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Localization of internal mammary lymph nodes by CT simulation: implications for breast radiation therapy planning
Radiotherapy and Oncology 73 (2004) 355–357 www.elsevier.com/locate/radonline
Technical note
Localization of internal mammary lymph nodes by CT simulation: implications for breast radiation therapy planning David B. Mansura,*, Issam El Naqaa, Fengming Kongb, Eric E. Kleina, Marie E. Taylora, Imran Zoberia, Jeffrey D. Bradleya, Carlos A. Pereza a
Department of Radiation Oncology and Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4921 Parkview Place, Box 8224, St. Louis, MO 63110, USA b Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA Received 23 February 2004; received in revised form 10 August 2004; accepted 24 August 2004 Available online 30 September 2004
Abstract The efficacy of post-operative radiation therapy in breast cancer management has been evident for several decades. In recent years there has been increasing interest in treating the internal mammary lymph nodes. In an attempt to simplify their localization for treatment planning purposes, the position of the internal mammary lymph nodes was systematically studied in 65 breast cancer patients undergoing CT simulation. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Internal mammary nodes; Radiation therapy
1. Introduction The indications for adjuvant radiation therapy to the breast or chest wall have been developed over the past few decades by retrospective data as well as randomized trials. However, controversies exist regarding the ideal radiation therapy volume. Increased interest in irradiating the internal mammary lymph nodes has been generated by reports of a survival benefit in select women whose post-operative radiation therapy portals included the internal mammary lymph node chain [8,9,12]. To localize the internal mammary lymph nodes in an attempt to simplify breast treatment planning, their location was systematically studied in a cohort of patients undergoing CT simulation at our institution.
retrospectively analyzed. At the time of image analysis these were all of the available CT simulations in the department. The internal mammary node locations ipsilateral to the treated breast in the first five intercostal spaces were identified based on available CT atlas guidelines [6]. Midline was defined as mid-sternum on any given slice. As a general indicator of body habitus, patient thickness was defined as the anterior–posterior patient diameter from anterior skin to posterior skin in the midline at a level corresponding to the central slice of the treated volume. The lateral distance from midline to the ipsilateral mid-internal mammary node location was recorded at the first five intercostal spaces. In addition, the anterior–posterior distance (depth) from the overlying skin surface to the mid-internal mammary node location for each nodal position at the first five intercostal spaces was recorded.
2. Materials and methods The volumetric scans from CT simulation of 65 breast conservation patients (33 right breast, 32 left breast) were * Corresponding author. 0167-8140/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2004.08.018
3. Results and discussion As summarized in Fig. 1, the median distance from midline to the ipsilateral internal mammary nodes ranges
356
D.B. Mansur et al. / Radiotherapy and Oncology 73 (2004) 355–357
Fig. 1. Box plots comparing internal mammary node (IMN) distance from midline (mid-sternum) for each intercostal space. The boxed extent shows the 25 and 75% quartiles of the distribution with the box ‘cinched’ by the dotted line representing the median. The 90% confidence is represented by the vertical lines (whiskers). Points beyond this distribution are considered outliers (C). The notches give an estimate of the uncertainty about the medians for box-to-box comparison.
from 2.6 to 3.4 cm depending on intercostal space for the right side. For the left side, the median distance from midline to the ipsilateral internal mammary nodes ranges from 2.5 to 3.4 cm depending on intercostal space. The median patient thickness (A–P diameter at the central slice) for this cohort is 21.2 cm (range 17–29.6 cm). The median depth of internal mammary nodes ranges from 2.7 to 3.9 cm for the right side, depending on intercostal space. The median depth of internal mammary nodes for the left side ranges from 2.5 to 3.7 cm depending on intercostal space. Since the depth of internal mammary nodes is primarily determined by general body habitus (i.e. the degree of truncal obesity), the median depth for each patient is presented in Fig. 2 as a function of patient thickness. We have previously shown that using adjoining fields rather than ‘deep tangents’ to treat the internal mammary nodes can significantly reduce the amount of heart and lung irradiated [3].
