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The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer
Practical Radiation Oncology (2013) 3, e131–e137
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Original Report
The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer Kim Ann Ung BMedSc, MBBS (Hons) a,⁎, Maria Portillo BSc, MRT a , Brigid Moran BAppSc (MedRad) a , Tomas Kron PhD, FCCPM, FACPSEM a , Brooke Sawyer MBBS, FRANZCR a , Alan Herschtal BE (Hons), BSc b , Boon H. Chua MBBS, PhD, FRANZCR a, c a
Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia c Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia b
Received 14 September 2012; revised 24 December 2012; accepted 26 December 2012
Abstract Purpose: The thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared the dosimetric impact of the following 2 RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to encompass the computed tomography (CT)-contoured SC nodal volume. Methods and Materials: The thyroid, SC nodal volumes, and organs at risk were contoured on the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50 (percentage of thyroid receiving ≥ 5 Gy, ≥ 30 Gy, and ≥ 50 Gy, respectively); SC nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic characteristics that influenced the dose distributions were investigated. Results: The 3DCRT planning technique significantly increased all thyroid dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9 Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P b .001). It improved HI for the SC nodal volumes (P b .001) but resulted in higher maximum doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4 Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the conventional technique (P = .004). Conclusions: The 3DCRT planning improved dosimetric coverage of the SC nodal volume but increased thyroid radiation doses. The potential adverse effects of incidental thyroid irradiation should be considered while improving dosimetric coverage in SC nodal irradiation for breast cancer. © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Conflicts of interest: None. ⁎ Corresponding author. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, 7 St. Andrews Place, East Melbourne, Victoria 3002, Australia. E-mail address: [email protected] (K.A. Ung). 1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.12.007
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Introduction Supraclavicular (SC) nodal irradiation is generally recommended in addition to whole breast or chest wall irradiation for the adjuvant treatment of patients with locally advanced breast cancer. Randomized trials showed that post-mastectomy chest wall and regional nodal irradiation improved locoregional control and overall survival. 1-3 There is also keen interest in regional nodal irradiation following breast-conserving surgery. Early data of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) MA.20 trial showed significant improvements in locoregional and distant recurrence rates as well as disease-free survival. 4 In these trials, the SC nodes were included in the comprehensive regional radiation therapy. The conventional technique of SC nodal irradiation involves target volume determination based on clinical and radiologic landmarks, which define the borders of a single anterior radiation therapy field used with an empirically derived dose prescription. 5 There has also been a more recent practice of delineating the SC nodal target volume on the planning computed tomography (CT) scan and utilizing 3-dimensional conformal radiation therapy (3DCRT) planning to ensure that the CT-contoured target volume is adequately covered by the intended isodose level. 6,7 In both techniques, a portion of the thyroid gland is often included in the treatment fields. However, the thyroid gland is not routinely considered a significant organ at risk. Prior studies showed that SC nodal irradiation in patients with breast cancer was associated with a higher incidence of hypothyroidism. 8,9 Similarly, studies in patients with head-and-neck cancer highlighted the need for long-term routine thyroid function testing as part of the follow-up after radiation therapy. 10,11 A retrospective study of 504 patients whose radiation therapy fields for head-and-neck cancer treatment included the thyroid gland revealed that at least 50% of patients developed biochemical hypothyroidism at 10 years. 12 Besides hypothyroidism, therapeutic or incidental irradiation of the thyroid gland increased the risk of thyroid tumors. 13,14 No prior studies have determined the radiation dose distribution to the thyroid gland when the conventional technique for SC nodal irradiation for breast cancer is used, and it is unclear how it changes with the CToptimized planning technique. Considering the long-term survival of patients with early breast cancer, study of radiation doses to the thyroid gland is clinically important due to the potential long-term adverse effects. The primary objective of this study was to determine the dosimetric impact on the thyroid gland by comparing 2 radiation therapy planning techniques for SC nodal irradiation: Technique 1 is a conventional technique using a single anterior-oblique photon field to encompass the target volume defined using clinical and radiologic landmarks; and technique 2 is 3DCRT planning to encompass the CT-
Practical Radiation Oncology: October-December 2013
contoured SC nodal target volumes. The secondary objectives were to compare the radiation dose distributions in the CT-contoured SC nodal target volumes between the 2 techniques; identify anatomic characteristics which influence dose distributions to the thyroid gland and the CTcontoured SC nodal target volumes; and compare the dose distributions of the organs at risk (ie, spinal cord, brachial plexus, and ipsilateral lung) between the 2 techniques.
Methods and materials Ethics approval was obtained from the Human Research and Ethics Committee at the Peter MacCallum Cancer Centre, Australia. Patients treated with breast conserving surgery or mastectomy for breast cancer and receiving adjuvant radiation therapy to the breast or chest wall and ipsilateral SC nodal region were included in the study. Twenty consecutive eligible patients treated from January 2010 to October 2010 were selected from the radiation therapy planning system database. Patients were excluded if they had previous surgery to the thyroid gland, ipsilateral neck, or SC region, or if the radiation therapy planning differed from departmental protocol.
Planning CT scan for SC nodal irradiation The patient was positioned supine, flat on back, with both arms extended above the head and immobilized using a breast board. The CT scan was obtained using a 16-slice wide bore CT scanner (Phillips Brilliance; Philips Healthcare, Andover, MA) with the patient in the treatment position. A helical free-breathing planning scan was obtained and contiguous CT slices were reconstructed at 3-mm thickness. The patient was scanned from the level of the mandible to below the diaphragm. The scan was exported to the treatment planning system (Eclipse; Varian Medical Systems, Palo Alto, CA) for subsequent contouring and computer dosimetric planning.
