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。     

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。     

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.     

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation

BACKGROUND:

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) using accelerated partial breast irradiation (APBI).

METHODS:

In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4‐Gy fractions). One thousand two hundred fifty‐five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow‐up was 60 months.

RESULTS:

Fifty patients (3.5%) developed an IBTR for a 5‐year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3‐year rates of disease‐free survival, cause‐specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.

CONCLUSIONS:

With 5 years of follow‐up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3‐year survival outcomes after salvage treatments. Cancer 2012. © 2012 American Cancer Society.     

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。     

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.     

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.     

Long-term efficacy and patterns of failure after accelerated partial breast irradiation: a molecular assay-based clonality evaluation

PURPOSE: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. METHODS AND MATERIALS: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for >or=10 years. RESULTS: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. CONCLUSIONS: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.     

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.     

Prospective trial of accelerated partial breast intensity-modulated radiotherapy

PURPOSE: To examine the feasibility and acute toxicities of an accelerated, partial breast, intensity-modulated radiotherapy (IMRT) protocol. METHODS AND MATERIALS: Between February 2004 and August 2005, 55 patients with Stage I breast cancer and initial follow-up were enrolled at four facilities on a HealthONE and Western institutional review board-approved accelerated partial breast IMRT protocol. All patients were treated in 10 equal fractions delivered twice daily within 5 consecutive days. The first 7 patients were treated to 34 Gy, and the remaining 48 patients were treated to 38.5 Gy. RESULTS: The median follow-up after IMRT was 10 months (range, <1-19) and after diagnosis was 11.5 months (range, 2-21). No local or distant recurrences developed. The T stage distribution was as follows: T1a in 11 patients, T1b in 24, and T1c in 20. The median tumor size was 9 mm (range, 1-20 mm). Breast cosmesis was judged by the patient as poor by 2, good by 12, and excellent by 40 (1 patient was legally blind) and by the physician as poor for 1, good for 10, and excellent for 44 patients. Breast pain, as judged by patient, was none in 34, mild in 19, moderate in 2, and severe in 0 patients. There was a single report of telangiectasia but no incidents of significant edema. Compared with historic controls for whom three-dimensional treatment planning techniques were used, IMRT provided similar dose delivery to the target while reducing the volume of normal breast included in the 100%, 75%, and 50% isodose lines. CONCLUSION: This initial report prospectively explored the feasibility of accelerated partial breast IMRT. After short-term follow-up, the dose delivery and clinical outcomes were very acceptable. We believe this regimen deserves additional investigation under institutional review board guidance.     

Cone beam computed tomography guidance for setup of patients receiving accelerated partial breast irradiation

PURPOSE: To evaluate the role of cone-beam CT (CBCT) guidance for setup error reduction and soft tissue visualization in accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: Twenty patients were recruited for the delivery of radiotherapy to the postoperative cavity (3850 cGy in 10 fractions over 5 days) using an APBI technique. Cone-beam CT data sets were acquired after an initial skin-mark setup and before treatment delivery. These were registered online using the ipsilateral lung and external contours. Corrections were executed for translations exceeding 3 mm. The random and systematic errors associated with setup using skin-marks and setup using CBCT guidance were calculated and compared. RESULTS: A total of 315 CBCT data sets were analyzed. The systematic errors for the skin-mark setup were 2.7, 1.7, and 2.4 mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. These were reduced to 0.8, 0.7, and 0.8 mm when CBCT guidance was used. The random errors were reduced from 2.4, 2.2, and 2.9 mm for skin-marks to 1.5, 1.5, and 1.6 mm for CBCT guidance in the right-left, anterior-posterior, and superior-inferior directions, respectively. CONCLUSION: A skin-mark setup for APBI patients is sufficient for current planning target volume margins for the population of patients studied here. Online CBCT guidance minimizes the occurrence of large random deviations, which may have a greater impact for the accelerated fractionation schedule used in APBI. It is also likely to permit a reduction in planning target volume margins and provide skin-line visualization and dosimetric evaluation of cardiac and lung volumes.     

Persistent seroma after intraoperative placement of MammoSite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors

PURPOSE: To investigate the incidence of, and possible factors associated with, seroma formation after intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation. METHODS AND MATERIALS: This study evaluated 38 patients who had undergone intraoperative MammoSite catheter placement at lumpectomy or reexcision followed by accelerated partial breast irradiation with 34 Gy in 10 fractions. Data were collected regarding dosimetric parameters, including the volume of tissue enclosed by the 100%, 150%, and 200% isodose shells, dose homogeneity index, and maximal dose at the surface of the applicator. Clinical and treatment-related factors were analyzed, including patient age, patient weight, history of diabetes and smoking, use of reexcision, interval between surgery and radiotherapy, total duration of catheter placement, total excised specimen volume, and presence or absence of postprocedural infection. Seroma was verified by clinical examination, mammography, and/or ultrasonography. Persistent seroma was defined as seroma that was clinically detectable >6 months after radiotherapy completion. RESULTS: After a median follow-up of 17 months, the overall rate of any detectable seroma was 76.3%. Persistent seroma (>6 months) occurred in 26 (68.4%) of 38 patients, of whom 46% experienced at least modest discomfort at some point during follow-up. Of these symptomatic patients, 3 required biopsy or complete cavity excision, revealing squamous metaplasia, foreign body giant cell reaction, fibroblasts, and active collagen deposition. Of the analyzed dosimetric, clinical, and treatment-related variables, only body weight correlated positively with the risk of seroma formation (p = 0.04). Postprocedural infection correlated significantly (p = 0.05) with a reduced risk of seroma formation. Seroma was associated with a suboptimal cosmetic outcome, because excellent scores were achieved in 61.5% of women with seroma compared with 83% without seroma. CONCLUSION: Intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation is associated with a high rate of clinically detectable seroma that adversely affects the cosmetic outcome. The seroma risk was positively associated with body weight and negatively associated with postprocedural infection.