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.     

Magnetic resonance imaging identifies multifocal and multicentric disease in breast cancer patients who are eligible for partial breast irradiation

BACKGROUND: In this retrospective study, the authors hypothesized that magnetic resonance imaging (MRI) would alter partial breast irradiation (PBI) eligibility by identifying cancers outside the PBI volume compared with mammography alone. METHODS: Since 2002, MRI was used nonselectively at the authors' institution for the staging of patients with nonmetastatic breast cancer. Of 450 consecutive patients with invasive breast cancer, 110 patients who were eligible for PBI were identified by using criteria outlined by National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Oncology Group trial 0413 based on mammography, ultrasonography, and initial pathology. In that trial, patients were randomized (stage I/II invasive cancers that measured 相似文献   

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。     

A pilot study of wider use of accelerated partial Breast irradiation: Intraoperative margin-directed re-excision combined with sole high-dose-rate interstitial brachytherapy

BACKGROUND: Accelerated partial breast irradiation (APBI) is generally limited to patients at extremely low risk of local recurrence. The significance of the risk factors, however, depends on the extent of surgery, radiation, and systemic therapy. In Japan, wide excision is generally supplemented by intraoperative margin-directed re-excision if the frozen section examination yields positive results. This approach combined with conventional radiotherapy achieved an excellent 10-year local control rate of 93%, and young age and ductal carcinoma in situ were not risk factors for local recurrence. To reduce the treatment duration, high-dose-rate interstitial brachytherapy (HDRIB) was employed. The first APBI phase I / II trial in Japan was conducted to determine if wider indications for early breast cancer patients were appropriate. METHODS: The subjects comprised 20 patients including those with extensive intraductal component (n=7), ductal carcinoma in situ (n=2), positive final margins (n=3), and of younger age (< or = 45 years; n=5). Breast-conserving surgery using an intraoperative re-excision approach was followed by intraoperative implantation of applicators. Sole HDRIB of a 36-42 Gy in 6-7 fractions was delivered postoperatively over 3-4 days. Tumors were staged as follows: cT1 (n=12), cT2 (n=8), cN0 (n=20). Systemic therapy was used in 16 patients (80%). The median follow-up period was 52 months (range, 26-86 months). RESULTS: Te five-year crude local, distant control, and Kaplan-Meier cause-specific survival rates were 95%, 95%, and 89%, respectively. Fat necrosis developed in 1 patient. CONCLUSIONS: Sole HDRIB with intraoperative margin-directed re-excision was feasible under wider indications compared to other contemporary APBI series, and achieved acceptable and similar results to these series in terms of the local control rate and complications.     

Preoperative breast magnetic resonance imaging in early breast cancer

BACKGROUND:

Accelerated partial breast irradiation (APBI) of patients with early breast cancer is being investigated on a multi‐institutional protocol National Surgical Adjuvant Breast and Bowel Project (NSABP) B‐39/RTOG 0413. Breast magnetic resonance imaging (MRI) is more sensitive than mammography (MG) and may aid in selection of patients appropriate for PBI.

METHODS:

Patients with newly diagnosed breast cancer or ductal carcinoma in situ (DCIS) routinely undergo contrast‐enhanced, bilateral breast MRI at the Cleveland Clinic. We retrospectively reviewed the medical records of all early‐stage breast cancer patients who had a breast MRI, MG, and surgical pathology data at our institution between June of 2005 and December of 2006. Any suspicious lesions identified on MRI were further evaluated by targeted ultrasound ± biopsy.

RESULTS:

A total of 260 patients met eligibility criteria for NSABP B‐39/RTOG 0413 by MG, physical exam, and surgical pathology. The median age was 57 years. DCIS was present in 63 patients, and invasive breast cancer was found in 197 patients. MRI identified suspicious lesions in 35 ipsilateral breasts (13%) and in 16 contralateral breasts (6%). Mammographically occult, synchronous ipsilateral foci were found by MRI in 11 patients (4.2%), and in the contralateral breast in 4 patients (1.5%). By univariate analysis, lobular histology (infiltrating lobular carcinoma [ILC]), pathologic T2, and American Joint Committee on Cancer stage II were significantly associated with additional ipsilateral disease. Of patients with ILC histology, 18% had ipsilateral secondary cancers or DCIS, compared with 3% in the remainder of histologic subtypes (P = .004). No patient older than 70 years had synchronous cancers or DCIS detected by MRI.

