Electronic brachytherapy as adjuvant therapy for early stage breast cancer: a retrospective analysis.

PURPOSE: This multicenter, retrospective study evaluated treatment and clinical outcomes of patients with early stage breast cancer who received adjuvant high-dose rate (HDR) electronic brachytherapy (EBT) treatment post-lumpectomy using the Axxent(®) EBT system. Dosimetric data from the EBT treatment plans were compared with those based on iridium-192 HDR brachytherapy. MATERIAL AND METHODS: Medical records of 63 patients with early stage breast cancer (Tis, T1a, T1b, T1c, and T2) who were treated post-lumpectomy with EBT alone or in combination with external beam radiation therapy were reviewed. The prescribed EBT dose was 34 Gy (10 fractions over 5 days, 3.4 Gy each) to 1 cm from the balloon surface. Dosimetry data from 12 patients were compared with these of treatment plans using an iridium-192 source prepared for the same 12 patients. RESULTS: The majority of patients (90.5%) were older than 50 years and had one or more risk factors for breast cancer (80.6%). Tumor sizes were 0.1 cm to 3.5 cm (mean 1.3 cm). Median follow-up was 7 months (1 to 18 months) post-EBT. Balloon applicators were implanted 0 to 85 days (mean 13.4 days) post-lumpectomy/re-excision. The most common adverse events were erythema, rash dermatitis, and pain or breast tenderness. No recurrences were reported. Dosimetric analyses demonstrated comparable target coverage, increased high-dose regions, and a significantly reduced dose to the ipsilateral breast and lungs as well as the heart with EBT as compared with the iridium-192 treatment plans. CONCLUSION: This retrospective, multicenter study showed that postsurgical adjuvant radiation therapy for early stage breast cancer can be administered using the EBT system with similar toxicity outcomes to those reported with iridium-192 brachytherapy. EBT offers a convenient, portable, nonisotope alternative to HDR brachytherapy using iridium-192.

Surgical perspectives from a prospective, nonrandomized, multicenter study of breast conserving surgery and adjuvant electronic brachytherapy for the treatment of breast cancer.

BACKGROUND: Accelerated partial breast irradiation (APBI) may be used to deliver radiation to the tumor bed post-lumpectomy in eligible patients with breast cancer. Patient and tumor characteristics as well as the lumpectomy technique can influence patient eligibility for APBI. This report describes a lumpectomy procedure and examines patient, tumor, and surgical characteristics from a prospective, multicenter study of electronic brachytherapy. METHODS: The study enrolled 65 patients of age 45-84 years with ductal carcinoma or ductal carcinoma in situ, and 44 patients, who met the inclusion and exclusion criteria, were treated with APBI using the Axxent® electronic brachytherapy system following lumpectomy. The prescription dose was 34 Gy in 10 fractions over 5 days. RESULTS: The lumpectomy technique as described herein varied by site and patient characteristics. The balloon applicator was implanted by the surgeon (91%) or a radiation oncologist (9%) during or up to 61 days post-lumpectomy (mean 22 days). A lateral approach was most commonly used (59%) for insertion of the applicator followed by an incision site approach in 27% of cases, a medial approach in 5%, and an inferior approach in 7%. A trocar was used during applicator insertion in 27% of cases. Local anesthetic, sedation, both or neither were administered in 45%, 2%, 41% and 11% of cases, respectively, during applicator placement. The prescription dose was delivered in 42 of 44 treated patients. CONCLUSIONS: Early stage breast cancer can be treated with breast conserving surgery and APBI using electronic brachytherapy. Treatment was well tolerated, and these early outcomes were similar to the early outcomes with iridium-based balloon brachytherapy.

Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.

OBJECTIVES: Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer. METHODS: Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions. RESULTS: Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events. CONCLUSIONS: Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.

Xoft Axxent electronic brachytherapy.

Balloon-based brachytherapy was developed to render accelerated partial-breast irradiation more accessible to breast cancer patients. Xoft Axxent electronic brachytherapy (eBX) is a novel method of accelerated partial-breast irradiation that utilizes an electronic source to produce x-rays. eBX does not require a high dose rate afterloader unit or a shielded vault and, thus, may appeal to a larger number of patients undergoing the accelerated partial-breast irradiation procedure. eBX is associated with a lower radiation dose to normal tissues and larger 'hot spots' than treatment with the MammoSite device. Additional applications are also being developed for eBX, including endometrial cancer treatment.

A dosimetric comparison of MammoSite and ClearPath high-dose-rate breast brachytherapy devices.

