|Year : 2017 | Volume
| Issue : 1 | Page : 56-61
A dosimetric analysis of cardiac dose with or without active breath coordinator moderate deep inspiratory breath hold in left sided breast cancer radiotherapy
Beena Kunheri1, Sanketh Kotne1, Sneha S Nair2, Dinesh Makuny1
1 Department of Radiotherapy, Amrita School of Medicine, Amrita Viswa Vidyapeetham University, Ernakulam, Kerala, India
2 Department of Medical Physics, Amrita School of Medicine, Amrita Viswa Vidyapeetham University, Ernakulam, Kerala, India
|Date of Web Publication||16-May-2017|
Amrita School of Medicine, Amrita Vishwa Vidyapeetham, Ernakulam, Kerala
Source of Support: None, Conflict of Interest: None
Background and Aim: Cardiac toxicity is a major concern for left breast tangential field irradiation. The left ventricle and left anterior descending (LAD) artery are suggested to be radiosensitive and radiation to these structures leads to late lethal cardiotoxicity. Moderate deep inspiration breath hold (mDIBH) during radiation treatment delivery helps in reducing the cardiac dose. This study compares dosimetric parameters of heart with and without active breath coordinator (ABC) mDIBH during tangential field breast cancer radiation.
Study Type: This is a dosimetric comparative study.
Materials and Methods: Forty-five consecutive patients with left-sided breast cancer who underwent breast-conserving surgery and adjuvant tangential field and radiotherapy with ABC mDIBH between November 2013 and September 2015 in our center were analyzed in this study. The ABC device was used for respiratory control and patients who could hold their breath for 20–30 s were considered for radiation with ABC mDIBH. Simulation scans of both free breathing (FB) and ABC mDIBH were done. Tangent field treatment plans with a dose prescription of 40 Gy/15 Fr were generated for each patient, in both scans. Target coverage, dose to the heart, LAD, and the left lung were documented with dose-volume histograms.
Results: Statistical Package for the Social Sciences, version 20 software, was used for analysis and the level of significance was set at P < 0.05. Mean heart dose was 308.5cGy with FB and 159cGy with ABC (P < 0.0001). Mean dose to the LAD was reduced by 53.81% (1320.64 cGy vs. 606.56 cGy, P < 0.001). Target coverage was equal in both the plans.
Conclusion: We report that the use of ABC mDIBH technique resulted in a significant reduction in cardiac dose and hence can be considered as a promising tool for cardiac sparing.
Keywords: ABC moderate deep inspiration breath hold, cardiac dose, radiotherapy, tangent field
|How to cite this article:|
Kunheri B, Kotne S, Nair SS, Makuny D. A dosimetric analysis of cardiac dose with or without active breath coordinator moderate deep inspiratory breath hold in left sided breast cancer radiotherapy. J Can Res Ther 2017;13:56-61
|How to cite this URL:|
Kunheri B, Kotne S, Nair SS, Makuny D. A dosimetric analysis of cardiac dose with or without active breath coordinator moderate deep inspiratory breath hold in left sided breast cancer radiotherapy. J Can Res Ther [serial online] 2017 [cited 2019 Nov 20];13:56-61. Available from: http://www.cancerjournal.net/text.asp?2017/13/1/56/206237
| > Introduction|| |
Breast cancer comprises the most common type of cancer in females worldwide. Radiation therapy (RT) is an integral part of breast cancer management after breast conservation surgery (BCS) and after mastectomy if risk factors are present. According to the most recent Early Breast Cancer Trialists' Collaborative Group meta-analyses, adjuvant RT after BCS reduces the rate of breast cancer mortality compared to surgery alone. However, as the survival improves for breast cancer patients, the long-term morbidity of RT becomes a concern. Comprehensive RT for breast cancer targets the breast, chest wall, and lymph nodes when indicated. The proximity of these targets to critical structures can cause radiation-induced toxicity. The common late side effects of RT include fibrosis, telangiectasia, pigmentation of skin, and lymphedema. Rare but serious problems are cardiac and lung morbidity. Many studies had shown increased cardiac mortality and morbidity after breast radiotherapy and any dose to heart is significant.,,,,,,,
Left-sided breast radiotherapy is associated with increased risk of coronary artery disease.,, The dose distribution in the heart is not homogeneous and the highest doses are likely to be delivered to the anterior heart, especially left anterior descending (LAD) artery, which is one of the typical sites of origin for ischemic heart disease. The dose to the LAD which is suggested to be radiosensitive may play a role in lethal cardiotoxicity.,, RT-related cardiotoxicity may be affected by several factors including volume of heart within radiation field, dose, fraction size, LAD, and left ventricular doses.,,,, Moreover, cardiotoxicity of RT in breast cancer patients may further be enhanced by the use of some chemotherapeutic agents such as anthracyclines. Cardiac dose-volume parameters should be thoroughly optimized in breast cancer RT to avoid potential cardiac toxicities of treatment.
