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Keywords:

  • balloon catheter;
  • brachytherapy;
  • breast-conserving therapy;
  • accelerated partial breast irradiation;
  • breast carcinoma

Abstract

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

BACKGROUND

Balloon catheter–based accelerated partial breast irradiation (APBI) is an alternative to whole-breast external-beam irradiation during breast-conserving therapy (BCT) for breast carcinoma, but it is limited by the size of the segmental mastectomy cavity. There are scant data on the average or optimal volume of resection (VR) in BCT. The objective of the current study was to evaluate the percentage of patients who would be eligible for balloon catheter–based APBI based on the selection criteria of the American Society of Breast Surgeons and the surgical VR.

METHODS

The authors reviewed the medical records of 443 patients with ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCT. Patient treatment and pathologic data were analyzed to assess VR and eligibility for APBI.

RESULTS

BCT was performed for 178 patients with DCIS and 267 patients with invasive breast carcinoma. The majority of invasive carcinomas (63.3%) were infiltrating ductal carcinomas. The median overall lumpectomy volume was 67.61 cm3, with no significant difference between DCIS and invasive carcinoma (P > 0.05). Although the majority (62.9–82.0%) of patients met the individual selection criteria for APBI, only 27.4% of the cohort was found to be eligible for any type of APBI when the selection criteria were considered together. Based on VR, only approximately one-half of the patients initially eligible for APBI would be candidates for immediate balloon catheter–based APBI using the 70 cm3 balloon device (13.3%). However, with the new, larger 125 cm3 balloon device, approximately three-fourths of patients initially eligible for APBI would be eligible for balloon catheter–based APBI at the time of the initial surgical procedure (20.7%). Although not evaluated in the current study, shrinkage of the lumpectomy cavity with time may increase the number of patients eligible based strictly on VR criteria. Patients with a very large VR (≥ 125 cm3) were more likely to have invasive carcinoma (P = 0.02; hazard ratio [HR], 7.4) and tumors ≥ 5 cm on final pathology (P < 0.01; HR, 22.0).

CONCLUSIONS

Approximately one-fifth to one-fourth of patients presenting for BCT may be eligible for balloon catheter–based APBI according to accepted national guidelines and VR. VR must be considered when selecting patients for balloon catheter–based APBI, because a minority of patients will have a lumpectomy cavity that exceeds the size limit of the current balloon device. Cancer 2004. © 2003 American Cancer Society.

Breast-conserving treatment (BCT), consisting of lumpectomy and whole breast radiotherapy (RT), has been accepted as an appropriate local treatment option for selected patients with early-stage breast carcinoma. Multiple prospective randomized trials have demonstrated equivalent disease-specific and overall survival rates comparing mastectomy with lumpectomy plus whole breast external-beam irradiation.1–5 Despite this equivalence, many patients who are candidates for BCT do not pursue this approach for various reasons, including the inability to complete 6 weeks of daily RT owing to logistic considerations.6–8 This has led several investigators to evaluate BCT options using more focused RT given over a shorter treatment time.9–11

Several studies have shown that the majority of in-breast disease recurrences occur in the immediate vicinity of the lumpectomy cavity.12–15 Disease recurrences elsewhere in the breast are found with extended follow-up in only 1–3% of patients.12–14 These data suggest that the impact of whole breast RT on reducing the in-breast recurrence rate is limited to the site of initial involvement. It has been suggested that equivalent local control rates can be achieved with partial breast RT.16, 17 As a result, interest in accelerated partial breast irradiation (APBI) has grown. For patients undergoing APBI, only the portion of the breast at highest risk of disease recurrence receives a course of high-dose RT. This can be delivered in a shorter time frame. Several different methods of APBI have been described, including brachytherapy via multiple catheters placed into the breast parenchyma9, 11 or via a balloon catheter inserted into the lumpectomy cavity,18, 19 localized conformal external-beam RT,20 brachytherapy with bead or seed implants, and single-dose intraoperative RT.21, 22 Although multicatheter implants are the best-studied means of APBI, balloon cathether-based brachytherapy has recently received enormous interest because of the ease of insertion and the potential for more uniform delivery of radiation to the breast parenchyma around the lumpectomy cavity. The U.S. Food and Drug Administration (FDA) has cleared a balloon interstitial device (MammoSite RTS; Proxima Therapeutics, Alpharetta, GA) for brachytherapy based on safety and performance data. However, there have been no prospective or long-term outcome studies using the balloon applicator device.

