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ORIGINAL ARTICLE
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Incidental radiation dose to internal mammary lymph nodal area in carcinoma breast patients treated with forward planning intensity-modulated radiation therapy technique: A single-institute dosimetric study


1 Department of Radiation Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Radiation Oncology, Mehdi Nawaz Jung Institute of Oncology and Regional Cancer Centre, Hyderabad, Telangana, India

Date of Submission02-Apr-2019
Date of Decision07-Aug-2019
Date of Acceptance18-Apr-2019
Date of Web Publication13-Oct-2020

Correspondence Address:
Aparna Suryadevara,
Department of Radiation Oncology, Basavatarakam Indo.American Cancer Hospital and Research Institute, Banjara Hills, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_225_19

 > Abstract 


Introduction: Breast cancer (BC) is the most common cancer in Indian females. The irradiation of internal mammary lymph nodal area (IMLN) is recommended by latest guidelines and literature, even in patients with N1 nodal disease, but it is not routinely done in many institutes due to the risk of late lung and heart toxicities. The incidence of isolated IMLN recurrence <1%. The incidental radiation therapy (RT) dose to axillary lymph nodal area (ALN) could result in lower local recurrences according to literature. The aim of this study is to assess the incidental IMLN area RT dose in patients treated with forward planning intensity-modulated RT (FIF-IMRT).
Materials and Methods: The aim of our study is to evaluate the RT dose received by IMLN area incidentally in FIF-IMRT and is a single-institute dosimetric study. The patients planned for RT after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were evaluated for IMLN incidental dose.
Results: The mean doses to IMLN area (Dmean) were comparable to literature for both BCS and MRM patients. All other dose parameters (D95, D90) in our study were slightly lower but comparable to literature for the FIF-IMRT planning. Interestingly, the incidental IMLN RT doses in our study are in the same range as the incidental ALN RT doses studied in the literature (48%–68%).
Conclusion: The IMLN area receives a major amount of incidental radiation dose during conformal RT by FIF-IMRT and higher doses for MRM than BCS. This RT dose is not in the therapeutic range but is comparable to the incidental dose to ALN area reported in the literature.

Keywords: Breast cancer, forward planning intensity-modulated radiation therapy, incidental, India, internal mammary lymph node radiation



How to cite this URL:
Suryadevara A, Ahamed S, Alluri KR, Sresty N V. Incidental radiation dose to internal mammary lymph nodal area in carcinoma breast patients treated with forward planning intensity-modulated radiation therapy technique: A single-institute dosimetric study. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 26]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298072




 > Introduction Top


Breast cancer (BC) is the most common cancer in Indian females, and the most common stage at diagnosis is Stage III.[1] Adjuvant radiation (RT) is required for almost all early BC and locally advanced BC patients. There is a controversy over the lymph nodal irradiation in BC patients. The irradiation of internal mammary lymph nodal area (IMLN) is recommended by latest National Comprehensive Cancer Network guidelines [2] and studies like MA.20 trial [3] and European Organization for Research and Treatment of Cancer 22922/10925 trial,[4] even in patients with N1 nodal disease, but it is not routinely done in BC patients in many institutes due to the risk of late lung and heart toxicities. In these studies, IMLN was a part of all lymph nodal areas and not assessed as an individual site.

In BC-treated cases, isolated IMLN recurrence rate is <1%.[5],[6] The incidental RT dose to axillary lymph nodal area (ALN) could result in lower rate of local disease recurrences according to literature in the American College of Surgeons Oncology Group (ACOSOG) Z0010 study.[7],[8] Similarly, the incidental IMLN RT dose could be a reason for lower IMLN recurrences. However, this is not measured in any large study, among the patients receiving forward planning or field-in-field IMRT (FIF-IMRT) for BC.

In our institute, we irradiated IMLN only in clinical or pathologically positive patients. The aim of this study is to assess the incidental IMLN area RT dose in patients treated with FIF-IMRT. We also wanted to evaluate if this was comparable to the incidental ALN area RT doses mentioned in the literature.


