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Dosimetric analysis of a simplified intensity modulation technique for prone breast radiotherapy
Int. J. Radiation Oncology Biol. Phys., Vol. 60, No. 1, pp. 95–102, 2004 Copyright © 2004 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/04/$–see front matter
doi:10.1016/j.ijrobp.2004.02.016
CLINICAL INVESTIGATION
Breast
DOSIMETRIC ANALYSIS OF A SIMPLIFIED INTENSITY MODULATION TECHNIQUE FOR PRONE BREAST RADIOTHERAPY KARYN A. GOODMAN, M.D.,* LINDA HONG, PH.D.,† RAQUEL WAGMAN, M.D.,* MARGIE A. HUNT, M.S.,† AND BERYL MCCORMICK, M.D.* Departments of *Radiation Oncology and †Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY Purpose: Prone-position breast radiotherapy (RT) has been described as an alternative technique to improve dose homogeneity for women with large, pendulous breasts. We report the feasibility and dosimetric analysis of a simplified intensity-modulated RT (IMRT) technique, previously reported for women in the supine treatment position, to plan prone-position RT to the intact breast. Methods and Materials: Twenty patients with clinical Stage TisN0-T1bN1 breast cancer undergoing breastconserving therapy underwent whole breast RT using a prone position technique. The treatment plans were developed using both conventional tangents and a simplified intensity-modulated tangential beam technique based on optimization of the intensity distributions across the breast. The plans were compared with regard to the dose–volume parameters. Results: Dose heterogeneity within the breast planning target volume was significantly greater for the conventional tangent plans. Of 20 patients, 16 (80%) received maximal doses of >110% using the conventional tangents vs. only 1 (5%) using the IMRT plan. The isodose level encompassing 5% of the planning target volume was reduced from an average of 110% with conventional tangents to 105% with IMRT. The maximal dose within the planning target volume was reduced from an average of 114% with conventional tangents to 107% with IMRT. The greatest improvement was seen in the patients with the most pendulous breasts. Conclusion: An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, pendulous breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact acute toxicity and cosmetic outcome in this cohort of women who have historically suffered from poor cosmesis after breast-conserving therapy. © 2004 Elsevier Inc. Intensity-modulated radiotherapy, Prone breast radiotherapy, Breast cancer.
13). The use of the prone position has been used at our institution as an option to improve dose homogeneity for women with large, pendulous breasts (11, 14). Treatment in the prone position has been shown to reduce the maximal dose in the high-dose regions usually found at the superior and inferior regions of the breast with the supine treatment technique and also to minimize the dose gradient from the apex to the base at the chest wall interface (11). These improvements in dose uniformity have been associated with superior cosmetic results (14). Preliminary data on local control and survival appear to be comparable to that found for patients treated in the supine position. Intensity-modulated RT (IMRT) has also been introduced for whole breast RT to improve dose homogeneity (15–20). This approach has been successful in reducing cardiac, lung, and contralateral breast doses, as well as in decreasing dose inhomogeneity within the breast. However, treatment plan-
INTRODUCTION Evidence from large randomized, controlled trials has established the equivalence in survival for breast-conserving therapy and mastectomy for most women with early-stage breast cancer (1–5). On the basis of these results, a clear national trend toward the use of conservative surgery and postoperative radiotherapy (RT) has occurred (6). Despite this widespread change in practice, some women are believed to be poor candidates for breast conservation owing to large breast size or pendulous breasts. Several studies have shown increased acute toxicity and inferior cosmetic outcomes among large-breasted patients. Consequently, large, pendulous breasts have been considered a relative contraindication to breast-conserving therapy (7–10). The technical challenges involved in irradiating women with large, pendulous breasts in the standard supine position have led to the investigation of alternative techniques (11– Reprint requests to: Beryl McCormick, M.D., Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Tel: (212) 639-6828; Fax: (212) 639-2417; E-mail: [email protected] Presented at the 44th Annual Meeting of the American Society
for Therapeutic Radiology and Oncology, New Orleans, LA, October 7, 2002. Received Sep 22, 2003, and in revised form Feb 3, 2004. Accepted for publication Feb 9, 2004. 95
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Fig. 1. Prone breast board. (a) Customized prone breast board with adjustable aperture and wedge for contralateral breast. (b) Ipsilateral breast and anterior chest wall hang in dependent fashion away from thorax with ipsilateral arm placed above head.
