, and the prescription is set to the remaining 30% of the prescription dose (i.e., 1250c-Gy dose for prescription dose of 4250c Gy or 1470c-Gy dose for a prescription dose of 5000c Gy). The plan is optimized using the “open-field” plan as a base dose plan and is calculated using fixed jaws and sliding window settings in the TPS. This optimized plan is also normalized in the
Fig. 3. A plot of the dose-volume histograms (DVHs) for all PTV_eval for patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy dose in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]] same manner as the “open-field” plan. The “open-field” and the optimized plans are then merged to create the final plan. The PTV_eval DVH is evaluated (the merged plan may be renormalized if necessary) to ensure that the plan meets the following criteria for the PTV_eval: V92% PD 4 99%, V95% PD 4 95%, and V105% PD o 1%. Indices for PTV_eval In addition to the evaluation of the DVH for the PTV_eval, the HI, UI, and the CI are also calculated for the PTV_eval. The HI, CI, and UI evaluate the dose homogeneity, conformity, and uniformity, respectively, within the PTV_eval and are calculated as D2 D98 HI ¼ DPD D5 UI ¼ D95 VRI CI ¼ TV where D2, D5, D95, and D98 are the doses received by 2%, 5%, 95%, and 98% of the PTV_eval, respectively. DPD is the prescribed dose, VRI is the volume of PTV_eval covered by the reference isodose line (in this case the 95% isodose line), and TV is the target volume (in this case the PTV_eval). The values of CI and UI close to unity indicate greater conformity and uniformity and values of HI close to zero indicate greater homogeneity.
Results and Discussions We have evaluated the dose distribution of the treatment plans of 623 patients with breast cancer treated at our center from January 2012 to June 2014 to assess the efficacy of a breast plan criterion that was already developed and institutionally acceptable (target coverage and doses to OAR). The Eclipse TPS version 10.0 (Varian Medical Systems, Palo Alto, CA) and the analytical anisotropic algorithm dose calculation algorithm version 10.0 were used for all treatment plans dose calculations. All the patients were randomly selected. For each patient, we determined the age; breast separation; and volumes of the PTV_eval, ipsilateral lung, and heart (for patients whose leftsided breast was treated for which the heart is usually contoured). For each treatment plan dose distribution, we determined the mean, maximum, minimum, and standard deviation of the PTV_eval, ipsilateral lung, and heart and analyzed the DVHs for all the structures. We also calculated the HI, UI, and the CI for the PTV_eval. Table 1 shows the summary of the statistical analysis of the HI, UI, and the CI for all 623 patients' PTV_eval structures. The
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mean patient age was 61.6 years (range: 25.2 to 93.0 years). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. Based on patient suitability and tolerance, 147 (23.6%) patients were treated using the DIBH technique and all others were treated with the freebreathing technique. PTV_eval dose evaluation Figure 1 displays the structure segmentation showing the PTV_eval, lung, and heart volumes. Figure 2 shows a plot of the PTV_eval for all the patients (Fig. 2A), a plot of breast separations for all the patients (Fig. 2B), and a plot of PTV_eval against breast separation (Fig. 2C) for all patients. Tables 2 to 4 show a summary of the statistical analysis of breast separations, PTV_eval, and dosevolumetric analysis for the PTV_eval for all patients (Table 2). Tables 3 and 4 show the dose-volumetric analysis for the PTV_eval when the patients were grouped into those treated with 42.5-Gy dose in 16 fractions (Table 3) and those treated with 50-Gy dose in 25 fractions (Table 4). Also shown in Tables 2 to 4 are similar statistical analysis after stratifying the patients by breast separation into 3 main groups: small (o 20 cm), medium (20 r x r 25), and large (4 25 cm). We stratified the patient population into these 3 different breast separations and prescription doses and analyzed the PTV_eval dosimetry to assess if different criteria are required for each subgroup. The mean breast separation for all the patients was 21.0 cm (range: 12.4 to 34.9 cm). The mean breast separation for the smallbreast group was 18.0 cm (range: 12.4 to 20.0 cm), the mediumbreast group was 22.1 cm (range: 20.0 to 24.9 cm), and the largebreast group was 27.0 cm (range: 25.0 to 34.9 cm). The corresponding mean PTV_eval for all patients was 884.0 cm3 (range: 73.6 to 3684.6 cm3), small-breast group was 551.3 cm3 (range: 73.6 to 1557.8 cm3), medium-breast group was 988.8 cm3 (range: 129.1 to 2456.6 cm3), and large-breast group was 1659.7 cm3 (range: 1018.0 to 3684.6 cm3). The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose are all more than 99% and 97%, respectively, for all groups. Mean normalized PTV_eval receiving at least 105% (V105% PD) of the prescribed dose are less than 1% for all groups. The mean HI, UI, and CI for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. A plot of the DVHs for all PTV_eval for all patients for both 42.5-Gy dose in
Table 5 A summary of the statistical analysis of the ipsilateral lung volumetric doses for all patients. Data have been separated into patients who were treated with the free-breathing technique and those treated with the deep inspiration breath-hold technique. nFB and nDIBH are the number of patients being treated with the free-breathing and the deep inspiration breath-hold techniques, respectively. The p value analysis of the tabulated results for the various doses when comparing the DIBH and the free-breathing techniques is also shown in the Table Free-breathing technique (n ¼ 476)
Deep inspiration breath-hold (DIBH) technique (n ¼ 147)
p Value
Minimum
Maximum
Mean
Standard deviation
Minimum
Maximum
Mean
Standard deviation
598.20
2737.59
1383.37
346.45
892.65
3091.41
2127.48
394.65
Ipsilateral lung dose parameters for 42.5-Gy dose in 16 fractions prescription dose (nFB ¼ 431 and nDIBH ¼ 139) 2.42 32.37 18.02 4.57 10.86 29.95 V5 Gy (%) V10 Gy (%) 1.37 22.72 11.48 3.49 3.76 19.15 1.04 19.81 9.45 3.15 2.75 15.98 V15 Gy (%) V20 Gy (%) 1.31 18.43 8.42 2.94 2.23 14.55 V30 Gy (%) 0.71 15.93 6.5 2.59 1.36 11.92 Maximum lung dose (%PD) (%) 90.48 103.88 97.67 2.35 90.33 100.96
18.58 11.07 9.04 8.05 6.22 96.03
3.85 2.86 2.52 2.35 2.00 2.15
0.200 0.218 0.159 0.201 0.236 o 0.001
Ipsilateral lung dose parameters for 50-Gy dose in 25 fractions prescription dose: The free-breathing technique (nFB ¼ 45 and nDIBH ¼ 8) V5 Gy (%) 9.28 30.5 21.57 5.15 16.31 26.57 20.72 3.71 3.89 20.2 13.09 3.95 8.19 15.23 12.13 2.31 V10 Gy (%) V15 Gy (%) 2.49 16.91 10.31 3.48 6.06 12.05 9.48 1.93 V20 Gy (%) 1.93 15.41 8.89 3.22 5.31 10.76 8.40 1.75 1.36 13.48 7.30 2.96 4.33 9.25 6.99 1.62 V30 Gy (%) Maximum lung dose (%PD) (%) 92.19 101.81 97.37 2.12 93.19 101.55 96.36 2.94
0.660 0.511 0.520 0.681 0.776 0.249
Lung volume (cc)
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16 fractions with free-breathing, DIBH technique and 50-Gy dose in 25 fractions with free-breathing technique are shown in Fig. 3, respectively. The mean PTV_eval DVH is also shown in Fig. 3. PTV_eval DVHs for new treatment plans can be evaluated along these mean DVH values to ensure consistency in treatment plans. Based on current data, it is possible to develop breast treatment plans that achieve dose coverage for the PTV_eval volume of 92% (V92% PD) and 95% (V95% PD) of the prescribed dose to at least 99% and 97% of the normalized volume, respectively, while at the same time, restricting the normalized volume of the PTV_eval receiving a hot spot of 105% (V105% PD) of the prescribed dose to less than 1%.
