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.     

Accelerated partial breast irradiation trials: Diversity in rationale and design

Seven randomised trials are currently testing accelerated partial breast irradiation against whole breast radiotherapy after breast conservation surgery. The trials are varied in the techniques used to deliver partial breast radiotherapy, reflecting the range of opportunities offered by advanced brachytherapy and teletherapy modalities. Dose schedules also vary between trials, but the most important point of difference between them reflects alternative concepts of clinical and planning target volumes. These are based mainly on the spatial pattern of relapse in retrospective and prospective studies, which report the majority of first local relapses close to the primary tumour site, and on the assumption that radiotherapy does not prevent the development of new primary tumours developing elsewhere in the breast. However, the pattern of ipsilateral breast tumour relapse is not accurately defined in the clinical literature and does not correspond closely to pathological findings. In addition, published data are consistent with a significant reduction in the rate of other quadrant relapse after whole breast radiotherapy. Regardless of the biological model of local tumour relapse and responsiveness to radiation, the ongoing trials will generate level I evidence for or against accelerated partial breast irradiation, provided patients are followed up long enough before the first reporting of results.     

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: Past,present, and future

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life.     

Current status of accelerated partial breast irradiation

Accelerated partial breast irradiation (APBI) is a radiotherapy method used in breast-conserving therapy. In APBI, the tumor bed is topically irradiated over a short period after breast-conserving surgery. The fundamental concept underlying APBI is that more than 70% of ipsilateral breast tumor recurrence occurs in the neighborhood of the original tumor, and that hypofractionated radiotherapy can be applied safely when the irradiated volume is small enough. It is expected to reduce the time and cost required for conventional whole breast irradiation while maintaining equivalent local control. Several techniques including multicatheter interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiation therapy, and 3D conformal external beam radiation therapy have been proposed, and each of them has its own advantages and drawbacks. Although APBI is increasingly used in the United States and Europe, and the short-term results are promising, its equivalence with whole breast radiation therapy is not fully established. In addition, because the average breast size in Japan is considerably smaller than in the West world, the application of APBI to Japanese patients is technically more challenging. At this point, APBI is still an investigational treatment in Japan, and the optimal method of radiation delivery as well as its long-term efficacy and safety should be clarified in clinical trials.     

Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial

BackgroundAccelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early–late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results.MethodsEligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2).FindingsNo significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01).InterpretationEarly BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited.     

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.     

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

Background and purpose

Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS).

Materials and methods

Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days.

Results

All patients completed PB-APBI. The median follow-up time was 59 months (range: 43–70 months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2 months that was not observed beyond 6 months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2 months, respectively, and decreased to 69% at 3 years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p = 0.02); however, it did not increase in patients treated with two-field PB-APBI (p = 0.3).

Conclusions

PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.     

Accelerated partial breast irradiation: consensus statement of 3 German Oncology societies

BACKGROUND: Breast-conserving surgery followed by whole-breast radiotherapy (WBRT) has become the standard treatment for the majority of patients with early breast cancer. Whereas the indications for systemic adjuvant treatment have continuously expanded, there is a tendency to restrict postoperative radiotherapy to accelerated partial breast irradiation (APBI) instead of WBRT. METHODS: The different techniques of APBI are described and their respective advantages or potential drawbacks outlined. Moreover, the results described in the literature are briefly reviewed as a basis for the consensus statements and recommendations of the German Society of Radiation Oncology, the German Society of Senology, and the Working Group for Gynecological Oncology of the German Cancer Society. RESULTS: The methods mainly used for APBI are: interstitial radiotherapy with multicatheter technique, intraoperative radiotherapy (IORT) using either electrons produced by linear accelerators or 50 kV x-rays (Intrabeam), the balloon-catheter technique (MammoSite), or 3D conformal external beam radiotherapy. These techniques have marked differences in dose distribution and homogeneity. The published range of local recurrence rates varies between 0% to 37%, the median follow-up from 8 to 72 months. CONCLUSIONS: To date, follow-up times mostly do not yet permit a definite judgment concerning the long-term effectiveness and side effects of APBI. The relevant societies in Germany support randomized clinical studies comparing APBI with WBRT in a well-defined subset of low-risk patients. However, the authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer.     

