Abstract
Background
This study aimed to compare the dosimetric characteristics of three radiotherapy techniques—supine free-breathing (FB), supine deep inspiration breath-hold (DIBH), and prone positioning—in terms of normal tissue sparing during whole-breast irradiation following breast-conserving surgery.
Methods
A total of 75 breast cancer patients (34 right-sided and 41 left-sided) were included in this dosimetric planning study. The study was approved by the local ethics board and registered at www.clinicaltrials.gov on 2023-1-31 (NCT05609058). They all underwent a computed tomography (CT) scan in standard supine position in free-breathing (FB), supine position with deep inspiratory breath hold (DIBH), and prone position (prone). Three-dimensional treatment plans were made for all 3 CTs. The primary endpoint of the study was the comparative evaluation of OAR dose reduction. Data were analyzed with ANOVA or Friedman test with appropriate post-hoc comparisons. Values of p < 0.05 were considered to be statistically significant.
Results
The Dmean to the ipsilateral lung was significantly lower in the prone position than in the supine position (3.31 Gy vs. 7.73 Gy, 7.25 Gy, P = 0.000). Despite a 62% increase in lung volume with DIBH (range: 15–132%), no pulmonary dose reduction was achieved versus FB. In light of the anatomical characteristics of the heart and the left anterior descending artery (LAD) and right coronary artery (RA), we conducted an analysis of these three indicators, which were divided into two categories: right breast cancer and left breast cancer. For left-sided breast cancer, DIBH significantly reduced the Dmean and Vx doses to the heart and LAD. For right-sided breast cancer, the prone position significantly increased the Dmean and Vx to the heart and RA. DIBH has not shown to significantly decrease the radiation dose to the heart.
Conclusion
For left-sided breast cancer, DIBH is optimal for heart protection, while prone positioning benefits lung sparing. For right-sided cancer, free-breathing suffices is adequate.
Trial registration
The study was approved by the local ethics board and registered on www.clinicaltrials.gov (NCT05609058).
Keywords: Breast cancer, Postoperative radiotherapy, Whole breast irradiation, DIBH, Prone position
Background
For women with breast cancer, whole-breast irradiation after breast-conserving surgery improves breast cancer-specific survival [1, 2]. The irradiation of breast tissue will bring a non-negligible dose to the heart and the lung, which may lead to an increase in the mortality of heart [3–5] and lung-related diseases [1, 6–9]. Both cardiac injury and secondary cancer induction are dose dependent [1, 10]. In order to reduce the dose of organs at risk (OARs), techniques such as deep inspiration breath-hold (DIBH) technique and prone position (prone) have been developed [11–14]. DIBH is becoming an increasingly preferred method for reducing the mean heart dose (MHD) in patients with left-sided breast cancer [6, 14–18], while prone positioning reduces lung exposure, thereby lowering the risk of radiation-induced lung cancer [19, 20]. Despite these established benefits, direct dosimetric comparisons between prone positioning and DIBH remain limited. In addition, most of the studies have mainly retrospectively analyzed data for left-sided breast cancer. Recent clinical research has demonstrated an increased focus on organ protection during radiotherapy for right-sided breast cancer [21, 22]. Therefore, we conducted a subgroup analysis of a prospective observational cohort to compare radiotherapy planning and OAR doses in whole-breast irradiation using three techniques: supine free-breathing (FB), supine DIBH, and prone positioning, for both left- and right-sided breast cancer.
Methods
Patient selection
This study is a subgroup analysis of a prospective observational clinical study conducted at our center, which aimed to evaluate treatment plans in different patient positions. The study was approved by the local ethics board and registered with ClinicalTrials.gov (NCT05609058). A subgroup analysis was performed on breast cancer patients who met the criteria for breast-conserving therapy and completed 3 required imaging scans, regardless of tumor laterality (left- or right-sided). Patients received 3 non-contrast computed tomographies (CT) in the following different positions during the simulation procedure: (1) standard supine position in free breath (FB); (2) supine position with gating in deep-inspiration breath-hold (DIBH); and (3) prone position (prone). For the supine position, patients were positioned on a breast board (R612 Carbon Fiber Baseplate). For the prone position, the Klarity R612-BE2 Prone Breast System was used. Prior to simulation, candidates were screened for their ability to tolerate these techniques. Selection for DIBH required good cardiopulmonary function, clear cognition, and the ability to maintain a stable breath-hold for over 20 s after training. We used the AlignRT system with three cameras for real-time 3D surface imaging.
Target contour and prescription design
Radiotherapy Oncology Group (RTOG) [23] delineation guidelines were used as a reference for the target and the OARs contour delineation. The clinical target volume (CTV) for the breast was defined by the superior margin at the clinical reference plus the image below the clavicle head and the inferior margin at the clinical reference plus loss of CT apparent breast. The anterior margin was confined by the skin and the posterior margin was just above the pectoralis muscles, with the lateral margin at the clinical reference plus mid-axillary line and the medial margin at the sternal-rib junction. The CTV for the tumor bed (CTV tb) was defined as surgical clips plus a 15-mm margin, and was limited to CTV. The OARs, including the lungs, the ipsilateral lung, the heart, the LAD, the RA, the spinal cord, and the contralateral breast, were contoured for dose calculation. The planning target volume (PTV) was expanded by 5 mm from CTV, but was restricted to the tissue within 5 mm from the skin. One radiation oncologist used a safety delineation margin consisting of a cylinder with a diameter of 10 mm surrounding the left anterior descending artery (LAD) and right coronary artery (RA) [24]. Treatments for all patients were planned using a hypofractionated fractionation scheme as defined by Wang SL et al. [25]. The prescribed dose for all treatment plans was a PTV boost of 49.5 Gy in 15 fractions and a PTV of 43.5 Gy in 15 fractions.
Plan design and evaluation
The 3D-CRT hybrid IMRT/VMAT technique provides the best benefits for the heart and the OARs in terms of radiation dose sparing, without compromising the target conformity and homogeneity in the treatment planning [15]. Specifically, a 3D-CRT plan with parallel opposed beams was created as the base plan to deliver 80% of the prescribed dose. The gantry and collimator angles of the beams were selected to have the minimum overlap with the ipsilateral lung. A VMAT plan was then created based on the 3D-CRT plan to deliver the rest of the prescribed dose. Patient treatment planning and treatment delivery were acceptable with patients in a supine or prone position. All treatment plans were optimized to cover 95% of the PTV by 100% of the prescribed dose, while minimizing the doses to the OARs as much as possible as specified in Table 1. In the context of organ preservation, the heart and ipsilateral lung were accorded a higher priority than other organs at risk. All target contours and treatment plans were independently reviewed by a senior radiation oncologist or a senior physicist who was not involved in the initial process. For any special or complex cases, a final decision was reached through discussion within our team, including the corresponding author and other senior experts. The final treatment plan was selected based on comprehensive clinical judgment.
Table 1.
Dose objectives used for plan evaluation
| Region of Interest | parameter | Target Goals | Variation Accepted |
|---|---|---|---|
| CTV | V100%•Dptv | 100% | V95%•Dptv≥95% |
| V107%•Dptv | ≤ 5% | V107%•Dptv≤10% | |
| PTV | V100%•Dptv | 95% | V95%•Dptv≥95% |
| V107%•Dptv | ≤ 5% | V107%•Dptv≤10% | |
| Ipsilateral lung | D mean | < 15 Gy | < 16 Gy |
| V20 | < 25% | < 32% | |
| V5 | < 55% | < 60% | |
| Contralateral lung | V5 | < 20% | < 25% |
| Heart (left) | D mean | < 5 Gy | < 8 Gy |
| V5 | < 45% | < 50% | |
| Heart (right) | D mean | < 3 Gy | < 6 Gy |
| V5 | < 30% | < 35% | |
| Contralateral breast | D mean | < 5 Gy | < 8 Gy |
| Spinal Cord | D max | < 30 Gy | < 32 Gy |
| LAD/RA | V40 | 20% | 25% |
| D mean | 10 Gy | 15 Gy |
Dosimetry analysis
Quantitative dose-volume parameters of heart, LAD, RA, contralateral breast and ipsilateral lung were extracted from the treatment planning system (Oncentra®by Elekta, V4.3). To analyze differences between the dose-volume parameters in the FB, DIBH, and prone group, statistical analyses were performed. The following parameters were derived from the dose-volume histogram of each treatment plan: the MHD as well as partial volume parameters of the receiving 5 Gy (V5), 10 Gy (V10), 15 Gy (V15), 20 Gy (V20),25 Gy (V25), 30 Gy (V30), 35 Gy (V35), and 40 Gy (V40); In the case of vital organs, for which the median dose is relatively low, an additional examination of the receiving 1 Gy (V1), 2 Gy (V2), 3 Gy (V3), 4 Gy (V4),5 Gy (V5), 6 Gy (V6), and 7 Gy (V7) data will also be conducted.
Statistical analysis
All data underwent normality testing using the Kolmogorov-Smirnov test (α = 0.05). Homogeneity of variance was assessed within datasets. Variables meeting normality assumptions were analyzed via repeated measures ANOVA, while non-normally distributed variables underwent Friedman tests. Following the identification of significant differences among the three groups, we conducted post-hoc pairwise comparisons. Crucially, to control for the inflation of Type I error rates due to multiple testing, we applied Bonferroni correction to adjust the significance level. P-values < 0.05 were considered statistically significant. Statistical analyses were performed using SPSS Statistics 28 software.
Results
Seventy-five women with eligibility for whole-breast irradiation after breast-conserving surgery were included between December 2022 and October 2024. The clinical features were consistent between the three groups. This is due to the fact that the same patients underwent 3 CT scans in the different positions. The median age was 41 (range, 27–60) years. There were 11 (14.7%) patients with Tis, 48 (64.0%) with T1 and 16 (21.3%) with T2. The median T size was 1.5 cm. All patients were lymph node negative at baseline. The study showed that 63 (84.0%) patients were hormone receptor positive, while 8 (10.7%) patients were HER2 receptor positive. Comparative analysis of target volumes revealed that while the differences in Clinical Target Volumes (CTV/CTVboost) among positions were statistically significant, they exhibited weak effect sizes (W < 0.3) and minimal absolute differences (< 5.3 cc), indicating negligible clinical relevance. In contrast, these differences were substantially amplified at the Planning Target Volume (PTV) level, demonstrating a moderate effect size (W = 0.599). PTV volumes in supine positions (FB/DIBH) were significantly larger than in the prone position (prone) (e.g., FB vs. prone: +37.1 cc). This amplification is attributed to the interplay between postural breast geometry and uniform margin expansion: the wider breast in supine positions leads to a greater absolute volume increase, whereas the narrower breast in the prone position results in a smaller expansion. Regarding normal organs, patient position primarily affected the volumes of the lung and heart. DIBH significantly increased ipsilateral lung volume, while FB resulted in the largest heart volume. No significant differences were found in LAD or RA volumes among the groups. The characteristics of patients in the FB, DIBH, and the prone groups are provided in Table 2.
Table 2.
Characteristics of patients in three groups
| Region of Interest | FB(cc) | DIBH(cc) | prone(cc) | Effect Size | p | FB vs. DIBH | FB vs. prone | DIBH vs. prone |
|---|---|---|---|---|---|---|---|---|
| CTV boosta |
49.3 (32.8–63.7) |
47.4 (31.6–64.1) |
55.8 (35.4–71.8) |
W = 0.123 | 0.000 |
0.0(−0.9, 0.5) p = 1.000 |
−4.0(−5.6, −1.8) p = 0.001 |
−3.4(−6.4, −1.8) p = 0.001 |
| CTVa |
341.8 (238.3–497.0) |
352.2 (245.0–481.1.0.1) |
339.3 (247.9–499.4.9.4) |
W = 0.044 | 0.036 |
−0.8(−6.2, 0.0) p = 0.072 |
−5.3*(−7.7, −1.3) p = 0.038 |
−1.0(−3.4, 2.9) p = 1.000 |
| PTVa |
503.7 (371.2–665.3.2.3) |
500.1 (370.2–673.2.2.2) |
437.5 (334.1–611.2.1.2) |
W = 0.599 | 0.000 |
−5.7(−8.4, −1.6) p = 0.362 |
37.1*(32.6, 48.7) p = 0.000 |
44.4*(36.0, 53.9) p = 0.000 |
| PTV boosta |
94.4 (66.6–118.3.6.3) |
89.4 (65.2–117.8.2.8) |
101.9 (73.6–136.2.6.2) |
W = 0.238 | 0.000 |
2.8*(0.8, 4.0) p = 0.008 |
−6.6*(−9.5, −2.9) p = 0.001 |
−8.9*(−11.0, −6.4) p = 0.000 |
| ipsilateral lungb |
1167.0 (937.5–1326.3.5.3) |
1864.7 (1553.6–2084.0) |
1301.8 (1063.2–1503.5.2.5) |
Partial η² =0.825 | 0.000 |
−686.8* (−755.5, −618.1), p < 0.001 |
−166.9* (−204.0, −129.8), p < 0.001 |
519.9* [435.3, 604.5], p < 0.001 |
| contralateral breastb |
450.4 (329.9–631.0) |
457.1 (337.0–645.5.0.5) |
464.5 (326.9–658.1.9.1) |
Partialη² = 0.048 | 0.057 | - | - | - |
| Heartb |
520.2 (475.7–583.5.7.5) |
509.4 (451.3–566.7.3.7) |
503.3 (474.5–573.6.5.6) |
Partialη² = 0.104 | 0.000 |
22.2*(8.6, 35.6), p < 0.001 |
14.7*(3.1, 26.2), p = 0.008 | −7.4(−22.2, 7.3), p = 0.661 |
| LADb |
5.3 (4.8–5.7) |
5.3 (4.8–5.7) |
5.2 (4.9–5.7) |
Partialη² = 0.048 | 0.087 | - | - | - |
| RAb |
4.4 (4.0–4.8.0.8) |
4.4 (4.1–4.8) |
4.3 (4.0–4.8.0.8) |
Partialη² = 0.001 | 0.772 | - | - | - |
*Indicates a statistically significant difference after Bonferroni correction (p < 0.05)
aAnalyzed using the Friedman test (non-parametric). Data presented as Median (Interquartile Range). Effect size reported as Kendall's W. Pairwise comparisons report Median Difference (95% CI)
bAnalyzed using repeated-measures ANOVA (parametric). Data presented as Mean (95% Confidence Interval). Effect size reported as Partial Eta Squared (Partial η²). Pairwise comparisons report Mean Difference (95% CI)
Dosimetric comparison
There were no statistically significant differences in CI metrics and HI metrics for PTV and PTVboost in the three study groups. In the case of OARs, the mean dose to the contralateral breast was not found to be statistically different among the three groups. With regard to all other metrics, a statistically significant difference was observed.
Ipsilateral lung dosimetric comparison
Dosimetric analysis revealed a significant reduction in radiation exposure to the ipsilateral lung in the prone position (prone) compared to both supine positions. The mean lung dose (Dmean) was substantially lower in prone (331 cGy) than in FB (773 cGy) or DIBH (725 cGy) (p = 0.000). This pronounced sparing effect was consistently observed across all Vx levels (V5–V45), as detailed in Table 3. In contrast, compared with free breathing (FB), the deep inspiration breath-hold (DIBH) technique did not confer a clinically meaningful advantage for most pulmonary dose parameters, showing only minor reductions in the high-dose range (V20–V35) and no significant improvement in low- and medium-dose volumes.
Table 3.