Ipsilateral lung dose evaluation The dose to the ipsilateral lung (i.e., the main OAR for breast and chest wall radiation treatment) was indexed by the percentage volume of ipsilateral lung receiving at least doses of 5 (V5 Gy), 10 (V10 Gy), 15 (V15 Gy), 20 (V20 Gy), and 30 Gy (V30 Gy). Table 5 shows the dose-volumetric analysis of the ipsilateral lung comparing patients treated with 42.5-Gy dose in 16 fractions and 50Gy dose in 25 fractions. Table 5 is further subdivided into patients treated using the free-breathing and the DIBH techniques. The mean ipsilateral lung volume for patients treated with the free-breathing and the DIBH techniques were 1383.4 cm3
Fig. 4. A plot of the dose-volume histograms (DVHs) for the ipsilateral lung for all patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy doses in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
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(range: 598.2 to 2737.6 cm3) and 2127.5 cm3 (range: 892.7 to 3091.4 cm3), respectively. The p value analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the lung when comparing the DIBH and free-breathing techniques are all more than 0.05 (i.e., p 4 0.05). This indicates that there is no significant difference in lung dose between the free-breathing and the DIBH techniques. The DVHs for the ipsilateral lung for all patients including the mean DVH are shown in Fig. 4. Lung DVHs for new treatment plans can be evaluated along these mean DVH values to ensure consistency in treatment plans. Based on current data, breast treatment planning can aim at achieving the mean values of V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the lung. Heart dose evaluation The main OAR for patients being treated with the disease in the left breast is the heart. Data are only available for patients who had the diseases in the left breast, because normally, it is only for those patients that the heart is contoured for planning. The dose to the heart was also indexed by the percentage volume of ipsilateral heart receiving at least doses of 5 (V5 Gy), 10 (V10 Gy), 15 (V15 Gy), 20 (V20 Gy), and 30 Gy (V30 Gy). Table 6 shows the dose-volumetric analysis of the heart comparing patients treated with 42.5-Gy dose in 16 fractions and 50-Gy dose in 25 fractions. Table 6 is further subdivided into patients treated with the free-breathing and the DIBH techniques. The mean heart volume for patients treated with the free-breathing and the DIBH techniques is 606.5 cm3 (range: 353.3 to 999.5 cm3) and 543.7 cm3 (range: 313.0 to 1169.7 cm3), respectively. Our results confirm the significant advantage of using the DIBH technique to reduce heart dose when compared with the free-breathing technique. The p value analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart comparing the DIBH and the free-breathing techniques are well less than 0.05 (i.e., p o 0.05). The DVHs for the heart for all patients including the mean DVH are shown in Fig. 5. Heart DVHs for new treatment plans can be evaluated along with these mean DVH values to ensure consistency in treatment plans. Based on current data, breast treatment planning can aim at achieving the mean values of V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart. The current data indicate that using the hybrid IMRT technique for tangential intact breast radiation therapy can result in
9
smaller “hot spots” while maintaining improved dose coverage and dose uniformity throughout the whole breast. This has also been demonstrated by other groups22-28 using similar techniques. Hot spots and dose inhomogeneity can lead to poor cosmetic outcomes and more skin reactions, especially in women with larger breasts. One such reaction—moist desquamation—has been correlated with increased pain and reduction in quality of life.22 Kestin et al.12 used IMRT to improve dose uniformity and potentially to reduce acute toxicity with tangential wholebreast radiotherapy. They concluded that the use of intensitymodulation techniques for tangential breast radiotherapy is an efficient and effective method for achieving uniform dose throughout the breast, and it is dosimetrically superior to treatment techniques that use wedges. They found lower overall areas of hot spots and lower maximum dose with IMRT. Abo-Madyan et al.23 evaluated intensity-modulated irradiation and other techniques by comparing dose homogeneity, target coverage, feasibility, and dosimetric reliability in patients with large breasts. They observed that aperture-based IMRT using 2 tangential beams with inverse optimization provides a better alternative to the standard wedged tangential beams for patients with large breasts while maintaining the efficiency of the treatment planning and delivery process. Pignol et al.22 conducted a multicenter, double-blind, randomized clinical trial to test if breast IMRT would reduce the rate of acute skin reaction, decrease pain, and improve quality of life when compared with standard radiotherapy using wedges. They concluded that breast IMRT technique significantly reduced the occurrence of moist desquamation compared with the standard wedged technique presumably because of lower hot spots and better homogeneity. We do not use hard wedges at our center for breast radiotherapy, as it has been recognized that the use of hard wedges increases scatter to the contralateral breast, which leads to an increased risk of radiation malignancies.1 Bhatnagar et al.24 compared the dose received by the contralateral breast during breast irradiation using IMRT and conventional tangential wedged field techniques and concluded that breast irradiation with tangential IMRT technique significantly reduces the dose to the contralateral breast when compared with conventional tangential wedged field techniques. Ludwig et al.26 compared 2 irradiation techniques for whole-breast irradiation—tangential wedged beams
Table 6 A summary of the statistical analysis of the heart volumetric doses for all patients. The data for the heart are only for those patients whose left breast was treated. Data have been separated into patients who were treated with the free-breathing technique and those treated with the deep inspiration breath-hold technique. nFB and nDIBH are the number of patients being treated with the free-breathing and the deep inspiration breath-hold techniques, respectively. The p value analysis of the tabulated results for the various doses when comparing the DIBH and the free-breathing techniques is also shown in the Table Free-breathing technique (n ¼ 167)
Heart volume (cc)
Deep Inspiration breath-hold technique (DIBH) (n ¼ 147)
Minimum
Maximum
Mean
Standard deviation
Minimum
Maximum
Mean
Standard deviation
353.34
999.51
606.52
98.75
312.98
1169.68
543.66
109.41
Heart dose parameters for 42.5-Gy dose in 16 fractions prescription dose (nFB ¼ 150 and nDIBH ¼ 139) V5 Gy (%) – 10.16 2.37 1.76 – – 7.68 1.13 1.17 – V10 Gy (%) V15 Gy (%) – 6.92 0.81 0.98 – V20 Gy (%) – 6.35 0.62 0.85 – V30 Gy (%) – 5.21 0.35 0.63 – Maximum heart dose (%PD) 8.35 101.19 79.06 26.67 7.67
5.42 3.55 2.72 2.14 1.21 103.47
0.52 0.14 0.09 0.06 0.02 31.45
Heart dose parameters for 50-Gy dose in 25 fractions prescription dose: The free-breathing technique (nFB ¼ 17 and nDIBH ¼ 8) 0.64 5.95 2.53 1.48 0.15 1.30 0.54 V5 Gy (%) V10 Gy (%) – 1.59 0.70 0.50 – 0.21 0.03 V15 Gy (%) – 0.95 0.37 0.31 – 0.10 0.01 – 0.76 0.23 0.22 – 0.06 0.01 V20 Gy (%) V30 Gy (%) – 0.47 0.09 0.12 – 0.02 – Maximum heart dose (%PD) 15.49 96.09 75.58 22.85 13.40 86.34 26.15 “–” Indicates that values are less than 0.01%. n
The mean values for the V30 Gy are so small that a calculated p value is not reliable.