SC nodal target volume determination The following structures were contoured on the planning CT: thyroid gland, spinal cord, ipsilateral brachial plexus, and ipsilateral lung. The SC nodal target volume was determined in each technique as follows. Technique 1 Clinical and radiologic landmarks as per the NCIC CTG MA.20 study were used to determine the field borders of the single anterior-oblique photon field: superior border, 1-cm superior to skin profile; inferior border, lower border of the ipsilateral clavicular head; medial border, lateral aspect of the vertebral pedicles; lateral border, lateral aspect of the coracoid process.
Practical Radiation Oncology: October-December 2013 Table 1
Impact of SC nodal RT on the thyroid
Patient and tumor characteristics
Characteristic Type of surgery Breast-conserving surgery Mastectomy Laterality Left Right Tumor stage Stage IIB Stage IIIA Stage IIIB Stage IIIC Mean thyroid volume (cm 3) a Mean CT-contoured SC nodal target volume (PTV) (cm 3) a Maximum SC nodal depth from anterior skin surface (SC nodal depth) (cm) a
No. of patients (of a total of 20)
%
4 16
20 80
11 9
55 45
6 7 3 4 14.5 (range, 3.5-51.7)
30 35 15 20
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Technique 2 Opposed anterior and posterior-oblique fields were used, angled off-cord with adjustments of beam energies (6 and 18 MV) and weightings, utilization of wedges, and field-infield techniques as necessary. They were manually optimized to cover the PTV within 95%-107% of the prescribed dose as per International Commission on Radiation Units and Measurements 50 (ICRU 50) prescribing guidelines. 15
Dosimetric parameters
162.9 (range, 111.1-201.9)
7.1 (range, 4.4-12.7)
CT, computed tomography; PTV, planning target volume; SC, supraclavicular. a Values averaged across 20 patients.
Technique 2 The SC nodal target volume consisted of the SC and level III axillary lymph nodes. They were contoured according to anatomic guidelines 6 as the clinical target volume (CTV). For the purpose of this study, the planning target volume (PTV) was created using a 1-cm expansion from the CTV, limited medially at the lateral aspect of the vertebral pedicles and inferiorly at the junction of the breast or chest wall tangents. All target volumes were contoured by 1 investigator and reviewed by a radiologist for accuracy and consistency.
SC nodal radiation therapy planning A total dose of 50 Gy in 25 fractions, to be administered in 2-Gy daily fractions at 5 fractions per week, was prescribed to the SC nodal target volumes. A monoisocentric technique was used; ie, the isocenter placed at the junction between the SC field and the breast or chest wall tangents. X-Y jaws and multileaf collimators were used to define the field borders. Technique 1 A single 6-MV anterior-oblique field was used with the gantry angled 15 degrees away from the spinal cord. A half-beam block was used such that the lower jaw was placed at the isocenter. The dose to the SC nodes was prescribed to a depth of 1.5 cm, at a point that was at least 1.5-cm superior to the lower border of the SC field and at the midpoint of the field width.
For each SC nodal radiation therapy technique, the following thyroid gland dosimetric measures were evaluated: mean dose (Gy), maximum dose (Gy), and V5, V20, V30, V40, and V50 (percentage of thyroid gland receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, ≥ 40 Gy, and ≥ 50 Gy, respectively). For the CT-contoured SC nodal target volume, the following PTV dosimetric measures were recorded for each technique: mean dose (Gy), maximum dose (Gy), homogeneity index (HI, percentage of the PTV receiving between 95% and 107% of the prescribed dose), V30, V35, V40, V45, and V50 (percentage of PTV receiving ≥ 30 Gy, ≥ 35 Gy, ≥ 40 Gy, ≥ 45 Gy, and ≥ 50 Gy, respectively), D2 and D98 (Gy) (doses received by 2% and 98% of the PTV, respectively). Anatomic data on thyroid gland volume (cm 3) and the maximum depth of the CT-contoured SC nodal target volumes measured from the anterior skin surface (SC nodal depth) (cm) were collected. In terms of organs at risk, the maximum doses to the spinal cord and brachial plexus (Gy) and V5, V20, and V30 of the ipsilateral lung (percentage of ipsilateral lung receiving ≥ 5 Gy, ≥ 20 Gy, and ≥ 30 Gy, respectively) were recorded for each technique.
Statistical analysis Descriptive statistics to summarize clinical data were reported in the form of means and ranges for quantitative variables. Categorical variables were reported as counts and percentages. Comparisons of the parameters between the 2 radiation therapy planning techniques were made using matched pairs t tests. For all tests, 2-sided P values were supplied for the null hypothesis that there was equality between the planning techniques. To identify the anatomic characteristics that influenced V5 and V30 of the thyroid gland, and HI of CTcontoured SC nodal target volume, linear regression models were constructed with the thyroid gland volume and SC nodal depth as candidate explanatory variables.
Results Of the 20 eligible patients, 16 patients had a total mastectomy and 4 patients had breast-conserving surgery.
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Figure 1 Digitally reconstructed radiographs (left) and the corresponding axial computed tomography demonstrating the contoured target volumes and isodose lines (right). (A) Technique 1. (B) Technique 2. The structures contoured are thyroid gland (yellow), clinical target volume (pink), planning target volume (cyan), and spinal cord (white).
The patient and tumor characteristics are summarized in Table 1. Figure 1 shows the target volumes and normal structures for techniques 1 and 2. The mean thyroid gland volume was 14.5 cm 3 (range, 3.5-51.7 cm 3). There was a significant increase in all thyroid gland dosimetric parameters using technique 2 compared with technique 1 (P b .001) (Table 2). The thyroid gland volume and the SC nodal depth did not influence the thyroid gland dosimetric parameters with either technique. For the CT-contoured SC nodal volumes, there was a significant increase in all dosimetric measures for PTV using technique 2 compared with technique 1 (P b .001) (Table 3). There was superior dose distribution with technique 2 as reflected by better HI, V30-50, and D98 values. The SC Table 2
nodal depth significantly influenced the HI of technique 1 with larger SC nodal depth resulting in worse HI (P = .01). The dosimetric measures for the organs at risk are listed in Table 4. Technique 2 resulted in higher maximum brachial plexus and spinal cord doses than technique 1 (P b .001). Doses received by the ipsilateral lung were also higher in technique 2 (P b .001).
