Brachytherapy: Applications and Technique, 1st Edition

5. Breast Brachytherapy

 

Joseph R. Kelley

Laurie W. Cuttino

Frank A. Vicini

Douglas W. Arthur

The local management of breast cancer has evolved from radical surgical therapy to a breast-conserving approach that combines both segmental mastectomy (lumpectomy) with whole breast radiotherapy. Initially, Halstead's radical mastectomy surgically removed en bloc the entire breast, pectoralis major muscle and axillary nodal contents. Although effective, this treatment was associated with significant morbidity. Over decades the surgical approach became more conservative. Modified radical mastectomy, where the lymphadenectomy is limited and the pectoralis major is spared, was adopted and subsequently the concept of breast preserving surgical techniques were introduced and explored. However, with the reduction in surgical intervention the concept that the entire breast required treatment persisted. Therefore, with the introduction of segmental mastectomy (lumpectomy) whole breast irradiation was added to address the concern of residual microscopic disease. This breast conservation approach further improved cosmesis, reduced morbidity, and showed equivalent local control and survival to removal of the entire breast.1,2 As a result, lumpectomy followed by whole breast irradiation has become the standard of care for the management of most early stage breast cancers.

Adjuvant whole breast radiotherapy is typically delivered using opposed external beam tangents with standard fractionation over a period of 6 weeks. The treatment approach is well tolerated, has a good or excellent cosmetic result, and offers local control rates of >90%.1,2,3 Despite excellent outcome, a significant percentage of patients eligible for breast-conserving therapy do not receive it. Standard adjuvant radiotherapy is delivered to the entire breast over 5 to 7 weeks. The long course of treatment is problematic for working women, elderly patients, and those who live at a significant distance from a treatment center and may contribute to the underutilization of breast-conserving therapy. As a result, whole breast irradiation becomes a logistic barrier that limits the option of breast conservation for many women.4,5,6,7,8 In response, accelerated partial breast irradiation (APBI) has been investigated as a possible alternative to conventional post-lumpectomy treatment. APBI delivers radiotherapy only to the breast tissue at greatest risk of recurrence following lumpectomy. With the reduced volume of breast tissue treated, dose delivery can then be accelerated to allow completion of therapy in 1 week. In the United States, APBI has predominantly been accomplished using brachytherapy, by multicatheter implant or by the MammoSite radiation therapy system (RTS), or by external beam radiotherapy (EBRT) through three-dimensional conformal radiotherapy (3D-CRT). This chapter will review the background information supporting the concept of APBI, describe the different brachytherapy techniques, examine the safety and efficacy of each approach, and explore the future role of breast brachytherapy in the management of early stage breast cancer.

Rationale

The actual target for adjuvant radiotherapy following a segmental mastectomy achieving negative margins has never been clearly defined and remains controversial. Standard whole breast irradiation is on the basis of the historical background that the whole breast has always been treated; mastectomy versus whole breast radiotherapy. At the initial investigation of breast conservation therapy, pathologic data suggested that the whole breast required treatment to eradicate residual microscopic disease potentially present anywhere within the breast.9 The most commonly quoted study, which describes this finding involved the thorough examination of mastectomy specimens from patients who presented over 20 years ago, most of whom had clinically palpable disease. Through an exhaustive process, the location of occult microscopic disease was mapped and its location in relationship to the edge of a simulated lumpectomy determined. When generated, the findings were central to establishing the known importance of adjuvant radiotherapy following lumpectomy. However, the detailed information as to how to define the postoperative partial breast target when considering APBI is difficult to apply for several reasons. First, it can be argued that with modern mammographic screening, contemporary patients present with much earlier stage disease that is frequently small and clinically undetectable. This is opposed to the tumors evaluated following mastectomy in the original pathologic evaluation described by Holland, et al.9 Second, it is difficult to extrapolate the findings from Holland's study, where measurement of the mapped microscopic disease was measured from the edge of a simulated gross excision, to patients managed presently with modern surgical and pathologic techniques where a lumpectomy routinely results in the removal of the primary with microscopically negative margins. As thorough as this original pathologic study was, it appears to be inappropriate to apply to patients presenting in the modern era. In fact, a review of modern pathologic data suggests that residual disease following lumpectomy is not multicentric but rather extends minimally beyond the primary lesion, thereby supporting the concept of a partial breast target.10,11,12 To summarize the pathologic data one can conclude that, in properly selected patients, there is yet to be any pathologic data suggesting a whole breast target is necessary and that it appears the anticipated residual microscopic disease can be covered with radiotherapy focused on a target defined 1 to 2 cm beyond the lumpectomy cavity.

Probably the strongest information that supports a partial breast target for early stage breast cancer is that from reports of in-breast failure patterns following lumpectomy versus lumpectomy and whole breast radiotherapy. In the three reports where the declaration of location of failure is clear, it is reported that the location of failure is predominantly in the immediate vicinity of the primary lesion.1,13,14 In fact, this literature indicates that the entire breast is not at risk for recurrence. Data from the European and Canadian trials compared in-breast failure patterns between patients treated with lumpectomy alone versus lumpectomy and whole breast radiotherapy. They demonstrated that when whole breast radiotherapy was not delivered most of the reported recurrences were at the site of lumpectomy and the rate of failure “elsewhere” in the breast, remote from the original primary lesion, was equivalent.15 The rate of “elsewhere failures” was reported to be <3.5%, with or without whole breast radiotherapy. It has been postulated that these elsewhere failures possibly represent new primary lesions developing years after the original treatment. Review of this failure pattern data suggests that the benefit of postlumpectomy whole breast radiotherapy is in its ability to reduce the risk of recurrence at the site of lumpectomy and that whole breast radiotherapy is unable to prevent the emergence of new lesions within the treated breast.16

This potential change in the treatment target provides the opportunity for a possible modification in the treatment paradigm. By reducing this target to only a portion of the whole breast volume, acceleration of the dose delivery and completion of treatment in <5 days becomes feasible. Also, with the advent of new, widely available radiotherapeutic treatment techniques, the accurate delivery of a conformal APBI dose to a limited target in the breast becomes possible. However, for APBI to become an accepted standard of care, we must verify that safe and reproducible treatment techniques have been developed, proper patient selection criteria has been established, and that there is confirmation that the long-term local control and risk of both early and late toxicity are equivalent.

