Postoperative whole-breast or chest wall radiotherapy has been documented to improve both locoregional disease control and overall survival in breast carcinoma patients.[1,2,3] Despite the benefits, radiation-induced toxicity is a major concern due to the observed long-term survival of breast carcinoma patients. An increased risk of long-term cardiac morbidity following adjuvant radiotherapy for left-sided breast carcinoma has been shown in studies using conventional radiotherapy techniques.[4,5]
In recent years, multiple attempts have been made to devise modifications in radiotherapy techniques to reduce critical organ doses, particularly pulmonary and cardiac doses, during adjuvant radiotherapy for breast carcinoma. Among the various radiotherapy techniques aimed at reducing adjacent normal tissue doses, particularly doses to the heart and lungs, the deep inspiration breath-hold (DIBH) technique is the most studied. DIBH is achieved using either the Elekta Active Breathing Coordinator™ or the Varian RPM (Real Time Position Management) System, and studies have shown that both techniques produce comparable results in terms of reproducibility and normal tissue sparing.[6]
Several studies have demonstrated the significant benefits of DIBH in sparing the heart and other structures, such as the left anterior descending artery, with appreciable reductions in mean heart dose compared to older radiotherapy techniques.[7,8,9] In addition, DIBH significantly reduces ipsilateral lung mean doses.[10,11,12] Although DIBH increases the absolute volume of the lung, it spares the lung tissue by reducing the relative volume of the lung irradiated.
Multiple studies have proven the benefit of DIBH in left-sided radiotherapy in terms of critical organ sparing. However, studies and clinical practices remain limited in the case of right-sided breast or chest wall irradiation. The few studies on right-sided radiotherapy using DIBH have primarily focused on cardiac and lung benefits, with limited data available on liver dose reduction despite the liver being an important organ at risk in right breast carcinoma adjuvant radiotherapy.[13,14,15,16]
The subsequent use of systemic therapy in breast cancer treatment for recurrence or distant metastasis, particularly targeted therapy and immunotherapy, which can affect organ function, including hepatic function, makes hepatic tissue sparing during radiotherapy even more critical alongside other normal tissue dose reductions.
This study aimed to demonstrate a single institution's experience with the dosimetric benefits of the DIBH technique in the irradiation of right breast carcinoma patients, focusing on sparing the heart, bilateral lungs, and liver while maintaining acceptable target volume coverage.
The study was carried out in the Radiotherapy Department of Chittaranjan National Cancer Institute, Kolkata, India. Twenty consecutive patients with right-sided breast carcinoma undergoing adjuvant whole-breast or chest wall radiotherapy using the DIBH technique were retrospectively included in the study. Trial was not funded and was conducted according to ethical guidelines established by the Declaration of Helsinki and other guidelines like Good Clinical Practice Guidelines and those established by the Indian Council of Medical Research.
Indications for the use of DIBH for right-sided breast carcinoma adjuvant radiotherapy in our institution included the presence of a breast implant or the need for irradiation of the axillary and/or internal mammary lymph nodal area. All patients were treated using the DIBH technique. An indexed breast board was used, with both arms placed above the head and the head rotated to the opposite side. Planning scans were obtained in both free breathing (FB) and DIBH for all patients using a wide-bore computed tomography (CT) simulator (GE 128 Wide Bore CT). During DIBH, respiratory motion was tracked using the Varian RGSC (Respiratory Gating for Scanners) gating system (Varian Medical System) with a surrogate block placed over the diaphragm, which provided a signal to the RGSC camera. Both planning scans for each patient were obtained with a 2.5-mm slice separation, with the patient in the same position and covering the same length, from the mentum to full coverage of the liver. The planning scans were then transferred to the Varian Treatment Planning System for target and normal tissue delineation and treatment planning.