The currently available balloon catheter device has limitations with respect to conformance to the size and shape of the segmental mastectomy cavity. The device has a capacity volume of approximately 70 cm3, although a newer device capable of treating volumes up to 125 cm3 recently has been approved by the FDA.18 Therefore, the lumpectomy volume of resection (VR) is a key determinant of eligibility for balloon-based APBI. The current literature provides little information that would indicate an average or optimal VR in patients undergoing lumpectomy. As a result, it is unknown what percentage of women treated with BCT would be eligible for balloon catheter–based APBI instead of external beam RT.

The American Society of Breast Surgeons (ASBS) recently published a consensus statement that outlines patient selection criteria for APBI (Table 1).23 In the current study, we reviewed our recent institutional experience with BCT for invasive breast carcinoma and ductal carcinoma in situ (DCIS) to determine the percentage of patients who would be eligible for balloon catheter–based APBI when assessed using ASBS criteria and surgical VR.

Table 1. Summary of the American Society of Breast Surgeons Consensus Statement for Accelerated Partial Breast Irradiation23
  1. APBI: accelerated partial breast irradiation.

The published data on APBI are neither extensive nor definitive. Therefore, it is  preferable that APBI be performed as part of ongoing experimental protocols.
Surgeons and radiation oncologists utilizing APBI techniques need to be adequately  trained.
Patients should be carefully selected for APBI and be informed of the risks and  benefits. Five selection criteria should be followed when considering patients for  APBI in lieu of whole breast irradiation: age ≥ 50 yrs; invasive ductal carcinoma or  ductal carcinoma in situ; total tumor size ≤ 2 cm; microscopically negative surgical  margins in all directions; and negative axillary/sentinel lymph nodes.
The treating physician and radiation oncologist should follow all patients closely to  identify adverse events as well as local disease recurrences.

MATERIALS AND METHODS

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

The medical records of 443 patients treated for invasive ductal carcinoma or DCIS by BCT at The University of Texas M. D. Anderson Cancer Center (MDACC) between January 6, 1998 and December 5, 2002 were reviewed and analyzed. Patients treated with mastectomy as a first procedure were not included in the current study. When patients required reoperations for close or positive margins (e.g., reexcisions or completion mastectomy), the first breast-conserving surgery performed at MDACC was analyzed. Among the 443 patients, there were 2 women with bilateral metachronous breast carcinoma, for a total of 445 treated breasts.

Preoperative diagnostic imaging was performed routinely and included ultrasonography, mammography or, commonly, both. All patients underwent excision of the tumor with macroscopically negative margins. Margins were inked for pathologic assessment. Margins were defined as microscopically negative or positive when tumor cells were absent or present, respectively, at the inked margin. All original pathology reports were reviewed for histologic subtype, margin status, lymphovascular invasion, lymph node status, size of tumor, and dimensions of the excised specimen(s). Three dimensions (width, length, and height) of the excised tissue specimen were required for the patient to be included in the analysis of VR. The VR was determined using the formula for an ellipsoid volume: 4π/3 × width axis radius × length axis radius × height axis radius.24 Tumor volume analysis demonstrates that use of the formula for rectangular solids (width × length × height) consistently overestimates the true volume of breast lesions. In contrast, the ellipsoid formula more accurately calculates the volume of breast specimens, which are commonly ellipsoid or spherical.24 Reexcision specimen volumes were also calculated. The total VR comprised the sum of VRs for all excisions at the time the index BCT operation was performed.

To assess the applicability of APBI in general, and balloon catheter–based therapy in particular, we analyzed whether patients in the current study who underwent BCT would be eligible for APBI based on the selection criteria recommended by the ASBS (Table 1). We also assessed the percentage of patients who would be eligible for balloon catheter–based APBI using maximum VRs of 70 cm3 and 125 cm3 and a combination of VR and the ASBS criteria.

