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Deep inspiration breathhold for left-sided breast cancer patients with unfavorable cardiac anatomy requiring internal mammary nodal irradiation
Practical Radiation Oncology (2017) xx, xxx–xxx
www.practicalradonc.org
Basic Original Report
Deep inspiration breathhold for left-sided breast cancer patients with unfavorable cardiac anatomy requiring internal mammary nodal irradiation Osama Mohamad MD, PhD a, Jean Shiao BS b, Bo Zhao PhD a, Karen Roach CMD a, Ezequiel Ramirez MS, CMD a, Dat T. Vo MD, PhD a, Kimberly Thomas MD a, Xuejun Gu PhD a, Ann Spangler MD a, Kevin Albuquerque MD, MS a, Asal Rahimi MD, MS a,⁎ a
Department of Radiation Oncology, University of Texas–Southwestern, Moncrief Radiation Oncology Center, Dallas, Texas School of Medicine, University of Texas–Southwestern, Dallas, Texas
b
Received 17 February 2017; revised 31 March 2017; accepted 8 April 2017
Abstract Purpose: The purpose of this study was to evaluate the utility of moderate deep inspiration breathhold (mDIBH) in reducing heart exposure in left breast cancer patients who have unfavorable cardiac anatomy and need internal mammary lymph node (IMLN) radiation therapy (RT). Methods and materials: We used maximum heart distance (MHD), defined as the maximum distance of the heart within the treatment field, N1 cm as a surrogate for unfavorable cardiac anatomy. Twenty-two left breast cancer patients with unfavorable cardiac anatomy requiring IMLN-RT underwent free-breathing (FB) and mDIBH computed tomography simulation and planning. Three-dimensional partially wide tangents (3D-PWTs) and intensity modulated RT plans were generated. Dose-volume histograms were used to compare heart and lung dosimetric parameters. Duration of treatment delivery was recorded for all fractions. Results: MHD decreased significantly in mDIBH scans. mDIBH significantly reduced mean heart dose (222.7 vs 578.4 cGy; P b .0001) and percentage of left lung receiving doses ≥20 Gy (V20; 31.93 vs 38.41%; P = .0006) in both 3D-PWT and intensity modulated RT plans. The change in MHD after breathhold reliably predicted mean heart dose reduction after mDIBH. Radiation was effectively delivered in 11.31 ± 3.40 minutes with an average of 10.06 ± 2.74 breathholds per fraction. Conclusions: mDIBH is efficient and can effectively decrease mean heart dose in patients with unfavorable cardiac anatomy who need IMLN-RT, thus simplifying planning and delivery for them. The reduction in mean heart dose is proportional to the reduction in maximum heart distance. Published by Elsevier Inc. on behalf of American Society for Radiation Oncolog.
Introduction Information from this article was presented at the American Society for Radiation Oncology meeting, September 25-28, 2016, Boston, Massachusetts. Supplementary material for this article (http://dx.doi.org/10.1016/j. prro.2017.04.006) can be found at www.practicalradonc.org. ⁎ Corresponding author. Department of Radiation Oncology, University of Texas–Southwestern, Moncrief Radiation Oncology Center, 5801 Forest Park Rd, Dallas, TX 75390. E-mail address: [email protected] (A. Rahimi).
Internal mammary lymph node (IMLN) radiation therapy (RT) in breast cancer patients remains controversial. 1-3 Randomized studies showing a survival advantage for RT included the IMLNs in their treatment fields. 2,4-6 Notably, the most recent 2016 joint American Society of Clinical Oncology, American Society for
http://dx.doi.org/10.1016/j.prro.2017.04.006 1879-8500/Published by Elsevier Inc. on behalf of American Society for Radiation Oncolog.
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Radiation Oncology, and Society of Surgical Oncology guideline recommended irradiating the IMLNs in postmastectomy patients with positive lymph nodes 7; however, left IMLN RT is associated with increased risk of delayed cardiovascular disease secondary to increased size of radiation fields. 8-10 As a result, every effort should be made to decrease cardiac exposure in left-sided breast cancer patients requiring IMLN RT, especially in those with preexisting heart conditions, or with unfavorable anatomy. Moderate deep inspiration breathhold (mDIBH) can reduce heart exposure during left-sided breast or chest wall irradiation even when the IMLNs are included. 11,12 The heart-sparing benefit of mDIBH arises from its ability to physically move the heart out of radiation fields. We used maximum heart distance (MHD), defined as the distance of heart within treatment fields, as a surrogate for unfavorable cardiac anatomy. In this study, we aimed to evaluate the efficacy of mDIBH in reducing heart exposure, to identify predictors of mean heart dose reduction, and to determine the duration of treatment delivery for patients with unfavorable cardiac anatomy who also require IMLN RT.
target volume delineation including the breast (after lumpectomy) or chest wall (after mastectomy), IMLNs, and axillary and supraclavicular lymph nodes was based on Radiation Therapy Oncology Group guidelines. 14 The left anterior descending (LAD) artery was also contoured. 15 Pinnacle (Philips Medical System, Andover, MA) treatment planning system was used for planning. Our standard approach in these patients (left-sided, unfavorable cardiac anatomy, and IMLN RT) is to start with a 3-dimensional partially wide tangent (3D-PWT) plan and use IMRT beams if cardiac and/or lung constraints are not met. For IMRT plans, MHD was calculated from tangents used in the initial 3D planning trial. Eleven patients had 3D-PWT plans, and 11 patients had IMRT plans. For 3D-PWT, medial and lateral coplanar tangent fields were widened superiorly to include the IMLNs of the first 3 intercostal spaces and narrowed inferiorly below the third intercostal space to exclude heart/lung. IMRT plans were generated with inverse-planning optimization.
