|Ahead of print
Dosimetric comparison of four different radiotherapy planning techniques for adjuvant radiotherapy of left-sided breast, axilla, and supraclavicular fossa
Ajinkya Gupte1, Ajay Sasidharan1, Beena Kunheri1, Amala N Kumar2, Sruthi Reddy1, Haridas Nair1, KU Pushpaja1, R Anoop1, Debnarayan Dutta1
1 Department of Radiation Oncology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
2 Department of Medical Physics, Amrita Institute of Medical Sciences, Kochi, Kerala, India
|Date of Submission||09-Apr-2021|
|Date of Decision||18-Jun-2021|
|Date of Acceptance||15-Jul-2021|
|Date of Web Publication||13-Oct-2021|
Department of Radiation Oncology, Amrita Institute of Medical Sciences, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose/Aim: Forward planned intensity-modulated radiotherapy (forward IMRT) with breath-hold (BH) technique is considered optimal by most practitioners for treating left-sided breast cancer. Regional nodal irradiation including axilla and supraclavicular fossa (SCF) increases can increase dose-to-organs at risk (OAR) especially lung. This study was done to assess the potential of inverse planned IMRT (inverse IMRT) to achieve significant reduction in dose to OAR. Materials and Methods: Ten patients with left-sided breast cancer treated with Active Breath Co-ordinator BH technique were included in the study. Forward IMRT plans were generated in both BH and free breathing (FB) scans. Inverse IMRT plans were generated in FB scan using Tomotherapy-Direct and Tomotherapy-Helical techniques. Contouring was done as per the ESTRO consensus contouring guidelines. The dose prescribed was 40 Gy in 15 fractions. Statistical significance was tested using one-way ANOVA for parametric data and Kruskall–Wallis test for nonparametric data. Multiple comparison tests were done by using Bonferroni test. P <0.05 was considered to denote statistical significance. Results: Inverse IMRT plans achieved superior homogeneity index compared to forward IMRT with BH. Tomotherapy-Direct reduced dose to ipsilateral lung, compared to the forward IMRT with BH while achieving similar doses to other OAR. Tomotherapy-Helical plans achieved significantly better conformity index and reduced maximum dose to left anterior descending artery compared to forward IMRT plans, but low dose to other OAR was significantly worse. Conclusion: For left-sided breast, axilla, and SCF radiotherapy, inverse IMRT with Tomotherapy-Direct plan achieved better homogeneity index and reduced dose to ipsilateral lung compared to forward IMRT with BH.
Keywords: Breast cancer, IMRT, radiotherapy, tomotherapy
|How to cite this URL:|
Gupte A, Sasidharan A, Kunheri B, Kumar AN, Reddy S, Nair H, Pushpaja K U, Anoop R, Dutta D. Dosimetric comparison of four different radiotherapy planning techniques for adjuvant radiotherapy of left-sided breast, axilla, and supraclavicular fossa. J Med Phys [Epub ahead of print] [cited 2021 Dec 2]. Available from: https://www.jmp.org.in/preprintarticle.asp?id=328154
| Introduction|| |
Breast cancer is the most common cancer in women, representing nearly a quarter of all cancers worldwide. It is also the leading cause of cancer mortality in women. In India, with 162,468 newly diagnosed cases and 87,090 deaths, breast cancer ranks 1st among cancers in women in terms of incidence and mortality.
Adjuvant radiotherapy in breast cancer improves local control and distant relapse-free survival and reduces breast cancer mortality rate. Radiation-induced cardiac events and pneumonitis are the major late effects associated with dose to heart and lungs. This decreases the overall survival benefit patients can have with radiotherapy., Breast fibrosis and pain also affect quality of life, and this increases with inhomogenous high-dose distribution in the standard bitangential field radiotherapy., Dose-to-organs at risk (OAR) has reduced with adoption of cardiac sparing breath-hold (BH) technique with forward planned intensity-modulated radiotherapy (forward IMRT).
