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Keywords:

  • breast carcinoma;
  • accelerated partial breast irradiation;
  • MammoSite;
  • brachytherapy;
  • radiation therapy

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

BACKGROUND

In interstitial brachytherapy (IB), cosmesis and toxicity correlate with volume of tissue irradiated, dose homogeneity index (DHI), and adjuvant doxorubicin/cyclophosphamide based chemotherapy (ACCT). MammoSite brachytherapy (MSB) irradiates smaller volumes than IB, and lower dose homogeneity does not appear to affect toxicity. However, clinical experience suggests that other factors may also play an important role in cosmesis and toxicity with MSB. We reviewed our prospectively maintained data base of women who underwent accelerated partial breast irradiation (APBI) to assess this issue.

METHODS

Beginning in September 1995, 115 women were enrolled in a trial evaluating APBI as monotherapy after lumpectomy. The first 75 eligible patients received IB, and the most recent 28 eligible patients received MSB. All patients received 34 gray (Gy) in 10 twice-daily fractions through high-dose rate iridium-192 brachytherapy; 19% of patients in the IB group and 0% of patients in the MSB group received ACCT.

RESULTS

At 1 year after treatment, MSB caused significantly less Grade 2–4 subcutaneous fibrosis (as graded by a radiation oncologist according to the Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group system) compared with IB (10.7% vs. 32%; P = 0.04). However, when only ACCT-naïve patients in the IB group were compared with patients in the MSB group, this finding became nonsignificant. Among the patients who received MSB, significantly smaller volumes were irradiated, and the DHI was lower.

CONCLUSIONS

Current studies suggest an improved toxicity profile with MSB compared with IB that is attributed to lower irradiated volumes with MSB. When only chemotherapy-naïve patients were compared, however, toxicity and cosmesis were found to be similar between MSB and IB, suggesting a more complex interplay between irradiated volumes, DHI, and chemotherapy. The relation of ACCT to toxicity in this scenario is intriguing and warrants further investigation. Cancer 2004. © 2004 American Cancer Society.

Breast-conserving therapy (BCT) has traditionally included whole-breast irradiation after tumor lumpectomy. This approach is based on the premise that irradiation will eliminate residual foci of tumor adjacent to the surgical bed and will reduce risk of recurrence from areas of in situ or infiltrating carcinoma elsewhere in the breast. Although earlier studies suggested a substantial risk of remote disease,1, 2 a growing body of data provides compelling evidence that irradiation after lumpectomy is effective only at the site of initial involvement and thus may safely be limited to tissues immediately surrounding the excision cavity, with an expected local control rate comparable to the rate achieved with whole-breast irradiation.3–10

In addition to its questionable value in local control outside of the region of the excision cavity, conventional whole-breast irradiation presents logistic obstacles for patients that limit its application to fewer women than otherwise may qualify.11–16 Accelerated partial-breast irradiation (APBI) has been proposed as a means to overcome this limitation by making BCT more attractive to a wider range of patients, and it has now been tested as the sole method of irradiation after lumpectomy in numerous trials. Initial studies evaluated APBI performed as multicatheter-based interstitial brachytherapy (IB), for which follow-up data of up to 5 years are now available. Those reports suggest that APBI is comparable to whole-breast irradiation in terms of safety and efficacy.16–30 However, IB and its associated treatment planning are time-consuming and complex, requiring extensive practitioner experience for optimal outcome. Formal training in the procedure is limited, and only a minority of institutions has adopted IB despite promising clinical results.