Treatment Techniques

There is presently no consensus on which APBI treatment approach is considered superior or even ideal for any given clinical situation. Biases in recommendations are evident, but what appears to be universally accepted is that the best techniques incorporate image guidance and computed tomography (CT) scan–based 3D treatment planning. The roots of APBI treatment technique initially started with conventional multicatheter brachytherapy. Multicatheter brachytherapy was frequently used worldwide to deliver a boost to the tumor bed following whole breast radiotherapy before the emergence and availability of electron treatment for boosting. With the increased interest in APBI, attention was focused on the details of breast brachytherapy with immediate improvements in the application of multicatheter brachytherapy through the addition of image guidance and the availability of 3D-treatment planning for brachytherapy.17,18,19 Soon innovations were introduced in an attempt to simplify and improve the reproducibility of APBI which led to the development, testing and subsequent availability of the MammoSite RTS.20 3D-CRT has recently been introduced offering a noninvasive treatment approach coupled with increased dose homogeneity.21,22,23 Although exciting, patients treated with these 3D-CRT techniques are few with limited follow-up.

Multicatheter Implants

With the application of multicatheter brachytherapy, afterloading can be accomplished using low dose rate (LDR) or high dose rate (HDR) dose delivery methods. Presently, LDR has largely been abandoned in favor of the more convenient, outpatient-based HDR approach that better controls the dose delivery and radiation safety concerns of LDR. Historically, construction of the breast implant was performed in the operating room and was heavily experience dependent. This was either done at the time of lumpectomy or as a separate procedure following lumpectomy with pathologic evaluation completed and information available. Although there are different techniques of catheter placement, general guidelines of catheter placement are consistent. When placing the catheters, either in or out of the operating room, the patient is first properly positioned to facilitate catheter placement and the breast prepped and draped in sterile fashion. Patient comfort during the procedure was originally achieved with general anesthesia and now usually with a local anesthetic and conscious sedation. Stainless steel trochars are then introduced into the breast tissue at the appropriate locations. Once trochar placement is complete the trochars are replaced with button-ended flexible afterloading catheters and secured with locking collar. Alternatively, if a template was used, the trochars can be kept in place and secured to the template for the duration of the implant. Implant construction has been governed by basic breast brachytherapy principles with the goal of optimizing target coverage and dose homogeneity.24,25 Intercatheter spacing is ideally between 1 and 1.5 cm and earlier implant construction typically comprised a two plane implant. Plane location was designed in a superficial and deep plane arrangement with a planar separation to maximize homogeneity. An example of a traditional fluoroscopically guided implant is seen in Figure 5.1. Target delineation was originally through breast inspection, palpation, and mammogram review that allowed estimation of the size and location of the lumpectomy bed. Dosimetric planning was managed with a two dimensional planning process utilizing dummy source strands in each catheter with subsequent orthogonal films to identify spatial location of catheters (see Fig. 5.2).

As experience with breast brachytherapy increased, the need for clear identification of the lumpectomy cavity target was recognized. As a result, methods of target visualization and image-based catheter placement techniques to assure proper catheter placement have now become standard components. Initial attempts at this included intraoperative orthogonal fluoroscopy with surgically placed clips or contrast injected into the lumpectomy cavity (Figure 5.1). Ultrasound was then incorporated and is still considered valuable. Further innovation in the methods of catheter placement in addition to the emergence of 3D brachytherapy planning allowed the transformation of multicatheter-based brachytherapy into a more adaptable, reproducible image-guided technique requiring less experience than previously needed and obtaining reliably excellent results. Kuske has described his original method of closed-cavity brachytherapy implantation that is performed under local anesthesia in the radiology department.17 In his approach, a contrast medium is injected into the lumpectomy cavity under ultrasound guidance immediately before brachytherapy catheter placement, clearly defining the dimensions and location of the lumpectomy cavity. Using real-time stereoscopic mammographic guidance, accurate coverage of the cavity with brachytherapy catheters can then be verified before the completion of the implant procedure. A template system is utilized to guide the necessary needles into position allowing for easy placement and accurate coverage of the clinical target volume. Virginia Commonwealth University developed a CT-guided catheter insertion technique (see Fig. 5.3).19 In this method, a CT scan is obtained to assure the lumpectomy cavity is well visualized and with the aid of three-dimensional (3D) planning software, the basis of an initial implant construction is designed. Catheter implantation is accomplished on the departmental CT simulator using local anesthesia and conscious sedation. The patient is properly positioned on the CT simulator table to facilitate scanning during the procedure without violating the sterile field. The patient is then prepared and draped in sterile fashion and the catheter entry and exit points are delineated on the skin. Using a freehand technique, trochars are placed in the standard superficial and deep planes with intermittent CT scan guidance as needed to optimize positioning. Typically one to two scans are performed to ensure adequate target coverage. The trochars are then exchanged for flexible button-ended afterloading catheters. A final CT scan is obtained for 3D dosimetric planning (Brachyvision Planning System; Varian Medical Systems, Inc., Palo Alto, CA.). In a comparison study, the Virginia Commonwealth University CT-guided technique yielded improved dosimetric coverage of the target and dose homogeneity as compared with a nonimage-guided technique. The entire procedure is typically completed with final CT scan ready for treatment planning in 1 to 2 hours (see Fig. 5.4).19

Figure 5.1 Intraoperative interstitial breast implant. A: The lumpectomy cavity is located by palpation and orthogonal fluoroscopy. Trochars are inserted along these planes, alignment is confirmed with fluoroscopy, and (B) the trochars are replaced with the flexible catheters as shown. C: The finalized implant is shown connected to a high dose rate afterloading device.

Figure 5.2 Traditional dosimetric planning. With dummy sources in place, orthogonal films are taken to determine spatial location of catheters. Source location is then digitized and a two-dimensional plan generated.