Targets and organs at risk were contoured in both planning scans using the same contouring method. Whole-breast or chest wall Clinical Target Volume (CTV) were delineated using the Radiation Therapy Oncology Group, RTOGBreast Contouring Atlas.[17] Regional lymph nodes, when indicated, were contoured using the same guidelines.[17] For whole-breast and chest wall CTVs, no Planning Target Volume (PTV) margin was added, with the dose prescribed directly to CTV (CTV=PTV) after cropping it 3 mm from the skin. For nodal CTVs, a 5-mm isotropic PTV margin was added, which was then cropped 3 mm from the skin. Both lungs were contoured using an automated segmentation tool, while the remaining normal tissues were contoured manually in both scans using the RTOG normal tissue contouring guidelines.[17]
Treatment planning was performed in Eclipse v16 (Varian Medical Systems). The prescribed dose was either 40 Gy in 15 fractions or 50 Gy in 25 fractions (in cases with implant-based reconstruction or internal mammary chain irradiation), with dose prescribed to whole-breast or chest wall with/without regional lymph nodes. For patients undergoing breast conservation surgery, sequential tumor bed boost was delivered with dose prescription of 12 Gy in four fractions. Treatment plans were generated using 6 MV photon beams with either static intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) technique. All patients were treated using the DIBH plan, but treatment was replanned using the FB scan with the same dose prescription and technique. Dose coverage was maintained as per ICRU (International Commission on Radiation Units and Measurements) recommendations. [18] Normal tissue doses were maintained within their documented tolerance limits as per QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines.[19]
The normal tissue constraints followed during plan approval included the following:
Hypofractionated dose (40 Gy/15 fractions)
- –
Heart – Dmean ≤ 6 Gy; V4 ≤ 40%; V20 ≤ 10%
- –
Ipsilateral lung – Dmean ≤ 12 Gy; V4 ≤ 60%; V16 ≤ 30%
- –
Contralateral lung – Dmean ≤ 3 Gy; V4 ≤ 10%
- –
Contralateral breast – Dmean ≤ 3 Gy; V10 ≤ 5%
Conventional fractionated dose (50 Gy/25 fractions)
- –
Heart – Dmean ≤ 8 Gy; V5 ≤ 40%; V25 ≤ 10 Gy
- –
Ipsilateral lung – Dmean ≤ 16 Gy; V5 ≤ 60%; V20 ≤ 30%
- –
Contralateral lung – Dmean ≤ 4 Gy; V5 ≤ 10%
- –
Contralateral breast – Dmean ≤ 4 Gy; V10 ≤ 10%
The treatment was delivered using a Varian TrueBeam Linear Accelerator. Patients undergoing post-mastectomy chest wall irradiation were treated with a 5-mm-thick bolus over the chest wall on alternate days. Before treatment delivery, patients were repositioned according to the fiducial reference points from CT simulation, and image verification with kV-CBCT (kilovoltage cone-beam computed tomography) was performed for the first three consecutive days, followed by weekly verification.
The dosimetric objectives of the study included PTV coverage and dose metrics for the liver, ipsilateral and contralateral lungs, heart, and contralateral breast. These metrics were obtained for both FB and DIBH plans and compared. Dosimetric endpoints for the heart included mean dose, maximum dose, and the percentage of volume receiving 2, 5, 10, 20, and 25 Gy, as well as the total volume of the heart included in the portal. For the ipsilateral lung, data were collected regarding the maximum point dose, mean dose, and volume receiving 5, 16, and 20 Gy. For the contralateral lung, mean and maximum point doses were recorded. Dosimetric data collected for the liver included the volume of liver, mean and maximum point doses, and the volume of liver covered by the 30 Gy, 10%, 50%, and 90% isodose curves. Mean dose and volume receiving 5 Gy for the contralateral breast were also documented and compared between the two plans.[20]
Statistical calculations included relative differences and absolute differences between DIBH and FB plans for all dosimetric endpoints, which were summarized as median and range values. Relative differences were calculated using the formula 100 × [(DIBH - FB)/FB], and absolute differences were calculated using the formula (DIBH - FB).[20] Dosimetric outcomes obtained for FB and DIBH scans were compared using the Wilcoxon signed-rank test to determine the presence of any statistically significant differences. All statistical calculations were carried out using Microsoft Excel version 2021.