The MammoSite balloon brachytherapy catheter (Proxima Therapeutics, Inc., Alpharetta, GA) ostensibly provides a relatively simple and less practitioner-dependent method through which APBI can be performed. There is evidence that, in IB, for which robust follow-up is available, toxicity and cosmetic outcomes are related to the volumes of tissue irradiated, dose homogeneity, and addition of adjuvant chemotherapy.17 Data are now becoming available regarding toxicity and cosmesis resulting from MammoSite brachytherapy (MSB). In this study, we report on the initial clinical experience and toxicity of a multiinstitutional protocol of APBI performed with IB or MSB. Our results with IB have been described previously.17, 31 Herein, we describe the relative roles of the various factors that affect toxicity and cosmesis in MSB.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Between June 1997 and September 2003, 115 patients with 116 AJCC Stage I and II breast carcinomas were enrolled in a multiinstitutional, Institutional Review Board-approved protocol of high-dose-rate (HDR) brachytherapy of the tumor bed plus margin after lumpectomy. Brachytherapy was performed as the sole form of irradiation, and no patients were treated with whole-breast irradiation. The first 75 consecutive, eligible patients, who were treated between February 1996 and December 2001, received IB; and the most recent 28 consecutive, eligible patients, who were treated between January 2001 and September 2003, received MSB. Twelve patients were not eligible for treatment, as described below.

Original eligibility criteria were specific to patients who were treated with IB and included the following: 1) unicentric primary tumors with invasive ductal histologic features; 2) T1, T2, N0, and N1 disease (≤ 3 metastatic axillary lymph nodes without extracapsular extension, a minimum of 6 lymph nodes in the specimen, or negative sentinel lymph node biopsy); 3) negative (≥ 1 mm) microscopic assessment of surgical margins; 4) no collagen-vascular disease or concurrent pregnancy; 5) no known unresected residual carcinoma and no diffuse microcalcifications; 6) negative postlumpectomy mammogram if the patient presented with malignancy-associated microcalcifications; (7) no prior malignancy except nonmelanoma skin carcinoma < 5 years before enrollment on study or continuously disease free ≥5 years; and 8) provision of a signed consent form. These criteria were modified for patients who were considered for treatment with MSB as follows: 1) patients with positive lymph node status were excluded, 2) tumors were required to measure ≤ 2 cm in greatest dimension, 3) the volume of the lumpectomy cavity had to be consistent with the manufacturer's recommendations with respect to the dimension of the balloon selected, and 4) a distance ≥ 5 mm was required between the balloon surface and the skin.

Regardless of the planned treatment, patients were considered ineligible for participation in the protocol if any of the following were present: 1) tumor histologic features with invasive or in situ lobular carcinoma or pure ductal carcinoma in situ, 2) skin involvement, 3) a breast unsatisfactory for brachytherapy (defined as having < 1 cm thickness of breast tissue within the entire implant volume, as measured from the skin to the pectoralis fascia or the subareolar position of the lumpectomy cavity), or 4) last breast surgery > 8 weeks before planned IB or MSB. Before implant loading, it was verified that the final pathologic margins measured > 1 mm. If inadequate margins were obtained, the patients were removed from the study, and the implant was either removed or used to deliver a boost to the tumor bed before conventional whole breast external beam radiation therapy (RT).

All tumor excisions were performed with the objective of complete macroscopic tumor removal. To be enrolled in the protocol, patients with margins < 1 mm underwent reexcision at a separate surgical procedure. Patients who were scheduled for IB who did not undergo perioperative implantation had the lumpectomy cavity marked by the surgeon with surgical clips. Patients who were scheduled for MSB who did not undergo perioperative implantation were assessed by ultrasound and computed tomography (CT) studies of the excision cavity prior to placement of the catheter. Axillary lymph node assessment was performed with either a Level I/II dissection or through identification of 1–4 sentinel lymph nodes using technetium tracer and blue dye. Although it was not a prerequisite to study participation, all interstitial implants in this study were comprised of two planes. Implants were performed without a rigid template. Catheter entry and exit points were marked on the skin with the use of a customized spacing device that could be adjusted at 1-mm intervals. Intraplanar separation was fixed at 1.0 cm, and interplanar separation was a variable that was dependent on tissue thickness, in accordance with an optimization algorithm designed to achieve maximal dose homogeneity.32 Specific details regarding the placement of IB catheters have been published.17, 31

