|Ahead of print publication
Dosimetric impact of different multileaf collimators on cardiac and left anterior descending coronary artery dose reduction
Leili Mahani1, Arezoo Kazemzadeh1, Mohsen Saeb2, Mahsa Kianinia3, Ali Akhavan3
1 Seyed-Al-Shohada Hospital, Isfahan University of Medical Science, Isfahan, Iran
2 Seyed-Al-Shohada Hospital, Isfahan University of Medical Science; Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences; Department of Radio-Oncology, Seyed-Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
3 Seyed-Al-Shohada Hospital, Isfahan University of Medical Science; Department of Radio-Oncology, Seyed-Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||25-Apr-2021|
|Date of Decision||13-May-2021|
|Date of Acceptance||03-Jun-2021|
|Date of Web Publication||25-Apr-2022|
Department of Radio-Oncology, Seyed-Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Introduction: Radiotherapy (RT) may increase the dose of heart structure like left anterior descending coronary artery (LAD). The purpose of this paper was to evaluate the impact of various multileaf collimators (MLCs) in shielding organ at risks (OARs), especially LAD, of patients with left breast cancer.
Materials and Methods: Forty-five patients with left breast cancer were selected. The treatment plans were created applying three techniques for all patients. In the first plan (uncovered LAD), the treatment plan was made without considering LAD as OARs. In the two other plans, two MLCs with different leaf widths (6.8 mm and 5 mm) were used to shield the LAD. For all plans, MLC was shielded as much of OAR as possible without compromising planning target volume (PTV) coverage. Dosimetric parameters of the heart, LAD, and ipsilateral lung were assessed.
Results: Compared to other plans, the covered LAD plan 1(CL1) obtained lower lung, cardiac, and LAD doses with the same PTV coverage. On average, the mean heart dose decreased from 6.2 Gy to 5.4 Gy by CL1, and the average mean dose to the LAD was reduced from 36.4 Gy to 33.7 Gy, which was statistically significant. The average lung volume receiving >20 Gy was significantly reduced from 24.6% to 23.4%. Moreover, the results show that covered LAD plan 2(CL2) is less useful for shielding OARs compared to CL1.
Conclusion: CL1 plans may reduce OAR dose for patients without compromising the target coverage. Hence, the proper implementation of MLC can decrease the side effects of RT.
Keywords: Left anterior descending coronary artery, left breast cancer, multileaf collimator, organs at risk, radiotherapy
|How to cite this URL:|
Mahani L, Kazemzadeh A, Saeb M, Kianinia M, Akhavan A. Dosimetric impact of different multileaf collimators on cardiac and left anterior descending coronary artery dose reduction. J Can Res Ther [Epub ahead of print] [cited 2022 Nov 29]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=343922
| > Introduction|| |
After breast-conserving surgery (BCS) or mastectomy, adjuvant radiotherapy (RT) is one of the standard treatments for early-stage breast cancer. RT significantly decreases the rate of local recurrence and increases overall survival.
However, due to incidental radiation exposure to the heart for left-sided breast patients, RT has been associated with an increased risk of heart complications.,
A long-term follow-up suggested that the death related to heart disease increases by 30%. Darby et al. reported that breast cancer patients treated with radiation have higher mortality from cardiac disease than other women.
The dose distribution in the heart is not homogeneous, and the anterior heart is supposed to a higher dose. It was reported that left anterior descending coronary artery (LAD) has the highest mean dose of cardiac substructures in left-sided breast patients. Wennstig et al. suggested that the LAD dose should be minimized in breast RT to reduce cardiac side effects. However, the LAD is not routinely contoured in left breast RT because it is time-consuming and unnecessary for all examinations.
It is essential to reduce the late side effects as much as possible. Different techniques have been developed to reduce the dose of the heart structures, such as intensity-modulated RT (IMRT), positioning of the patient in the prone position, or treatment in deep inspiration like the use of breath-hold and gating techniques.