Methods and materials
Dose-volume histograms were used to compare target coverage and constraints of organs at risk (OAR). D95% breast PTV, percentage of IMLN volume receiving doses ≥90% (V90%), heart (mean dose, V5, V20, and V25), LAD (maximum and mean dose), left lung (mean dose, V5, V13, and V20), right lung (V5), total lung (mean dose, V5, and V20), and spinal cord (mean and maximum dose) parameters were collected on both FB and mDIBH plans. Percentage change (%change) between FB and mDIBH, in all dosimetric parameters, was calculated using the formula:
Patient population Between December 2013 and June 2016, 22 patients with left-sided breast cancer underwent mastectomy or breast-conserving surgery followed by whole breast/chest wall and regional nodal RT including the IMLNs using mDIBH on the Active Breathing Coordinator (ABC) system (ELEKTA, Stockholm, Sweden). All patients had unfavorable heart anatomy defined per Taylor et al, 13 as free-breathing (FB) MHD N1 cm; which is the maximum distance between the heart contour and the posterior edge of the tangent as measured on the medial or lateral beams-eye view images.
CT simulation All patients underwent FB and breathhold (BH) computed tomography (CT) simulation scans in the supine position on a Vac-Lok bag on a breast board. Patients were coached to use the ABC system and were included only if they were able to maintain mDIBH for ≥25 seconds, with the threshold determined at 70% to 80% of deep inspiratory capacity. The difference in MHD between FB and BH scans, ΔMHD(FB-BH), was calculated by subtracting MHD of the BH scan from MHD of the FB scan. Therapists recorded the total duration of each daily treatment and the number and duration of breathholds.
Dosimetric evaluation
%change ¼
Parameter ðFB Þ−Parameter ðmDIBH Þ Parameter ðFB Þ
Statistics All values were reported as mean ± standard deviation. GraphPad Prism 7.01 (La Jolla, CA) was used for statistical analysis. Dosimetric parameters were analyzed for correlation with MHD and ΔMHD(FB-BH) using simple linear regression. All other comparisons were performed using the Wilcoxon matched-pairs test or the unpaired t test as needed. All statistical tests were 2-sided and a P value ≤.05 was considered statistically significant for all comparisons.
Results
Target volumes and treatment planning
Patient characteristics
Breast (or chest wall) extent was clinically defined during CT simulation using anatomic landmarks. Clinical
Baseline clinical and treatment characteristics are shown in eTable 1, available as supplementary material
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DIBH reduces dose in unfavorable breast XRT
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Figure 1 Reduction in maximum heart distance between free-breathing (A, red arrow) and moderate deep inspiration breathhold scans (B, red line).
online only at www.practicalradonc.org. MHD (Fig 1A,B and Table 1) was significantly reduced after mDIBH (2.39 ± 0.84 cm vs 0.99 ± 0.67 cm; P b .0001). mDIBH completely displaced the heart out of the tangent fields in 3 cases (14%). MHD decreased by N50% in 14 cases (64%). Notably, IMRT patients had higher MHD compared with 3D-PWT patients. ΔMHD(FB-BH) was greater in the 3D versus IMRT cases but the difference was not statistically significant (Table 1).
Target coverage and OAR radiation doses Typical 3D-PWT and IMRT plans are shown in Fig 2A-D. A direct comparison of dose parameters of target volumes and OAR in both mDIBH and FB is shown in Table 2 and eTable 2. All plans achieved sufficient target coverage for the left breast and the IMLNs (D95% breast PTV or V90% IMLN PTV) independent of the treatment technique (3D-PWT vs IMRT or mDIBH vs FB). For all patients, mDIBH significantly reduced mean heart dose and left lung V20. Likewise, there was a significant reduction in other heart and lung parameters, but not V5 contralateral right lung. mDIBH equally reduced all heart parameters and mean total lung, mean left lung, and left lung V13 and V20 in both 3D-PWT and IMRT plans (Table 2). In addition, when considering the mastectomy or lumpectomy groups separately, mDIBH reduced mean heart, heart V25, and maximum and mean LAD doses independent of the treatment technique used (3D-PWT and IMRT).
Table 1
Correlation between MHD and dosimetric parameters Simple linear regression was used to calculate the coefficient of determination (r 2 ) for the correlation between MHD and different parameters (eTable 3). MHD in the FB scans correlated well with mean heart dose in the FB plans (r 2 = 0.72, P b .0001) and predicted percentage change in mean heart dose (ie, higher MHD predicted a larger mean heart dose reduction after mDIBH: r 2 = 0.38, P = .0023, Fig 3A, C). Figure 3A shows how the mean heart dose best-fit lines from the FB and mDIBH plans separate with increasing MHD. ΔMHD(FB-BH), on the other hand, showed the strongest correlation with the percentage change in mean heart dose (r 2 = 0.75, P b .0001; Fig 3B, D) as shown by the more dramatic separation of the mean heart dose best-fit lines between the FB and mDIBH plans with increasing ΔMHD(FB-BH). Patients with ΔMHD(FB-BH) N1 cm had an average 65% reduction in mean heart dose compared with patients who had ΔMHD(FB-BH) ≤ 1 cm who achieved an average of 37% improvement (P b .0001). Still, patients with 0.5 ≤ ΔMHD(FB-BH) ≤ 1 cm and those with 0 ≤ ΔMHD(FB-BH) b 0.5 cm achieved an average of 40% and 23% reduction in mean heart dose, respectively. The absolute reductions in mean heart dose were 4.5, 2, and 1.9 Gy for patients with ΔMHD(FB-BH) N1 cm, 0.5 ≤ΔMHD(FB-BH) ≤1 cm and 0 ≤ΔMHD(FB-BH) b0.5 cm, respectively.
