Accelerated partial breast irradiation utilizing balloon brachytherapy techniques

To overcome the barriers to BCT, methods of PBI in the setting of breast conservation have been explored. The method of PBI with the longest published follow-up is multi-catheter interstitial brachytherapy. Balloon-based brachytherapy with the MammoSite brachytherapy applicator was designed to simplify the brachytherapy procedure for PBI, enhance the reproducibility of the dosimetry, and improve patient comfort. The rates of local recurrence following PBI with the MammoSite applicator have been low, but there are few published reports and follow-up has been relatively short. The cosmetic outcomes and toxicity of MammoSite PBI are comparable to those seen after multicatheter-based PBI. Additional methods of balloon brachytherapy, including Xoft and SenoRx Contura have been developed. Finally, long-term follow-up after PBI is important for the welfare of individual patients and in order to establish the efficacy, late toxicity and cosmetic outcomes of this technique.     

Investigation of interfraction variations of MammoSite balloon applicator in high-dose-rate brachytherapy of partial breast irradiation

PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.     

Persistent seroma after intraoperative placement of MammoSite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors

PURPOSE: To investigate the incidence of, and possible factors associated with, seroma formation after intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation. METHODS AND MATERIALS: This study evaluated 38 patients who had undergone intraoperative MammoSite catheter placement at lumpectomy or reexcision followed by accelerated partial breast irradiation with 34 Gy in 10 fractions. Data were collected regarding dosimetric parameters, including the volume of tissue enclosed by the 100%, 150%, and 200% isodose shells, dose homogeneity index, and maximal dose at the surface of the applicator. Clinical and treatment-related factors were analyzed, including patient age, patient weight, history of diabetes and smoking, use of reexcision, interval between surgery and radiotherapy, total duration of catheter placement, total excised specimen volume, and presence or absence of postprocedural infection. Seroma was verified by clinical examination, mammography, and/or ultrasonography. Persistent seroma was defined as seroma that was clinically detectable >6 months after radiotherapy completion. RESULTS: After a median follow-up of 17 months, the overall rate of any detectable seroma was 76.3%. Persistent seroma (>6 months) occurred in 26 (68.4%) of 38 patients, of whom 46% experienced at least modest discomfort at some point during follow-up. Of these symptomatic patients, 3 required biopsy or complete cavity excision, revealing squamous metaplasia, foreign body giant cell reaction, fibroblasts, and active collagen deposition. Of the analyzed dosimetric, clinical, and treatment-related variables, only body weight correlated positively with the risk of seroma formation (p = 0.04). Postprocedural infection correlated significantly (p = 0.05) with a reduced risk of seroma formation. Seroma was associated with a suboptimal cosmetic outcome, because excellent scores were achieved in 61.5% of women with seroma compared with 83% without seroma. CONCLUSION: Intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation is associated with a high rate of clinically detectable seroma that adversely affects the cosmetic outcome. The seroma risk was positively associated with body weight and negatively associated with postprocedural infection.     

部分乳腺加速照射近距离治疗技术设备进展

组织间插植是目前随访时间最长的部分乳腺加速照射（ＡＰＢＩ）近距离技术,但其技术实施复杂。球囊设备是简化的ＡＰＢＩ设备。ＭａｍｍｏＳｉｔｅ是第一个ＡＰＢＩ球囊近距离设备,其技术设备简单,很受医生和患者青睐。ＸｏｆｔＡｘｘｅｎｔＥｌｅｃｔｒｏｎｉｃＢｒａｃｈｙｔｈｅｒａｐｙ是改进的基于电子射线源的球囊设备,ＳｅｎｏＲｘＣｏｎｔｕｒａ相对ＭａｍｍｏＳｉｔｅ增加了４个放射源通道,可以更好地根据靶区调整剂量分布。Ｓｔｒｕｔａｄｊｕｓｔｅｄｖｏｌｕｍｅｉｍｐｌａｎｔ和ＣｌｅａｒＰａｔｈ是组织间插植与球囊结合的设备,结合了球囊设备单点插入的优点和组织间插植的剂量学优势。ＡｃｃｕＢｏｏｓｔ是基于乳腺Ｘ线摄影机的无创近距离设备,无需外科插入导管,对瘤腔形状的依赖性小,且无感染风险。     

