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Background: To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement. Methods and Materials: Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose. Results: The mean coverage of the level I/II axillary volume by the 95% isodose line (V ) was 23.9% (range 0.3 - D95% 65.4%). The mean Ipsilateral Lung V was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume D50% correlated to Axillary V in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those D95% with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung V correlated with angle of the expander from D50% midline (p = 0.05). Conclusions: In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated. Keywords: post-mastectomy radiation, axillary dose, tissue expander, breast reconstruction, tangent fields Introduction patient preference and improved breast reconstruction Mastectomy is a component of therapy for many options [1,2]. women with breast cancer, both in the locally advanced Post-mastectomy breast reconstruction rates have increased in the past 3 decades . Options regarding and early stages. Recently, several institutions have reported increased mastectomy rates owing to several timing of reconstruction include immediate, delayed, factors including MRI use, genetic testing, shifting and most recently immediate-delayed. Currently, between 25-42% of women undergo immediate recon- * Correspondence: firstname.lastname@example.org struction and expander placement is a frequently uti- † Contributed equally lized modality [4,5]. Delayed-immediate reconstruction Department of Radiation Oncology, Hollings Cancer Center, Medical using tissue expanders is an attractive option in patients University of South Carolina: 169 Ashley Ave Room 168 MSC 318, Charleston, SC 29425, USA requiring radiation because of the decreased Full list of author information is available at the end of the article © 2011 Russo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Russo et al. Radiation Oncology 2011, 6:179 Page 2 of 8 http://www.ro-journal.com/content/6/1/179 complications and increased aesthetics associated with Table 1 Patient and Treatment Characteristics not radiating autologous tissue or a permanent implant Characteristic [6,7]. Age (n = 23) 49 (25-71)* Post-mastectomy radiation therapy (PMRT) is indi- Race cated in many of these patients to improve local control White 16 and overall survival [8-11]. As curability supersedes AA 6 cosmesis in these patients, it is important to ask the Hispanic 1 question: “Does immediate reconstruction with tissue Tumor Laterality expanders impact the quality of PMRT?” Studies show L16 that the unique geometry of immediate reconstruction using various reconstruction modalities can compromise R4 coverage of the chest wall and internal mammary nodes B/L 3 and increase lung and heart dose [12-14]. These studies Tumor Location† included few women with expanders and most patients UOQ 9 had regional nodal irradiation. LOQ 2 Although axillary dose has been addressed in the UIQ 4 breast-conservation setting it has not been studied in LIQ 2 reconstructed patients. Expanders contain 20-30% Chest Wall 1 more saline compared with the final implant. There- Overlapping 4 fore, it is important to analyze the population of Unknown 1 women with tissue expanders. Recent attempts to elim- inate axillary dissection with small numbers of positive Histology nodes on sentinel node biopsy in early stage breast IDC 21 cancer are promising and do not appear to compro- ILC 2 mise outcomes in appropriately selected women who Nodal Surgery Radiated Side receive breast only radiation with tangents . In SLNB alone 4 light of this new paradigm, the dose delivered to the ALND 19 axilla is increasingly important as incidentally delivered Type of Reconstruction axillary dose will be relied on to control potential resi- Ipsilateral Alone 10 dual disease. The purpose of this study is to define the Bilateral†† 13 dosimetric coverage of axillary volumes (level I/II) and Expander Location the lung volume irradiated in patients treated with tan- gent fields following mastectomy and tissue expander Sub Pec Major 33 placement and to identify variables that impact dose to Sub Latissimus Flap§ 2 these structures. Unknown 1 Clinical Stage Methods and Materials Tis|| 3 Between 2006- 2010 a cohort of twenty-three patients IA 5 who had undergone postmastectomy radiotherapy fol- IIA 7 lowing tissue expander placement and expansion was IIB 7 identified. IRB approval was