ning for breast IMRT can be time-consuming, thereby making the technique impractical in a busy clinical practice. At our institution, we have developed a simplified IMRT (sIMRT) technique that achieves dose homogeneity comparable to that with the full-fledged contour-based IMRT technique but requires no more planning and treatment time than standard wedged tangent fields (21). This technique focuses on the treatment volume only, using inverse planning to deliver a uniform dose across the breast. Using the standard opposed tangential beam arrangement, the optimal intensity of each pencil beam is determined to equalize the dose to the mid-point of the pencil beam segment that intersects the treatment volume. This method eliminates the need for contour delineation, which is necessary for the full-fledged IMRT technique. By combining IMRT and prone breast RT, we have been able to optimize dose homogeneity within the breast further, thereby allowing women with large, pendulous breasts to undergo breast-conserving therapy without compromising cosmetic outcomes. The purpose of this study was to report the feasibility and dosimetric analysis of our sIMRT technique, previously reported for women in the supine treatment position, to plan prone-position RT of the intact breast. METHODS AND MATERIALS Clinical characteristics Twenty patients with early-stage breast cancer undergoing breast-conserving therapy at Memorial Sloan-Kettering Cancer Center were treated with prone breast RT using the sIMRT technique. The institutional review board approved our review of patient information. Patient age ranged from 39 to 79 years (median 61). All the patients had clinical Stage TisN0-T1bN1 breast cancer and underwent conservative surgery consisting of excisional biopsy and sentinel lymph node biopsy (n ⫽ 11), excisional biopsy and axillary lymph node dissection (n ⫽ 6), or excisional biopsy alone (n ⫽ 3). Two of the patients undergoing lymph node biopsy or dissection had one positive node. The final pathologic di-
agnosis was ductal carcinoma in situ in 3 and infiltrating ductal or lobular carcinoma in 17. Five patients underwent adjuvant chemotherapy with either Cytoxan, methotrexate, and 5-fluorouracil (n ⫽ 2) or adriamycin and Cytoxan with or without Taxol (n ⫽ 3). Procedure A prototype prone-breast board with an adjustable aperture for the breast was designed (Fig. 1) with a platform height and width allowing clearance through a CT simulator (Picker 5000, Cleveland, OH). The CT simulator has a 70-cm bore and 48-cm field of view. To fit the patient through the CT scan aperture and obtain images of the whole breast without distortion, we designed the height of the platform for the simulation at 17 cm, instead of 25 cm, the height of the standard platform of the prone breast board. Patient eligibility for the prone breast IMRT technique was, therefore, subject to the limitation of the CT scan aperture and field of view. The indication for treatment in the prone position was large or pendulous breast size, history of tobacco use, or patient preference for most patients. The objectives of the prone technique at our institution have been previously described (11, 14). In brief, patients underwent simulation lying prone on the custom board with the ipsilateral breast positioned over the aperture to hang through in a dependent fashion. The ipsilateral arm was placed superolaterally, and the patient held on to an adjustable handle on the board. The contralateral breast was placed on a custom support wedge with the contralateral arm down close to the body. The patient was rotated slightly to allow the ipsilateral chest wall to extend into the board aperture. The physician placed posterior border marks on the medial and lateral aspects of the breast; superior and inferior borders were also indicated by the physician. CT wires were placed on these markers and on the lumpectomy scar. The patient was scanned at least 5 cm beyond the superior and inferior borders of the breast. The orientation of the posterior field edge of the coplanar tangent beams was set in
Dosimetric analysis of sIMRT for prone breast RT
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Fig. 2. Computed tomography simulation images used to determine arrangement of tangent beams.
virtual simulation by the radiation oncologist using the CT images. This was checked through each cut of the simulation scan for breast tissue coverage (Fig. 2). The CT data set was then transferred to a treatment planning workstation. Planning target volumes (PTVs) were defined as the entire breast delineated on the CT data set, extending to within 5 mm of the skin surface and 1 cm from the field edge. Breast size was measured on the axial CT images at both the posterior field edge and the isocenter. The median separation at the posterior field edge was 16.5 cm (range, 11.5–23 cm), and the median separation at the isocenter was 9.6 cm (range, 7.5–14 cm). The median breast volume, calculated using parameters that define the PTV, was 862 cm3 (range, 366 –2023 cm3). As a gauge of whether the breast was pendulous, we determined the breast depth, which was measured from the chest wall to the most gravity-dependent skin surface. The median breast depth was 11 cm (range, 7.6 –18.6 cm). Because the linear accelerators available at our institution (Varian series) restrict the dynamic delivered field width to ⬍15 cm, for very pendulous breasts, a beam splitting technique was necessary to cover the entire breast depth plus a 2-cm skin flash anteriorly. Therefore, for an IMRT beam width of ⱖ15 cm, the field was split into two subfields. To minimize field-matching errors, the adjacent subfields overlapped by at least 2 cm, with intensity feathering in the overlapping region (22). Seven patients required the use of beam splitting for breast widths ⬎15 cm. Treatment plans were developed using both conventional tangents and our sIMRT tangential beam technique based on optimization of intensity distributions across the breast, using a 6-MV beam. The details of the sIMRT technique for
supine breast RT at our institution have been previously described (21). All treatment plans were done by a single, experienced planner. The plans were compared with regard to dose–volume parameters. These parameters were chosen to reflect the dose homogeneity across the treatment volume and included the maximal dose, defined as the maximal point dose within the treatment volume, and the dose to 5% of the PTV. RESULTS Dosimetric analysis of the conventional and sIMRT plans showed that dose heterogeneity within the breast PTV was significantly greater for the conventional tangent plans. Table 1 summarizes the dosimetric parameters from the conventional tangent and sIMRT plans for the 20 patients. Of the 20 patients, 16 (80%) received a maximal dose of Table 1. Comparison of dosimetric variables between IMRT and conventional breast RT techniques Variable Dmax Mean Range D05 Mean Range
IMRT/Conv ratio (%)
IMRT (%)
Conventional (%)
107.3 ⫾ 1.8 104.9–111.8
113.8 ⫾ 4.3 108.2–123.4
94.4 ⫾ 2.4
105.4 ⫾ 1.3 103.8–108.8
109.9 ⫾ 3.4 105.7–117.8
96.0 ⫾ 2.1
Abbreviations: IMRT ⫽ intensity-modulated radiotherapy; Conv ⫽ conventional; Dmax ⫽ maximal dose; D05 ⫽ dose to 5% of planning target volume.
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Fig. 3. Dose–volume histogram for prone breast intensity modulated radiation therapy (IMRT) technique: (a) 5 mm of skin was excluded from planning target volume (PTV) and (b) buildup region was included in PTV.