All patients were treated with interstitial implants using HDR brachytherapy and iridium-192 (192Ir) (3–10 Ci). Both IB and MSB implants were placed either perioperatively (e.g., at the time of reexcision) or within 8 postoperative weeks. Treatment planning for IB was initiated by obtaining orthogonal radiographs with dummy source loading of the implant catheters for computerized reconstruction. Because an HDR remote afterloader was used, implants could be optimized to maximize homogeneity throughout the implant volume by adjusting the dwell times of the 192Ir source. The dwell spacing in all patients was fixed at 0.5 cm. Treatment planning for MSB required ultrasound and CT guidance for device placement. The balloon was inflated with 50–120 cm3 of sterile saline and 5 cm3 of contrast material to achieve a final balloon dimension of 4–6 cm. After final pathologic review, CT imaging was performed in all patients to assess suitability for HDR brachytherapy. The distances between the applicator and the skin and chest wall were measured. A minimum of 5 mm from each was required to proceed with treatment. Conformance was also assessed, and device placement was considered acceptable if the balloon was in contact uniformly with ≥ 90% of the lumpectomy cavity surface.

The Nucletron Planning System (Nucletron, B.V., Veenendaal, The Netherlands) was used for isodose calculations and treatment implementation for both IB and MSB. For IB, the target volume was defined as that volume encompassed by the excision cavity plus a 2-cm margin of breast tissue, as delineated by direct visualization or by surgical clips using orthogonal radiography and ultrasonography. For MSB, the target volume was defined as the spherical volume of tissue that encompassed the balloon within 1 cm of its surface, in a plane transverse to the balloon axis at its center, minus the volume of the balloon. Volumes were calculated using the formula 4/3(πr3), with r representing the radii of the treatment cavity and the balloon, as measured on planning CT scans performed for each patient. For both IB and MSB, 34 Gy were delivered to the target volume (defined above for each type of implant) in 3.4-Gy fractions (twice daily) over 5–7 elapsed days. Treatment fractions were separated by a minimum of 6 hours.

The dose homogeneity index (DHI) was used to assess implant quality and has been described previously.20 For both the IB group and the MSB group, the DHI was calculated (Eq. 1) as the difference between the volume of tissue receiving the prescribed dose (V100) and the volume of tissue receiving 1.5 times the prescribed dose (V150) divided by V100. Higher values for DHI corresponded with increased uniformity of the dose distribution within a treatment volume.

  • equation image(1)

For both IB and MSB, patients were examined twice daily to monitor for complications and to ensure that any displacement of the implant catheter(s) was not significant. The entire treatment was administered in an outpatient setting. After the 10th treatment fraction, the implant catheters were removed in the outpatient clinic, and the patients were immediately discharged home.

Patients were seen in follow-up at 1–3-month intervals. Mammograms were obtained at 6 months and 12 months after the implant and then yearly thereafter. A global cosmetic score was assigned in accordance with a previously published scale33 (excellent: perfect symmetry, no visible distortion or skin changes, and no visible catheter entry/exit sequelae; good: slight skin distortion, retraction, or edema and any visible telangiectasia, any visible catheter entry/exit scar, or mild hyperpigmentation; fair: moderate distortion of the nipple or breast symmetry, moderate hyperpigmentation, or prominent skin retraction, edema, or telangiectasia; and poor: marked distortion, edema, fibrosis, or severe hyperpigmentation). Cosmetic scoring was performed by a radiation oncologist, surgeon, and clinic nurse; and the lowest of the three scores was retained for analysis. Skin and subcutaneous toxicity were graded by a radiation oncologist according to the Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group system (Table 1). The scores recorded at the last follow-up visit were used for analysis and, in all patients, reflect cosmesis and toxicity at 1 year after completion of the procedure.