MammoSite Radiation Treatment System (Cytyc Corp, Marlboro, MA)

Although the multicatheter interstitial technique is quite flexible and can be applied to any size of breast or lumpectomy cavity, it can be technically challenging and adds a degree of trauma with the potential for pain during the treatment process. In light of these considerations, the MammoSite RTS was developed in an attempt to simplify the partial breast irradiation (PBI) implantation process and to improve the reproducibility of dosimetric target coverage. The MammoSite is a 15 cm long double-lumen balloon catheter designed for HDR afterloading (see Fig. 5.5). One port allows easy balloon fill volume control, the second as the afterloading source access. The catheter can be placed at the time of resection or postoperatively following the determination of pathologic size, margin and nodal status. To accommodate differing lumpectomy sizes, varying shapes and sizes of balloon devices have been developed included two spherical balloons measuring 4 to 5 and 5 to 6 cm in diameter and a 4 × 6 cm ellipsoid balloon (see Fig. 5.6). Placement of the balloon catheter can be easily accomplished by the surgeon or radiation oncologist either at the time of lumpectomy, re-excision or postoperatively in a close cavity setting. Regardless of placement method, verification of balloon symmetry, balloon/cavity conformance and overlying skin thickness is essential to assure target coverage and toxicity avoidance. CT scan–based evaluation and 3D brachytherapy planning are recommended to assure that dosimetric goals are achieved and the intended dose is delivered safely (see Fig. 5.7).

Figure 5.3 Computed tomography (CT)-guided breast implant. CT scan guidance is used to improve interstitial implant geometry over freehand technique. The seroma cavity can be easily visualized and used to guide catheter placement. CT scan intraprocedure evaluation is shown with a deep and superficial implant plane. Two additional catheters have been placed to improve anticipated dosimetry.

Figure 5.4 The MammoSite Radiation Treatment System. A MammoSite Radiation treatment system consists of a 15 cm long plastic catheter with a 6 mm external diameter. The dual lumen catheter allows. An inflatable balloon as the tip provides a uniform separation distance between the treatment source and the surrounding tissue. Both a 4 to 5 cm and 5 to 6 cm spherical catheters are commonly used and a 4 × 6 cm elliptical balloon catheter is also available.

 

Figure 5.5 The MammoSite Radiation Treatment System. A MammoSite Radiation treatment system consists of a 15 cm long plastic catheter with a 6 mm external diameter. The dual lumen catheter allows an inflatable balloon as the tip provides a uniform separation distance between the treatment source and the surrounding tissue. Both 4 to 5 cm and 5 to 6 cm spherical catheters are commonly used and a 4 × 6 cm elliptical balloon catheter is also available.

The MammoSite catheter can be placed either at the time of final surgery or in a closed technique after the final pathology report. These techniques are visually detailed in Figures 5.8, 5.9, 5.10, 5.11 and 5.12.

Figure 5.6 The MammoSite comes in small 4 × 5 cm, 5 × 6 cm spherical and a 4 × 6 elliptical balloon sizes to accommodate a common tumor cavity shape.

 

Figure 5.7 A: External component of MammoSite Catheter exits skin through a small wound. B and C: Axial and saggital CT reconstruction of catheter balloon, CTV and isodose lines.

 

Figure 5.8 Trochar insertion: A suitable trajectory and entrance site is chosen. A simple skin nick with a scalpel allows easy transdermal passage of the trochar to make the tract for the catheter.

Figure 5.9 Introducing the catheter: The catheter is test-inflated before insertion. A rigid metal obturator eases the passage of the catheter through skin and tissue to the cavity site.

 

Figure 5.10 Inflating the catheter: The catheter is inflated to assess best filling. A fluid displacement of the resected specimen can assist. The balloon is deflated for wound suturing.

Figure 5.11 Closed skin with contour: The subcutaneous layer is also sutured so as to maintain the distance between balloon and skin.

 

Figure 5.12 Closed technique with ultrasound probe: The technique begins after an initial ultrasound study to determine size of seroma and distance to skin. A sterile preparation is used. The skin is anesthetized and a scalpel nick is created. The trochar is introduced under ultrasound guidance through the skin nick and breast tissue to the seroma cavity. Some of the fluid is released. With the rigid obturator the catheter is passed into the seroma cavity. Ultrasound guides the filling and correct position of the catheter. No suturing is performed. The wound is managed with daily dressing changes and wound care. Oral antibiotics and pain medications may be needed.

Treatment Dose, Planning, and Dosimetric Evaluation

Several successful treatment schemes have been reported using brachytherapy to deliver partial breast therapy. The doses applied vary depending on the philosophy of the facility and a consensus on how to optimize the doses has not been reached. However, the most commonly used dose schemes for accelerated partial breast brachytherapy use HDR to deliver 34 Gy in 10 twice-daily fractions over a 1-week period.26,27,28,29,30,31 This dose fractionation scheme is used for both multicatheter and MammoSite RTS–based brachytherapy. Similar dose delivery schemes using LDR, pulsed dose rate (PDR) and HDR are in use and have been reported with successful results.32,33,34,35

Successful treatment planning and dose delivery depends on the appropriate delineation of a treatment target and a thorough quality assurance program that assures accurate treatment with homogeneous dosimetric coverage of the target. Historically, dosimetric planning for breast brachytherapy was based on experience as the target was poorly visualized and dosimetric coverage was confirmed only with two-dimensional planning methods. With the incorporation of CT scan evaluation and the availability of CT scan–based 3D brachytherapy treatment planning, target volumes can be clearly outlined and dosimetric coverage documented.

The treatment target presently accepted is the lumpectomy cavity plus a 1 to 2 cm margin. It should be recognized that the dimensions of the treatment target are bounded by the limits of breast tissue extension. Equating the target dimensions regardless of treatment method is necessary for standardization of APBI but presents a challenge. Multicatheter brachytherapy has the ability to vary the target volume as desired by the treating physician. On the other hand, the MammoSite RTS is more dosimetrically restrictive and is dependent on the relationship between the final balloon dimensions and lumpectomy cavity characteristics. At first evaluation, the dose delivered appears to be limited to a nominal treatment distance of 1 cm from the balloon surface. However, the actual treatment distance can be notably further and is dependent on the degree of stretching that occurs to the circumferential tissue as the balloon is inflated.36 Therefore, >1 cm from the cavity edge is typically treated thereby supporting the target definition of 1.5 cm in the American phase III trial, National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiation Therapy Oncology Group (RTOG) 0413.37

Once the target has been clearly delineated, dosimetric coverage can then be assured. Target delineation carries with it a degree of uncertainty due to operator dependence and the accuracy of the imaging software used. As a result, holding to the ideal 100% target coverage with 100% of the prescription dose may be unrealistic and at present it is uncertain whether it is necessary.38 Relaxing the dose coverage goals would appear appropriate until clinical data suggests otherwise. Although striving for optimal coverage is appropriate, one should require that at least 90% of the desired dose be delivered to at least 90% of the delineated target.