Deep inspiration breath-hold (DIBH) during left breast radiation therapy treatments are proposed to decrease the heart's exposure.,,, For example, in the RT of left-sided breast, Lee et al. reported a reduction in mean heart dose (MHD) from 4.53 Gy for free breathing (FB) to 2.52 Gy for breath-hold and LAD dose from 26.26 to 16.01 Gy for FB and DIBH, respectively. Moreover, Joo et al. reported a reduction in the MHD from 7.24 Gy (forward-planned IMRT) to 2.79 Gy in breath-hold. Furthermore, they found that the probability of coronary events was decreased with the DIBH technique.
However, in some countries with limited facilities, the other approaches are more useful. Beam angle modulation or shielding the heart structures by multileaf collimators (MLCs) is another way to minimizing the heart and LAD doses.,
Among the mentioned methods, the LAD shielding techniques that applied MLC have been the best RT technique in most RT departments for breast cancer.
The purpose of this study was to develop an optimal treatment plan by using the MLC shielding technique for LAD to minimize the risk of cardiac and LAD artery irradiation for patients with left-sided breast cancer. Two different kinds of MLCs were used: TiGRT DMLC (51 pairs), LinaTech Co., and Siemens ONCOR 41 pairs. Then, different dosimetry parameters of target and organ at risks (OARs) were investigated.
| > Materials and Methods|| |
Forty-five consecutive patients with left-sided breast cancer who underwent adjuvant RT between 2019 and 2020 were identified. Patients were treated using 6 MV photons with a prescription dose of 50 Gy in 25 fractions over 5 weeks.
At the time of surgery, the titanium clips were inserted into the tumor bed for most patients who underwent BCS.
All patients were scanned in the supine position and were lied on a breast board, and the arms were extended above the head. Computed tomography (CT) data of thorax were obtained without contrast in FB and with 0.5-cm slice intervals. To locate the scars on CT images, the radiopaque wires were placed.
Target and organ at risk delineation
The planning target volume (PTV) was the clinical target volume (CTV) with a 5-mm margin up to the midline and cropped 5 mm under the skin surface. The radiation oncologist has contoured the CTV of the whole breast on the CT scans following the Radiation Therapy Oncology Group atlas and development and validation of a heart atlas. Organs at risk, such as the heart, LAD, contralateral breast, humorous, left lung, and spinal cord, were also contoured by the radiation oncologist.
For each patient, three treatment plans were created. The uncovered LAD plan (UCL) and two other plans with different MLC types (covered LAD plans) with as much as possible MLC shielding to further coverage of the LAD. To create the uncovered LAD plan, two tangential fields were applied, and the angles of the fields are considered to maximize the dose coverage of PTV while minimizing the dose to the lung and heart [Figure 1]. A 0.5-cm margin of MLC field shaping on PTV was used. For optimizing dosimetry and making the best dose coverage of PTV, appropriate wedges and beam weightings were used.
|Figure 1: Beam's eye view demonstrating the left breast plan without considering the left anterior descending coronary artery|
Click here to view
To create the covered LAD plan1 (CL1), another plan was defined to access more coverage of LAD with MLC compared to the uncovered plan [Figure 2].
|Figure 2: Beam's eye view demonstrating shielding of the left anterior descending coronary artery (light blue) with TiGRT DMLC (51 pairs) from the tangential field|
Click here to view
In the third plan, the type of MLC in CL1 changed from TiGRT DMLC (51 pairs), LinaTech Co., to Siemens ONCOR 41 pairs and named as covered LAD plan 2(CL2) to investigate the impact of MLC dimension on organ dose [Figure 3]. The third plan is similar to the second one, but only the MLC type was changed from TiGRT DMLC to Siemens.
|Figure 3: Beam's eye view demonstrating shielding of the left anterior descending coronary artery (light blue) with Siemens ONCOR (41 pairs) from the tangential field|
Click here to view
A comparison of the dosimetric values was performed between all plans. From the DVHs, comparisons were performed for the following parameters including organs at risk and target. The percentage of the maximum dose (Dmax %) and mean dose (Dmean %) of OARs (heart and LAD and left lung) and target (PTV) was calculated. For this analysis, an ideal plan was considered to be such a plan that at least 95% of the PTV received 95% of the prescribed dose.