ⱖ110% using conventional tangents vs. only 1 (5%) using the sIMRT plan. The isodose level encompassing 5% of the PTV, an indicator of the high-dose region within PTV, was reduced from an average of 110% with conventional tangents to 105% with sIMRT. The high-dose region, or maximal dose, was reduced from an average of 114% to 107% of the prescribed dose with sIMRT. The range for the maximal dose was 108 –123% for the conventional plans but was 105–112% for the sIMRT plans. A typical dose– volume histogram for the PTV is shown in Fig. 3. No difference was found in PTV dose homogeneity in the sIMRT plans between patients treated with or without beam splitting. The largest improvement was seen among patients with the most pendulous breasts. For example, 1 patient had a breast depth of 18.6 cm and a separation of 19.8 cm at the posterior field edge. This case required beam splitting to cover the entire field using IMRT tangential beams. The IMRT plan resulted in a decrease in the dose to 5% of the PTV from 118% to 107%. The maximal dose region was reduced from 123% to 110% of the prescribed dose. Figure 4 shows a comparison of the isodose distributions on the transverse, coronal, and sagittal slices for this patient. This case clearly demonstrates the reduction in hot spots using the sIMRT plan. Figure 5 demonstrates the trend for improvement in the reduction of hot spots for patients with larger, more pendulous breasts. The treatment planning times were recorded by one experienced planner to determine whether sIMRT breast planning would exceed the time allocated by the physics staff for breast treatment planning. Overall, the planning time for the sIMRT technique was comparable to that of the standard technique because contour delineation or multiple iterations were not needed using the sIMRT technique. The total treatment planning time, excluding the transfer of CT im-
ages from the simulator, was approximately 63 min for sIMRT and 54 min for conventional tangents. The setup time and treatment time were also equivalent for the two techniques, fitting into the 15 min allotted for breast patients. Setup error in the prone position was evaluated by weekly port films as a part of our institutional quality assurance program. Compared with supine breast setup, no difference occurred in the number of shifts based on the port films of prone breast patients requested by two experienced attending radiation oncologists during a 6-week treatment course. All patients completed the prescribed course of external beam RT. None of the patients required a treatment break or experienced Radiation Therapy Oncology Group Grade 3 or worse acute or late skin toxicity. With a median follow-up of 8.5 months (range, 1–18 months), none of the patients have developed local recurrence. One patient with ductal carcinoma in situ was diagnosed with contralateral invasive breast cancer, and a second patient was diagnosed with inoperable lung cancer 4 months after completion of her breast RT. DISCUSSION Breast-conserving therapy has allowed women to preserve an intact breast without compromising overall survival for early-stage breast cancer. Implicit in the decision to preserve the breast is the expectation of acceptable cosmetic outcomes after lumpectomy and RT. Dose inhomogeneity from conventional tangent beam RT has been implicated in poor cosmesis and late adverse effects (7–10). Traditional supine tangent RT is characterized by hot spots at the apex and periphery of the breast. This may be as much as 20% in very large patients. Prone breast RT has been shown to improve the dose homogeneity by reducing the
Dosimetric analysis of sIMRT for prone breast RT
● K. A. GOODMAN et al.
Fig. 4. Dose distributions for intensity modulated radiation therapy (IMRT) vs. conventional plans. (a) Transverse, (b) sagittal, and (c) coronal dose distributions.
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Fig. 5. Maximal dose (Dmax, diamonds) as function of breast depth for simplified intensity modulated radiation therapy (sIMRT) and conventional (Conv, squares) tangent plans.
breast separation when it hangs in a dependent fashion (11). Grann et al. (14) reported excellent long-term cosmesis among 59 patients treated with conventional tangents in the prone position. The mean cosmesis score as reported by 53 patients was 9.37 of 10. The overall long-term cosmesis was scored as excellent by the attending surgeon or radiation oncologist in 86% of patients (14). Only 21% of patients had evidence of fibrosis, edema, or breast retraction. Despite improvements in dose homogeneity in the prone position, hot spots still exist, often exceeding 105% of the prescribed dose at the superior aspect of the breast, particularly among women with the largest, most pendulous, breasts (12). In our series, with conventional tangents used for prone RT, the maximal dose range was 108 –123% of the prescribed dose. This was reduced using the sIMRT plan, reducing the hot spots in the breast on average by 7%. As depicted in Fig. 4, the volume of breast receiving a dose ⬎105% of that prescribed was also reduced. Although treatment in the prone position using standard tangential fields has some advantages over the supine technique with regard to dose homogeneity and reduction of normal tissue RT, some concern has existed regarding target volume coverage for patients with biopsy cavities in the upper outer quadrants (13). Eleven patients undergoing simulation in the prone position were analyzed at Fox Chase Cancer Center. Of those patients, 8 did not have the entire minimal target volume, defined as the biopsy cavity with a 2-cm margin, included in the lateral opposed tangential fields. The ability to cover the minimal target volume was mainly determined by the proximity of the biopsy cavity to the chest wall. Although the authors contended that local control may be compromised using prone breast RT for patients with a biopsy cavity abutting the chest wall, margins beyond the lung– chest wall interface may not need to be as generous in these cases. The ability to perform CT data acquisition has overcome this limitation regarding target volume delineation and has also allowed for the use of IMRT planning for both supine