Regional nodal irradiation including axilla in the target volume is usually indicated in the setting of inadequate axillary dissection or sentinel node positivity without axillary clearance and in selected high-risk patients.,, Axilla and supraclavicular fossa (SCF) radiation can increase the dose to lung. Inverse planned IMRT (inverse IMRT) has the potential to further reduce dose to the OAR in this setting.
This study is a dosimetric comparative study between four different external beam radiation therapy techniques namely forward planned IMRT with and without BH, and inverse planned IMRT using Tomotherapy-Direct and Tomotherapy-Helical. The aim of the study is to establish the merits and demerits of each technique and assess the ideal technique for treating left-sided breast with regional nodal irradiation including axilla.
| Materials and Methods|| |
Ten patients who underwent forward planned IMRT with tangential fields and BH technique for left-sided breast, axilla, and supraclavicular radiotherapy were included. At the time of simulation, computed tomography (CT) scans were obtained both in free breathing (FB) and moderate deep inspiratory BH (mDIBH) with active breath coordinator (ABC).
Tomotherapy-helical and tomotherapy-direct plans were generated in the FB scan. Forward IMRT plans with field-in-field technique were generated in both FB scan and mDIBH scan.
Radiation treatment workflow
Pretreatment patient education
Informed consent was taken from all patients. Before CT simulation, all the patients underwent a 20–30-min-long training session for 2 days with the Active Breathing Coordinator R2.0 (Elekta, Stockholm, Sweden) to enhance patient compliance and to determine individual mDIBH (levels set at 75% of maximum inspiratory capacity). Verbal instructions were given during the training process to motivate the patients to achieve a constant breathing pattern. BH was practiced at moderate deep inspiration until a steady and reproducible breathing pattern is reached. Patients with a comfortable BH duration of 20–25 s were considered eligible to undergo treatment with ABC–mDIBH.
Planning CT simulation scan was obtained using a GE Optima580WRT CT Simulator (GE Healthcare, Chicago, Illinois, USA). All patients were treated in supine position with both arms above the head, using a MEd-TecM350 breast board (Civco Radiotherapy, Orange City, Iowa, USA) with an inclination of 15°–30°. Radio-opaque wires were used to outline the palpable breast tissue, visible surgical scar, midline, and the mid-axillary line to assist in target delineation. ABC device was used for assisting mDIBH. A nose clip was used to ensure breathing through the mouth only. After acquiring a steady breathing pattern, two sets of CT images were acquired for each patient with a slice thickness of 3 mm. The first scan was acquired at mDIBH with ABC system which was used for actual treatment. This was followed by a second scan in FB. CT data were acquired superiorly from the infra-orbital margin, extending inferiorly till the L2 vertebral level.
For consistency, all contours were done by the same physician. The clinical target volume–breast and SCF + axilla were contoured as per the ESTRO consensus contouring guidelines. A 0.5-cm margin was added around the clinical target volumes to generate the planning target volume (PTV) and were labeled as PTV-breast and PTV-SCF + axilla. PTV-combined was generated as the sum of PTV-breast and PTV-SCF + axilla. The delineated OARs included the ipsilateral and contralateral lung, heart, contralateral breast, spinal cord, esophagus, and the left anterior descending artery (LAD). The LAD was contoured using the cardiac contouring atlas for radiotherapy.
For consistency, all treatment plans were generated by the same medical physicist. Tomotherapy-direct and tomotherapy-helical plans were generated using Accuray Precision Treatment Planning Station (Version 22.214.171.124; California, USA). All the plans were optimized using 2.5-cm jaw and modulation factor of 2.2. Pitch for all Tomotherapy-Helical plans was 0.26 and 0.251 for all Tomotherapy-Direct plans. The dose calculation grid size was set to “fine” and final dose resolution to “high.” The optimization parameters were kept the same initially for both calculations and changed accordingly during optimization. The number of iterations for all plans was kept between 200 and 300.