The patient and tumor characteristics included in the study are summarized in Table 1. The median age of the patients analyzed in the study was 45.5 years (standard deviation [SD] =10.68), with the youngest patient being 24 years old and the oldest being 66 years old.
Distribution of Patient and Treatment Characteristics.
| CHARACTERISTICS | NUMBER | PERCENTAGE (%) | |
|---|---|---|---|
| Clinical T stage | T1 | 0 | 0 |
| T2 | 9 | 45 | |
| T3 | 6 | 30 | |
| T4 | 5 | 25 | |
| Clinical N stage | N0 | 4 | 20 |
| N1 | 5 | 25 | |
| N2 | 7 | 35 | |
| N3 | 4 | 20 | |
| Composite stage | IIA | 3 | 15 |
| IIB | 4 | 20 | |
| IIIA | 5 | 25 | |
| IIIB | 4 | 20 | |
| IIIC | 4 | 20 | |
| Type of surgery | MRM | 18 | 90 |
| BCS + ALND | 2 | 10 | |
| Presence of implant | Yes | 9 | 45 |
| No | 11 | 55 | |
| Nodal irradiation | Axillary nodes | 13 | 65 |
| IMN nodes | 5 | 25 | |
| No nodal RT | 1 | 5 | |
| Radiation dose | 50 Gy in 25# | 12 | 60 |
| 40 Gy in 15# | 8 | 40 | |
| Tumor bed boost | Yes | 2 | 10 |
| No | 18 | 90 | |
| Radiation technique | VMAT | 10 | 50 |
| IMRT | 10 | 50 |
IMRT: intensity-modulated radiotherapy, MRM: modified radical mastectomy, VMAT: volumetric modulated arc therapy, BCS: Breast conservation surgery, IMN: Internal mammary nodes, RT: radiotherapy, ALND: Axillary lymph node dissection,
radiation fractions.
Sixty-five percent (65%) of the included patients had stage III disease, while the remaining presented with stage II disease. Most of the patients (90%) had undergone modified radical mastectomy (MRM) followed by post-mastectomy chest wall irradiation. Implant-based reconstruction was performed in nine patients during MRM, while the remaining MRM patients underwent simple wound closure with or without flap-based reconstruction.
Nodal irradiation to the axillary nodes, internal mammary nodes, or both was prescribed in 16 patients (80%), while four patients were irradiated using the DIBH technique solely due to the presence of implant-based reconstruction.
The total radiation dose prescribed was 50 Gy in 25 fractions for 60% of patients, while a hypofractionated dose of 40 Gy in 15 fractions was prescribed for 40% of patients. Radiation was delivered using the VMAT technique in 10 patients and the IMRT technique in the remaining 10 patients.
In all the tables, the dosimetric endpoints are presented as median and range for DIBH plan, FB plan, and for absolute and relative differences between the two treatment methods. The dosimetric variables were compared between DIBH and FB plans using Wilcoxon signed-rank test to calculate the p-value.
Dose–volume data for target volume coverage between FB and DIBH plans are summarized in Table 2. There was no difference in plan quality between the FB and DIBH plans in terms of target volume coverage. The target volume criteria were met for both FB and DIBH plans.
Summary of Target Volume Coverage in DIBH- or FB-Based Treatment Planning.
| TARGET VOLUME COVERAGE | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| V95% (%) | Median | 97 | 97 | 0 | 0 | 0.662492922 |
| Range | 88 | 88 | −0.6 | −0.621118012 | ||
| 99 | 99 | 0.4 | 0.421052632 | |||
| V90% (%) | Median | 98.5 | 99.1 | −0.8 | −1.204819277 | 0.139625473 |
| Range | 95 | 90.4 | −1.2 | −1.210898083 | ||
| 99.9 | 99.9 | 4.6 | 5.088495575 |
DIBH: deep inspiration breath hold, FB: free breathing
A less than 1% absolute difference in mean PTV coverage was observed in terms of V95% and V90% between the two breathing patterns of irradiation. This indicated that, regardless of the treatment technique, target volume coverage did not need to be compromised to meet normal tissue constraints.