Univariate tests (Pearson chi-square tests) were used to compare VR with age, size of primary tumor, margin status, localization method of the primary tumor, and whether the patient ultimately required mastectomy. The factors that were identified by univariate analysis to have a significant impact on VR were entered into a Cox proportional hazards model to test for significant effects while adjusting for multiple factors simultaneously. P < 0.05 was considered to be statistically significant.

RESULTS

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

Among the 443 patients, 2 patients underwent metachronous bilateral surgery, for a total of 445 treated breasts (cases). Patient and treatment characteristics are listed in Table 2. BCT was performed for 178 cases of DCIS and 267 cases of invasive carcinoma. The median patient age at diagnosis was the same for the groups with DCIS and invasive carcinoma (54 years; range, 18–89 years; P > 0.05).

Table 2. Patient and Treatment Characteristics
CharacteristicCarcinoma in situ (n = 178) (%)Invasive carcinoma (n = 267) (%)
  1. Data represent number of cases unless otherwise indicated.

Patient age (yrs)  
 Median (range) 54 (18–89) 54 (29–78)
Histologic type  
 Ductal carcinoma in situ178 (100) 
 Infiltrating ductal carcinoma 169 (63.3)
 Infiltrating lobular carcinoma  31 (11.6)
 Other infiltrating carcinoma  67 (25.1)
T status  
 Tis178 (100) 
 T1 176 (65.9)
 T2  80 (30.0)
 T3   9 (3.4)
 T4   2 (0.7)
N status  
 N0178 (100)177 (66.3)
 N1  0 90 (33.7)
Initial resection margin  
 Negative142 (79.8)223 (83.5)
 Positive 33 (18.5) 42 (15.7)
 Unavailable  3 (1.7)  2 (0.8)
Volume of resection (cm3)  
 Median (range)67.66 (1.47–588.43)67.57 (2.00–461.81)
Eventual mastectomy 17 (9.6) 28 (10.5)

Among the patients with DCIS, preoperative mammographically guided needle localization (n = 130 [73.0%]), intraoperative ultrasonography (n = 6 [3.4%]), or palpation (n = 5 [2.8%]) was used to identify the DCIS lesions and direct surgical management. In 37 cases (20.8%), the patient had previously undergone an open biopsy at an outside institution and the scar and biopsy cavity were reexcised. The median size of the DCIS lesion on preoperative diagnostic imaging was 1.5 cm (range, 0.2–10.5 cm) and the median size of the DCIS lesion at final pathologic assessment was 1.0 cm (range, 0.1–7.0 cm). The median lumpectomy volume for the DCIS group was 67.66 cm3 (range, 1.47–588.43 cm3). At the conclusion of the first BCT procedure at MDACC, the margin status was positive for 33 patients (18.5%). Seventeen (9.6%) of these patients eventually underwent mastectomy, whereas negative margins were achieved in the remaining 16 patients (8.9%) after reexcision.

The majority of invasive carcinomas were infiltrating ductal carcinoma (n = 169 [63.3%]). The others were infiltrating lobular carcinoma (n = 31 [11.6 %]) or another type of invasive carcinoma (n = 67 [25.1%]). Most cases (n = 176 [65.9%]) of invasive carcinoma were T1 (tumors < 2 cm in maximal dimension), but 80 cases (30.0%) were T2 (tumors ≥ 2 cm but not > 5 cm in greatest dimension). A small number of highly selected tumors were T3 lesions (tumors > 5 cm in greatest dimension; n = 9 [3.4%]) or T4 lesions (tumors with direct extension to the chest wall or skin; n = 2 [0.7%]). All cases of T3 and T4 disease were treated with neoadjuvant chemotherapy before lumpectomy. Preoperative mammographically guided needle localization remained the main method to identify breast lesions (n = 133 [49.8%]). Intraoperative ultrasonography was used in 37 cases (13.9%). Not surprisingly, more cases of invasive carcinoma had lesions that could be identified by palpation (n = 66 [24.7%]). Similar to the DCIS group, a few (n = 31 [11.6%]) patients with invasive carcinoma presented with a history of previous excisional biopsy. In these patients, the preexisting scar and biopsy cavity were used to direct BCT. Preoperatively, the median size of the invasive tumors on diagnostic imaging was 1.5 cm (range, 0.5–7.0 cm). The final pathologic assessment revealed an actual median tumor size of 1.0 cm (range, 0.1–8.0 cm). Lymph node metastases were identified in 90 cases (33.7%). The median lumpectomy VR was 67.57 cm3 (range, 2.0–461.81 cm3) and was not significantly different from the VR in the DCIS group (P > 0.05; Fig. 1). Margins were positive in 42 patients (15.7%). Of these, 28 (10.5%) patients eventually underwent a completion mastectomy, and 14 (5.2%) patients underwent reexcision with negative margins.