Improvements in techniques of RT have helped decrease cardiac doses over the years. Besides 3D-based planning and intensity modulation, nowadays, respiratory management strategies are also being used to reduce cardiac dose in breast cancer RT. Active breath coordinator (ABC) system, first developed by Wong et al., offers an effective respiratory management strategy which can be used to improve cardiac sparing in breast cancer RT with the advantages of separating heart and target by changing the internal anatomy with moderate deep inspiration breath hold (mDIBH). The benefit with different techniques largely depends on the individual patient anatomy.
To analyze the proposed benefit with mDIBH, in our population, we have compared the dosimetric parameters with and without using ABC-mDIBH technique in left-sided breast cancer tangential irradiation.
| > Materials and Methods|| |
From December 2013 to August 2015, 45 consecutive patients with left-sided breast cancer after BCS or breast reconstruction who underwent tangential RT with ABC-mDIBH technique were included in this analysis. Inclusion criteria included age ≤65 years, Eastern Cooperative Oncology Group performance score 0–1, no previous RT to the breast, no history of any cardiac and lung disease, and patients with a comfortable breath hold duration of 20–25 s.
Radiation treatment workflow
Pretreatment patient education
All the patients were explained regarding ABC mDIBH procedure. Before simulation computed tomography (CT) scan, all patients were given training for 3 days with the ABC (Elekta) device to enhance patient compliance and to determine individual (mDIBH) levels, which was set at 75% of maximum inspiratory capacity.
Simulation and treatment planning
All patients were simulated in supine position with both arms above head, using a breast board. Palpable breast tissue and visible surgical scar were marked with radiopaque wires. After acquiring a steady breathing pattern, two sets of CT images were acquired for each patient with a slice thickness of 2.5 mm, one with mDIBH with ABC system and the other with free breathing (FB). Threshold for breath holding and breath hold duration were documented.
The gross tumor volume, clinical target volume (CTV), and organ at risk were delineated on the Monaco contouring station on both the scans as per the Radiation Therapy Oncology Group breast contouring guidelines for breast cancer. Treatment Planning was done using XiO Planning system [Figure 1] and [Figure 2]. To improve consistency, the same physician performed all contouring procedures and the same physicist performed the treatment planning procedures. All patients were planned to receive a whole breast dose of 40 Gy in 15 fractions as in START B protocol  using 6 MV photons.
|Figure 1: Radiation plan in ABC moderate deep inspiration breath hold scan|
Click here to view
Total lung volume (TLV), total cardiac volume, and maximum heart distance (MHD) were all documented in both scans for each patient. Dose-volume histograms (DVHs) were generated for all delineated structures in both plans. For the heart, mean dose (Dmean), maximum dose (Dmax), and percentage volumes receiving doses ≥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) were recorded. MHD is defined as the maximum perpendicular distance from the posterior border of the tangential field to the cardiac border. For the ipsilateral lung, Dmean, Dmax, and percentage volumes receiving doses ≥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) were recorded. For the LAD, Dmean and Dmax were recorded, and for the breast, D90%, D95%, Dmean, and Dmax were recorded. V20, mean lung dose (MLD), and TLV were calculated for both right and left lungs.
The Kolmogorov–Smirnov test was used to detect whether the variables were normally distributed or not. After the assessment of all variables for normal distribution, variables with normal distribution were analyzed using paired t-test while variables with nonnormal distributions were analyzed using Wilcoxon signed-rank test. In descriptive statistics, mean and standard deviation was used for normally distributed variables which were analyzed using the paired t-test. Statistical Package for the Social Sciences, version 20 software (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corporation), was used for analysis and the level of significance was set at P< 0.05.
