Role of template guided interstitial implants in breast conservation therapy

Breast conservation therapy is currently considered as a viable alternative to mastectomy in early breast cancer. Radiotherapy by virtue of its ability to reduce local recurrences is an integral component of breast conservation therapy. Apart from irradiating the whole breast, the tumor bed is usually delivered a boost dose in breast conservation therapy to increase the local control rate. One of the methods which has been adopted to selectively boost the tumor bed to high doses is the use of per-operative high dose rate interstitial implants. This particular paper deals with our department's experience with breast conservation therapy using per-operative template guided, High Dose Rate (HDR) interstitial implants in early breast cancer. Local control rates, disease free survival and cosmetic benefit with this technique will be discussed along with literature review.     

Impact of boost technique on outcome in early-stage breast cancer patients treated with breast-conserving therapy

We reviewed our institution's experience treating early-stage breast cancer patients with breast-conserving therapy (BCT) to determine the impact of boost technique on outcome. A total of 552 patients with stage I and II breast cancer were managed with BCT. All patients were treated with a partial mastectomy and radiation therapy (RT). RT consisted of 45 Gy to 50 Gy external beam irradiation to the whole breast followed by a boost to the tumor bed using either electrons (232 patients), photons (15 patients), or an interstitial implant (316 patients). Local control and cosmetic outcome was compared among three patient groups based on the type of boost used. Forty-one patients had a recurrence of cancer in the treated breast for 5-, 10-, and 13-year actuarial local recurrence rates of 2.8%, 7.5%, and 11.2%, respectively. There were no significant differences in the local recurrence rates or cosmetic outcome using electrons, photons, or an interstitial implant. On multivariate analysis, only young age and margin status were associated with local recurrence. Stage I and II breast cancer patients undergoing BCT can be effectively managed with electron, photon, or interstitial implant boost techniques. Long-term local control and cosmetic outcome are excellent regardless of which boost technique is used.     

High Dose Rate versus Low Dose Rate Interstitial Radiotherapy for Carcinoma of the Floor of Mouth

Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth.Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using ¹⁹⁸Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6–7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5–6 days in HDR or 65 Gy within 1 week in LDR were delivered.Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with ¹⁹⁸Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR.Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.     

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial

BACKGROUND: This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma. METHODS: From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR. RESULTS: The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant. CONCLUSIONS: The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR.     

Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial

PURPOSE: To report the 5-year results of a randomized study comparing the survival and cosmetic results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and 2004, 258 selected patients with T1 N0-1mi, Grade 1-2, nonlobular breast cancer without presence of extensive intraductal component and resected with negative margins were randomized after breast-conserving surgery to receive 50 Gy/25 fractions WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy high-dose-rate (HDR) multicatheter brachytherapy (BT; n = 88) or 50 Gy/25 fractions electron beam (EB) irradiation (n = 40). RESULTS: At a median follow-up of 66 months, the 5-year actuarial rate of local recurrence was 4.7% and 3.4% in the PBI and WBI arms, respectively (p = 0.50). There was no significant difference in the 5-year probability of overall survival (94.6% vs. 91.8%), cancer-specific survival (98.3% vs. 96.0%), and disease-free survival (88.3% vs. 90.3%). The rate of excellent to good cosmetic result was 77.6% in the PBI group (81.2% after HDR BT; 70.0% after EB) and 62.9% in the control group (52.2% after telecobalt; 65.6% after 6-9-MV photons; p(WBI/PBI) = 0.009). CONCLUSIONS: Partial breast irradiation using interstitial HDR implants or EB to deliver radiation to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with carefully designed HDR multicatheter implants compared with the outcome after WBI.     

