Concepts and techniques of intraoperative radiotherapy (IORT) for breast cancer

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality. This article is based on an invited lecture delivered at the 15th Annual Meeting of the Japanese Breast Cancer Society, held in Yokohama June 29-30, 2007.     

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment

Background and purpose

The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials.

Patients and methods

Data from 1331 patients (?50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n = 922), and a CT-scan-based treatment plan (Young Boost Trial, n = 409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates.

Results

Median V_95% in the conventional simulation-based treatment plans was 99 cc (range 9-628) for photons and was 98 cc (13-651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37-2699) and 150 cc (43-1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size (p < 0.0067), lumpectomy size (p < 0.0002), and boost technique (p < 0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant (p < 0.0001).

Conclusions

The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5-1.8, compared to conventional simulator-based plans.     

早期乳腺癌保乳术后瘤床同步加量短疗程放疗临床观察

目的 探讨早期乳腺癌保乳术后瘤床同步加量短疗程放疗疗效、不良反应以及美容效果。方法 2008—2010年本院收治早期乳腺癌保乳术后患者 306例,其中 160例行常规分割放疗(常规组),两野切线全乳照射,后续瘤床电子线推量,总疗程 46~48 d;146例行短疗程放疗(短程组),两野切线全乳照射,同步瘤床电子线推量,总疗程 30~32 d。Kaplan-Meier法计算生存率和局部复发率并Logrank检验差异,χ²检验两组资料可比性、不良反应及美容效果。结果 中位随访时间26个月,随访率为100%。两组1、2、3年生存率均为100%,均无局部复发(χ²=0.00,P=1.000)。常规组与短程组1、2级急性皮肤反应发生率分别为46.9%与45.1%(χ²=0.73,P=0.695)、16.3%与13.7%(χ²=0.73,P=0.695),1级皮肤及皮下组织晚期反应发生率分别为16.9%与17.1%(χ²=0.00,P=0.954);1级中性粒细胞减少发生率分别为11.9%与13.7%(χ²=0.23,P=0.633);美容优良率分别为66.2%与65.5%(χ²=0.01,P=0.927)。结论 保乳术后全乳放疗同步瘤床加量的短疗程方案与常规放疗的疗效相似,美容效果相当且未加重皮肤反应,但还需进一步研究。     

T4期乳腺癌患者改良根治术后胸壁放疗加量的疗效及预后分析

目的分析T4期乳腺癌患者改良根治术后胸壁放疗加量的疗效。方法回顾分析2000-2016年收治的148例T4期、改良根治术后放疗的乳腺癌患者资料,胸壁放疗加量组57例,不加量组91例。放疗采用常规+胸壁电子线、三维适形+胸壁电子线、调强放疗+胸壁电子线照射,加量组EQD2>50Gy。全组患者均接受新辅助化疗。Kaplan-Meier法生存分析并Logrank检验差异,Cox模型多因素预后分析。结果中位随访时间67.2个月,5年胸壁复发(CWR)、局部区域复发(LRR)、无瘤生存(DFS)、总生存(OS)率分别为9.9%、16.2%、58.0%、71.4%。胸壁放疗加量和不加量的5年CWR、LRR、DFS、OS率分别为14%和7%、18%和15%、57%和58%、82%和65%(P>0.05)。多因素分析显示胸壁加量与否对预后无显著影响(P>0.05)。45例复发高危组患者中放疗加量组似乎有较高的OS率(P=0.058)、DFS率(P=0.084)和较低的LRR率(P=0.059)。结论T4期乳腺癌患者异质性较强,胸壁放疗加量对全组患者无明显获益。对于有脉管瘤栓阳性、pN2-N3、激素受体阴性中2~3个高危因素患者胸壁放疗加量有改善疗效趋势。     

Intraoperative radiation therapy delivered prior to lumpectomy for early-stage breast cancer: a single institution study

Objective: To evaluate the safety, cosmesis, and clinical outcome of intraoperative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. Methods: From December 2008 to March 2012, 75 breast cancer patients (ages 34-66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile linear accelerator. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by post-operative external beam radiation therapy of 50 Gy/25F; the others had 15 Gy, prescribed to the 90% isodose depth. Adjuvant treatment consisted of chemotherapy (55 patients), hormonal therapy (59 patients), or combined chemotherapy and hormonal therapy (41 patients). The safety, cosmesis, and short-term outcome were evaluated. Results: Median follow-up was 54 months (range: 30-66 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.0%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.3%. No distant metastases or deaths were observed. The 3-year disease free survival was 94.6%. Conclusions: Intraoperative electron radiation therapy delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of late side effects and long-term outcome.     