PURPOSE: A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI. METHODS AND MATERIALS: The dimensions of the CP device were reconstructed onto the MS planning CT scans for 15 previously treated patients. The mean %V(100), %V(150), %V(200) (percent of the PTV that received 100%, 150%, and 200% of the prescription dose, respectively), ipsilateral breast %V(50) (percent of the ipsilateral normal breast that received 50% of the prescription dose), ipsilateral lung %V(30) (percent of the ipsilateral lung that received 30% of the prescription dose), the heart %V(5) (percent of the heart that received 5% of the prescription dose), and the maximum skin point dose per fraction were then determined for each patient using the two methods of balloon-based PBI. RESULTS: The mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 42.1% vs. 42.9% (p=ns), and the mean V(200) was 11.4% vs. 15.2% (p<.05) for the MS and CP methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs.18.0% (p<.05), the mean ipsilateral lung %V(30) was 3.7% vs. 2.8% (p<.05), the mean heart %V(5) was 57.0% vs. 54.3% (p<.05), and the maximum skin point dose per fraction was 312.2 and 273.6cGy (p<.05) for the MS and CP methods, respectively. CONCLUSIONS: The MS and CP methods of PBI offer comparable target volume coverage; however, the CP device achieves increased normal tissue sparing.

Patterns of failure after MammoSite brachytherapy partial breast irradiation: a detailed analysis.

PURPOSE: To report the results of a detailed analysis of treatment failures after MammoSite breast brachytherapy for partial breast irradiation from our single-institution experience. METHODS AND MATERIALS: Between October 14, 2002 and October 23, 2006, 78 patients with early-stage breast cancer were treated with breast-conserving surgery and accelerated partial breast irradiation using the MammoSite brachytherapy applicator. We identified five treatment failures in the 70 patients with >6 months' follow-up. Pathologic data, breast imaging, and radiation treatment plans were reviewed. For in-breast failures more than 2 cm away from the original surgical bed, the doses delivered to the areas of recurrence by partial breast irradiation were calculated. RESULTS: At a median follow-up time of 26.1 months, five treatment failures were identified. There were three in-breast failures more than 2 cm away from the original surgical bed, one failure directly adjacent to the original surgical bed, and one failure in the axilla with synchronous distant metastases. The crude failure rate was 7.1% (5 of 70), and the crude local failure rate was 5.7% (4 of 70). Estimated progression-free survival at 48 months was 89.8% (standard error = 4.5%). CONCLUSIONS: Our case series of 70 patients with >6 months' follow-up and a median follow-up of 26 months is the largest single-institution report to date with detailed failure analysis associated with MammoSite brachytherapy. Our failure data emphasize the importance of patient selection when offering partial breast irradiation.

A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy.

PURPOSE: Over 20,000 patients have been treated with partial breast irradiation (PBI) using the MammoSite balloon brachytherapy applicator (IBB). Recently, a new form of balloon-based PBI, Xoft Axxent electronic brachytherapy (KVB), which uses a 50-kV x-ray source, has been introduced. This analysis was undertaken to dosimetrically compare the results of treatment using these two methods of PBI. METHODS AND MATERIALS: The study population consisted of 15 patients previously treated with IBB. The planning CT scans from these 15 patients were used to construct hypothetical treatment plans using the source characteristics of the KVB device. The plans were then compared using the dosimetric parameters discussed below. RESULTS: The mean %V(90) was 99.6% vs. 99.0% (p=nonsignificant [ns]), the mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 41.8% vs. 59.4% (p<0.05), the mean %V(200) was 11.3% vs. 32.0% (p<0.05), and the mean %V(300) was 0.4% vs. 6.7% (p<0.05) for the IBB and KVB methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs. 13.0% (p<0.05), the mean ipsilateral lung %V(30) was 3.7% vs. 1.1% (p<0.05), and the mean heart %V(5) was 59.2% vs. 9.4% (p<0.05) for the IBB and KVB methods, respectively. CONCLUSIONS: The IBB and KVB methods of PBI offer comparable target volume coverage; however, the KVB method is associated with an increased volume of breast tissue in the high-dose regions and a decreased dose to the adjacent normal tissues.

Cosmetic outcome and incidence of infection with the MammoSite breast brachytherapy applicator.

We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002, to February 13, 2004. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose), and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow-up was also recorded. At a median follow-up of 13 months (range 1-16 months), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome and 40.0% (12/30) had a good cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.5 cm versus 1.2 cm) (p = 0.164). The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% versus 93.0%, 34.7%, and 7.6% in the good cosmetic outcome group (p = 0.642, 0.926, and 0.853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3, respectively (p = 0.063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy (p = 0.286), respectively. Infection occurred in 13.3% of the patients (4/30). An excellent or good cosmetic outcome was achieved in 93.3% of patients and infection occurred in 13.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume; however, the results did not reach statistical significance.

Surface optimization technique for MammoSite breast brachytherapy applicator.