Local control rates are optimized with consistent target coverage but toxicity is avoided by assuring the dose delivered is acceptably homogeneous. The toxicity of breast brachytherapy appears to be related to the volume of tissue receiving increased levels of dose above prescription dose. In an early study of the toxicity of breast brachytherapy, the rate of grade 3 and 4 fibrosis and fat necrosis was shown to correlate with dose–volume analysis.30,31,39,40 Toxicity was predicted by both the volume of breast tissue receiving 150% of the prescribed dose (V150) and 200% of the prescribed dose (V200%) when the total prescribed dose was 34 Gy in 10 fractions delivered b.i.d. Patients who developed only grade 1 or grade 2 fibrosis had an average volume of tissue receiving 5.1 Gy per fraction (V150) of 36 cm3. Patients who developed grade 3 or 4 fibrosis had an average V150 of 69 cm3. The V200 for patients in this study was 11 cm3 and 21 cm3 for grade 1 to 2 fibrosis and grade 3 to 4 fibrosis, respectively.30 As a result, it is recommended that these two dose–volume histogram parameters be monitored with each implant to account for potential long-term complications. As brachytherapy is an inherently inhomogeneous treatment, dosimetric planning of an implant must include evaluation of the dose distribution. An isolated area of excessive dose within the implant may result in acute toxicity and long-term complications. The dose homogeneity index (DHI) is a dosimetric parameter currently used to evaluate the dose distribution of an implant. DHI was first reported in RTOG protocol 95–17 and was defined as the ratio of the prescription dose to the mean central dose.41 Another definition used for DHI has now been more widely adopted.42 By that definition, the DHI is defined as the ratio of V150 to V100. The DHI appears to correlate with the incidence of skin toxicity, fibrosis, and the development of fat necrosis.30,40,43 Recommendations require a DHI of >0.75 when using this definition.

On the basis of these and other reports, the current NSABP B39/RTOG 0413 phase III, partial breast protocol requires that implants be designed to minimize both V150 and V200 still maintaining adequate planning target volume coverage of 90% of the prescribed dose received by 90% of the target.37 The V150 must be ≤70 cc for an interstitial HDR implant and ≤50 cc for a MammoSite brachytherapy. The adopted V200 guidelines are ≤20 cc for an HDR implant and ≤10 cc for a MammoSite brachytherapy.

A major advantage of HDR therapy over LDR treatment is the ability to alter source dwell times to compensate for suboptimal implant geometry.44 Minor changes in dwell times have been shown to increase the percentage of the target receiving the prescribed dose from 87% to 97%. However, this improvement in coverage resulted in an increase in the mean V150 from 26 cm3 to as much at 70 cm3, which may lead to an increase in toxicity. Consequently, HDR treatment offers some flexibility in dosimetric planning, but the alteration of dwell times cannot fully compensate for poor implant geometry.

With the use of the MammoSite RTS, balloon symmetry, cavity conformance, and skin thickness are important parameters to evaluate to assure proper use. Deviation in these parameters may affect dosimetric target coverage and effect degree of dose homogeneity. The skin separation distance and the dose to the skin is an important parameter that requires close monitoring. This has a direct effect on the risk of toxicity and long-term cosmesis. Increased acute and late skin toxicity has been reported when the distance from balloon surface to skin is <7 mm.45,46 As a result, to decrease the risk of skin toxicity, recommendations are to strive for >7 mm skin thickness and if a thickness of 5 to 7 mm is encountered then optimization measures should be taken to avoid skin doses of >145% of the prescription dose. The lowest skin doses achievable are preferred and treatment with a skin distance of <5 mm should be avoided.

Patient Selection

Most mature institutional series of breast brachytherapy have shown excellent rates of local control. The successful series all employed patient selection criteria and none of these series treated patients who were not already eligible for standard breast conservation therapy. Two societies have published conservative patient selection criteria.47,48,49 The American Brachytherapy Society (ABS) has listed patient guidelines of age >45 years, infiltrating ductal histology with a size <3 cm and negative margins and negative axillary nodes.47 The American Society of Breast Surgeons (ASBS) adopted similar selection criteria of age >50, infiltrating ductal or ductal carcinoma in situ histology with a size <2 cm, margins negative by >2 mm and negative nodes.48,50 Both groups continue to exclude patients with positive margins, positive nodes, or lobular histology from accelerated partial breast brachytherapy. If offering APBI off protocol, this conservative patient selection approach should be maintained until more definitive data are available.

Treatment Toxicity and Cosmesis

Multicatheter Implants

Numerous studies have shown that breast brachytherapy has a modest treatment-related toxicity that compares favorably with whole breast irradiation. The implant is well tolerated and most studies report a low incidence of complication and a good or excellent cosmetic result. The Ochsner Clinic series reported a good or excellent cosmetic result in 75% of patients.27 It indicated a 2% rate of infection and a 4% rate of fat necrosis related to treatment. Grade 1 to 2 telangiectasia and fibrosis were noted in up to 22% of patients but a good cosmetic outcome was preserved in most patients. Similar rates of complication have been reported in other studies. At Tufts University, no patients developed grade 3 to 4 skin toxicity, but it was noted that 34% experienced grade 3 to 4 subcutaneous toxicity related to fat necrosis. Over 90% of patients were found to have a good or excellent cosmetic result.31 In the series from Virginia Commonwealth University, infection was noted in only 1 of 44 patients.28 Cosmetic changes following APBI were noted in 13.4% of patients, with 80% of patients graded as having an overall good or excellent cosmetic outcome following lumpectomy and APBI.