Local-regional control in breast cancer patients with a possible genetic predisposition

PURPOSE: Local control rates for breast cancer in genetically predisposed women are poorly defined. Because such a small percentage of breast cancer patients have proven germline mutations, surrogates, such as a family history for breast cancer, have been used to examine this issue. The purpose of this study was to evaluate local-regional control following breast conservation therapy (BCT) in patients with bilateral breast cancer and a breast cancer family history. METHODS AND MATERIALS: We retrospectively reviewed records of all 58 patients with bilateral breast cancer and a breast cancer family history treated in our institution between 1959 and 1998. The primary surgical treatment was a breast-conserving procedure in 55 of the 116 breast cancer cases and a mastectomy in 61. The median follow-up was 68 months for the BCT patients and 57 months for the mastectomy-treated patients. RESULTS: Eight local-regional recurrences occurred in the 55 cases treated with BCT, resulting in 5- and 10-year actuarial local-regional control rates of 86% and 76%, respectively. In the nine cases that did not receive radiation as a component of their BCT, four developed local-regional recurrences (5- and 10-year local-regional control rates of BCT without radiation: 49% and 49%). The 5- and 10-year actuarial local-regional control rates for the 46 cases treated with BCT and radiation were 94% and 83%, respectively. In these cases, there were two late local recurrences, developing at 8 years and 9 years, respectively. A log rank comparison of radiation versus no radiation actuarial data was significant at p = 0.009. In the cases treated with BCT, a multivariate analysis of radiation use, patient age, degree of family history, margin status, and stage revealed that only the use of radiation was associated with improved local control (Cox regression analysis p = 0.021). The 10-year actuarial rates of local-regional control following mastectomy with and without radiation were 91% and 89%, respectively. CONCLUSIONS: Patients with a possible genetic predisposition to breast cancer had low 5-year rates of local recurrence when treated with breast conserving surgery and radiation, but the local failure rate exceeded 50% when radiation was omitted. Our data are consistent with the hypothesis that patients with an underlying genetic predisposition develop cancers with radiosensitive phenotypes.     

Factors associated with local recurrence of mammographically detected ductal carcinoma in situ in patients given breast-conserving therapy

BACKGROUND: The authors reviewed their institution's experience treating patients with mammographically detected ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine 10-year rates of local control and survival and to identify factors associated with local recurrence. METHODS: From January 1980 to December 1993, 132 breasts in 130 patients were treated with BCT for mammographically detected DCIS at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent an excisional biopsy, and 64% were reexcised. All patients received postoperative whole-breast irradiation to a median dose of 45.0 Gray (Gy) (range: 43.1-56.0 Gy). One hundred twenty-four cases (94%) received a boost to the tumor bed for a median total dose of 60.4 Gy (range: 45.0-71.8 Gy). All cases underwent complete pathologic review by one pathologist. The median follow-up was 7.0 years. RESULTS: Of the entire study group, 13 patients developed recurrence within the ipsilateral breast, for 5- and 10-year actuarial rates of 8.9% and 10.3%, respectively. Nine of the 13 recurrences (69%) occurred within or immediately adjacent to the lumpectomy cavity and were designated as true recurrences or marginal misses (TR/MM). Four patients (31%) had recurrence elsewhere in the breast. Ten of the 13 recurrences (77%) were invasive, whereas 3 (23%) were pure DCIS. Only 1 patient died of disease, corresponding to 5- and 10-year actuarial cause specific survival rates of 100% and 99.0%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with ipsilateral breast failure or TR/MM. In multivariate analysis, only the absence of pathologic calcifications was significantly associated with ipsilateral breast failure. When specifically analyzed for TR/MM, younger age at diagnosis, number of slides with DCIS, number of DCIS and cancerization of lobules (COL) foci within 5 mm of the margin, and the absence of pathologic calcifications demonstrated a statistically significant association. Close or positive margin status did not significantly predict for either TR/MM (P = 0.14) or ipsilateral breast failure (P = 0.19). CONCLUSIONS: In patients with mammographically detected DCIS treated with BCT, adequate excision of all DCIS prior to RT can result in improved rates of local control. However, margin status may not adequately predict complete tumor extirpation. The volume of DCIS within 5 mm of the margin appears to be a more reliable surrogate for the adequacy of excision. In addition, young patient age and the absence of pathologic calcifications are independent risk factors for the development of local recurrence.     