and prone breast RT. With the use of CT simulation, the breast tissue and surgical clips can be better visualized, allowing for more accurate localization of the biopsy cavity. Adequate coverage of the target volume can be verified with the patient in the treatment position in the simulator. Patients with biopsy cavities that cannot be covered with sufficient margins using lateral opposed tangents in the prone position can be identified before treatment and alternative techniques can be used. In our experience, CT information has been invaluable in improving the accuracy of the PTV delineation, particularly in distinguishing the extent of the breast tissue laterally and in the upper outer quadrant. Finally, with the use of sIMRT planning, a homogeneous dose distribution can be achieved throughout the breast, so that not only are potential hot spots reduced, but cold spots in critical areas such as the PTV can be avoided. Our results for prone breast sIMRT are comparable to the published studies of IMRT for supine breast RT. Initial work at our institution with a sIMRT technique demonstrated a 3% reduction in the hottest dose encompassing 5% of the volume. Also statistically significant improvements occurred in the lung, heart, and contralateral breast doses achieved by the sIMRT plans for supine breast RT. Investigators at William Beaumont Hospital also found a reduction in the median maximal dose from 117% with standard tangents to 110% using their sIMRT technique (16). An update of their experience in 157 patients showed that the improved dosimetry translated into better clinical outcomes (17). Acute Grade 3 skin toxicity occurred in only 1% of patients and the cosmetic results at 12 months were scored as excellent/good in 94 of 95 patients analyzed. Acute toxicity was associated with larger irradiated volumes, which reflected breast size. Dose inhomogeneity was associated with increased skin toxicity on univariate analysis. Hurkmans and colleagues (23) reported the results of a comparison of breast IMRT with simple rectangular tangential fields and tangential fields with conformal blocks for 17
Dosimetric analysis of sIMRT for prone breast RT
left-sided breast cancer patients. Normal tissue complication probability rates for radiation pneumonitis and late cardiac morbidity were reduced using IMRT planning (23). The dose variation in the PTV was not significantly different among the three techniques. Although the sIMRT planning technique achieves superior dose distributions than conventional tangential plans, it is not more labor intensive (15). The planning and treatment times are comparable to conventional prone treatments, allowing for implementation into a busy clinical practice. Unlike the volume-based IMRT technique, contouring of the entire CT data set is not necessary for the sIMRT planning process. With only two fields, using the same gantry angles as would be applied to conventional tangential fields, the setup and treatment delivery time is the same or even less than that of the conventional prone RT technique. The primary goal of using prone breast IMRT is to reduce the dose variation in the breast, thus making breast RT an option for women at high risk of both acute and late complications from RT to the intact breast. None of the 20 patients in our study experienced Grade 3 or worse acute skin toxicity, and most only had Grade 1 skin erythema. With a median follow-up of 8.5 months, no statistically significant late cosmetic effects were noted by either the radiation oncologist or surgical oncologist who evaluated these patients. A true assessment of the late cosmesis was limited because the physicians were not specifically asked to grade the cosmetic result, nor did we obtain information from the patients as to how they assessed the cosmetic outcome. With the use of the prone sIMRT technique, the goal of limiting the dose to the lungs, heart, and contralateral breast can be achieved without compromising coverage of the breast tissue. As shown in Fig. 6, treatment of the left breast can be performed without unnecessary doses to the left ventricle or coronary arteries. Moreover, although concern exists that the use of IMRT increases the low dose to normal tissue in other sites through the use of multiple beams and longer beam-on times, this is not an issue for the sIMRT technique. The same beam arrangements are used for sIMRT as for conventional prone breast RT. In addition, a
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Fig. 6. Left breast radiation therapy using prone breast intensity modulated radiation therapy (IMRT) technique can spare left ventricle and coronary arteries.
medial wedge is not needed and, therefore, sIMRT further decreases the scatter to the contralateral breast. CONCLUSION An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, more pendulous, breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact on cosmetic outcome in this cohort of women who have historically had poor cosmesis after breast-conserving therapy. Finally, longer follow-up is needed to determine whether local control is comparable to that after standard tangents for adjuvant breast RT.
REFERENCES 1. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347: 1233–1241. 2. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227–1232. 3. Jacobson JA, Danforth DN, Cowan KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995;332:907–911. 4. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving
therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92:1143–1150. 5. Blichert-Toft M, Rose C, Andersen JA, et al., for the Danish Breast Cancer Cooperative Group. Danish randomized trial comparing breast conservation therapy with mastectomy: Six years of life-table analysis. J Natl Cancer Inst Monogr 1992;:19 –25. 6. Lazovich D, Solomon CC, Thomas DB, et al. Breast conservation therapy in the United States following the 1990 National Institutes of Health Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma. Cancer 1999;86:628–637. 7. Gray JR, McCormick B, Cox L, et al. Primary breast irradiation in large-breasted or heavy women: Analysis of cosmetic outcome. Int J Radiat Oncol Biol Phys 1991;21:347–354.