Table 1. Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group Late Radiation Morbidity Scoring Scheme for Skin- and Subcutaneous Tissues
GradeDescription
Skin 
 0No change from baseline
 1Slight atrophy; pigmentation change; some hair loss
 2Patchy atrophy; moderate telangiectasia; total hair loss
 3Marked atrophy; macroscopic telangiectasia
 4Ulceration
Subcutaneous tissues 
 0No change from baseline
 1Slight induration (fibrosis) and loss of subcutaneous fat
 2Moderate fibrosis (asymptomatic); slight field contracture; < 10% linear reduction
 3Severe induration and loss of subcutaneous tissue; field contracture > 10% linear measurement
 4Necrosis

Statistical Analysis

Clinical and therapeutic features were compared for complications and cosmetic outcomes. A 5% probability level was used to determine statistical significance. Sample means of continuous variables were compared using a two-sample Student t test. For those variables that had a skewed distribution, a nonparametric rank-sum test was used. Discrete variables were analyzed using a chi-square test to compare rates.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

The clinical and therapy-related features of the patient cohort are listed in Table 2. The median follow-up was 61 months (range, 29–106 months) for the 75 eligible patients in the IB group and 19 months (range, 8–40 months) for the 28 eligible patients in the MSB group. Comparisons of toxicity and cosmesis reflected assessments at 1 year for both groups. All patients in the MSB group had positive estrogen receptor (ER) status, whereas 15% of patients in the IB group had negative ER status. Patients who were treated early in the study period were more likely to have negative ER status or positive axillary lymph nodes, reflecting the more liberal eligibility criteria felt to be acceptable for breast brachytherapy in the mid-1990s. Beginning in 1999, only women who had negative axillary lymph node status were enrolled. The volumes of excised tissue did not differ significantly between the IB group and the MSB group in the current series, although patients who received MSB were more likely to have undergone a sentinel lymph node biopsy rather than a full axillary lymph node dissection. This is consistent with the evolution and increasing acceptance of sentinel lymph node biopsy for axillary lymph node assessment during the study period.

Table 2. Distribution of Patient-Related Variables
VariableNo. of patients (%)P value
IB (n = 75)MSB (n = 28)
  1. IB: interstitial brachytherapy; MSB: MammoSite brachytherapy; SD: standard deviation; ER: estrogen receptor.

Mean ± SD patient age (yrs)63.5 ± 10.762.0 ± 10.00.50
Total volume of excised tissue (cm3)117 ± 100102 ± 620.46
Greatest tumor dimension (cm)   
 Mean1.31.10.07
 Range0.3–4.00.3–2.0
Mean pathologic margin (mm)450.21
Sentinel lymph node biopsy only41 (55)25 (89)0.0003
Full axillary dissection33 (44) 2 (7)0.0001
Positive axillary lymph nodes 8 (10.7) 0 (0)0.10
Positive ER status64 (85)28 (100)0.03
Follow-up (mos)   
 Mean6119< 0.0001
 Range29–1068–40
Procedure aborted for device-related issue 5 (6.3) 7 (20)0.04

Five patients (6.3%) who were originally scheduled to receive IB did not receive treatment, as described previously.17 A significantly higher rate of aborted procedures was noted among patients who were scheduled to undergo MSB (20%). This included 5 patients in whom the balloon ruptured prior to treatment, 1 patient who developed hemorrhage in the treatment cavity, and 1 patient whose treatment was aborted because of suboptimal placement of the balloon, as reflected by a balloon-to-skin distance < 5 mm. The majority of such problems occurred early in the course of our MSB experience. Of the first 26 MSB procedures, 6 procedures were aborted. Thereafter, only one of the next nine treatments was aborted. Reasons for this likely relate to increasing familiarity with the limitations of the device and greater utilization of the smaller balloon size.

For patients who completed treatment with either IB or MSB, the acute tolerance of the brachytherapy catheters and HDR RT was excellent. Of the 103 treated patients, 99 patients required no analgesic medication except that received in the immediate postoperative period. Four patients in the IB group noted mild discomfort, and two patients reported moderate discomfort that was managed successfully with acetaminophen and codeine.