This study was approved by the Institutional Review Board. All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or the National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This is only a dosimetric comparison with no intervention in the actual treatment delivered, and patient identity was not revealed.
| > Results|| |
All the 45 patients' data with ninety CT scans were analyzed. The median age was 45.2 years (29–62 years). Nine patients had Stage I (20%), 24 patients had Stage IIA (53.3%), eight patients had Stage IIB (17.8%), and four patients had Stage IIIA (8.9%) disease.
The mean threshold for breath holding was 1.33 L. The mean breath hold duration was 24.28 s. CT scans using mDIBH showed a significant larger TLV. The mean increase in the TLV was 73.98%. Smaller MHD was observed in mDIBH scan when compared with scans performed in FB. The mean MHD in FB and mDIBH scans was 2.37 cm and 1.3 cm, respectively.
The dose-volume parameters of the heart, LAD, left lung, both lungs, and CTV volume were compared for each patient using DVH generated for FB and mDIBH scans as shown in [Table 1],[Table 2],[Table 3]. The mDIBH with ABC technique significantly reduced Dmean and Dmax heart dose compared to FB. There was also a significant reduction in all the heart dose-volume parameters.
|Table 3: Dose-volume parameters of both lungs, left anterior descending, and breast|
Click here to view
The average mean heart dose (Dmean) was reduced from 308.5 cGy (with FB) to 159 cGy (with ABC) (P < 0.0001). The relative reduction in average mean heart dose was 45.3%. The average relative reduction in average Dmax heart dose was 12.94%. The corresponding relative reductions in the average maximum and mean doses to LAD were 37.3% and 53.81%, respectively.
The MLD with mDIBH was 608.75 cGy and with FB was 646.08 cGy which showed a nonsignificant reduction of 1.53%. The difference in the lung dose-volume parameters was not significant. There was no significant difference in the breast CTV target dose parameters in both plans.
| > Discussion|| |
Late cardiac morbidity is a serious concern for left-sided breast cancer patients who receive tangential RT, especially in the younger age group. Hence, integration of respiratory motion management to reduce the cardiac dose has been widely studied in the past few years. Delivering treatment to left breast using ABC technique has been shown to reduce dose to both heart and LAD artery.
Lu et al. had shown that mDIBH could reduce the volume of heart by increasing the intrathoracic pressure, thereby increasing the distance between the heart and chest wall.
Vikström et al. in their study with 17 patients had shown that respiratory gating with deep inspiration breath hold (DIBH) significantly reduces cardiac and pulmonary doses for tangentially treated left-sided breast cancer patients. The mean heart dose was reduced from 3.7 Gy to 1.7 Gy. The study also showed reduction in pulmonary doses from 12% to 10%.
Aznar et al. in their review of 24 patients who received adjuvant RT for left-sided breast cancer indicated that both whole heart and LAD should be taken into account while delivering RT for breast cancer. They reported that the arch of the LAD is considered to receive an unacceptably high dose when any part of the contoured volume receives 20 Gy or more. The whole LAD is considered to be receiving a high dose when over 10% of the contoured volume received 20 Gy or more. It has been suggested that if 5% of the heart receives 40 Gy, the risk of cardiac mortality exceeds 2%.
Lee et al. showed a statistically significant reduction in mean heart dose and LAD. The mean heart doses with DIBH and FB were 2.52 Gy and 4.53 Gy, respectively. The mean LAD dose with DIBH was 16.01 Gy and with FB was 26.26 Gy, and all had P< 0.001. However, the mean left lung doses with DIBH and FB were 7.53 Gy and 8.03 Gy, respectively, which were not different significantly compared with FB.
Limitations of most of these earlier studies were small sample size and most of the authors commented that the absolute benefit in an individual patient is decided by the patients' chest wall and cardiac relationship. Published literature in this regard from our country and our continent is sparse and hence this well-powered dosimetric comparison was aimed to quantify the proposed benefit in our population.
In our study, we have analyzed 45 patients' dosimetric data. The patients in our study were younger with a median age of 45.2 years. The volume of the heart was smaller with mDIBH when compared to FB. There was a significant reduction in the mean heart dose with mDIBH (45.3%) when compared to FB. Our study showed a benefit of 53.81% reduction in the mean LAD dose when compared to FB. There was a 73% increase in mean TLV with mDIBH when compared to FB. However, there was no significant difference in the lung dose-volume parameters. Our study is well powered compared to other studies and it proves that mDIBH with ABC is feasible and effective in our population also.
