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.     

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。     

Current status and perspectives of brachytherapy for breast cancer

Before the era of breast-conserving therapy, brachytherapy implants were used to treat large inoperable breast tumors. In later years, interstitial brachytherapy with rigid needles or multiple flexible catheters has been used to deliver an additional (boost) dose to the tumor bed after breast-conserving surgery and whole-breast irradiation. Reexcision followed by reirradiation using interstitial breast implants has also been implemented as an alternative to mastectomy to treat ipsilateral breast local recurrence after previous breast-conserving therapy. In the past two decades, the new concept of accelerated partial breast irradiation opened a new perspective for breast brachytherapy. The first technique utilized in early accelerated partial breast irradiation studies was multicatheter interstitial brachytherapy. Beyond classical interstitial brachytherapy, recently, new intracavitary applicators have been developed in the United States to decrease the existing barriers against the widespread use of multicatheter brachytherapy. Furthermore, interstitial low-dose-rate seed implants have also been implemented as an alternative for stepping-source multicatheter brachytherapy. In this article, we give an overview of the past achievements, current status, and future perspectives of breast brachytherapy.     

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: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.     

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.     

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 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.     

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.     

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.     

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。     

Patterns of failure after MammoSite brachytherapy partial breast irradiation: a detailed analysis

PURPOSE: To report the results of a detailed analysis of treatment failures after MammoSite breast brachytherapy for partial breast irradiation from our single-institution experience. METHODS AND MATERIALS: Between October 14, 2002 and October 23, 2006, 78 patients with early-stage breast cancer were treated with breast-conserving surgery and accelerated partial breast irradiation using the MammoSite brachytherapy applicator. We identified five treatment failures in the 70 patients with >6 months' follow-up. Pathologic data, breast imaging, and radiation treatment plans were reviewed. For in-breast failures more than 2 cm away from the original surgical bed, the doses delivered to the areas of recurrence by partial breast irradiation were calculated. RESULTS: At a median follow-up time of 26.1 months, five treatment failures were identified. There were three in-breast failures more than 2 cm away from the original surgical bed, one failure directly adjacent to the original surgical bed, and one failure in the axilla with synchronous distant metastases. The crude failure rate was 7.1% (5 of 70), and the crude local failure rate was 5.7% (4 of 70). Estimated progression-free survival at 48 months was 89.8% (standard error = 4.5%). CONCLUSIONS: Our case series of 70 patients with >6 months' follow-up and a median follow-up of 26 months is the largest single-institution report to date with detailed failure analysis associated with MammoSite brachytherapy. Our failure data emphasize the importance of patient selection when offering partial breast irradiation.