早期乳腺癌保乳术后加速部分乳腺放疗相关研究进展

早期乳腺癌保乳术后全乳放疗是目前标准的治疗方式,可有效降低复发率。由于大多数复发发生在肿瘤切除腔的附近,加速部分乳腺照射(APBI)作为一种只针对原发病灶周围有限体积的组织进行大分割照射的特殊放疗方式,引起了越来越多的关注。近年来,多项前瞻性的随机对照研究证实了其安全性及有效性,对特定的低危保乳术后患者是可行的选择。与全乳放疗相比,APBI缩短了治疗时间,降低了治疗成本,改善了美容效果。同时越来越多的APBI治疗技术被开发出来,增强了患者的可及性,对于部分早期乳腺癌保乳术后患者而言有其独特的优势。尽管如此,APBI技术在疗效及不良反应上存在不同,需区别看待。本文主要就APBI的各种治疗技术、国内外研究进展以及适用人群进行综述,提出尚待解决的问题,展望其发展前景,为临床应用提供参考。     

Long-term efficacy and patterns of failure after accelerated partial breast irradiation: a molecular assay-based clonality evaluation

PURPOSE: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. METHODS AND MATERIALS: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for >or=10 years. RESULTS: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. CONCLUSIONS: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.     

Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purpose

To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI).

Patients and methods

Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results.

Results

After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01).

Conclusions

Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.     

Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17

PURPOSE: Accelerated partial breast irradiation (APBI) can be delivered with brachytherapy within 4-5 days compared with 5-6 weeks for conventional whole breast external beam radiotherapy. Radiation Therapy Oncology Group 95-17 is the first prospective phase I-II cooperative group trial of APBI alone after lumpectomy in select patients with breast cancer. The toxicity rates are reported for low-dose-rate (LDR) and high-dose-rate (HDR) APBI on this trial. METHODS AND MATERIALS: The inclusion criteria for this study included invasive nonlobular tumors < or =3 cm after lumpectomy with negative surgical margins and axillary dissection with zero to three positive axillary nodes without extracapsular extension. The patients were treated with either LDR APBI (45 Gy in 3.5-5 days) or HDR APBI (34 Gy in 10 twice-daily fractions within 5 days). Chemotherapy (> or =2 weeks after APBI) and/or tamoxifen could be given at the discretion of the treating physicians. RESULTS: Between August 1997 and March 2000, 100 women were enrolled in this study, and 99 were evaluated. Of the 99 women, 33 were treated with LDR and 66 with HDR APBI. The median follow-up for all patients was 2.7 years (range, 0.6-4.4 years) and was 2.9 years for LDR and 2.7 years for HDR patients. Toxicities attributed to APBI included erythema, edema, tenderness, pain, and infection. Of the 66 patients treated with HDR APBI, 2 (3%) had Grade 3 or 4 toxicity. Of the 33 patients treated with LDR, 3 (9%) had Grade 3 or 4 toxicity during brachytherapy. Late toxicities included skin thickening, fibrosis, breast tenderness, and telangiectasias. No patient experienced late Grade 4 toxicity; the rate of Grade 3 toxicity was 18% for the LDR and 4% for the HDR groups. CONCLUSION: Acute and late toxicity for this invasive breast radiation technique was modest and acceptable. Patients receiving chemotherapy, a nonprotocol therapy, had a greater rate of Grade 3 toxicity. The study design did not allow for this to be tested statistically.     

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.     

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BackgroundAccelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC.MethodsThis study was performed at the University of Florence (Florence, Italy). Women aged more than 40 years affected by early BC, with a maximum pathological tumour size of 25 mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50 Gy in 25 fractions, followed by a boost on the tumour bed of 10 Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895.FindingsA total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4–7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1–3.0) and in the WBI group (three cases; 95% CI 0.0–2.8). No significant difference emerged between the two groups (log rank test p = 0.86). We identified seven deaths in the WBI group and only one in the APBI group (p = 0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p = 0.0001), late (p = 0.004), and cosmetic outcome (p = 0.045).InterpretationTo our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.