Dosimetric comparison of the ipsilateral lung in three groups
| Lung | FB | DIBH | prone | p | Effect Size | FB vs. DIBH | FB vs. prone | DIBH vs. prone |
|---|---|---|---|---|---|---|---|---|
|
Dmean (Gy)a |
7.73 (6.22–9.26) |
7.25 (6.25–8.62) |
3.31 (2.50–4.52) |
0.000 | W = 0.514 |
0.32 (−0.01, 0.72) p = 0.662 |
3.97* (3.65, 4.52) p < 0.001 |
3.79* (3.34, 4.35) p < 0.001 |
|
V5b (%) |
28.1 (23.6–32.0) |
27.8 (24.2–33.6) |
11.3 (8.0–15.0) |
0.000 | Partial η² = 0.835 |
−1.05 (−2.74, 0.65) p = 0.403 |
15.71* (14.25, 17.17) p < 0.001 |
16.76* (14.89, 18.63) p < 0.001 |
|
V10b (%) |
18.7 (15.1–22.4) |
17.8 (14.9–22.6) |
7.3 (3.8–10.8) |
0.000 | Partial η² = 0.811 |
0.31 (−0.72, 1.34) p = 1.000 |
10.93* (9.77, 12.09) p < 0.001 |
10.62* (9.22, 12.03) p < 0.001 |
|
V15a (%) |
16.0 (12.2–20.2) |
14.3 (12.2–18.9) |
6.0 (2.9–8.6) |
0.000 | W = 0.508 |
0.9 (0.2, 1.8) p = 0.259 |
9.5* (8.9, 10.3) p < 0.001 |
9.0* (7.2, 10.2) p < 0.001 |
|
V20a (%) |
14.6 (10.6–18.2) |
12.9 (10.0–17.0) |
4.9 (2.3–7.4) |
0.000 | W = 0.501 |
1.1* (0.6, 1.6) p = 0.027 |
9.0* (8.4, 9.8) p < 0.001 |
7.9* (6.8, 8.9) p < 0.001 |
|
V25a (%) |
13.1 (9.3–16.6) |
11.7 (8.9–15.1) |
4.0 (1.8–6.3) |
0.000 | W = 0.476 |
1.2* (0.9, 2.1) p = 0.017 |
8.5* (7.8, 9.5) p < 0.001 |
7.0* (6.1, 7.8) p < 0.001 |
|
V30a (%) |
11.70 (7.9–14.8) |
10.1 (7.7–13.0) |
3.2 (1.4–5.5) |
0.000 | W = 0.474 |
1.4* (0.8, 1.8) p = 0.015 |
7.6* (6.8, 8.7) p < 0.001 |
6.3* (4.7, 7.1) p < 0.001 |
|
V35a (%) |
8.8 (5.7–11.8) |
7.5 (5.4–9.1) |
2.1 (0.7–4.0.7.0) |
0.000 | W = 0.476 |
0.9* (0.1, 1.4) p = 0.021 |
6.0* (5.0, 6.7) p < 0.001 |
5.0* (3.7, 5.8) p < 0.001 |
|
V40a (%) |
3.8 (2.1–5.3) |
3.7 (2.1–5.2) |
0.6 (0.1–1.6) |
0.000 | W = 0.475 |
0.0 (−0.4, 0.4) p = 1.000 |
3.0* (2.1, 3.6) p < 0.001 |
2.6* (2.1, 3.3) p < 0.001 |
|
V45a (%) |
0.2 (0.0–0.6.0.6) |
0.4 (0.1–0.6) |
0.0 (0.0–0.1.0.1) |
0.000 | W = 0.282 |
0.0 (−0.1, 0.0) p = 0.922 |
0.2* (0.1, 0.3) p < 0.001 |
0.3* (0.1, 0.4) p < 0.001 |
*Indicates a statistically significant difference after Bonferroni correction (p < 0.05)
aAnalyzed using the Friedman test (non-parametric). Data presented as Median (Interquartile Range). Effect size reported as Kendall's W. Pairwise comparisons report Median Difference (95% CI)
bAnalyzed using repeated-measures ANOVA (parametric). Data presented as Mean (95% Confidence Interval). Effect size reported as Partial Eta Squared (Partial η²). Pairwise comparisons report Mean Difference (95% CI)
Although dose limitation in the ipsilateral lung is mainly the V5, V20 and Dmean, the overall DVH is also important. For each individual to be analyzed on a patient-by-patient basis, we drew DVH maps. Detailed results are shown in Fig. 1.
Fig. 1.
Dose-Volume Histograms (DVHs) of the Lung for Each Patient under Different Positioning Techniques (Free Breathing, Deep Inspiration Breath-Hold, and Prone Positioning)
Heart dosimetric comparison
In light of the anatomical characteristics of the heart and the LAD and RA, we conducted an analysis of these three indicators, which were divided into two categories: right breast cancer and left breast cancer.
For left-sided breast cancer, the Dmean to the heart and the LAD, the Vx of the heart and the LAD when using DIBH was significantly reduced. Vx indices are summarized in Table 4. DVH details results are shown in Fig. 2.
Table 4.
