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.     

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。      

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。     

乳腺癌保乳术后图像引导放疗技术研究进展

保乳治疗是早期乳腺癌的标准治疗模式。保乳术后全乳照射能有效提高局部控制率和长期生存率。近年来,随着对早期乳腺癌保乳术后复发模式的深入研究,人们认识到保乳术后最常见复发部位为瘤床及其边缘,因此术后加速部分乳腺照射技术在临床上应用越来越广泛,这就对早期乳腺癌保乳术后靶区的准确施照提出了更高要求。利用图像引导放疗(image-guided radiotherapy,IGRT)技术能在线采集患者解剖图像,并与定位图像进行对比,从而发现并纠正治疗过程中的误差,提高放疗施照精度。笔者总结IGRT技术在乳腺癌保乳术后放疗过程中的应用,并对其下一步研究方向进行展望,希望能为更好地开展乳腺癌IGRT技术相关临床研究提供帮助。     

早期乳腺癌保乳术后全乳放疗替代模式

全乳房照射已被用于降低早期乳腺癌保乳术后同侧乳腺肿瘤复发的风险,并且多项随机临床试验和荟萃分析已经证明这一放疗模式安全有效,但随着放疗技术的进步以及患者生存期的延长,这种标准治疗模式目前也面临着一些挑战,其替代模式受到了越来越多的关注.其中部分乳腺照射、全乳大分割放疗、省略放疗针对不同的乳腺癌患者,疗效与全乳腺常规照射相当,且降低了不良反应,同时缩短了治疗时程,减轻了患者负担,值得在临床推广应用.     

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。     

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。     

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: 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.     

Altered fractionation: rationale and justification for whole and partial breast hypofractionated radiotherapy

Over the last 2 decades, we have seen major advances in the application of radiotherapy after breast-conserving surgery. Two important contributions are the use of whole-breast hypofractionation and accelerated partial-breast irradiation. Three large randomized trials comparing whole-breast hypofractionation versus conventional fractionation for early breast cancer have shown similar rates of local recurrence and morbidity. As a result, whole-breast hypofractionation is now an option for selected patients after breast-conserving surgery. The delivery of accelerated partial-breast irradiation (APBI) has been studied using techniques of multicatheter interstitial brachytherapy, balloon-based brachytherapy, external-beam radiotherapy, and intraoperative radiotherapy. Multiple single and multi-institutional data have been published indicating good long-term results with APBI (in highly selected, low-risk patients) in terms of tumor control and toxicity. However, the long-term results of large, phase III trials comparing APBI with whole-breast irradiation are still pending.     

The evolution of accelerated, partial breast irradiation as a potential treatment option for women with newly diagnosed breast cancer considering breast conservation

Breast conservation therapy (BCT) is a safe, effective alternative to mastectomy for many women with newly diagnosed breast cancer. This approach involves local excision of the malignancy with tumor-free margins, followed by 5-7 weeks of external beam whole breast (WB) radiotherapy (XRT) to minimize the risk of an in-breast tumor recurrence (IBTR). Though clearly beneficial, the extended course of almost daily postoperative radiotherapy interrupts normal activities and lengthens care. Additional options are now available that shorten the radiotherapy treatment time to 1-5 days (accelerated) and focus an increased dose of radiation on just the breast tissue around the excision cavity (partial breast). Recent trials with accelerated, partial breast irradiation (APBI) have shown promise as a potential replacement to the longer, whole breast treatments for select women with early-stage breast cancer. Current APBI approaches include interstitial brachytherapy, intracavitary (balloon) brachytherapy, and accelerated external beam (3-D conformal) radiotherapy, all of which normally complete treatment over 5 days, while intraoperative radiotherapy (IORT) condenses the entire treatment into a single dose delivered immediately after tumor excision. Each approach has benefits and limitations. This study covers over 2 decades of clinical trials exploring APBI, discusses treatment variables that appear necessary for successful implementation of this new form of radiotherapy, compares and contrasts the various APBI approaches, and summarizes current and planned randomized trials that will shape if and how APBI is introduced into routine clinical care. Some of the more important outcome variables from these trials will be local toxicity, local and regional recurrence, and overall survival. If APBI options are ultimately demonstrated to be as safe and effective as current whole breast radiotherapy approaches, breast conservation may become an even more appealing choice, and the overall impact of treatment may be further reduced for certain women with newly diagnosed breast cancer.     