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8. Moody AM, Mayles WP, Bliss JM, et al. The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity. Radiother Oncol 1994;33: 106–112. 9. Taylor ME, Perez CA, Halverson KJ, et al. Factors influencing cosmetic results after conservation therapy for breast cancer. Int J Radiat Oncol Biol Phys 1995;31:753–764. 10. Johansen J, Overgaard J, Rose C, et al. Cosmetic outcome and breast morbidity in breast-conserving treatment—Results from the Danish DBCG-82TM national randomized trial in breast cancer. Acta Oncol 2002;41:369–380. 11. Merchant TE, McCormick B. Prone position breast irradiation. Int J Radiat Oncol Biol Phys 1994;30:197–203. 12. Mahe MA, Classe JM, Dravet F, et al. Preliminary results for prone-position breast irradiation. Int J Radiat Oncol Biol Phys 2002;52:156–160. 13. Algan O, Fowble B, McNeeley S, et al. Use of the prone position in radiation treatment for women with early stage breast cancer. Int J Radiat Oncol Biol Phys 1998;40:1137– 1140. 14. Grann A, McCormick B, Chabner ES, et al. Prone breast radiotherapy in early-stage breast cancer: A preliminary analysis. Int J Radiat Oncol Biol Phys 2000;47:319–325. 15. Hong L, Hunt M, Chui C, et al. Intensity-modulated tangential beam irradiation of the intact breast. Int J Radiat Oncol Biol Phys 1999;44:1155–1164. 16. Kestin LL, Sharpe MB, Frazier RC, et al. Intensity modulation
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to improve dose uniformity with tangential breast radiotherapy: Initial clinical experience. Int J Radiat Oncol Biol Phys 2000;48:1559–1568. Vicini FA, Sharpe M, Kestin L, et al. Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2002;54:1336–1344. Lo YC, Yasuda G, Fitzgerald TJ, et al. Intensity modulation for breast treatment using static multi-leaf collimators. Int J Radiat Oncol Biol Phys 2000;46:187–194. Zackrisson B, Arevarn M, Karlsson M. Optimized MLC-beam arrangements for tangential breast irradiation. Radiother Oncol 2000;54:209–212. van Asselen B, Raaijmakers CP, Hofman P et al. An improved breast irradiation technique using three-dimensional geometrical information and intensity modulation. Radiother Oncol 200;58:341–347. Chui CS, Hong L, Hunt M, et al. A simplified intensity modulated radiation therapy technique for the breast. Med Phys 2002;29:522–529. Hong L, Alektiar K, Chui C, et al. IMRT of large fields: Whole-abdomen irradiation. Int J Radiat Oncol Biol Phys 2002;54:278–289. Hurkmans CW, Cho BC, Damen E, et al. Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation. Radiother Oncol 2002;62:163–171.
doi:10.1016/j.ijrobp.2004.02.016
CLINICAL INVESTIGATION
Breast
DOSIMETRIC ANALYSIS OF A SIMPLIFIED INTENSITY MODULATION TECHNIQUE FOR PRONE BREAST RADIOTHERAPY KARYN A. GOODMAN, M.D.,* LINDA HONG, PH.D.,† RAQUEL WAGMAN, M.D.,* MARGIE A. HUNT, M.S.,† AND BERYL MCCORMICK, M.D.* Departments of *Radiation Oncology and †Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY Purpose: Prone-position breast radiotherapy (RT) has been described as an alternative technique to improve dose homogeneity for women with large, pendulous breasts. We report the feasibility and dosimetric analysis of a simplified intensity-modulated RT (IMRT) technique, previously reported for women in the supine treatment position, to plan prone-position RT to the intact breast. Methods and Materials: Twenty patients with clinical Stage TisN0-T1bN1 breast cancer undergoing breastconserving therapy underwent whole breast RT using a prone position technique. The treatment plans were developed using both conventional tangents and a simplified intensity-modulated tangential beam technique based on optimization of the intensity distributions across the breast. The plans were compared with regard to the dose–volume parameters. Results: Dose heterogeneity within the breast planning target volume was significantly greater for the conventional tangent plans. Of 20 patients, 16 (80%) received maximal doses of >110% using the conventional tangents vs. only 1 (5%) using the IMRT plan. The isodose level encompassing 5% of the planning target volume was reduced from an average of 110% with conventional tangents to 105% with IMRT. The maximal dose within the planning target volume was reduced from an average of 114% with conventional tangents to 107% with IMRT. The greatest improvement was seen in the patients with the most pendulous breasts. Conclusion: An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, pendulous breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact acute toxicity and cosmetic outcome in this cohort of women who have historically suffered from poor cosmesis after breast-conserving therapy. © 2004 Elsevier Inc. Intensity-modulated radiotherapy, Prone breast radiotherapy, Breast cancer.
13). The use of the prone position has been used at our institution as an option to improve dose homogeneity for women with large, pendulous breasts (11, 14). Treatment in the prone position has been shown to reduce the maximal dose in the high-dose regions usually found at the superior and inferior regions of the breast with the supine treatment technique and also to minimize the dose gradient from the apex to the base at the chest wall interface (11). These improvements in dose uniformity have been associated with superior cosmetic results (14). Preliminary data on local control and survival appear to be comparable to that found for patients treated in the supine position. Intensity-modulated RT (IMRT) has also been introduced for whole breast RT to improve dose homogeneity (15–20). This approach has been successful in reducing cardiac, lung, and contralateral breast doses, as well as in decreasing dose inhomogeneity within the breast. However, treatment plan-
INTRODUCTION Evidence from large randomized, controlled trials has established the equivalence in survival for breast-conserving therapy and mastectomy for most women with early-stage breast cancer (1–5). On the basis of these results, a clear national trend toward the use of conservative surgery and postoperative radiotherapy (RT) has occurred (6). Despite this widespread change in practice, some women are believed to be poor candidates for breast conservation owing to large breast size or pendulous breasts. Several studies have shown increased acute toxicity and inferior cosmetic outcomes among large-breasted patients. Consequently, large, pendulous breasts have been considered a relative contraindication to breast-conserving therapy (7–10). The technical challenges involved in irradiating women with large, pendulous breasts in the standard supine position have led to the investigation of alternative techniques (11– Reprint requests to: Beryl McCormick, M.D., Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Tel: (212) 639-6828; Fax: (212) 639-2417; E-mail: [email protected] Presented at the 44th Annual Meeting of the American Society
for Therapeutic Radiology and Oncology, New Orleans, LA, October 7, 2002. Received Sep 22, 2003, and in revised form Feb 3, 2004. Accepted for publication Feb 9, 2004. 95
96
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, 2004
Fig. 1. Prone breast board. (a) Customized prone breast board with adjustable aperture and wedge for contralateral breast. (b) Ipsilateral breast and anterior chest wall hang in dependent fashion away from thorax with ipsilateral arm placed above head.