Baseline characteristics
MHD on FB scans (cm, range) MHD on mDIBH scans (cm, range) ΔMHD(FB-BH) (cm, average±SD)
3D-PWT (n = 11)
IMRT (n = 11)
All patients (n = 22)
2.28 (1.27-3.99) 0.69 (0-1.4) 1.59±0.67
2.49 (1.11-3.94) 1.28 (0-2.18) 1.21±0.95
2.39 (1.11-3.99) 0.99 (0-2.18) 1.40±0.82
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Figure 2 Representative treatment plans showing prescription isodose line in red and internal mammary lymph node planning target volume contour in yellow (medial planning target volume border) for free-breathing (A, C) and moderate deep inspiration breathhold (B, D) in both 3-dimensional partially wide tangent (3D-PWT; A, B) and intensity modulated radiation therapy (IMRT;C, D) plans. Isodose lines color map: pink 5393 cGy, red 5040 cGy, orange 4939 cGy, light orange 4788 cGy, yellow 4536 cGy, yellow-green 4032 cGy, green 3528 cGy, blue 2520 cGy.
Treatment times On average, from setup to the end of radiation delivery, patients spent about 11 minutes on the table during regular treatment days and about 29 minutes on imaging (+treatment) days. Time from first to last breathhold (time from finalizing setup to the time until last beam completed) was comparable between 3D-PWT and IMRT (Table 3). The average number of breathholds per fraction and the duration of each breathhold were significantly increased in IMRT cases on treatment days.
Discussion In this study, we evaluated the role of mDIBH for IMLN RT in patients with unfavorable cardiac anatomy. We showed that mDIBH is efficient and can decrease heart and lung doses after lumpectomy or mastectomy in both 3D-PWT and IMRT plans without affecting plan quality or IMLN coverage. In addition, we have shown that the greater the reduction in MHD after mDIBH (larger
ΔMHD(FB-BH)), the more reduction in mean heart dose we achieved. By using mDIBH in these patients, we were able to avoid complex older techniques such as the electron-photon match, which can be timely, tedious, create heterogeneous plans, and can have deleterious cardiac morbidity and mortality consequences. 16-20 A recent review reported mean heart doses for left breast radiation using various techniques. 21 Notably, IMLN irradiation doubled mean heart dose (4.2 vs 8.4 Gy). Average mean heart doses were 9.4, 8.6, 4.0, and 2.6 Gy for tangents without breathing control, IMRT, tangents with breathing control, and protons, respectively. Women with unfavorable anatomy and left-sided cancer had a mean heart dose of 7.1 Gy. Interestingly, IMRT alone was not very effective in decreasing heart exposure when the IMLN are included. In our study, we showed that mDIBH can reduce mean heart doses to an average of 2.2 Gy in patients with both IMLN RT and unfavorable anatomy, with both 3D-PWT and IMRT. This dose is comparable to what could be achieved with protons. The reduction in cardiac exposure with mDIBH is well substantiated. 12,22,23 Only a few studies, however, have
Practical Radiation Oncology: Month 2017 Table 2
DIBH reduces dose in unfavorable breast XRT
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Average dose parameters to target volumes and to organs at risk mDIBH (Mean ± SD)
D95%, PTV (cGy) 3D-PWT IMRT All patients V90%, IMLN (%) 3D-PWT IMRT All patients Mean heart dose (cGy) 3D-PWT IMRT All patients V25Gy, Heart (%) 3D-PWT IMRT All patients Mean LAD dose (cGy) 3D-PWT IMRT All patients Mean total lung dose (cGy) 3D-PWT IMRT All patients Mean left lung dose (cGy) 3D-PWT IMRT All patients V20Gy, Left lung (%) 3D-PWT IMRT All patients
FB (Mean ± SD)
P value
4998 ± 137.80 4891 ± 177.70 4910 ± 165.60
4878 ± 110.20 4998 ± 45.01 4979 ± 76.00
0.2500 0.0371 0.1930
N/A
92.73 ± 16.99 94.73 ± 5.39 93.73 ± 12.34
94.36 ± 6.65 97.00 ± 3.80 95.68 ± 5.45
0.4753 0.2277 0.8700
N/A
194.5 ± 65.50 250.8 ± 127.20 222.7 ± 102.80
502.9 ± 164.20 653.9 ± 374.10 578.4 ± 292.40
0.0010 0.0010 b0.0001
-59.94 ± 9.40 -52.15 ± 26.67 -56.04 ± 19.91
0.93 ± 1.03 1.36 ± 1.86 1.15 ± 1.49
7.09 ± 3.53 9.82 ± 8.12 8.46 ± 6.27
0.0038 0.0038 b0.0001
-89.52 ± 11.09 -82.98 ± 21.59 -86.25 ± 17.08
1977 ± 599.00 2273 ± 1273.00 2125 ± 982.60
0.0010 0.0068 b0.0001
-52.36 ± 25.79 -46.12 ± 36.21 -49.24 ± 30.85
933.2 ± 607.70 946.1 ± 581.50 939.7 ± 580.50
%change (Mean ± SD)
704.10 ± 139.00 729.30 ± 151.80 716.70 ± 142.60
818.80 ± 105.00 855.90 ± 181.90 837.30 ± 146.20
0.0420 0.0068 0.0015
-13.50 ± 16.49 -13.90 ± 12.46 -13.70 ± 14.26
