1. bookVolume 54 (2020): Issue 4 (December 2020)
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1581-3207
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30 Apr 2007
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Breast size and dose to cardiac substructures in adjuvant three-dimensional conformal radiotherapy compared to tangential intensity modulated radiotherapy

Published Online: 29 Sep 2020
Volume & Issue: Volume 54 (2020) - Issue 4 (December 2020)
Page range: 470 - 479
Received: 18 Mar 2020
Accepted: 10 May 2020
Journal Details
License
Format
Journal
eISSN
1581-3207
First Published
30 Apr 2007
Publication timeframe
4 times per year
Languages
English
Introduction

Cardiovascular diseases are becoming the most critical competing mortality risk in women with early breast cancer treated with present-day radiotherapy (RT).1,2, The relative risk of radiation-induced heart failure increases with rising cardiac radiation exposure, typically reported as mean absorbed dose to the whole heart (MWHD).3,4,5 MWHD values reflect local radiation therapy practices, and with the help of modern RT approaches, now ranging from 1.7–5.4 Gy6,7,8 and 1.22–1.65 Gy9, for mean and median values, respectively. However, even very low cardiac exposure does not eliminate the risk of radiotherapy-mediated cardiotoxicity, which has been demonstrated in recent studies.3,5,10

In many recent publications, authors favor the use of intensity modulated techniques over three-dimensional conformal radiotherapy (3D-CRT) in node negative breast cancer adjuvant RT, arguing for lower MWHD, decreased skin toxicity and more homogeneous dose distribution in the target volume.11,12,13 Besides the RT technique used, MWHD depends on the position of the patient’s heart relative to the irradiated breast and the shape of their chest wall.14 Different simple anatomical measures were evaluated to predict increased MWHD and subsequently for the need to use one of the heart-sparing techniques, namely deep inspiration breath hold technique (DIBH). Useful anatomical measures are increased chest wall separation (CWS)9, maximum heart distance (the distance between the anterior cardiac contour crossing over the posterior edge of the tangential fields)15, multidimensional assessment of the presence of the heart in contact with the chest wall14 and linear heart contact distance from the left sternal to the beginning of the lung parenchyma edges at the 4th costal arch in the axial axis.16 It has also been shown that the shape and size of the clinical target volume (CTV) result in increased mean and/or maximum point heart doses.9,17,18 If a cohort of breast cancer patients with similar breast volume is defined, specific problems and resolutions can be proposed, because breast contours according to breast size and shape may be associated with the variations in the target volume coverage and calculated dose to organs at risk.19 Three-dimensional treatment planning allows target volume to be measured and CTVs of ≤ 500–975 cm3, 975–1.600 cm3 and ≥ 1.600 cm3 have been typically, but not consistently, defined as small, medium and large breasts, respectively.20,21 Additionally, quite a few clinical studies have reported a comparison of the clinical adverse events in regard to the three groups of breast sizes.22

Although observed average MWHD in a population of breast cancer survivors is low, smaller fragments of the heart might have received doses exceeding 25–40 Gy.4,10,23,24 Subclinical cardiac dysfunction was observed early after adjuvant radiotherapy for breast cancer with molecular bio-markers25,26 radionuclide myocardial perfusion imaging27,28,29, echocardiography30,31,32, and functional magnetic resonance imaging.31 Limited data exist regarding the range of doses received by individual heart substructures with adjuvant free-breathing 3D-CRT or tangential intensity modulated radiotherapy (t-IMRT) for left-sided breast cancer. It has been shown that MWHD does not necessarily correlate to mean radiation doses, absorbed by cardiac chambers or coronary arteries in adjuvant breast cancer radiotherapy.33,34,35,36 Lately, detailed studies of the specific cardiac structures’ absorbed radiation dose in thoracic radiation therapy24,36,37, and the efforts to understand the specific radiation dose-volume effects in the heart have emerged. 4,38,39,40,41 With expanding knowledge in this field, German Society of Radiation Oncology (DEGRO) recommends new stringent dose constraints for the heart and its substructures: MWHD < 2.5 Gy, left ventricle (LV) Dmean < 3 Gy (LV mean dose), LV V5 < 17% (volume of LV receiving ≤ 5 Gy), LV V23 < 5% (volume of LV receiving ≤ 23 Gy), left anterior descending coronary (LADCA) Dmean < 10 Gy (LADCA mean dose), LADCA V30 < 2% (volume of LADCA receiving ≤ 30 Gy), and LADCA V40 < 1% (volume of LADCA receiving ≤ 40 Gy).42

To standardize the reporting of cardiac imaging regardless of diagnostic modality, both The American Society of Echocardiography and the European Association of Cardiovascular Imaging recommend using a segmentation model of the LV to assess regional LV function.42,44 The LV segmentation model reflects coronary arteries’ territories and permits to compare echocardiography with other imaging modalities.43 Five main LV segments, defined in a cardiac atlas by Duane et al.24 are based on a previously described 17-segmentation model.44

In this work, we hypothesized that in the setting of the node-negative left-sided breast cancer adjuvant radiotherapy, the lowest median MWHD and doses to the cardiac substructures would be achieved with the t-IMRT, compared to 3D-CRT. In addition, we assumed that individual patient characteristics, which include chest wall separation and breast volume, would contribute to the differences in absorbed doses to the heart and cardiac substructures, regardless of the treatment planning technique. To test our hypothesis, we aimed to quantify doses to the heart and cardiac substructures in present-day free-breathing adjuvant 3D-CRT and t-IMRT and to analyze the differences in dosimetric metrics to organs at risk between three different groups of CTV according to breast size and other individual anatomical information.

Patients and methods
Patient selection and CT simulation

The study was approved by the ethics review board committee (approval number KME 78/07/15). Based on the size of the CTV, we randomly selected patients with early left-sided node-negative breast cancer. The definitions of the small, medium, and large breast volumes were like those made available elsewhere.22 The patients were referred to adjuvant radiotherapy between the years 2014 and 2015. All patients underwent a free-breathing non-enhanced simulation computed tomography (CT) scan with a 3 mm slice thickness. The treatment position for all women was supine, on an inclined simulation table using a breast board, with both arms positioned above the head.

Delineation, treatment planning, and data collection

Whole heart, LV with its anterior, apical, inferior, lateral, and septal walls, right ventricle (RV), left atrium (LA), right atrium (RA), LADCA with proximal, middle and distal segments, right coronary artery (RCA), left circumflex coronary artery (LCX), and left main coronary artery (LMCA) were delineated by one radiation oncologist. We followed identification of the individual structure segments by the instructions proposed by Duane et al.24 in a recently published heart atlas. We used a 6 mm diameter for all coronary arteries’ segments, as previously proposed.23 The thickness of the LV wall was set to 10 mm. An experienced cardiac radiologist reviewed the contoured cardiac segments. We delineated CTV to include total glandular breast tissue according to published guidelines.45 Planning target volume (PTV) was generated by adding a 5 mm uniform margin to the CTV, and the planning target volume for evaluation (PTVeval) was created similarly, with a modification that excludes 5 mm below the skin surface. Additionally, we collected anatomically based distance metrics, such as chest wall separation (CWS) and a previously described “4th arch” metric.16

We used Monaco (Elekta AB®, Stockholm, Sweden) as a contouring and treatment planning platform. The prescribed dose was 42.72 Gy in 16 fractions, 5 days per week. For the 3D-CRT treatment planning, we used 6MV photon tangential beam arrangement with wedge filters and additional 6MV or 15MV small beams in tangential or non-tangential beam direction where needed to achieve a homogeneous dose distribution. The “Collapsed Cone” algorithm was used to calculate the dose. For t-IMRT plans we used the same isocenter position as with 3D-CRT planning and two tangential 6 MV photon beams positioned in the same direction as for 3D-CRT plans. The plans were calculated using inverse dose optimization with “Monte-Carlo” algorithm. Dynamic Multileaf Collimator (dMLC) technique was used with minimum segment size 1 cm and 30 control points, which generated 25–30 segments per beam. Although “the dose-to-water” reporting is typically used in clinical routine for the inverse optimization treatment plans and since “Collapsed Cone” algorithm does not have that option for calculation, we used “the dose-to-medium” reporting in our study for both 3D-CRT and t-IMRT planning in order to improve treatment plan comparability.

In the planning optimization procedure, we used institutional target goals for both treatment plans (Table 1). Dose constraints for the specific cardiac substructures were not incorporated into the optimization process but we strived to keep the dose to the whole heart as low as possible without compromising the target coverage for both techniques. Each plan was thoroughly evaluated for target coverage and OAR. We reported nominal median absolute doses, without EQD2 (equivalent dose in 2 Gy per fraction) conversion. All treatment plans were created by one dosimetrist and one medical physicist.

Target goals used in the planning process

StructureTarget goals
PTVD2%< 108%
PTVevalV95%> 95%
Whole Body ContourGlobal Dmax < V110%
Dmean < 3.2 Gy
HeartV17 Gy < 10%
V35 Gy < 5%
Dmean < 10 Gy
Ipsilateral LungV17 Gy < 25%
V26 Gy < 20%
Bilateral lungDmean < 3.2 Gy

Dmax = maximum dose; Dmean = mean dose; Dx % = absorbed dose, received by x % of the PTV; PTV = planning target volume; PTVeval = planning target volume for evaluation; Vx % = fractional volume, receiving x % of the prescribed dose; Vx Gy = fractional volume receiving x Gy

Statistical analyses

Calculated dose distributions were compared amongst the two techniques and the three different groups of CTV. Due to mostly non-parametrically distributed data, dose distributions data between the groups were compared using the Kruskal-Wallis and Mann-Whitney tests. Friedman ANOVA and Wilcoxon signed-rank test were also used to compare values between the two techniques. All numbers are presented as median values with a range. Statistical analyses were performed with IBM® SPSS® version 24.0 (SPSS Inc., Armonk: NY, IBM corporation). We considered a p-value ≤ 0.05 as statistically significant.

Results
Patient population and treatment plans

Sixty patients with left-sided breast cancer were included in this analysis, divided into groups of small (N = 22, 36.6%), medium (N = 21, 35.0%) and large (N = 17, 28.4%) CTV size. Target volumes’ and OAR’s metrics are presented in Table 2.