PURPOSE: We present a technique to optimize the dwell times and positions of a high-dose-rate (192)Ir source using the MammoSite breast brachytherapy applicator. The surface optimization method used multiple dwell positions and optimization points to conform the 100% isodose line to the surface of the planning target volume (PTV). METHODS AND MATERIALS: The study population consisted of 20 patients treated using the MammoSite device between October 2002 and February 2004. Treatment was delivered in 10 fractions of 3.4 Gy/fraction, twice daily, with a minimum of 6 h between fractions. The treatment of each patient was planned using three optimization techniques. The dosimetric characteristics of the single-point, six-point, and surface optimization techniques were compared. RESULTS: The surface optimization technique increased the PTV coverage compared with the single- and six-point methods (mean percentage of PTV receiving 100% of the prescription dose was 94%, 85%, and 91%, respectively). The surface method, single-point, and six-point method had a mean dose homogeneity index of 0.62, 0.68, and 0.63 and a mean full width at half maximum value of 189, 190, and 192 cGy/fraction, respectively. CONCLUSION: The surface technique provided greater coverage of the PTV than did the single- and six-point methods. Using the FWHM method, the surface, single-, and six-point techniques resulted in equivalent dose homogeneity.

Early experience with balloon brachytherapy for breast cancer.

HYPOTHESIS: Partial-breast irradiation for carcinoma by a single source of radiation placed in the center of a balloon inserted in the lumpectomy cavity is an effective method of treating breast cancer. Previous interstitial radiation therapy using iridium seeds placed within multiple catheters has been shown to be effective but impractical and cosmetically unacceptable to women. DESIGN: Prospective registry study. SETTING: Three university and community hospitals. PATIENTS: Women 40 years and older with histologically diagnosed in situ and invasive T1 through T2 and N0 or N1 breast cancer treated with lumpectomy and axillary node sampling were invited to enter this institutional review board-approved study. MAIN OUTCOME MEASURES: Evaluation of immediate and short-term complications, patients' acceptance of the treatment, and cosmesis are reported. RESULTS: Of the 129 eligible patients enrolled, 112 completed the treatment. Of these, transient skin erythema was noted in 28, localized edema in 3, and skin blisters adjacent to the balloon in 9. Infection developed in 7, necessitating drainage and antibiotic administration. In 10 patients, sonographically demonstrated seromas that developed after removal of the device were aspirated percutaneously. In 4 patients, punctured or ruptured balloons had to be replaced before the treatment could be completed. Patients quickly adjusted to the breast distension caused by the balloon, and their acceptance of the procedure was good. The cosmetic outcome was rated high. There were no recurrences during this very short follow-up. CONCLUSIONS: Our early short-term experience indicates balloon brachytherapy to be an acceptable alternative to external beam radiation for selected operable breast cancers. The 1-week treatment time allows working women and those who live at a distance from radiation centers to choose breast conservation rather than mastectomy.

Treatment volume and dose optimization of MammoSite breast brachytherapy applicator.

PURPOSE: Limited information has been reported on the dosimetry achieved with the MammoSite breast brachytherapy applicator. We present our results regarding the volume of treatment and a comparison of a single prescription point, single dwell position optimization technique with a six prescription point, multiple dwell position method. METHODS AND MATERIALS: Between October 14, 2002 and February 28, 2003, 21 patients with early-stage breast cancer were treated using the MammoSite device. The treatment was delivered in 10 fractions of 3.4 Gy/fraction, b.i.d., with a minimum of 6 hours between the daily fractions. CT of the lumpectomy cavity was obtained both with and without the inflated balloon. A planning target volume was constructed using a three-dimensional planning system. A three-dimensional expansion of the balloon surface was performed using the chest wall and skin as limiting structures. The volume of the inflated balloon was removed from this volume, and the volume of tissue treated in each patient was determined. A sequential expansion in 1-mm increments around the empty lumpectomy cavity was performed until the closest equivalent volume to the planning target volume was obtained. The treatment for the patients in this study was planned using both a single prescription point, single dwell position optimization technique and a six-prescription point, multiple dwell position technique. The single prescription point method has been described in a previous publication. The six-prescription point method used six points placed 1 cm from the balloon surface. Four points are in a plane transverse to the balloon axis perpendicular to the axis of the catheter, and two points are placed along the axis of the catheter. The prescription points along the catheter axis are used to compensate for the decreased dose coverage owing to anisotropy dose distribution of the source. The Nucletron HDR Plato Brachytherapy planning system was used to optimize the source positions and dwell times. RESULTS: The volume of breast tissue treated by the MammoSite device was equal to the volume encompassed by a mean 1.6-cm (SD, 0.1) margin around the empty lumpectomy cavity. Compared with the single prescription point optimization method, the six prescription point method provided better dose coverage, with a mean percentage of volume receiving 90% of the prescription dose of 97.2% (SD = 2.1) vs. 89.5% (SD = 4.6) for the single-point method. The mean percentage of volume receiving 100% of the prescription dose was 88.9% (SD = 3.3) for the six-point method vs. 77.6% (SD = 6.1) for the single-point method. However, compared with the single-point method, the six-point optimization method resulted in treatment that was less uniform, with a mean dose homogeneity index of 0.62 (SD =.07) vs. 0.66 (SD =.08) for the single-point method. CONCLUSION: The volume of normal breast tissue treated by the MammoSite device is comparable to other methods of interstitial brachytherapy that treat a 1-2-cm margin of tissue around the excision cavity. The six-prescription point, multiple dwell position method improved dose coverage with a slight decrease in dose homogeneity. The six-point method offers greater reliability of dose coverage compared with the single-point method by providing an increased number of reference points.