Dosimetric comparison of Heart-Related parameters in three groups for Left-Sided breast cancer
| FB | DIBH | prone | Effect Size | p | FB vs DIBH | FB vs prone | DIBH vs prone | |
|---|---|---|---|---|---|---|---|---|
| Heart | ||||||||
| Dmean (Gy) |
3.35 (2.43–4.90.43.90) |
1.87 (1.35–2.70.35.70) |
3.91 (2.98–5.51.98.51) |
W=0.616 | 0.000 |
1.33*(0.95,1.80) p = 0.000 |
1.02(0.31,1.14) p = 0.232 |
1.82*(1.48,2.44) p = 0.000 |
|
V5 (%) |
11.3 (6.3–15.9.3.9) |
3.4 (1.3–7.4.3.4) |
12.6 (8.2–18.9.2.9) |
W=0.580 | 0.000 |
5.8*(3.3, 6.9) p = 0.000 |
3.2(1.5,4.7) p = 0.293 |
7.7*(5.8,10.0) p = 0.000 |
|
V6 (%) |
8.8 (4.9–13.1.9.1) |
2.5 (0.6–5.5.6.5) |
9.7 (6.0–14.9.0.9) |
W=0.597 | 0.000 |
5.0*(3.3,5.8) p = 0.000 |
2.2(1.6,3.5) p = 0.181 |
6.6*(4.9,8.9) p = 0.000 |
|
V8 (%) |
6.1 (3.5–10.9.5.9) |
1.5 (0.1–3.8.1.8) |
7.7 (4.7–12.4.7.4) |
W=0.597 | 0.000 |
3.9*(2.7,5.7) p = 0.000 |
2.3(0.7,3.3) p = 0.328 |
4.9*(3.7,7.0) p = 0.000 |
|
V10 (%) |
5.5 (2.7–9.6.7.6) |
1.0 (0.0–3.0.0.0) |
6.7 (4.0–11.3.0.3) |
W=0.568 | 0.000 |
3.7*(2.5,5.1) p = 0.000 |
2.0(0.3,3.0) p = 0.408 |
4.5*(3.8,6.4) p = 0.000 |
|
V20 (%) |
4.0 (1.4–6.9.4.9) |
0.3 (0.0–1.5.0.5) |
4.4 (2.1–7.7.1.7) |
W=0.595 | 0.000 |
3.0*(2.1,4.6) p = 0.000 |
1.2(0.4,2.0) p = 1.000 |
3.4*(2.2,4.4) p = 0.000 |
|
V30 (%) |
2.9 (0.8–4.4.8.4) |
0.0 (0.0–0.9.0.9) |
2.7 (1.1–5.4.1.4) |
W=0.598 | 0.000 |
2.3*(1.5,3.3) p = 0.000 |
0.9(0.4,1.4) p = 1.000 |
2.4*(1.2,2.7) p = 0.000 |
|
V40 (%) |
0.5 (0.0–1.4.0.4) |
0.0 (0.0-0.0.0.0) |
0.4 (0.1–1.4.1.4) |
W=0.403 | 0.000 |
0.3*(0.1,0.6) p = 0.000 |
0.0(0.0,0.1) p = 1.000 |
0.3*(0.1,0.4) p = 0.000 |
| LAD | ||||||||
|
Dmean (Gy) |
24.01 (13.64–30.45.64.45) |
6.65 (3.76–12.18.76.18) |
22.83 (17.84–29.78.84.78) |
W=0.618 | 0.000 |
10.00*(8.78,15.13) p = 0.000 |
3.20(−0.41,5.62) p = 1.000 |
6.59*(4.59,9.33) p = 0.000 |
|
V5 (%) |
78.8 (69.1–91.2.1.2) |
53.2 (16.5–77.6.5.6) |
86.0 (74.7–97.6.7.6) |
W=0.483 | 0.000 |
24.8*(16.4,29.3) p = 0.000 |
6.6(1.7,10.4) p = 0.071 |
28.4*(20.1,44.8) p = 0.000 |
|
V6 (%) |
73.2 (63.4–88.4.4.4) |
39.1 (5.1–71.6.1.6) |
82.8 (69.5–96.0.5.0) |
W=0.453 | 0.000 |
28.4*(18.1,37.9) p = 0.000 |
7.1(0.5,11.5) p = 0.261 |
45.2*(21.6,54.3) p = 0.000 |
|
V8 (%) |
69.4 (55.7–86.0.7.0) |
23.5 (0.1–60.5.1.5) |
78.0 (64.5–90.4.5.4) |
W=0.526 | 0.000 |
31.3*(15.6,40.4) p = 0.000 |
7.8(1.3,13.9) p = 0.293 |
46.5*(28.4,62.8) p = 0.000 |
|
V10 (%) |
67.9 (47.5–84.7.5.7) |
18.2 (0.0–43.1.0.1) |
73.9 (61.4–85.4.4.4) |
W=0.544 | 0.000 |
32.2*(17.4,41.5) p = 0.000 |
8.8(0.2,16.7) p = 0.555 |
53.9*(32.2,61.6) p = 0.000 |
|
V20 (%) |
62.9 (22.9–77.4.9.4) |
3.4 (0.0–25.7.0.7) |
61.8 (40.9–74.6.9.6) |
W=0.578 | 0.000 |
31.2*(20.7,48.5) p = 0.000 |
7.3(3.4,21.4) p = 0.673 |
46.7*(28.6,58.0) p = 0.000 |
|
V30 (%) |
50.0 (8.7–67.6.7.6) |
0.0 (0.0–12.1.0.1) |
41.2 (21.1–66.8.1.8) |
W=0.557 | 0.000 |
30.3*(16.3,38.2) p = 0.000 |
7.5(1.4,13.9) p = 0.555 |
37.3*(21.7,41.2) p = 0.000 |
|
V40 (%) |
3.6 (0.0–25.1.0.1) |
0.0 (0.0-0.0.0.0) |
5.8 (0.2–21.3.2.3) |
W=0.418 | 0.000 |
3.3*(0.2,9.3) p = 0.000 |
0.0(−1.2,3.0) p = 1.000 |
2.6*(0.8,7.2) p =.000 |
Analyzed using the Friedman test (non-parametric). Data presented as Median (Interquartile Range) reported as Kendall's W. Pairwise comparisons report Median Difference (95% CI)
*Indicates a statistically significant difference after Bonferroni correction (p < 0.05)
Fig. 2.