Target volumes’ and organs at risk’s metrics

Target volume/ Organ at riskThe whole group N = 60Small CTV N = 22Medium CTV N = 21Large CTV N = 17p value
CTV [cm3]800.6 (124.8–2970.9)425.7 (124.8–545.5)867.0 (652.1–1295.1)1586.8 (1348.9–2970.9)0.021
PTVeval [cm3]990.7 (233.5–3336.1)583.0 (233.5–711.1)1035.9 (834.3–1576.5)1874.3 (1605.8–3336.1)< 0.005
PTV [cm3]1163.3 (340.1–3792.2)730.7 (340.1–856.6)1212.3 (985.1–1805)2134.8 (1826.4–3792.2)< 0.005
CWS [cm]23.1 (17.9–33.2)19.5 (17.9–23.2)24.0 (19.9–28.5)27.5 (22.9–33.2)< 0.005
4th arch metrics [cm]4.4 (0–11.6)1.6 (0–9.6)5.5 (0–11.6)7.1 (0–10.7)0.008
Heart [cm3]677.7 (432.9–1192.7)625.2 (432.9–912.8)671.1 (563.5–872.4)817.9 (620.1–1192.7)< 0.005
Left Ventricle [cm3]173.8 (116–277.4)161.3 (116–251.7)173.8 (120.8–229.8)188.7 (147.4–277.4)0.018
Left Lung [cm3]1245.1 (809.3–2127.9)1458.9 (824.5–2127.9)1123.8 (944.2–1619.2)1230.6 (809.3–1541.7)0.003
Right Lung [cm3]1563.4 (855–2560.1)1721.9 (992.9–2560.1)1466.4 (855.1–1838.2)1493.2 (1089.6–1925.6)0.002
Lungs [cm3]2879.7 (1504.6–4789.2)3241.3 (1877.5–4789.2)2634.4 (1504.6–3513.6)2799.8 (1960.2–3479.2)0.001

CTV = clinical target volume; CWS = chest wall separation distance at isocenter; PTV = planning target volume; PTVeval = planning target volume for evaluation

There was a statistically significant difference between the three groups for all measured target volumes, OAR volumes, and anatomically based simple distance metrics. Regarding target coverage, all except two dosimetric parameters (PTVeval V107%, PTVeval D2%), were superior in the 3D-CRT group (Tables 3 and 4). Nevertheless, the t-IM-RT approach resulted in lower high-dose areas (PTVeval V105%) across all three CTV groups.

Target volume dosimetric metrics

Target volume3D-CRTt-IMRTp value
PTVeval D98% [Gy]40.6 (39.8–41.4)40.3 (38.7–41.6)0.002
PTVeval D2% [Gy]44.7 (44.4–45.5)43.8 (43.8–47.1)NS
PTVeval D50% [Gy]43.3 (42.7–43.7)42.9 (42.2–43.9)< 0.005
PTVeval V95% [%]98.1 (95.3–99.6)96.8 (79.9–99.9)0.001
PTVeval V105% [%]1.3 (0.1–10.3)4.3 (0.01–85.9)< 0.005
PTVeval V105% [cm3]11.7 (0.08–656.7)5.4 (0.06–68.0)0.014
PTVeval V107% [%]0 (0–1.4)0.1 (0–9.6)< 0.005
PTVeval V107% [cm3]0 (0–321.4)0 (0–7.2)NS
PTVeval V110% [%]0 (0–0)0 (0–0)NS
Dmax [Gy]45.7 (45.1–46.9)46.9 (45.3–51)< 0.005

3D-CRT = three-dimensional conformal radiotherapy; D2% = near maximum dose, D50% = median dose; D98% = near minumum dose, Dmax = maximal absorbed dose, NS = not significant; PTVeval = planning target volume for evaluation; t-IMRT = tangential intensity modulated radiation therapy; Vx% = fractional volume, receiving x % of the prescribed dose

Target volume dosimetric metrics and CTV size

Target volumeSmall CTVMedium CTVLarge CTVp value (S vs. M vs. L)
3D-CRT PTVeval V95% [%]97.7 (95.3–99.6)98.3 (96.2–99.5)98.8 (97.5–99.4)0.022 (S vs. M, S vs. L)
t-IMRT PTVeval V95% [%]97.9 (96.3–99.2)97.3 (95.3–99.0)96.8 (79.9–99.9)NS
p value (3D-CRT vs. T-IMRT)NSp = 0.003p = 0.013
3D-CRT PTVeval V105% [cm3]8.1 (0.5–17.5)12.5 (0.08–91.3)87.3 (9.5–656.6)< 0.005 (S vs. M, S vs. L, M vs. L)
t-IMRT PTVeval V105% [cm3]7.4 (0.1–61.5)5.9 (0.09–54)4.2 (0.06–68.2)NS
p value (3D-CRT vs. T-IMRT)NSNSp = 0.012

3D-CRT = three-dimensional conformal radiotherapy; L = large; M = medium; NS = not significant; PTVeval = planning target volume for evaluation; S = small; t-IMRT = tangential intensity modulated radiation therapy; Vx% = fractional volume, receiving x % of the prescribed dose

Whole heart

For the whole group of evaluated patients, 3D-CRT technique showed significant lower MWHD compared to t-IMRT (Table 5) with an absolute difference of 0.2 Gy.

Radiotherapy technique and selected dose-volume parameters for the whole heart and selected cardiac substructures

Parameter3D-CRTt-IMRTp value*
MWHD [Gy]1.90 (0.61–4.14)2.13 (1.06–4.4)< 0.005
LV-Dmean [Gy]2.98 (0.78–8.03)3.22 (1.31–7.25)< 0.005
LV-V5 Gy [%]8.67 (0–26.3)9.21 (0–26.02)0.455
LV-V23 Gy [%]2.46 (0–14.32)1.86 (0–10.58)0.003
LV anterior-Dmean [Gy]5.00 (1.27–20.17)5.42 (1.94–19.18)< 0.005
LV apical-Dmean [Gy]8.97 (1.22–24.89)8.47 (1.64–22.16)< 0.005
LADCA-Dmean [Gy]8.20 (1.23–27.92)8.39 (1.8–27.62)< 0.005
LADCA-V30 Gy [%]5.39 (0–66.34)2.01 (0–84.20)< 0.005
LADCA-V40 Gy [%]0 (0–37.8)0 (0–43.09)< 0.005
LADCA-prox-Dmean [Gy]2.17 (0.62–8.68)2.66 (1.22–12.43)< 0.005
LADCA-mid-Dmean [Gy]9.63 (1.67–40.07)11.05 (2.26–39.63)0.956
LADCA-dist-Dmean [Gy]13.73 (1.44–41.11)15.93 (2.03–3.89)0.132

*Wilcoxon signed-rank test; 3D-CRT = three-dimensional conformal radiotherapy; dist = distal; Dmean = mean dose; Gy = Gray; LADCA = left anterior descending artery; LV = left ventricle; mid = middle; MWHD = whole heart mean dose; prox = proximal; t-IMRT = tangential intensity modulated radiation therapy; Vx Gy = fractional volume receiving x Gy

Absolute difference in MWHD between the two techniques ranged from 0.06, 0.46 and 0.7 for the groups of medium-, large- and small-sized CTVs, respectively (Table 6). CTV size had an impact on MWHD regardless of the RT technique, while other parameters were not statistically different except for heart-V5 Gy in 3D-CRT technique. In 3D-CRT, MWHD correlated with increased CWS relative to 18.0 cm (0.09 Gy/1 cm, p = 0.0022) and with CTV size (0.06 Gy/100 cm3, p = 0.0015). Low MWHD values (< 2.5 Gy) were achieved in 44 (73.3%) and 41 (68.3%) patients for 3D-CRT and t-IMRT techniques, correspondingly (Figure 1).

Figure 1

Mean whole heart dose and number of plans within each CTV groups, concerning optimal mean dose value.

3D-CRT = three-dimensional conformal radiotherapy; CTV = clinical target volume; Gy = Gray; t-IMRT = tangential intensity modulated radiation therapy

Breast size and selected dose-volume parameters for the whole heart and cardiac substructures

Small CTVMedium CTVLarge CTV
Parameterp value
3D-CRTt-IMRT3D-CRTt-IMRT3D-CRTt-IMRT
MWHD [Gy]1.29 (0.61–3.75)1.99 (1.06–3.98)2.05 (1.06–3.84)2.11 (1.62–3.54)2.26 (1.04–4.14)2.72 (1.46–4.4)< 0.005*; 0.047†
Heart-V5 Gy [%]2.56 (0.02–10.84)3.77 (0.1–11.01)4.99 (0.59–10.87)4.34 (1.19–9.58)5.29 (0–12.81)6.19 (0.04–12.83)0.043*
Heart-V10 Gy [%]1.28 (0–7.91)2.01 (0–7.59)2.71 (0.01–7.73)2.24 (0.12–68.14)3.09 (0–8.24)3.17 (0–8.54)NS
Heart-V17 Gy [%]0.76 (0–6.61)1.22 (0–6.08)2.03 (0–6.52)1.36 (0–4.79)2.37 (0–6.92)3.36 (0–6.42)NS
Heart-V20 Gy [%]0.62 (0–6.22)1 (0–5.63)1.83 (0–6.16)1.17 (0–4.38)2.15 (0–6.51)2.01 (0–5.81)NS
Heart-V35 Gy [%]0.15 (0–4.12)0.2 (0–3.4)0.93 (0–4.15)0.31 (0–2.3)1.06 (0–4.32)0.63 (0–2.91)NS
Heart-V40 Gy [%]0.02 (0–1.41)0.01 (0–1.65)0.24 (0–1.45)0.03 (0–0.42)0.03 (0–1.93)0.04 (0–1.69)NS
LV-Dmean [Gy]2.3 (0.7–5.7)2.9 (1.31–5.84)3.2 (1.1–6.9)3.15 (1.78–5.97)3.5 (1.3–8.0)3.92 (1.83–7.25)0.019*
LV-V5 Gy [%]6.8 (0–17.4)8.27 (0–17.39)9.7 (0–22.0)8.47 (0.46–19.87)10.8 (0–26.3)12 (0–26.02)0.052*
LV-V23 Gy [%]1.4 (0–9.5)1.73 (0–8.47)2.8 (0–12.0)1.81 (0–8.18)3.3 (0–14.3)3.1 (0–10.58)NS
LV anterior-Dmean [Gy]3.6 (1.2–12.8)4.86 (1.94–12.35)6.8 (2.0–15.9)5.71 (2.69–14.48)6.8 (1.9–20.1)6.94 (2.58–19.18)0.017*
LV lateral-Dmean [Gy]1.6 (0.7–2.8)2.16 (1.18–3.38)1.8 (0.9–6.3)2.24 (1.55–5.12)2.5 (1.2–8.7)2.98 (1.73–7.59)< < 0.0010.001*,
LV inferior-Dmean [Gy]0.5 (0.3–3.3)0.96 (0.77–1.17)0.6 (0.5–0.9)1.07 (0.9–1.32)0.8 (0.6–2.0)1.33 (0.96–1.98)< < 0.0050.005*,
LV septal-Dmean [Gy]1.2 (0.4–3.4)1.8 (1.01–3.71)1.6 (1.1–3.4)2.19 (1.77–3.74)1.9 (1.2–3.9)2.56 (1.72–4.46)< < 0.0050.005*,
LV apical-Dmean [Gy]6.9 (1.2–19.6)8.54 (1.64–19.79)9.0 (1.7–21.9)8.42 (2.46–19.68)9.5 (1.2–24.8)8.91 (1.76–22.16)NS
LADCA-Dmean [Gy]5.2 (1.2–27.9)6.84 (1.8–27.62)13.8 (2.6–25.2)10.76 (3.01–20.73)11.1 (2.2–21.2)8.24 (2.84–21.22)NS
LADCA-V30 Gy [%]0.2 (0–66.3)0.36 (0–63.48)17.8 (0–59.0)7.39 (0–84.2)8.9 (0–43.3)2.13 (0–46.34)NS
LADCA-V40 Gy [%]0 (0–37.8)0 (0–43.09)0.5 (0–32.9)0 (0–3.22)0 (0–19.2)0 (0–7.26)NS
LADCA-prox-Dmean [Gy]1.6 (0.6–8.6)2.22 (1.22–7.95)2.9 (0.6–7.2)2.96 (1.96–5.19)2.5 (1.4–7.2)2.84 (2.07–12.43)< 0.001*, 0.002†
LADCA-mid-Dmean [Gy]7.9 (1.6–40.0)9.12 (2.26–39.63)17.9 (2.0–38.7)13.81 (4.22–30.95)10.4 (2.5–29.8)11.14 (3.23–36.01)NS
LADCA-dist-Dmean [Gy]5.5 (1.4–41.1)8.58 (2.03–40.65)26.9 (3.5–39.4)17.46 (3.98–35.39)14.0 (2.4–39.7)16.32 (2.87–34.95)NS

*intergroup comparison within 3D-CRT technique, using Kruskal-Wallis test; † intergroup comparison within t-IMRT technique using Kruskal-Wallis test; 3D-CRT = three-dimensional conformal radiotherapy; CTV = clinical target volume; Dmean = mean dose; dist = distal; Gy = Gray; LADCA = left anterior descending artery; LV = left ventricle; mid = middle; MWHD = whole heart mean dose; NS = not significant; prox = proximal; t-IMRT = tangential intensity modulated radiation therapy; Vx Gy = fractional volume receiving x Gy

Heart chambers

Selected dose-volume parameters for the LV are presented in Table 5 and 6. For the whole group, 3D-CRT showed lower dosimetric metrics for the LV contour, except for LV apical-Dmean and LV-V23 Gy. The lowest Dmean values of the dosimetric metrics for LV, including anterior, lateral, septal, and inferior LV wall, were obtained in the small CTV group, regardless of treatment technique.

In 3D-CRT, apical and anterior LV walls received the highest Dmean (Table 5), while lateral, septal, and inferior regions, received 1.9, 1.6, and only 0.6 Gy, respectively. The Dmean of RV, RA, and LA were 1.41 Gy (range, 0.5–4.8), 0.5 Gy (0.3–1.2), and 0.6 Gy (0.4–1.5), respectively and were not statistically significantly different among different groups of the CTV size. Likewise, with IMRT, apical and anterior LV walls received similarly high mean radiation doses. The Dmean varied from 8.5 Gy (range, 1.64– 22.16), 5.4 Gy (1.94–19.18), 2.33 Gy (1.18–7.59), 2.18 Gy (1.01–4.46), and 1.11 Gy (0.77–1.98) for apical, anterior, lateral, septal and inferior LV walls, correspondingly. Seventeen-segmental LV models, represented as a Bull’s eye diagram, with respective Dmean dose distributions, are presented in Figure 2. Low LV-Dmean (< 3 Gy), LV-V5 (< 17%), and LV-V23 (< 5%) values were achieved in 51.6%, 88.3%, and 73.3% of treatment plans in 3D-CRT and in 41.6%, 88.3%, and 85.0% of treatment plans in t-IMRT, respectively.

Figure 2

Bull’s eye diagrams of the left ventricle and segment models of the coronary arteries with reported median Dmean distributions in three-dimensional conformal radiotherapy plans, divided in groups according to clinical target volume size. Contouring segments of left ventricle consisted of anterior (segments 1 and 7), apical (segments 13–17), inferior (segments 4 and 10), lateral (segments 5, 6, 11, 12) and septal regions (segments 2, 3, 8, 9).

CTV = clinical target volume; Gy = Gray; LADCA = left anterior descending artery; LCX = left circumflex artery; LMCA = left main coronary artery; RCA = right coronary artery

Coronary arteries

Planned median Dmean values for LADCA and its segments are presented in Table 5. Median mean doses to other coronary arteries, namely RCA, LCX, and LMCA were 0.7 Gy (range, 0.3–4.7), 0.7 Gy (0.3–2.0), and 0.8 Gy (0.5–2.0), in the 3D-CRT group and 1.14 Gy (0.77–1.86), 1.10 Gy (0.79–2.18) and 1.31 Gy (0.96–2.17) in the t-IMRT group, respectively. For the entire group, only parameter LADCA-V30 Gy was found to be lower with t-IMRT compared to 3D-CRT technique, but the reduction was seen only in the medium and large CTV-size groups.

Compared to t-IMRT, 3D-CRT technique showed advantages in terms of lower planned Dmean values of proximal, middle and distal LADCA segments (Table 5). However, dose to the proximal LADCA segment increased with the CTV size, regardless of the planning method. The highest Dmean values of the middle and distal LADCA segments were achieved in patients with the medium or large target volumes.

Low LADCA-Dmean (< 10 Gy), LADCA-V30 Gy (< 2%), and LADCA-V30 Gy (< 1%) values were achieved in 55.0%, 48.3%, and 71.6% of treatment plans in 3D-CRT and in 56.6%, 51.6%, and 86.6% of treatment plans in t-IMRT, respectively. Figure 2 represents Bull’s eye diagrams of the LV and segment models of the coronary arteries with reported median Dmean distributions for 3D-CRT technique.

Discussion

By tradition and its contouring pragmatism, MWHD is the most frequently reported surrogate for the assessment of the potential subsequent cardiotoxic effects after radiation therapy for breast cancer. In the present study, we aimed to compare doses to the individual cardiac structures in the circumstances that represent everyday practice in free-breathing node-negative left-sided breast cancer adjuvant 3D-CRT or t-IMRT. Herein, we report reasonably low median MWHD values achieved with both techniques, 1.9 Gy with 3D-CRT and 2.1 Gy with t-IMRT. In the contemporary series, measured mean or median MWHD values in free-breathing node-negative left-sided breast cancer adjuvant RT are in the range of 2.6–3.6 Gy for 3D-CRT6,33,35,36 and 1.8–4.8 for the intensity modulated techniques.11,46,47

In both evaluated techniques, we observed statistically significant differences between the groups of small, medium, and large CTV sizes for the following dose-volume parameters: MWHD, mean doses for proximal LADCA segment, anterior, lateral, inferior, and septal LV walls. In medium and large-sized CTV, we observed reduction of LADCA-Dmean with t-IMRT technique, which was not statistically different. Our results are consistent with previously published studies showing increased CWS, relative to 22 cm, to be one of the predictors for a higher MWHD, in both normo-and hypofractionation.9 Other studies have also demonstrated the correlation between the calculated heart dose and increasing breast size, especially when PTV exceeds 1500 cm3.17,18 Compared to small-sized CTV, MWHD increased with medium-and large- sized CTVs in our study, although the absolute differences between the groups were relatively small, ranging from 0.73 Gy and 0.97 Gy for the t-IMRT and 3D-CRT, respectively. Our results imply that patients’ anatomy, including CWS and/ or CTV/PTV volume, should be also considered when choosing the appropriate radiotherapy technique (3D-CRT vs. modulated approaches), patient setup (prone or lateral vs. supine), and breathing adaptation techniques. As previously mentioned, breast size grouping could be useful in this context, helping to tailor whole breast irradiation.19

Despite the low MWHD for the whole group, our study confirms that apical and anterior parts of LV and mid or distal LADCA segments in both 3D-CRT and t-IMRT techniques receive disproportionately higher Dmean radiation doses. Likewise, in the study by Tang et al., segments corresponding to anterior and apical LV wall absorbed the highest doses, 9.2 Gy and 14.9 Gy, respectively. Patients were treated with tangential breast RT, with or without regional nodal irradiation and with or without DIBH.36 Corresponding values in our study were lower in both evaluated techniques, 3D-CRT vs. t-IMRT for anterior and apical LV walls were 5.0 vs. 5.4 Gy and 8.5 vs. 8.9 Gy, respectively. Lower numbers might reflect a difference in contoured thickness of the LV wall, 6-9 mm in the study of Tang et al. compared to 10 mm used in our study, as suggested by Duane et al.24

In our work, the LADCA-Dmean was 8.2 Gy (range, 1.2–27.9) in 3D-CRT and 8.4 Gy (range, 1.8–27.6) in t-IMRT, respectively. Drost et al. in their systematic review of heart doses reported varying dose-volume measurements for the LADCA. The LADCA-Dmean ranged from 1.9–40.8 Gy (average 12.4 Gy)6, which is similar to our data. In our series of treatment plans, we have demonstrated the highest Dmean for the middle LADCA segment in the group of women with medium-sized CTVs (17.9 Gy) but was not significantly different compared to the smallest or the largest CTV groups. With t-IMRT, it was possible to lower LADCA high-dose areas (V30 Gy), but not low-dose areas or mean doses to the coronary arteries. Carosi et al. observed no difference in MWHD when t-IM-RT was compared to 3D-CRT (2.0 vs. 1.9 Gy) in 24 patients with a median breast volume of 645 cm3. However, the authors showed a statistically meaningful difference in LADCA Dmean (10.3 vs. 11.9 Gy, p=0.0003), LADCA-Dmax and LADCA-V17 Gy parameters using t-IMRT compared to 3D-CRT.48

There are many possible explanations for the dissimilar reported heart and heart substructures’ absorbed doses in free-breathing left-breast only RT. The differences may arise from the discrepancy in the total dose prescription and the size of the radiation field, CTV definition and size, OAR contouring, including diameter of the coronary arteries and LV thickness, the lack of detailed heart contouring atlases, individual coronary topology, heart size, body mass index, CWS distance, and finally radiotherapy technique used.9,33,49,50,51,52 The use of contrast agent53 or automatic substructures’ segmentation without54 or with cardiac magnetic resonance imaging55 could improve contouring consistency, but these technical solutions are unlikely to be widely adopted in the near future. Non-automatic contouring is feasible as showed in a study by Francolini et al. Authors made multiple comparisons of delineated cardiac chambers and 5 left LV wall segments according to aforementioned cardiac atlas24 and confirmed high interobserver delineation consistency.56

Spatial variation in contouring has been shown to result in less than 1 Gy dose variation for most segments and in most regimens in adjuvant breast cancer RT, but higher dose variations up to 21.8 Gy were seen for segments close to the radiation field edge.24 Substantial variation in the estimated dose was observed for LADCA, regardless of which particular delineation guidelines were used.57 Except for proximal LADCA (2.6 Gy vs. 2.5 Gy), absorbed mean Dmean values of LADCA segments and LV were lower in our study compared to the partially wide tangential technique used in Duane and coworkers’ research; 15.1 Gy vs. 25.1 Gy for middle LADCA segment, 17.6 Gy vs. 35.8 Gy for distal LADCA segment, and 3.2 vs. 6.7 Gy for LV. In the study of Wennstig et al., three radiation oncologists, using the heart atlas of Feng et al., achieved substantial spatial agreement in delineating coronary arteries on 32 CT study sets. The agreement was the highest for LMCA and LADCA, and less for RCA.23,58 In our study, the coronary vessel diameter was set to 6 mm considering both cardiac and respiratory motion, similar to Wennstig and colleagues’ work.23

Based on recent clinical reports, the DEGRO group proposed stringent dose constraints for the heart and its substructures in adjuvant breast cancer radiation treatment.42 We surpassed at least one of the proposed optimal dose constraints for LV (Dmean < 3 Gy, V5 < 17%, and V23 < 5%) or LADCA (Dmean < 10 Gy, V30 < 2%, and V40 < 1%) in 11.7–51.7% of all evaluated plans. In our plan optimization process, we did not use specific dose-volume constraints for cardiac substructures. However, it has been shown that additional LADCA or LV constraints in breast cancer adjuvant 3D-CRT or IMRT treatment planning might help to optimize heart dosimetric metrics further.23,59

In our study, the evaluation of the planned dose to the heart and specific cardiac substructures was performed in a free-breathing simulation CT scan and in the supine position. Ideally, the dose to cardiac substructures should also be evaluated for patients treated using alternative treatment positions (lateral decubitus or prone) or with DIBH. Due to various reasons, most patients are still treated in the conventional free-breathing supine position, whereas prone positioning or DIBH is in the best-case scenario offered to only 28–83% of breast cancer patients.15,60 All delineations were performed on a non-enhanced CT scan, an approach that may impact the visibility of the small cardiac segments. Additional drawback of our study is not including patients receiving peri-clavicular regional nodal irradiation with or without internal mammary lymph chain irradiation. Strengths of this study include careful contouring of individual cardiac substructures and using a cardiac atlas based on individual anatomy. An experienced cardiac radiologist thoroughly evaluated the contours.

Conclusions

This is the first study to evaluate the cardiac contouring atlas for radiotherapy by Duane et al.24 simultaneously considering different CTV size. We confirmed that regardless of very low Dmean values for the whole heart achieved using a 3D-CRT or t-IMRT free-breathing adjuvant RT technique for breast cancer, a small volume of the heart may receive disproportionate Dmean or Dmax values exceeding 40 Gy. We observed differences in heart dosimetric metrics between the small, medium, and large CTV sizes for both evaluated techniques, which may disappear with DIBH technique. With t-IMRT technique, only few dosimetric metrics were improved compared to 3D-CRT. The observed results in our study suggest that anatomic differences, especially breast volume and CWS, should be considered in clinical practice as well as in the dosimetric studies of various treatment planning techniques. Subdividing breast target volume into similar cohorts could be helpful in this context and further research is warranted. The quantification of the radiation dose variability of individual cardiac substructures is an important first step to understand the unique cardiac structures’ dose-volume predictors for cardiotoxicity in adjuvant, free-breathing breast cancer radiation therapy. In the future, reported absorbed doses may be paired with cardiac imaging and help to choose patients for whom more intense cardiac function monitoring is warranted.

Figure 1

Mean whole heart dose and number of plans within each CTV groups, concerning optimal mean dose value.3D-CRT = three-dimensional conformal radiotherapy; CTV = clinical target volume; Gy = Gray; t-IMRT = tangential intensity modulated radiation therapy
Mean whole heart dose and number of plans within each CTV groups, concerning optimal mean dose value.3D-CRT = three-dimensional conformal radiotherapy; CTV = clinical target volume; Gy = Gray; t-IMRT = tangential intensity modulated radiation therapy

Figure 2

Bull’s eye diagrams of the left ventricle and segment models of the coronary arteries with reported median Dmean distributions in three-dimensional conformal radiotherapy plans, divided in groups according to clinical target volume size. Contouring segments of left ventricle consisted of anterior (segments 1 and 7), apical (segments 13–17), inferior (segments 4 and 10), lateral (segments 5, 6, 11, 12) and septal regions (segments 2, 3, 8, 9).CTV = clinical target volume; Gy = Gray; LADCA = left anterior descending artery; LCX = left circumflex artery; LMCA = left main coronary artery; RCA = right coronary artery
Bull’s eye diagrams of the left ventricle and segment models of the coronary arteries with reported median Dmean distributions in three-dimensional conformal radiotherapy plans, divided in groups according to clinical target volume size. Contouring segments of left ventricle consisted of anterior (segments 1 and 7), apical (segments 13–17), inferior (segments 4 and 10), lateral (segments 5, 6, 11, 12) and septal regions (segments 2, 3, 8, 9).CTV = clinical target volume; Gy = Gray; LADCA = left anterior descending artery; LCX = left circumflex artery; LMCA = left main coronary artery; RCA = right coronary artery

Target volumes’ and organs at risk’s metrics

Target volume/ Organ at riskThe whole group N = 60Small CTV N = 22Medium CTV N = 21Large CTV N = 17p value
CTV [cm3]800.6 (124.8–2970.9)425.7 (124.8–545.5)867.0 (652.1–1295.1)1586.8 (1348.9–2970.9)0.021
PTVeval [cm3]990.7 (233.5–3336.1)583.0 (233.5–711.1)1035.9 (834.3–1576.5)1874.3 (1605.8–3336.1)< 0.005
PTV [cm3]1163.3 (340.1–3792.2)730.7 (340.1–856.6)1212.3 (985.1–1805)2134.8 (1826.4–3792.2)< 0.005
CWS [cm]23.1 (17.9–33.2)19.5 (17.9–23.2)24.0 (19.9–28.5)27.5 (22.9–33.2)< 0.005
4th arch metrics [cm]4.4 (0–11.6)1.6 (0–9.6)5.5 (0–11.6)7.1 (0–10.7)0.008
Heart [cm3]677.7 (432.9–1192.7)625.2 (432.9–912.8)671.1 (563.5–872.4)817.9 (620.1–1192.7)< 0.005
Left Ventricle [cm3]173.8 (116–277.4)161.3 (116–251.7)173.8 (120.8–229.8)188.7 (147.4–277.4)0.018
Left Lung [cm3]1245.1 (809.3–2127.9)1458.9 (824.5–2127.9)1123.8 (944.2–1619.2)1230.6 (809.3–1541.7)0.003
Right Lung [cm3]1563.4 (855–2560.1)1721.9 (992.9–2560.1)1466.4 (855.1–1838.2)1493.2 (1089.6–1925.6)0.002
Lungs [cm3]2879.7 (1504.6–4789.2)3241.3 (1877.5–4789.2)2634.4 (1504.6–3513.6)2799.8 (1960.2–3479.2)0.001

Radiotherapy technique and selected dose-volume parameters for the whole heart and selected cardiac substructures

Parameter3D-CRTt-IMRTp value*
MWHD [Gy]1.90 (0.61–4.14)2.13 (1.06–4.4)< 0.005
LV-Dmean [Gy]2.98 (0.78–8.03)3.22 (1.31–7.25)< 0.005
LV-V5 Gy [%]8.67 (0–26.3)9.21 (0–26.02)0.455
LV-V23 Gy [%]2.46 (0–14.32)1.86 (0–10.58)0.003
LV anterior-Dmean [Gy]5.00 (1.27–20.17)5.42 (1.94–19.18)< 0.005
LV apical-Dmean [Gy]8.97 (1.22–24.89)8.47 (1.64–22.16)< 0.005
LADCA-Dmean [Gy]8.20 (1.23–27.92)8.39 (1.8–27.62)< 0.005
LADCA-V30 Gy [%]5.39 (0–66.34)2.01 (0–84.20)< 0.005
LADCA-V40 Gy [%]0 (0–37.8)0 (0–43.09)< 0.005
LADCA-prox-Dmean [Gy]2.17 (0.62–8.68)2.66 (1.22–12.43)< 0.005
LADCA-mid-Dmean [Gy]9.63 (1.67–40.07)11.05 (2.26–39.63)0.956
LADCA-dist-Dmean [Gy]13.73 (1.44–41.11)15.93 (2.03–3.89)0.132

Breast size and selected dose-volume parameters for the whole heart and cardiac substructures

Small CTVMedium CTVLarge CTV
Parameterp value
3D-CRTt-IMRT3D-CRTt-IMRT3D-CRTt-IMRT
MWHD [Gy]1.29 (0.61–3.75)1.99 (1.06–3.98)2.05 (1.06–3.84)2.11 (1.62–3.54)2.26 (1.04–4.14)2.72 (1.46–4.4)< 0.005*; 0.047†
Heart-V5 Gy [%]2.56 (0.02–10.84)3.77 (0.1–11.01)4.99 (0.59–10.87)4.34 (1.19–9.58)5.29 (0–12.81)6.19 (0.04–12.83)0.043*
Heart-V10 Gy [%]1.28 (0–7.91)2.01 (0–7.59)2.71 (0.01–7.73)2.24 (0.12–68.14)3.09 (0–8.24)3.17 (0–8.54)NS
Heart-V17 Gy [%]0.76 (0–6.61)1.22 (0–6.08)2.03 (0–6.52)1.36 (0–4.79)2.37 (0–6.92)3.36 (0–6.42)NS
Heart-V20 Gy [%]0.62 (0–6.22)1 (0–5.63)1.83 (0–6.16)1.17 (0–4.38)2.15 (0–6.51)2.01 (0–5.81)NS
Heart-V35 Gy [%]0.15 (0–4.12)0.2 (0–3.4)0.93 (0–4.15)0.31 (0–2.3)1.06 (0–4.32)0.63 (0–2.91)NS
Heart-V40 Gy [%]0.02 (0–1.41)0.01 (0–1.65)0.24 (0–1.45)0.03 (0–0.42)0.03 (0–1.93)0.04 (0–1.69)NS
LV-Dmean [Gy]2.3 (0.7–5.7)2.9 (1.31–5.84)3.2 (1.1–6.9)3.15 (1.78–5.97)3.5 (1.3–8.0)3.92 (1.83–7.25)0.019*
LV-V5 Gy [%]6.8 (0–17.4)8.27 (0–17.39)9.7 (0–22.0)8.47 (0.46–19.87)10.8 (0–26.3)12 (0–26.02)0.052*
LV-V23 Gy [%]1.4 (0–9.5)1.73 (0–8.47)2.8 (0–12.0)1.81 (0–8.18)3.3 (0–14.3)3.1 (0–10.58)NS
LV anterior-Dmean [Gy]3.6 (1.2–12.8)4.86 (1.94–12.35)6.8 (2.0–15.9)5.71 (2.69–14.48)6.8 (1.9–20.1)6.94 (2.58–19.18)0.017*
LV lateral-Dmean [Gy]1.6 (0.7–2.8)2.16 (1.18–3.38)1.8 (0.9–6.3)2.24 (1.55–5.12)2.5 (1.2–8.7)2.98 (1.73–7.59)< < 0.0010.001*,
LV inferior-Dmean [Gy]0.5 (0.3–3.3)0.96 (0.77–1.17)0.6 (0.5–0.9)1.07 (0.9–1.32)0.8 (0.6–2.0)1.33 (0.96–1.98)< < 0.0050.005*,
LV septal-Dmean [Gy]1.2 (0.4–3.4)1.8 (1.01–3.71)1.6 (1.1–3.4)2.19 (1.77–3.74)1.9 (1.2–3.9)2.56 (1.72–4.46)< < 0.0050.005*,
LV apical-Dmean [Gy]6.9 (1.2–19.6)8.54 (1.64–19.79)9.0 (1.7–21.9)8.42 (2.46–19.68)9.5 (1.2–24.8)8.91 (1.76–22.16)NS
LADCA-Dmean [Gy]5.2 (1.2–27.9)6.84 (1.8–27.62)13.8 (2.6–25.2)10.76 (3.01–20.73)11.1 (2.2–21.2)8.24 (2.84–21.22)NS
LADCA-V30 Gy [%]0.2 (0–66.3)0.36 (0–63.48)17.8 (0–59.0)7.39 (0–84.2)8.9 (0–43.3)2.13 (0–46.34)NS
LADCA-V40 Gy [%]0 (0–37.8)0 (0–43.09)0.5 (0–32.9)0 (0–3.22)0 (0–19.2)0 (0–7.26)NS
LADCA-prox-Dmean [Gy]1.6 (0.6–8.6)2.22 (1.22–7.95)2.9 (0.6–7.2)2.96 (1.96–5.19)2.5 (1.4–7.2)2.84 (2.07–12.43)< 0.001*, 0.002†
LADCA-mid-Dmean [Gy]7.9 (1.6–40.0)9.12 (2.26–39.63)17.9 (2.0–38.7)13.81 (4.22–30.95)10.4 (2.5–29.8)11.14 (3.23–36.01)NS
LADCA-dist-Dmean [Gy]5.5 (1.4–41.1)8.58 (2.03–40.65)26.9 (3.5–39.4)17.46 (3.98–35.39)14.0 (2.4–39.7)16.32 (2.87–34.95)NS

Target goals used in the planning process

StructureTarget goals
PTVD2%< 108%
PTVevalV95%> 95%
Whole Body ContourGlobal Dmax < V110%
Dmean < 3.2 Gy
HeartV17 Gy < 10%
V35 Gy < 5%
Dmean < 10 Gy
Ipsilateral LungV17 Gy < 25%
V26 Gy < 20%
Bilateral lungDmean < 3.2 Gy

Target volume dosimetric metrics

Target volume3D-CRTt-IMRTp value
PTVeval D98% [Gy]40.6 (39.8–41.4)40.3 (38.7–41.6)0.002
PTVeval D2% [Gy]44.7 (44.4–45.5)43.8 (43.8–47.1)NS
PTVeval D50% [Gy]43.3 (42.7–43.7)42.9 (42.2–43.9)< 0.005
PTVeval V95% [%]98.1 (95.3–99.6)96.8 (79.9–99.9)0.001
PTVeval V105% [%]1.3 (0.1–10.3)4.3 (0.01–85.9)< 0.005
PTVeval V105% [cm3]11.7 (0.08–656.7)5.4 (0.06–68.0)0.014
PTVeval V107% [%]0 (0–1.4)0.1 (0–9.6)< 0.005
PTVeval V107% [cm3]0 (0–321.4)0 (0–7.2)NS
PTVeval V110% [%]0 (0–0)0 (0–0)NS
Dmax [Gy]45.7 (45.1–46.9)46.9 (45.3–51)< 0.005

Target volume dosimetric metrics and CTV size

Target volumeSmall CTVMedium CTVLarge CTVp value (S vs. M vs. L)
3D-CRT PTVeval V95% [%]97.7 (95.3–99.6)98.3 (96.2–99.5)98.8 (97.5–99.4)0.022 (S vs. M, S vs. L)
t-IMRT PTVeval V95% [%]97.9 (96.3–99.2)97.3 (95.3–99.0)96.8 (79.9–99.9)NS
p value (3D-CRT vs. T-IMRT)NSp = 0.003p = 0.013
3D-CRT PTVeval V105% [cm3]8.1 (0.5–17.5)12.5 (0.08–91.3)87.3 (9.5–656.6)< 0.005 (S vs. M, S vs. L, M vs. L)
t-IMRT PTVeval V105% [cm3]7.4 (0.1–61.5)5.9 (0.09–54)4.2 (0.06–68.2)NS
p value (3D-CRT vs. T-IMRT)NSNSp = 0.012

Abdel-Qadir H, Austin PC, Lee DS, Amir E, Tu J V, Thavendiranathan P, et al. A population-based study of cardiovascular mortality following early-stage breast cancer. JAMA Cardiol 2017; 2: 88. doi: 10.1001/jamacar-dio.2016.3841Abdel-QadirHAustinPCLeeDSAmirETuJ VThavendiranathanPet alA population-based study of cardiovascular mortality following early-stage breast cancerJAMA Cardiol201728810.1001/jamacar-dio.2016.3841Open DOISearch in Google Scholar

Weberpals J, Jansen L, Müller OJ, Brenner H. Long-term heart-specific mortality among 347 476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study. Eur Heart J 2018; 39: 3896903. doi: 10.1093/eurheartj/ehy167WeberpalsJJansenLMüllerOJBrennerHLong-term heart-specific mortality among 347 476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort studyEur Heart J201839389690310.1093/eurheartj/ehy167Open DOISearch in Google Scholar

Darby SC, Ewertz M, Hall P. Ischemic heart disease after breast cancer radiotherapy. N Engl J Med 2013; 368: 2527. doi: 10.1056/NEJMc1304601DarbySCEwertzMHallPIschemic heart disease after breast cancer radiotherapyN Engl J Med2013368252710.1056/NEJMc1304601Open DOISearch in Google Scholar

van den Bogaard VAB, Ta BDP, van der Schaaf A, Bouma AB, Middag AMH, Bantema-Joppe EJ, et al. Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures. J Clin Oncol 2017; 35: 1171-8; doi: 10.1200/JCO.2016.69.8480vanden Bogaard VABTaBDPvander Schaaf ABoumaABMiddagAMHBantema-JoppeEJet alValidation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructuresJ Clin Oncol2017351171810.1200/JCO.2016.69.8480Open DOISearch in Google Scholar

Saiki H, Petersen IA, Scott CG, Bailey KR, Dunlay SM, Finley RR, et al. Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer. Circulation 2017; 135: 1388-96. doi: 10.1161/CIRCULATIONAHA.116.025434SaikiHPetersenIAScottCGBaileyKRDunlaySMFinleyRRet alRisk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancerCirculation201713513889610.1161/CIRCULATIONAHA.116.025434Open DOISearch in Google Scholar

Drost L, Yee C, Lam H, Zhang L, Wronski M, McCann C, et al. A systematic review of heart dose in breast radiotherapy. Clin Breast Cancer 2018; 18: e819-24. doi: 10.1016/j.clbc.2018.05.010DrostLYeeCLamHZhangLWronskiMMcCannCet alA systematic review of heart dose in breast radiotherapyClin Breast Cancer201818e8192410.1016/j.clbc.2018.05.010Open DOISearch in Google Scholar

Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys 2015; 93: 84553. doi: 10.1016/j.ijrobp.2015.07.2292TaylorCWWangZMacaulayEJagsiRDuaneFDarbySCExposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013Int J Radiat Oncol Biol Phys2015938455310.1016/j.ijrobp.2015.07.2292Open DOISearch in Google Scholar

Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials J Clin Oncol 2017; 35: 1641-9. doi: 10.1200/JCO.2016.72.0722TaylorCCorreaCDuaneFKAznarMCAndersonSJBerghJet alEstimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trialsJ Clin Oncol2017351641910.1200/JCO.2016.72.0722Open DOISearch in Google Scholar

Pierce LJ, Feng M, Griffith KA, Jagsi R, Boike T, Dryden D, et al. Recent time trends and predictors of heart dose from breast radiation therapy in a large quality consortium of radiation oncology practices. Int J Radiat Oncol 2017; 99: 1154-61. doi: 10.1016/j.ijrobp.2017.07.022PierceLJFengMGriffithKAJagsiRBoikeTDrydenDet alRecent time trends and predictors of heart dose from breast radiation therapy in a large quality consortium of radiation oncology practicesInt J Radiat Oncol20179911546110.1016/j.ijrobp.2017.07.022Open DOISearch in Google Scholar

Jacobse JN, Duane FK, Boekel NB, Schaapveld M, Hauptmann M, Hooning MJ, et al. Radiation dose-response for risk of myocardial infarction in breast cancer survivors. Int J Radiat Oncol Biol Phys 2018; 103: 595-604. doi: 10.1016/j.ijrobp.2018.10.025JacobseJNDuaneFKBoekelNBSchaapveldMHauptmannMHooningMJet alRadiation dose-response for risk of myocardial infarction in breast cancer survivorsInt J Radiat Oncol Biol Phys201810359560410.1016/j.ijrobp.2018.10.025Open DOISearch in Google Scholar

Karpf D, Sakka M, Metzger M, Grabenbauer GG. Left breast irradiation with tangential intensity modulated radiotherapy (t-IMRT) versus tangential volumetric modulated arc therapy (t-VMAT): trade-offs between secondary cancer induction risk and optimal target coverage. Radiat Oncol 2019; 14: 156. doi: 10.1186/s13014-019-1363-4KarpfDSakkaMMetzgerMGrabenbauerGGLeft breast irradiation with tangential intensity modulated radiotherapy (t-IMRT) versus tangential volumetric modulated arc therapy (t-VMAT): trade-offs between secondary cancer induction risk and optimal target coverageRadiat Oncol20191415610.1186/s13014-019-1363-4Open DOISearch in Google Scholar

Halasz LM, Patel SA, McDougall JA, Fedorenko C, Sun Q, Goulart BHL, et al. Intensity modulated radiation therapy following lumpectomy in early-stage breast cancer: patterns of use and cost consequences among Medicare beneficiaries. PLoS One 2019; 14: e0222904. doi: 10.1371/jour-nal.pone.0222904HalaszLMPatelSAMcDougallJAFedorenkoCSunQGoulartBHLet alIntensity modulated radiation therapy following lumpectomy in early-stage breast cancer: patterns of use and cost consequences among Medicare beneficiariesPLoS One201914e022290410.1371/jour-nal.pone.0222904Open DOISearch in Google Scholar

Jin G, Chen LX, Deng XW, Liu XW, Huang Y, Huang XB. A comparative dosimetric study for treating left-sided breast cancer for small breast size using five different radiotherapy techniques: conventional tangential field; filed-in-filed; tangential-IMRT; multi-beam IMRT and VMAT. Radiat Oncol 2013; 8: 89. doi: 10.1186/1748-717X-8-89JinGChenLXDengXWLiuXWHuangYHuangXBA comparative dosimetric study for treating left-sided breast cancer for small breast size using five different radiotherapy techniques: conventional tangential field; filed-in-filed; tangential-IMRT; multi-beam IMRT and VMATRadiat Oncol201388910.1186/1748-717X-8-89Open DOISearch in Google Scholar

Lee G, Rosewall T, Fyles A, Harnett N, Dinniwell RE. Anatomic features of interest in women at risk of cardiac exposure from whole breast radiotherapy. Radiother Oncol 2015; 115: 355-60. doi: 10.1016/j.radonc.2015.05.002LeeGRosewallTFylesAHarnettNDinniwellREAnatomic features of interest in women at risk of cardiac exposure from whole breast radiotherapyRadiother Oncol20151153556010.1016/j.radonc.2015.05.002Open DOISearch in Google Scholar

Desai N, Currey A, Kelly T, Bergom C. Nationwide trends in heart-sparing techniques utilized in radiation therapy for breast cancer. Adv Radiat Oncol 2019; 4: 246-52. doi: 10.1016/j.adro.2019.01.001DesaiNCurreyAKellyTBergomCNationwide trends in heart-sparing techniques utilized in radiation therapy for breast cancerAdv Radiat Oncol201942465210.1016/j.adro.2019.01.001Open DOISearch in Google Scholar

Mendez LC, Louie A V., Moreno C, Wronski M, Warner A, Leung E, et al. Evaluation of a new predictor of heart and left anterior descending artery dose in patients treated with adjuvant radiotherapy to the left breast. Radiat Oncol 2018; 13: 124. doi: 10.1186/s13014-018-1069-zMendezLCLouieA V.MorenoCWronskiMWarnerALeungEet alEvaluation of a new predictor of heart and left anterior descending artery dose in patients treated with adjuvant radiotherapy to the left breastRadiat Oncol20181312410.1186/s13014-018-1069-zOpen DOISearch in Google Scholar

Guan H, Dong Y-L, Ding L-J, Zhang Z-C, Huang W, Liu C-X, et al. Morphological factors and cardiac doses in whole breast radiation for left-sided breast cancer. Asian Pac J Cancer Prev 2015; 16: 2889-94. doi: 10.7314/ap-jcp.2015.16.7.2889GuanHDongY-LDingL-JZhangZ-CHuangWLiuC-Xet alMorphological factors and cardiac doses in whole breast radiation for left-sided breast cancerAsian Pac J Cancer Prev20151628899410.7314/ap-jcp.2015.16.7.2889Open DOISearch in Google Scholar

Hannan R, Thompson RF, Chen Y, Bernstein K, Kabarriti R, Skinner W, et al. Hypofractionated whole-breast radiation therapy: does breast size matter? Int J Radiat Oncol 2012; 84: 894-901. doi: 10.1016/j.ijrobp.2012.01.093HannanRThompsonRFChenYBernsteinKKabarritiRSkinnerWet alHypofractionated whole-breast radiation therapy: does breast size matter?Int J Radiat Oncol20128489490110.1016/j.ijrobp.2012.01.093Open DOISearch in Google Scholar

Yang DS, Lee JA, Yoon WS, et al. Whole breast irradiation for small-sized breasts after conserving surgery: is the field-in-field technique optimal? Breast Cancer 2014; 21: 162-9. doi: 10.1007/s12282-012-0365-yYangDSLeeJAYoonWSet alWhole breast irradiation for small-sized breasts after conserving surgery: is the field-in-field technique optimal?Breast Cancer201421162910.1007/s12282-012-0365-yOpen DOISearch in Google Scholar

Vicini FA, Sharpe M, Kestin L, Martinez A, Mitchell CK, Wallace MF, et al. Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2002; 54: 1336-44. doi: 10.1016/S0360-3016(02)03746-XViciniFASharpeMKestinLMartinezAMitchellCKWallaceMFet alOptimizing breast cancer treatment efficacy with intensity-modulated radiotherapyInt J Radiat Oncol Biol Phys20025413364410.1016/S0360-3016(02)03746-XOpen DOISearch in Google Scholar

Michalski A, Atyeo J, Cox J, Rinks M, Morgia M, Lamoury G. A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes. Med Dosim 2014; 39: 163-8. doi: 10.1016/j.med-dos.2013.12.003MichalskiAAtyeoJCoxJRinksMMorgiaMLamouryGA dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumesMed Dosim201439163810.1016/j.med-dos.2013.12.003Open DOISearch in Google Scholar

Ratosa I, Jenko A, Oblak I. Breast size impact on adjuvant radiotherapy adverse effects and dose parameters in treatment planning. Radiol Oncol 2018; 52: 233-44. doi: 10.2478/raon-2018-0026RatosaIJenkoAOblakIBreast size impact on adjuvant radiotherapy adverse effects and dose parameters in treatment planningRadiol Oncol2018522334410.2478/raon-2018-0026Open DOISearch in Google Scholar

Wennstig A-K, Garmo H, Hållström P, Nyström PW, Edlund P, Blomqvist C, et al. Inter-observer variation in delineating the coronary arteries as organs at risk. Radiother Oncol 2017; 122: 72-8. doi: 10.1016/j.radonc.2016.11.007WennstigA-KGarmoHHållströmPNyströmPWEdlundPBlomqvistCet alInter-observer variation in delineating the coronary arteries as organs at riskRadiother Oncol201712272810.1016/j.radonc.2016.11.007Open DOISearch in Google Scholar

Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, et al. A cardiac contouring atlas for radiotherapy. Radiother Oncol 2017; 122: 416-22. doi: 10.1016/j.radonc.2017.01.008DuaneFAznarMCBartlettFCutterDJDarbySCJagsiRet alA cardiac contouring atlas for radiotherapyRadiother Oncol20171224162210.1016/j.radonc.2017.01.008Open DOISearch in Google Scholar

Skyttä T, Tuohinen S, Boman E, Virtanen V, Raatikainen P, Kellokumpu-Lehtinen P-L. Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy. Radiat Oncol 2015; 10: 141. doi: 10.1186/s13014-015-0436-2SkyttäTTuohinenSBomanEVirtanenVRaatikainenPKellokumpu-LehtinenP-L.Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapyRadiat Oncol20151014110.1186/s13014-015-0436-2Open DOISearch in Google Scholar

D’Errico MP, Petruzzelli MF, Gianicolo EAL, Grimaldi L, Loliva F, Tramacere F, et al. Kinetics of B-type natriuretic peptide plasma levels in patients with left-sided breast cancer treated with radiation therapy: results after one-year follow-up. Int J Radiat Biol 2015; 91: 804-9. doi: 10.3109/09553002.2015.1027421D’ErricoMPPetruzzelliMFGianicoloEALGrimaldiLLolivaFTramacereFet alKinetics of B-type natriuretic peptide plasma levels in patients with left-sided breast cancer treated with radiation therapy: results after one-year follow-upInt J Radiat Biol201591804910.3109/09553002.2015.1027421Open DOISearch in Google Scholar

Kaidar-Person O, Zagar TM, Oldan JD, Matney J, Jones EL, Das S, et al. Early cardiac perfusion defects after left-sided radiation therapy for breast cancer: is there a volume response? Breast Cancer Res Treat 2017; 164: 253-62. doi: 10.1007/s10549-017-4248-yKaidar-PersonOZagarTMOldanJDMatneyJJonesELDasSet alEarly cardiac perfusion defects after left-sided radiation therapy for breast cancer: is there a volume response?Breast Cancer Res Treat20171642536210.1007/s10549-017-4248-yOpen DOISearch in Google Scholar

Lind PA, Pagnanelli R, Marks LB, Borges-Neto S, Hu C, Zhou SM, et al. Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution. Int J Radiat Oncol Biol Phys 2003; 55: 914-20. doi: 10.1016/s0360-3016(02)04156-1LindPAPagnanelliRMarksLBBorges-NetoSHuCZhouSMet alMyocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distributionInt J Radiat Oncol Biol Phys2003559142010.1016/s0360-3016(02)04156-1Open DOISearch in Google Scholar

Zyromska A, Malkowski B, Wisniewski T, Majewska K, Reszke J, Makarewicz R. (15)O-H2O PET/CT as a tool for the quantitative assessment of early post-radiotherapy changes of heart perfusion in breast carcinoma patients. Br J Radiol 2018; 91: 20170653. doi: 10.1259/bjr.20170653ZyromskaAMalkowskiBWisniewskiTMajewskaKReszkeJMakarewiczR(15)O-H2O PET/CT as a tool for the quantitative assessment of early post-radiotherapy changes of heart perfusion in breast carcinoma patientsBr J Radiol2018912017065310.1259/bjr.20170653Open DOISearch in Google Scholar

Tuohinen SS, Skyttä T, Virtanen V, Virtanen M, Luukkaala T, Kellokumpu-Lehtinen P-L, et al. Detection of radiotherapy-induced myocardial changes by ultrasound tissue characterisation in patients with breast cancer. Int J Cardiovasc Imaging 2016; 32: 767-76. doi: 10.1007/s10554-016-0837-9TuohinenSSSkyttäTVirtanenVVirtanenMLuukkaalaTKellokumpu-LehtinenP-Let alDetection of radiotherapy-induced myocardial changes by ultrasound tissue characterisation in patients with breast cancerInt J Cardiovasc Imaging2016327677610.1007/s10554-016-0837-9Open DOISearch in Google Scholar

Heggemann F, Grotz H, Welzel G, Dösch C, Hansmann J, Kraus-Tiefenbacher U, et al. Cardiac function after multimodal breast cancer therapy assessed with functional magnetic resonance imaging and echocardiography imaging. Int J Radiat Oncol Biol Phys 2015; 93: 836-44. doi: 10.1016/j.ijrobp.2015.07.2287HeggemannFGrotzHWelzelGDöschCHansmannJKraus-TiefenbacherUet alCardiac function after multimodal breast cancer therapy assessed with functional magnetic resonance imaging and echocardiography imagingInt J Radiat Oncol Biol Phys2015938364410.1016/j.ijrobp.2015.07.2287Open DOISearch in Google Scholar

Erven K, Florian A, Slagmolen P, Sweldens C, Jurcut R, Wildiers H, et al. Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy. Int J Radiat Oncol 2013; 85: 1172-8. doi: 10.1016/j.ijrobp.2012.09.022ErvenKFlorianASlagmolenPSweldensCJurcutRWildiersHet alSubclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapyInt J Radiat Oncol2013851172810.1016/j.ijrobp.2012.09.022Open DOISearch in Google Scholar

Jacob S, Camilleri J, Derreumaux S, Walker V, Lairez O, Lapeyre M, et al. Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study). Radiat Oncol 2019; 14: 29. doi: 10.1186/s13014-019-1234-zJacobSCamilleriJDerreumauxSWalkerVLairezOLapeyreMet alIs mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study)Radiat Oncol2019142910.1186/s13014-019-1234-zOpen DOISearch in Google Scholar

Duma MN, Herr A-C, Borm KJ, Trott KR, Molls M, Oechsner M, et al. Tangential field radiotherapy for breast cancer—the dose to the heart and heart subvolumes: what structures must be contoured in future clinical trials? Front Oncol 2017; 7: 130. doi: 10.3389/fonc.2017.00130DumaMNHerrA-CBormKJTrottKRMollsMOechsnerMet alTangential field radiotherapy for breast cancer—the dose to the heart and heart subvolumes: what structures must be contoured in future clinical trials?Front Oncol2017713010.3389/fonc.2017.00130Open DOISearch in Google Scholar

Becker-Schiebe M, Stockhammer M, Hoffmann W, Wetzel F, Franz H. Does mean heart dose sufficiently reflect coronary artery exposure in left-sided breast cancer radiotherapy? Strahlenther Onkol 2016; 192: 624-31. doi: 10.1007/s00066-016-1011-yBecker-SchiebeMStockhammerMHoffmannWWetzelFFranzH.Does mean heart dose sufficiently reflect coronary artery exposure in left-sided breast cancer radiotherapy?Strahlenther Onkol20161926243110.1007/s00066-016-1011-yOpen DOISearch in Google Scholar

Tang S, Otton J, Holloway L, Delaney GP, Liney G, George A, et al. Quantification of cardiac subvolume dosimetry using a 17 segment model of the left ventricle in breast cancer patients receiving tangential beam radiotherapy. Radiother Oncol 2019; 132: 257-65. doi: 10.1016/j.radonc.2018.09.021TangSOttonJHollowayLDelaneyGPLineyGGeorgeAet alQuantification of cardiac subvolume dosimetry using a 17 segment model of the left ventricle in breast cancer patients receiving tangential beam radiotherapyRadiother Oncol20191322576510.1016/j.radonc.2018.09.021Open DOISearch in Google Scholar

Tong Y, Yin Y, Cheng P, Lu J, Liu T, Chen J, et al. Quantification of variation in dose–volume parameters for the heart, pericardium and left ventricular myocardium during thoracic tumor radiotherapy. J Radiat Res 2018; 59: 462-8. doi: 10.1093/jrr/rry026TongYYinYChengPLuJLiuTChenJet alQuantification of variation in dose–volume parameters for the heart, pericardium and left ventricular myocardium during thoracic tumor radiotherapyJ Radiat Res201859462810.1093/jrr/rry026Open DOISearch in Google Scholar

Taylor C, McGale P, Brønnum D, Correa C, Cutter D, Duane FK, et al. Cardiac structure injury after radiotherapy for breast cancer: cross-sectional study with individual patient data. J Clin Oncol 2018; 36: 2288-96. doi: 10.1200/JCO.2017.77.6351TaylorCMcGalePBrønnumDCorreaCCutterDDuaneFKet alCardiac structure injury after radiotherapy for breast cancer: cross-sectional study with individual patient dataJ Clin Oncol20183622889610.1200/JCO.2017.77.6351Open DOISearch in Google Scholar

Abouegylah M, Braunstein LZ, Alm El-Din MA, Niemierko A, Salama L, Elebrashi M, et al. Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy. Breast Cancer Res Treat 2018; 174: 179-85. doi: 10.1007/s10549-018-5053-yAbouegylahMBraunsteinLZAlmEl-Din MANiemierkoASalamaLElebrashiMet alEvaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapyBreast Cancer Res Treat20181741798510.1007/s10549-018-5053-yOpen DOISearch in Google Scholar

Moignier A, Broggio D, Derreumaux S, Beaudré A, Girinsky T, Paul J-F, et al. Coronary stenosis risk analysis following Hodgkin lymphoma radiotherapy: a study based on patient specific artery segments dose calculation. Radiother Oncol 2015; 117: 467-72. doi: 10.1016/j.radonc.2015.07.043MoignierABroggioDDerreumauxSBeaudréAGirinskyTPaulJ-Fet alCoronary stenosis risk analysis following Hodgkin lymphoma radiotherapy: a study based on patient specific artery segments dose calculationRadiother Oncol20151174677210.1016/j.radonc.2015.07.043Open DOISearch in Google Scholar

Jacobse JN, Duane FK, Boekel NB, Schaapveld M, Hauptmann M, Hooning MJ, et al. Radiation dose-response for risk of myocardial infarction in breast cancer survivors. Int J Radiat Oncol Biol Phys 2019; 103: 595-604. doi: 10.1016/j.ijrobp.2018.10.025JacobseJNDuaneFKBoekelNBSchaapveldMHauptmannMHooningMJet alRadiation dose-response for risk of myocardial infarction in breast cancer survivorsInt J Radiat Oncol Biol Phys201910359560410.1016/j.ijrobp.2018.10.025Open DOISearch in Google Scholar