Accelerated partial breast irradiation:advances and controversies

The management of localized breast cancer has changed dramatically over the past three to four decades. Breast-conserving therapy, which involved lumpectomy followed by adjuvant irradiation, is now widely considered the standard of care in women with early-stage breast cancer. Accelerated partial breast irradiation (APBI), which involves focal irradiation of the lumpectomy cavity over a short period of time, has developed over the past two decades as an alternative to whole breast irradiation (WBI). Multiple APBI modalities have been developed including brachytherapy, external beam irradiation, and intraoperative irradiation. These new techniques have provided early-stage breast can-cer patients with shorter treatment duration and more focused irradiation, delivering very high biological doses to the region at a high risk of failures over a much shorter treatment course as compared with conventional radiotherapy. However, the advantages of APBI over conventional radiotherapy are controversial, including a higher risk of compli-cations reported in retrospective literature and shorter follow-up duration in the intraoperative APBI trials. Neverthe-less, APBI presents a valuable alternative to WBI for a selected population of women with early-stage breast cancer.     

Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results

PURPOSE: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use of multiple dwell positions reduced the risk of severe hyperpigmentation (p = 0.0278). Infection was associated with an increased risk of fair or poor overall cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS seems to have acceptable toxicity rates and cosmetic outcomes, comparable to those with whole-breast radiotherapy. On the basis of these data, the closed-cavity placement technique, use of prophylactic antibiotics, use of multiple dwell positions, and a minimum skin spacing of 6 mm seem to improve patient outcome.     

Accelerated partial breast irradiation: an analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy

PURPOSE: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. METHODS AND MATERIALS: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 (相似文献   

Biologic comparison of partial breast irradiation protocols

PURPOSE: To analyze the dose/fractionation schedules currently used in ongoing clinical trials of partial breast irradiation (PBI) by comparing their biologically effective dose (BED) values to those of three standard whole breast protocols commonly used after segmental mastectomy in the treatment of breast cancer. METHODS AND MATERIALS: The BED equation derived from the linear-quadratic model for radiation-induced cell killing was used to calculate the BEDs for three commonly used whole breast radiotherapy regimens, in addition to a variety of external beam radiotherapy, as well as high-dose-rate and low-dose-rate brachytherapy, PBI protocols. RESULTS: The BED values of most PBI protocols resulted in tumor control BEDs roughly equivalent to a 50-Gy standard treatment, but consistently lower than the BEDs for regimens in which the tumor bed receives a total dose of either 60 Gy or 66 Gy. The BED values calculated for the acute radiation responses of erythema and desquamation were nearly all lower for the PBI schedules, and the late-response BEDs for most PBI regimens were in a similar range to the BEDs for the standard treatments. CONCLUSION: Biologically effective dose modeling raises the concern that inadequate doses might be delivered by PBI to ensure optimal in-field tumor control.     

Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis

Background and Purpose

To compare 12-year outcomes of accelerated partial breast irradiation (APBI) versus whole-breast irradiation (WBI) in patients treated with breast conservation.

Materials and Methods

A matched-pair analysis was performed using 199 patients receiving WBI and 199 patients receiving interstitial APBI. Match criteria included tumor size, age, nodal status, ER status, and the use of adjuvant hormonal therapy. Patterns of failure and efficacy of salvage treatments were examined.

Results

No differences were seen in the 12-year rates of local recurrence (3.8% vs. 5.0%, p = 0.40), regional recurrence (0% vs. 1.1%, p = 0.15), disease free survival (DFS) (87% vs. 91%, p = 0.30), cause-specific survival (CSS) (93% vs. 95%, p = 0.28), or overall survival (OS) (78% vs. 71%, p = 0.06) between the WBI and APBI groups, respectively. The rate of distant metastases was lower in the APBI group (10.1% vs. 4.5%, p = .05). Following LR, no difference in outcome was seen between the two groups with 5 year post-LR rates of DFS (80% vs. 86%, p = 0.55), CSS (88% vs. 75%, p = 0.77), and OS (88% vs. 75%, p = 0.77), respectively.

Conclusions

With 12-year follow-up, APBI produced outcomes equivalent to WBI. Following LR, patients treated with APBI also had similar failure patterns to those managed with WBI.     

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation

BACKGROUND:

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) using accelerated partial breast irradiation (APBI).

METHODS:

In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4‐Gy fractions). One thousand two hundred fifty‐five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow‐up was 60 months.

RESULTS:

Fifty patients (3.5%) developed an IBTR for a 5‐year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3‐year rates of disease‐free survival, cause‐specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.

CONCLUSIONS:

With 5 years of follow‐up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3‐year survival outcomes after salvage treatments. Cancer 2012. © 2012 American Cancer Society.     