However, some report an increased incidence of complications with increased doses delivered and with the addition of Anthracycline-based chemotherapy. A dose escalation trial conducted at Massachusetts General Hospital treated patients with LDR brachytherapy to doses of 50, 55, and 60 Gy.32 At 50 Gy no patient developed a significant degree of fibrosis in the breast following treatment. However, when the dose was increased to 55 Gy and 60 Gy, fibrosis was seen in 7% and 25% of patients, respectively. The combination of APBI with chemotherapy appears to increase the risk of soft tissue complications.28,30,31,40The Tufts experience demonstrated a trend toward an increased risk of fat necrosis when anthracycline-based chemotherapy was added. The rate of fat necrosis was 50% for those patients receiving chemotherapy versus 19% for those who did not. Patients who received chemotherapy were also less likely to have an excellent cosmetic score (33% vs. 81%).30 At Virginia Commonwealth University, 43% of patients treated developed skin erythema in a recall phenomenon overlying the brachytherapy target when Adriamycin was administered following APBI.28

MammoSite Radiation Treatment System

Partial breast brachytherapy delivered by a MammoSite catheter, has been well tolerated. The initial Phase I/II trial used to support Food and Drug Administration (FDA) approval of the MammoSite device included 43 women.20,45,51 After 29 months of follow-up the procedure carried little or no acute phase toxicity. The primary acute phase adverse effects, associated with MammoSite treatment are infection and radiation-induced skin toxicity which appear to be reduced with proper catheter management technique and appropriate dosimetry. Initial reports of MammoSite use brought concerns of increased rate of infection. Two early experiences reported a high rate of infection, 16%, which in the follow-up report improved with improved catheter care.52,53 In the early report of the large registry trial managed by the ASBS, the rate of MammoSite device–related infection was acceptably low at 5.3%.54 Review suggests that as experience with the device increases, the implant duration times shorten, catheter management improves and the risk of infection decreases. Several subsequent studies of MammoSite treatment have reported infection rates ranging from 4% to 6%.55,56 This low rate of infection compares similarly with lumpectomy followed by adjuvant whole breast irradiation.57 Although the rate of infection is low, the development of an infection can be a challenging event that may require aggressive intervention due to the soft tissue environment created by the accelerated dose scheme used.27,53,56 Proper nursing care at the catheter site is crucial and close follow-up with early intervention when infection is suspected is strongly advised.

In almost all cases, acute skin erythema resolves with minimal supportive care and 86% to 90% of patients maintain an excellent cosmetic result.39,52 This skin toxicity is directly proportional to the dose received, which is predominantly controlled by the distance between skin and balloon surface. Skin separation of <7 mm has been shown to result in suboptimal cosmesis.45,58 Long-term follow-up is needed to evaluate the potential for late effects. The Tufts and Virginia Commonwealth experiences suggest that the MammoSite may offer a lower incidence of fibrosis as compared with multicatheter treatment (12% vs. 32%).39 However, there was a strong correlation between suboptimal cosmetic outcome and the use of chemotherapy and very few patients treated with the MammoSite RTS received chemotherapy in this study. Subgroup analysis of patients treated without chemotherapy showed no difference in outcome.

Treatment Experience and Results

The number of published breast brachytherapy experiences continues to increase yearly. Most patients in the mature series were treated with a multicatheter technique. The published multicatheter experiences are summarized in Table 5-1. These data represent hundreds of patients treated with APBI with excellent local control at follow-up intervals of 2 to >5 years. Most series that have employed conservative patient selection criteria and a quality assurance program report local recurrence rates of <5%. Institutions that varied from these criteria experienced higher local recurrence rates.59,60

One of the original groups in North America to systematically treat patients with breast brachytherapy was the Ochsner Clinic.27 From January 1992 to October 1993, 50 patients with 51 breast cancers were treated with either LDR (45 Gy over 3.5 to 6 days) or HDR (32 Gy in 8 twice-daily fractions) brachytherapy. At a median follow-up of 75 months, one breast recurrence (2%) and three regional nodal failures (6%) were noted. This rate of local/regional recurrence was similar to a group of matched control patients treated with standard whole breast radiotherapy.

The William Beaumont Hospital group published the largest treatment experience, with the longest follow-up.26 A total of 199 patients with early stage breast cancer were treated with breast-conserving therapy and brachytherapy. One hundred and twenty patients were treated with LDR (50 Gy over 96 hours). Seventy-nine patients were treated with HDR (32 Gy in 8 twice-daily fractions or 34 Gy in 10 twice-daily fractions). To compare potential differences in local recurrence rates, a matched-pair analysis was performed with 199 patients treated with whole breast radiotherapy. When last reported the median follow-up was 65 months (range = 12 to 115 months). Five ipsilateral breast recurrences (1%) were observed. On matched-pair analysis, the rate of local recurrence was not statistically different between the partial and whole breast treatment groups.

Table 5.1 Published Experience of Multicatheter Delivery of Accelerated Partial Breast Irradiation

Multicatheter Trials

Number of Cases

Median Follow-Up

Local Recurrence 5-year (%)

Elsewhere Failure 5-year (%)

William Beaumont Hospital26

Total

199

65

1

0.6

Low dose rate

120

85

0.9

0

High dose rate

79

52

2.1

2.1

Ochsner clinic27

51

75

2.0

0

RTOG 95-17 (Radiation therapy oncology group)61

99

44

3

Virginia Commonwealth University28

44

42

0

0

University of Kansas62

25

47

0

Massachusetts General Hospital32

48

23

0

Tufts/Brown Universities31

33

58

6

6

Florence63

90

27

4.4

National Hungarian Phase I/II33,64

45

80

6.7

6.7

National Hungarian Phase III33,64,65

119

30

2.5

1.7

German Austrian Phase II66

176

24

0

0

Czech Republic67

19

11

0

5

Guys Hospital I59

27

72

37

Guys Hospital II68

50

60

18

4

London Regional Cancer Center60

39

91

16.2

10

At Virginia Commonwealth University, 44 patients were treated with breast brachytherapy between 1995 and 2000.28 Thirteen patients were treated with LDR (45 Gy at 50 cGy/hr). Thirty-one patients received 34 Gy in 10 twice-daily fractions with HDR. After a median follow-up of 42 months (range = 18 to 86 months), all patients remained locally controlled. Two patients developed metastatic disease. No regional nodal failures were observed.