For PTV comparison of different plans, the homogeneity index (HI) and conformity index (CI) were analyzed. The following equations defined the CI and HI:
V47.5 Gy represents the volume receiving 47.5 Gy and D2%, D50%, and D98% clarify the doses of 2%, 50%, and 98% volume of the target volume.
Data are presented as mean ± standard error of the mean. Statistical analyses were performed using GraphPad Prism software (GraphPad Software, CA, USA). The normal distribution of data was evaluated using the Kolmogorov–Smirnov normality test. ANOVA test was used to establish comparisons between groups. Statistical significance was defined as P < 0.05.
| > Results|| |
A typical example of the DVHs for various plans obtained for PTV and OAR was demonstrated for one patient [Figure 4]. Thirty-five (78%) patients underwent BCS and 10 (22%) underwent mastectomy.
|Figure 4: Dose–volume histograms are comparing UCL plan (-) (a) and CL1 (-.-) (b) and CL2 (-×-) (c) plans for the same patient. PTV line in red and left anterior descending coronary artery in light blue|
Click here to view
[Table 1] shows the PTV-related variables and dosimetric parameters, including CI, HI, mean dose, and the target volume isodose coverage V95%. All plans fulfilled the planning criterion on PTV coverage, V95%, CI, and HI. There was a small difference between mean doses in all plans, but statistically significant differences were not observed. Moreover, there were no significant differences in PTV coverage as measured by the V95% among the three different plans.
|Table 1: Dosimetric comparison between different plans for all 45 patients|
Click here to view
The homogeneity and CI of the UCL plans were not significantly better than the other two plans. HI for CL1, CL2, and UCL was 0.15, 0.16, and 0.16, respectively. Moreover, the same trend was observed for CI (0.35, 0.34, and 0.37, respectively).
[Table 2] provides the numerical findings from the DVH analysis of the LAD. Significant differences were observed between the dosimetric parameters of LAD. The values of V5, V10, V25, and V30 were lower for CL1 plans compared to the others, but it was significant for V10, V25, and V30 (P < 0.05). Nevertheless, the differences between CL2 and UCL were not statistically significant except for V5 (92.97 vs. 90.32 [P = 0.02]). The Dmean parameter was 33.71, 35.11, and 36.47 Gy for CL1, CL2, and UCL, respectively, which was statistically significant between only CL1 and UCL (P < 0.05).
The comparisons of the heart parameters are summarized in [Table 3]. It shows significant differences for almost all factors. The obtained result showed a notable reduction in V5, V20, V25, and Dmean for CL1 plan compared to CL2 and UCL plan. However, there was no important variation between CL2 and UCL.
|Table 2: Comparison of dosimetric parameters of the left anterior descending coronary artery between plans|
Click here to view
The Dmax, Dmean, V5, and V20 of the left lung are tabulated in [Table 4]. The mean dose to the ipsilateral lung was lowest with CL1 compared to CL2 and UCL, which was meaningful (P < 0.0001). However, there was no beneficial reduction in the lung's mean dose when applying CL2 for shielding LAD compared to UCL (13.7 vs. 13.1 Gy, respectively). Moreover, the differences between V5 and V20 Gy for all groups were significant. The CL1 plans reduced these parameters compared to UCL.
| > Discussion|| |
The risk of the RT's late heart toxicity may affect the survival of left breast cancer patients as a portion of heart tissue includes tangential fields.
Several kinds of research have reported increases in heart dose due to RT of left breast cancer patients.
Several studies demonstrated that MHD correlates with cardiac deaths and coronary disease.