Discussion In SC nodal irradiation for patients with breast cancer, a portion of the thyroid gland is often incidentally encompassed in the target volume. However, there are limited data in the literature on the radiation doses
Comparison of thyroid gland dosimetric measures between technique 1 a and technique 2 b
Dosimetric measure
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
Mean dose (Gy) Maximum dose (Gy) V5 d (%) V20 d (%) V30 d (%) V40 d (%) V50 d (%)
17.2 (7.8-25.4) 48.5 (42.3-51.4) 45.7 (42.3-51.4) 38.7 (14.1-59.7) 33.7 (5.8-54.1) 24.4 (1.1-47.5) 0.6 (0-4.3)
4.9 2.3 8.8 11.2 12.4 12.9 1.3
26.7 (17.9-41.2) 51.9 (50.6-53.1) 64.9 (40.2-100) 50.5 (31.8-84.5) 48 (30.3-75.1) 46.1 (28.9-68.7) 26.7 (5.6-57.1)
5.2 0.6 15.7 11.2 9.7 8.9 15.8
a b c d
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. V5, V20, V30, V40, and V50 = percentage volume receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, ≥ 40 Gy, and ≥ 50 Gy, respectively.
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Table 3 Comparison of computed tomography (CT)-contoured supraclavicular nodal target volume dosimetric measures between technique 1 a and technique 2 b Dosimetric measure
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
Mean dose (Gy) Maximum dose (Gy) Homogeneity index d (HI) (%) V30 e (%) V35 e (%) V40 e (%) V45 e (%) V50 e (%) D2 f (Gy) D98 f (Gy)
41.3 (37.3-44.6) 50.3 (46.9-52.1) 16.0 (0-40.7) 93.4 (83.1-98.7) 89.7 (76-97) 71.8 (33.3-92.7) 35.7 (2-68.2) 2.0 (0-9.3) 49.0 (45-51.2) 16.8 (0.7-32.2)
2.3 1.4 13.3 5.2 5.8 16 20 2.9 1.6 12
50.1 (48.8-51.3) 52.7 (51.5-53.9) 93.2 (79.3-99.1) 100.0 (99.5-100) 100.0 (99.1-100) 99.7 (98-100) 98.1 (91.8-100) 55.3 (28.5-84.6) 52.2 (51.3-53.3) 45.2 (40.1-47.9)
0.7 0.6 4.8 0.1 0.3 0.7 2.1 16 0.5 2.4
a b c d e f
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. Homogeneity index = percentage volume receiving 95%-107% of prescribed dose. V30, V35, V40, V45 and V50 = volume receiving ≥ 30 Gy, ≥ 35 Gy, ≥ 40 Gy, ≥ 45 Gy and ≥ 50 Gy, respectively. D2 and D98 = dose received by 2% and 98% of volume, respectively.
received by the thyroid gland in SC nodal irradiation. Our study provided the data for 2 contemporary radiation therapy planning techniques used in clinical practice. The 3DCRT planning technique resulted in a greater proportion of the thyroid gland receiving higher doses. The addition of a posterior-oblique field, field-in-fields, and the adjustment of beam energies and weightings improved dose coverage of the SC nodal target volumes but at the expense of increased doses to the thyroid gland. The addition of a PTV margin to the SC nodal CTV also resulted in extension of the PTV beyond the conventional field borders, thus contributing further to the thyroid gland doses. Interestingly, the thyroid gland volume and SC nodal depth did not influence the dose distribution of the thyroid gland, suggesting that the dose distribution effect of the radiation therapy planning techniques was not significantly related to patient anatomy. A possible explanation is that the
Table 4
Comparison of organs at risk dosimetric measures between technique 1 a and technique 2 b
Organs at risk Brachial plexus Maximum dose (Gy) Spinal cord Maximum dose (Gy) Ipsilateral lung V5 (%) d V20 (%) d V30 (%) d a b c d
thyroid gland is an anteriorly located structure irrespective of the SC nodal depth. In addition, multiple parameters of the planning technique may influence the thyroid gland dose distribution such that the 2 anatomic factors studied did not reach independent statistical significance. While the thyroid gland is not routinely considered an organ at risk in SC nodal irradiation for patients with breast cancer, radiation to the thyroid gland has been shown to be associated with adverse functional effects. 16 A retrospective study of 200 patients with breast cancer who underwent regional lymph nodal irradiation of 40-50 Gy showed an increase in the prevalence of subclinical and clinical primary hypothyroidism when compared with the control group (P = .00001). 8 Similarly, in patients with head-and-neck cancers, low-neck field irradiation of 50 Gy was associated with 30%-50% incidence of hypothyroidism at 5 years. 17 Thyroid under-activity was more common in patients who had hemi-thyroidectomy and radiation therapy
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
43.2 (36.8-48.8)
3.2
51.4 (49.6-52.6)
0.7
6.0 (2.6-20.1)
3.8
29.5 (17.5-38.3)
5.5
4.2 3.5 3.2
11.4 (4.9-17.1) 8.6 (3.1-13.6) 7.7 (2.6-12.6)
3.8 3.3 3.1
10.3 (0-16.5) 7.9 (0-13.6) 6.3 (0-12.2)
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. V5, V20, V30, = volume receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, respectively (radiation dose contribution from supraclavicular nodal fields only).