The paired tangential angles were chosen same as those of conventional linear accelerator. The beam angles were arranged to include PTV and minimize OARs. For PTV breast, a total of six angles were used. Medial tangential angles ranged from 315 to 340°, and lateral tangential angles ranged from 110 to 130°. A flash of 2 cm was given for two main tangential fields. For SCF, four angles were given. The angles ranged from 318 to 110°. To avoid field junction hotspot, a separation of one slice thickness, i.e. 3 mm, was given during the optimization. Adequate coverage was achieved in that slice [Figure 1].
To avoid the low-dose spillage to OARs, dose-limiting volumes for the right breast and lung were used and defined “exit only” during optimization. Unwanted spillage was avoided using a spill structure which was created by giving 1-cm margin from PTV [Figure 2].
Forward IMRT planning
Three-dimensional conformal plans with forward IMRT field-in-field technique were generated in XIO planning station (version v. 5.10.02) (Elekta, Stockholm, Sweden). Tangential fields (medial tangent MT and lateral tangent LT) were given with photon energy ×6, while SCF fields which are given anteroposterior beams were a combination of ×6 and ×15. The weightages of the said beams were chosen such that lung doses were minimized and optimal coverage was achieved. One field-in-field beam (MT subfield) helped to reduce the hotspots and heart dose. Both set of beams were matched at the lower end of the head of clavicle. A dose of 40 Gy in 15 fractions was prescribed for each dose reference point for PTV breast and SCF [Figure 3].
Statistical analysis was done using IBM SPSS 20.0 (SPSS Inc., Chicago, USA). To test the statistically significant comparison of parameters among the different external beam radiation therapy techniques, one-way ANOVA was applied for parametric data and Kruskall–Wallis test was applied for nonparametric data. Multiple comparison tests were done by using Bonferroni test. P <0.05 was considered to denote statistical significance.
| Results|| |
The mean dosimetric parameters of the four techniques of radiation planning namely forward IMRT, forward IMRT with BH, tomotherapy direct, and tomotherapy helical for the ten patients are summarized in [Table 1] and [Table 2].
Target coverage was given priority during planning and hence the coverage was not different among the four techniques. Conformity index was calculated using the following formula: volume of reference isodose (95%) divided by the PTV volume, and homogeneity index was calculated using the RTOG formula of ratio of maximum isodose to reference isodose and the ICRU formula of D2%–D98% divided by D50%., There was a significant difference in conformity index for “PTV COMBINED” among the four groups (P ≤ 0.001). Tomotherapy-Helical had a better conformity index compared to that of forward IMRT with BH (P = 0.001) and forward IMRT (P = 0.010). The homogeneity index was similar between the tomotherapy plans, and both were statistically superior over both the forward IMRT plans.
The mean values of V107% in forward IMRT with BH, forward IMRT, Tomotherapy-Direct, and Tomotherapy-Helical were 4.005 ± 2.577, 4.054 ± 4.432, 0.050 ± 0.108, and 0.190 ± 0.567, respectively, indicating lesser “hot” in the tomotherapy plans. Both inverse IMRT plans showed a significant difference compared to that of forward IMRT plans.
Organs at risk
The mean dose to the heart was 383.40 ± 151.341 cGy in forward IMRT with BH, 488.80 ± 165.611 cGy in forward IMRT technique, 348.20 ± 139.335 cGy in tomotherapy-direct, and 599.90 ± 78.720 cGy in the tomotherapy-helical. The comparison shows a statistically significant difference with P = 0.001. The mean dose to the heart was greater in the tomotherapy-helical group and showed a statistically significant difference when compared to forward IMRT with BH (P = 0.001) and tomotherapy-direct (P = 0.007).
The tomotherapy-direct plan had the lowest V20 Gy dose to combined lung. V20 Gy of 14.263 ± 1.467% in forward IMRT with BH, V20 Gy of 16.109 ± 2.531% in forward IMRT, V20 Gy of 10.20 ± 1.289% in tomotherapy-direct, and V20 Gy of 14.190 ± 2.487% in the tomotherapy-helical technique. The comparison shows a statistically significant difference with P < 0. 001.