The cardiac toxicity induced by radiation depends on the dose and volume of cardiac exposure.
Darby et al. reported an increased risk of heart diseases by 7.4% for each gray (Gy) MHD. Likewise, examining studies during 10 years conclude an overall MHD of 5.4 Gy among all left-sided breast cancer patients. Another study showed that 5 years after irradiation of the breast, the increased risk of cardiac abnormalities was started and continued for at least 20 years.
There has not been any specific threshold for heart dose until now. Due to the absence of an apparent threshold dose for cardiac complications, all patients can benefit from reducing heart doses in breast RT.
So far, various techniques like DIBH have been proposed to reduce heart dose. It has been reported that the performance of DIBH techniques leads to decreased cardiac dose by 1.5–3 Gy reduction in the mean dose of heart and mean and max dose of LAD.,
Nevertheless, the DIBH technique is not achievable for all patients because it strongly depends on the patient's ability to breath-holding. This technique employs specific equipment and therefore imposes cost and more overall planning and treatment time for a RT department which is not possible in all of them.
Therefore, to reduce the side effects of left breast radiation therapy on the heart, it is beneficial to implement an economical and appropriate technique.
Our department decided to investigate the level of protection of the heart and its sensitive structures, such as the LAD, using different types of MLC shielding.
A MHD of 5.5–7 Gy was reported for different plans in left-sided breast irradiation in the current study. A statistically significant reduction in the mean dose of heart, mean dose of LAD, and max dose of LAD was observed with the implementation of the LAD shielding technique [Table 3].
The primary objective of the current study was reducing the LAD and cardiac radiation dose to decrease the risk of heart failure. According to Derby et al. with decrease of each 1 Gy in the mean heart radiation dose, the rate of major coronary events decreased by 7.4%. A reduction of >1 Gy in the mean dose of heart and approximately 3 Gy reduction in mean LAD dose were obtained using this technique [Table 2] and [Table 3].
The current study is another effort to investigate whether the use of shielding resulted in an additional decrease of the cardiac and LAD dose.
This study demonstrates that shielding of the heart and LAD by MLC can be a good alternative method to provide a homogeneous dose distribution. Also, it could protect the cardiac structures in some departments like ours, which DIBH technique is not achievable.
Lawler and Leech reported a reduction in mean of heart and LAD dose to 0.5 Gy and 6 Gy, respectively, using DIBH, which is comparable to our LAD shielding technique giving 0.8 Gy and 3 Gy, respectively.
However, implementation of the LAD-sparing technique may reduce the 95% isodose coverage of PTV of the breast, but it was preferable in our department to prescribe almost 95% of the dose for PTV breast to prevent recurrence of the tumor and try to decrease the dose of LAD as low as possible.
With shielding technique by MLC, we found a statistically significant reduction in all dose-volume parameters specified for the heart, with maximal sparing of LAD among two plans (CL1 and CL2) between all plans.
These results are in agreement with the data of this current study which showed about 0.8 Gy reduction in MHD and a reduction of 2.76 Gy for mean LAD dose for CL1 plan compared with UCL plan. Our results showed no significant advantage for decreasing heart dose in the case of CL2 plans. Moreover, the mean LAD dose decreased just about 1.4 Gy in CL2 plans.
As can be seen in the results in CL1, because of the smaller dimension of MLC, the LAD has been better covered, and in a similar trend, the dose to the heart and ipsilateral lung also decreased. However, the second plan (CL2) was not very suitable for covering LAD and other OARs due to its larger dimension of leaves.
As mentioned above, in our department, 95% of isodose covered PTV, but in other studies and considering the policy of each hospital, it is possible to compromise between the dose of target and LAD. This approach will reduce the dose of LAD as much as possible. Hence, the reduction in OARs dose was more evident in comparison to our results.
| > Conclusion|| |
This planning study showed that using suitable MLC for left-sided breast cancer patients allows a significant reduction in heart dose, LAD dose, and left lung dose while maintaining target coverage. This study suggests that MLC shielding may be used as an alternative way to protect OARs in the RT of left-sided breast cancer patients where it is impossible to apply the DIBH technique.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al
. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet (London, England) 2011;378:1707-16.