Effective Treatment of Stage I Uterine Papillary Serous Carcinoma with High Dose-Rate Vaginal Apex Radiation (192Ir) and Chemotherapy

Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC.Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using ²²⁶Ra or ¹³⁷Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using ¹⁹²Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy.Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients.Conclusion: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.     

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.

PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.     

Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy

BACKGROUND: We retrospectively reviewed our institution's experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. METHODS: Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. RESULTS: A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age < or =35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age < or = 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age < or = 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. CONCLUSION: In patients with early-stage breast cancer treated with BCT, age < or = 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence.     

Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma

PURPOSE: Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma. METHODS AND MATERIALS: A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule. RESULTS: The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% (p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% (p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% (p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups (p = 0.23). CONCLUSION: Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personnel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB.     

Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer

: Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma.

: The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h.

: Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in LDR group are were 85, compared with 79% in the HDR group.

: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.     

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.     

Partial breast brachytherapy after lumpectomy: low-dose-rate and high-dose-rate experience

PURPOSE: The use of partial breast brachytherapy (PBB) after lumpectomy for selected patients with early-stage breast cancer reduces the adjuvant radiotherapy treatment time to <1 week. Despite the advantages of accelerated treatment, maintaining an acceptable cosmetic outcome is important. In a cohort of patients who received low-dose-rate (LDR) or high-dose-rate (HDR) PBB after lumpectomy, the clinical characteristics and treatment parameters were analyzed to identify predictors for an unfavorable cosmetic outcome. METHODS AND MATERIALS: Early-stage breast cancer patients with clear resection margins and 0-3 positive lymph nodes were eligible for PBB. Uniform guidelines for target definition and brachytherapy catheter placement were applied. The HDR PBB dose was 34 Gy in 10 fractions within 5 days, and the LDR dose was 45 Gy given at a rate of 50 cGy/h. The end points included incidence of radiation recall reaction, telangiectasias, and cosmetic-altering fibrosis. RESULTS: Between 1995 and 2000, 44 patients with early-stage breast cancer received PBB without adjuvant external beam radiotherapy after lumpectomy (31 HDR PBB, 13 LDR PBB). After a median follow-up of 42 months (range 18-86), all patients remained locally controlled. The overall rate of good/excellent cosmetic outcome was 79.6% overall and 90% with HDR PBB. Radiation recall reactions occurred in 43% of patients (6 of 14) who received adriamycin. LDR PBB and adriamycin were significant predictors for late unfavorable cosmetic changes in univariate analysis (p = 0.003 and p = 0.005, respectively). CONCLUSION: Although a high rate of local control and good/excellent cosmetic outcome is provided with HDR PBB, the risk of unfavorable cosmetic changes when treated with both LDR PBB and adriamycin is noteworthy. This suggests that HDR PBB is preferred in patients for whom adriamycin is indicated.     

The influence of the boost technique on local control in breast conserving treatment in the EORTC 'boost versus no boost' randomised trial.

BACKGROUND AND PURPOSE: The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy. PATIENTS AND METHODS: From 1989 to 1996, 2661 patients were randomised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost technique was left to the treating investigator. Treatment data were prospectively recorded as well as the clinical outcome in terms of local control and fibrosis. Sixty-three percent of the patients received a boost dose with fast electrons, 28% with photon beams and 9% with interstitial brachytherapy. RESULTS: At 5 years, local recurrences were seen in 74 of the 1635 patients who received an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast as well as at the primary tumour bed, as scored by the treating radiation oncologist, was similar in the three groups. CONCLUSIONS: Although the three groups are of a rather unequal size, the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control, despite a lower treatment volume and a longer overall treatment time.     