High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast-conserving surgery: seven-year results of a comparative study

PURPOSE: To report the 7-year results of a prospective study of accelerated partial breast irradiation (APBI) using interstitial high-dose-rate brachytherapy and compare the treatment results with those achieved by standard, whole breast radiotherapy (WBRT), with or without a tumor bed boost (TBB). METHODS AND MATERIALS: Between 1996 and 1998, 45 prospectively selected patients with T1N0-N1mi (single nodal micrometastasis), nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI using interstitial high-dose-rate implants. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumor bed plus a 1-2-cm margin. During the same period, 80 patients, who met the eligibility criteria for APBI but who were treated with 50 Gy WBRT with (n = 36) or without (n = 44) a 10-16-Gy TBB, were selected as controls. The median follow-up for the APBI and control groups was 81 and 83 months, respectively. Local control, relapse-free survival, cancer-specific survival, late side effects, and cosmetic results were assessed. RESULTS: The crude rate of total ipsilateral breast failure was 6.7% (3 of 45), 11.4% (5 of 44), and 8.3% (3 of 36) for patients treated with APBI, WBRT, and WBRT + TBB, respectively. The differences in the 5- and 7-year actuarial rates of ipsilateral breast recurrence were not statistically significant among patients treated with APBI (4.4% and 9.0%), WBRT (4.7% and 14.8%), and WBRT + TBB (5.7% and 9.5%). No statistically significant difference in either the 7-year probability of relapse-free survival (79.8%, 73.5%, and 77.7% for APBI, WBRT, and WBRT + TBB, respectively) or cancer-specific survival (93.3%, 92.9%, and 93.9% for APBI, WBRT, and WBRT + TBB, respectively) was found. The 7-year actuarial elsewhere breast failure rate was 9.0% in the APBI group and 8.3% in the control group (p = 0.80). The rate of excellent/good cosmetic results was 84.4% in the APBI group and 68.3% in the control group (p = 0.04). The corresponding rates of asymptomatic fat necrosis were 20.0% and 20.6%. Symptomatic fat necrosis occurred in 1 patient (2.2%) treated with APBI. The incidence of Grade 2 or worse late radiation side effects was similar for both groups (26.7% vs. 28.6%). CONCLUSION: Accelerated partial breast irradiation using interstitial high-dose-rate implants, with proper patient selection and quality assurance, yields similar 7-year results to those achieved with standard breast-conserving therapy. APBI does not increase the risk of elsewhere breast failures.     

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.     

Accelerated partial breast irradiation: a concept to individualize treatment in breast cancer]

Whole breast irradiation delivering an equivalent dose of 50 Gy in 5 weeks, followed by a 10 to 16 Gy-boost to the tumor bed is the standard of care after breast-conserving surgery for early-breast cancer. Accelerated partial breast irradiation (APBI) is currently under investigations in large multi-institutional, prospective, randomized trials to objectively address the critical endpoints of treatment efficacy, toxicity and cosmesis. Patient's selection for this new approach is crucial to individualise treatments and define the subgroups of patients who will really benefit from APBI in terms of quality of life without decreasing long-term results of the disease control and cosmesis. In this review, we will discuss the patients' profiles selection for APBI regarding their general and tumor criteria. The differences between APBI techniques either performed intra or post operatively will be also discussed.     

早期乳腺癌保乳术后全乳大分割照射同步瘤床加量的临床分析

目的：观察早期乳腺癌保乳术后全乳大分割照射同步瘤床加量的短期疗效与不良反应。方法64例早期乳腺癌患者保乳术后行两野切线全乳照射,全乳腺照射40．5 Gy／15 f,单次剂量2．7 Gy／f,同步瘤床推量至48 Gy／15 f,单次剂量3．2 Gy／f,总疗程3周,观察分析患者局部复发情况、美容效果及不良反应。结果中位随访时间17月,随访率为100％,无局部复发情况发生。3例患者表现乳腺中度胀痛;Ⅰ、Ⅱ、Ⅲ级急性皮肤反应发生率分别为17．2％、4．7％、1．6％;Ⅰ级血小板下降发生率与Ⅰ～Ⅱ级中性粒细胞减少发生率分别为1．6％、4．7％;放疗完成后4、7月美容优良率分别为90．6％、87．5％。结论早期乳腺癌保乳术后全乳放疗同步瘤床加量的短期疗效与以往常规放疗方式相似,缩短放疗时间,不会增加皮肤不良反应及降低美容效果。