Dosimetric parameters of the heart in DIBH and FB plans are presented in Table 3. Although the cardiac volume was larger in the FB breathing pattern, with an absolute difference of 42 ml, the difference from the DIBH plan did not reach statistical significance.
Summary of Dosimetric Findings of OAR ( Organ at Risk) Heart Between DIBH and FB Techniques of Irradiation.
| HEART VARIABLES | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| Volume (ml) | Median | 520.5 | 537.95 | 18.15 | 3.18936175 | 0.622128586 |
| Range | 403.1 | 381.1 | −1076.5 | −72.75615031 | ||
| 681.7 | 1479.6 | 102.6 | 25.07331378 | |||
| Mean dose (cGy) | Median | 359.5 | 472.15 | −78.1 | −17.48974806 | 0.000218629 |
| Range | 79.7 | 97.4 | −235 | −43.63163758 | ||
| 755 | 805 | 22.4 | 17.63779528 | |||
| V2 Gy (%) | Median | 65.25 | 80.45 | −10.3 | −12.85026338 | 0.024153571 |
| Range | 17.37 | 33.1 | −34.3 | −66.00782779 | ||
| 95.7 | 100 | 4.1 | 4.475982533 | |||
| V5 Gy (%) | Median | 18.7 | 35.425 | −13.9 | −42.24616432 | 0.001596809 |
| Range | 1.2 | 6.78 | −35.5 | −86.26609442 | ||
| 63.5 | 67.7 | −2.3 | −5.793450882 | |||
| V10 Gy (%) | Median | 0.795 | 5.3 | −3.85 | −82.81993532 | 0.0001 |
| Range | 0 | 0.26 | −11.83 | −100 | ||
| 23.5 | 27.4 | 11.62 | 2472.340426 | |||
| V20 Gy (%) | Median | 0 | 0 | 0 | 0 | 0.193353996 |
| Range | 0 | 0 | −8.83 | −100 | ||
| 2.73 | 9.66 | 0.11 | 66.66666667 | |||
| V25 Gy (%) | Median | 0 | 0 | 0 | 0 | 0.088106998 |
| Range | 0 | 0 | −1.6 | −100 | ||
| 0.7 | 1.6 | 0.001 | 14.28571429 | |||
| Max dose (cGy) | Median | 1987 | 2930.3 | −796.1 | −32.19124322 | 0.000397958 |
| Range | 663.7 | 1503.5 | −1309 | −55.85633522 | ||
| 2657 | 3706 | −607.7 | −28.30545062 |
DIBH: deep inspiration breath hold, FB: free breathing
Both the mean dose and the percentage of cardiac volume covered by the 2-Gy isodose were lower with DIBH (mean absolute difference of 85.8 cGy and 12.8%, respectively) compared to FB, and this difference was statistically significant (p-value: 0.0002 and 0.02, respectively).
In addition, the percentage of cardiac volume covered by the 5-Gy and 10-Gy isodoses was significantly reduced with the DIBH technique compared to FB.
The study also found a significantly reduced cardiac Dmax in favor of the DIBH plan, with a mean absolute difference of 708.6 cGy (p-value: 0.0003).
All dose–volume parameters of the ipsilateral lung showed significant normal tissue dose sparing with the DIBH technique of irradiation, as shown in Table 4. The DIBH technique nearly doubled the lung volume, as evident in the planning scan, compared to the FB technique (1710 vs. 1024.7 ml, p-value: <0.0001).