Using this technique, our data indicate the internal mammary nodes can be covered in 90% of breast conservation patients with a target width extending from midline to 4 cm. This is evident from Fig. 1 since the 90% confidence interval is always within 4 cm of midline. The actual field width will be larger to account for margin and beam penumbra. However, to account for the outliers in this cohort of patients, Fig. 1 demonstrates that to cover nodal locations in 100% of patients a target width of almost 5 cm is required. Unfortunately, this would result in excessive field size for many patients. Adequate prescription depth of an internal mammary node beam is dependent on body habitus. The data in Fig. 2 allows the estimation of depth based on body habitus, with 3.5 cm adequate in 95% of thin patients, but depths of 5 cm are required for more obese patients. Yet, if 100% of patients are to be treated adequately, a depth of 4 and 6 cm for thin and obese patients, respectively, must be prescribed.
Fig. 2. Comparison of internal mammary node (IMN) depth with patient thickness (A–P diameter). (A) Right breast, the best line fit is given by depthZ0.26 APK2.54 and the goodness of the fit measured by R2 is 0.45 (correlation coefficient squared). The 95% confidence intervals of the estimated slope is [0.15, 0.37] and for the intercept is [K4.89, K0.17]. (B) Left breast, the best line fit is given by depthZ0.3 APK3.28 and the goodness of the fit measured by R2 is 0.81. The 95% confidence intervals of the estimated slope is [0.24, 0.35] and for the intercept is [K4.53, K2.02].
D.B. Mansur et al. / Radiotherapy and Oncology 73 (2004) 355–357
There are several limitations in this analysis. The use of the A–P diameter as a surrogate for body habitus or truncal obesity can be misleading in the case of patients with severe chronic obstructive pulmonary disease (COPD) and resultant ‘barrel’ shaped chests. These patients can have a large A–P diameter, yet have thin chest walls and internal mammary node depths. Therefore these data cannot be generalized to patients with COPD. The exact location of clinically negative internal mammary nodes is difficult to assess. Unlike the axial appearance of other nodal regions in the neck, axilla, or pelvis, in the internal mammary node region often no actual lymph nodes or fat regions or vessels are visualized. Rather their position is inferred based on position of the sternum and ribs. This leaves the definition of the internal mammary location somewhat imprecise and open to some inter-observer variation. In this study, we chose the mid-point of the region defined by Martinez-Monge et al. [6] as a best estimate of their location. From Figs. 1 and 2 it is evident that there exists significant variability with regard to the internal mammary node location. Therefore, optimal dosimetry requires individualized CT based treatment planning. Nonetheless, recognizing the limitations of this study, and acknowledging that these data have not been prospectively tested, this report can offer some assistance and general guidelines for conventional treatment planning. The use of lymphoscintigraphy and ultrasound were early advances in the localization of internal mammary lymph nodes and these methods were investigated for treatment planning at some institutions [13–15]. However CT simulation has allowed simple high-resolution localization of lymph node regions during breast cancer radiation therapy planning [1,14]. Bentel et al. previously demonstrated the advantage of this approach [1]. They analyzed the central slice in patients undergoing CT simulation for breast cancer and reported widely variable positions of the internal mammary nodal regions. In addition, they noted a correlation between internal mammary node depth and body habitus. The benefit of treating the internal mammary lymph nodes has been the subject of debate. Three prospective randomized trials showed a survival benefit to postmastectomy radiation therapy (chest wall and regional lymphatics including internal mammary nodes) compared to no radiation therapy [8,9,12]. However, retrospective radiation therapy data [2,7], and one randomized surgery trial [4,16] demonstrate no benefit to treating this nodal region. This controversy as to whether or not to irradiate the internal mammary nodal region has been addressed in a prospective randomized trial conducted by the European Organization for Research and Treatment of Cancer. This trial (EORTC 22922/10925) includes meticulous quality assurance of radiotherapy technique and, once the data are mature, will help to settle this question [5,10,11]. If one does decide to treat the internal mammary chain, the best approach is individual CT based planning. However,
357
the information in this report, when carefully applied, will help to guide conventional treatment planning.