obtained for the study. IIIA 2 Characteristics of the population are in Table 1. The Unknown 2 study cohort had a tissue expander placed on the radiated side prior to radiation as part of a delayed- Pathologic Stage immediate reconstruction paradigm. Patients were ypTis 1 excluded who had a reconstruction modality other than pTis 2 tissue expander such as an implant or autologous tissue ypT0N0 4 without an expander. Patients with regional nodal radia- ypIA 3 tion were allowed, however, these patients were ypIIA 2 replanned with tangents only. Therefore, no treatment pIIA 3 plans incorporated a supraclavicular, internal mammary ypIIB 2 or posterior axillary boost field. None of the patients pIIB 5 received a boost. Inverse-planned IMRT was not ypIIIA 3 allowed. Russo et al. Radiation Oncology 2011, 6:179 Page 3 of 8 http://www.ro-journal.com/content/6/1/179 Table 1 Patient and Treatment Characteristics (Continued) recorded. The expander angle was defined as the angle between the patient’s sagittal midline and the most lat- pIIIA 1 eral border of the expander in the axial plane (Figure 1). Systemic Therapy Intra-expander distance was only recorded in patients Neoadjuvant 13 with bilateral reconstruction and was defined as the clo- Adjuvant 10 sest distance between the most medial portions of the * Median (range) expanders. Lung V was chosen because the 50% iso- D50% † Irradiated side only dose line corresponds to the medial border of the half- †† 3 for contralateral synchronous primary and 10 prophylactically beam blocked treatment fields, thus it should correlate § 1 on irradiated side, 1 contralateral with variables that change the treatment geometry. Also, || All Tis had contralateral invasive disease the median prescription dose was 50 Gy; therefore the 50% isodose line corresponds to 25 Gy which is approxi- All patients underwent CT simulation from the mand- mately the same as 20 Gy which has been shown to cor- ible through the lungs using 3 mm slices in the supine relate with pneumonitis rates. position with an indexed breast board. No patient had Summary statistics describe the various patient char- their ipsilateral or contralateral expander deflated prior acteristics. Pearson correlation coefficients and their to or during radiation therapy. Tangents were designed to incorporate the chest wall with expander. In no patient were the tangents designed to treat the axilla. Field borders were initially defined on the CT simula- tion and were as follows: superior - base of clavicular head, inferior - 2 cm below the contralateral breast, medial - mid-sternum, lateral - mid-axillary line or appropriately lateral to insure adequate coverage of the most lateral extent of the expander. In case of bilateral reconstruction, the inferior border was placed in the area reasonably thought by the treating physician to include the pre-mastectomy breast extent. Treatment planning was performed using step-and- shoot forward-planned IMRT using opposed tangential beams. A field-in-field technique was used to achieve dose homogeneity of 98 - 105% within the CTV. Half- beam blocks were used to prevent beam divergence into the lung. The prescription was normalized to a point just superficial to the surface of the pectoralis major in a plane perpendicular to the central axis at mid-separa- tion. The prescription was delivered to the isodose line which best covered the breast CTV. This line was usually the 98-99% isodose line. The tangent angles were designed to include a minimum of lung tissue while maximizing coverage of the CTV. Axillary levels I and II were contoured retrospectively using the RTOG contouring atlas . Dose distribu- tions to volumes of interest were determined using dose volume histograms. The following variables were exam- ined to determine their relationship to the axillary V and lung V : Superior-to-inferior location of D95% D50% expander, expander angle, intra-expander distance expander volume and axillary volume. The superior-to- inferior location of the expander was defined as the dis- Figure 1 Measurement of expander angle. Lateral location of the expander defined by the expander angle (black arrow) measured tance between the inferior border of the humeral head on the axial slice with the most lateral expander location from and the superior border of the expander. To normalize midline to the lateral expander border in patient with a small (30° - this to patient height, the distance between the humeral top) and large (48° - bottom) angle. head and the tip of the