 > Materials and Methods Top


The aim of our study is to dosimetrically evaluate the RT dose received by IMLN area incidentally in BC patients treated with conformal radiation (FIF-IMRT). This is a single-institute dosimetric observational study done on BC patients treated with RT after surgery. All female BC patients (n = 56) aged 20–80 years and who were planned for radiation to intact breast after breast conservation surgery (BCS) or chest wall after modified radical mastectomy (MRM) with or without axillary and supraclavicular fossa (SCF) radiation, from September 2018 to January 2019 were included into the study. All study patients had a thermoplastic mask done followed by intravenous contrast and 5-mm slice thickness was computed tomography (CT) scan for radiation planning was done. All these patients were not planned for IMLN radiation. All the study patients were planned by a FIF-IMRT technique. The planning target volume (PTV) prescription was given as D95 of PTV to receive at least 95% of the prescribed dose. The organ-at-risk constraints were given according to the Quantitative Analysis of Normal Tissue Effects in the Clinic guidelines as lung mean dose <20 Gy and V20 <20%, heart mean dose <5 Gy and V25 <10%, spinal cord max dose <40 Gy, and esophagus mean <40 Gy and V40 <30%. After planning by FIF-IMRT technique, appropriate plan was approved for treatment of the patient. Then, the IMLN area contoured as internal mammary vessels on the planning CT scan, in the first three intercostal spaces and a 10-mm margin was given to create PTV to generate the IMLN area. All the contours were done by a single radiation oncologist without changing the RT plan.

The dose (incidental dose) received by the IMLN area was recorded from the dose–volume histogram (DVH). All patients received conventional fractionation of 50 Gy in 25 fractions except nine patients with intact breast (hypofractionation with 40.05 Gy in 15 fractions for seven patients and 45 Gy in 20 fractions for two patients). The PTV doses were evaluated by DVH parameters−Dmean (mean dose), D95 (dose received by 95% volume of PTV), and D90 (dose received by 90% volume of PTV). Doses were recorded as percentages. As there were some patients treated by hypofractionation, the DVH doses were noted as a percentage rather than an absolute value.


 > Results Top


There was higher number of patients with left-sided BC (n = 31) than right-sided BC (n = 25). The median age of patients at disease presentation was 46 years.

There were a total of 56 patients in the study. Of these, 39 had MRM and remaining had BCS followed by adjuvant radiation. There were 8 out of 17 BCS patients who had SCF irradiation. Out of these eight patients, one patient also had ALN radiation. In the MRM patients (n = 31), there were only two patients who had chest wall RT. Remaining 29 patients needed lymph nodal RT (13 had ALN and SCF RT and 16 had only SCF LN RT along with chest wall RT).

The internal mammary lymphnodal area (IMNLN) mean radiation doses were 60% and 44% for MRM and BCS patients, respectively (55% overall). The D95 (dose received by 95% of the volume) of IMLN area was 12% and 8% for MRM versus BCS patients, while D90 (dose received by 90% of the volume) was 17% versus 9%.

The results of the study are shown in [Table 1]. The dose distribution showing IMLN area for BCS and MRM patients is shown in [Figure 1] and [Figure 2].
Table 1: The results of the study patients

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Figure 1: A field-in-field intensity-modulated radiation therapy plan for a modified radical mastectomy study patient showing dose distribution to the planning target volume contour (in red) and internal mammary lymph nodal contour (in yellow)

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Figure 2: A field-in-field intensity-modulated radiation therapy plan for a breast conservation surgery study patient showing dose distribution to the planning target volume contour (in red) and internal mammary lymph nodal contour (in yellow)

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 > Discussion Top


In BC planning, the incidental dose to ALN area is measured in many studies. The literature on incidental radiation dose to IMLN is sparse. The studies evaluating the IMLN radiation were mostly measuring dose in conventional two-dimensional (2D) planning or three-dimensional conformal radiotherapy (3DCRT) technique. There were two studies which studied the incidental IMLN dose in the FIF-IMRT technique, but the sample size was small for these two studies. In one study by Govardhan et al.,[8] there were 20 patients and another study by Leite et al.[9] had no MRM patients. The current study is a single-institute study with larger sample size which would reduce the contouring and RT planning variations during dosimetric evaluation. The incidental IMLN RT doses in the current study and literature are compared in [Table 1].