p Value
0.84 0.44 0.32 0.24 0.12 27.27
o0.001 o0.001 o0.001 o0.001 o0.001 o0.001
0.39 0.07 0.04 0.02 0.01 24.63
0.001 0.001 0.003 0.008 *
o 0.001
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Fig. 5. A plot of the dose-volume histograms (DVHs) for the heart volumes for all patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy dose in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
vs “open” fields (without wedges) with forward planned segments —and indicated that partial volume segments can replace wedges for improved dose coverage and homogeneity in the PTV. Our data indicate very low volumes of V105%, V107%, V108%, and V110% using the hybrid IMRT technique, and although we have not correlated the dosimetry with clinical outcomes, the advantages of improved dose homogeneity in breast radiotherapy has been demonstrated by several authors.12,13,22,25 According to Vicini et al.,13 the breast volume receiving 105% (V105%) and 110% (V110%) of the prescribed
dose is significantly associated with an increased risk of developing acute skin toxicity. They observed that for patients with V110% o 200 cm,3 the risk of developing grade II or grade III acute skin toxicity was 31% vs 61%, respectively, in patients with V110% Z 200 cm.3 The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based radiotherapy.25
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Our treatment planning process including beam alignment, collimation, and optimization takes approximately 20 to 30 minutes. The planner focuses on examining the 3-D dose distribution including the DHVs and making minor adjustments, if necessary. Treatment delivery, including setup, takes approximately 10 to 15 minutes on both the Varian TrueBeam and EX treatment machines (Varian Oncology Systems) equipped with 120-millennium MLC. It is therefore possible to standardize the implementation of this technique and significantly improve the quality of radiotherapy delivery to all patients receiving intact breast radiotherapy without a negative effect on clinic time and economic resources. In addition, acute toxicity can in theory be reduced through a reduction in the breast volume receiving high doses.12,13 Vicini et al.13 presented their clinical experience with an intensity-modulated technique to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer and concluded that the intensity-modulation technique is an efficient method for achieving a uniform and standardized dose throughout the whole breast. They also indicated that a widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints.
Conclusion The use of hybrid IMRT technique for tangential intact breast radiation therapy is an efficient and reliable method for achieving dose uniformity throughout the whole breast. Predefined dosevolume constraints and objectives can be achieved, resulting in improved dose coverage of target breast tissue, reduction in breast volume receiving high doses and dose to adjacent normal tissue, and therefore with the potential to reduce the rate of acute skin reaction, decrease pain, and improve quality of life.22 Based on current data, it is possible to develop breast treatment plans that achieve dose coverage for the PTV_eval volume of 92% (V92% PD) and 95% (V95% PD) of the prescribed dose to at least 99% and 97% of the normalized volume, respectively, while at the same time, restricting the normalized volume of the PTV_eval receiving a hot spot of 105% (V105% PD) of the prescribed dose to less than 1%. Treatment planning of intact breast should also aim at minimizing doses to both the heart and the lung. The clinical implementation of this technology for patients with breast cancer can be achieved with minimal or no imposition on resources and time constraints.
Acknowledgment We gratefully acknowledge the support from all the treatment planners and radiation therapists at the cancer center for their dedication and commitment to patient care and ensuring a smooth implementation of the hybrid IMRT technology. References 1. Asbury K. 3D versus hybrid IMRT breast treatment planning: data, tips, and techniques. University of Maryland School of Medicine, 2012. 2. Falahatpour, Z.; Aghamiri, S.; Anbiaee, R. External radiotherapy of intact breast: a comparison between 2D (single CT-slice) and 3D (full CT-slices) plans. Int. J. Radiat. Res. 9(2):121–5; 2011. 3. Gursel, B.; Meydan, D.; Ozbek, N.; et al. Dosimetric comparison of three different external beam whole breast irradiation techniques. Adv. Ther. 28 (12):1114–25; 2011.
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4. Onal, C.; Sonmez, A.; Arslan, G.; et al. Dosimetric comparison of the field-infield technique and tangential wedged beams for breast irradiation. Jpn. J. Radiol. 30(3):218–26; 2012. 5. Sun, L.; Meng, F.; Yang, T.; et al. Field-in-field plan does not improve the dosimetric outcome compared with the wedged beams plan for breast cancer radiotherapy. Med. Dosim. 39(1):79–82; 2014. 6. Yao, W. A two-point scheme for optimal breast IMRT treatment planning. J. Appl. Clin. Med. Phys. 14(6):4525; 2013. 7. Yavas, G.; Yavas, C.; Acar, H. Dosimetric comparison of whole breast radiotherapy using field in field and conformal radiotherapy techniques in early stage breast cancer. Int. J. Radiat. Res. 10(3-4):131–8; 2012. 8. van der Laan, H.; Hurkmans, C.; Kuten, A.; et al. Current technological clinical practice in breast radiotherapy; results of a survey in EORTC-radiation oncology group affiliated institutions. Radiother. Oncol. 94(3):280–5; 2010. 9. Tanaka, H.; Hayashi, S.; Ohtakara, K.; et al. Impact of respiratory motion on breast tangential radiotherapy using the field-in-field technique compared to irradiation using physical wedges. Radiother. Oncol. 48(1):94–8; 2014. 10. Emmens, D.; James, H. Irregular surface compensation for radiotherapy of the breast: correlating depth of the compensation surface with breast size and resultant dose distribution. Br. J. Radiol. 83(986):159–65; 2010. 11. Hideki, F.; Nao, K.; Hiroyuki, H.; et al. Improvement of dose distribution with irregular surface compensator in whole breast radiotherapy. J. Med. Phys. 38 (3):115–9; 2013. 12. Kestin, L.; Sharpe, M.; Frazier, R.; et al. Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience. Int. J. Radiat. Oncol. Biol. Phys. 48(5):1559–68; 2000. 13. Vicini, F.; Sharpe, M.; Kestin, L.; et al. Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 54(5):1336–44; 2002. 14. Chin, L.; Cheng, C.; Siddon, R.; et al. Three-dimensional photon dose distributions with, and without lung corrections for tangential breast intact treatments. Int. J. Radiat. Oncol. Biol. Phys. 17(6):1327–35; 1989. 15. Buchholz, T.; Gurgoze, E.; Bice, W.; et al. Dosimetric analysis of intact breast irradiation in off-axis planes. Int. J. Radiat. Oncol. Biol. Phys. 39(1):261–7; 1997. 16. Cheng, C.; Das, I.; Baldassarre, S. The effect of the number of computed tomographic slices on dose distributions and evaluation of treatment planning systems for radiation therapy of intact breast. Int. J. Radiat. Oncol. Biol. Phys. 30 (1):183–95; 1994. 17. Solin, L.; Chu, J.; Sontag, M.; et al. Three-dimensional photon treatment planning of the intact breast. Int. J. Radiat. Oncol. Biol. Phys. 21(1):193–203; 1991. 18. Fraass, B.; Lichter, A.; McShan, D.; et al. The influence of lung density corrections on treatment planning for primary breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 14(1):179–90; 1988. 19. Das, I.; Cheng, C.; Fosmire, H.; et al. Tolerances in setup and dosimetric errors in the radiation treatment of breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 26 (5):883–90; 1993. 20. Jassem, J. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 355:1757–70; 2000. 21. Canney, P.; Deehan, C.; Glegg, M.; et al. Reducing cardiac dose in post-operative irradiation of breast cancer patients: the relative importance of patient positioning and CT scan planning. Br. J. Radiol. 72(862):986–93; 1999. 22. Pignol Jean, Philippe; Olivotto, Ivo; Rakovitch, Eileen; et al. A multicenter randomized trial of breast intensity modulated radiation therapy to reduce acute radiation dermatitis. J. Clin. Oncol. 26(13):2085–92; 2008. 23. Abo-Madyan, Yasser; Polednik, Martin; Angelika, Rahn; et al. Improving dose homogeneity in large breasts by IMRT efficacy and dosimetric accuracy of different techniques. Strahlenther. Onkol. 2008(184):86–92; 2008. 24. Bhatnagar, A.K.; Brander, E.; Sonnik, D.; et al. Intensity modulated radiation therapy (IMRT) reduces the dose to the contralateral breast when compared to conventional tangential fields for primary breast irradiation. Breast Cancer Res. Treat. 96(41):41–6; 2006. 25. Harsolia, Asif; Kestin, Larry; Grills, Inga; et al. Intensity-modulated radiotherapy results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 68(5):1375–80; 2007. 26. Ludwig, Veronika; Schwab, Franz; Guckenberger, Matthias; et al. Comparison of wedge versus segmented techniques in whole breast irradiation. Strahlenther. Onkol. 184(6):307–12; 2008. 27. Charles, Mayo S.; Marcia, Urie M.; Thomas, Fitzgerald 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 (3):922–32; 2005. 28. Wendy, Smith; Geetha, Menon; Nathan, Wolfe; et al. IMRT for the breast: a comparison of tangential planning techniques. Phys. Med. Biol. 55:1231–41; 2010.