MSB resulted in significantly smaller volumes of tissue irradiated to each of the volumes assessed, as shown in Table 3. At the 3.4-Gy isodose line, the volumes irradiated with MSB and IB were 101 cm3 and 176 cm3, respectively (P < 0.0001). Volumes irradiated at the 5.1-Gy isodose lines for MSB and IB were 26 cm3 and 40 cm3, respectively (P = 0.0006). Volumes irradiated to the 6.8-Gy isodose line were 0 cm3 and 12 cm3 for MSB and IB, respectively. With a mean DHI of 0.83, IB yielded a significantly more homogeneous dose distribution compared with MSB, for which the mean DHI was 0.73.

Table 3. Distribution of Treatment-Related Variables
VariableIB (range)MSB (range)P value
  • IB: interstitial brachytherapy; MSB: MammoSite brachytherapy; DHI: dose homogeneity index; SD: standard deviation.

  • a

    V100, V150, and V200 are defined as the volumes of tissue encompassed by the 3.4-gray (Gy), 5.1-Gy, and 6.1-Gy isodose lines, respectively.

V100 (cm3)a176 (63–560)101 (39–127)< 0.0001
V150 (cm3)a 40 (12–144) 26 (0–45)0.0006
V200 (cm3)a 12 (0–45)  0 (0–11)< 0.0001
DHI (mean ± SD)0.83 ± 0.10.73 ± 0.1< 0.0001

Toxicity and cosmetic outcomes for the entire cohort are shown in Table 4. Significant differences were noted in Grade 1 skin erythema and Grade > 1 subcutaneous fibrosis. Consistent with greater skin dose, which is known to occur with MSB, mild erythema was more common with MSB compared with IB (42.9% and 17.3%, respectively). Subcutaneous fibrosis was more likely to be moderate or worse in the IB group than in the MSB group (32% and 10.7%, respectively). Skin cosmesis, erythema > Grade 1, and symptomatic fat necrosis did not differ significantly between treatment modalities.

Table 4. Toxicity and Cosmetic Outcomes for All Patients
VariableIB (%)MSB (%)P value
  1. IB: interstitial brachytherapy; MSB: MammoSite brachytherapy.

Good/excellent cosmesis89.392.80.72
Cosmesis < excellent34.732.11.00
Skin erythema = Grade 117.342.90.01
Skin erythema > Grade 15.30.00.06
Subcutaneous ribrosis > Grade 132.010.70.04
Symptomatic fat necrosis12.07.10.73

We previously showed that adjuvant doxorubicin/cyclophosphamide (A/C)-based chemotherapy may have an adverse effect on cosmetic outcomes in patients who undergo IB.17 Table 5 shows that 64.3% of patients in the IB group who were treated with A/C chemotherapy, compared with 27.9% of patients who did not receive A/C chemotherapy, were judged to have less than excellent cosmesis (P = 0.01). The rate of skin erythema also increased with adjuvant A/C chemotherapy; a significantly greater proportion of patients in the IB group who received chemotherapy developed mild (Grade 1) skin erythema compared with patients who did not receive chemotherapy (42.9% vs. 11.5%, respectively; P = 0.01). This association became nonsignificant when higher grades of erythema were compared. In additional, there was a trend toward increased symptomatic fat necrosis in patients who were treated with A/C chemotherapy. Based upon these findings, we concluded that A/C chemotherapy has a definite role in adverse cosmetic and toxic outcomes. Because of the evolving criteria for enrollment in our MSB protocol, the patients who qualified were those who were not offered chemotherapy based upon the current standard of care (Table 6). Thus, we elected to assess the outcomes of patients in our MSB group (none of whom received A/C chemotherapy) compared only with patients in the IB group who received no A/C chemotherapy (Table 7).

Table 5. The Role of Doxorubicin/Cytoxan Chemotherapy in Patients who Received Interstitial Brachytherapy
VariableChemotherapy (%)No chemotherapy (%)P value
Good/excellent cosmesis85.790.20.64
Cosmesis < excellent64.327.90.01
Skin erythema = Grade 142.911.50.01
Skin erythema > Grade 114.33.30.16
Subcutaneous fibrosis > Grade 128.616.40.28
Symptomatic fat necrosis28.68.20.057
Table 6. Adjuvant Systemic Therapy
VariableIB (%)MSB (%)P value
  1. IB: interstitial brachytherapy; MSB: MammoSite brachytherapy; A/C: doxorubicin/cytoxan.