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compared with radiation therapy alone. 11 In addition to functional impact, structural changes such as the reduction in thyroid gland size and radiation fibrosis had been reported, 18 which might lead to hypothyroidism. The potential late development of hypothyroidism and monitoring of thyroid function in long-term survivors of breast cancer who had SC nodal irradiation should be considered particularly in patients treated using the 3DCRT planning technique and patients who had prior thyroid surgery. Another potential detrimental effect of therapeutic or incidental irradiation of the thyroid gland is the increase in the risk of thyroid tumors. Two-thirds of thyroid tumors diagnosed after external beam irradiation are benign and one-third are malignant. 19 The risk of second thyroid malignancy is 15- to 33-fold greater in irradiated patients than in a nonirradiated population. This risk increased up to a dose of 15 Gy and then decreased with higher doses, presumably due to cell killing. 13 Our study showed that 45.7% and 64.9% of thyroid volumes received at least 5 Gy (V5) in techniques 1 and 2, respectively. With second malignances being a stochastic process, radiation exposure of large volumes of the thyroid gland would be of concern in long-term survivors of breast cancer. Thyroid examination should be undertaken in the follow-up of these patients. The potential adverse effects of incidental thyroid gland irradiation in SC nodal radiation therapy should be considered in the context of adequate dosing of the SC target volume to optimize disease control. Our study showed that the 3DCRT technique achieved superior radiation dose distribution to the CT-contoured SC nodal volumes consistent with previous studies. 6,7 This technique produced a better HI than the conventional singlefield technique (16% vs 93%), with 98% of the PTV receiving 45 Gy or more. In the conventional technique, 95% of the prescribed dose (45 Gy) was delivered to 35.7% of the PTV only; indicating that on average, 64.3% of the PTV received suboptimal doses. One patient in our study had a HI of 0 using the conventional technique. These findings highlighted the inadequacy of SC nodal dose coverage using the conventional technique. On balance, multiple studies have reported good localregional control rates using the conventional technique. 1–4 It is unclear if SC nodal irradiation using a 3DCRT technique or the delivery of at least 45 Gy to the target volume is essential for optimal treatment efficacy. Thus, currently there is no conclusive evidence to support routine application of a 3DCRT technique in SC nodal irradiation, particularly when the technique is commonly associated with an increase in normal tissue doses including the thyroid as shown in our study. Although these doses may be within clinically acceptable dose tolerances, they may not be justified based on the ALARA (as low as reasonably achievable) principle in the adjuvant treatment of an otherwise well patient. Our study confirmed the findings of a previous report that the SC nodal depth significantly influenced the dose
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distribution of the CT-contoured SC nodal volumes using the conventional technique. 6 The SC nodal depth had also been shown to correlate with the body mass index. A study showed that 80% of patients with a body mass index of ≥ 30 had suboptimal SC nodal dose coverage using the conventional technique. 7 Thus, the radiation therapy planning technique should be tailored to the patient's anatomy to achieve adequate radiation doses in SC nodal irradiation. Previous studies have recommended the use of CToptimized plans in SC nodal irradiation to ensure adequate dosimetric coverage. 6,7 Our study found that the 3DCRT technique resulted in significantly higher doses to the thyroid gland. Modifications of the dosimetric criteria, for example, to deliver at least 90% of the prescribed dose to 90% of the target volume, may be a measure to achieve a balance between SC nodal volume coverage and doses to the surrounding structures. Although increasing the depth of dose prescription from 1.5 cm to 3 cm would improve SC nodal coverage, it may result in “hot spots” within the irradiated volume 7 and potentially normal structures including the thyroid gland. Achieving a balance between the competing considerations of optimizing nodal volume coverage and minimizing doses to the thyroid remains a clinical judgment. The dosimetric information provided by 3DCRT planning enables clinicians to make an informed decision on the selection of a balanced treatment plan tailored to the clinical requirements of each individual patient. To place the study findings into clinical context, the primary aim of SC nodal irradiation in patients with high-risk breast cancer is to reduce the risk of disease relapse in the SC region. In comparison with the 3DCRT technique, the conventional technique delivers suboptimal radiation doses to the SC nodal target volumes especially in patients with large SC nodal depths. Doses to the critical organs at risk, including the spinal cord and brachial plexus, increased but could be kept within clinically acceptable safety limits with judicious application of the 3DCRT technique. However, our study established that the 3DCRT technique resulted in significantly higher doses to the thyroid gland with the potential attendant increased risks of hypothyroidism and radiation-related thyroid malignancy. Thus, patients who receive SC nodal irradiation as a component of their breast cancer treatment should be monitored for these potential long-term consequences of incidental thyroid gland irradiation.
References 1. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337:949-955. 2. Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients
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given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641-1648. Ragaz J, Olivotto IA, Spinelli JJ, 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;97:116-126. Whelan T, Olivotto I, Ackerman I, et al. NCIC CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer. [Abstract]. J Clin Oncol. 2011;29 (Suppl; LBA1003). Morgia M, Lamoury G, Morgan G. Survey of radiotherapy planning and treatment of the supraclavicular fossa in breast cancer. J Med Imaging Radiat Oncol. 2009;53:207-211. Madu CN, Quint DJ, Normolle DP, Marsh RB, Wang EY, Pierce LJ. Definition of the supraclavicular and infraclavicular nodes: implications for three-dimensional CT-based conformal radiation therapy. Radiology. 2001;221:333-339. Liengsawangwong R, Yu TK, Sun TL, et al. Treatment optimization using computed tomography-delineated targets should be used for supraclavicular irradiation for breast cancer. Int J Radiat Oncol Biol Phys. 2007;69:711-715. Bruning P, Bonfrèr J, De Jong-Bakker M, Nooyen W, Burgers M. Primary hypothyroidism in breast cancer patients with irradiated supraclavicular lymph nodes. Br J Cancer. 1985;51: 659-663. Reinertsen KV, Cvancarova M, Wist E, et al. Thyroid function in women after multimodal treatment for breast cancer stage II/III: comparison with controls from a population sample. Int J Radiat Oncol Biol Phys. 2009;75:764-770.