Summary of Dosimetric Findings of OAR Ipsilateral Lung between DIBH and FB Techniques of Irradiation.
| IPSILATERAL LUNG VARIABLES | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| Volume (ml) | Median | 1807.75 | 1005.95 | 741.8 | 72.93396796 | <0.0001 |
| Range | 951.9 | 605.4 | 22.3 | 1.868610692 | ||
| 2234.1 | 1344 | 1216 | 119.4381691 | |||
| Mean dose (cGy) | Median | 1191.4 | 1415.45 | −141.85 | −8.529702109 | 0.010001072 |
| Range | 774.1 | 926.3 | −572.9 | −42.5315516 | ||
| 1587 | 1725.8 | 50 | 3.253090436 | |||
| V5 Gy (%) | Median | 57.35 | 72.85 | −11.89 | −17.91653481 | <0.0001 |
| Range | 32.5 | 49.5 | −43.4 | −49.09502262 | ||
| 82.4 | 88.4 | 4.4 | 5.641025641 | |||
| V16 Gy (%) | Median | 21.265 | 32.7 | −9.15 | −31.35642415 | 0.000397958 |
| Range | 10.3 | 13.6 | −28.2 | −68.20987654 | ||
| 36.7 | 44.7 | 4.2 | 30.88235294 | |||
| V20 Gy (%) | Median | 19.315 | 25.05 | −6.11 | −26.41222344 | 0.00111909 |
| Range | 10.1 | 6.3 | −12.67 | −49.24623116 | ||
| 29.3 | 33.1 | 6.9 | 109.5238095 | |||
| Max dose (cGy) | Median | 4012.65 | 4569.35 | −429.55 | −10.24967229 | 0.002666834 |
| Range | 2924.6 | 3980.4 | −1401.8 | −31.27482082 | ||
| 5828.4 | 6184.8 | 4 | 0.099226037 |
DIBH: deep inspiration breath hold, FB: free breathing
The dose–volume parameters of the ipsilateral lung also favored the DIBH technique. The mean dose to the ipsilateral lung decreased from 14 Gy in the FB plan to 12 Gy with DIBH (p-value: 0.01). Other dose–volume metrics, including V5 Gy, V16 Gy, and V20 Gy, all showed a significantly lower percentage of lung volume irradiated with the DIBH technique compared to FB.
The maximum dose to the ipsilateral lung in the DIBH plan differed by an average absolute value of 534.1 cGy from the FB technique, which proved statistically significant in favor of the DIBH plan.
Dosimetric outcomes for the contralateral lung and breast are summarized in Tables 5 and 6, respectively. The DIBH technique resulted in a statistically significant reduction in contralateral lung mean doses compared to the FB technique, implying a meaningful dose-sparing effect of breath hold in radiotherapy (207.9 vs. 319.3, p-value: 0.03). The maximum dose to the contralateral lung was also reduced with the DIBH technique, but the difference did not reach statistical significance.
Summary of Dosimetric Findings of OAR Contralateral Lung between DIBH And FB Techniques of Irradiation.
| CONTRALATERAL LUNG VARIABLES | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| Max dose (cGy) | Median | 1578.45 | 1773 | −202.9 | −12.39397995 | 0.061554407 |
| Range | 470.6 | 460.3 | −875.9 | −34.09763314 | ||
| 2444.2 | 2741.8 | 146.3 | 11.40655106 | |||
| Mean dose (cGy) | Median | 229.8 | 321.85 | −63.75 | −20.52377012 | 0.032927742 |
| Range | 38 | 40.4 | −882.7 | −73.3505069 | ||
| 342 | 1203.4 | 56.4 | 20.35366294 |
DIBH: deep inspiration breath hold, FB: free breathing
Summary of Dosimetric Findings of OAR Contralateral Breast Between DIBH and FB Techniques of Irradiation.
