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...     

早期乳腺癌保乳术后放射治疗新进展

早期乳腺癌保乳术后放射治疗可以显著降低局部复发率,但是传统模式的全乳腺放疗对于一部分低危人群而言并非必要,属于过度治疗,因此在保证局部控制率的前提下,寻求新的放疗模式,如缩小照射范围、缩短治疗时间以及避免不必要的放疗成为乳腺癌研究与治疗的新方向.     

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.     

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。     

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。     

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。      

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。     

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.     

Breast cancer: new radiation treatment options

Conventional radiotherapeutic treatment for early and advanced breast cancer has been based on broad-field radiation treatment principles that date back several decades. Although these strategies have been successful, newer techniques now offer the ability to incorporate improved target imaging, dosimetric planning, and treatment delivery into the treatment design. These newer techniques include accelerated partial-breast irradiation and hypofractionated whole-breast irradiation for early-stage breast cancer, and intensity-modulated radiotherapy (IMRT) for both early and advanced breast cancer. Accelerated partial-breast irradiation and hypofractionated whole-breast radiotherapy are treatment approaches that promise both reduced overall treatment times and the potential for increased use of breast-conservation therapy. IMRT offers unparalleled dose homogeneity and conformality that enables dose reduction to normal structures with the potential to reduce treatment toxicity and improve cosmesis. Based on the published literature, an increasing number of treatment facilities are offering treatment with these techniques. However, further clinical study remains important to thoroughly define the appropriate clinical setting, patient selection criteria, and limitations for each of these innovative treatment approaches.     

Local Recurrence of Invasive Micropapillary Breast Cancer After MammoSite Brachytherapy: A Case Report and Literature Review

Controversy exists over the optimal patient selection criteria for accelerated partial-breast irradiation (APBI), which has been introduced as an alternative to whole-breast irradiation. The goal is to select patients with the lowest risk for tumor spread outside of the original lumpectomy bed targeted by the local internal radiation dose. Therefore, patients with more aggressive types of breast cancer might not be ideal candidates for partial breast irradiation. We discuss the case of a 67-year-old woman who presented with local recurrence of invasive micropapillary breast cancer, a rare aggressive tumor type, 5 years after MammoSite brachytherapy. The patient's primary tumor possessed all favorable indicators except for the histology of invasive micropapillary carcinoma. This is the first report of invasive micropapillary carcinoma recurring after APBI. Although this is a single case, it supports the hypothesis that more aggressive types of breast cancer have a higher risk of local recurrence after APBI. We propose that invasive micropapillary carcinoma be considered a potential exclusion criterion until it can be validated in prospective clinical trials. More aggressive treatment approaches including whole-breast irradiation and/or chemotherapy might be needed to reduce the risk of local recurrence for invasive micropapillary breast cancer.     

Image-guided breast brachytherapy: an alternative to whole-breast radiotherapy

Lumpectomy and whole-breast radiotherapy (ie, breast-conservation treatment) are accepted as viable alternatives to mastectomy in locoregional management of breast cancer. These techniques are used to keep morbidity to a minimum, optimise cosmesis, and maintain treatment outcomes. Pathological and clinical data suggest that most recurrences of cancer in the ipsilateral breast are in the vicinity of the index lesion, and that remote recurrences are uncommon, whether or not whole-breast radiotherapy is delivered. These data lend support to the idea of partial-breast radiotherapy. Such a restricted treatment volume allows safe delivery of an accelerated hypofractionated regimen over a shortened course of 1 week. This technique differs from that of standard whole-breast tangential external-beam radiotherapy and necessitates investigation of accelerated partial-breast irradiation (APBI). Several techniques of APBI are being investigated; however, most experience, and the most favourable early outcomes, has been obtained with image-guided breast brachytherapy. This review highlights the rationale and outcomes of brachytherapy techniques.     

Clinical experience using hypofractionated radiation schedules in breast cancer

Hypofractionation is attractive for whole- or partial-breast irradiation because it permits treatment to be given with fewer fractions in a shorter period of time and at less cost. A number of cohort studies suggest that hypofractionation may be given to the whole breast safely and with good local control. Recent randomized trials have confirmed that hypofractioned whole-breast irradiation is equivalent to more conventional whole-breast irradiation with respect to local recurrence and cosmetic outcome. Recently, there has been a renewed interest in hypofractionation for the delivery of partial-breast irradiation using a number of techniques including high-dose rate brachytherapy, 3-dimensional conformal radiation using external-beam techniques, and intraoperative therapy. Early cohort studies report good local control and acceptable morbidity. Randomized trials are now underway to compare this approach to conventional whole-breast irradiation.     

