Robert R. Kuske

Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for Tis,1,2 breast cancer

BACKGROUND We hypothesized that wide-field brachytherapy (BRT) after margin negative excision would result in complication rates, local recurrence rates, and cosmesis scores equivalent to external beam radiotherapy (ERT). METHODS Patients with T(is,1,2) tumors less than or equal to 4 cm, 0 to 3 positive axillary nodes, and negative inked surgical margins were entered prospectively into BRT phase I/II trial. Patients who met the eligibility criteria for BRT but were treated with ERT during the same time period were retrospectively identified as controls. A blinded panel of healthcare professionals graded cosmetic outcome. RESULTS Fifty patients with 51 breast cancers received BRT from January 1992 to October 1993. We identified 94 patients eligible for BRT but concurrently treated with ERT. At a median follow-up of 75 months, the two groups were similar for grade III treatment toxicities, local/regional recurrence rates, and cosmesis scores. CONCLUSIONS For selected breast cancer patients undergoing breast-conserving therapy, BRT is an attractive alternative to ERT.

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.

Factors influencing cosmetic results after conservation therapy for breast cancer

PURPOSE Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. METHODS AND MATERIALS Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15%, T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. RESULTS At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). CONCLUSIONS Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy.

Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.

PURPOSE To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. PATIENTS AND METHODS An analysis was performed of 270 intraductal breast carcinomas in 268 women from 10 institutions in Europe and the United States. In all patients, breast-conserving surgery included complete gross excision of the primary tumor followed by definitive breast irradiation. When performed, pathologic axillary lymph node staging was node-negative (n=86). The median follow-up time was 10.3 years (range, 0.9 to 26.8). RESULTS The 15-year actuarial overall survival rate was 87%, and the 15-year actuarial cause-specific survival rate was 96%. The 15-year actuarial rate of freedom from distant metastases was 96%. There were 45 local recurrences in the treated breast, and the 15-year actuarial rate of local failure was 19%. The median time to local failure was 5.2 years (range, 1.4 to 16.8). A number of clinical and pathologic parameters were evaluated for correlation with local failure, and none were predictive for local failure (all P > or = .15). CONCLUSION The results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of DCIS of the breast using breast-conserving surgery and definitive breast irradiation. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of DCIS of the breast.

Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity

PURPOSE Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. METHODS AND MATERIALS Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. RESULTS Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. CONCLUSIONS This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis.

A Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: Tumor control and survival outcomes of RTOG 95-17

PURPOSE Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. METHODS AND MATERIALS Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. RESULTS Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. CONCLUSION Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up.

Radiation therapy alone in the treatment of carcinoma of the uterine cervix: A 20-year experience

A retrospective analysis is reported on the results of irradiation alone in the treatment of 970 patients with histologically proven invasive carcinoma of the uterine cervix. The development of the radiation therapy techniques, survival, pelvic tumor control, and major sequelae of therapy are described in detail. The tumor-free 5-year survival rate was 100% in 29 patients with stage IA, 85% in 312 cases with stage IB, 70% in 98 patients with stage IIA, 68% in 276 patients with stage IIB, 45% in 237 stage III cases, and one survivor in 18 stage IV patients. No pelvic recurrences or distant metastases were observed in stage IA patients. In stage IB the overall incidence of pelvic recurrences was 7.3%, in stages IIA and IIB 14%, and in stage III 37%. Distant metastases were noted in 13% of the patients with stage IB, 22% of those with stages IIA and IIB, and 32% of patients with stage III tumors. Higher doses of irradiation delivered with intracavitary insertions and extenal beam were correlated with a lower incidence of pelvic recurrences in stages IIA, IIB, and III. However, doses to point A over 7000 cGy did not improve pelvic tumor control in stage IB. Grade 2 treatment sequelae were observed in about 10% of all patients and grade 3 complications in approximately 4% of the patients with stage I and 8% in those with more advanced tumors (IIA and beyond). The need is emphasized to carefully evaluate the dosimetric aspects of new techniques, including phantom studies before they are applied to patients. A close integration of external and intracavitary irradiation will result in better tumor control and fewer complications.

Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society

Logistical barriers of time and travel created by the conventional six-week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.

Ten‐year results of breast‐conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10‐year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow‐up time was 78 months (range, 11 to 197 months). The 10‐year actuarial overall survival rate was 94%, and the 10‐year actuarial cause‐specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10‐year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10‐year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty‐four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow‐up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node‐positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause‐specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow‐up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow‐up of patients after breast‐conservation and definitive irradiation is required. Cancer 68:2337–2344, 1991.

Isolated local-regional recurrence of breast cancer following mastectomy: Radiotherapeutic management

Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local-regional control.(ABSTRACT TRUNCATED AT 400 WORDS)