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Figure 1. Comparison of overall volume of resection (VR) after breast-conserving surgery for ductal carcinoma in situ versus invasive breast carcinoma (P > 0.05). The VR was calculated using the formula for an ellipsoid volume: 4π/3 × width axis radius × length axis radius × height axis radius.

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When patients were assessed for APBI eligibility using each ASBS selection criterion independently, a large percentage were found to be potentially eligible for APBI. The overwhelming majority of patients satisfied each selection criterion. For example, 280 patients (62.9%) were > 50 years, 345 (77.5%) had either invasive ductal carcinoma or DCIS, 312 (70.1%) had a total tumor size ≤ 2 cm, 365 (82.0%) had microscopically negative surgical margins, and 329 (73.9%) had negative axillary/sentinel lymph nodes. There was no significant difference in the eligibility rates between the DCIS and invasive carcinoma groups when each selection criterion was analyzed separately (P > 0.05). However, when the five selection criteria were considered together, only 122 patients (27.4%) were potentially eligible for APBI (72 with DCIS and 50 with invasive ductal carcinoma; P > 0.05).

One limitation of the balloon catheter–based technology is not having applicators of sufficient volumes to treat the entire area at risk. The manufacturer currently makes a balloon-based device with a spherical diameter that theoretically can treat up to 70 cm3. A more recent model can theoretically treat a volume of 125 cm3. In reviewing the 445 cases in the current series, the median overall lumpectomy volume was 67.61 cm3 (range, 2.0–588.4 cm3), with no significant difference between the DCIS and invasive carcinoma groups. Using a treatment volume of 70 cm3 as the sole selection criterion for balloon catheter–based APBI, 213 patients (47.9%) would be eligible for adjuvant treatment with balloon catheter–based brachytherapy (DCIS: n = 101 [56.7%]; invasive carcinoma: n = 112 [41.9%]). When patients with T1 tumors were analyzed as a separate group, still only 50% (88 of 176) were eligible for balloon catheter–based APBI. As expected, using the higher 125 cm3 cutoff value of the newer balloon device significantly increased the number of patients who would be eligible for balloon catheter–based therapy (n = 348 [78.2%]). In fact, analysis of only patients with T1 disease indicated that most would be eligible for balloon catheter–based APBI using the larger 125 cm3 device (146 of 176 [83.0%]).

Incorporating VR into the ASBS consensus statement as a sixth selection criterion, we analyzed how many patients would become ineligible for balloon catheter–based APBI. We found that 122 patients (27.4%) were eligible for APBI when the five selection criteria of the ASBS were applied to the cohort of patients comprising the current study. If these patients were being considered for balloon catheter–based APBI, VR would also need to be taken into account. Using a 70 cm3 VR cutoff, the percentage of patients eligible for balloon catheter–based APBI with the ASBS criteria—27.4% (n = 122)—would decrease to 13.3% (n = 59), corresponding to a 51% reduction in the overall percentage of eligible patients. However, using a 125 cm3 VR cutoff, 20.7% (n = 92) of patients would still be eligible for balloon catheter–based APBI—a relative decrease of approximately 24%.