1483 ± 296.70 1513 ± 280.70 1498 ± 282.30
1802 ± 230.60 1804 ± 332.00 1803 ± 279.00
0.0137 0.0029 0.0002
-17.05 ± 16.51 -15.25 ± 12.94 -16.15 ± 14.51
31.55 ± 6.56 32.32 ± 7.11 31.93 ± 6.69
38.18 ± 5.72 38.64 ± 8.64 38.41 ± 7.16
0.0195 0.0112 0.0006
-16.31 ± 18.09 -15.26 ± 13.94 -15.78 ± 15.77
investigated the role of mDIBH with IMLN irradiation and showed cardiac sparing but either increased lung dose or showed no lung benefit at all. 24-26 We, however, report significant reduction in V20Gy left lung. The unfavorable cardiac anatomy of our patients makes cardiac sparing more complicated and thus makes mDIBH more essential. Herein, we chose MHD as a surrogate for unfavorable cardiac anatomy. Other markers of unfavorable anatomy such as cardiac contact distances in the axial or para-sagittal planes have been also investigated for their correlation with heart doses with variable degrees of success. 13,27-30 For example, heart V50 N10 cm 3 was used to select patients for mDIBH in patients requiring IMLN RT. 31,32 Automated IMRT FB plans were generated before the decision was made to proceed with mDIBH. Although the authors achieved an impressive 9-minute turnaround time for these automated plans, MHD, as used in our study, can be estimated visually without the need for dosimetric planning. In our study, ΔMHD(FB-BH) showed the strongest association with mean heart dose reduction after mDIBH. Interestingly,
although patients with ΔMHD(FB-BH) N1 cm achieved the most benefit, even patients with 0≤ΔMHD(FB-BH) b0.5 cm achieved an average 23% reduction in mean heart dose, corresponding to an absolute reduction of 1.9 Gy. Postulating that the relative risk of major coronary events after RT increases linearly with mean heart dose by 7.4% per Gray, 33 even patients with 0 ≤ΔMHD(FB-BH) b0.5 cm can still achieve a 14% reduction in cardiac morbidity with mDIBH. Previous studies showed that IMRT further reduces heart doses in patients undergoing whole breast radiation using mDIBH. 34 Our results, however, showed that both IMRT and 3D-PWT achieved similar reductions in heart and lung doses after mDIBH. We have 2 explanations for this. First, as explained previously, we only use IMRT after 3D plans fail to meet heart/lung constraints. Indeed, MHD was higher in the IMRT patients, indicating selection bias, which makes cardiac sparing more difficult. Second, we did not compare IMRT and 3D-PWT plans on the same patients; thus, the question of whether this cohort would achieve more benefit with the addition of IMRT to
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Figure 3 Correlation between mean heart dose or percentage change in mean heart dose and MHD or ΔMHD(FB-BH). DIBH, deep inspiration breathhold.
mDIBH remains to be addressed, which is beyond the scope of this paper. Interestingly, the number of breathholds and the duration of each breathhold were higher in the IMRT group, reflecting the increased number of fields and control points in IMRT plans. When considering the significant heart and lung sparing in this group of patients, mDIBH should not be considered as a burden on work flow, especially in patients with baseline cardiovascular risk factors. Although we did not compare treatment
Table 3
logistics between mDIBH and non-ABC treatment delivery, the time needed to complete treatments with mDIBH did not affect our workflow and was within the frame we usually reserve for non-ABC patients. In conclusion, we exclusively evaluated the role of mDIBH in patients with left-sided breast cancer and unfavorable cardiac anatomy requiring IMLN RT. mDIBH decreases heart and lung dose in both 3D-PWT and IMRT plans in these difficult cases, and ΔMHD(FB-BH) can predict improvements in mean heart dose after mDIBH.
Average treatment times and the number and duration of each breathhold Time from first to last BH, in mins (mean ± SD)
Treatment days 3D-PWT IMRT All patients Treatment days with portal imaging 3D-PWT IMRT All patients CT simulation 3D-PWT IMRT All patients
10.73 ± 3.64 11.84 ± 3.26 11.31 ± 3.40 28.17 ± 8.08 30.71 ± 13.89 29.50 ± 11.29 5.96 ± 1.72 4.62 ± 1.65 5.29 ± 1.78
P value
Number of BHs per fraction (mean ± SD)
0.4731
8.792 ± 2.32 11.22 ± 2.67 10.06 ± 2.74
0.6195
18.30 ± 5.19 18.18 ± 5.69 18.24 ± 5.32
0.1311
3.80 ± 0.92 3.40 ± 1.27 3.60 ± 1.10
P values are for statistical significance for the unpaired t-test comparing 3D-PWT vs. IMRT.
P value
Duration of each BH, in secs (Mean ± SD)
P value
0.0393
12.88 ± 0.54 17.18 ± 3.92 15.13 ± 3.56
0.0028
0.9610
11.03 ± 1.60 11.63 ±2.52 11.34 ± 2.10
0.5283
0.4286
20.06 ± 1.18 21.28 ± 2.43 20.67 ± 1.97
0.1685
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Basic Original Report
Deep inspiration breathhold for left-sided breast cancer patients with unfavorable cardiac anatomy requiring internal mammary nodal irradiation Osama Mohamad MD, PhD a, Jean Shiao BS b, Bo Zhao PhD a, Karen Roach CMD a, Ezequiel Ramirez MS, CMD a, Dat T. Vo MD, PhD a, Kimberly Thomas MD a, Xuejun Gu PhD a, Ann Spangler MD a, Kevin Albuquerque MD, MS a, Asal Rahimi MD, MS a,⁎ a
Department of Radiation Oncology, University of Texas–Southwestern, Moncrief Radiation Oncology Center, Dallas, Texas School of Medicine, University of Texas–Southwestern, Dallas, Texas
b
Received 17 February 2017; revised 31 March 2017; accepted 8 April 2017
Abstract Purpose: The purpose of this study was to evaluate the utility of moderate deep inspiration breathhold (mDIBH) in reducing heart exposure in left breast cancer patients who have unfavorable cardiac anatomy and need internal mammary lymph node (IMLN) radiation therapy (RT). Methods and materials: We used maximum heart distance (MHD), defined as the maximum distance of the heart within the treatment field, N1 cm as a surrogate for unfavorable cardiac anatomy. Twenty-two left breast cancer patients with unfavorable cardiac anatomy requiring IMLN-RT underwent free-breathing (FB) and mDIBH computed tomography simulation and planning. Three-dimensional partially wide tangents (3D-PWTs) and intensity modulated RT plans were generated. Dose-volume histograms were used to compare heart and lung dosimetric parameters. Duration of treatment delivery was recorded for all fractions. Results: MHD decreased significantly in mDIBH scans. mDIBH significantly reduced mean heart dose (222.7 vs 578.4 cGy; P b .0001) and percentage of left lung receiving doses ≥20 Gy (V20; 31.93 vs 38.41%; P = .0006) in both 3D-PWT and intensity modulated RT plans. The change in MHD after breathhold reliably predicted mean heart dose reduction after mDIBH. Radiation was effectively delivered in 11.31 ± 3.40 minutes with an average of 10.06 ± 2.74 breathholds per fraction. Conclusions: mDIBH is efficient and can effectively decrease mean heart dose in patients with unfavorable cardiac anatomy who need IMLN-RT, thus simplifying planning and delivery for them. The reduction in mean heart dose is proportional to the reduction in maximum heart distance. Published by Elsevier Inc. on behalf of American Society for Radiation Oncolog.
Introduction Information from this article was presented at the American Society for Radiation Oncology meeting, September 25-28, 2016, Boston, Massachusetts. Supplementary material for this article (http://dx.doi.org/10.1016/j. prro.2017.04.006) can be found at www.practicalradonc.org. ⁎ Corresponding author. Department of Radiation Oncology, University of Texas–Southwestern, Moncrief Radiation Oncology Center, 5801 Forest Park Rd, Dallas, TX 75390. E-mail address: [email protected] (A. Rahimi).
Internal mammary lymph node (IMLN) radiation therapy (RT) in breast cancer patients remains controversial. 1-3 Randomized studies showing a survival advantage for RT included the IMLNs in their treatment fields. 2,4-6 Notably, the most recent 2016 joint American Society of Clinical Oncology, American Society for
http://dx.doi.org/10.1016/j.prro.2017.04.006 1879-8500/Published by Elsevier Inc. on behalf of American Society for Radiation Oncolog.
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Radiation Oncology, and Society of Surgical Oncology guideline recommended irradiating the IMLNs in postmastectomy patients with positive lymph nodes 7; however, left IMLN RT is associated with increased risk of delayed cardiovascular disease secondary to increased size of radiation fields. 8-10 As a result, every effort should be made to decrease cardiac exposure in left-sided breast cancer patients requiring IMLN RT, especially in those with preexisting heart conditions, or with unfavorable anatomy. Moderate deep inspiration breathhold (mDIBH) can reduce heart exposure during left-sided breast or chest wall irradiation even when the IMLNs are included. 11,12 The heart-sparing benefit of mDIBH arises from its ability to physically move the heart out of radiation fields. We used maximum heart distance (MHD), defined as the distance of heart within treatment fields, as a surrogate for unfavorable cardiac anatomy. In this study, we aimed to evaluate the efficacy of mDIBH in reducing heart exposure, to identify predictors of mean heart dose reduction, and to determine the duration of treatment delivery for patients with unfavorable cardiac anatomy who also require IMLN RT.
target volume delineation including the breast (after lumpectomy) or chest wall (after mastectomy), IMLNs, and axillary and supraclavicular lymph nodes was based on Radiation Therapy Oncology Group guidelines. 14 The left anterior descending (LAD) artery was also contoured. 15 Pinnacle (Philips Medical System, Andover, MA) treatment planning system was used for planning. Our standard approach in these patients (left-sided, unfavorable cardiac anatomy, and IMLN RT) is to start with a 3-dimensional partially wide tangent (3D-PWT) plan and use IMRT beams if cardiac and/or lung constraints are not met. For IMRT plans, MHD was calculated from tangents used in the initial 3D planning trial. Eleven patients had 3D-PWT plans, and 11 patients had IMRT plans. For 3D-PWT, medial and lateral coplanar tangent fields were widened superiorly to include the IMLNs of the first 3 intercostal spaces and narrowed inferiorly below the third intercostal space to exclude heart/lung. IMRT plans were generated with inverse-planning optimization.