The tomotherapy-helical plan had the highest dose to the contralateral breast. The mean dose to the contralateral breast among the different external beam radiation therapy techniques was as follows: 25.7 ± 9.581 in forward IMRT with BH, 20.2 ± 40.77 in forward IMRT, 50.50 ± 19.896 in tomotherapy-direct, and 267.80 ± 36.54 in tomotherapy-helical technique. There was a statistically significant difference between tomotherapy-helical and other three plans with P < 0.001.
Left anterior descending artery
Maximum dose to the LAD artery among the different external beam radiation therapy techniques was as follows: 3595.50 ± 589.145 cGy in forward IMRT with BH, 3744.00 ± 186.351 cGy in the forward IMRT, 3231.50 ± 688.427 cGy in tomotherapy-direct, and 2908.00 ± 248.503 cGy in tomotherapy-helical. There were a significant difference between tomotherapy-helical technique and forward IMRT with BH technique with P = 0.017 and a significant difference between tomotherapy-helical technique and forward IMRT technique with P = 0.002.
| Discussion|| |
This is the first study done using the ESTRO breast contouring guidelines for postoperative radiation therapy including the axilla and supraclavicular area in patients with breast cancer, comparing forward IMRT, forward IMRT with BH, tomotherapy-direct, and tomotherapy-helical modes.
Qi et al. had conducted a dosimetric study for patients with left-sided breast cancer requiring regional nodal irradiation using tomotherapy-direct, tomotherapy-helical, and elekta-based volumetric-modulated arc therapy (VMAT). VMAT plans were more inhomogenous compared to those of tomotherapy-helical. They demonstrated better sparing of the contralateral lung and contralateral breast, which was consistent with that of the current study. On the contrary, cardiac sparing was superior in the rotational techniques such as tomotherapy-helical and VMAT. This could be due to inclusion of internal mammary nodes in the target volume.
A recently conducted study by Takano et al. based on which tomotherapy-direct planning technique was used in our study reported similar outcomes to those of the current study in terms of tomotherapy-direct and tomotherapy-helical having a superior homogeneity and conformity index over the forward three-dimensional conformal radiation therapy (3DCRT) or IMRT plans. The findings of this study were also consistent with results from dosimetric studies by Zhou et al. who conducted a clinical dosimetric study for postoperative radiation therapy in breast cancer patients using helical tomotherapy, step and shoot IMRT, and 3DCRT and with the study conducted by Shiau et al. wherein they made a dosimetric comparison between hybrid IMRT and helical tomotherapy in thirty patients with early-stage left-sided breast cancer to be treated with whole-breast irradiation.,
Data from the Cambridge IMRT trial comparing two-dimensional and IMRT techniques for early-stage breast cancer have shown that improved dose homogeneity correlated with a risk reduction of skin telangiectasia and superior overall cosmesis. A thorough literature search by Ratosa et al. demonstrated that inhomogeneity and excessive radiation dose (hotspots) in the planning of target volume contributed to a higher rate of acute adverse events and suboptimal final cosmetic outcome in adjuvant breast cancer radiotherapy, regardless of the fractionation schedule, and improved homogeneity leads to a lower rate of ≥Grade 2 toxicity.
Radiation pneumonitis is a concern in women receiving radiation therapy to the breast. In the current study, the volume of ipsilateral lung receiving 5 Gy was similar to that in tomotherapy-direct and forward IMRT with BH but had significantly superior dose suppression as compared to that of tomotherapy-helical and forward IMRT plan. The mean dose to the ipsilateral lung was significantly less in tomotherapy-direct as compared to that of tomotherapy-helical. V20 was also significantly lesser in tomotherapy-direct arm compared to that of the other techniques. The mean dose to the contralateral lung was highest in the tomotherapy-helical arm as well as the V2.5, V4, and V5, thereby highlighting that low dose spill to OARs is seen maximally with tomotherapy-helical. The V20 of the combined lung was significantly the least in tomotherapy-direct. These findings were consistent with those of Takano et al., which showed a significant difference between tomotherapy-direct and 3DCRT in terms of mean dose to the combined lung, ipsilateral lung, and contralateral lung. The low dose spill was highest in tomotherapy-helical arm. The findings were also similar to the study conducted by Zhou et al. Tomotherapy-direct had superior dosimetry in high-dose region of ipsilateral lung. Low-dose spread also affects the induction of second primary cancers. Santos et al. estimated the risk of second primary cancer following postoperative radiation therapy for breast cancer and concluded that the lungs and contralateral breast had high life-attributed risk estimates.