Given that VR appears to be an important criterion for women potentially receiving balloon catheter–based APBI, we evaluated whether there were any associations between VR and patient characteristics, treatment parameters, or tumor pathologic factors. Using univariate analysis, patient age (P = 0.94), neoadjuvant therapy (P = 0.71), intraoperative localization method (P = 0.82), lymphovascular invasion (P = 0.64), final margin status (P = 0.35), and surgeon (P = 0.07) were not significantly associated with VR. The only two factors significantly associated with VR were the presence of invasion (i.e., DCIS vs. invasive carcinoma) and the size of the tumor on final pathologic assessment. Patients with invasive carcinoma were more likely to have a VR ≥ 125 cm3 compared with patients with DCIS (P = 0.02; hazard ratio [HR], 7.4). Similarly, patients with tumors ≥ 5 cm at final pathology determination were significantly more likely to have a VR ≥ 125 cm3 (P < 0.01; HR, 22.0). Using multivariate analysis, both the presence of invasion (P = 0.02) and final pathologic size (P < 0.01) maintained significance.

DISCUSSION

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

BCT is an accepted and appropriate local treatment option for women with early-stage breast carcinoma. Numerous randomized studies have proven that local surgical extirpation plus whole breast RT is equally as effective as mastectomy for the treatment of breast carcinoma.1–5 Currently, conventional RT after breast-conserving surgery is generally delivered to the whole breast over 5 weeks with a boost to the operative bed over the following 1–1.5 weeks depending on margin status. However, the protracted course of whole breast RT has been cited as one of the main reasons that patients decline BCT. Issues such as inability to find a radiation facility close to home or to bear the cost of relocating to be near a radiation facility, difficulty finding transportation to and from a radiation facility on a daily basis, and extreme age or physical handicap are all potential hurdles facing a patient who requires prolonged RT. In an extensive review, Malin et al.25 found that reported rates of RT after lumpectomy vary greatly. Data from the Surveillance, Epidemiology, and End Results registry from the late 1980s showed that the rate of radiation use varied depending on the region of the country where women lived. For example, only 60% of women in Iowa received RT as part of BCT, compared with 81% of women in Seattle. Overall, it is estimated that approximately 20% of women treated in the United States in the late 1990s still did not receive RT as part of BCT.25 The use of RT also has been shown to be related to the age of the patient.26–28 Elderly patients are much less likely to receive RT after lumpectomy than are their younger counterparts. Given that many patients with breast carcinoma in the United States are not receiving appropriate RT as part of BCT, alternatives to traditional external-beam RT are needed. APBI may represent a more attractive RT option because it is delivered over a much shorter period and is delivered to only a portion of the breast. However, there currently are scant data to indicate how many patients would be eligible for APBI after lumpectomy. Applying the ASBS criteria to the current cohort of 445 cases, we found that approximately 30% of patients may be eligible for some type of APBI.

APBI can be delivered using brachytherapy, hypofractionated conformal RT, or intraoperative RT with either a linear accelerator or electrons. Brachytherapy, the placement of radioactive sources within (interstitial) or very close to the tumor bed (intracavitary), has been used since the early 1920s.29 Generally, with standard brachytherapy, the radiation source is added to multiple catheters surrounding the tumor bed using an afterloading device. The main potential benefit of brachytherapy is the ability to limit the toxicity to healthy tissues while delivering the maximum dose to the tissue at risk for residual or recurrent disease. As a rule, the treatment duration for brachytherapy is also considerably shorter than that needed for a full course of whole breast irradiation. With brachytherapy, delivery of RT to the breast usually is completed over 4–5 days, compared with the 5–6 weeks needed for whole breast RT.

Although initial published reports on the use of brachytherapy as the sole type of RT after BCT were promising, standard catheter-based interstitial brachytherapy has a number of potential disadvantages.9, 30–32 It is technically difficult to perform and only a few clinicians in the United States are familiar with the technique. In addition, many patients and health care providers find the placement of catheters and the appearance of the multiple puncture sites required for insertion of traditional brachytherapy catheters disturbing. There are also issues with cosmesis, as catheter-based techniques often result in a pattern of punctuate hyperpigmentation with hypersensitivity at the catheter entry and exit sites. Given all of this, the widespread use of traditional brachytherapy has been limited. In contrast, there has been much interest in balloon catheter–based intracavitary irradiation.