| CONTRALATERAL BREAST VARIABLES | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| Mean dose (cGy) | Median | 306.35 | 297.7 | −1.2 | −0.283243356 | 0.284999874 |
| Range | 31.9 | 26.8 | −148.6 | −49.30325149 | ||
| 448.2 | 506.6 | 89.4 | 101.6233766 | |||
| V5 Gy (%) | Median | 15.3 | 14.95 | −0.105 | −2.77459486 | 0.553793068 |
| Range | 0.25 | 0.01 | −17.4 | −68.99696049 | ||
| 32 | 36.5 | 15.9 | 2400 |
DIBH: deep inspiration breath hold, FB: free breathing
The mean dose to the contralateral breast and V5 Gy were reduced with the DIBH technique, with an average absolute difference of 12.6 cGy and 1.01%, respectively. However, the difference did not reach statistical significance (Dmean p-value: 0.28 and V5 Gy p-value: 0.55). These dose–volume metrics also favored the DIBH technique in reducing contralateral breast dose, although no statistically significant difference was found compared to the FB technique.
Us of the DIBH technique for the irradiation of the right whole-breast or chest wall resulted in a significant reduction in all hepatic dose–volume metrics, as shown in Table 7. There was a significant increase in hepatic volume with DIBH compared to FB (mean volume: 1503.8 vs. 1374.39 ml, p-value: 0.04).
Summary of Dosimetric Findings of OAR Liver Between DIBH and FB Techniques of Irradiation.
| LIVER VARIABLES | DIBH | FB | ABSOLUTE DIFFERENCE | RELATIVE DIFFERENCE | p-VALUE | |
|---|---|---|---|---|---|---|
| Volume (ml) | Median | 1462.2 | 1318.45 | 153.8 | 9.552907368 | 0.046760925 |
| Range | 1066.9 | 1000.2 | −129.3 | −5.304615385 | ||
| 2308.2 | 2437.5 | 402.8 | 31.8948452 | |||
| Mean dose (cGy) | Median | 271.65 | 783.6 | −453.5 | −62.26498393 | <0.0001 |
| Range | 54.8 | 201.6 | −875.3 | −91.38674884 | ||
| 582.7 | 1344.7 | −146.8 | −38.69565217 | |||
| Max dose (cGy) | Median | 3952.35 | 4965.2 | −917.45 | −19.42725463 | 0.001022183 |
| Range | 1081.6 | 2984.5 | −3590.7 | −72.77167525 | ||
| 5765.1 | 6217.6 | −28.3 | −0.713835288 | |||
| V30 Gy Isodose (%) | Median | 0.885 | 3.405 | −2.48 | −68.82016467 | 0.00206989 |
| Range | 0 | 0 | −8 | −100 | ||
| 4.72 | 11.4 | 0.02 | 200 | |||
| V30 Gy Isodose (ml) | Median | 16.675 | 47.515 | −31.6 | −66.86010887 | 0.002253843 |
| Range | 0 | 0 | −109.38 | −100 | ||
| 70.3 | 179.68 | 0.3 | 150 | |||
| V10% isodose (%) | Median | 15.55 | 49.35 | −31.2 | −65.46855922 | <0.0001 |
| Range | 0.01 | 4.02 | −727 | −99.75124378 | ||
| 35.4 | 755.2 | −4.01 | −31.16062521 | |||
| V10% isodose (ml) | Median | 170.45 | 578 | −357.3 | −64.1423338 | <0.0001 |
| Range | 0.25 | 71.3 | −1180.5 | −99.64936886 | ||
| 575.1 | 1280.16 | 230.1 | 305.1724138 | |||
| V50% isodose (ml) | Median | 31.7 | 114.945 | −63.115 | −72.51538516 | <0.0001 |
| Range | 0 | 9.7 | −242.4 | −100 | ||
| 120 | 306.3 | 8.08 | 83.29896907 | |||
| V90% isodose (%) | Median | 0.045 | 0.625 | −0.285 | −89.94968553 | 0.000740489 |
| Range | 0 | 0 | −4.02 | −100 | ||
| 0.97 | 4.5 | 0 | 0 | |||
| V90% isodose (ml) | Median | 0.6 | 7.955 | −3.9955 | −89.38940265 | 0.000775787 |
| Range | 0 | 0 | −42.27 | −100 | ||
| 11.3 | 48.5 | 0 | 0 |
DIBH: deep inspiration breath hold, FB: free breathing
The mean hepatic dose was significantly reduced with the use of DIBH (3.8 vs. 7.9 Gy, p-value: 0.0001), as was Dmax, when compared to the FB technique (36.7 vs. 46.3 Gy, p-value: 0.001). The volume of liver receiving 30 Gy, as well as the volume irradiated by the 50% and 90% isodoses, also showed a significant reduction with DIBH, with a relative difference of more than 50% in all dose–volume coverages compared to the FB technique.