References [1] Bentel G, Marks LB, Hardenbergh P, Prosnitz L. Variability of the location of internal mammary vessels and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning. Int J Radiat Oncol Biol Phys 1999;44:1017–25. [2] Fowble B, Hanlon A, Freedman G, et al. Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer. Int J Radiat Oncol Biol Phys 2000;47:883–94. [3] Kong FM, Klein EE, Bradley JD, et al. The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation. Int J Radiat Oncol Biol Phys 2002;54:963–71. [4] Lacour J, Bucalossi P, Cacers E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study. Cancer 1976;37:206–14. [5] Lievens Y, Poortmans P, Van den Bogaert W. A glance on quality assurance in EORTC study 22922 evaluating techniques for internal mammary and medial supraclavicular lymph node chain irradiation in breast cancer. Radiother Oncol 2001;60:257–65. [6] Martinez-Monge R, Fernandes PS, Gupta N, Gahbauer R. Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in threedimensional radiation therapy planning. Radiology 1999;211:815–28. [7] Obedian E, Haffty BG. Internal mammary nodal irradiation in conservatively-managed breast cancer patients: is there a benefit? Int J Radiat Oncol Biol Phys 1999;44:997–1003. [8] Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. New Engl J Med 1997;337:949–55. [9] Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomized trial. Lancet 1999;353:1641–8. [10] Poortmans P, Kouloulias VE, Venselaar JL, et al. Quality assurance of EORTC trial 22922/10925 investigating the role of internal mammary–medial supraclavicular irradiation in stage I–III breast cancer: the individual case review. Eur J Cancer 2003;39:2035–42. [11] Poortmans PMP, Venselaar JLM, Struikmans H, et al. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC phase III randomized trial 22922/10925 in stage I–III breast cancer. Int J Radiat Oncol Biol Phys 2001;49:1399–408. [12] Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956–62. [13] Recht A, Siddon RL, Kaplan WD, Andersen JW, Harris JR. Threedimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J Radiat Oncol Biol Phys 1988;14:477–81. [14] Saarnak AE, Hurkmans CW, Pieters BR, et al. Accuracy of internal mammary lymph node localization using lymphoscintigraphy, sonography and CT. Radiother Oncol 2002;65:79–88. [15] Struikmans H, Scheijmans LJEE, van Dalen A, Harmelink M, Westers P, van Isselt JW. Lateralization and depth of the internal mammary chain determined by scintigraphy and by ultrasonography: a comparative study in 124 primary breast cancer patients. Radiother Oncol 2002;62:159–62. [16] Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R. The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomized trial. Eur J Cancer 1999;35:1320–5.
Technical note
Localization of internal mammary lymph nodes by CT simulation: implications for breast radiation therapy planning David B. Mansura,*, Issam El Naqaa, Fengming Kongb, Eric E. Kleina, Marie E. Taylora, Imran Zoberia, Jeffrey D. Bradleya, Carlos A. Pereza a
Department of Radiation Oncology and Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4921 Parkview Place, Box 8224, St. Louis, MO 63110, USA b Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA Received 23 February 2004; received in revised form 10 August 2004; accepted 24 August 2004 Available online 30 September 2004
Abstract The efficacy of post-operative radiation therapy in breast cancer management has been evident for several decades. In recent years there has been increasing interest in treating the internal mammary lymph nodes. In an attempt to simplify their localization for treatment planning purposes, the position of the internal mammary lymph nodes was systematically studied in 65 breast cancer patients undergoing CT simulation. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Internal mammary nodes; Radiation therapy
1. Introduction The indications for adjuvant radiation therapy to the breast or chest wall have been developed over the past few decades by retrospective data as well as randomized trials. However, controversies exist regarding the ideal radiation therapy volume. Increased interest in irradiating the internal mammary lymph nodes has been generated by reports of a survival benefit in select women whose post-operative radiation therapy portals included the internal mammary lymph node chain [8,9,12]. To localize the internal mammary lymph nodes in an attempt to simplify breast treatment planning, their location was systematically studied in a cohort of patients undergoing CT simulation at our institution.
retrospectively analyzed. At the time of image analysis these were all of the available CT simulations in the department. The internal mammary node locations ipsilateral to the treated breast in the first five intercostal spaces were identified based on available CT atlas guidelines [6]. Midline was defined as mid-sternum on any given slice. As a general indicator of body habitus, patient thickness was defined as the anterior–posterior patient diameter from anterior skin to posterior skin in the midline at a level corresponding to the central slice of the treated volume. The lateral distance from midline to the ipsilateral mid-internal mammary node location was recorded at the first five intercostal spaces. In addition, the anterior–posterior distance (depth) from the overlying skin surface to the mid-internal mammary node location for each nodal position at the first five intercostal spaces was recorded.