Balloon catheter–based intracavitary brachytherapy after lumpectomy can be administered with a new breast brachytherapy applicator called the MammoSite (Fig. 2). The MammoSite device consists of a high–dose rate (HDR) radiation source at the center of an inflatable balloon that can be placed into the lumpectomy cavity at the time of surgery or after surgery when the definitive margin status is known. The current device looks similar to a Foley catheter, is 18.7 cm in length and approximately 6 mm in diameter, and is designed to be inflated to a diameter of either 4–5 cm or 5–6 cm, with a maximum inflation volume of 70 cm3 or 125 cm3, respectively. The balloon is usually filled with normal saline combined with a contrast agent to allow for radiographic imaging to verify optimal positioning. The MammoSite device has an inflation channel and a central treatment channel that connects to a computerized afterloading device for delivery of the HDR radiation source. The device is pliable and can be worn within a brassiere, making it potentially more appealing to patients and clinicians than traditional brachytherapy applicators. Because of its simplicity and patient acceptance, balloon catheter–based brachytherapy has been increasingly employed despite the lack of studies comparing its efficacy with standard postoperative external-beam RT.

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Figure 2. Depiction of the MammoSite applicator (Proxima Therapeutics, Alpharetta, GA) showing the radiation source port pathway, injection port, and balloon, which can be filled to a maximum of 70 cm3 or 125 cm3, depending on the model used.

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In the manufacturer-sponsored, multiinstitutional device safety trial at the William Beaumont Hospital (Royal Oak, MI), Edmundson et al.19 found that reproducible placement of the device was easily achieved, that the mean dose homogeneity index was less uniform compared with traditional brachytherapy (0.77 vs. 0.93, respectively), but that coverage of the planned target tissue was improved.19 When the MammoSite balloon conforms to the lumpectomy cavity, the prescribed radiation dose extends to 1 cm beyond the balloon, although the effective radiation penetration may be closer to 2 cm, because as the balloon is inflated beyond the volume of the lumpectomy cavity, the surrounding tissue is circumferentially stretched, with subsequent thinning of the surrounding tissue. Dosimetry studies reveal that with the 4 cm balloon device, only 35% of the initial brachytherapy dose extends to 3 cm. The 6 cm balloon device is only slightly better (43%). This may be of concern, given that the optimal volume of breast tissue that needs to be treated to effectively prevent local disease recurrence is currently unknown. Critics of balloon brachytherapy caution that the rapid decline in the radial dose of irradiation from the balloon brachytherapy source may preclude treatment of an adequate volume of surrounding breast tissue. Future randomized trials comparing local balloon brachytherapy with traditional external-beam irradiation are needed to determine whether this concern is valid.

The results of the initial clinical experience with the MammoSite breast brachytherapy device in women with invasive ductal carcinomas < 2 cm were reported recently.18 Seventy patients were enrolled in this eight-center prospective trial evaluating safety and applicator performance after device placement. A dose of 34 Gy was delivered in 10 fractions over 5 days with HDR brachytherapy prescribed to 1 cm from the balloon surface. Of the 70 patients enrolled, 16 (23%) did not have the MammoSite device implanted, due to either a cavity that was too large (n = 10), final pathology findings (n = 4), or inadequate skin spacing (n = 2). Fifty-four patients had the MammoSite device placed, 43 (80%) of whom completed brachytherapy. The MammoSite device was removed because of inadequate conformance to the cavity in seven patients, patient age in one patient, pathologic findings in one patient, and skin spacing in two patients. Therefore, even with very stringent entry criteria, only 61% of patients enrolled in the study actually completed brachytherapy with the MammoSite catheter.18

An important consideration when using balloon catheter–based APBI is the size and shape of the segmental mastectomy cavity. For balloon catheter–based therapy to be efficacious, it must conform to every border of the lumpectomy cavity. The two devices currently available have capacity volumes of 70 cm3 and 125 cm3. There are limitations to increasing the capacity volume. As the balloon size increases, both the amount of time needed for treatment and the dose delivered to the heart and lung become prohibitive.19 A review of the literature reveals that there is little, if any, empiric data regarding the average or optimal VR in BCT.33 To our knowledge, the current study represents the largest published series characterizing VR in BCT. Because the extent of resection may affect the disease recurrence rate, this information is critical. In addition, the surgical VR is a key determinant when considering the clinical applicability of balloon catheter–based APBI.