Besides the high-dose volume, DIBH also resulted in a significantly lower volume of the liver irradiated by the 10% isodose, with a relative difference of 68% (16.6% vs. 79.8%, p-value: 0.0001) from the low-dose coverage of the FB plan.
Thus, this study demonstrated that the use of DIBH for right-sided breast or chest wall irradiation led to a significant reduction in both high- and low-dose volumes compared to the FB technique of irradiation.
This study presented the dosimetric outcomes of DIBH in adjuvant radiotherapy for right-sided breast carcinoma patients by comparing the dose–volume metrics of the technique with that of the FB technique. The observations showed significant improvements in all dosimetric endpoints, suggesting the dose-sparing efficacy of DIBH for the lungs, heart, and liver during irradiation of right-sided breast carcinoma.
However, this study included patients undergoing both right-sided whole-breast irradiation and right-sided chest wall irradiation. Mader et al.[20] and Pandeli et al.[21] included only patients undergoing localized right-sided breast radiotherapy post-lumpectomy. In contrast, Haji et al.[22] included patients undergoing post-mastectomy chest wall radiotherapy for right-sided breast carcinoma in their analysis.
In this study, radiotherapy was delivered using VMAT for 10 patients, while the remaining 10 patients received treatment via static field IMRT. Borgonovo et al.[15] also used both VMAT and IMRT plans, with five patients in each group, while Mader et al.[20] and Dumane et al.[8] used only VMAT plans with DIBH for radiotherapy. Three-dimensional conformal radiotherapy with tangential beams was the radiotherapy planning technique used in the studies conducted by Pandeli et al.[21]
In the present study, both the mean dose and the percentage volume covered by the 2-Gy isodose were lower with DIBH (mean absolute difference of 85.8 cGy and 12.8%, respectively) compared to FB, reaching statistical significance (p-value: 0.0002 and 0.02, respectively). In addition, the percentage volume of the heart covered by 5 Gy and 10 Gy isodoses was significantly reduced with the DIBH technique compared to FB. Furthermore, there was a significantly reduced cardiac Dmax in favor of the DIBH plan, with a mean absolute difference of 708.6 cGy (p-value: 0.0003).
Borgonovo et al.[15] reported a 2.2 Gy reduction in heart Dmean with the DIBH technique compared to FB, along with a 25.2% reduction in V5 Gy and a significant reduction in heart Dmax, favoring DIBH. Similarly, Mader et al.[20] observed a statistically significant reduction in cardiac Dmax with DIBH compared to the FB plan.
All dose–volume parameters of the ipsilateral lung demonstrated significant normal tissue dose sparing with the DIBH technique. While DIBH nearly doubled the lung volume compared to FB, the dose–volume parameters of the ipsilateral lung still favored DIBH. The mean dose to the ipsilateral lung decreased from 14 Gy in the FB plan to 12 Gy with DIBH (p-value: 0.01). Other dose–volume metrics such as V5 Gy, V16 Gy, and V20 Gy showed significantly lower percentages of irradiated volume when using the DIBH technique compared to FB. The maximum dose to the ipsilateral lung in the DIBH plan differed by an average absolute value of 534.1 cGy from the FB technique, proving statistical significance in favor of the DIBH plan.
