加速部分乳腺照射的研究进展

加速部分乳腺照射(accelerated partial breast irradiation,APBI)作为早期乳腺癌保乳术后的治疗手段,相较于全乳照射(whole breast irradiation,WBI)具有时间短、费用低等优势,成为近年来该领域的研究热点之一。目前已经确立的受Ⅰ级证据支持的APBI技术主要是近距离放疗和外照射放疗,此外也出现了许多新技术,如术中放疗、立体定向部分乳腺照射、无创图像引导近距离乳腺放疗、术前加速部分乳腺照射和质子加速部分乳腺照射等,不同技术各具特点。本文将从APBI技术及其疗效、安全性及新技术应用等方面进行综述。     

乳腺癌保乳术后部分乳腺照射

保乳治疗作为早期乳腺癌的标准治疗选择目前已经成为国内外学者的共识，而且局部肿瘤扩大切除术作为原发肿瘤的主导手术模式也基本得到公认。多年来，全乳腺照射（whole breast irradiation，WBI）一直作为保乳术后相对固定的放疗模式，但随着对保留乳房术后复发模式认识的深入及放疗技术的进展，自20世纪90年代末期开始，加速部分乳腺照射（accelerated parial breast irradiation，APBI）作为WBI的替代模式用于部分保乳治疗的患者，目前APBI已经成为乳腺癌放疗研究的热点之一。     

早期乳腺癌保乳术后加速部分乳腺照射的研究进展

早期乳腺癌保乳术后行全乳腺照射（whole breast irradiation,WBI）已成为乳腺癌的标准治疗模式之一，具有与根治术相似的效果。对于早期乳腺癌患者，加速部分乳腺照射（accelerated partial breast irradiation,APBI）作为全乳腺照射的替代治疗是临床研究热点，其特点是短时间内单纯对瘤床进行局部照射。本文将APBI的照射技术、剂量分割模式和人群选择作一综述。     

乳腺癌保乳术后加速部分乳腺照射的靶区确定

目前,保乳治疗已经成为Ⅰ、Ⅱ期乳腺癌的主要治疗方式.保乳术后放疗的目的主要是提高局部肿瘤控制率和乳房保全率.一直以来,全乳房照射加瘤床补量的放疗模式是乳腺癌保乳术后放疗的常规选择,因为这种放疗模式明显降低了局部肿瘤复发率.大量研究证明,保乳术后复发绝大多数发生在瘤床及其附近区域,因此单纯针对瘤床的部分乳腺照射（partial breast irradiation,PBI）成为近期乳腺癌放疗研究的热点.PBI的剂量分割方式通常为加速分割,因此亦可称其为加速部分乳腺照射（accelerated partial breast irradiation,APBI）.以下重点综述APBI的靶区确定.     

近距离加速部分乳房照射对比全乳照射在早期乳腺癌患者保乳术后放疗中的疗效差异：GEC-ESTRO APBI研究10年随访结果解读

摘 要：GEC-ESTRO APBI是一项探索加速部分乳房照射（APBI）应用于早期乳腺癌保乳术后辅助放疗中的Ⅲ期临床研究，旨在对比多导管插植近距离照射技术的APBI与体外全乳照射（WBI）的疗效和副反应差异。研究设计上，采用国际多中心、非盲、随机对照、非劣效设计。主要研究终点为同侧乳腺局部复发率，次要研究终点为不良反应发生率、美容效果、10年无病生存率和10年总生存率等。研究共纳入1 328例早期乳腺癌患者，随机分配至外照射WBI组或多导管插植近距离照射APBI组，两组中位随访时间分别为10.3年和10.18年，符合分析条件的患者数分别为551例和633例。WBI组的10年局部复发率为1.58%（95%CI：0.37%~2.80%），而APBI组为3.51%（95%CI：1.99%~5.03%），两组局部复发差异率为1.93%（95%CI：-0.018%~3.870%，P=0.074）。7.5年和/或10年随访数据表明，两组不良事件大多为1~2级，3级副反应发生率方面，APBI组优于WBI组（1% vs 4%，P=0.021）。结果表明，多导管插植近距离照射技术APBI与外照射WBI相比，疗效类似且晚期副反应较少，可作为早期乳腺癌患者保乳术后辅助放疗的新选择。尽管该研究的10年随访结果进一步确认了APBI在早期乳腺癌保乳术后辅助放疗中的应用价值，但在非劣效研究设计的解读和临床实践中的推广应用等方面仍值得进一步讨论和思考。     

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.     

影像引导保乳术后部分乳腺外照射靶区的确定

随着对保乳治疗后乳房内肿瘤复发模式认识的统一,部分乳腺照射(partial breast irradiation,PBI)受到广泛关注,而且近几年来的相关研究迅速开展.而通过三维适形放疗(three dimensional conformalradiotherapy,3D-CRT)和调强放疗(intensity-modulated radiotherapy,IMRT)技术实施的部分乳腺外照射(external-beam partial breast irradiation,EB-PBI),则是PBI的主要实现方式之一.     