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10. Smith GL, Smith BD, Garden AS, et al. Hypothyroidism in older patients with head and neck cancer after treatment with radiation: a population-based study. Head Neck. 2009;31:1031-1038. 11. Turner SL, Tiver KW, Boyages SC. Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 1995;31:279-283. 12. Garcia-Serra A, Amdur RJ, Morris CG, Mazzaferri E, Mendenhall WM. Thyroid function should be monitored following radiotherapy to the low neck. Am J Clin Oncol. 2005;28:255-258. 13. Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Radiat Res. 1998;150(Suppl 5):S30-S41. 14. Hieu TT, Russell AW, Cuneo R, et al. Cancer risk after medical exposure to radioactive iodine in benign thyroid diseases: a metaanalysis. Endocr Relat Cancer. 2012;19:645-655. 15. International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon beam therapy. ICRU Report 50. Bethesda, MD: ICRU. 1993. 16. Jereczek-Fossa BA, Alterio D, Jassem J, Gibelli B, Tradati N, Orecchia R. Radiotherapy-induced thyroid disorders. Cancer Treat Rev. 2004;30:369-384. 17. Norris AA, Amdur RJ, Morris CG, Mendenhall WM. Hypothyroidism when the thyroid is included only in the low neck field during head and neck radiotherapy. Am J Clin Oncol. 2006;29:442-445. 18. Ryu WG, Oh KK, Kim EK, et al. The effect of supraclavicular lymph node irradiation upon the thyroid gland in the post-operative breast carcinoma patients. Yonsei Med J. 2003;44:828-835. 19. Roman SA. Endocrine tumors: evaluation of the thyroid nodule. Curr Opin Oncol. 2003;15:66-70.
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Original Report
The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer Kim Ann Ung BMedSc, MBBS (Hons) a,⁎, Maria Portillo BSc, MRT a , Brigid Moran BAppSc (MedRad) a , Tomas Kron PhD, FCCPM, FACPSEM a , Brooke Sawyer MBBS, FRANZCR a , Alan Herschtal BE (Hons), BSc b , Boon H. Chua MBBS, PhD, FRANZCR a, c a
Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia c Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia b
Received 14 September 2012; revised 24 December 2012; accepted 26 December 2012
Abstract Purpose: The thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared the dosimetric impact of the following 2 RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to encompass the computed tomography (CT)-contoured SC nodal volume. Methods and Materials: The thyroid, SC nodal volumes, and organs at risk were contoured on the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50 (percentage of thyroid receiving ≥ 5 Gy, ≥ 30 Gy, and ≥ 50 Gy, respectively); SC nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic characteristics that influenced the dose distributions were investigated. Results: The 3DCRT planning technique significantly increased all thyroid dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9 Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P b .001). It improved HI for the SC nodal volumes (P b .001) but resulted in higher maximum doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4 Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the conventional technique (P = .004). Conclusions: The 3DCRT planning improved dosimetric coverage of the SC nodal volume but increased thyroid radiation doses. The potential adverse effects of incidental thyroid irradiation should be considered while improving dosimetric coverage in SC nodal irradiation for breast cancer. © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Conflicts of interest: None. ⁎ Corresponding author. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, 7 St. Andrews Place, East Melbourne, Victoria 3002, Australia. E-mail address: [email protected] (K.A. Ung). 1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.12.007
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Introduction Supraclavicular (SC) nodal irradiation is generally recommended in addition to whole breast or chest wall irradiation for the adjuvant treatment of patients with locally advanced breast cancer. Randomized trials showed that post-mastectomy chest wall and regional nodal irradiation improved locoregional control and overall survival. 1-3 There is also keen interest in regional nodal irradiation following breast-conserving surgery. Early data of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) MA.20 trial showed significant improvements in locoregional and distant recurrence rates as well as disease-free survival. 4 In these trials, the SC nodes were included in the comprehensive regional radiation therapy. The conventional technique of SC nodal irradiation involves target volume determination based on clinical and radiologic landmarks, which define the borders of a single anterior radiation therapy field used with an empirically derived dose prescription. 5 There has also been a more recent practice of delineating the SC nodal target volume on the planning computed tomography (CT) scan and utilizing 3-dimensional conformal radiation therapy (3DCRT) planning to ensure that the CT-contoured target volume is adequately covered by the intended isodose level. 6,7 In both techniques, a portion of the thyroid gland is often included in the treatment fields. However, the thyroid gland is not routinely considered a significant organ at risk. Prior studies showed that SC nodal irradiation in patients with breast cancer was associated with a higher incidence of hypothyroidism. 8,9 Similarly, studies in patients with head-and-neck cancer highlighted the need for long-term routine thyroid function testing as part of the follow-up after radiation therapy. 10,11 A retrospective study of 504 patients whose radiation therapy fields for head-and-neck cancer treatment included the thyroid gland revealed that at least 50% of patients developed biochemical hypothyroidism at 10 years. 12 Besides hypothyroidism, therapeutic or incidental irradiation of the thyroid gland increased the risk of thyroid tumors. 13,14 No prior studies have determined the radiation dose distribution to the thyroid gland when the conventional technique for SC nodal irradiation for breast cancer is used, and it is unclear how it changes with the CToptimized planning technique. Considering the long-term survival of patients with early breast cancer, study of radiation doses to the thyroid gland is clinically important due to the potential long-term adverse effects. The primary objective of this study was to determine the dosimetric impact on the thyroid gland by comparing 2 radiation therapy planning techniques for SC nodal irradiation: Technique 1 is a conventional technique using a single anterior-oblique photon field to encompass the target volume defined using clinical and radiologic landmarks; and technique 2 is 3DCRT planning to encompass the CT-
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contoured SC nodal target volumes. The secondary objectives were to compare the radiation dose distributions in the CT-contoured SC nodal target volumes between the 2 techniques; identify anatomic characteristics which influence dose distributions to the thyroid gland and the CTcontoured SC nodal target volumes; and compare the dose distributions of the organs at risk (ie, spinal cord, brachial plexus, and ipsilateral lung) between the 2 techniques.