Medical Dosimetry journal homepage: www.meddos.org
Dosimetric evaluation of whole-breast radiation therapy: clinical experience Ernest Osei, Ph.D.,*†‡ Johnson Darko, Ph.D.,*† Andre Fleck, M.Sc.,* Jana White, B.Sc.,M.R.T.T.,§ Alexander Kiciak ,† Rachel Redekop ,† and Darin Gopaul, M.D.║ Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada; †Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada; ‡Department of Systems Design, University of Waterloo, Waterloo, Ontario, Canada; §Department of Radiation Therapy, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada; and ║Department of Radiation Oncology, Grand River Regional Cancer Centre, Kitchener, Ontario, Canada
*
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 November 2014 Received in revised form 15 April 2015 Accepted 9 May 2015
Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of earlystage breast cancer following breast conservation surgery. To improve patient standard of care, there is a need to define a consistent and transparent treatment path for all patients that reduces significance variations in the acceptability of treatment plans. There is lack of consistency among institutions or individuals about what is considered an acceptable treatment plan: target coverage vis-à-vis dose to organs at risk (OAR). Clinical trials usually resolve these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. We developed an institutional criterion for accepting breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed plan acceptability criteria and any possible changes necessary to further improve patient care. The mean patient age is 61.6 years (range: 25.2 to 93.0 years). The mean breast separation for all the patients is 21.0 cm (range: 12.4 to 34.9 cm), and the mean planning target volume (PTV_eval) (breast volume for evaluation) is 884.0 cm3 (range: 73.6 to 3684.6 cm3). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. A total of 147 (23.6%) patients were treated using the deep inspiration breath-hold (DIBH) technique. The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose (PD) are more than 99% and 97%, respectively, for all patients. The mean normalized PTV_eval receiving at least 105% (V105% PD) of the PD is less than 1% for all groups. The mean homogeneity index (HI), uniformity index (UI), and conformity index (CI) for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. Our data confirm the significant advantage of using DIBH to reduce heart dose when compared with the free-breathing technique. The p values analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart comparing DIBH and free-breathing techniques are well less than 0.05 (i.e., p o 0.05). However, similar analyses for the lung give values greater than 0.05 (i.e., p 4 0.05), indicating that there is no significant difference in lung dose comparing the 2 treatment techniques. & 2015 American Association of Medical Dosimetrists.
Keywords: Dose-volume histogram Breast treatment Breath-hold technique Free-breathing technique Hybrid treatment Radiation therapy
Introduction Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of early-stage breast cancer
Reprint requests to Ernest Osei, Ph.D., Department of Medical Physics, Grand River Cancer Center, 835 King Street West, Kitchner, Ontario, Canada N2G1G3. E-mail: [email protected] http://dx.doi.org/10.1016/j.meddos.2015.05.001 0958-3947/Copyright Ó 2015 American Association of Medical Dosimetrists
following breast conservation surgery. To improve patient standard of care, we have developed an evaluation process to define a consistent and transparent treatment path for all patients that reduces significant variations in the acceptability of treatment plans. Over the past few years, many studies have investigated the dosimetric differences between traditional treatment planning techniques using wedges and more recently developed methods such as the field-in-field (FnF), irregular surface compensation,
2
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hybrid technique, and inverse planned intensity-modulated radiation therapy (IMRT).1-28 Target coverage and dose uniformity parameters such as the planning target volume (PTV) doses, V95, V100, V105, and V107 (PTV volume receiving 95%, 100%, 105%, and 107% of the prescribed dose, respectively) as well as doses to the organs at risk (OAR) such as the ipsilateral lung, heart, and contralateral breast have been compared.1-4,24 A number of studies have reported significantly better dose distributions with FnF2,4,7 and significant dose reduction to the OAR.3,7,24 Gursel et al.3 attributed these improvements to the fact that the FnF technique reduces both the scatter and treatment time. On the contrary, Sun et al.5 reported that the use of the FnF technique is not superior to the physical wedges technique, as it does not improve the dosimetric results. They found that although the number of monitor units delivered was lower and the uniformity index (UI) was higher for the FnF technique, the physical wedges technique had a decreased homogeneity index
(HI) and maximum dose to the OAR, along with an increased conformity index (CI).5 The effect of respiratory motion on breast radiotherapy treatment has also been investigated.6,9 Tanaka et al.9 conducted an investigation to determine whether the FnF technique was more susceptible to respiratory motion than the physical wedges technique. By comparing data from the free-breathing and the deep inspiration breath-hold (DIBH) methods, they concluded that the FnF technique is less affected by respiratory motion when compared with the physical wedges technique.9 The dose-volume histogram (DVH) data showed that the difference in the volume of PTV receiving 90%, 95%, and 107% of the prescribed dose between the free-breathing and the DIBH techniques was less pronounced for the FnF technique than for the physical wedges technique.9 The dosimetric aspect involved in the use of an irregular surface compensator has been compared with treatment plans involving physical wedges.11 The use of the irregular surface
Fig. 1. Structure segmentation showing PTV_eval, lung, and heart volumes. The 50% isodose line is converted to a structure known as the treated volume. The breast contour is created by removing the lung and heart (where applicable) overlap from the treated volume contour. The PTV_eval contour is a contraction of 5 mm (in all directions) of the breast contour. (A) A transverse slice through the isocenter and digitally reconstructed radiograph (DRR) showing the projected (B) medial field and (C) lateral field and showing the PTV_eval, lung, and heart volumes. (Color version of figure is available online.)
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]] Table 1 Summary of the statistical analysis of the homogeneity Index, the uniformity Index, and the conformity index for the PTV_eval for all the patients studied
Age (years) Homogeneity index Uniformity index Conformity index
Minimum
Maximum
Mean
Standard deviation
25.20 0.05 0.46 0.92
93.0 0.15 1.11 1.00
61.56 0.09 1.07 0.98
11.49 0.01 0.03 0.01
compensator technique has been found to result in a decrease in the HI, maximum dose, lung dose, heart dose, and PTV V105 while keeping the number of monitor units delivered constant.11 According to Gursel et al,3 the use of the irregular surface compensator
3
algorithm in Eclipse treatment planning system (TPS) is a promising solution for patients with a larger breast size, where the use of the FnF technique or IMRT alone may be less favorable.3 Other researchers have investigated the use of IMRT and hybrid (“open” beams plus optimized beams) techniques for the treatment of breast cancer.12-19,22-28 The hybrid treatment planning uses “open” and optimized beams to produce a homogeneous dose distribution, and to decrease the effect of respiratory motion, the “open” beams are usually assigned weights that are as high as possible, and the tangential posterior field edges are matched to spare lung dose.20,21 There is a lack of consistency among institutions or individuals on what is considered an acceptable treatment plan: target coverage vis-à-vis dose to OAR. Clinical trials usually resolve some of
Fig. 2. Plot of (A) the PTV_eval volumes, (B) breast separation, and (C) a plot of PTV_eval against separation for all patients.