Sardaro A, Petruzzelli MF, D'Errico MP, Grimaldi L, Pili G, Portaluri M. Radiation-induced cardiac damage in early left breast cancer patients: Risk factors, biological mechanisms, radiobiology, and dosimetric constraints. Radiother Oncol 2012;103:133-42.
McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson NO, Bennet AM, et al
. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol 2011;100:167-75.
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.
Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al.
Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013;368:987-98.
Gocer GP, Ozer EE. Effect of radiotherapy on coronary arteries and heart in breast-conserving surgery: A dosimetric analysis. Radiol Oncol 2020;54:128-34.
Wennstig AK, Garmo H, Isacsson U, Gagliardi G, Rintelä N, Lagerqvist B, et al.
The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol 2019;14:40.
Lee HY, Chang JS, Lee IJ, Park K, Kim YB, Suh CO, et al.
The deep inspiration breath hold technique using Abches reduces cardiac dose in patients undergoing left-sided breast irradiation. Radiat Oncol J 2013;31:239-46.
Sakka M, Kunzelmann L, Metzger M, Grabenbauer GG. Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation: Is IMRT more beneficial than VMAT? Strahlenther Onkol 2017;193:800-11.
Joo JH, Kim SS, Ahn SD, Kwak J, Jeong C, Ahn SH, et al.
Cardiac dose reduction during tangential breast irradiation using deep inspiration breath hold: A dose comparison study based on deformable image registration. Radiat Oncol (London, England) 2015;10:264.
Lastrucci L, Borghesi S, Bertocci S, Gasperi C, Rampini A, Buonfrate G, et al.
Advantage of deep inspiration breath hold in left-sided breast cancer patients treated with 3D conformal radiotherapy. Tumori 2017;103:72-5.
Bartlett FR, Yarnold JR, Donovan EM, Evans PM, Locke I, Kirby AM. Multileaf collimation cardiac shielding in breast radiotherapy: Cardiac doses are reduced, but at what cost? Clin Oncol (R Coll Radiol) 2013;25:690-6.
Welsh B, Chao M, Foroudi F. Reducing cardiac doses: A novel multi-leaf collimator modification technique to reduce left anterior descending coronary artery dose in patients with left-sided breast cancer. J Med Radiat Sci 2017;64:114-9.
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.
Aiello D, Borzì GR, Marino L, Umina V, Di Grazia AM. Comparison of deep inspiration breath hold and free breathing technique in left breast cancer irradiation: A dosimetric evaluation in 40 patients. J Radiat Oncol 2019;8:89-96.
Sripathi LK, Ahlawat P, Simson DK, Khadanga CR, Kamarsu L, Surana SK, et al.
Cardiac dose reduction with deep-inspiratory breath hold technique of radiotherapy for left-sided breast cancer. J Med Phys 2017;42:123-7.
] [Full text]
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.
Mast ME, van Kempen-Harteveld L, Heijenbrok MW, Kalidien Y, Rozema H, Jansen WP, et al.
Left-sided breast cancer radiotherapy with and without breath-hold: Does IMRT reduce the cardiac dose even further? Radiother Oncol 2013;108:248-53.
Pedersen AN, Korreman S, Nyström H, Specht L. Breathing adapted radiotherapy of breast cancer: Reduction of cardiac and pulmonary doses using voluntary inspiration breath-hold. Radiother Oncol 2004;72:53-60.
Lawler G, Leech M. Dose sparing potential of deep inspiration breath-hold technique for left breast cancer radiotherapy organs-at-risk. Anticancer Res 2017;37:883-90.Tate nonsentem int
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]