In a study of women who received radiation therapy for breast cancer between 1985 and 1999, Stovall et al. showed that that the risk of secondary breast cancer in the contralateral breast increased in women younger than 40 years who received >1.0 Gy maximum dose to the breast tissue. These results suggest that low-dose spread should be avoided as much as possible. In the current study, the mean dose to the breast was least in the forward IMRT and tomotherapy-direct but significantly higher in the tomotherapy-helical arm. A study by Takano et al. also showed lower doses to the opposite breast with tomotherapy-direct as compared to 3DCRT and tomotherapy-helical techniques. The low dose spill to contralateral breast was controlled in the current study by defining it as exit only for optimization and also unwanted spillage was controlled by a spill structure 1 cm around PTV.
According to a population-based, case–control study by Sarah Darby, from the University of Oxford, the rate of major coronary event increases by 7.4% for every increase of 1 Gy. The update of adjuvant breast radiation by the Early Breast Cancer Trialists Collaborative Group analyzed over 30,000 women followed up for up to 20 years, and there is a clear evidence that radiation-related heart disease (RRHD) increases by 3% per Gy.
Correa et al. in a retrospective review of cardiac morbidity in postirradiation patients of breast cancer had found out that coronary stenosis especially in the LAD was the most common cause of RRHD. In a previous study by Meyer et al., it was demonstrated that tomotherapy-direct reduces mean dose by 40% compared to non-BH technique and noninferior to BH technique in breast-alone radiotherapy. In the current study, the mean dose to the heart was similar between forward IMRT with BH and tomotherapy-direct, however significantly lesser compared to tomotherapy-helical. On review of the plans, it was seen that the BH was not ideal in three elderly patients, which resulted in significant mean dose reduction with tomotherapy-direct plan. Hence, this finding may not be considered significant in an ideal DIBH scenario. The maximum dose to the LAD artery was significantly lowest in tomotherapy-helical compared to that of the forward IMRT plans. The mean dose to the LAD was lowest in tomotherapy-helical arm but statistically different from that of forward IMRT plan alone.
The present study demonstrates that for adjuvant radiotherapy in left-sided breast, axilla, and SCF, inverse IMRT with tomotherapy-direct achieved better homogeneity and lung constraint, compared to that of the forward IMRT with BH technique while achieving safe doses to other OAR. Both tomotherapy techniques achieved a significantly superior homogeneity index. Tomotherapy-helical plans achieved significantly better conformity indices, and maximum dose to LAD compared to 3D plans. However, other OAR doses were significantly worse in tomotherapy-helical plans. Based on these dosimetric parameters, tomotherapy-direct can be considered the complementary technique to forward IMRT with BH technique for better lung sparing. However, larger clinical prospective series is needed to identify whether a certain subgroup of patients should be routinely offered tomotherapy-direct planning.
Limitations of the study
This study included contouring of target volumes and OAR in two study sets. Despite all contours being done by the same physician, certain degree of intra-observer variation is expected.
The study highlights dosimetric quality of different techniques but does not incorporate use of radiobiological parameters such as tumor control probability and normal tissue complication probability based on clinical outcome.
As this was a proof-of-concept study, the sample size was small, limiting definite conclusions. Larger studies exploring inverse IMRT using tomotherapy must be done to identify subgroup of patients benefitting with appropriate techniques.
| Conclusion|| |
For left-sided breast, axilla, and SCF radiotherapy, inverse IMRT with tomotherapy-direct plan achieved better homogeneity index and reduced dose to ipsilateral lung compared to forward IMRT with BH. The mean dose to heart was not significantly reduced, and most patients with an ideal BH might still benefit with BH technique.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
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.