Interstitial high-dose-rate brachytherapy boost: the feasibility and cosmetic outcome of a fractionated outpatient delivery scheme

Purpose: To evaluate the feasibility, potential toxicity, and cosmetic outcome of fractionated interstitial high dose rate (HDR) brachytherapy boost for the management of patients with breast cancer at increased risk for local recurrence.

Methods and Materials: From 1994 to 1996, 18 women with early stage breast cancer underwent conventionally fractionated whole breast radiotherapy (50–50.4 Gy) followed by interstitial HDR brachytherapy boost. All were considered to be at high risk for local failure. Seventeen had pathologically confirmed final surgical margins of less than 2 mm or focally positive. Brachytherapy catheter placement and treatment delivery were conducted on an outpatient basis. Preplanning was used to determine optimal catheter positions to enhance dose homogeneity of dose delivery. The total HDR boost dose was 15 Gy delivered in 6 fractions of 2.5 Gy over 3 days. Local control, survival, late toxicities (LENT-SOMA), and cosmetic outcome were recorded in follow-up. In addition, factors potentially influencing cosmesis were analyzed by logistic regression analysis.

Results: The minimum follow-up is 40 months with a median 50 months. Sixteen patients were alive without disease at last follow-up. There have been no in-breast failures observed. One patient died with brain metastases, and another died of unrelated causes without evidence of disease. Grade 1–2 late toxicities included 39% with hyperpigmentation, 56% with detectable fibrosis, 28% with occasional discomfort, and 11% with visible telangiectasias. Grade 3 toxicity was reported in one patient as persistent discomfort. Sixty-seven percent of patients were considered to have experienced good/excellent cosmetic outcomes. Factors with a direct relationship to adverse cosmetic outcome were extent of surgical defect (p = 0.00001), primary excision volume (p = 0.017), and total excision volume (p = 0.015).

Conclusions: For high risk patients who may benefit from increased doses, interstitial HDR brachytherapy provides a convenient outpatient method for boosting the lumpectomy cavity following conventional whole breast irradiation without overdosing normal tissues. The fractionation scheme of 15 Gy in 6 fractions over 3 days is well tolerated. The volume of tissue removed from the breast at lumpectomy appears to dominate cosmetic outcome in this group of patients.     

Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy

The overall rate of an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) ranges from 1% to 2% per year. Risk factors include young age but data on the impact of BRCA1/2 mutations or a definite positive family history for breast cancer are scarce. We investigated IBTR after BCT in patients with hereditary breast cancer (HBC). Through our family cancer clinic we identified 87 HBC patients, including 26 BRCA1/2 carriers, who underwent BCT between 1980 and 1995 (cases). They were compared to 174 patients with sporadic breast cancer (controls) also treated with BCT, matched for age and year of diagnosis. Median follow up was 6.1 years for the cases and 6.0 years for controls. Patient and tumour characteristics were similar in both groups. An IBTR was observed in 19 (21.8%) hereditary and 21 (12.1%) sporadic patients. In the hereditary patients more recurrences occurred elsewhere in the breast (21% versus 9.5%), suggestive of new primaries. Overall, the actuarial IBTR rate was similar at 2 years, but higher in hereditary as compared to sporadic patients at 5 years (14% versus 7%) and at 10 years (30% versus 16%) (P=0.05). Post-relapse and overall survival was not different between hereditary and sporadic cases. Hereditary breast cancer was therefore associated with a higher frequency of early (2-5 years) and late (>5 years) local recurrences following BCT. These data suggest an indication for long-term follow up in HBC and should be taken into account when additional 'risk-reducing' surgery after primary BCT is eventually considered.     

Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapy

BACKGROUND AND OBJECTIVES: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. METHODS: From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. RESULTS: Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5 mm) the margin, and a smaller volume of excision (< 60 cm(3)) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. CONCLUSIONS: These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy.