Coral A. Quiet

Initial clinical experience with the MammoSite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE We present the results of the initial clinical testing of the MammoSite balloon breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS Seventy patients were enrolled in a multicenter prospective trial testing the applicator for safety and performance. Fifty-four patients were implanted, and 43 patients were ultimately eligible for and received brachytherapy as the sole radiation modality after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required for treatment. Device performance, complications, and cosmesis were assessed. RESULTS Computed tomography imaging post-balloon inflation showed 8, 14, and 21 patients with 5-6 mm, 7-9 mm, and >10 mm of skin spacing, respectively. Two patients were explanted because of inadequate skin spacing and 7 because of suboptimal conformance of the surgical cavity to the applicator balloon. One patient was explanted because of positive nodal status and another because of age. The most common side effects related to device placement included mild erythema, drainage, pain, and echymosis. No severe side effects related to implantation, brachytherapy, or explantation occurred. Side effects related to radiation therapy were generally mild with erythema, pain, and dry desquamation being the most common. At 1 month, 88% of patients were evaluated as having good-to-excellent cosmetic results. CONCLUSIONS The MammoSite balloon breast brachytherapy applicator performed well clinically. All eligible patients completed treatment. Side effects were mild to moderate and self-limiting. Skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the device.

Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation.

PURPOSE To present 5-year data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial. METHODS AND MATERIALS A total of 1440 patients (1449 cases) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Of 1449 cases, 1255 (87%) had invasive breast cancer (IBC) (median size, 10 mm) and 194 (13%) had ductal carcinoma in situ (DCIS) (median size, 8 mm). Median follow-up was 54 months. RESULTS Thirty-seven cases (2.6%) developed an ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial rate of 3.80% (3.86% for IBC and 3.39% for DCIS). Negative estrogen receptor status (p=0.0011) was the only clinical, pathologic, or treatment-related variable associated with IBTR for patients with IBC and young age (<50 years; p=0.0096) and positive margin status (p=0.0126) in those with DCIS. The percentage of breasts with good/excellent cosmetic results at 60 months (n=371) was 90.6%. Symptomatic breast seromas were reported in 13.0% of cases, and 2.3% developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 60.5 months, the 5-year actuarial rate of IBTR was 3.04%. CONCLUSION Treatment efficacy, cosmesis, and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.

Natural history of node-negative breast cancer: a study of 826 patients with long-term follow-up.

PURPOSE We were interested in examining the long-term outcome of patients with node-negative breast cancer to address the following questions: (1) Is node-negative breast cancer a disease that is curable by local modalities? (2) Are there predictors of disseminated disease in node-negative breast cancer? (3) Are there subgroups of tumors that have different times to recurrence? METHODS From 1927 to 1984, 826 women with node-negative breast cancer were treated at the University of Chicago. Patients underwent either a radical or extended radical mastectomy (83%) or a modified radical mastectomy (13%). RESULTS Follow-up evaluation ranged from 9 to 523 months (43.6 years); the mean follow-up period of survivors is 162 months (13.5 years). On multivariate analysis, the strongest predictor of outcome and time to relapse was pathologic tumor size. Patients with tumors less than 2 cm had a 20-year disease-free survival (DFS) rate of 79% and a median time to recurrence of 48 months as compared with patients with tumors greater than 2 cm, who had a survival rate of 64% (P < .001) and a median time to recurrence of 37 months (P = .01). CONCLUSION With extended follow-up evaluation, node-negative breast cancer is a curable disease. Size is the strongest predictor of dissemination and rate of relapse. These data suggest that given the natural history of node-negative breast cancer, analysis of clinical trials with short follow-up periods can be misleading, since it may identify those patients whose tumors have a greater virulence but not necessarily a greater likelihood to metastasize.

Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI)

This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial.

Natural history of node-positive breast cancer: the curability of small cancers with a limited number of positive nodes.

PURPOSE The long-term outcome of node-positive breast cancer was analyzed to determine the risk of metastatic disease as a function of tumor size and number of positive nodes. METHODS From 1927 to 1987, 501 women with node-positive breast cancer were treated at the University of Chicago Medical Center. Patients were treated with radical, extended radical, or modified radical mastectomy. Forty-eight patients received multiagent chemotherapy, and 118 were treated with hormonal therapy. The mean survival duration is 120 months, with a maximal follow-up time of 485 months (40 years). RESULTS The number of nodes that contained metastatic disease and the pathologic size of the primary tumor were significant determinants of disease-free-survival (DFS) by multivariate analysis (P < .001). In patients with fewer than four positive nodes, tumor size was of prognostic importance, with small tumors more likely to be cured by local-regional therapy. The 20-year DFS rate for patients with one positive node was 69%; however, if the primary tumor was < or = 2 cm, the 20-year DFS rate was 81%, compared with 59% if the tumor was larger than 2 cm. Patients with two or three positive nodes had a 73% 20-year DFS rate if the tumor size was < or = 2 cm, compared with 53% 20-year DFS in patients with tumors larger than 2 cm. CONCLUSION In patients with T1 lesions with less than four nodes positive, the long-term DFS rate is comparable to that for node-negative breast cancer of the same size. Four or more nodes positive is an indicator of likely systemic disease.

Initial outcomes for patients treated on the American Society of Breast Surgeons MammoSite Clinical Trial for ductal carcinoma-in-situ of the breast

BackgroundThe MammoSite device was designed as a breast brachytherapy applicator and is currently used to deliver accelerated partial breast irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device would be well tolerated and be associated with a good cosmetic outcome in patients with ductal carcinoma-in-situ (DCIS).MethodsFrom 2002 to 2004, 191 patients with DCIS were enrolled in a registry trial to assess the MammoSite applicator. Fifteen patients were excluded from analysis because of device- or patient-related factors; 7 patients were excluded after receiving a radiotherapy boost, thus leaving 169 patients available for study. Follow-up information was available for 158 patients. The average length of follow-up was 7.35 months. Forty-three patients had at least 1 year of follow-up.ResultsSkin spacing for the MammoSite applicator was as follows: < 5 mm, 3 patients (1.78%); 5 to 7 mm, 18 patients (10.65%); and ≥7 mm, 148 patients (87.57%). Patients with a device-to-skin distance of ≥7 mm had the best cosmetic result. Patients with a device-to-skin distance of ≥7 mm also had a lower incidence of radiation dermatitis. Data on 43 patients who were followed up for at least 1 year confirmed these findings. Additional adverse events were primarily related to skin changes, with breast infections occurring in five patients (3.16%). No patient in the study has experienced a recurrence.ConclusionsAPBI delivered via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity was obtained in patients with the greatest device-to-skin distance. Long-term follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed and will be determined from a recently opened large randomized study.

Four-year clinical update from the American Society of Breast Surgeons MammoSite brachytherapy trial

BACKGROUND We present a 4-year update on the efficacy, cosmetic results, and complications of MammoSite breast brachytherapy in patients enrolled in the American Society of Breast Surgeons registry trial. METHODS A total of 1,449 breasts in 1,440 patients with early stage breast cancer undergoing breast-conserving therapy were treated with adjuvant, accelerated partial breast irradiation (APBI) (34 Gy in 3.4-Gy fractions) delivered with the MammoSite device. The median follow-up period for the entire group was 36.1 months. RESULTS The 3-year actuarial rate of ipsilateral breast tumor recurrence was 2.15%. The 3-year actuarial rate of axillary recurrence was .36%. Complication rates were as follows: infection, 9.5%; seroma, 26.8% (symptomatic seroma, 12.7%); and fat necrosis, 2.0%. The percentages of breasts with good or excellent cosmetic results were as follows: 12 months, 95%; 24 months, 94%; 36 months, 94%; and 48 months, 91%. CONCLUSIONS Locoregional control, complications, and cosmetic outcomes from MammoSite APBI at the 4-year update are acceptable and similar to results seen with other forms of APBI.

Initial clinical experience with the Strut-Adjusted Volume Implant (SAVI) breast brachytherapy device for accelerated partial-breast irradiation (APBI): first 100 patients with more than 1 year of follow-up.

PURPOSE The Strut-Adjusted Volume Implant (SAVI; Cianna Medical, Aliso Viejo, CA) is a multichannel single-entry brachytherapy device designed to allow dose modulation to minimize normal tissue dose while simultaneously maximizing target coverage. This is the first report on the initial 102 patients with nearly 2 years of median follow-up. METHODS AND MATERIALS One hundred two patients were treated at two institutions. Data were collected on eligibility and dosimetry and followed for toxicity and recurrence. RESULTS The median follow-up is 21 months. Overall dosimetry is outstanding (median percent of target volume receiving 90% of the prescription dose was 95.9%, volume of target receiving 150% of the prescription dose was 27.8 mL, and volume of target receiving 200% of the prescription dose was 14.0 cm(3)). No devices were pulled prior to treatment completion. For patients with a skin bridge of less than 7 mm, the maximum median skin dose was 280 cGy (median percent of target volume receiving 90% of the prescription dose was 95.2%, volume of target receiving 150% of the prescription dose was 25.8 cm(3) and volume of target receiving 200% of the prescription dose was 12.7 mL). For patients with both chest wall and skin of less than 7 mm, the maximum median lung dose was 205 cGy with simultaneous skin dose of 272 cGy. The rate of telangiectasia was 1.9%. Grade 1 hyperpigmentation developed in 10 patients (9.8%) and Grade 2 fibrosis in 2 patients (1.9%). There were 2 symptomatic seromas and 2 cases of asymptomatic fat necrosis (1.9%). Of the patients, 27% were not eligible for MammoSite balloon brachytherapy (Hologic, Inc., Marlborough, MA) and 5% were not eligible for any balloon brachytherapy. The recurrence rate was 1%. CONCLUSIONS The SAVI appears to safely allow an increase in eligibility for APBI over balloon brachytherapy or three-dimensional conformal radiation, highlighting the outstanding device flexibility to maximize the target dose and minimize the normal tissue dose. The device was well tolerated by patients.

Postoperative ultrasound-guided percutaneous placement of a new breast brachytherapy balloon catheter

BACKGROUND The optimal technique and timing for the implantation of a recently developed breast brachytherapy balloon catheter (MammoSite; Proxima Therapeutics, Alpharetta, Georgia) have not been well defined. We hypothesized that placing this postoperatively, utilizing percutaneous ultrasound-guided placement, would be preferable. METHODS Patients who met eligibility requirements for breast brachytherapy were implanted with the MammoSite device utilizing percutaneous ultrasound-guided technique. Additionally, to study optimal timing, a historical cohort of patients operated upon for breast cancer by two of the authors were analyzed to compare the intraoperative and postoperative candidacy for MammoSite placement. RESULTS Twenty-one of 23 patients successfully completed brachytherapy after implantation, with only 2 (9%) requiring catheter removal secondary to unfavorable balloon positioning. There were no serious complications. Of 343 historical patients with breast cancer, 137 were intraoperative candidates for brachytherapy, but final postoperative histology disqualified 40 (29%). CONCLUSIONS Implantation of the MammoSite brachytherapy device is optimally performed postoperatively, after the final pathology is defined, utilizing ultrasound-guided percutaneous technique.

Variation in radiation sensitivity during the cell cycle of two human squamous cell carcinomas

Changes in the radiation age response are described in two cell lines derived from human squamous cell carcinomas. A radioresistant tumor cell line, JSQ-3, has a DO of 240 cGy and is polyploid with a DNA content of 2.68. A relatively radiosensitive tumor cell line, SCC-61, has a DO of 126 cGy and has a DNA index of 1.16. Tumor cells were separated and synchronized by centrifugal elutriation; flow cytometry was used to determine cell-cycle parameters and relative synchrony. The radioresistant cell line, JSQ-3B, was found to have twice the number of cells in S-phase than the more sensitive cell line (28% and 13% for JSQ-3B and SCC-61B, respectively). Both cell lines, despite differences in intrinsic radiosensitivity, were most resistant during S-phase (DOs of 258 and 157 cGy for JSQ-3B and SCC-61B, respectively) and were maximally sensitive during G1 (DOs of 193 and 95 cGy for JSQ-3B and SCC-61B, respectively). Clinical implications of our findings are discussed.