Dose-Volume Histograms (DVHs) of the herat and LAD for Each left Patient under Different Positioning Techniques (Free Breathing, Deep Inspiration Breath-Hold, and prone Positioning)
For right-sided breast cancer, the prone position (prone) resulted in significantly higher radiation doses to the heart and right coronary artery (RA) compared to the supine positions. The two supine techniques (FB and DIBH) were dosimetrically comparable for the vast majority of parameters, with DIBH offering only minor, statistically significant advantages at isolated low-dose points (e.g., RA V4). Vx indices are summarized in Table 5. DVH details results are shown in Fig. 3.
Table 5.
Dosimetric comparison of Heart-Related parameters in three groups for right-sided breast cancer
| Heart | FB | DIBH | prone | Effect Size | p | FB vs DIBH | FB vs prone | DIBH vs prone |
|---|---|---|---|---|---|---|---|---|
|
Dmean (Gy) |
1.46 (1.00–1.82.00.82) |
1.27 (0.98–1.45.98.45) |
2.08 (1.30–2.34.30.34) |
W=0.304 | 0.000 |
0.06(−0.10,0.33) p = 0.825 |
0.57*(0.36,0.69) p = 0.003 |
0.66*(0.49,0.83) p = 0.000 |
|
V1 (%) |
59.1 (40.2–84.7.2.7) |
56.4 (33.8–73.4.8.4) |
85.3 (56.0–93.8.0.8) |
W=0.273 | 0.001 |
−1.4(−12.1,9.25) p = 0.609 |
20.9*(0.5,28.7) p = 0.011 |
25.0*(12.3,32.8) p = 0.000 |
|
V2 (%) |
20.7 (8.1–31.1.1.1) |
14.7 (7.9–20.6.9.6) |
40.7 (16.0–46.4.0.4) |
W=0.271 | 0.000 |
−4.0(−10.7,−0.5) p = 0.345 |
14.7*(6.9,19.8) p = 0.023 |
21.3*(11.9,26.8) p = 0.000 |
|
V3 (%) |
8.1 (1.1–14.9.1.9) |
2.8 (0.4–5.8.4.8) |
18.2 (5.7–21.3.7.3) |
W=0.382 | 0.000 |
−2.2*(−5.4,−0.5) p = 0.016 |
6.0*(3.5,8.1) p = 0.015 |
11.6*(5.9,16.7) p = 0.000 |
|
V4 (%) |
1.9 (0.0–7.7.0.7) |
0.5 (0.0–2.0.0.0) |
8.1 (1.8–9.4.8.4) |
W=0.308 | 0.000 |
−0.6(−2.7,0.0) p = 0.157 |
1.9*(0.7,4.2) p = 0.039 |
6.1*(1.7,7.5) p = 0.000 |
|
V5 (%) |
0.4 (0.0–2.1.0.1) |
0.0 (0.0–0.3.0.3) |
2.8 (0.3–3.7.3.7) |
W=0.338 | 0.000 |
−0.1(−0.9,0.0) p = 0.207 |
1.1*(0.1,2.2) p = 0.033 |
2.0*(0.5,3.3) p = 0.000 |
| RA | FB | DIBH | prone | Effect Size | p | FB vs DIBH | FB vs prone | DIBH vs prone |
|
Dmean (Gy) |
2.99 (2.22–3.91.22.91) |
2.54 (2.00–3.13.00.13) |
4.59 (3.01–5.34.01.34) |
W=0.522 | 0.000 |
0.43(0.15,0.85) p = 0.207 |
1.39*(1.06,2.01) p = 0.000 |
1.97*(1.53,2.30) p = 0.000 |
|
V1 (%) |
100.0 (100.0-100.0.0.0) |
100.0 (100.0-100.0.0.0) |
100.0 (100.0-100.0.0.0) |
W=0.09 | 0.052 | - | - | - |
|
V2 (%) |
88.9 (61.4–100.0.4.0) |
78.8 (52.8–92.7.8.7) |
100.0 (96.5–100.0.5.0) |
W=0.443 | 0.000 |
5.2(1.3,11.7) p = 0.087 |
8.6*(0.0,22.9) p = 0.011 |
14.2*(7.9,27.9) p = 0.000 |
|
V3 (%) |
44.1 (13.4–77.9.4.9) |
16.4 (5.5–53.2.5.2) |
93.0 (72.0–100.0.0.0) |
W=0.39 | 0.000 |
17.2(5.6,27.9) p = 0.087 |
34.9*(21.1,53.3) p = 0.000 |
48.0*(44.5,69.9) p = 0.000 |
|
V4 (%) |
9.9 (0.3–45.3.3.3) |
0.7 (0.0–18.3.0.3) |
68.0 (28.6–92.0.6.0) |
W=0.613 | 0.000 |
7.6(0.9,17.1) p = 0.033 |
29.6*(16.2,48.4) p = 0.001 |
51.0*(38.7,67.5) p = 0.000 |
|
V5 (%) |
1.9 (0.0–14.6.0.6) |
0 (0.0–2.0.0.0) |
33.9 (1.7–55.1.7.1) |
W=0.396 | 0.000 |
1.1(0.0,9.6) p = 0.054 |
17.2*(1.4,29.8) p = 0.001 |
28.7*(10.1,41.5) p = 0.000 |
Fig. 3.
Dose-Volume Histograms (DVHs) of the heart and LAD for Each right Patient under Different Positioning Techniques (Free Breathing, Deep Inspiration Breath-Hold, and Prone Positioning)
Deep-inspiration breath-hold has also been shown to significantly decrease the radiation dose to the heart, but only for cancer of the left breast.