A/C chemotherapy18.70,00.01
Hormonal therapy68.089.30.04
Table 7. Toxicity and Cosmesis in Patients who Received Doxorubicin/Cytoxan Chemotherapy
VariableIB and chemotherapyMSB (%)P value
  1. IB: interstitial brachytherapy; MSB: MammoSite brachytherapy.

Good/excellent cosmesis90.292.81.0
Cosmesis < excellent27.932.10.61
Skin erythema = Grade 111.542.90.002
Skin erythema > Grade 13.30.01.0
Subcutaneous fibrosis > Grade 116.410.70.75
Symptomatic fat necrosis8.27.11.0

When patients in the IB group who did not receive A/C chemotherapy were compared with patients in the MSB group, there were no statistically significant differences in any treatment parameter except Grade 1 skin erythema, which was observed more commonly in the MSB group compared with the IB group (42.9% vs. 11.5%, respectively; P = 0.002). It is noteworthy that patients in the MSB group were significantly more likely than patients in the IB group to have received hormonal therapy, which did not affect any treatment parameter (data not shown).

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Local recurrences after conservative surgery and whole-breast RT are most likely to occur in the immediate vicinity of the lumpectomy site. This fact has prompted the investigation of postlumpectomy RT confined to breast tissue surrounding the excision cavity as an alternative to whole-breast irradiation. Several methods are now available to accomplish this, including (in addition to MSB and IB) intensity-modulated RT and intracavitary electron-based modalities. Each has particular strengths and weaknesses, although the best studied to date are IB and MSB. The current series is a review of our prospectively maintained data base of women from three institutions who underwent either IB or MSB only to the region of the breast immediately surrounding the excision cavity after undergoing lumpectomy for early-stage breast carcinoma. Existing series have demonstrated acceptable outcomes with IB regarding both local control and toxicity.17–30, 34 Despite these promising results, IB has not become widely available. IB can be challenging technically, and optimal results can be achieved only with extensive operator and institutional experience. Furthermore, the placement of multiple catheters in the operating room is time consuming and can strain limited personnel resources. Finally, patients' perceptions of IB treatment may affect its utilization. Because of these limitations, the introduction of the MammoSite catheter has been well received both by many practitioners and by patients. Specifically, MSB offers the relatively simplified placement of only one catheter. It can be placed intraoperatively in substantially less time than is required for placement of numerous IB catheters. More importantly, the simplified device placement, dosimetry, and treatment delivery of MSB may theoretically avoid many of the technical obstacles that prohibit the widespread acceptance of IB.

Several series have now been published reporting initial experiences with MSB. Certain themes have emerged regarding MSB treatments: volumes irradiated are consistently smaller than the volumes irradiated with IB, dose homogeneity is lower, and outcomes appear better than would be expected with IB at similar DHI levels.34, 35 Despite this, little is known concerning the relative importance of these factors on toxicity and cosmesis with MSB. Furthermore, although A/C-based chemotherapy has clearly been linked to suboptimal outcomes in IB,17 data regarding the relationship of chemotherapy to MSB is nonexistent. Currently, patient-selection criteria for MSB, coupled with the standard of care regarding chemotherapy, render it unlikely that a large series of MSB patients who also receive chemotherapy will be available for analysis. Therefore, we believe it is of value to compare the outcomes of chemotherapy-naïve IB patients with our MSB cohort. This comparison offers two advantages. First, the adverse effects of chemotherapy on outcome in some IB patients can be excluded, permitting evaluation of the contribution of radiation treatments alone. Second, our IB experience spanned nearly 6 years, during which selection criteria changed considerably. Patients in the IB group who did not receive chemotherapy were more similar to patients who received MSB regarding tumor size and other characteristics.