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4
Table 2 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) All prescriptions
Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
Small (o 20 cm, n ¼ 229) Mean 17.98 Standard 1.52 deviation Maximum 19.99 Minimum 12.40
All patients (n ¼ 623) Mean 20.99 Standard 3.04 deviation Maximum 34.91 Minimum 12.4
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
551.33 271.6
99.95 0.08
99.76 0.29
98.33 1.15
76.84 10.28
0.24 0.75
– –
– –
– –
1557.78 73.60
100 99.6
100 98.23
100 92.98
92.89 29.47
4.95 –
0.02 –
– –
– –
99.87 0.34
99.58 0.55
98.0 1.38
76.73 7.66
0.48 0.93
– –
– –
– –
100 94.92
100 94.67
99.99 92.14
95.93 45.33
4.81 –
0.02 –
– –
– –
1659.69 493.03
99.59 0.32
98.95 0.50
96.28 0.99
73.03 8.15
1.06 1.43
0.06 0.28
0.03 0.13
– –
3684.61 1017.97
99.98 98.74
99.81 97.7
98.13 94.32
86.35 51.53
4.94 –
1.71 –
0.83 –
0.01 –
884.0 458.07
99.87 0.29
99.59 0.51
97.98 1.38
76.46 8.80
0.44 0.95
0.01 0.08
– 0.04
– –
3684.61 73.6
100 94.92
100 94.67
100 92.14
95.93 29.47
4.95 –
1.71 –
0.83 –
0.01 –
Medium (Z 20 cm and r 25 cm, n ¼ 342) Mean 22.09 988.82 Standard 1.37 346.36 deviation Maximum 24.93 2456.60 Minimum 20.00 129.13 Large (4 25 cm, n ¼ 52) Mean 27.03 Standard 2.03 deviation Maximum 34.91 Minimum 25.04
PD
PD
“–” Indicates that values are less than 0.01%.
these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. Any plan fulfilling the criteria is considered acceptable, whereas any plan not fulfilling all the criteria may be considered unacceptable. In such cases, there is relatively less stress on treatment planners, as
they can present treatment plans to radiation oncologists, which are less likely to be rejected. This more likely improves confidence in planners, reduces variation in treatment plans, and improves workflow and patient care. Despite these benefits, some institutions have still not developed local institutional criteria for
Table 3 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients receiving 42.5-Gy dose in 16 fractions. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) 42.5 Gy/16 Prescription
Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
Small (o 20 cm, n ¼ 212) Mean 16.2 Standard deviation 1.52 Maximum 19.99 Minimum 12.4
PD
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
550.93 272.72 1557.78 108.57
99.95 0.08 100 99.6
99.77 0.28 100 98.23
98.36 1.12 100 92.98
76.89 10.32 92.89 29.47
0.23 0.74 4.95 –
– – 0.02 –
– – – –
– – – –
970.58 331.5 231.20 129.13
99.87 0.34 100 94.92
99.59 0.54 100 94.67
98.05 1.35 99.99 93.1
76.85 7.50 95.93 45.33
0.47 0.91 4.81 –
– – 0.02 –
– – – –
– – – –
Large (4 25 cm, n ¼ 38) Mean 26.77 Standard deviation 1.61 Maximum 32.60 Minimum 25.28
1468.37 299.51 2313.34 1017.97
99.59 0.32 99.98 98.74
98.95 0.51 99.81 97.7
96.31 0.92 97.91 94.34
73.22 7.19 83.68 53.65
0.86 1.34 4.75 –
– 0.01 0.09 –
– – – –
– – – –
Total (n ¼ 570) Mean Standard deviation Maximum Minimum
847.69 402.56 2313.34 108.57
99.88 0.28 100 94.92
99.62 0.49 100 94.67
98.05 1.34 100 92.98
76.62 8.68 95.93 29.47
0.41 0.90 4.95 –
– – 0.09 –
– – – –
– – – –
Medium (Z 20 cm and r 25 cm, n ¼ 320) Mean 22.09 Standard deviation 1.37 Maximum 24.93 Minimum 20.00
20.88 2.89 32.60 12.4
“–” Indicates that values are less than 0.01%.
PD
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accepting treatment plans. It was for these reasons that we developed an institutional criterion for accepting volume-based breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed breast plan acceptability criteria and any possible changes necessary to further improve patient care.
Methods and Materials We reviewed the treatment plans of 623 randomly selected patients with breast cancer who were treated at our cancer center from January 2013 to June 2014. Based on staging criteria, patients are treated with either a prescription dose of 50 Gy in 25 fractions or a prescription dose of 42.5 Gy in 16 fractions. For the data reviewed, 53 (8.5%) patients were treated with a prescription dose of 50 Gy in 25 fractions and 570 (91.5%) were treated with a prescription dose of 42.5 Gy in 16 fractions. Based on patient suitability and tolerance, 147 (23.6%) patients were treated using the DIBH technique and 476 (76.4%) were treated with free-breathing technique.
5
same level 1.0 cm posterior to palpable breast tissue, and a third BB is placed on the contralateral side at this same level. A wire is placed to delineate the scar, and another wire is placed around the entire breast to delineate the edge of palpable breast tissue. The patient is scanned using the center's “breast” CT scan protocol, with a slice thickness of 0.3 cm. The scan extends superiorly from just below the mandible to inferiorly to include lungs and breast tissue. The scan data are exported to the virtual simulator, where the laser origin is marked at the location of the BBs. If the BB location is acceptable for breast tissue coverage and lung volume, then this point is used for marking. If the BB position is not acceptable, then a new tattoo point is created and placed as appropriate. This point is then marked on the patient. The patient is tattooed at the anterior, right lateral, and left lateral setup points. Additional tattoos can be placed inferiorly for leveling if the patient's anatomy requires a more stable setup point. Marks are also placed on the Vac-Lok for straightening (a mark in line with the AP tattoo and lateral marks).
Field borders placement The superior field border is set at the level of the second intercostal space but may be adjusted to clinically cover the entire breast tissue. The inferior border is set at 1.5 cm inferior to the inframammary fold. The medial border is set at midline and the lateral border is set at the midaxillary line, or 1.0 cm posterior to palpable breast tissue.
Patient positioning
Radiation treatment planning
As part of the standard protocol for breast treatment at our institution, the patients were positioned supine, with both the arms raised above the head. A VacLok cushion is used to support the arms, and a kneefix is placed under the knees. This positioning can be modified if required. If the positioning of the patient results in breast tissue falling superiorly to the level of the second intercostal space, a breast board is used at an appropriate inclined angle, and a headrest is placed under the head. In such a case, the ipsilateral arm is raised above the head, the contralateral arm is placed by the patient's side, and a kneefix remains under the knees. In the case where a pendulous breast falls too far laterally, resulting in a large volume of lung being included in the treatment field, a breast sling may be used. A sling may also be used if the breast falls inferiorly and creates a fold.
The CT scan data set and all points are exported into the Eclipse (Version 10: Varian Medical Systems) TPS. The scar is contoured, and the CT value is set to zero Hounsfield units. The isocenter is placed at the International Commission on Radiation Units and Measurements point at midbreast separation, and the gantry, collimator, couch, and jaws/multi-leaf collimator of the medial field are adjusted such that the entire breast is covered and the lung volume included in the field is acceptable. An opposing lateral field is created from the approved medial field, and the lateral gantry angle is adjusted for divergence on the posterior border.