The mean dose (Dmean) in our study was 44% for BCS and 60% for MRM, which was comparable to the studies reported in the literature. The other dose parameters (D95, D90) were slightly lower but comparable to literature for the FIF-IMRT planning, so the FIF-IMRT plans were more conformal in our study.[8],[9] There was another study by Arora et al. on incidental dose in BC patients with a large sample size, but the RT planning technique was not uniform in all the study patients. After planning was done by 3D technique, the RT plan was modified by FIF-IMRT technique for patients, in whom better coverage was needed. In this study, the IMCLN in the first five and first three intercostal spaces were evaluated rather than in the first three spaces, as done in our study and other studies in the literature.[10]

The incidental IMLN RT doses were higher for chest wall than for intact breast, comparable to literature. The planning images with dose distribution is shown in [Figure 1] and [Figure 2], and it is obvious that in chest wall patients, the PTV is much closer to the IMLN area and hence receiving higher dose than an intact BC patient.

The incidental ALN radiation was evaluated in many studies.[11],[12],[13],[14],[15],[16],[17] The incidental axillary RT dose with BCS radiation with standard tangential fields was ranging from 48% to 66% (mean dose) in different studies. Most of these studies were assessed by 2D technique, and in some studies, 3D evaluation with DVH was done after planning CT. In RT planning by IMRT techniques in a study done by Zhang et al., the incidental ALN radiation dose was 54%–58% (mean dose). In RT planning with high tangential fields, the ALN radiation is slightly higher than standard tangential fields – 60% versus 40% in a study done by Belkacemi et al., while it was 86% versus 66% in a study done by Reznik et al.[15],[16] However, in none of these studies, the RT dose in the therapeutic range, mainly for the Level I and Level II ALN.

Interestingly, the incidental IMLN RT doses in our study are in the same range as the incidental ALN RT doses studied in literature. The ACOSOG Z0011 and the National Surgical Adjuvant Breast and Bowel Project B32 trials stated that the incidental ALN RT dose could explain the low ALN recurrences in patients who never had axillary dissection. Similarly, incidental IMLN RT doses can explain the lower IMLN recurrences. Moreover, with the advances in chemotherapy, targeted therapy, and newer risk assessment tools to individualize the treatment in BC patients, the routine RT to IMLN in lymph node-positive patients, should be considered with caution.

The merits of our study are that all the contouring was done by a single radiation oncologist, to decrease variations in contouring. This is a single-institute study evaluating a single RT planning (FIF-IMRT) technique. The demerits of the study are the number of patients with intact breast radiation is small, and the study needs to be extended to follow-up the patients long term to evaluate for IMLN recurrences to enhance the clinical importance of the study.


 > Conclusion Top


The IMLN area receives a major amount of incidental radiation dose during conformal RT by FIF-IMRT of intact breast or chest wall, but these doses to the IMLN area are not in the therapeutic range. Higher doses are received during chest wall radiation than during intact breast RT.

This RT dose is comparable to the incidental dose to ALN area reported in the literature. Neither the IMLN nor ALN incidental RT doses are in the therapeutic range in BC patients.