Although most series have excellent rates of local control, which compare favorably with whole breast irradiation, three reports have shown unacceptable in-breast control rates. These higher rates of in-breast failure appear to be related to lack of patient selection criteria and/or treatment quality assurance. Guy's Hospital reported a local recurrence rate of 37% after partial breast therapy with 10 of 27 patients experiencing in breast recurrences by 6 years.59 All successful treatment experiences have required negative margins as part of the patient selection criteria. In this study microscopic margin assessment was not employed. In addition, the authors themselves have introduced questions regarding the methods used for target delineation and confirmation of dosimetric coverage. The London Regional Cancer Center reported a local recurrence rate of 15% at only 18 months.60 In this report dosimetric coverage of an appropriately defined target is questionable, as treatment was limited to the seroma cavity itself and not to the surrounding breast tissue at risk.65

The published experience of the MammoSite RTS is shown in Table 5-2. No local failures have been reported; however the series with the most mature data has follow-up of only 29 months. Results are encouraging, but additional follow-up is necessary to truly determine the efficacy of this device.

Table 5.2 The Published Experience of the MammoSite Rts Delivered Accelerated Partial Breast Irradiation

MammoSite Trials

Number of Patients

Median Follow-Up (Months)

Cosmetic Results (Good/Excellent) (Percentage)

Adverse Effects (%)

Local Recurrence (%)

Keisch M et al.20,45,51

43

29

84

3.7

0

Tufts/Virginia Commonwealth39

28

19

93

0

0

St. Vincent's52

32

11

86

16

0

Rush University56

30

18

93

13

0

Kaiser Permanente69

40

13.3

97

8

0

Tulane70

19

31

90

16

0

American Society of Breast Surgeons54

1,400

5

92

8

0.1

Future Directions

Continued studies are necessary to address questions regarding patient selection criteria and the equivalence of APBI to traditional whole breast radiotherapy. Proposed and activated phase III trials from The United States and Europe are presented in Table 5-3. To definitively answer the question of long-term efficacy and toxicity the (NSABP) and RTOG have combined to sponsor a clinical trial directly comparing whole breast irradiation with partial breast brachytherapy. NSABP B-39/RTOG 0413 will enroll 3,000 women for randomization between APBI and standard whole breast irradiation. When patients are randomized to the PBI arm, the physician will have the option of using any of the three acceptable APBI techniques (multicatheter, MammoSite, or 3D-CRT). A rigorous quality assurance program will ensure that the intended target is appropriately defined and that the dose coverage is acceptable by standards outlined in the protocol. Patients will be followed for toxicity, cosmetic outcome, local control, and survival data. Biologic samples will be collected for a tissue bank to allow genetic and proteomic analysis of cohorts in the future. The results of these trials will certainly determine the next chapter on the efficacy of partial breast brachytherapy. With the continued reporting of the initial trials and the initiation of additional single and multiinstitutional phase I/II trials and phase III prospective randomized trials, these questions will be appropriately addressed and further define the role of APBI in the management of early-stage breast cancer.

Table 5.3 American and European Phase III Clinical Trials of Accelerated Partial Breast Irradiation

 

NSABP B39/RTOG 0413a

GEC-ESTROb Multicenter Phase III Trial

Delivery method

Multicatheter Implant
MammoSite RTS
3D Conformal external beam

Multicatheter implant

Patient age

All ages

≥40 y

Tumor size

≤3 cm

≤3 cm

Histology

All invasive histologies ductal carcinoma in situ

All invasive histologies
Ductal carcinoma in situ (Van Nuys prognostic index71<8 only)

Margin status

Negative (No tumor extending to inked margin)

Nonlobular invasive carcinoma >2 mm
Invasive lobular carcinoma >5 mm
Ductal carcinoma in situ >5 mm

Node status

pN0–pN1
No extracapsular extension

pN0–pN1mic

a National Surgical Adjuvant Breast and Bowel Project B39 & Radiation Therapy Oncology Group 0413.37
b Groupe Europeen de Curietherapie European Society for Therapeutic Radiology and Oncology.35

Post Mastectomy Scar Boost Brachytherapy with Surface Applicator

For patients judged to have a high risk of local recurrence after mastectomy, a scar boost is often recommended. A CT computer-optimized HDR brachytherapy technique has been proposed to deliver conformal boost radiation dose to the surgical scar in the setting of immediate reconstruction after mastectomy. Stewart et al.72 described the rationale, methodology, and improved dosimetric outcome when comparing this method to either single or matched en face electron fields. In both cases of TRAM reconstruction and saline implant reconstruction, the surface applicator technique provided a uniform skin dose of 100%, at the same time avoiding hot and cold spots and allowed a rapid falloff of dose in the reconstructed breast.

Figure 5.13 Applicator with catheters. A CT scan computer-optimized brachytherapy plan was developed in the Plato Treatment Planning System (Nucletron B.V., Veenendal Netherlands).

 

Figure 5.14 Isodose distribution of surface applicator applied to scar of TRAM flap reconstruction demonstrating excellent conformance and normal tissue sparing.

The methodology involved setting the patient in a supine position with the ipsilateral arm akimbo. An Aquaplast mold was constructed over the reconstructed breast and extended to include the setup position of the arm. Skin fiducials were matched to mold fiducials. HDR catheters were affixed to the mold over the scar in parallel manner with the central catheter directly over the surgical scar. Figure 5.13 demonstrates applicator with catheters A CT computer-optimized brachytherapy plan was developed in the Plato Treatment Planning System (Nucletron B.V., Veenendal Netherlands). Figure 5.14 shows isodoses on TRAM flap reconstruction. The boost was then delivered in a dose and fractionation scheme identical to the usual electron scar boost prescription—2 Gy per day to the surface for 5 consecutive days, (after 50.4 Gy in 20 fractions to the comprehensive initial target volume).

References

1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227–1232.

2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–1241.

3. Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project. World J Surg. 1994;18:63–69.

4. Hebert-Croteau N, Brisson J, Latreille J, et al. Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women. Cancer. 1999;85: 1104–1113.

5. Du X, Freeman JL, Freeman DH, et al. Temporal and regional variation in the use of breast-conserving surgery and radiotherapy for older women with early-stage breast cancer from 1983 to 1995. J Gerontol A Biol Sci Med Sci. 1999;54:M474–M478.

6. Athas WF, Adams-Cameron M, Hunt WC, et al. Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery. J Natl Cancer Inst. 2000;92: 269–271.