Discussion
As survival rates for breast cancer continue to rise, the reduction of late non-cancer mortality, primarily from radiotherapy-associated cardiotoxicity and pulmonary effects, has become a primary therapeutic objective. Prone positions and DIBH that are two important techniques developed to improve the sparing of OARs [11–13]. A key strength of our study is the direct comparison of three radiotherapy techniques (FB, DIBH, and prone) in the same cohort of patients (n = 75), with each patient serving as their own control. Our findings provide clear dosimetric insights. For left-sided breast cancer patients, DIBH achieved a 40% reduction in mean heart dose compared to FB and a 151.5% reduction compared to Pro, with the greatest benefit observed for the LAD (mean dose reduction: ~10.0 Gy). No cardiac benefit was observed for right-sided cancers. For lung sparing, the prone position definitively reduced lung doses by > 50%, while DIBH showed no significant lung dose reduction compared to FB.
Radiotherapy related cardiac irradiation can reduce the survival rate due to late cardiac adverse events in some patients [3, 16, 26–29]. Primary prevention of radiation-induced cardiovascular toxicity is to reduce the heart dose [5]. In our study of left-sided cancers, the DIBH technique achieved a reduction in mean cardiac dose ranging from 0.95 to 2.44 Gy. This reduction is consistent with those observed in previous clinical trials [6, 14–16, 30], thereby supporting its role in mitigating radiation-induced coronary events. This dose reduction corresponds to a potential decrease in the long-term risk of major coronary events by approximately 7.0–18.1% according to Darby et al. [3]. This estimate underscores the considerable potential of DIBH technology in averting long-term cardiac toxicity associated with radiotherapy.
A particular focus of our analysis was the left anterior descending artery (LAD). In published studies, the mean dose reduction to the LAD with DIBH versus FB varies substantially, ranging from 11% to 71% [14, 17, 31–33], with the present study reporting 11%. This variability is attributed to the lack of consistency in how LADs are sketched. The importance of dose reductions in coronary artery segments is further supported by a dosimetric analysis study on the dose distribution in individual coronary segments of patients, where the study showed that the middle and distal LAD segments (segments 7–8) received significantly higher doses [30]. Therefore, a reasonable method of outlining the LAD is very important. In our study, to ensure reproducibility and objectivity, we use a safety delineation margin consisting of a cylinder with a diameter of 10 mm surrounding the LAD and RA [24]. Consequently, Our research has found a significant reduction in V5, V6, V8, V10, V20, V30, and V40 for the heart and LAD in DIBH was observed compared with values in FB and prone. To our knowledge, our study is among the first to present such individualized DVH analyses for a larger patient dataset, providing a detailed and robust characterization of the dosimetric benefits of DIBH.
Our study found that for right-sided, DIBH did not provide a clinically meaningful dosimetric benefit to the heart compared with FB, consistent with previous research [21]. Although statistically significant differences were observed in certain parameters, such as heart V3 and right coronary artery V4, these were consistent with some previous studies suggesting a cardiac protective effect of DIBH in right-sided cancer [22]. However, the median differences in the results of this study were small (2.2% and 7.6%, respectively), and thus likely insufficient to constitute a clinically relevant improvement. The contradictory results regarding the cardiac protective role of DIBH between right- and left-sided breast cancer may be attributed to anatomical displacement of the heart during DIBH, which could draw more right-sided cardiac structures into the high-dose region. Moreover, the inherently low cardiac irradiation dose in the FB position for right-sided breast cancer may limit the potential for further dose reduction with DIBH.
Importantly, our results indicate that prone results in higher doses to the heart and RA than the FB and DIBH techniques, witch is statistically significant.Nevertheless, it is noteworthy that 100% of the patients in the Pro group exhibited cardiac Dmean < 3 Gy. When the mean heart dose is kept low with modern radiation planning techniques, no increased risk of cardiac events in breast patients was observed within the first 10 years after RT [34–38]. Killander, F. et al. [34] observed no increased cardiac mortality in irradiated patients with doses to the heart were median Dmean 3.0 Gy for left-sided RT. Considering this, our data showed that almost almost all patients (98%) had a mean MHD below 3.0 Gy and even 100% patients with prone had a mean MHD below 3.0 Gy. This demonstrates that excellent heart protection was achieved across all techniques in our study, underscoring the overall safety of modern radiotherapy planning in our cohort.
Currently, there are several models that quantitatively relate dose to the lungs to the risk of secondary lung cancer [1, 6, 8, 9, 39, 40]. Thus, reducing the amount of radiation to the lungs during treatment planning could reduce the long-term overall mortality of early-stage breast cancer patients [19]. All studies found prone position to be superior for lung sparing [13], hence reducing the risk of secondary lung cancer [1, 19, 39]. Our results confirm the general strong benefit of prone positioning on lung dose, which resulted in a reduction of 50% or more in comparison to the supine position.
In contrast, the clinical benefit of DIBH for lung sparing appears more limited. Our study suggests that while DIBH demonstrates statistical advantages over FB in certain dosimetric parameters, its corresponding clinical relevance requires careful evaluation. The absence of significant differences in primary endpoints like V5 and mean lung dose aligns with several prior studies [6, 41]. Our study confirms the reduction in V20 with DIBH (median: 12.9% vs. 14.6%, p = 0.027) observed in some literatures [14, 18, 42], however, the absolute difference was modest (1.7% points) and may fall below the threshold for clinical significance.