早期乳腺癌部分乳腺加速放疗

随着乳腺癌术后复发模式的研究进展,部分乳腺照射方法 成为乳腺癌放疗的热点.组织间插植、球囊近距离治疗、术中放疗及三维适形放疗和调强放疗等部分乳腺加速放疗已进入临床研究.其局部控制率和安全性与全乳腺照射比较相当,同时具有治疗周期短、方便患者等优势.部分乳腺加速放疗在部分患者有望代替全乳腺放疗,成为早期乳腺癌保乳术后放疗的标准治疗之一.

Abstract：

With a view to patterns of local recurrence after breast conserving surgery, whole breast irradiation(WBI) after surgery is controversial and partial-breast irradiation(PBI) came up. Many clinical trials related with accelerated partial-breast irradiation using a variety of radiotherapeutic techniques such as interstitial brachytherapy (IBT), MammoSite Radiation Therapy System, intraoperative radiotherapy(IORT), threedimensional conformal radiotherapy(3-DCRT)and intensity modulated radiation therapy(IMRT) in selected patients have been carried out. Accelerated partial-breast irradiation that provides faster, more convenient treat-ment demonstrates local control rate and safety comparable to that of whole breast irradiation. Partial breast irradiation may be an alternative way to whole breast radiotherapy and will be one of the standard treatments in women with early breast cancer seeking breast conservation.     

Partial breast irradiation with interstitial high-dose-rate brachytherapy in early breast cancer: Results of a phase II prospective study

Aim

To investigate, in a phase II prospective study, the efficacy of partial breast irradiation administered with high-dose-rate brachytherapy.

Methods

After conservative surgery 80 patients with low-risk early-stage breast cancer received 4 Gy twice a day for 4 days (total dose 32 Gy). Catheter implantation was performed during surgery in 15 cases and postoperatively, at a median of 8 weeks from surgery, in 65 patients. Adjuvant therapy was chemotherapy (8) and/or hormone therapy (61).

Results

Cosmetic results were good/excellent in 79 patients. Perioperative toxicity was very low. Acute skin toxicity developed in seven cases (six G1; one G2); late G3 cutaneous toxicity in one patient and late subcutaneous toxicity in five (three G1; two G2). Grade 1 teleangiectasia occurred in eight patients and grade 2 in one. Fat necrosis was symptomatic in one patient and asymptomatic in five. Only one patient presented pain after brachytherapy. A significantly (p = 0.001) higher frequency of late toxicity was observed in patients implanted during surgery, the group, which included the only patient with a fair cosmetic result. No local or regional relapses have occurred to date. The median follow-up was 30 months (range 3–52).

Conclusion

This strategy is a viable option in selected patients with early-stage breast cancer as it is feasible, reproducible and associated with very low perioperative and acute toxicity. The low incidence of late side effects will probably change as follow-up lengthens.     

Interim cosmetic results and toxicity using 3D conformal external beam radiotherapy to deliver accelerated partial breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy

PURPOSE: We present our ongoing clinical experience utilizing three-dimensional (3D)-conformal radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS: Ninety-one consecutive patients were treated with APBI using our previously reported 3D-CRT technique. The clinical target volume consisted of the lumpectomy cavity plus a 10- to 15 -mm margin. The prescribed dose was 34 or 38.5 Gy in 10 fractions given over 5 consecutive days. The median follow-up was 24 months. Twelve patients have been followed for > or =4 years, 20 for > or =3.5 years, 29 for >3.0 years, 33 for > or =2.5 years, and 46 for > or =2.0 years. RESULTS: No local recurrences developed. Cosmetic results were rated as good/excellent in 100% of evaluable patients at > or = 6 months (n = 47), 93% at 1 year (n = 43), 91% at 2 years (n = 21), and in 90% at > or =3 years (n = 10). Erythema, hyperpigmentation, breast edema, breast pain, telangiectasias, fibrosis, and fat necrosis were evaluated at 6, 24, and 36 months after treatment. All factors stabilized by 3 years posttreatment with grade I or II rates of 0%, 0%, 0%, 0%, 9%, 18%, and 9%, respectively. Only 2 patients (3%) developed grade III toxicity (breast pain), which resolved with time. CONCLUSIONS: Delivery of APBI with 3D-CRT resulted in minimal chronic (> or =6 months) toxicity to date with good/excellent cosmetic results. Additional follow-up is needed to assess the long-term efficacy of this form of APBI.