Mader et al.[20] documented a significant reduction in ipsilateral lung mean dose and V20 Gy with the DIBH technique, despite the significantly increased lung volume when irradiated using DIBH. Borgonovo et al.[15] also reported a reduction in ipsilateral lung mean dose and V20 Gy with DIBH, along with an increase in lung volume compared to FB, though the difference was not statistically significant. In addition, Haji et al.[22] reported a significant reduction in ipsilateral lung mean dose, V20 Gy, and V30 Gy, along with a significant increase in lung volume when using DIBH for right chest wall radiotherapy. Pandeli et al.[21] also observed significant ipsilateral lung dose sparing with DIBH, as evidenced by a significantly reduced ipsilateral lung mean dose, V5 Gy, and V20 Gy compared to FB in patients undergoing right-sided breast radiotherapy with or without regional lymph node irradiation.
Using the DIBH technique for irradiation of the right whole breast or chest wall resulted in a significant reduction in all hepatic dose–volume metrics. There was a significant increase in hepatic volume with DIBH compared to FB (mean volume: 1503.8 vs. 1374.39 ml, p-value: 0.04). The mean hepatic dose was significantly reduced with DIBH (3.8 vs. 7.9 Gy, p-value: 0.0001), as was Dmax (36.7 vs. 46.3 Gy, p-value: 0.001). The volume of the liver receiving 30 Gy and the volume irradiated by the 50% and 90% isodoses also showed significant reductions with DIBH, with a relative difference of more than 50% in all dose–volume coverages compared to FB.
In addition, DIBH significantly reduced the volume of the liver irradiated by the 10% isodose, with a relative difference of 68% (16.6% vs. 79.8%, p-value: 0.0001) compared to the low-dose coverage of the FB plan. Thus, this study demonstrated that the use of DIBH for right-sided breast or chest wall irradiation led to a significant reduction in both high- and low-dose volumes compared to the FB technique.
In the study conducted by Haji et al.,[22] the DIBH technique for right chest wall irradiation resulted in a significant reduction in liver mean dose, liver V20 Gy, and liver V10 Gy compared to the FB technique. In another study by Pandeli et al.,[21] evaluating dosimetric outcomes of DIBH in adjuvant irradiation of the intact right breast, statistically significant reductions were observed in liver V20 Gy and maximum liver dose compared to FB, with the greatest reduction seen in patients receiving whole-breast plus regional lymph node irradiation. Mader et al.[20] found that DIBH significantly reduced hepatic mean and maximum doses as well as the low-dose volume of the liver covered by the 10% isodose level, further establishing the beneficial organ-sparing effects of DIBH compared to FB.
The DIBH technique resulted in a statistically significant reduction in contralateral lung mean doses compared to FB (p-value: 0.03), implying a meaningful dose-sparing effect of breath-hold radiotherapy. The contralateral lung maximum dose was also reduced by DIBH, though the difference did not reach statistical significance (p-value: 0.06). Contralateral breast mean dose and V5 Gy were lower with DIBH, with an average absolute difference of 12.6 cGy and 1.01%, respectively.
This study thus demonstrated significant normal tissue sparing with the addition of DIBH in adjuvant radiotherapy for right-sided breast carcinoma, as evident by the reduction in high- and low-dose volumes for the ipsilateral lung, heart, and liver. However, this study included a small cohort of patients, making it difficult to predict whether these dosimetric findings would ultimately translate into significant clinical benefits. Nevertheless, in terms of dosimetric parameters, the DIBH technique in right-sided breast cancer radiotherapy demonstrated a clear advantage. Therefore, DIBH should be incorporated into right breast carcinoma radiotherapy where available to help reduce potential late normal tissue toxicities in breast carcinoma patients.