ning for breast IMRT can be time-consuming, thereby making the technique impractical in a busy clinical practice. At our institution, we have developed a simplified IMRT (sIMRT) technique that achieves dose homogeneity comparable to that with the full-fledged contour-based IMRT technique but requires no more planning and treatment time than standard wedged tangent fields (21). This technique focuses on the treatment volume only, using inverse planning to deliver a uniform dose across the breast. Using the standard opposed tangential beam arrangement, the optimal intensity of each pencil beam is determined to equalize the dose to the mid-point of the pencil beam segment that intersects the treatment volume. This method eliminates the need for contour delineation, which is necessary for the full-fledged IMRT technique. By combining IMRT and prone breast RT, we have been able to optimize dose homogeneity within the breast further, thereby allowing women with large, pendulous breasts to undergo breast-conserving therapy without compromising cosmetic outcomes. The purpose of this study was to report the feasibility and dosimetric analysis of our sIMRT technique, previously reported for women in the supine treatment position, to plan prone-position RT of the intact breast. METHODS AND MATERIALS Clinical characteristics Twenty patients with early-stage breast cancer undergoing breast-conserving therapy at Memorial Sloan-Kettering Cancer Center were treated with prone breast RT using the sIMRT technique. The institutional review board approved our review of patient information. Patient age ranged from 39 to 79 years (median 61). All the patients had clinical Stage TisN0-T1bN1 breast cancer and underwent conservative surgery consisting of excisional biopsy and sentinel lymph node biopsy (n ⫽ 11), excisional biopsy and axillary lymph node dissection (n ⫽ 6), or excisional biopsy alone (n ⫽ 3). Two of the patients undergoing lymph node biopsy or dissection had one positive node. The final pathologic di-
agnosis was ductal carcinoma in situ in 3 and infiltrating ductal or lobular carcinoma in 17. Five patients underwent adjuvant chemotherapy with either Cytoxan, methotrexate, and 5-fluorouracil (n ⫽ 2) or adriamycin and Cytoxan with or without Taxol (n ⫽ 3). Procedure A prototype prone-breast board with an adjustable aperture for the breast was designed (Fig. 1) with a platform height and width allowing clearance through a CT simulator (Picker 5000, Cleveland, OH). The CT simulator has a 70-cm bore and 48-cm field of view. To fit the patient through the CT scan aperture and obtain images of the whole breast without distortion, we designed the height of the platform for the simulation at 17 cm, instead of 25 cm, the height of the standard platform of the prone breast board. Patient eligibility for the prone breast IMRT technique was, therefore, subject to the limitation of the CT scan aperture and field of view. The indication for treatment in the prone position was large or pendulous breast size, history of tobacco use, or patient preference for most patients. The objectives of the prone technique at our institution have been previously described (11, 14). In brief, patients underwent simulation lying prone on the custom board with the ipsilateral breast positioned over the aperture to hang through in a dependent fashion. The ipsilateral arm was placed superolaterally, and the patient held on to an adjustable handle on the board. The contralateral breast was placed on a custom support wedge with the contralateral arm down close to the body. The patient was rotated slightly to allow the ipsilateral chest wall to extend into the board aperture. The physician placed posterior border marks on the medial and lateral aspects of the breast; superior and inferior borders were also indicated by the physician. CT wires were placed on these markers and on the lumpectomy scar. The patient was scanned at least 5 cm beyond the superior and inferior borders of the breast. The orientation of the posterior field edge of the coplanar tangent beams was set in
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Fig. 2. Computed tomography simulation images used to determine arrangement of tangent beams.
virtual simulation by the radiation oncologist using the CT images. This was checked through each cut of the simulation scan for breast tissue coverage (Fig. 2). The CT data set was then transferred to a treatment planning workstation. Planning target volumes (PTVs) were defined as the entire breast delineated on the CT data set, extending to within 5 mm of the skin surface and 1 cm from the field edge. Breast size was measured on the axial CT images at both the posterior field edge and the isocenter. The median separation at the posterior field edge was 16.5 cm (range, 11.5–23 cm), and the median separation at the isocenter was 9.6 cm (range, 7.5–14 cm). The median breast volume, calculated using parameters that define the PTV, was 862 cm3 (range, 366 –2023 cm3). As a gauge of whether the breast was pendulous, we determined the breast depth, which was measured from the chest wall to the most gravity-dependent skin surface. The median breast depth was 11 cm (range, 7.6 –18.6 cm). Because the linear accelerators available at our institution (Varian series) restrict the dynamic delivered field width to ⬍15 cm, for very pendulous breasts, a beam splitting technique was necessary to cover the entire breast depth plus a 2-cm skin flash anteriorly. Therefore, for an IMRT beam width of ⱖ15 cm, the field was split into two subfields. To minimize field-matching errors, the adjacent subfields overlapped by at least 2 cm, with intensity feathering in the overlapping region (22). Seven patients required the use of beam splitting for breast widths ⬎15 cm. Treatment plans were developed using both conventional tangents and our sIMRT tangential beam technique based on optimization of intensity distributions across the breast, using a 6-MV beam. The details of the sIMRT technique for
supine breast RT at our institution have been previously described (21). All treatment plans were done by a single, experienced planner. The plans were compared with regard to dose–volume parameters. These parameters were chosen to reflect the dose homogeneity across the treatment volume and included the maximal dose, defined as the maximal point dose within the treatment volume, and the dose to 5% of the PTV. RESULTS Dosimetric analysis of the conventional and sIMRT plans showed that dose heterogeneity within the breast PTV was significantly greater for the conventional tangent plans. Table 1 summarizes the dosimetric parameters from the conventional tangent and sIMRT plans for the 20 patients. Of the 20 patients, 16 (80%) received a maximal dose of Table 1. Comparison of dosimetric variables between IMRT and conventional breast RT techniques Variable Dmax Mean Range D05 Mean Range
IMRT/Conv ratio (%)
IMRT (%)
Conventional (%)
107.3 ⫾ 1.8 104.9–111.8
113.8 ⫾ 4.3 108.2–123.4
94.4 ⫾ 2.4
105.4 ⫾ 1.3 103.8–108.8
109.9 ⫾ 3.4 105.7–117.8
96.0 ⫾ 2.1
Abbreviations: IMRT ⫽ intensity-modulated radiotherapy; Conv ⫽ conventional; Dmax ⫽ maximal dose; D05 ⫽ dose to 5% of planning target volume.