CONCLUSIONS:

Breast MRI identified synchronous mammographically occult foci in 5.8% of early breast cancer patients who would otherwise be candidates for APBI. Cancer 2009. © 2009 American Cancer Society.     

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.     

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。     

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.     

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.     

The role of magnetic resonance imaging in early breast cancer

Despite recent evidence that fails to detect a benefit in surgical and local recurrence outcomes in those who receive optimal surgery and adjuvant systemic and radiotherapy, magnetic resonance imaging (MRI) is still being employed. We review the recent literature to clarify the role in the use of MRI in early breast cancer. A literature search using the Medline and Ovid databases was conducted between 2004 and 2011 using the terms "magnetic resonance imaging' and 'early breast cancer'. Only articles with clinical trials published in English in adult humans with available abstracts were included. Articles on high-risk women, response to neoadjuvant therapy, advanced breast cancer, the occult primary, the contralateral breast and technical articles were excluded. Articles examining the role of MRI in the staging of early breast cancer were retained. Over 260 articles regarding breast MRI have been published in the last 5 years. Additional foci may be found in 16% of patients but the impact on the extent of surgery and local recurrence rate is yet to be defined. Certain sub-groups who may benefit include those with invasive lobular carcinoma and mammographically dense breasts and those for consideration of partial breast irradiation. With standard adjuvant radiotherapy, there is no benefit in routine MRI with respect surgical extent and local recurrence. Should MRI be used, pre-operative biopsy to confirm additional disease must be undertaken prior to a change in surgical extent of resection. However, MRI may be useful in the evaluation of those who can be considered for partial breast irradiation. Centres undertaking breast MRI must have MRI-biopsy capabilities and constantly audit the reporting of MRI with correlation to the final pathology.     

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.     

早期乳腺癌保乳术后三维适形加速部分乳腺照射的疗效

目的 分析早期低危乳腺癌保乳术后三维适形加速部分乳腺照射(APBI)的局部控制情况、美容评价及不良反应,并对剂量学结果进行质量评估。方法 2008—2010年前瞻性临床Ⅱ期研究入组 39例早期(0~Ⅰ期)乳腺癌保乳术后患者,其中浸润性导管癌 28例、导管原位癌 5例、其他类型浸润性癌 6例。放疗处方剂量为38.5 Gy分10次,2 次/d,间隔6 h以上。不良反应评价采用NCI-CTC 3.0标准,美容评价依据Harris美容级别标准。结果 三维适形APBI技术应用于早期乳腺癌保乳术后获得了满意的剂量学结果,85%(33例)患者完全满足放疗质量控制评估标准。与ASTRO、GEC-ESTRO共识比较中危/高危患者比例分别为46%、18%和31%、3%。随访率100%,无一局部复发,无3、4级不良反应。放疗后6个月美容评价优异加良好者占90%(35例)。结论 三维适形APBI入组患者选择恰当,局部控制、不良反应和美容评价初步结果较好。     

Complementary role of adjunctive breast magnetic resonance imaging and scintimammography in patients of all ages undergoing breast cancer surgery

The aims of this study were to assess breast MRI and scintimammography (SMM) for the detection of breast cancer, and to determine any complementary role of these tests to each other and conventional imaging. Seventy‐two patients (age 35–81 years) with a suspicious breast mass were investigated by mammography, breast ultrasound, breast MRI and SMM before undergoing surgical excision of the breast mass. Sensitivity, specificity and area under receiver operator characteristic curves were calculated for each test. Of the 72 patients, there were 66 proven malignant tumours, including two patients with bilateral breast cancer. When comparing the diagnostic sensitivity of breast MRI and SMM for lesion size, both tests showed higher sensitivities for lesions >25 mm in size, particularly for SMM. When these tests were compared for patient age, patients less than 51 years showed higher sensitivities for both tests. This was statistically significant for breast MRI. The overall respective diagnostic sensitivities for mammography, mammography with breast ultrasound, breast MRI and SMM were 56, 67, 86 and 85%. The differences were significant between mammography, mammography/ultrasound and both breast MRI and SMM. Breast MRI and SMM offer incremental diagnostic advantage in the diagnosis of breast cancer. Although improved diagnostic accuracy is seen in patients of all ages, those patients less than 51 years of age receive the greatest diagnostic benefit.