xiphoid process was also Russo et al. Radiation Oncology 2011, 6:179 Page 4 of 8 http://www.ro-journal.com/content/6/1/179 respective p-values were used to evaluate the relation- ship between the axillary V , lung V , and patient D95% D50% and expander physical characteristics. Results Patient, tumor, and treatment characteristics are shown in table 1. The median patient age was 49. Nineteen patients had a full axillary dissection while 4 had senti- nel node biopsy alone. Thirty-six breasts were recon- structed in 23 patients - 13 patients with bilateral procedures and 10 ipsilateral only. The most common type of reconstruction was a subpectoral expander occurring in 30 breasts. Two patients had the expander placed below a pedicled latissimus myocutaneous flap. All patients received chemotherapy, 57% received it neoadjuvantly and 43% adjuvantly. Table 2 shows descriptive statistics of the metrics that were analyzed. The mean level I/II axillary volume 3 3 Figure 2 Box and whisker plots of the Axillary Volume and was 117.6 cm (range 49.7 - 192.9 cm ) and the mean Axillary V D95% volume of the level I/II axilla covered by the 95% line 3 3 was 31.6 cm (range 0.4-90.6 cm )(Figure 2).No patient had complete coverage of the level I/II axillary V did not correlate with the expander volume (p = D95% volume by the 95% isodose line. The mean percent of 0.60). The contralateral expander volume correlated to the level I/II axillary volume covered by the 95% iso- the ipsilateral expander volume with an r of 0.95. The dose line was 23.9% (range 0.3-65.4%). Inspection of superior-to-inferior position of the expander as mea- the isodose curves revealed that underdosing mainly sured from the humeral head did not correlate to the occurred in the posterior-superior axilla as shown in axillary dose. This also held true when this distance was Figure 3. The mean percent of the ipsilateral lung normalized to the patient’s thoracic size using the hum- receiving 50% of the prescription dose was 8.8% (range eral head to xiphoid process distance. Neither the dis- 2.2-20.9%). tance between expanders nor the expander angle The volume of both the ipsilateral and contralateral impacted axillary V . D95% expander and the level I/II axillary volume correlated Regarding the dose to the lung, only the expander with % axillary V (Table 3). The volume of the ipsi- D95% angle correlated with the lung dose. Neither the super- lateral expander in all patients correlated to axillary ior-to-inferior expander position nor the volume of the V with an r = 0.51 (p = 0.012). In the thirteen D95% expanders impacted lung dose. Axillary V did not D95% patients with bilateral reconstruction, the axillary V D95% correlate with the Lung V (r = 0.19). D50% correlated with the ipsilateral and contralateral expander volume (p = 0.01 and 0.006 respectively). However, in Discussion patients with ipsilateral reconstruction only, the axillary In this study, we found that in patients undergoing post- mastectomy radiation therapy and delayed-immediate reconstruction with an inflated expander, the coverage Table 2 Descriptive statistics of the axilla is impacted by the volume of the expander, Range Median Mean StdDev but only in patients with bilateral reconstruction. The Axillary Volume* 49.7-192.9 113.6 117.6 41.4 underdosing occurred primarily in the posterior-superior Axillary V † 0.4-90.6 21.9 31.6 28.1 D95% extent of axillary levels I and II. The inferior portion of % Axillary V †† 0.3-65.4 24.6 23.9 17 D95% the axilla is difficult to define radiographically in this Expander Volume 170-492 437.4 485.4 190.4 population of patients. Also, dose to the lung is corre- Intra-Expander Distance 1.6-13.3 5.8 6.1 2.9 lated with the angle of the expander. The superior-to- Expander Angle 30-49° 41° 41° 5.2° inferior extent of the expander did not impact the axil- lary or lung dose. Ipsilateral Lung V 2.2-20.9 7.9 8.8 4.2 D50% 3 A possible explanation for the correlation of axillary * All volumes in (cm ) coverage and expander volume in bilaterally recon- † Volume that receives at least 95% of the Rx dose †† Percent of axilla that receives at least 95% of the Rx dose structed patients is that the expander was used as a Russo et al. Radiation Oncology 2011, 6:179 Page 5 of 8 http://www.ro-journal.com/content/6/1/179 Figure 3 Axillary coverage. Coverage by the 95% isodose line as it relates to the axilla in a patient with 65% (left) and a patient with 3% (right) axillary coverage. surrogate for the pre-mastectomy breast tissue because