This series was consistent with other reports regarding both the lower volumes of tissue that received irradiation at each of the three dose levels and the lower mean DHI with MSB.34, 35 The volume of tissue irradiated has been correlated with subcutaneous fibrosis and is uniformly greater in IB compared with MSB. The mean DHI was lower with MSB, but it did not appear to increase the risk of toxicity or poor cosmesis. Analyses of low-dose-rate breast brachytherapy have shown improved cosmetic outcomes and lower toxicity with higher DHI.36, 37 Although this correlation also has been suggested for IB,17 existing series of MSB fail to show this association.34, 35 Thus, it has been hypothesized that the dramatically lower V100, V150, and V200 in MSB are more important than DHI in determining toxicity. Consistent with these data, subcutaneous toxicity was lower in the MSB group compared with all patients in the IB group (including those who received chemotherapy).

Our experience with IB, as noted above, has revealed a significant negative impact of A/C chemotherapy on cosmetic outcomes. The updated data in the current series confirm our prior findings in this patient group. IB patients who received chemotherapy were significantly more likely to develop mild skin erythema and to have cosmesis that was judged less than excellent. A trend was also noted toward increased symptomatic fat necrosis with the use of chemotherapy. Given the confounding effect of chemotherapy upon assessment of the role of IB or MSB irradiation on cosmesis and toxicity, we elected to exclude patients who received chemotherapy and reanalyze the cohort. Surprisingly, the previously noted advantage of lower subcutaneous fibrosis with MSB disappeared compared with chemotherapy-naïve IB patients. This is in contrast to our expectations, given the low treatment volumes with MSB. Reasons for this outcome are not clear. It is possible that DHI may play a greater role in toxicity than previously suspected, given the equivalent rate of subcutaneous fibrosis with IB despite the differences in irradiated volumes. The longer follow-up interval of the IB group, compared with the MSB group, would not have affected these results, because assessments reflect the maximum toxicity achieved and were not downgraded. In addition, because of the nature of the parameters studied, all events were complete within 1 year after treatment. Despite the different lengths of follow-up, the toxicity and cosmesis scores reflect findings that occurred within 1 year of treatment for both groups.

Finally, mild skin erythema was also more common in the MSB group. This held true regardless of whether patients in the IB group who received chemotherapy were excluded from analysis. It is interesting to note that chemotherapy was found to be independently associated with the risk of mild skin erythema among patients in the IB group. Although those patients were removed from the analysis, MSB maintained a greater risk of mild erythema. Compared with MSB, the dosimetric characteristics of IB result in a skin dose that, in general, is lower than the prescription dose of 3.4 Gy.34, 35 The currently approved treatment-delivery technique for MSB, with a single-source dwell position, allows little opportunity to moderate the skin dose, which is uniformly higher compared with the skin dose used for IB. Extensive experience with external beam RT raises concern that areas of high skin dose may be at substantial risk of developing telangiectasias, atrophic dermatitis, fibrosis, or other well characterized dose-related skin toxicities. This is of concern, because (to our knowledge) the implications of a high risk of such skin toxicity on long-term outcomes with MSB are not yet known. Clinical outcomes reflecting treatment with eccentric-shaped devices and/or multiple-source dwell positions are awaited with interest, because such maneuvers may improve skin toxicity substantially. However, to our knowledge to date, the only method that lowers this risk is maintenance of as large a distance as feasible between the device and the skin.

Studies to date suggest an improved toxicity profile with MSB compared with IB that has been attributed to the lower irradiated volumes with MSB. When only chemotherapy-naïve patients are compared, however, toxicity and cosmesis were found to be similar between MSB and IB, suggesting a more complex interplay between irradiated volumes, dose homogeneity, and chemotherapy. The relationship of A/C chemotherapy to toxicity in this scenario is intriguing and warrants further investigation.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

The authors thank Robin Ruthazer, M.P.H., Tufts-New England Medical Center Institute for Clinical Research and Health Policy Studies, for her assistance with biostatistics.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES
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