全乳腺照射与加速部分乳腺照射治疗早期乳腺癌术后患者的效果和安全性的Meta分析

目的系统评价全乳腺照射(WBI)与加速部分乳腺照射(APBI)治疗早期乳腺癌术后患者的效果和安全性,为早期乳腺癌保乳手术术后放疗措施提供循证参考。方法计算机检索PubMed、The Cochrane Library、CNKI、维普和万方数据库中的相关文献,依据纳入和排除标准筛选关于WBI与APBI治疗早期乳腺癌保乳手术术后效果和安全性的随机对照实验,并进行资料提取,采用Cochrane Reviewers’Handbook 5.1.0进行质量评价,RevMan 5.4统计软件进行Meta分析。结果共纳入9项研究,合计11238例患者。Meta分析结果显示,术后接受WBI与APBI治疗的早期乳腺癌患者的总生存率和淋巴结转移率比较,差异均无统计学意义(P﹥0.05);与术后接受WBI治疗的早期乳腺癌患者相比,术后接受APBI患者的特异性生存率更高、远处转移率更低、急性皮肤毒性更低、不良美容评分更低,但差异均无统计学意义(P﹥0.05)。术后接受APBI治疗的早期乳腺癌患者的复发率明显高于WBI,差异有统计学意义(OR=0.74,95%CI:0.62~0.89,P=0.001)。术后接受WBI治疗的早期乳腺癌患者的迟发性皮肤毒性发生率明显低于APBI,差异有统计学意义(OR=0.76,95%CI:0.67~0.87,P﹤0.01)。结论APBI与WBI对早期乳腺癌保乳手术术后疗效相当,因纳入研究的治疗方法差异和样本量的限制,该结论有待更多高质量的大样本、双盲、随机对照试验加以验证。     

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。     

乳腺导管原位癌术后辅助放疗

 保乳术已成为导管原位癌(DCIS)最常见的治疗手段,术后放疗可降低其复发风险。然而,对于DCIS放疗的照射范围、可不行术后放疗低危人群的选择、部分乳腺加速放疗（APBI）在DCIS中的作用等还存在争议。然而,多数研究均显示DCIS保乳术患者均能从术后放疗中获益。进一步的前瞻性研究主要证实低危组的DCIS患者是否可以安全地省去术后放疗。对单纯保乳术后患者的长期随访结果显示,除有禁忌症的患者外,放疗成为保乳术后所有患者的常规治疗方式。     

Accelerated partial breast irradiation

Whole breast irradiation (WBI) is the standard after breast conservation surgery. However, WBI in selected patients has been questioned. Accelerated partial breast irradiation (APBI) focuses treatment on the lumpectomy bed. Many modalities of delivering APBI have been developed: multicatheter interstitial brachytherapy, MammoSite balloon catheter, single insertion multicatheter devices, three-dimensional conformal external-beam radiation therapy and intraoperative techniques. Numerous studies of APBI have demonstrated excellent local control and cosmetic outcomes in early-stage breast cancer patients.     

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.     

Partial-breast treatment for early breast cancer: emergence of a new paradigm

Although hailed as a paradigm shift, the breast conservative treatment that emerged in the 1980s was in fact an extension of the Halstedian concept, wherein whole-breast irradiation (WBI) compensated for the limited surgery. Observations that 80-90% of breast recurrences after breast conservative surgery and WBI occur in the tumor bed questions the need for protracted elective WBI, and provides the rationale for accelerated-partial-breast irradiation (APBI) of small cancers without adverse features predisposing to multicentric recurrence. APBI can be given over a week with various external beam, intraoperative or brachytherapy (interstitial or MammoSite) techniques. Since the approval of MammoSite by the US FDA in May 2002, a surge of interest has been evident, with 4,000 cases treated using this technique in the past 2 years. Several phase II APBI brachytherapy studies show that 4 to 7-year breast control rates (95%), survival and cosmetic outcome obtained from more than 600 appropriately selected women are comparable to matched or historic controls receiving WBI. The 2 to 3-year interim results of two ongoing randomized trials do not show any early detriment with APBI. If mature results of randomized trials confirm equivalence of APBI to conventional WBI in selected women, it would mark a paradigm shift and a major advance in treatment. This would allow many more women to opt for breast conservation, resolve the dilemmas regarding chemotherapy and radiotherapy sequencing and perhaps would be more cost effective.     

Is Partial Breast Irradiation a Safe and Effective Treatment Approach for Women with Early-Stage Breast Cancer?

Breast-conserving therapy (BCT) represents the standard care in the management of early-stage breast cancer, because long-term outcomes with breast conservation are comparable with those of mastectomy. Adjuvant radiation therapy remains an essential component of BCT with standard techniques requiring 5–6½?weeks. Accelerated partial breast irradiation (APBI) is a technique developed over the past two decades that enables completion of treatment in one week or less. Review of the expanding literature reveals increasing support for APBI using several techniques, including interstitial brachytherapy, balloon-based brachytherapy, and external beam therapy. Novel treatment strategies, including intraoperative radiation therapy, hypofractionated APBI, and proton therapy, require further results before definitive conclusions can be made. Although there is currently a lack of level I evidence, with the pending publication of multiple phase III trials comparing whole-breast irradiation and APBI, modern treatment incorporating APBI should soon be developed.     

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.     

Accelerated Partial Breast Irradiation (APBI): A review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.     

Overview of accelerated partial breast irradiation

Breast conserving therapy (BCT) has become an accepted option in the management of patients with early-stage breast cancer. However, studies have suggested that a lengthy course of adjuvant whole breast irradiation, as a component of BCT, may not always be necessary and that radiation therapy delivered only to the region of the tumor bed may be acceptable in appropriately selected patients. Several modalities are currently being explored as a means to deliver accelerated partial breast irradiation (APBI), including multicatheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Cytyc Corporation, Marlborough, MA), and three-dimensional conformal external-beam radiation therapy. To date, phase 1/2 published data have demonstrated excellent local control rates and cosmesis. As additional data addressing the effectiveness of this treatment approach accumulate, a new standard of care may emerge. This review discusses data accumulated to date exploring the experience with all APBI modalities and presents future studies exploring this concept.