Laser therapy of breast cancer with 3-year follow-up.

Breast cancer is the commonest female malignancy in the United States and is increasingly being detected at a non-palpable stage by annual mammography. Minimally invasive methods of its local treatment have been recently introduced as alternative to its surgical removal. The case reported in this article illustrates the advantages of in-situ ablation with minimal discomfort to the patient and deformity of the breast. More importantly, it demonstrates the absence of any adverse effect on health and survival of the patient during this intermediate period of follow-up.

Sentinel lymph node biopsy lowers the rate of lymphedema when compared with standard axillary lymph node dissection.

Arm edema occurs in 20 to 30 per cent of patients who undergo axillary lymph node dissection (ALND) for carcinoma of the breast. Sentinel lymph node biopsy (SLNB) in lieu of ALND for staging of breast cancer significantly lowers this morbidity. We hypothesized that SLNB would have a lower lymphedema rate than conventional axillary dissection. Patients who underwent SLNB were compared with those who underwent level I and II axillary node dissection. A total of 125 patients were evaluated with 77 patients who underwent SLNB and 48 patients who underwent ALND. The arm circumference 10 cm above and 10 cm below the olecranon process was measured on both arms. In this series a difference in arm circumference greater than 3 cm between the operated and nonoperated side was defined as significant for lymphedema. Lymphedema was seen in two of 77 (2.6%) patients in the SLNB group as compared with 13 of 48 (27%) ALND patients. Given the above data patients who underwent sentinel lymph node biopsy show a significantly lower rate of lymphedema than those who had axillary lymph node dissection. This has an important impact on long-term postoperative management of patients with breast cancer.

Laser therapy for small breast cancers.

BACKGROUND: Widespread mammography has resulted in the increased detection of breast cancer <1.5 cm. It may be possible to treat these small tumors with in-situ laser ablation. Prior to ablation tumor size is determined by ultrasound and mammogram. Histologic diagnosis and determination of prognostic factors are obtained from image-guided needle core samples. Invasive and in-situ tumors may be percutaneously ablated by a stereotactically guided laser needle and subsequently evaluated by imaging methods and needle biopsy. METHODS: Fifty-four patients (50 invasive, 4 in-situ); 51 mass, 3 microcalcification; mean diameter 12 (5 to 23) mm were treated by a stereotactically guided 805 nm laser beam via a fiber in a 16G needle delivered to the cancer. One to 8 weeks later the coagulated lesions were surgically removed for pathologic evaluation. In 2 additional patients, the laser-treated tumors were not removed but were monitored by mammography, ultrasonography, and needle core biopsy. RESULTS: None of the patients sustained any adverse effect. The average treatment time was 30 minutes. Pathology analysis revealed a 2.5 to 3.5 hemorrhagic ring surrounding the necrotic tumor. Under steady conditions, in two groups of 14 patients, 93% and 100% of the tumors showed complete destruction, with no residual cancer report. In the 2 unresected cases kept under surveillance for 6 to 24 months, the laser-treated tumors first showed shrinkage, followed by a 2 to 3 cm oil cyst. Fibrosis was demonstrated on needle core biopsies. CONCLUSIONS: Laser energy delivered through a stereotactically guided needle appears to ablate mammographically detected breast cancer. A multicenter clinical trail is planned.

Heparanase-1 expression is associated with the metastatic potential of breast cancer.

BACKGROUND: Metastasis of malignant breast cells is in part mediated through degradation of the extra-cellular matrix by proteolysis, enabling malignant cells to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of proteoglycans, a component of the extracellular matrix and basement membrane. METHODS: Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1 expression using immunohistochemical staining. The functional role of HPR1 expression was determined by examining HS deposition using immunofluorescence staining. RESULTS: Sixteen of 30 breast carcinomas (53%) with sentinel node metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1 and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors < or =1 cm. Statistical analysis revealed that HPR1 expression was associated with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting an inverse correlation between HPR1 expression and HS deposition. CONCLUSIONS: HPR1 expression correlates with the lack of HS deposition and with the metastatic potential of breast cancers. The frequency of HPR1 is significantly higher in breast tumors between 1 and 5 cm than in tumors < or =1 cm.