CT simulation Before CT scan, the second intercostal space is palpated, and a wire is placed on the patient's skin, midway along the breast at that level. Another wire is also placed 1.5 cm inferior to the inframammary fold, and a small ball bearing (BB) is placed midline at the level middistance between the 2 wires. A second BB is placed at the
Target volumes and OAR The body and lung contours are created using an automated contouring feature of the TPS. To ensure less cleanup and maintain consistent PTV_eval (breast volume for evaluation) creation, a treated volume (50% isodose line) is first created by reducing the field lengths by 1.0 cm in the superior and inferior directions and calculating the dose distribution. The 50% isodose line is then converted to a structure known as the treated volume. The ipsilateral lung and heart (for left-sided treatment) are contoured. The breast contour is created by removing the lung and
Table 4 A summary of the statistical analysis of the breast separation, PTV_eval volume, and normalized PTV_eval volume receiving 90%, 92%, 95%, 100%, 105%, 107%, 108%, and 110% of the prescribed dose for all patients receiving 50-Gy dose in 25 fractions. Also shown are the results when patients have been stratified by breast separation into 3 main groups (o 20 cm, Z 20 r 25 cm, and 4 25 cm) 50 Gy/25 Prescription Breast separation (cm)
PTV_eval volume (cm3)
Normalized PTV_eval volume receiving the percentage of the prescribed dose V90% (%)
PD
V92% (%)
PD
V95% (%)
PD
V100% (%)
PD
V105% (%)
PD
V107% (%)
PD
V108% (%)
PD
V110% (%)
Small (o 20 cm, n ¼ 17) Mean 17.86 Standard deviation 1.56 Maximum 19.82 Minimum 14.37
556.23 265.12 1010.98 73.60
99.95 0.09 100 99.66
99.71 0.36 100 98.84
98.04 1.46 99.88 94.85
76.22 9.92 91.75 57.32
0.37 0.86 2.97 –
– – – –
– – – –
– – – –
Medium (Z 20 cm and r 25 cm, n ¼ 22) Mean 22.07 Standard deviation 1.37 Maximum 24.78 Minimum 20.32
1254.12 447.09 2456.60 567.45
99.76 0.37 100 98.62
99.34 0.68 99.96 97.37
97.25 1.50 99.18 92.14
74.86 9.64 86.41 56.76
0.66 1.21 4.06 –
– – 0.01 –
– – – –
– – – –
Large (4 25 cm, n ¼ 14) Mean 27.74 Standard 2.82 deviation Maximum 34.91 Minimum 25.04
1713.82 81.70
99.59 0.33
98.94 0.50
96.20 1.20
72.53 10.62
1.60 1.57
0.21 0.53
0.09 0.25
– –
3684.61 1654.20
99.91 98.84
99.58 97.86
98.13 94.32
86.35 51.53
4.94 –
1.71 –
0.83 –
0.01 –
Total (n ¼ 53) Mean Standard deviation Maximum Minimum
1274.58 752.78 3684.61 73.60
99.77 0.32 100 98.62
99.36 0.62 100 97.37
97.23 1.56 99.88 92.14
74.68 9.90 91.75 51.53
0.81 1.30 4.94 –
0.06 0.28 1.71 –
0.02 0.13 0.83 –
– – 0.01 –
22.21 4.23 34.91 14.37
“–” Indicates that values are less than 0.01%.
PD
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heart (where applicable) overlap from the treated volume contour. The PTV_eval contour is a contraction of 5 mm (in all directions) of the breast contour (Fig. 1).
Hybrid IMRT technique The hybrid IMRT technique uses both “open” and optimized beams for generating the treatment plans of the patients with breast cancer. This technique has the potential to produce a homogeneous dose distribution. To decrease the effect of respiratory motion, the “open” beams are usually assigned weights that are as high as possible. The superior and inferior field borders of the “open fields” are
now reset to their original positions, and the dose distribution is recalculated using the desired energy. The prescription of this “open-field” plan is set to 70% of the prescription dose (i.e., 3000c-Gy dose for a prescription dose of 4250 Gy in 16 fractions or 3530c-Gy dose for a prescription dose of 5000c Gy in 25 fractions). The plan is normalized to the isocenter or a normalization point (if required). The “open-field” plan is copied to create a plan for optimization. We usually use lowenergy beams for the optimized field, and the prescription is set to the remaining 30% of the prescription dose (i.e., 1250c-Gy dose for prescription dose of 4250c Gy or 1470c-Gy dose for a prescription dose of 5000c Gy). The plan is optimized using the “open-field” plan as a base dose plan and is calculated using fixed jaws and sliding window settings in the TPS. This optimized plan is also normalized in the
Fig. 3. A plot of the dose-volume histograms (DVHs) for all PTV_eval for patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy dose in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]] same manner as the “open-field” plan. The “open-field” and the optimized plans are then merged to create the final plan. The PTV_eval DVH is evaluated (the merged plan may be renormalized if necessary) to ensure that the plan meets the following criteria for the PTV_eval: V92% PD 4 99%, V95% PD 4 95%, and V105% PD o 1%. Indices for PTV_eval In addition to the evaluation of the DVH for the PTV_eval, the HI, UI, and the CI are also calculated for the PTV_eval. The HI, CI, and UI evaluate the dose homogeneity, conformity, and uniformity, respectively, within the PTV_eval and are calculated as D2 D98 HI ¼ DPD D5 UI ¼ D95 VRI CI ¼ TV where D2, D5, D95, and D98 are the doses received by 2%, 5%, 95%, and 98% of the PTV_eval, respectively. DPD is the prescribed dose, VRI is the volume of PTV_eval covered by the reference isodose line (in this case the 95% isodose line), and TV is the target volume (in this case the PTV_eval). The values of CI and UI close to unity indicate greater conformity and uniformity and values of HI close to zero indicate greater homogeneity.