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Fig. 3. Dose–volume histogram for prone breast intensity modulated radiation therapy (IMRT) technique: (a) 5 mm of skin was excluded from planning target volume (PTV) and (b) buildup region was included in PTV.
ⱖ110% using conventional tangents vs. only 1 (5%) using the sIMRT plan. The isodose level encompassing 5% of the PTV, an indicator of the high-dose region within PTV, was reduced from an average of 110% with conventional tangents to 105% with sIMRT. The high-dose region, or maximal dose, was reduced from an average of 114% to 107% of the prescribed dose with sIMRT. The range for the maximal dose was 108 –123% for the conventional plans but was 105–112% for the sIMRT plans. A typical dose– volume histogram for the PTV is shown in Fig. 3. No difference was found in PTV dose homogeneity in the sIMRT plans between patients treated with or without beam splitting. The largest improvement was seen among patients with the most pendulous breasts. For example, 1 patient had a breast depth of 18.6 cm and a separation of 19.8 cm at the posterior field edge. This case required beam splitting to cover the entire field using IMRT tangential beams. The IMRT plan resulted in a decrease in the dose to 5% of the PTV from 118% to 107%. The maximal dose region was reduced from 123% to 110% of the prescribed dose. Figure 4 shows a comparison of the isodose distributions on the transverse, coronal, and sagittal slices for this patient. This case clearly demonstrates the reduction in hot spots using the sIMRT plan. Figure 5 demonstrates the trend for improvement in the reduction of hot spots for patients with larger, more pendulous breasts. The treatment planning times were recorded by one experienced planner to determine whether sIMRT breast planning would exceed the time allocated by the physics staff for breast treatment planning. Overall, the planning time for the sIMRT technique was comparable to that of the standard technique because contour delineation or multiple iterations were not needed using the sIMRT technique. The total treatment planning time, excluding the transfer of CT im-
ages from the simulator, was approximately 63 min for sIMRT and 54 min for conventional tangents. The setup time and treatment time were also equivalent for the two techniques, fitting into the 15 min allotted for breast patients. Setup error in the prone position was evaluated by weekly port films as a part of our institutional quality assurance program. Compared with supine breast setup, no difference occurred in the number of shifts based on the port films of prone breast patients requested by two experienced attending radiation oncologists during a 6-week treatment course. All patients completed the prescribed course of external beam RT. None of the patients required a treatment break or experienced Radiation Therapy Oncology Group Grade 3 or worse acute or late skin toxicity. With a median follow-up of 8.5 months (range, 1–18 months), none of the patients have developed local recurrence. One patient with ductal carcinoma in situ was diagnosed with contralateral invasive breast cancer, and a second patient was diagnosed with inoperable lung cancer 4 months after completion of her breast RT. DISCUSSION Breast-conserving therapy has allowed women to preserve an intact breast without compromising overall survival for early-stage breast cancer. Implicit in the decision to preserve the breast is the expectation of acceptable cosmetic outcomes after lumpectomy and RT. Dose inhomogeneity from conventional tangent beam RT has been implicated in poor cosmesis and late adverse effects (7–10). Traditional supine tangent RT is characterized by hot spots at the apex and periphery of the breast. This may be as much as 20% in very large patients. Prone breast RT has been shown to improve the dose homogeneity by reducing the
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Fig. 4. Dose distributions for intensity modulated radiation therapy (IMRT) vs. conventional plans. (a) Transverse, (b) sagittal, and (c) coronal dose distributions.