encompass these larger expanders and the amount of there is no contralateral native breast to use as a tem- axillary volume incidentally included in the tangents plate. Thus, if larger volume expanders are placed, then would increase. Conversely, if smaller volume expanders the tangents would be designed to completely were placed, then the tangents would conform to the Russo et al. Radiation Oncology 2011, 6:179 Page 6 of 8 http://www.ro-journal.com/content/6/1/179 Table 3 Pearson correlation (r) and p values of variables with axillary and lung dose r value: % Axillary V p value r value: % Ipsilateral Lung V P value D95% D50% HH to Expander 0.13 0.56 0.005 0.98 HH to Exp/HH to XP 0.16 0.46 0.03 0.88 Expander Angle -0.25 0.24 0.41 0.05 Expander Distance 0.34 0.28 0.50 0.10 Ipsi Exp Volume 0.51 0.012 0.01 0.95 Ipsi Exp Vol* 0.18 0.60 0.21 0.54 Ipsi Exp Vol† 0.70 0.01 0.10 0.77 Contralat Exp Volume 0.76 0.006 0.19 0.56 Axillary Volume 0.52 0.011 N/A N/A * Only patients with ipsilateral expanders † Only patients with bilateral expanders size of the expander and the amount of axillary volume as in our study. Our data are consistent with McCor- incidentally included in the tangents would decrease. mick et al who reported that axillary hemostasis clips in A relationship was also seen between the axillary 45 patients are included in 2D planned tangents on 38% volume and the axillary V . This may be due to the of patients and that incomplete clip coverage occurred D95% difficulty in delineating the inferior extent of axillary in the posterior-superior portion . Krasin et al level I in this population of patients. The RTOG con- reconstructed 2D plans to obtain 3D dose-volume data touring atlas defines the inferior extent of level I as the in patients treated with standard breast tangents and insertion of the pectoralis major into the ribs . We found that out of 25 patients, one had more than 95% found this insertion point difficult to locate due to dis- coverage of level I and none had more than 95% cover- ruptions in the normal anatomy from the expanders’ ageoflevel II.Also, themeanV was 7.5% which is subpectoral location and also that an alloderm graft was slightly less than our 8.8% mean amount of lung receiv- often used in the inferior-lateral portion of the expander ing 50% of the prescription dose of 50 Gy . to hold it in place on the chest wall. Published data also conflicts with our results. Good- The only parameter in our study that impacted lung manetal reportedthatinpatientsundergoingtangen- dose was the lateral location of the expander as measured tial only radiation, levels I and II were covered in 8 of 9 by the angle of the expander from midline sagittal plane. patients . Details regarding anatomic boundaries of This is likely because deeper tangents are required to the axillary were not provided. However, the anatomic treat the more lateral expanders thus resulting in a higher landmarks for contouring the axilla likely differed from lung dose. As modern systemic agents used in breast can- our study as the RTOG contouring atlas had not been cer can be associated with a small increased risk of pneu- published. Also, the surgical therapeutic and reconstruc- monitis, this should be taken into account when placing tive management of these patients varied. expanders. Also, the risk of secondary pulmonary malig- In a similar investigation to ours, Reed et al performed nancies, especially in smokers, may be reduced by mini- an analysis of axillary levels I and II dose using 3D plan- mizing exposure of the lung [17,18]. ning in patients with breast conservation and found that Our study findings of poor axillary coverage relative to a mean of 55% of the axilla was covered by the 95% line the prescription dose agree with data from several inves- which is more than double our finding of 23.9% . tigators. Aristei et al showed that the median D of Reasons for this difference are that axillary contouring levels I and II was 6.75 Gy and 1.75 Gy, respectively, in landmarks were different which could lead to more gen- breast conserved patients treated with tangents only erous contouring in well covered areas like low level I undergoing 2D simulation with 3D dose analysis . and less generous in poorly covered areas such as in the This represented, as a percent of the prescription dose posterior-superior direction, an area often underdosed of 50 Gy, a median D of 13.5% to level I and 3.5% to in our study. Indeed the mean axillary volume in their 3 3 level II. Smitt et al