An optimal lumpectomy for MammoSite technology would remove a sufficient, but not unnecessarily large, amount of tissue concentrically around the tumor. It is common, however, for the shape of the lumpectomy cavity to be oblong rather than spherical. Furthermore, tumors are rarely situated at the center of the lumpectomy specimen, resulting in final margins that may be 3 or 4 cm on one side yet only a few millimeters on the opposite side. Some investigators have suggested that a more directed and limited resection can best be achieved utilizing intraoperative ultrasonography (for tumors with mass lesions) or mammographically guided needle localization (for tumors with no mass lesions) to direct the surgery.34, 35 In the current study, however, we found that VR was not significantly associated with the intraoperative localization method (P = 0.82). Similarly, patient age, final margin status, and the surgeon who performed the surgery were not significantly associated with the size of the final lumpectomy specimen (P > 0.05). VR was associated with both invasive status and size of the tumor at final pathologic assessment. Patients with an invasive tumor ≥ 5 cm were most likely to have a large (≥ 125 cm3) VR. Others have shown that elderly patients with DCIS are more likely to have a larger VR, which may explain, at least in part, the observation that elderly patients have a lower local disease recurrence rate.33

In the initial MammoSite study, which used the smaller 70 cm3 balloon device, Keisch et al.18 reported that 86% of patients were eligible for balloon catheter–based APBI as dictated by the size of the lumpectomy cavity, whereas only 14% were ineligible. In the current series, however, the volume of tissue specimen removed during lumpectomy at MDACC was often greater than this volume (median VR, 67.61 cm3). Using VR alone, less than one-half (47.9%) of patients were eligible for balloon catheter–based APBI using the smaller device. However, with the introduction of the larger balloon catheter device, which can treat volumes up to 125 cm3, significantly more patients were eligible for balloon catheter–based therapy (78.2%). Based on our findings, only a relatively small number of patients (approximately 24%) who otherwise would be eligible for APBI would not ultimately be candidates for balloon catheter–based therapy because of VR considerations. That is, whereas 27.4% of all patients were eligible for APBI, only 13.3% were candidates for balloon catheter–based therapy using the smaller 70 cm3 device and 20.7% were eligible using the larger 125 cm3 device.

It is important to make a distinction between initial VR of tissue specimen resected and the seroma cavity that forms after surgical resection. Empirically, it is clear that the seroma cavity shrinks with healing. Therefore, with shrinkage of the lumpectomy cavity, patients initially deemed unacceptable candidates for balloon catheter–based APBI may actually become eligible at a later date. A limitation of the current study is that it may underestimate the number of patients who are eligible for APBI based strictly on initial volume considerations. Theoretically, if lumpectomy cavities retract concentrically and symmetrically, the appropriate breast tissue at risk could be treated with balloon brachytherapy placed after surgery. However, if there is asymmetric shrinkage of the cavity, it is possible that some areas of the cavity would not be adequately treated with this technique. Although we evaluated the potential number of patients who would be eligible for APBI based on immediate VR considerations, issues of delayed balloon placement and cavity shrinkage were beyond the scope of the current study. Future studies evaluating delayed balloon placement in relation to cavity shrinkage/contraction are needed.

In addition to VR considerations, other selection criteria make the applicability of balloon catheter–based APBI somewhat limited. When all 5 ASBS selection criteria were applied, only 27.4% of patients in the current study were eligible for APBI. The American Brachytherapy Society (ABS) has also established criteria for APBI that are, perhaps, not as stringent as those of the ASBS (Table 3).36 The ABS selection criteria for APBI are, in some respects, more inclusive. Criteria such as age (≥ 45 years), tumor size (≤ 3 cm), and margin status (microscopically negative without depth restrictions) are all more liberal. However, the ABS currently recommends that APBI be reserved only for patients with invasive carcinoma, not for patients with DCIS. Therefore, in the current cohort evaluated, fewer patients eligible for APBI based on ASBS criteria would be eligible based on ABS criteria (122 patients [27.4%] vs. 98 patients [22.0%], respectively). However, if only patients with invasive carcinoma are considered, not surprisingly, more patients would be eligible by the ABS selection criteria than by the ASBS criteria (98 patients [22.0%] vs. 77 patients [17.3%], respectively).