2. Materials and methods The volumetric scans from CT simulation of 65 breast conservation patients (33 right breast, 32 left breast) were * Corresponding author. 0167-8140/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2004.08.018
3. Results and discussion As summarized in Fig. 1, the median distance from midline to the ipsilateral internal mammary nodes ranges
356
D.B. Mansur et al. / Radiotherapy and Oncology 73 (2004) 355–357
Fig. 1. Box plots comparing internal mammary node (IMN) distance from midline (mid-sternum) for each intercostal space. The boxed extent shows the 25 and 75% quartiles of the distribution with the box ‘cinched’ by the dotted line representing the median. The 90% confidence is represented by the vertical lines (whiskers). Points beyond this distribution are considered outliers (C). The notches give an estimate of the uncertainty about the medians for box-to-box comparison.
from 2.6 to 3.4 cm depending on intercostal space for the right side. For the left side, the median distance from midline to the ipsilateral internal mammary nodes ranges from 2.5 to 3.4 cm depending on intercostal space. The median patient thickness (A–P diameter at the central slice) for this cohort is 21.2 cm (range 17–29.6 cm). The median depth of internal mammary nodes ranges from 2.7 to 3.9 cm for the right side, depending on intercostal space. The median depth of internal mammary nodes for the left side ranges from 2.5 to 3.7 cm depending on intercostal space. Since the depth of internal mammary nodes is primarily determined by general body habitus (i.e. the degree of truncal obesity), the median depth for each patient is presented in Fig. 2 as a function of patient thickness. We have previously shown that using adjoining fields rather than ‘deep tangents’ to treat the internal mammary nodes can significantly reduce the amount of heart and lung irradiated [3].
Using this technique, our data indicate the internal mammary nodes can be covered in 90% of breast conservation patients with a target width extending from midline to 4 cm. This is evident from Fig. 1 since the 90% confidence interval is always within 4 cm of midline. The actual field width will be larger to account for margin and beam penumbra. However, to account for the outliers in this cohort of patients, Fig. 1 demonstrates that to cover nodal locations in 100% of patients a target width of almost 5 cm is required. Unfortunately, this would result in excessive field size for many patients. Adequate prescription depth of an internal mammary node beam is dependent on body habitus. The data in Fig. 2 allows the estimation of depth based on body habitus, with 3.5 cm adequate in 95% of thin patients, but depths of 5 cm are required for more obese patients. Yet, if 100% of patients are to be treated adequately, a depth of 4 and 6 cm for thin and obese patients, respectively, must be prescribed.
Fig. 2. Comparison of internal mammary node (IMN) depth with patient thickness (A–P diameter). (A) Right breast, the best line fit is given by depthZ0.26 APK2.54 and the goodness of the fit measured by R2 is 0.45 (correlation coefficient squared). The 95% confidence intervals of the estimated slope is [0.15, 0.37] and for the intercept is [K4.89, K0.17]. (B) Left breast, the best line fit is given by depthZ0.3 APK3.28 and the goodness of the fit measured by R2 is 0.81. The 95% confidence intervals of the estimated slope is [0.24, 0.35] and for the intercept is [K4.53, K2.02].