Results and Discussions We have evaluated the dose distribution of the treatment plans of 623 patients with breast cancer treated at our center from January 2012 to June 2014 to assess the efficacy of a breast plan criterion that was already developed and institutionally acceptable (target coverage and doses to OAR). The Eclipse TPS version 10.0 (Varian Medical Systems, Palo Alto, CA) and the analytical anisotropic algorithm dose calculation algorithm version 10.0 were used for all treatment plans dose calculations. All the patients were randomly selected. For each patient, we determined the age; breast separation; and volumes of the PTV_eval, ipsilateral lung, and heart (for patients whose leftsided breast was treated for which the heart is usually contoured). For each treatment plan dose distribution, we determined the mean, maximum, minimum, and standard deviation of the PTV_eval, ipsilateral lung, and heart and analyzed the DVHs for all the structures. We also calculated the HI, UI, and the CI for the PTV_eval. Table 1 shows the summary of the statistical analysis of the HI, UI, and the CI for all 623 patients' PTV_eval structures. The
7
mean patient age was 61.6 years (range: 25.2 to 93.0 years). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. Based on patient suitability and tolerance, 147 (23.6%) patients were treated using the DIBH technique and all others were treated with the freebreathing technique. PTV_eval dose evaluation Figure 1 displays the structure segmentation showing the PTV_eval, lung, and heart volumes. Figure 2 shows a plot of the PTV_eval for all the patients (Fig. 2A), a plot of breast separations for all the patients (Fig. 2B), and a plot of PTV_eval against breast separation (Fig. 2C) for all patients. Tables 2 to 4 show a summary of the statistical analysis of breast separations, PTV_eval, and dosevolumetric analysis for the PTV_eval for all patients (Table 2). Tables 3 and 4 show the dose-volumetric analysis for the PTV_eval when the patients were grouped into those treated with 42.5-Gy dose in 16 fractions (Table 3) and those treated with 50-Gy dose in 25 fractions (Table 4). Also shown in Tables 2 to 4 are similar statistical analysis after stratifying the patients by breast separation into 3 main groups: small (o 20 cm), medium (20 r x r 25), and large (4 25 cm). We stratified the patient population into these 3 different breast separations and prescription doses and analyzed the PTV_eval dosimetry to assess if different criteria are required for each subgroup. The mean breast separation for all the patients was 21.0 cm (range: 12.4 to 34.9 cm). The mean breast separation for the smallbreast group was 18.0 cm (range: 12.4 to 20.0 cm), the mediumbreast group was 22.1 cm (range: 20.0 to 24.9 cm), and the largebreast group was 27.0 cm (range: 25.0 to 34.9 cm). The corresponding mean PTV_eval for all patients was 884.0 cm3 (range: 73.6 to 3684.6 cm3), small-breast group was 551.3 cm3 (range: 73.6 to 1557.8 cm3), medium-breast group was 988.8 cm3 (range: 129.1 to 2456.6 cm3), and large-breast group was 1659.7 cm3 (range: 1018.0 to 3684.6 cm3). The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose are all more than 99% and 97%, respectively, for all groups. Mean normalized PTV_eval receiving at least 105% (V105% PD) of the prescribed dose are less than 1% for all groups. The mean HI, UI, and CI for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. A plot of the DVHs for all PTV_eval for all patients for both 42.5-Gy dose in
Table 5 A summary of the statistical analysis of the ipsilateral lung volumetric doses for all patients. Data have been separated into patients who were treated with the free-breathing technique and those treated with the deep inspiration breath-hold technique. nFB and nDIBH are the number of patients being treated with the free-breathing and the deep inspiration breath-hold techniques, respectively. The p value analysis of the tabulated results for the various doses when comparing the DIBH and the free-breathing techniques is also shown in the Table Free-breathing technique (n ¼ 476)
Deep inspiration breath-hold (DIBH) technique (n ¼ 147)
p Value
Minimum
Maximum
Mean
Standard deviation
Minimum
Maximum
Mean
Standard deviation
598.20
2737.59
1383.37
346.45
892.65
3091.41
2127.48
394.65
Ipsilateral lung dose parameters for 42.5-Gy dose in 16 fractions prescription dose (nFB ¼ 431 and nDIBH ¼ 139) 2.42 32.37 18.02 4.57 10.86 29.95 V5 Gy (%) V10 Gy (%) 1.37 22.72 11.48 3.49 3.76 19.15 1.04 19.81 9.45 3.15 2.75 15.98 V15 Gy (%) V20 Gy (%) 1.31 18.43 8.42 2.94 2.23 14.55 V30 Gy (%) 0.71 15.93 6.5 2.59 1.36 11.92 Maximum lung dose (%PD) (%) 90.48 103.88 97.67 2.35 90.33 100.96
18.58 11.07 9.04 8.05 6.22 96.03
3.85 2.86 2.52 2.35 2.00 2.15
0.200 0.218 0.159 0.201 0.236 o 0.001
Ipsilateral lung dose parameters for 50-Gy dose in 25 fractions prescription dose: The free-breathing technique (nFB ¼ 45 and nDIBH ¼ 8) V5 Gy (%) 9.28 30.5 21.57 5.15 16.31 26.57 20.72 3.71 3.89 20.2 13.09 3.95 8.19 15.23 12.13 2.31 V10 Gy (%) V15 Gy (%) 2.49 16.91 10.31 3.48 6.06 12.05 9.48 1.93 V20 Gy (%) 1.93 15.41 8.89 3.22 5.31 10.76 8.40 1.75 1.36 13.48 7.30 2.96 4.33 9.25 6.99 1.62 V30 Gy (%) Maximum lung dose (%PD) (%) 92.19 101.81 97.37 2.12 93.19 101.55 96.36 2.94
0.660 0.511 0.520 0.681 0.776 0.249
Lung volume (cc)
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16 fractions with free-breathing, DIBH technique and 50-Gy dose in 25 fractions with free-breathing technique are shown in Fig. 3, respectively. The mean PTV_eval DVH is also shown in Fig. 3. PTV_eval DVHs for new treatment plans can be evaluated along these mean DVH values to ensure consistency in treatment plans. Based on current data, it is possible to develop breast treatment plans that achieve dose coverage for the PTV_eval volume of 92% (V92% PD) and 95% (V95% PD) of the prescribed dose to at least 99% and 97% of the normalized volume, respectively, while at the same time, restricting the normalized volume of the PTV_eval receiving a hot spot of 105% (V105% PD) of the prescribed dose to less than 1%.
Ipsilateral lung dose evaluation The dose to the ipsilateral lung (i.e., the main OAR for breast and chest wall radiation treatment) was indexed by the percentage volume of ipsilateral lung receiving at least doses of 5 (V5 Gy), 10 (V10 Gy), 15 (V15 Gy), 20 (V20 Gy), and 30 Gy (V30 Gy). Table 5 shows the dose-volumetric analysis of the ipsilateral lung comparing patients treated with 42.5-Gy dose in 16 fractions and 50Gy dose in 25 fractions. Table 5 is further subdivided into patients treated using the free-breathing and the DIBH techniques. The mean ipsilateral lung volume for patients treated with the free-breathing and the DIBH techniques were 1383.4 cm3
Fig. 4. A plot of the dose-volume histograms (DVHs) for the ipsilateral lung for all patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy doses in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]]
(range: 598.2 to 2737.6 cm3) and 2127.5 cm3 (range: 892.7 to 3091.4 cm3), respectively. The p value analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the lung when comparing the DIBH and free-breathing techniques are all more than 0.05 (i.e., p 4 0.05). This indicates that there is no significant difference in lung dose between the free-breathing and the DIBH techniques. The DVHs for the ipsilateral lung for all patients including the mean DVH are shown in Fig. 4. Lung DVHs for new treatment plans can be evaluated along these mean DVH values to ensure consistency in treatment plans. Based on current data, breast treatment planning can aim at achieving the mean values of V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the lung. Heart dose evaluation The main OAR for patients being treated with the disease in the left breast is the heart. Data are only available for patients who had the diseases in the left breast, because normally, it is only for those patients that the heart is contoured for planning. The dose to the heart was also indexed by the percentage volume of ipsilateral heart receiving at least doses of 5 (V5 Gy), 10 (V10 Gy), 15 (V15 Gy), 20 (V20 Gy), and 30 Gy (V30 Gy). Table 6 shows the dose-volumetric analysis of the heart comparing patients treated with 42.5-Gy dose in 16 fractions and 50-Gy dose in 25 fractions. Table 6 is further subdivided into patients treated with the free-breathing and the DIBH techniques. The mean heart volume for patients treated with the free-breathing and the DIBH techniques is 606.5 cm3 (range: 353.3 to 999.5 cm3) and 543.7 cm3 (range: 313.0 to 1169.7 cm3), respectively. Our results confirm the significant advantage of using the DIBH technique to reduce heart dose when compared with the free-breathing technique. The p value analyses of the results for the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart comparing the DIBH and the free-breathing techniques are well less than 0.05 (i.e., p o 0.05). The DVHs for the heart for all patients including the mean DVH are shown in Fig. 5. Heart DVHs for new treatment plans can be evaluated along with these mean DVH values to ensure consistency in treatment plans. Based on current data, breast treatment planning can aim at achieving the mean values of V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V30 Gy for the heart. The current data indicate that using the hybrid IMRT technique for tangential intact breast radiation therapy can result in