Has Hypofractionated Whole-Breast Radiation Therapy Become the Standard of Care in the United States? An Updated Report from National Cancer Database

Introduction/BackgroundWe aimed to update the previous evaluation of hypofractionated whole-breast irradiation (HF-WBI) use over time in the United States and factors related to its adoption for patients undergoing a lumpectomy from 2004 to 2016.Materials and MethodsAmong the patients who underwent a lumpectomy, we identified 688,079 patients with early-stage invasive breast cancer and 248,218 patients with ductal carcinoma in situ in the National Cancer Database from 2004 to 2016. We defined HF-WBI as 2.5 to 3.33 Gy/fraction to the breast and conventional fractionated whole-breast irradiation as 1.8 to 2.0 Gy/fraction. We evaluated the trend of HF-WBI use and examined factors associated with HF-WBI use using logistic regression models.ResultsAmong invasive cancer patients, the use of HF-WBI increased exponentially from 0.7% in 2004 to 15.6% in 2013 and then to 38.1% in 2016. Among patients with ductal carcinoma in situ, the use of HF-WBI has increased significantly from 0.42% in 2004 to 13.4% in 2013 and then to 34.3% in 2016. Factors found to be associated with HF-WBI use included age, patient geographical location, race/ethnicity, tumor stage, grade, treating facility type, and volume.ConclusionHF-WBI use in the United States has more than doubled from 2013 to 2016. Although its use is close to that of conventional fractionated whole-breast irradiation, HF-WBI is still far from the preferred standard of care in the United States. We identified several patient and facility factors that can impact the uptake of HF-WBI treatment.MicroabstractUsing the National Cancer Database from 2004 to 2016, we evaluated the trend of hypofractionated whole-breast radiation therapy use and factors associated with use. Use in the United States has more than doubled from 2013 to 2016, but it has not become the standard of care. We identified several patient and facility factors that impact the uptake of hypofractionated whole-breast radiation therapy treatment.     

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.     

Lessons of studies of breast-conserving therapy with and without whole-breast irradiation for patient selection for partial-breast irradiation

Partial-breast irradiation is a promising approach for treating patients with early-stage invasive breast cancer. There are still few studies of partial-breast irradiation that address critical issues, such as criteria for patient selection. However, an enormous body of experience has been accumulated regarding the results in patients treated with "conventional" breast-conserving therapy using whole-breast irradiation and for patients treated with conservative surgery without radiotherapy of any kind. This article will therefore review portions of this existing experience that may aid the development of partial-breast irradiation and give perspective on the overall role that partial-breast irradiation may ultimately play in our therapeutic armamentarium.     

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。      

Pattern of local recurrence after conservative surgery and whole-breast irradiation

PURPOSE: Most recurrences in the breast after conservative surgery and whole-breast irradiation have been reported to occur within the same quadrant as the initial primary tumor. We analyzed the long-term risk of recurrence by area of the breast after whole-breast irradiation. MATERIALS AND METHODS: In all, 1,990 women with Stage 0-II breast cancer were treated with conservative surgery and whole-breast irradiation from 1970-1998. Stage was ductal carcinoma in situ in 237, T1 in 1273, and T2 in 480 patients. Of 120 local recurrences, 71 were classified as true local (confined to the original quadrant) and 49 as elsewhere (involving outside the original quadrant). Kaplan-Meier methodology was used to calculate 5-year, 10-year, and 15-year rates of recurrence (95% confidence intervals in parentheses). The median follow-up is 80 months. RESULTS: There was no apparent difference in the 15-year rate of true local vs. elsewhere recurrence, but the time to recurrence was different. The rate of true local recurrence was 2%, 5%, and 7% (5-9%) at 5, 10, and 15 years, respectively. The recurrences elsewhere in the breast were rare at 5 (1%) and 10 (2%) years, but increased to 6 (3-9%) at 15 years. This 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers of 13% (10-16%). CONCLUSIONS: Recurrence elsewhere in the breast is rare for the first 10 years, but by 15 years is nearly equal to true local recurrence even after whole-breast irradiation. The 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers. This may indicate a therapeutic effect of whole-breast radiation for other areas of the breast. Very long follow-up will be needed for partial breast irradiation with or without tamoxifen to show that the risk of elsewhere recurrence is not significantly different than after whole-breast irradiation.     

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.