Methods and materials Ethics approval was obtained from the Human Research and Ethics Committee at the Peter MacCallum Cancer Centre, Australia. Patients treated with breast conserving surgery or mastectomy for breast cancer and receiving adjuvant radiation therapy to the breast or chest wall and ipsilateral SC nodal region were included in the study. Twenty consecutive eligible patients treated from January 2010 to October 2010 were selected from the radiation therapy planning system database. Patients were excluded if they had previous surgery to the thyroid gland, ipsilateral neck, or SC region, or if the radiation therapy planning differed from departmental protocol.
Planning CT scan for SC nodal irradiation The patient was positioned supine, flat on back, with both arms extended above the head and immobilized using a breast board. The CT scan was obtained using a 16-slice wide bore CT scanner (Phillips Brilliance; Philips Healthcare, Andover, MA) with the patient in the treatment position. A helical free-breathing planning scan was obtained and contiguous CT slices were reconstructed at 3-mm thickness. The patient was scanned from the level of the mandible to below the diaphragm. The scan was exported to the treatment planning system (Eclipse; Varian Medical Systems, Palo Alto, CA) for subsequent contouring and computer dosimetric planning.
SC nodal target volume determination The following structures were contoured on the planning CT: thyroid gland, spinal cord, ipsilateral brachial plexus, and ipsilateral lung. The SC nodal target volume was determined in each technique as follows. Technique 1 Clinical and radiologic landmarks as per the NCIC CTG MA.20 study were used to determine the field borders of the single anterior-oblique photon field: superior border, 1-cm superior to skin profile; inferior border, lower border of the ipsilateral clavicular head; medial border, lateral aspect of the vertebral pedicles; lateral border, lateral aspect of the coracoid process.
Practical Radiation Oncology: October-December 2013 Table 1
Impact of SC nodal RT on the thyroid
Patient and tumor characteristics
Characteristic Type of surgery Breast-conserving surgery Mastectomy Laterality Left Right Tumor stage Stage IIB Stage IIIA Stage IIIB Stage IIIC Mean thyroid volume (cm 3) a Mean CT-contoured SC nodal target volume (PTV) (cm 3) a Maximum SC nodal depth from anterior skin surface (SC nodal depth) (cm) a
No. of patients (of a total of 20)
%
4 16
20 80
11 9
55 45
6 7 3 4 14.5 (range, 3.5-51.7)
30 35 15 20
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Technique 2 Opposed anterior and posterior-oblique fields were used, angled off-cord with adjustments of beam energies (6 and 18 MV) and weightings, utilization of wedges, and field-infield techniques as necessary. They were manually optimized to cover the PTV within 95%-107% of the prescribed dose as per International Commission on Radiation Units and Measurements 50 (ICRU 50) prescribing guidelines. 15
Dosimetric parameters
162.9 (range, 111.1-201.9)
7.1 (range, 4.4-12.7)
CT, computed tomography; PTV, planning target volume; SC, supraclavicular. a Values averaged across 20 patients.
Technique 2 The SC nodal target volume consisted of the SC and level III axillary lymph nodes. They were contoured according to anatomic guidelines 6 as the clinical target volume (CTV). For the purpose of this study, the planning target volume (PTV) was created using a 1-cm expansion from the CTV, limited medially at the lateral aspect of the vertebral pedicles and inferiorly at the junction of the breast or chest wall tangents. All target volumes were contoured by 1 investigator and reviewed by a radiologist for accuracy and consistency.
SC nodal radiation therapy planning A total dose of 50 Gy in 25 fractions, to be administered in 2-Gy daily fractions at 5 fractions per week, was prescribed to the SC nodal target volumes. A monoisocentric technique was used; ie, the isocenter placed at the junction between the SC field and the breast or chest wall tangents. X-Y jaws and multileaf collimators were used to define the field borders. Technique 1 A single 6-MV anterior-oblique field was used with the gantry angled 15 degrees away from the spinal cord. A half-beam block was used such that the lower jaw was placed at the isocenter. The dose to the SC nodes was prescribed to a depth of 1.5 cm, at a point that was at least 1.5-cm superior to the lower border of the SC field and at the midpoint of the field width.
For each SC nodal radiation therapy technique, the following thyroid gland dosimetric measures were evaluated: mean dose (Gy), maximum dose (Gy), and V5, V20, V30, V40, and V50 (percentage of thyroid gland receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, ≥ 40 Gy, and ≥ 50 Gy, respectively). For the CT-contoured SC nodal target volume, the following PTV dosimetric measures were recorded for each technique: mean dose (Gy), maximum dose (Gy), homogeneity index (HI, percentage of the PTV receiving between 95% and 107% of the prescribed dose), V30, V35, V40, V45, and V50 (percentage of PTV receiving ≥ 30 Gy, ≥ 35 Gy, ≥ 40 Gy, ≥ 45 Gy, and ≥ 50 Gy, respectively), D2 and D98 (Gy) (doses received by 2% and 98% of the PTV, respectively). Anatomic data on thyroid gland volume (cm 3) and the maximum depth of the CT-contoured SC nodal target volumes measured from the anterior skin surface (SC nodal depth) (cm) were collected. In terms of organs at risk, the maximum doses to the spinal cord and brachial plexus (Gy) and V5, V20, and V30 of the ipsilateral lung (percentage of ipsilateral lung receiving ≥ 5 Gy, ≥ 20 Gy, and ≥ 30 Gy, respectively) were recorded for each technique.
Statistical analysis Descriptive statistics to summarize clinical data were reported in the form of means and ranges for quantitative variables. Categorical variables were reported as counts and percentages. Comparisons of the parameters between the 2 radiation therapy planning techniques were made using matched pairs t tests. For all tests, 2-sided P values were supplied for the null hypothesis that there was equality between the planning techniques. To identify the anatomic characteristics that influenced V5 and V30 of the thyroid gland, and HI of CTcontoured SC nodal target volume, linear regression models were constructed with the thyroid gland volume and SC nodal depth as candidate explanatory variables.