Acknowledgments

The authors would like to thank Medical physicists, Department of Radiation Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Banjara Hills, Hyderabad, Telangana, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr. [Last accessed on 2018 Aug 05].  Back to cited text no. 1
    
2.
Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. [Last accessed on 2019 Sep 01].  Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
Poortmans P, Collette S, Struikmans H, De Winter K, Van Limbergen E, Budach V. Fifteen-year results of the randomised EORTC trial 22922/10925 investigating internal mammary and medial supraclavicular (IM-MS) lymph node irradiation in stage I-III breast cancer. N Eng J Med 2015;373:317-27.  Back to cited text no. 4
    
5.
Galper S, Recht A, Silver B, Manola J, Gelman R, Schnitt SJ, et al. Factors associated with regional nodal failure in patients with early stage breast cancer with 0-3 positive axillary nodes following tangential irradiation alone. Int J Radiat Oncol Biol Phys 1999;45:1157-66.  Back to cited text no. 5
    
6.
Stefanik D, Goldberg R, Byrne P, Smith F, Ueno W, Smith L, et al. Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1985;3:660-5.  Back to cited text no. 6
    
7.
Giuliano AE, McCall LM, Beitsch PD, Whitworth PW, Morrow M, Blumencranz PW, et al. ACOSOG Z00sssssss11: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node. J Clin Oncol 2010;28(18_suppl):CRA506.  Back to cited text no. 7
    
8.
Govardhan HB, Thimmaiah N, Khaleel IA, Pradhan S, Jain R, Sridhar P. Comparison of incidental radiation dose to axilla and internal mammary nodal area by conventional, 3DCRT, and IMRT technique in carcinoma of breast. J Nucl Med Radiat Ther 2017;8:325.  Back to cited text no. 8
    
9.
Leite ET, Ugino RT, Santana MA, Ferreira DV, Lopes MR, Pelosi EL, et al. Incidental irradiation of internal mammary lymph nodes in breast cancer: Conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy. Radiol Bras 2016;49:170-5.  Back to cited text no. 9
    
10.
Arora D, Frakes J, Scott J, Opp D, Johnson C, Song J, et al. Incidental radiation to uninvolved internal mammary lymph nodes in breast cancer. Breast Cancer Res Treat 2015;151:365-72.  Back to cited text no. 10
    
11.
Zhang L, Yang ZZ, Chen XX, Tuan J, Ma JL, Mei X, et al. Dose coverage of axillary level I-III areas during whole breast irradiation with simplified intensity modulated radiation therapy in early stage breast cancer patients. Oncotarget 2015;6:18183-91.  Back to cited text no. 11
    
12.
Aristei C, Chionne F, Marsella AR, Alessandro M, Rulli A, Lemmi A, et al. Evaluation of level I and II axillary nodes included in the standard breast tangential fields and calculation of the administered dose: Results of a prospective study. Int J Radiat Oncol Biol Phys 2001;51:69-73.  Back to cited text no. 12
    
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Orecchia R, Huscher A, Leonardi MC, Gennari R, Galimberti V, Garibaldi C, et al. Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: Using a three-dimensional tool to evaluate the first level coverage of the axillary nodes. Br J Radiol 2005;78:51-4.  Back to cited text no. 13
    
14.
Reed DR, Lindsley SK, Mann GN, Austin-Seymour M, Korssjoen T, Anderson BO, et al. Axillary lymph node dose with tangential breast irradiation. Int J Radiat Oncol Biol Phys 2005;61:358-64.  Back to cited text no. 14
    
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Reznik J, Cicchetti MG, Degaspe B, Fitzgerald TJ. Analysis of axillary coverage during tangential radiation therapy to the breast. Int J Radiat Oncol Biol Phys 2005;61:163-8.  Back to cited text no. 15
    
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Belkacemi Y, Allab-Pan Q, Bigorie V, Khodari W, Beaussart P, Totobenazara JL, et al. The standard tangential fields used for breast irradiation do not allow optimal coverage and dose distribution in axillary levels I-II and the sentinel node area. Ann Oncol 2013;24:2023-8.  Back to cited text no. 16
    
17.
Krasin M, McCall A, King S, Olson M, Emami B. Evaluation of a standard breast tangent technique: A dose-volume analysis of tangential irradiation using three-dimensional tools. Int J Radiat Oncol Biol Phys 2000;47:327-33.  Back to cited text no. 17
    


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