Methods and materials
Dose-volume histograms were used to compare target coverage and constraints of organs at risk (OAR). D95% breast PTV, percentage of IMLN volume receiving doses ≥90% (V90%), heart (mean dose, V5, V20, and V25), LAD (maximum and mean dose), left lung (mean dose, V5, V13, and V20), right lung (V5), total lung (mean dose, V5, and V20), and spinal cord (mean and maximum dose) parameters were collected on both FB and mDIBH plans. Percentage change (%change) between FB and mDIBH, in all dosimetric parameters, was calculated using the formula:
Patient population Between December 2013 and June 2016, 22 patients with left-sided breast cancer underwent mastectomy or breast-conserving surgery followed by whole breast/chest wall and regional nodal RT including the IMLNs using mDIBH on the Active Breathing Coordinator (ABC) system (ELEKTA, Stockholm, Sweden). All patients had unfavorable heart anatomy defined per Taylor et al, 13 as free-breathing (FB) MHD N1 cm; which is the maximum distance between the heart contour and the posterior edge of the tangent as measured on the medial or lateral beams-eye view images.
CT simulation All patients underwent FB and breathhold (BH) computed tomography (CT) simulation scans in the supine position on a Vac-Lok bag on a breast board. Patients were coached to use the ABC system and were included only if they were able to maintain mDIBH for ≥25 seconds, with the threshold determined at 70% to 80% of deep inspiratory capacity. The difference in MHD between FB and BH scans, ΔMHD(FB-BH), was calculated by subtracting MHD of the BH scan from MHD of the FB scan. Therapists recorded the total duration of each daily treatment and the number and duration of breathholds.
Dosimetric evaluation
%change ¼
Parameter ðFB Þ−Parameter ðmDIBH Þ Parameter ðFB Þ
Statistics All values were reported as mean ± standard deviation. GraphPad Prism 7.01 (La Jolla, CA) was used for statistical analysis. Dosimetric parameters were analyzed for correlation with MHD and ΔMHD(FB-BH) using simple linear regression. All other comparisons were performed using the Wilcoxon matched-pairs test or the unpaired t test as needed. All statistical tests were 2-sided and a P value ≤.05 was considered statistically significant for all comparisons.
Results
Target volumes and treatment planning
Patient characteristics
Breast (or chest wall) extent was clinically defined during CT simulation using anatomic landmarks. Clinical
Baseline clinical and treatment characteristics are shown in eTable 1, available as supplementary material
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Figure 1 Reduction in maximum heart distance between free-breathing (A, red arrow) and moderate deep inspiration breathhold scans (B, red line).
online only at www.practicalradonc.org. MHD (Fig 1A,B and Table 1) was significantly reduced after mDIBH (2.39 ± 0.84 cm vs 0.99 ± 0.67 cm; P b .0001). mDIBH completely displaced the heart out of the tangent fields in 3 cases (14%). MHD decreased by N50% in 14 cases (64%). Notably, IMRT patients had higher MHD compared with 3D-PWT patients. ΔMHD(FB-BH) was greater in the 3D versus IMRT cases but the difference was not statistically significant (Table 1).
Target coverage and OAR radiation doses Typical 3D-PWT and IMRT plans are shown in Fig 2A-D. A direct comparison of dose parameters of target volumes and OAR in both mDIBH and FB is shown in Table 2 and eTable 2. All plans achieved sufficient target coverage for the left breast and the IMLNs (D95% breast PTV or V90% IMLN PTV) independent of the treatment technique (3D-PWT vs IMRT or mDIBH vs FB). For all patients, mDIBH significantly reduced mean heart dose and left lung V20. Likewise, there was a significant reduction in other heart and lung parameters, but not V5 contralateral right lung. mDIBH equally reduced all heart parameters and mean total lung, mean left lung, and left lung V13 and V20 in both 3D-PWT and IMRT plans (Table 2). In addition, when considering the mastectomy or lumpectomy groups separately, mDIBH reduced mean heart, heart V25, and maximum and mean LAD doses independent of the treatment technique used (3D-PWT and IMRT).
Table 1
Correlation between MHD and dosimetric parameters Simple linear regression was used to calculate the coefficient of determination (r 2 ) for the correlation between MHD and different parameters (eTable 3). MHD in the FB scans correlated well with mean heart dose in the FB plans (r 2 = 0.72, P b .0001) and predicted percentage change in mean heart dose (ie, higher MHD predicted a larger mean heart dose reduction after mDIBH: r 2 = 0.38, P = .0023, Fig 3A, C). Figure 3A shows how the mean heart dose best-fit lines from the FB and mDIBH plans separate with increasing MHD. ΔMHD(FB-BH), on the other hand, showed the strongest correlation with the percentage change in mean heart dose (r 2 = 0.75, P b .0001; Fig 3B, D) as shown by the more dramatic separation of the mean heart dose best-fit lines between the FB and mDIBH plans with increasing ΔMHD(FB-BH). Patients with ΔMHD(FB-BH) N1 cm had an average 65% reduction in mean heart dose compared with patients who had ΔMHD(FB-BH) ≤ 1 cm who achieved an average of 37% improvement (P b .0001). Still, patients with 0.5 ≤ ΔMHD(FB-BH) ≤ 1 cm and those with 0 ≤ ΔMHD(FB-BH) b 0.5 cm achieved an average of 40% and 23% reduction in mean heart dose, respectively. The absolute reductions in mean heart dose were 4.5, 2, and 1.9 Gy for patients with ΔMHD(FB-BH) N1 cm, 0.5 ≤ΔMHD(FB-BH) ≤1 cm and 0 ≤ΔMHD(FB-BH) b0.5 cm, respectively.