showed that in patients with con- study was 146.3 cm compared with 117.6 cm in ours. served breasts undergoing CT planning with the goal of However, similar to our study the posterior-superior covering the breast alone, a mean axillary dose of more area was not well covered. Second, these patients were than 90% of the prescription dose was only achieved in not planned with step-and-shoot techniques as in our 1of6patients.Also, underdosing occurred in the study and it is possible that more traditional breast only posterior-superior portion of levels I and II of the axilla irradiation techniques deliver a higher dose to the axilla. Russo et al. Radiation Oncology 2011, 6:179 Page 7 of 8 http://www.ro-journal.com/content/6/1/179 A limitation of our study is the small number of Author information patients.Nonetheless,toourknowledgeitrepresents Dr. Harper is a radiation oncologist, certified by the the largest study of axillary and lung doses in delayed- American Board of Radiology. Her primary focus is in immediate reconstructed women undergoing modern the treatment of breast cancer, palliative care, and head radiotherapy, many of whom had bilateral and neck cancer. In the field of breast cancer, Dr. Har- reconstruction. per has published extensive clinical research on the Our results are important for several reasons. Recent topic of accelerated partial breast irradiation. She is a studies have shown that both mastectomy rates and member of Hollings Cancer Center Protocol Review reconstruction rates are increasing [1-3]. As such we Committee, must analyze this group of post-mastectomy women Hollings Cancer Center Cancer Registry Data with respect to delivery of radiation and outcomes. In Reviewer and Southwest Oncology Group Breast Cancer addition, the results of our study have implications in Committee Member. th light of the recently reported ACOSOG Z0011 trial Dr Russo is a resident in radiation oncology in his 4 which showed that women with less than 3 positive year of training. He has an interest in breast cancer nodes on sentinel node biopsy who received tangent research and has published in this area as well as CNS, only radiation had overall survival, locoregional control lung and GYN. and disease-free survival that is not inferior to those who received axillary node dissection and the same Acknowledgements radiation . Although in this trial women received Accepted for poster presentation at the Annual Meeting of the American breast conservation and not mastectomy, as in our Society for Therapeutic Radiology and Oncology October 31 - Nov 4, 2010, San Diego, California study, the results may be applicable to women who The research presented in this article was supported in part by the choose mastectomy but were otherwise eligible for the Biostatistics Shared Resource as part of the Hollings Cancer Center at the trial. As these women may decide to pursue post-mas- Medical University of South Carolina, United States of America, which is funded by a Cancer Center Support Grant P30 CA138313. tectomy reconstruction, it is important to quantify the dose to the axilla. This is particularly important consid- Author details ering 27.3% of women on the ACOSOG trial with posi- Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina: 169 Ashley Ave Room 168 MSC 318, Charleston, tive sentinel nodes had additional metastatic nodes on SC 29425, USA. Division of Biostatistics and Epidemiology, Hollings Cancer subsequent axillary dissection. Center, Medical University of South Carolina: 86 Jonathan Lucas St., Charleston, SC 29425, USA. Conclusions Authors’ contributions Efforts to reduce morbidity by decreasing the extent of JR carried out the data collection, assisted in the statistical analysis and axillary dissection must be accompanied by comprehen- drafted the manuscript, KA performed the statistical analysis, RR assisted in data collection and manuscript drafting, MS assisted in data collection, JH sively quantifying dose and factors that impact dose to conceived of the study and assisted in drafting of the manuscript. All the axilla in all subgroups of patients, including those authors have read and approved the final manuscript. with tissue expanders. This information will be helpful Competing interests both for recurrence and morbidity endpoints. Our study The authors declare that they have no competing interests. is the first report of axillary dose in women with tissue expanders undergoing breast only irradiation. 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