Piroth MD, Baumann R, Budach W, Dunst J, Feyer P, Fietkau R, et al. Heart toxicity from breast cancer radiotherapy. Strahlenther Onkol 2019; 195: 1-12. doi: 10.1007/s00066-018-1378-zPirothMDBaumannRBudachWDunstJFeyerPFietkauRet alHeart toxicity from breast cancer radiotherapyStrahlenther Onkol201919511210.1007/s00066-018-1378-zOpen DOISearch in Google Scholar

Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1-39.e14. doi: 10.1016/j.echo.2014.10.003LangRMBadanoLPMor-AviVAfilaloJArmstrongAErnandeLet alRecommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular ImagingJ Am Soc Echocardiogr20152813910.1016/j.echo.2014.10.003Open DOISearch in Google Scholar

Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002; 105: 539-42. doi: 10.1161/hc0402.102975CerqueiraMDWeissmanNJDilsizianVJacobsAKKaulSLaskeyWKet alStandardized myocardial segmentation and nomenclature for tomographic imaging of the heartA statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation20021055394210.1161/hc0402.102975Open DOISearch in Google Scholar

Offersen B V., Boersma LJ, Kirkove C, Hol S, Aznar MC, Sola AB, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer, version 1.1. Radiother Oncol 2015; 114: 3-10. doi: 10.1016/j.radonc.2014.11.030OffersenB V.BoersmaLJKirkoveCHolSAznarMCSolaABet alESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer, version 1.1Radiother Oncol201511431010.1016/j.radonc.2014.11.030Open DOISearch in Google Scholar

De Rose F, Fogliata A, Franceschini D, Iftode C, Torrisi R, Masci G, et al. Hypofractionated volumetric modulated arc therapy in ductal carcinoma in situ: toxicity and cosmetic outcome from a prospective series. Br J Radiol 2018; 91: 20170634. doi: 10.1259/bjr.20170634De RoseFFogliataAFranceschiniDIftodeCTorrisiRMasciGet alHypofractionated volumetric modulated arc therapy in ductal carcinoma in situ: toxicity and cosmetic outcome from a prospective seriesBr J Radiol2018912017063410.1259/bjr.20170634Open DOISearch in Google Scholar

Fogliata A, De Rose F, Franceschini D, Stravato A, Seppälä J, Scorsetti M, et al. Critical appraisal of the risk of secondary cancer induction from breast radiation therapy with volumetric modulated arc therapy relative to 3D conformal therapy. Int J Radiat Oncol Biol Phys 2018; 100: 785-93. doi: 10.1016/j.ijrobp.2017.10.040FogliataADe RoseFFranceschiniDStravatoASeppäläJScorsettiMet alCritical appraisal of the risk of secondary cancer induction from breast radiation therapy with volumetric modulated arc therapy relative to 3D conformal therapyInt J Radiat Oncol Biol Phys20181007859310.1016/j.ijrobp.2017.10.040Open DOISearch in Google Scholar

Carosi A, Ingrosso G, Turturici I, Valeri S, Barbarino R, Di Murro L, et al. Whole breast external beam radiotherapy in elderly patients affected by left-sided early breast cancer: a dosimetric comparison between two simple free-breathing techniques. Aging Clin Exp Res 2020; 32: 1335-41. doi: 10.1007/s40520-019-01312-5CarosiAIngrossoGTurturiciIValeriSBarbarinoRDiMurro Let alWhole breast external beam radiotherapy in elderly patients affected by left-sided early breast cancer: a dosimetric comparison between two simple free-breathing techniquesAging Clin Exp Res20203213354110.1007/s40520-019-01312-5Open DOISearch in Google Scholar

Moignier A, Broggio D, Derreumaux S, El Baf F, Mandin A-M, Girinsky T, et al. Dependence of coronary 3-dimensional dose maps on coronary topologies and beam set in breast radiation therapy: a study based on CT angiographies. Int J Radiat Oncol Biol Phys 2014; 89: 182-90. doi: 10.1016/j.ijrobp.2014.01.055MoignierABroggioDDerreumauxSElBaf FMandinA-MGirinskyTet alDependence of coronary 3-dimensional dose maps on coronary topologies and beam set in breast radiation therapy: a study based on CT angiographiesInt J Radiat Oncol Biol Phys2014891829010.1016/j.ijrobp.2014.01.055Open DOISearch in Google Scholar

Mkanna A, Mohamad O, Ramia P, Thebian R, Makki M, Tamim H, et al. Predictors of cardiac sparing in deep inspiration breath-hold for patients with left sided breast cancer. Front Oncol 2018; 8: 564. doi: 10.3389/fonc.2018.00564MkannaAMohamadORamiaPThebianRMakkiMTamimHet alPredictors of cardiac sparing in deep inspiration breath-hold for patients with left sided breast cancerFront Oncol2018856410.3389/fonc.2018.00564Open DOISearch in Google Scholar

Wollschläger D, Karle H, Stockinger M, Bartkowiak D, Bührdel S, Merzenich H, et al. Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy. Radiother Oncol 2016; 119: 65-70. doi: 10.1016/j.radonc.2016.01.020WollschlägerDKarleHStockingerMBartkowiakDBührdelSMerzenichHet alRadiation dose distribution in functional heart regions from tangential breast cancer radiotherapyRadiother Oncol2016119657010.1016/j.radonc.2016.01.020Open DOISearch in Google Scholar

Appelt AL, Vogelius IR, Bentzen SM. Modern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heart. Clin Oncol (R Coll Radiol) 2013; 25: 147-52. doi: 10.1016/j.clon.2012.07.012AppeltALVogeliusIRBentzenSMModern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heartClin Oncol (R Coll Radiol)2013251475210.1016/j.clon.2012.07.012Open DOISearch in Google Scholar

Lee J, Hua K-L, Hsu S-M, Lin J-B, Lee C-H, Lu K-W, et al. Development of delineation for the left anterior descending coronary artery region in left breast cancer radiotherapy: an optimized organ at risk. Radiother Oncol 2017; 122: 423-30. doi: 10.1016/j.radonc.2016.12.029LeeJHuaK-LHsuS-MLinJ-BLeeC-HLuK-Wet alDevelopment of delineation for the left anterior descending coronary artery region in left breast cancer radiotherapy: an optimized organ at riskRadiother Oncol20171224233010.1016/j.radonc.2016.12.029Open DOISearch in Google Scholar

Van Dijk-Peters FBJ, Sijtsema NM, Kierkels RGJ, Vliegenthart R, Langendijk JA, Maduro JH, et al. OC-0259: validation of a multi-atlas based auto-segmentation of the heart in breast cancer patients. Radiother Oncol 2015; 115: S132-3. doi: 10.1016/S0167-8140(15)40257-9VanDijk-Peters FBJSijtsemaNMKierkelsRGJVliegenthartRLangendijkJAMaduroJHet alOC-0259: validation of a multi-atlas based auto-segmentation of the heart in breast cancer patientsRadiother Oncol2015115S132310.1016/S0167-8140(15)40257-9Open DOISearch in Google Scholar

Morris ED, Ghanem AI, Pantelic M V, Walker EM, Han X, Glide-Hurst CK. Cardiac substructure segmentation and dosimetry using a novel hybrid MR/CT cardiac atlas. Int J Radiat Oncol Biol Phys 2018; 103: 985-93; doi: 10.1016/j.ijrobp.2018.11.025MorrisEDGhanemAIPantelicM VWalkerEMHanXGlide-HurstCKCardiac substructure segmentation and dosimetry using a novel hybrid MR/CT cardiac atlasInt J Radiat Oncol Biol Phys20181039859310.1016/j.ijrobp.2018.11.025Open DOISearch in Google Scholar

Francolini G, Desideri I, Meattini I, Becherini C, Terziani F, Olmetto E, et al. Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy: quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014). Strahlenther Onkol 2019; 195: 43-51. doi: 10.1007/s00066-018-1388-xFrancoliniGDesideriIMeattiniIBecheriniCTerzianiFOlmettoEet alAssessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy: quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014)Strahlenther Onkol2019195435110.1007/s00066-018-1388-xOpen DOISearch in Google Scholar

Lorenzen EL, Taylor CW, Maraldo M, Nielsen MH, Offersen B V, Andersen MR, et al. Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: a multi-centre study from Denmark and the UK. Radiother Oncol 2013; 108: 254-8. doi: 10.1016/j.radonc.2013.06.025LorenzenELTaylorCWMaraldoMNielsenMHOffersenB VAndersenMRet alInter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: a multi-centre study from Denmark and the UKRadiother Oncol2013108254810.1016/j.radonc.2013.06.025Open DOISearch in Google Scholar

Feng M, Moran JM, Koelling T, Chughtai A, Chan JL, Freedman L, et al. Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys 2011; 79: 10-8. doi: 10.1016/j.ijrobp.2009.10.058FengMMoranJMKoellingTChughtaiAChanJLFreedmanLet alDevelopment and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancerInt J Radiat Oncol Biol Phys20117910810.1016/j.ijrobp.2009.10.058Open DOISearch in Google Scholar

Tan W, Wang X, Qiu D, Liu D, Jia S, Zeng F, et al. Dosimetric comparison of intensity-modulated radiotherapy plans, with or without anterior myocardial territory and left ventricle as organs at risk, in early-stage left-sided breast cancer patients. Int J Radiat Oncol Biol Phys 2011; 81: 1544-51. doi: 10.1016/j.ijrobp.2010.09.028TanWWangXQiuDLiuDJiaSZengFet alDosimetric comparison of intensity-modulated radiotherapy plans, with or without anterior myocardial territory and left ventricle as organs at risk, in early-stage left-sided breast cancer patientsInt J Radiat Oncol Biol Phys20118115445110.1016/j.ijrobp.2010.09.028Open DOISearch in Google Scholar

Park HJ, Oh DH, Shin KH, Kim JH, Choi DH, Park W, et al. Patterns of practice in radiotherapy for breast cancer in Korea. J Breast Cancer 2018; 21: 244-50. doi: 10.4048/jbc.2018.21.e37ParkHJOhDHShinKHKimJHChoiDHParkWet alPatterns of practice in radiotherapy for breast cancer in KoreaJ Breast Cancer2018212445010.4048/jbc.2018.21.e37Open DOISearch in Google Scholar

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