Baseline characteristics
MHD on FB scans (cm, range) MHD on mDIBH scans (cm, range) ΔMHD(FB-BH) (cm, average±SD)
3D-PWT (n = 11)
IMRT (n = 11)
All patients (n = 22)
2.28 (1.27-3.99) 0.69 (0-1.4) 1.59±0.67
2.49 (1.11-3.94) 1.28 (0-2.18) 1.21±0.95
2.39 (1.11-3.99) 0.99 (0-2.18) 1.40±0.82
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Figure 2 Representative treatment plans showing prescription isodose line in red and internal mammary lymph node planning target volume contour in yellow (medial planning target volume border) for free-breathing (A, C) and moderate deep inspiration breathhold (B, D) in both 3-dimensional partially wide tangent (3D-PWT; A, B) and intensity modulated radiation therapy (IMRT;C, D) plans. Isodose lines color map: pink 5393 cGy, red 5040 cGy, orange 4939 cGy, light orange 4788 cGy, yellow 4536 cGy, yellow-green 4032 cGy, green 3528 cGy, blue 2520 cGy.
Treatment times On average, from setup to the end of radiation delivery, patients spent about 11 minutes on the table during regular treatment days and about 29 minutes on imaging (+treatment) days. Time from first to last breathhold (time from finalizing setup to the time until last beam completed) was comparable between 3D-PWT and IMRT (Table 3). The average number of breathholds per fraction and the duration of each breathhold were significantly increased in IMRT cases on treatment days.
Discussion In this study, we evaluated the role of mDIBH for IMLN RT in patients with unfavorable cardiac anatomy. We showed that mDIBH is efficient and can decrease heart and lung doses after lumpectomy or mastectomy in both 3D-PWT and IMRT plans without affecting plan quality or IMLN coverage. In addition, we have shown that the greater the reduction in MHD after mDIBH (larger
ΔMHD(FB-BH)), the more reduction in mean heart dose we achieved. By using mDIBH in these patients, we were able to avoid complex older techniques such as the electron-photon match, which can be timely, tedious, create heterogeneous plans, and can have deleterious cardiac morbidity and mortality consequences. 16-20 A recent review reported mean heart doses for left breast radiation using various techniques. 21 Notably, IMLN irradiation doubled mean heart dose (4.2 vs 8.4 Gy). Average mean heart doses were 9.4, 8.6, 4.0, and 2.6 Gy for tangents without breathing control, IMRT, tangents with breathing control, and protons, respectively. Women with unfavorable anatomy and left-sided cancer had a mean heart dose of 7.1 Gy. Interestingly, IMRT alone was not very effective in decreasing heart exposure when the IMLN are included. In our study, we showed that mDIBH can reduce mean heart doses to an average of 2.2 Gy in patients with both IMLN RT and unfavorable anatomy, with both 3D-PWT and IMRT. This dose is comparable to what could be achieved with protons. The reduction in cardiac exposure with mDIBH is well substantiated. 12,22,23 Only a few studies, however, have
Practical Radiation Oncology: Month 2017 Table 2
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Average dose parameters to target volumes and to organs at risk mDIBH (Mean ± SD)
D95%, PTV (cGy) 3D-PWT IMRT All patients V90%, IMLN (%) 3D-PWT IMRT All patients Mean heart dose (cGy) 3D-PWT IMRT All patients V25Gy, Heart (%) 3D-PWT IMRT All patients Mean LAD dose (cGy) 3D-PWT IMRT All patients Mean total lung dose (cGy) 3D-PWT IMRT All patients Mean left lung dose (cGy) 3D-PWT IMRT All patients V20Gy, Left lung (%) 3D-PWT IMRT All patients
FB (Mean ± SD)
P value
4998 ± 137.80 4891 ± 177.70 4910 ± 165.60
4878 ± 110.20 4998 ± 45.01 4979 ± 76.00
0.2500 0.0371 0.1930
N/A
92.73 ± 16.99 94.73 ± 5.39 93.73 ± 12.34
94.36 ± 6.65 97.00 ± 3.80 95.68 ± 5.45
0.4753 0.2277 0.8700
N/A
194.5 ± 65.50 250.8 ± 127.20 222.7 ± 102.80
502.9 ± 164.20 653.9 ± 374.10 578.4 ± 292.40
0.0010 0.0010 b0.0001
-59.94 ± 9.40 -52.15 ± 26.67 -56.04 ± 19.91
0.93 ± 1.03 1.36 ± 1.86 1.15 ± 1.49
7.09 ± 3.53 9.82 ± 8.12 8.46 ± 6.27
0.0038 0.0038 b0.0001
-89.52 ± 11.09 -82.98 ± 21.59 -86.25 ± 17.08
1977 ± 599.00 2273 ± 1273.00 2125 ± 982.60
0.0010 0.0068 b0.0001
-52.36 ± 25.79 -46.12 ± 36.21 -49.24 ± 30.85
933.2 ± 607.70 946.1 ± 581.50 939.7 ± 580.50
%change (Mean ± SD)
704.10 ± 139.00 729.30 ± 151.80 716.70 ± 142.60
818.80 ± 105.00 855.90 ± 181.90 837.30 ± 146.20
0.0420 0.0068 0.0015
-13.50 ± 16.49 -13.90 ± 12.46 -13.70 ± 14.26
1483 ± 296.70 1513 ± 280.70 1498 ± 282.30
1802 ± 230.60 1804 ± 332.00 1803 ± 279.00
0.0137 0.0029 0.0002
-17.05 ± 16.51 -15.25 ± 12.94 -16.15 ± 14.51