Results Of the 20 eligible patients, 16 patients had a total mastectomy and 4 patients had breast-conserving surgery.
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Figure 1 Digitally reconstructed radiographs (left) and the corresponding axial computed tomography demonstrating the contoured target volumes and isodose lines (right). (A) Technique 1. (B) Technique 2. The structures contoured are thyroid gland (yellow), clinical target volume (pink), planning target volume (cyan), and spinal cord (white).
The patient and tumor characteristics are summarized in Table 1. Figure 1 shows the target volumes and normal structures for techniques 1 and 2. The mean thyroid gland volume was 14.5 cm 3 (range, 3.5-51.7 cm 3). There was a significant increase in all thyroid gland dosimetric parameters using technique 2 compared with technique 1 (P b .001) (Table 2). The thyroid gland volume and the SC nodal depth did not influence the thyroid gland dosimetric parameters with either technique. For the CT-contoured SC nodal volumes, there was a significant increase in all dosimetric measures for PTV using technique 2 compared with technique 1 (P b .001) (Table 3). There was superior dose distribution with technique 2 as reflected by better HI, V30-50, and D98 values. The SC Table 2
nodal depth significantly influenced the HI of technique 1 with larger SC nodal depth resulting in worse HI (P = .01). The dosimetric measures for the organs at risk are listed in Table 4. Technique 2 resulted in higher maximum brachial plexus and spinal cord doses than technique 1 (P b .001). Doses received by the ipsilateral lung were also higher in technique 2 (P b .001).
Discussion In SC nodal irradiation for patients with breast cancer, a portion of the thyroid gland is often incidentally encompassed in the target volume. However, there are limited data in the literature on the radiation doses
Comparison of thyroid gland dosimetric measures between technique 1 a and technique 2 b
Dosimetric measure
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
Mean dose (Gy) Maximum dose (Gy) V5 d (%) V20 d (%) V30 d (%) V40 d (%) V50 d (%)
17.2 (7.8-25.4) 48.5 (42.3-51.4) 45.7 (42.3-51.4) 38.7 (14.1-59.7) 33.7 (5.8-54.1) 24.4 (1.1-47.5) 0.6 (0-4.3)
4.9 2.3 8.8 11.2 12.4 12.9 1.3
26.7 (17.9-41.2) 51.9 (50.6-53.1) 64.9 (40.2-100) 50.5 (31.8-84.5) 48 (30.3-75.1) 46.1 (28.9-68.7) 26.7 (5.6-57.1)
5.2 0.6 15.7 11.2 9.7 8.9 15.8
a b c d
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. V5, V20, V30, V40, and V50 = percentage volume receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, ≥ 40 Gy, and ≥ 50 Gy, respectively.
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Table 3 Comparison of computed tomography (CT)-contoured supraclavicular nodal target volume dosimetric measures between technique 1 a and technique 2 b Dosimetric measure
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
Mean dose (Gy) Maximum dose (Gy) Homogeneity index d (HI) (%) V30 e (%) V35 e (%) V40 e (%) V45 e (%) V50 e (%) D2 f (Gy) D98 f (Gy)
41.3 (37.3-44.6) 50.3 (46.9-52.1) 16.0 (0-40.7) 93.4 (83.1-98.7) 89.7 (76-97) 71.8 (33.3-92.7) 35.7 (2-68.2) 2.0 (0-9.3) 49.0 (45-51.2) 16.8 (0.7-32.2)
2.3 1.4 13.3 5.2 5.8 16 20 2.9 1.6 12
50.1 (48.8-51.3) 52.7 (51.5-53.9) 93.2 (79.3-99.1) 100.0 (99.5-100) 100.0 (99.1-100) 99.7 (98-100) 98.1 (91.8-100) 55.3 (28.5-84.6) 52.2 (51.3-53.3) 45.2 (40.1-47.9)
0.7 0.6 4.8 0.1 0.3 0.7 2.1 16 0.5 2.4
a b c d e f
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. Homogeneity index = percentage volume receiving 95%-107% of prescribed dose. V30, V35, V40, V45 and V50 = volume receiving ≥ 30 Gy, ≥ 35 Gy, ≥ 40 Gy, ≥ 45 Gy and ≥ 50 Gy, respectively. D2 and D98 = dose received by 2% and 98% of volume, respectively.
received by the thyroid gland in SC nodal irradiation. Our study provided the data for 2 contemporary radiation therapy planning techniques used in clinical practice. The 3DCRT planning technique resulted in a greater proportion of the thyroid gland receiving higher doses. The addition of a posterior-oblique field, field-in-fields, and the adjustment of beam energies and weightings improved dose coverage of the SC nodal target volumes but at the expense of increased doses to the thyroid gland. The addition of a PTV margin to the SC nodal CTV also resulted in extension of the PTV beyond the conventional field borders, thus contributing further to the thyroid gland doses. Interestingly, the thyroid gland volume and SC nodal depth did not influence the dose distribution of the thyroid gland, suggesting that the dose distribution effect of the radiation therapy planning techniques was not significantly related to patient anatomy. A possible explanation is that the
Table 4
Comparison of organs at risk dosimetric measures between technique 1 a and technique 2 b
Organs at risk Brachial plexus Maximum dose (Gy) Spinal cord Maximum dose (Gy) Ipsilateral lung V5 (%) d V20 (%) d V30 (%) d a b c d
thyroid gland is an anteriorly located structure irrespective of the SC nodal depth. In addition, multiple parameters of the planning technique may influence the thyroid gland dose distribution such that the 2 anatomic factors studied did not reach independent statistical significance. While the thyroid gland is not routinely considered an organ at risk in SC nodal irradiation for patients with breast cancer, radiation to the thyroid gland has been shown to be associated with adverse functional effects. 16 A retrospective study of 200 patients with breast cancer who underwent regional lymph nodal irradiation of 40-50 Gy showed an increase in the prevalence of subclinical and clinical primary hypothyroidism when compared with the control group (P = .00001). 8 Similarly, in patients with head-and-neck cancers, low-neck field irradiation of 50 Gy was associated with 30%-50% incidence of hypothyroidism at 5 years. 17 Thyroid under-activity was more common in patients who had hemi-thyroidectomy and radiation therapy
Technique 1 c (range)
Standard deviation
Technique 2 c (range)
Standard deviation
43.2 (36.8-48.8)
3.2
51.4 (49.6-52.6)
0.7
6.0 (2.6-20.1)
3.8
29.5 (17.5-38.3)
5.5
4.2 3.5 3.2
11.4 (4.9-17.1) 8.6 (3.1-13.6) 7.7 (2.6-12.6)
3.8 3.3 3.1
10.3 (0-16.5) 7.9 (0-13.6) 6.3 (0-12.2)
Technique 1 = conventional single-field technique. Technique 2 = 3-dimensional conformal radiation therapy planning technique. Values averaged across 20 patients. V5, V20, V30, = volume receiving ≥ 5 Gy, ≥ 20 Gy, ≥ 30 Gy, respectively (radiation dose contribution from supraclavicular nodal fields only).