Bradshaw PT, Stevens J, Khankari N, Teitelbaum SL, Neugut AI, Gammon MD. Cardiovascular disease mortality among breast cancer survivors. Epidemiology 2016;27:6-13.
Taghian AG, Assaad SI, Niemierko A, Kuter I, Younger J, Schoenthaler R, et al.
Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 2001;93:1806-11.
Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: Mechanisms and implications for therapy. J Cancer Res Clin Oncol 2015;141:1985-94.
Lundstedt D, Gustafsson M, Steineck G, Malmström P, Alsadius D, Sundberg A, et al.
Risk factors of developing long-lasting breast pain after breast cancer radiotherapy. Int J Radiat Oncol Biol Phys 2012;83:71-8.
Buwenge M, Cammelli S, Ammendolia I, Tolento G, Zamagni A, Arcelli A, et al.
Intensity modulated radiation therapy for breast cancer: Current perspectives. Breast Cancer (Dove Med Press) 2017;9:121-6.
Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, et al.
Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015;373:317-27.
Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, et al.
Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015;373:307-16.
Hennequin C, Bossard N, Servagi-Vernat S, Maingon P, Dubois JB, Datchary J, et al.
Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys 2013;86:860-6.
Lee HH, Chen CH, Luo KH, Chuang HY, Huang CJ, Cheng YK, et al.
Five-year survival outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) using forward IMRT or tomotherapy for breast cancer. Sci Rep 2020;10:4342.
Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A, et al.
ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol 2015;114:3-10.
Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, et al
. A cardiac contouring atlas for radiotherapy. Radiother Oncol 2017;122:416-22.
Petrova D, Smickovska S, Lazarevska E. Conformity index and homogeneity index of the postoperative whole breast radiotherapy. Open Access Maced J Med Sci 2017;5:736-9.
Mrozowska M, Kukołowicz P. Relationships between various indices of doses distribution homogeneity. Rep Pract Oncol Radiother 2015;20:278-83.
Qi XS, Liu TX, Liu AK, Newman F, Rabinovitch R, Kavanagh B, et al.
Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy. Med Dosim 2014;39:227-34.
Takano S, Omura M, Suzuki R, Tayama Y, Matsui K, Hashimoto H, et al.
Intensity-modulated radiation therapy using TomoDirect for postoperative radiation of left-sided breast cancer including lymph node area: Comparison with TomoHelical and three-dimensional conformal radiation therapy. J Radiat Res 2019;60:694-704.
Shiau AC, Hsieh CH, Tien HJ, Yeh HP, Lin CT, Shueng PW, et al.
Left-sided whole breast irradiation with hybrid-IMRT and helical tomotherapy dosimetric comparison. Biomed Res Int 2014;2014:741326.
Zhou GX, Xu SP, Dai XK, Ju ZJ, Gong HS, Xie CB, et al.
Clinical dosimetric study of three radiotherapy techniques for postoperative breast cancer: Helical Tomotherapy, IMRT, and 3D-CRT. Technol Cancer Res Treat 2011;10:15-23.
Mukesh MB, Qian W, Wilkinson JS, Dorling L, Barnett GC, Moody AM, et al.
Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: Results from the Cambridge Breast IMRT trial. Radiother Oncol 2014;111:270-5.
Ratosa I, Jenko A, Oblak I. Breast size impact on adjuvant radiotherapy adverse effects and dose parameters in treatment planning. Radiol Oncol 2018;52:233-44.
Santos AM, Marcu LG, Wong CM, Bezak E. Risk estimation of second primary cancers after breast radiotherapy. Acta Oncol 2016;55:1331-7.
Stovall M, Smith SA, Langholz BM, Boice JD Jr, Shore RE, Andersson M, et al.
Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the WECARE study. Int J Radiat Oncol Biol Phys 2008;72:1021-30.
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.
Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, et al.
Radiation-related heart disease: Current knowledge and future prospects. Int J Radiat Oncol Biol Phys 2010;76:656-65.
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.
Meyer P, Niederst C, Scius M, Jarnet D, Dehaynin N, Gantier M, et al.
Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments? Phys Med 2016;32:644-50.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]