7. Hahn CA, Marks LB, Chen DY, et al. Breast conservation rates-barriers between tertiary care and community practice. Int J Radiat Oncol Biol Phys. 2003;55:1196–1199.

8. Nattinger AB, Hoffmann RG, Kneusel RT, et al. Relation between appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery. Lancet. 2000;356:1148–1153.

9. Holland R, Veling SH, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985;56: 979–990.

10. Ohtake T, Abe R, Kimijima I, et al. Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems. Cancer. 1995;76:32–45.

11. Imamura H, Haga S, Shimizu T, et al. Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age. Breast Cancer Res Treat. 2000;62:177–184.

12. Faverly DR, Burgers L, Bult P, et al. Three dimensional imaging of mammary ductal carcinoma in situ: Clinical implications. Semin Diagn Pathol. 1994;11:193–198.

13. Liljegren G, Holmberg L, Bergh J, et al. 10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: A randomized trial. J Clin Oncol. 1999;17:2326–2333.

14. Clark RM, Wilkinson RH, Miceli PN, et al. Breast cancer. Experiences with conservation therapy. Am J Clin Oncol. 1987;10:461–468.

15. Recht A, Houlihan MJ. Conservative surgery without radiotherapy in the treatment of patients with early-stage invasive breast cancer. A review. Ann Surg. 1995;222:9–18.

16. Morrow M. Rational local therapy for breast cancer. N Engl J Med. 2002;347:1270–1271.

17. Kuske RR. Breast brachytherapy. Hematol Oncol Clin North Am 1999;13:543–558, vi–vii.

18. Das RK, Patel R, Shah H, et al. 3D CT-based high-dose-rate breast brachytherapy implants: Treatment planning and quality assurance. Int J Radiat Oncol Biol Phys. 2004;59:1224–1228.

19. Cuttino LW, Todor D, Arthur DW. CT-guided multi-catheter insertion technique for partial breast brachytherapy: Reliable target coverage and dose homogeneity. Brachytherapy. 2005;4:10–17.

20. Keisch M, Vicini F, Kuske RR, et al. Initial clinical experience with the MammoSite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2003;55:289–293.

21. Vicini FA, Baglan KL, Kestin LL, et al. Accelerated treatment of breast cancer. J Clin Oncol. 2001;19:1993–2001.

22. Vicini FA, Remouchamps V, Wallace M, et al. Ongoing clinical experience utilizing 3D conformal external beam radiotherapy to deliver partial-breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2003;57:1247–1253.

23. Baglan KL, Sharpe MB, Jaffray D, et al. Accelerated partial breast irradiation using 3D conformal radiation therapy (3D-CRT). Int J Radiat Oncol Biol Phys. 2003;55:302–311.

24. Zwicker RD, Schmidt-Ullrich R. Dose uniformity in a planar interstitial implant system. Int J Radiat Oncol Biol Phys. 1995;31:149–155.

25. Zwicker RD, Arthur DW, Kavanagh BD, et al. Optimization of planar high-dose-rate implants. Int J Radiat Oncol Biol Phys. 1999;44:1171–1177.

26. Vicini FA, Kestin L, Chen P, et al. Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst. 2003;95:1205–1210.

27. King TA, Bolton JS, Kuske RR, et al. Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer. Am J Surg. 2000;180:299–304.

28. Arthur DW, Koo D, Zwicker RD, et al. Partial breast brachytherapy after lumpectomy: Low-dose-rate and high-dose-rate experience. Int J Radiat Oncol Biol Phys. 2003;56: 681–689.

29. Kuske RR, Winter K, Arthur D, et al. A phase II trial of brachytherapy alone following lumpectomy for stage I or II breast cancer: Initial outcomes of RTOG 95-17. Proc 40th Ann Meeting of Am Soc Clin Oncol. 2004;23:18.

30. Wazer DE, Lowther D, Boyle T, et al. Clinically evident fat necrosis in women treated with high-dose-rate brachytherapy alone for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2001;50:107–111.

31. Wazer D, Berle L, Graham R, et al. Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer. Int J Radiat Oncol Biol Phys. 2002;53:889–897.

32. Lawenda BD, Taghian AG, Kachnic LA, et al. Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant. Int J Radiat Oncol Biol Phys. 2003;56:671–680.

33. Polgar C, Major T, Fodor J, et al. High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast-conserving surgery: Seven-year results of a comparative study. Int J Radiat Oncol Biol Phys. 2004;60:1173–1181.

34. Polgar C, Strnad V, Major T. Brachytherapy for partial breast irradiation: The European experience. Semin Radiat Oncol. 2005;15:116–122.

35. Strnad VPC, Study Protocol, European Brachytherapy Breast Cancer GEC-ESTRO Working Group. Phase III Multicenter Trial - Interstitial Brachytherapy alone versus external beam radiation therapy after breast conserving surgery for low risk invasive carcinoma and low risk Duct Carcinoma in situ (DCIS) of the female breast. 2004.

36. Edmundson GK, Vicini FA, Chen PY, et al. Dosimetric characteristics of the MammoSite RTS, a new breast brachytherapy applicator. Int J Radiat Oncol Biol Phys. 2002;52:1132–1139.

37. Vicini F, White J, Arthur D, et al. NSABP Protocol B39/RTOG Protocol 0413 A randomized phase III study of conventional whole breast irradiation versus partial breast irradiation for women with stage 0.I, or II breast cancer. 2004.

38. Vicini FA, Jaffray DA, Horwitz EM, et al. Implementation of 3D-virtual brachytherapy in the management of breast cancer: A description of a new method of interstitial brachytherapy. Int J Radiat Oncol Biol Phys. 1998;40:629–635.

39. Shah NM, Tenenholz T, Arthur D, et al. MammoSite and interstitial brachytherapy for accelerated partial breast irradiation: Factors that affect toxicity and cosmesis. Cancer. 2004;101:727–734.

40. Wazer DE, Kaufman S, Cuttino L, et al. Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2006;64(2):489–495.

41. Kuske RR. A phase I/II trial to evaluate brachytherapy as the sole method of radiation therapy for stage I and II breast carcinoma. Philadelphia, PA, (RTOG Publication No. 1055): Radiation Therapy Oncology Group; 1995.

