乳腺癌保乳术后加速部分乳腺照射的研究进展

传统的乳腺癌保乳术后放疗是对全乳腺进行5周-6周的放疗.随着放射治疗技术的发展,加速部分乳腺照射可能会成为另一选择.该文就加速部分乳腺照射在乳腺癌治疗中的研究进展作一综述.     

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...     

早期乳腺癌保乳手术后的部分乳腺照射

早期乳腺癌保乳术后的放射治疗已被证实能提高肿瘤控制率及生存率。保乳术后放疗中最早应用且疗效肯定的是全乳腺放疗加局部瘤床加量。近年来,全乳加速放疗和加速部分乳腺照射研究也在逐渐展开。研究结果提示,早期乳腺癌保乳术后行部分乳腺照射能获得与全乳腺放疗同等的疗效,且有放疗总疗程短、毒副作用更小的优点。全文对早期乳腺癌术后的放射治疗情况进行回顾,并重点探讨部分乳腺照射的研究进展。     

加速部分乳腺照射多通道插植近距离治疗——经验和技巧

近年来,随着乳腺影像检查技术普遍用于早期乳腺癌诊断,保乳手术患者的比例大幅提高^[1]。保乳手术后接受辅助放疗已成为标准的治疗方法,该方法在LC率和OS率方面都显示了良好的效果^[2-4]。然而,常规的放疗全程需要5~6周时间,这为部分患者接受放疗造成了困难,一部分患者因此选择了全乳切除^[5]。加速部分乳腺照射为患者提供了一个新的选择。该技术可以显著缩短总治疗时间。对那些不能长时间离开工作岗位,或者从外地前来接受放疗的患者,加速部分乳腺照射提供了很好的选择,可以避免部分患者接受不必要的全乳切除手术。加速部分乳腺照射治疗技术有很多种类,例如:术中放疗、球囊治疗、外照射治疗和多通道插植近距离治疗^[6-8]。本文主要研究多通道插植近距离治疗加速部分乳腺照射技术的应用,包括临床适应证、不同插植方法比较以及实现好的插植结果的经验和技巧。     

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.     

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.     

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。     

乳腺癌保乳术后大分割放疗的临床研究进展

乳腺癌保乳术后行全乳腺放疗在降低局部肿瘤复发同时也可改善患者生存情况。虽然全乳腺标准放疗可以实现良好的肿瘤控制及美容效果,且具有不良反应轻的特点,但5~7周的治疗时间对患者相对较长,甚至可能造成医疗资源浪费,因此临床上越来越倾向大分割放疗和加速部分乳腺照射的短疗程放疗。短疗程放疗与常规分割放疗均为安全有效的治疗模式,具有与常规放疗相似的生存和局部肿瘤控制效果,不良反应可以耐受。相较于常规分割放疗,短疗程放疗具有缩短治疗总时间,减少治疗费用,节约医疗资源,改善患者生存质量的显著优势。      

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。     

放射治疗在早期乳腺癌中的应用

目前保乳治疗已经成为早期乳腺癌的标准治疗方案,而放射治疗在保乳治疗中的作用也日益得到体现.由于传统的全乳放射治疗存在着诸多的劣势,所以近些年来,部分乳腺放疗逐渐为人们所重视.相对于传统全乳腺照射,部分乳腺放疗可使患者的保乳治疗更快捷,且降低了远期并发症的风险.但是部分乳腺放疗研究的长期结果尚缺乏,而且病例选择及放疗实施也存在很多不确定性.部分乳腺放疗是有前途的方法,但在病例选择治疗技术以及处方剂量上仍有很多工作要完成.本文对放射治疗在早期乳腺癌保乳治疗中的应用情况做一综述.     

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.     

乳腺癌保乳术后加速部分乳腺照射研究进展

保乳手术加术后全乳腺放疗(whole breast irradiation, WBI)已成为早期乳腺癌的标准治疗模式之一, 但是传统的WBI照射范围大, 疗程长。近年来, 缩小照射范围、缩短总疗程的加速部分乳腺照射(accelerated partial breast irradiation, APBI)作为保乳术后WBI的替代治疗方法, 得到了广泛的认同。APBI常用的治疗方式有术中放疗、外照射和近距离放疗三种。术中放疗为保乳手术中给予一次性照射, 照射范围准确, 但是对设备的要求较高。外照射由专业的放疗科医师和物理师执行, 相对容易实现, 而且可以通过治疗计划系统使靶区剂量均匀分布。近距离治疗目前常用的有组织间插植和mammosite球囊治疗, mammosite设备技术简单、实施容易, 目前应用较广泛。然而, 由于APBI技术应用时间尚短、临床随访数据有限, 应用时必须进行严格的病例筛选以及合理的计划, 以降低局部复发的风险。      

Tumor bed delineation for external beam accelerated partial breast irradiation: A systematic review

In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1–2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer’s ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed.     

Accelerated partial breast irradiation using TARGIT: the pros,cons and the need for long-term results

Evaluation of: Vaidya JS, Joseph DJ, Tobias JS et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority Phase 3 trial. Lancet 376(9735), 91–102 (2010).

The Targeted Intraoperative Radiotherapy A (TARGIT-A) trial comparing accelerated partial breast irradiation (APBI) using targeted intraoperative radiotherapy (TARGIT) versus whole-breast irradiation in early-stage breast cancer reports noninferiority of local failure rates at 4-year follow-up. These promising early results will be followed closely in coming years by results from additional randomized clinical trials comparing whole-breast irradiation with APBI. Validation of APBI by these trials as a safe and effective treatment for a select group of early-stage breast cancers will usher in a new era and a welcome advance in the treatment of early-stage breast cancer. APBI has the potential to significantly decrease treatment time and cost, allow patients not previously able to undergo breast-conserving therapy given limited access to radiation facilities to undergo breast-conserving therapy, and decrease morbidity, all while maintaining adequate local control rates. However, caution and collection of further follow-up data must be advised before implementing APBI as a standard of care and before using the relatively untested technique of TARGIT as a means of delivering APBI.     

Comparison of radiation-induced fatigue across 3 different radiotherapeutic methods for early stage breast cancer

BACKGROUND:

Radiation‐induced fatigue is a common side effect of breast cancer radiotherapy (RT). This study compares the induction and persistence of radiation‐induced fatigue in accelerated partial breast irradiation (APBI), accelerated hypofractionated RT, and standard whole breast RT.

METHODS:

Eighty patients were treated with a novel, 3‐week accelerated regimen with 333 centigrays (cGy) for 15 fractions to 4995 cGy; of these, 45 were treated using APBI, whereas 35 patients were treated using accelerated hypofractionated RT. These patients were matched with patients receiving 200 cGy for 30 fractions using standard whole breast irradiation. Fatigue score, using Common Terminology Criteria for Adverse Events version 4.0, was obtained at 5 time points: consultation before RT, first on‐treatment visit, halfway through treatment, last on‐treatment visit, and first follow‐up.

RESULTS:

Maximum fatigue and average fatigue since treatment were calculated. Maximum fatigue was 1.5, 2.4, and 2.3, and average fatigue was 0.46, 0.81, and 0.92 for the APBI, accelerated hypofractionated RT, and standard whole breast RT groups, respectively. The accelerated schedules did not have significantly less fatigue than standard whole breast RT at first on‐treatment visit. Maximum fatigue in APBI was reduced compared with standard whole breast RT. Accelerated hypofractionated RT had fatigue trajectory similar to standard whole breast RT. Multivariate analysis found that increased age and whole breast treatment are associated with more fatigue. Chemotherapy, hormone therapy, race, and T stage were not significant predictors of maximum fatigue. Results were similar for average fatigue, except that magnitudes were smaller.

CONCLUSIONS:

Field sizes and age in breast RT were positively associated with maximum radiation‐induced fatigue. Accelerated hypofractionated RT and standard whole breast RT had similar fatigue trajectories compared with APBI, which reduced fatigue at all times. Cancer 2011. © 2011 American Cancer Society.     

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.     

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation.

PURPOSE AND BACKGROUND: Conventional early breast cancer treatment consists of a lumpectomy followed by whole breast radiation therapy. Accelerated partial breast irradiation (APBI) is an investigational approach to post-lumpectomy radiation for early breast cancer. The purpose of this study is to compare four external beam APBI techniques, including tomotherapy, with conventional whole breast irradiation for their radiation conformity index, dose homogeneity index, and dose to organs at risk. METHODS AND MATERIALS: Small-field tangents, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and helical tomotherapy were compared for each of 15 patients (7 right, 8 left). One radiation conformity and two dose homogeneity indices were used to evaluate the dose to the target. The mean dose to organs at risk was also evaluated. RESULTS: All proposed APBI techniques improved the conformity index significantly over whole breast tangents while maintaining dose homogeneity and without a significant increase in dose to organs at risk. CONCLUSION: The four-field IMRT plan produced the best dosimetric results; however this technique would require appropriate respiratory motion management. An alternative would be to use a four-field conformal technique that is less sensitive to the effects of respiratory motion.     

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.     

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。