Respiratory management for breast cancer patients is relatively easy to implement in clinical practice compared to other novel techniques such as intensity-modulated radiation therapy (IMRT) which has been favored as another alternative method in reducing cardiac doses. Low-dose spill to critical normal structures in IMRT can also be avoided using respiratory gating with mDIBH technique.
Since it is a dosimetric study, clinical endpoints in terms of cardiac morbidity and survival were not evaluated. Correlation of clinical outcome with cardiac dose-volume parameters in the future may enable to predict the dose reduction needed to reduce the cardiac morbidity and mortality in adjuvant left-sided breast cancer RT. Darby et al. from Oxford after a retrospective study concluded that rate of coronary event increases by 7.4% for increase of every 1 Gy to the heart [10,24] and NSABP 51 study recommended a mean cardiac dose of <4 Gy for left-sided breast irradiation, and both emphasize the need for cardiac dose reduction in breast cancer radiotherapy.
| > Conclusion|| |
From this dosimetric comparison, we can conclude that mDIBH with ABC technique has a great impact on dose-volume parameters of heart and LAD. The mean heart dose and mean LAD dose showed a significant reduction of 45.3% and 53.81%, respectively, with ABC mDIBH technique. These reductions achieved are likely to result in reduced long-term cardiac morbidity and mortality. Therefore, respiratory management strategy is a promising tool which can be routinely implemented for the tangential field radiation treatment of patients with left-sided breast cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, et al.
The global breast cancer burden: Variations in epidemiology and survival. Clin Breast Cancer 2005;6:391-401.
Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al.
Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353:1641-8.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, 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 2011;378:1707-16.
Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al.
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005;366:2087-106.
Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, et al.
Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005;97:116-26.
Danish Breast Cancer Cooperative Group, Nielsen HM, Overgaard M, Grau C, Jensen AR, Overgaard J. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: Long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol 2006;24:2268-75.
Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol 2000;18:1220-9.
Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 2000;355:1757-70.
Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol 2007;25:3031-7.
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.
Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, et al.
Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol 2006;24:4100-6.
Bouillon K, Haddy N, Delaloge S, Garbay JR, Garsi JP, Brindel P, et al.
Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol 2011;57:445-52.
Aznar MC, Korreman SS, Pedersen AN, Persson GF, Josipovic M, Specht L. Evaluation of dose to cardiac structures during breast irradiation. Br J Radiol 2011;84:743-6.
Schultz-Hector S, Trott KR. Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data? Int J Radiat Oncol Biol Phys 2007;67:10-8.
Højris I, Andersen J, Overgaard M, Overgaard J. Late treatment-related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone. Acta Oncol 2000;39:355-72.
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.
Marks LB, Yu X, Prosnitz RG, Zhou SM, Hardenbergh PH, Blazing M, et al.
The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys 2005;63:214-23.
Borger JH, Hooning MJ, Boersma LJ, Snijders-Keilholz A, Aleman BM, Lintzen E, et al.
Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: The role of irradiated heart volume. Int J Radiat Oncol Biol Phys 2007;69:1131-8.
Wong JW, Sharpe MB, Jaffray DA, Kini VR, Robertson JM, Stromberg JS, et al.
The use of active breathing control (ABC) to reduce margin for breathing motion. Int J Radiat Oncol Biol Phys 1999;44:911-9.
START Trialists' Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al.
The UK standardisation of breast radiotherapy (START) trial B of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet 2008;371:1098-107.
Lu HM, Cash E, Chen MH, Chin L, Manning WJ, Harris J, et al.
Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: A CT study. Int J Radiat Oncol Biol Phys 2000;47:895-904.
Vikström J, Hjelstuen MH, Mjaaland I, Dybvik KI. Cardiac and pulmonary dose reduction for tangentially irradiated breast cancer, utilizing deep inspiration breath-hold with audio-visual guidance, without compromising target coverage. Acta Oncol 2011;50:42-50.
Lee HY, Chang JS, Lee MY, Lee IJ, Park K, Kim YB, et al
. The deep inspiration breath hold technique using Abches reduces cardiac dose in patients undergoing left-sided breast irradiation. Radiation Oncol J 2013;31:239-46.
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;93:845-53.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]