Table 3. Comparison of Patient Selection Criteria for Accelerated Partial Breast Irradiation
CriterionAmerican Brachytherapy Society recommendations36American Society of Breast Surgeons recommendations23
  1. DCIS: ductal carcinoma in situ.

Age (yrs)≥ 45≥ 50
DiagnosisUnifocal, invasive ductal carcinomaInvasive ductal carcinoma or DCIS
Tumor size (cm)≤ 3≤ 2
Surgical marginsMicroscopically negative excision marginsMicroscopically negative excision margins ≥ 2 mm in all directions
Lymph node statusN0N0

The current study has a number of limitations with regard to accurately predicting the percentage of patients eligible for balloon catheter–based APBI. First, patients who had undergone an initial open biopsy at an outside institution were included (n = 68 [15.3%]). Because the VR removed at the outside institution was unknown, the measurements used in the VR calculations represent an underestimation of the total volume removed, which may have led to an overestimation of the percentage of women eligible for balloon catheter–based APBI who presented for reexcision. Second, we were unable to account for the balloon-skin distance. Balloon-skin distance is critical in not exceeding appropriate doses to the skin overlying the balloon. An additional exclusion criterion for balloon catheter–based APBI, therefore, is a balloon-skin distance < 7 mm. Due to the retrospective nature of our study and the limited pathologic data available, we were not able to account for this factor. Therefore, the number of patients eligible for balloon catheter–based therapy may have been overestimated.

Recently, the National Surgical Adjuvant Breast and Bowel Project proposed a randomized trial comparing partial breast irradiation with whole breast irradiation in patients with invasive or noninvasive breast carcinoma who have undergone a successful lumpectomy. Partial breast irradiation would consist of multicatheter brachytherapy, MammoSite brachytherapy, or three-dimensional conformal external-beam RT. Patients would receive hormonal therapy or chemotherapy before whole breast irradiation or after partial breast irradiation. The primary endpoint would be in-breast tumor recurrence. Secondary endpoints would be survival and disease-free survival. Important eligibility criteria would include a microscopically negative margin, invasive or noninvasive breast carcinoma ≤ 3.0 cm, 0–3 positive axillary lymph nodes, and a life expectancy ≥ 10 years. Using these selection criteria to analyze the current cohort of 445 cases, 278 cases (62.5%) would be potentially eligible for this trial. However, if cases were being considered for MammoSite balloon catheter–based APBI, only 156 cases (35.1%) would be eligible using the smaller 70 cm3 device and 227 cases (51.0%) using the larger 125 cm3 balloon device.

In conclusion, we show that based on both ASBS and ABS criteria, approximately 20–30% of patients presenting for BCT may be eligible for APBI. However, an important additional criterion for balloon catheter–based APBI is VR. Our series is the largest to date providing information on VR in BCT. Based on VR, only approximately one-half of patients initially eligible for APBI would be appropriate candidates for balloon catheter–based therapy at the time of surgery using the smaller 70 cm3 balloon device. Approximately three-fourths of patients would be eligible with the new, larger 125 cm3 balloon device. Balloon devices placed into a closed cavity after surgery most likely will increase patient eligibility based strictly on VR. Additional studies are needed to quantitate this difference. We still believe that, currently, it would be unwise to decrease the standard VR to better conform to the volume limitations of the balloon catheter device, as this could potentially increase local disease recurrence rates. Although the FDA has approved the balloon catheter device for clinical use, continued prospective clinical trials are necessary to establish not only its lack of toxicity, but also the effects of balloon catheter–based APBI on cosmesis, quality of life, and long-term disease-free and overall survival.

REFERENCES

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