D.B. Mansur et al. / Radiotherapy and Oncology 73 (2004) 355–357
There are several limitations in this analysis. The use of the A–P diameter as a surrogate for body habitus or truncal obesity can be misleading in the case of patients with severe chronic obstructive pulmonary disease (COPD) and resultant ‘barrel’ shaped chests. These patients can have a large A–P diameter, yet have thin chest walls and internal mammary node depths. Therefore these data cannot be generalized to patients with COPD. The exact location of clinically negative internal mammary nodes is difficult to assess. Unlike the axial appearance of other nodal regions in the neck, axilla, or pelvis, in the internal mammary node region often no actual lymph nodes or fat regions or vessels are visualized. Rather their position is inferred based on position of the sternum and ribs. This leaves the definition of the internal mammary location somewhat imprecise and open to some inter-observer variation. In this study, we chose the mid-point of the region defined by Martinez-Monge et al. [6] as a best estimate of their location. From Figs. 1 and 2 it is evident that there exists significant variability with regard to the internal mammary node location. Therefore, optimal dosimetry requires individualized CT based treatment planning. Nonetheless, recognizing the limitations of this study, and acknowledging that these data have not been prospectively tested, this report can offer some assistance and general guidelines for conventional treatment planning. The use of lymphoscintigraphy and ultrasound were early advances in the localization of internal mammary lymph nodes and these methods were investigated for treatment planning at some institutions [13–15]. However CT simulation has allowed simple high-resolution localization of lymph node regions during breast cancer radiation therapy planning [1,14]. Bentel et al. previously demonstrated the advantage of this approach [1]. They analyzed the central slice in patients undergoing CT simulation for breast cancer and reported widely variable positions of the internal mammary nodal regions. In addition, they noted a correlation between internal mammary node depth and body habitus. The benefit of treating the internal mammary lymph nodes has been the subject of debate. Three prospective randomized trials showed a survival benefit to postmastectomy radiation therapy (chest wall and regional lymphatics including internal mammary nodes) compared to no radiation therapy [8,9,12]. However, retrospective radiation therapy data [2,7], and one randomized surgery trial [4,16] demonstrate no benefit to treating this nodal region. This controversy as to whether or not to irradiate the internal mammary nodal region has been addressed in a prospective randomized trial conducted by the European Organization for Research and Treatment of Cancer. This trial (EORTC 22922/10925) includes meticulous quality assurance of radiotherapy technique and, once the data are mature, will help to settle this question [5,10,11]. If one does decide to treat the internal mammary chain, the best approach is individual CT based planning. However,
357
the information in this report, when carefully applied, will help to guide conventional treatment planning.
References [1] Bentel G, Marks LB, Hardenbergh P, Prosnitz L. Variability of the location of internal mammary vessels and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning. Int J Radiat Oncol Biol Phys 1999;44:1017–25. [2] Fowble B, Hanlon A, Freedman G, et al. Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer. Int J Radiat Oncol Biol Phys 2000;47:883–94. [3] Kong FM, Klein EE, Bradley JD, et al. The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation. Int J Radiat Oncol Biol Phys 2002;54:963–71. [4] Lacour J, Bucalossi P, Cacers E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study. Cancer 1976;37:206–14. [5] Lievens Y, Poortmans P, Van den Bogaert W. A glance on quality assurance in EORTC study 22922 evaluating techniques for internal mammary and medial supraclavicular lymph node chain irradiation in breast cancer. Radiother Oncol 2001;60:257–65. [6] Martinez-Monge R, Fernandes PS, Gupta N, Gahbauer R. Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in threedimensional radiation therapy planning. Radiology 1999;211:815–28. [7] Obedian E, Haffty BG. Internal mammary nodal irradiation in conservatively-managed breast cancer patients: is there a benefit? Int J Radiat Oncol Biol Phys 1999;44:997–1003. [8] Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. New Engl J Med 1997;337:949–55. [9] Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomized trial. Lancet 1999;353:1641–8. [10] Poortmans P, Kouloulias VE, Venselaar JL, et al. Quality assurance of EORTC trial 22922/10925 investigating the role of internal mammary–medial supraclavicular irradiation in stage I–III breast cancer: the individual case review. Eur J Cancer 2003;39:2035–42. [11] Poortmans PMP, Venselaar JLM, Struikmans H, et al. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC phase III randomized trial 22922/10925 in stage I–III breast cancer. Int J Radiat Oncol Biol Phys 2001;49:1399–408. [12] Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956–62. [13] Recht A, Siddon RL, Kaplan WD, Andersen JW, Harris JR. Threedimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J Radiat Oncol Biol Phys 1988;14:477–81. [14] Saarnak AE, Hurkmans CW, Pieters BR, et al. Accuracy of internal mammary lymph node localization using lymphoscintigraphy, sonography and CT. Radiother Oncol 2002;65:79–88. [15] Struikmans H, Scheijmans LJEE, van Dalen A, Harmelink M, Westers P, van Isselt JW. Lateralization and depth of the internal mammary chain determined by scintigraphy and by ultrasonography: a comparative study in 124 primary breast cancer patients. Radiother Oncol 2002;62:159–62. [16] Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R. The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomized trial. Eur J Cancer 1999;35:1320–5.