In light of the increasing utilization of varied fractionation regimens, lung dose evaluation now incorporates a broader set of metrics (e.g., V10, V25, V30) beyond V20 [43–45]. Our systematic analysis of these parameters revealed a highly consistent pattern: the benefit of DIBH is strictly confined to the high-dose region (V20 to V35), yielding only marginal reductions (median difference: 1%−2%). In contrast, no significant improvement is observed in low-to-moderate dose parameters (V5, V10). This consistent profile reinforces that the pulmonary protective effect of DIBH in routine practice is likely limited.
Our study has several limitations. Firstly, in contrast to some previous reports, we did not observe a significant pulmonary dose reduction with DIBH, however, we were unable to identify explanatory variables for this finding. Secondly, as this study was primarily focused on dosimetric comparisons, data on clinical workflow aspects, such as patient tolerability, comfort, and setup times for the different positioning techniques (e.g., the prone position), were not systematically collected. These factors are important considerations for technique selection. Future studies incorporating patient-reported outcomes and time-motion analyses would be valuable for a more comprehensive assessment of the overall clinical feasibility of these techniques. Thirdly, and importantly, this is a dosimetric planning study. Consequently, we lack data on long-term clinical outcomes such as cardiac events, symptomatic pulmonary toxicity, or survival. While our findings demonstrate significant differences in organ-at-risk exposure, the direct translation of these dosimetric advantages into improved patient prognosis remains to be validated through prospective studies with long-term follow-up. Fourthly, the sample size of 75 patients was not based on a formal prospective power calculation but was a convenience sample derived from an observational cohort who completed all three scanning protocols. Although this sample size is substantial for a dosimetric planning study and allows for a robust within-subject comparison, the findings, particularly for the subgroup analyses (e.g., right-sided vs. left-sided), should be interpreted as exploratory and require validation in larger cohorts.
In summary, our results demonstrate that for left-sided breast cancer, DIBH remains the preferred technique for cardiac protection. Conversely, for right-sided cancers, the marginal benefit of DIBH calls into question its cost-effectiveness and routine application, suggesting that Free Breathing (FB) may often be sufficient. Furthermore, the prone position represents a valuable alternative for patients at high risk of pulmonary toxicity, offering significant lung sparing without the need for expensive gating equipment. The practical challenges associated with this technique, particularly the increased complexity in daily setup and Cone-Beam CT (CBCT) verification, can be mitigated through comprehensive training and stringent imaging protocols. Consequently, an optimal approach should integrate tumor laterality, individual patient risk factors, and a pragmatic assessment of institutional resources and expertise.
Clinical implications
Based on these findings, a stratified clinical strategy is recommended, guided by three key principles: First, tumor laterality should determine the primary technique: prioritize DIBH for left-sided cancers and adopt FB as the baseline for right-sided cases. Second, individual risk profiles can modify this choice: consider the prone position as a valuable option for patients at high risk of pulmonary toxicity. Third, successful implementation depends on institutional capacity: the practical challenges of techniques like prone positioning require investment in comprehensive staff training and standardized imaging protocols. Ultimately, integrating considerations of laterality, patient-specific risks, and available resources will optimize radiotherapy planning.
Conclusions
In conclusion, our findings indicate that DIBH is optimal for left-sided cases with cardiac risk, the prone position benefits lung protection, and FB is adequate for right-sided breast cancer without additional lung concerns.
Acknowledgements
Not applicable.
Abbreviations
- CT
computed tomography
- CTV
clinical target volume
- DIBH
deep inspiratory breath hold
- FB
free-breathing
- LAD
left anterior descending artery
- MHD
mean heart dose
- OARs
organs at risk
- prone
prone position
- PTV
planning target volume
- RA
right coronary artery
- RT
radiotherapy
- RTOG
Radiotherapy Oncology Group
Authors’ contributions
Lingling Feng and Ying Liang: Writing-original draft and data interpretation; Jiaxin Huang, and Sisi Xu: Data analysis and interpretation; Wenjue Zhang,, Xiaoye Su, Yutong Tan, Tongda Lei, Xiaoyong Xiang, Lining Chen, JunQin Lei, Nan Hu: Clinical management of patients; Jing Jin, and Ning Li: Study design, Writing-review and editing; All authors critically reviewed and approved the final manuscript.Lingling Feng and Ying Liang contributed equally to this work.
Funding
This work was supported by traditional Chinese Medicine Research Project of Shanxi Provincial Health Commission (No. 2023102), supported by Sanming Project of Medicine in Shenzhen(No.SZSM202211030), supported by Shenzhen High-level Hospital Construction Fund, supported by the Shenzhen Key Medical Discipline Construction Fund (No. SZXK013), Shenzhen Science and Technology Program (No. JCYJ20220530153803008), and National Natural Science Foundation of China (No. 12305295), Supported by National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (E010322038).
Data availability
The data used and/or analyzed during the current study available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
1. This study was approved by two ethical review boards: The Ethics Committee of Shanxi Hospital of Cancer Hospital, Chinese Academy of Medical Sciences (Approval No. KY2023013), and The Ethics Committee of Shenzhen Hospital of Cancer Hospital, Chinese Academy of Medical Sciences (Approval No. JS2023-10). The study was registered on www.clinicaltrials. gov (NCT05609058).
2. The study was conducted in strict accordance with the principles of the Declaration of Helsinki (2013 revision).
3. Written informed consent was obtained from all individual participants prior to their inclusion in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Lingling Feng and Ying Liang contributed equally to this work.
Contributor Information
Jing Jin, Email: jinjing@csco.org.cn.
Qin Xiao, Email: xiaoqin@cicams-sz.org.cn.
Ning Li, Email: lee_ak@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data used and/or analyzed during the current study available from the corresponding author on reasonable request.