42. Wu A, Ulin K, Sternick E. A dose homogeneity index for evaluating 192Ir interstitial breast implants. Med Phys. 1988;15:104–107.

43. Arthur D, Wazer D, Koo D, et al. The importance of dose-volume histogram evaluation in partial breast brachytherapy: A study of dosimetric parameters. Int J Radiat Oncol Biol Phys. 2003;57:S361–S362.

44. Kestin LL, Jaffray DA, Edmundson GK, et al. Improving the dosimetric coverage of interstitial high-dose-rate breast implants. Int J Radiat Oncol Biol Phys. 2000;46:35–43.

45. Keisch M, Vicini F, Kuske RR. Two-year outcome with the mammosite breast brachytherapy applicator: Factors associated with optimal cosmetic results when performing partial breast irradiation. Int J Radiat Oncol Biol Phys. 2003;60(Suppl. 1):s315.

46. Dickler A, Kirk MC, Chu J, et al. The MammoSite breast brachytherapy applicator: A review of technique and outcomes. Brachytherapy. 2005;4:130–136.

47. Arthur DW, Vicini FA, Kuske RR, et al. Accelerated partial breast irradiation: An updated report from the American Brachytherapy Society. Brachytherapy. 2002;1:184–190.

48. Arthur D. Accelerated partial breast irradiation: A change in treatment paradigm for early stage breast cancer. J Surg Oncol. 2003;84:185–191.

49. Arthur DW, Vicini FA. Accelerated partial breast irradiation as a part of breast conservation therapy. J Clin Oncol. 2005;23:1726–1735.

50. Consensus statement for Accelerated Partial Breast Irradiation from the American Society of Breast Surgeons, 2005. http://www.breastsurgeons.org/officialstmt3.html.

51. Keisch M, Vicini F, Scroggins T, et al. Thirty month results with the mammosite breast brachytherapy applicator: Cosmesis, toxicity, local control in partial breast irradiation. Int J Radiat Oncol Biol Phys. 2004;60(Suppl. 1):s272.

52. Richards GM, Berson AM, Rescigno J, et al. Acute toxicity of high-dose-rate intracavitary brachytherapy with the MammoSite applicator in patients with early-stage breast cancer. Ann Surg Oncol. 2004;11:739–746.

53. Harper JL, Jenrette JM, Vanek KN, et al. Acute complications of MammoSite brachytherapy: A single institution's initial clinical experience. Int J Radiat Oncol Biol Phys. 2005;61:169–174.

54. Vicini FA, Beitsch PD, Quiet CA, et al. First analysis of patient demographics, technical reproducibility, cosmesis, and early toxicity: Results of the American Society of Breast Surgeons MammoSite breast brachytherapy trial. Cancer. 2005;104:1138–1148.

55. Streeter OE Jr, Vicini FA, Keisch M, et al. MammoSite radiation therapy system. Breast 2003;12:491–496.

56. Dowlatshahi K, Snider HC, Gittleman MA, et al. Early experience with balloon brachytherapy for breast cancer. Arch Surg. 2004;139:603–607; discussion 607–608.

57. Benitez PR, Chen PY, Vicini FA, et al. Partial breast irradiation in breast conserving therapy by way of interstitial brachytherapy. Am J Surg. 2004;188:355–364.

58. Dickler A, Kirk MC, Choo J, et al. Cosmetic outcome and incidence of infection with the MammoSite breast brachytherapy applicator. Breast J. 2005;11:306–310.

59. Fentiman IS, Poole C, Tong D, et al. Inadequacy of iridium implant as sole radiation treatment for operable breast cancer. Eur J Cancer. 1996;32A:608–611.

60. Perera F, Yu E, Engel J, et al. Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years' minimum follow-up. Int J Radiat Oncol Biol Phys. 2003;57:1239–1246.

61. Kuske RR, Winter K, Arthur DW, et al. A phase II trial of brachytherapy alone following lumpectomy for stage I or II breast cancer: Initial outcomes of RTOG 95-17. Annu Meet Proc (Post-meeting Edition). 2004;22(14 Suppl):565.

62. Krishnan L, Jewell WR, Tawfik OW, et al. Breast conservation therapy with tumor bed irradiation alone in a selected group of patients with stage I breast cancer. Breast J. 2001;7:91–96.

63. Cionini L, Pacini P, Marzano S. Exclusive brachytherapy after conservative surgery in cancer of the breast. Lyon Chir. 1993;89:128.

64. Polgar C, Sulyok Z, Fodor J, et al. Sole brachytherapy of the tumor bed after conservative surgery for T1 breast cancer: Five-year results of a phase I-II study and initial findings of a randomized phase III trial. J Surg Oncol. 2002;80:121–128; discussion 129.

65. Vicini F, Arthur D, Polgar C, et al. Defining the efficacy of accelerated partial breast irradiation: The importance of proper patient selection, optimal quality assurance, and common sense. Int J Radiat Oncol Biol Phys. 2003;57:1210–1213.

66. Strnad V, Ott O, Potter R, et al. Interstitial brachytherapy alone after breast conserving surgery: Interim results of a German-Austrian multicenter phase II trial. Brachytherapy. 2004;3:115–119.

67. Slampa P, Soumarova R, Ruzickova J, et al. Pilot study of sole conformal preoperative interstitial brachyradiotherapy of early stage breast carcinoma using high-dose rate afterloading. Neoplasma. 2005;52:292–296.

68. Fentiman IS, Deshmane V, Tong D, et al. Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial. Radiother Oncol. 2004;71:281–285.

69. DiFronzo LA, Tsai PI, Hwang JM, et al. Breast conserving surgery and accelerated partial breast irradiation using the MammoSite system: Initial clinical experience. Arch Surg. 2005;140:787–794.

70. Stolier AJ, Fuhrman GM, Scroggins TG, et al. Postlumpectomy insertion of the MammoSite brachytherapy device using the scar entry technique: Initial experience and technical considerations. Breast J. 2005;11:199–203.

71. Silverstein MJ. An argument against routine use of radiotherapy for ductal carcinoma in situOncology (Huntingt). 2003;17:1511–1533; discussion 1533-1514, 1539, 1542 passim.

72. Stewart AJ, et al. HDR surface applicator boost after immediate reconstruction from mastectomy. Brachytherapy. 2005;4:229–239.



If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!