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compared with radiation therapy alone. 11 In addition to functional impact, structural changes such as the reduction in thyroid gland size and radiation fibrosis had been reported, 18 which might lead to hypothyroidism. The potential late development of hypothyroidism and monitoring of thyroid function in long-term survivors of breast cancer who had SC nodal irradiation should be considered particularly in patients treated using the 3DCRT planning technique and patients who had prior thyroid surgery. Another potential detrimental effect of therapeutic or incidental irradiation of the thyroid gland is the increase in the risk of thyroid tumors. Two-thirds of thyroid tumors diagnosed after external beam irradiation are benign and one-third are malignant. 19 The risk of second thyroid malignancy is 15- to 33-fold greater in irradiated patients than in a nonirradiated population. This risk increased up to a dose of 15 Gy and then decreased with higher doses, presumably due to cell killing. 13 Our study showed that 45.7% and 64.9% of thyroid volumes received at least 5 Gy (V5) in techniques 1 and 2, respectively. With second malignances being a stochastic process, radiation exposure of large volumes of the thyroid gland would be of concern in long-term survivors of breast cancer. Thyroid examination should be undertaken in the follow-up of these patients. The potential adverse effects of incidental thyroid gland irradiation in SC nodal radiation therapy should be considered in the context of adequate dosing of the SC target volume to optimize disease control. Our study showed that the 3DCRT technique achieved superior radiation dose distribution to the CT-contoured SC nodal volumes consistent with previous studies. 6,7 This technique produced a better HI than the conventional singlefield technique (16% vs 93%), with 98% of the PTV receiving 45 Gy or more. In the conventional technique, 95% of the prescribed dose (45 Gy) was delivered to 35.7% of the PTV only; indicating that on average, 64.3% of the PTV received suboptimal doses. One patient in our study had a HI of 0 using the conventional technique. These findings highlighted the inadequacy of SC nodal dose coverage using the conventional technique. On balance, multiple studies have reported good localregional control rates using the conventional technique. 1–4 It is unclear if SC nodal irradiation using a 3DCRT technique or the delivery of at least 45 Gy to the target volume is essential for optimal treatment efficacy. Thus, currently there is no conclusive evidence to support routine application of a 3DCRT technique in SC nodal irradiation, particularly when the technique is commonly associated with an increase in normal tissue doses including the thyroid as shown in our study. Although these doses may be within clinically acceptable dose tolerances, they may not be justified based on the ALARA (as low as reasonably achievable) principle in the adjuvant treatment of an otherwise well patient. Our study confirmed the findings of a previous report that the SC nodal depth significantly influenced the dose
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distribution of the CT-contoured SC nodal volumes using the conventional technique. 6 The SC nodal depth had also been shown to correlate with the body mass index. A study showed that 80% of patients with a body mass index of ≥ 30 had suboptimal SC nodal dose coverage using the conventional technique. 7 Thus, the radiation therapy planning technique should be tailored to the patient's anatomy to achieve adequate radiation doses in SC nodal irradiation. Previous studies have recommended the use of CToptimized plans in SC nodal irradiation to ensure adequate dosimetric coverage. 6,7 Our study found that the 3DCRT technique resulted in significantly higher doses to the thyroid gland. Modifications of the dosimetric criteria, for example, to deliver at least 90% of the prescribed dose to 90% of the target volume, may be a measure to achieve a balance between SC nodal volume coverage and doses to the surrounding structures. Although increasing the depth of dose prescription from 1.5 cm to 3 cm would improve SC nodal coverage, it may result in “hot spots” within the irradiated volume 7 and potentially normal structures including the thyroid gland. Achieving a balance between the competing considerations of optimizing nodal volume coverage and minimizing doses to the thyroid remains a clinical judgment. The dosimetric information provided by 3DCRT planning enables clinicians to make an informed decision on the selection of a balanced treatment plan tailored to the clinical requirements of each individual patient. To place the study findings into clinical context, the primary aim of SC nodal irradiation in patients with high-risk breast cancer is to reduce the risk of disease relapse in the SC region. In comparison with the 3DCRT technique, the conventional technique delivers suboptimal radiation doses to the SC nodal target volumes especially in patients with large SC nodal depths. Doses to the critical organs at risk, including the spinal cord and brachial plexus, increased but could be kept within clinically acceptable safety limits with judicious application of the 3DCRT technique. However, our study established that the 3DCRT technique resulted in significantly higher doses to the thyroid gland with the potential attendant increased risks of hypothyroidism and radiation-related thyroid malignancy. Thus, patients who receive SC nodal irradiation as a component of their breast cancer treatment should be monitored for these potential long-term consequences of incidental thyroid gland irradiation.
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