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Fig. 5. Maximal dose (Dmax, diamonds) as function of breast depth for simplified intensity modulated radiation therapy (sIMRT) and conventional (Conv, squares) tangent plans.
breast separation when it hangs in a dependent fashion (11). Grann et al. (14) reported excellent long-term cosmesis among 59 patients treated with conventional tangents in the prone position. The mean cosmesis score as reported by 53 patients was 9.37 of 10. The overall long-term cosmesis was scored as excellent by the attending surgeon or radiation oncologist in 86% of patients (14). Only 21% of patients had evidence of fibrosis, edema, or breast retraction. Despite improvements in dose homogeneity in the prone position, hot spots still exist, often exceeding 105% of the prescribed dose at the superior aspect of the breast, particularly among women with the largest, most pendulous, breasts (12). In our series, with conventional tangents used for prone RT, the maximal dose range was 108 –123% of the prescribed dose. This was reduced using the sIMRT plan, reducing the hot spots in the breast on average by 7%. As depicted in Fig. 4, the volume of breast receiving a dose ⬎105% of that prescribed was also reduced. Although treatment in the prone position using standard tangential fields has some advantages over the supine technique with regard to dose homogeneity and reduction of normal tissue RT, some concern has existed regarding target volume coverage for patients with biopsy cavities in the upper outer quadrants (13). Eleven patients undergoing simulation in the prone position were analyzed at Fox Chase Cancer Center. Of those patients, 8 did not have the entire minimal target volume, defined as the biopsy cavity with a 2-cm margin, included in the lateral opposed tangential fields. The ability to cover the minimal target volume was mainly determined by the proximity of the biopsy cavity to the chest wall. Although the authors contended that local control may be compromised using prone breast RT for patients with a biopsy cavity abutting the chest wall, margins beyond the lung– chest wall interface may not need to be as generous in these cases. The ability to perform CT data acquisition has overcome this limitation regarding target volume delineation and has also allowed for the use of IMRT planning for both supine
and prone breast RT. With the use of CT simulation, the breast tissue and surgical clips can be better visualized, allowing for more accurate localization of the biopsy cavity. Adequate coverage of the target volume can be verified with the patient in the treatment position in the simulator. Patients with biopsy cavities that cannot be covered with sufficient margins using lateral opposed tangents in the prone position can be identified before treatment and alternative techniques can be used. In our experience, CT information has been invaluable in improving the accuracy of the PTV delineation, particularly in distinguishing the extent of the breast tissue laterally and in the upper outer quadrant. Finally, with the use of sIMRT planning, a homogeneous dose distribution can be achieved throughout the breast, so that not only are potential hot spots reduced, but cold spots in critical areas such as the PTV can be avoided. Our results for prone breast sIMRT are comparable to the published studies of IMRT for supine breast RT. Initial work at our institution with a sIMRT technique demonstrated a 3% reduction in the hottest dose encompassing 5% of the volume. Also statistically significant improvements occurred in the lung, heart, and contralateral breast doses achieved by the sIMRT plans for supine breast RT. Investigators at William Beaumont Hospital also found a reduction in the median maximal dose from 117% with standard tangents to 110% using their sIMRT technique (16). An update of their experience in 157 patients showed that the improved dosimetry translated into better clinical outcomes (17). Acute Grade 3 skin toxicity occurred in only 1% of patients and the cosmetic results at 12 months were scored as excellent/good in 94 of 95 patients analyzed. Acute toxicity was associated with larger irradiated volumes, which reflected breast size. Dose inhomogeneity was associated with increased skin toxicity on univariate analysis. Hurkmans and colleagues (23) reported the results of a comparison of breast IMRT with simple rectangular tangential fields and tangential fields with conformal blocks for 17
Dosimetric analysis of sIMRT for prone breast RT
left-sided breast cancer patients. Normal tissue complication probability rates for radiation pneumonitis and late cardiac morbidity were reduced using IMRT planning (23). The dose variation in the PTV was not significantly different among the three techniques. Although the sIMRT planning technique achieves superior dose distributions than conventional tangential plans, it is not more labor intensive (15). The planning and treatment times are comparable to conventional prone treatments, allowing for implementation into a busy clinical practice. Unlike the volume-based IMRT technique, contouring of the entire CT data set is not necessary for the sIMRT planning process. With only two fields, using the same gantry angles as would be applied to conventional tangential fields, the setup and treatment delivery time is the same or even less than that of the conventional prone RT technique. The primary goal of using prone breast IMRT is to reduce the dose variation in the breast, thus making breast RT an option for women at high risk of both acute and late complications from RT to the intact breast. None of the 20 patients in our study experienced Grade 3 or worse acute skin toxicity, and most only had Grade 1 skin erythema. With a median follow-up of 8.5 months, no statistically significant late cosmetic effects were noted by either the radiation oncologist or surgical oncologist who evaluated these patients. A true assessment of the late cosmesis was limited because the physicians were not specifically asked to grade the cosmetic result, nor did we obtain information from the patients as to how they assessed the cosmetic outcome. With the use of the prone sIMRT technique, the goal of limiting the dose to the lungs, heart, and contralateral breast can be achieved without compromising coverage of the breast tissue. As shown in Fig. 6, treatment of the left breast can be performed without unnecessary doses to the left ventricle or coronary arteries. Moreover, although concern exists that the use of IMRT increases the low dose to normal tissue in other sites through the use of multiple beams and longer beam-on times, this is not an issue for the sIMRT technique. The same beam arrangements are used for sIMRT as for conventional prone breast RT. In addition, a
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Fig. 6. Left breast radiation therapy using prone breast intensity modulated radiation therapy (IMRT) technique can spare left ventricle and coronary arteries.
medial wedge is not needed and, therefore, sIMRT further decreases the scatter to the contralateral breast. CONCLUSION An IMRT planning approach is feasible for prone-position breast RT and improves dose homogeneity, particularly in women with larger, more pendulous, breasts. Additional follow-up is necessary to determine whether the improvements in dose homogeneity impact on cosmetic outcome in this cohort of women who have historically had poor cosmesis after breast-conserving therapy. Finally, longer follow-up is needed to determine whether local control is comparable to that after standard tangents for adjuvant breast RT.
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