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smaller “hot spots” while maintaining improved dose coverage and dose uniformity throughout the whole breast. This has also been demonstrated by other groups22-28 using similar techniques. Hot spots and dose inhomogeneity can lead to poor cosmetic outcomes and more skin reactions, especially in women with larger breasts. One such reaction—moist desquamation—has been correlated with increased pain and reduction in quality of life.22 Kestin et al.12 used IMRT to improve dose uniformity and potentially to reduce acute toxicity with tangential wholebreast radiotherapy. They concluded that the use of intensitymodulation techniques for tangential breast radiotherapy is an efficient and effective method for achieving uniform dose throughout the breast, and it is dosimetrically superior to treatment techniques that use wedges. They found lower overall areas of hot spots and lower maximum dose with IMRT. Abo-Madyan et al.23 evaluated intensity-modulated irradiation and other techniques by comparing dose homogeneity, target coverage, feasibility, and dosimetric reliability in patients with large breasts. They observed that aperture-based IMRT using 2 tangential beams with inverse optimization provides a better alternative to the standard wedged tangential beams for patients with large breasts while maintaining the efficiency of the treatment planning and delivery process. Pignol et al.22 conducted a multicenter, double-blind, randomized clinical trial to test if breast IMRT would reduce the rate of acute skin reaction, decrease pain, and improve quality of life when compared with standard radiotherapy using wedges. They concluded that breast IMRT technique significantly reduced the occurrence of moist desquamation compared with the standard wedged technique presumably because of lower hot spots and better homogeneity. We do not use hard wedges at our center for breast radiotherapy, as it has been recognized that the use of hard wedges increases scatter to the contralateral breast, which leads to an increased risk of radiation malignancies.1 Bhatnagar et al.24 compared the dose received by the contralateral breast during breast irradiation using IMRT and conventional tangential wedged field techniques and concluded that breast irradiation with tangential IMRT technique significantly reduces the dose to the contralateral breast when compared with conventional tangential wedged field techniques. Ludwig et al.26 compared 2 irradiation techniques for whole-breast irradiation—tangential wedged beams
Table 6 A summary of the statistical analysis of the heart volumetric doses for all patients. The data for the heart are only for those patients whose left breast was treated. Data have been separated into patients who were treated with the free-breathing technique and those treated with the deep inspiration breath-hold technique. nFB and nDIBH are the number of patients being treated with the free-breathing and the deep inspiration breath-hold techniques, respectively. The p value analysis of the tabulated results for the various doses when comparing the DIBH and the free-breathing techniques is also shown in the Table Free-breathing technique (n ¼ 167)
Heart volume (cc)
Deep Inspiration breath-hold technique (DIBH) (n ¼ 147)
Minimum
Maximum
Mean
Standard deviation
Minimum
Maximum
Mean
Standard deviation
353.34
999.51
606.52
98.75
312.98
1169.68
543.66
109.41
Heart dose parameters for 42.5-Gy dose in 16 fractions prescription dose (nFB ¼ 150 and nDIBH ¼ 139) V5 Gy (%) – 10.16 2.37 1.76 – – 7.68 1.13 1.17 – V10 Gy (%) V15 Gy (%) – 6.92 0.81 0.98 – V20 Gy (%) – 6.35 0.62 0.85 – V30 Gy (%) – 5.21 0.35 0.63 – Maximum heart dose (%PD) 8.35 101.19 79.06 26.67 7.67
5.42 3.55 2.72 2.14 1.21 103.47
0.52 0.14 0.09 0.06 0.02 31.45
Heart dose parameters for 50-Gy dose in 25 fractions prescription dose: The free-breathing technique (nFB ¼ 17 and nDIBH ¼ 8) 0.64 5.95 2.53 1.48 0.15 1.30 0.54 V5 Gy (%) V10 Gy (%) – 1.59 0.70 0.50 – 0.21 0.03 V15 Gy (%) – 0.95 0.37 0.31 – 0.10 0.01 – 0.76 0.23 0.22 – 0.06 0.01 V20 Gy (%) V30 Gy (%) – 0.47 0.09 0.12 – 0.02 – Maximum heart dose (%PD) 15.49 96.09 75.58 22.85 13.40 86.34 26.15 “–” Indicates that values are less than 0.01%. n
The mean values for the V30 Gy are so small that a calculated p value is not reliable.
p Value
0.84 0.44 0.32 0.24 0.12 27.27
o0.001 o0.001 o0.001 o0.001 o0.001 o0.001
0.39 0.07 0.04 0.02 0.01 24.63
0.001 0.001 0.003 0.008 *
o 0.001
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Fig. 5. A plot of the dose-volume histograms (DVHs) for the heart volumes for all patients treated with (A) 42.5-Gy dose in 16 fractions with regular breathing, (B) 42.5-Gy dose in 16 fractions with the deep inspiration breath-hold (DIBH) technique, and (C) 50-Gy dose in 25 fractions with the regular-breathing technique. Also shown are the mean DHVs. (Color version of figure is available online.)
vs “open” fields (without wedges) with forward planned segments —and indicated that partial volume segments can replace wedges for improved dose coverage and homogeneity in the PTV. Our data indicate very low volumes of V105%, V107%, V108%, and V110% using the hybrid IMRT technique, and although we have not correlated the dosimetry with clinical outcomes, the advantages of improved dose homogeneity in breast radiotherapy has been demonstrated by several authors.12,13,22,25 According to Vicini et al.,13 the breast volume receiving 105% (V105%) and 110% (V110%) of the prescribed
dose is significantly associated with an increased risk of developing acute skin toxicity. They observed that for patients with V110% o 200 cm,3 the risk of developing grade II or grade III acute skin toxicity was 31% vs 61%, respectively, in patients with V110% Z 200 cm.3 The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based radiotherapy.25
E. Osei et al. / Medical Dosimetry ] (2015) ]]]–]]]
Our treatment planning process including beam alignment, collimation, and optimization takes approximately 20 to 30 minutes. The planner focuses on examining the 3-D dose distribution including the DHVs and making minor adjustments, if necessary. Treatment delivery, including setup, takes approximately 10 to 15 minutes on both the Varian TrueBeam and EX treatment machines (Varian Oncology Systems) equipped with 120-millennium MLC. It is therefore possible to standardize the implementation of this technique and significantly improve the quality of radiotherapy delivery to all patients receiving intact breast radiotherapy without a negative effect on clinic time and economic resources. In addition, acute toxicity can in theory be reduced through a reduction in the breast volume receiving high doses.12,13 Vicini et al.13 presented their clinical experience with an intensity-modulated technique to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer and concluded that the intensity-modulation technique is an efficient method for achieving a uniform and standardized dose throughout the whole breast. They also indicated that a widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints.
Conclusion The use of hybrid IMRT technique for tangential intact breast radiation therapy is an efficient and reliable method for achieving dose uniformity throughout the whole breast. Predefined dosevolume constraints and objectives can be achieved, resulting in improved dose coverage of target breast tissue, reduction in breast volume receiving high doses and dose to adjacent normal tissue, and therefore with the potential to reduce the rate of acute skin reaction, decrease pain, and improve quality of life.22 Based on current data, it is possible to develop breast treatment plans that achieve dose coverage for the PTV_eval volume of 92% (V92% PD) and 95% (V95% PD) of the prescribed dose to at least 99% and 97% of the normalized volume, respectively, while at the same time, restricting the normalized volume of the PTV_eval receiving a hot spot of 105% (V105% PD) of the prescribed dose to less than 1%. Treatment planning of intact breast should also aim at minimizing doses to both the heart and the lung. The clinical implementation of this technology for patients with breast cancer can be achieved with minimal or no imposition on resources and time constraints.
Acknowledgment We gratefully acknowledge the support from all the treatment planners and radiation therapists at the cancer center for their dedication and commitment to patient care and ensuring a smooth implementation of the hybrid IMRT technology. References 1. Asbury K. 3D versus hybrid IMRT breast treatment planning: data, tips, and techniques. University of Maryland School of Medicine, 2012. 2. Falahatpour, Z.; Aghamiri, S.; Anbiaee, R. External radiotherapy of intact breast: a comparison between 2D (single CT-slice) and 3D (full CT-slices) plans. Int. J. Radiat. Res. 9(2):121–5; 2011. 3. Gursel, B.; Meydan, D.; Ozbek, N.; et al. Dosimetric comparison of three different external beam whole breast irradiation techniques. Adv. Ther. 28 (12):1114–25; 2011.
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