31.55 ± 6.56 32.32 ± 7.11 31.93 ± 6.69
38.18 ± 5.72 38.64 ± 8.64 38.41 ± 7.16
0.0195 0.0112 0.0006
-16.31 ± 18.09 -15.26 ± 13.94 -15.78 ± 15.77
investigated the role of mDIBH with IMLN irradiation and showed cardiac sparing but either increased lung dose or showed no lung benefit at all. 24-26 We, however, report significant reduction in V20Gy left lung. The unfavorable cardiac anatomy of our patients makes cardiac sparing more complicated and thus makes mDIBH more essential. Herein, we chose MHD as a surrogate for unfavorable cardiac anatomy. Other markers of unfavorable anatomy such as cardiac contact distances in the axial or para-sagittal planes have been also investigated for their correlation with heart doses with variable degrees of success. 13,27-30 For example, heart V50 N10 cm 3 was used to select patients for mDIBH in patients requiring IMLN RT. 31,32 Automated IMRT FB plans were generated before the decision was made to proceed with mDIBH. Although the authors achieved an impressive 9-minute turnaround time for these automated plans, MHD, as used in our study, can be estimated visually without the need for dosimetric planning. In our study, ΔMHD(FB-BH) showed the strongest association with mean heart dose reduction after mDIBH. Interestingly,
although patients with ΔMHD(FB-BH) N1 cm achieved the most benefit, even patients with 0≤ΔMHD(FB-BH) b0.5 cm achieved an average 23% reduction in mean heart dose, corresponding to an absolute reduction of 1.9 Gy. Postulating that the relative risk of major coronary events after RT increases linearly with mean heart dose by 7.4% per Gray, 33 even patients with 0 ≤ΔMHD(FB-BH) b0.5 cm can still achieve a 14% reduction in cardiac morbidity with mDIBH. Previous studies showed that IMRT further reduces heart doses in patients undergoing whole breast radiation using mDIBH. 34 Our results, however, showed that both IMRT and 3D-PWT achieved similar reductions in heart and lung doses after mDIBH. We have 2 explanations for this. First, as explained previously, we only use IMRT after 3D plans fail to meet heart/lung constraints. Indeed, MHD was higher in the IMRT patients, indicating selection bias, which makes cardiac sparing more difficult. Second, we did not compare IMRT and 3D-PWT plans on the same patients; thus, the question of whether this cohort would achieve more benefit with the addition of IMRT to
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Figure 3 Correlation between mean heart dose or percentage change in mean heart dose and MHD or ΔMHD(FB-BH). DIBH, deep inspiration breathhold.
mDIBH remains to be addressed, which is beyond the scope of this paper. Interestingly, the number of breathholds and the duration of each breathhold were higher in the IMRT group, reflecting the increased number of fields and control points in IMRT plans. When considering the significant heart and lung sparing in this group of patients, mDIBH should not be considered as a burden on work flow, especially in patients with baseline cardiovascular risk factors. Although we did not compare treatment
Table 3
logistics between mDIBH and non-ABC treatment delivery, the time needed to complete treatments with mDIBH did not affect our workflow and was within the frame we usually reserve for non-ABC patients. In conclusion, we exclusively evaluated the role of mDIBH in patients with left-sided breast cancer and unfavorable cardiac anatomy requiring IMLN RT. mDIBH decreases heart and lung dose in both 3D-PWT and IMRT plans in these difficult cases, and ΔMHD(FB-BH) can predict improvements in mean heart dose after mDIBH.
Average treatment times and the number and duration of each breathhold Time from first to last BH, in mins (mean ± SD)
Treatment days 3D-PWT IMRT All patients Treatment days with portal imaging 3D-PWT IMRT All patients CT simulation 3D-PWT IMRT All patients
10.73 ± 3.64 11.84 ± 3.26 11.31 ± 3.40 28.17 ± 8.08 30.71 ± 13.89 29.50 ± 11.29 5.96 ± 1.72 4.62 ± 1.65 5.29 ± 1.78
P value
Number of BHs per fraction (mean ± SD)
0.4731
8.792 ± 2.32 11.22 ± 2.67 10.06 ± 2.74
0.6195
18.30 ± 5.19 18.18 ± 5.69 18.24 ± 5.32
0.1311
3.80 ± 0.92 3.40 ± 1.27 3.60 ± 1.10
P values are for statistical significance for the unpaired t-test comparing 3D-PWT vs. IMRT.
P value
Duration of each BH, in secs (Mean ± SD)
P value
0.0393
12.88 ± 0.54 17.18 ± 3.92 15.13 ± 3.56
0.0028
0.9610
11.03 ± 1.60 11.63 ±2.52 11.34 ± 2.10
0.5283
0.4286
20.06 ± 1.18 21.28 ± 2.43 20.67 ± 1.97
0.1685
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