A cosmetic evaluation of breast cancer treatment: a randomized study of radiotherapy boost technique

PURPOSE: To compare cosmetic results of two different radiotherapy (RT) boost techniques used in the treatment of breast cancer after whole breast radiotherapy and to identify factors affecting cosmetic outcomes. METHODS AND MATERIALS: Between 1996 and 1998, 142 patients with Stage I and II breast cancer were treated with breast conservative surgery and adjuvant RT. Patients were then randomly assigned to receive a boost dose of 15 Gy delivered to the tumor bed either by iridium 192, or a combination of photons and electrons. Cosmetic evaluations were done on a 6-month basis, with a final evaluation at 36 months after RT. The evaluations were done using a panel of global and specific subjective scores, a digitized scoring system using the breast retraction assessment (BRA) measurement, and a patient's self-assessment evaluation. As cosmetic results were graded according to severity, the comparison of boost techniques was done using the ordinal logistic regression model. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) are presented. RESULTS: At 36 months of follow-up, there was no significant difference between the two groups with respect to the global subjective cosmetic outcome (OR = 1.40; 95%CI = 0.69-2.85, p = 0.35). Good to excellent scores were observed in 65% of implant patients and 62% of photon/electron patients. At 24 months and beyond, telangiectasia was more severe in the implant group with an OR of 9.64 (95%CI = 4.05-22.92, p < 0.0001) at 36 months. The only variable associated with a worse global cosmetic outcome was the presence of concomitant chemotherapy (OR = 3.87; 95%CI = 1.74-8.62). The BRA value once adjusted for age, concomitant chemotherapy, and boost volume showed a positive association with the boost technique. The BRA value was significantly greater in the implant group (p = 0.03). There was no difference in the patient's final self-assessment score between the two groups. Three variables were statistically associated with an adverse self-evaluation: an inferior quadrant tumor localization, postoperative hematoma, and concomitant chemotherapy. CONCLUSIONS: Although this trial showed that at 36 months of follow-up, there were no significant differences in the overall global cosmetic scores between the implant boost group and the photon/electron boost group, telangiectasia was more severe and the BRA value was greater in the implant group.     

Ⅰ、Ⅱ期乳腺癌保乳术后的三维适形调强放射治疗

目的对Ⅰ、Ⅱ期乳腺癌施行保乳术后的病人进行根治性三维适形调强放射治疗,提高局部控制率,减轻放疗副作用,提高了生存质量.方法2004年4月～2004年10月的11例接受过标准保存乳房手术的Ⅰ、Ⅱ期乳腺癌病人,均为女性,年龄31～46岁,平均34.7岁.术前触诊肿瘤大小为6mm～30mm,术后病理结果为:单纯癌4例、浸润性导管癌5例、高分化管状腺癌1例、中分化腺癌1例.手术后三个月内接受三维适形调强放射治疗.乳房切线照射剂量47～50Gy/24～31次,局部电子线补量10～15Gy/5～8次.结果全部病人顺利完成全程放疗,最长1例接受放疗后已经2年半,局部及全身未见复发征象,乳房外观形状良好,放疗反应轻微.结论通过对Ⅰ、Ⅱ期乳腺癌病人进行三维适形调强放射治疗,达到了提高病人的生存质量,提高肿瘤控制率的目的.     

乳腺癌的术中放疗

乳腺癌是全球女性最高发的恶性肿瘤,不仅威胁患者生命,同时也影响患者的生存质量和生理功能。因此,采用优化的综合治疗策略,延长患者生命,改善患者生存质量,是目前乳腺癌治疗的趋势。放射治疗是乳腺癌综合治疗的重要组成部分,近年来,乳腺癌放射治疗具有照射范围缩小,分割次数减少两大趋势。术中放疗(intraoperative radiotherapy,IORT)由于在手术中直视下给予单次大剂量照射,具有缩短疗程,有效保护正常组织的优势。目前IORT对接受保乳术的乳腺癌患者可作为外照射的局部剂量追加技术方法,或作为替代术后外照射的技术方法。现就IORT技术的优缺点及其临床适应证、疗效和不良反应进行系统回顾,为指导临床开展IORT提供依据。     

Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer

This study reports on the treatment results in 508 patients with 514 AJCC stage I–II invasive breast carcinomas treated between July 1980 and July 1989. All patients underwent a lumpectomy with axillary lymph node dissection with postoperative irradiation. Adjuvant chemotherapy was given to premenopausal node-positive patients. Postmenopausal node-positive patients received adjuvant hormonal treatment. The median follow-up period was 68 months (range, 40–152 months). The 5-year survival rates were 92.6%, 81.4% and 65.5% for stage I, stage IIA and stage IIB, respectively. Distant metastases were the main cause of death. Locoregional failures occurred in 4.9%. Breast recurrences were detected in 17 patients (3.3%). In a Cox proportional hazards analysis, T-stage, pathological margins and interval between surgery and radiotherapy were identified as independent factors predictive of breast recurrence (p < 0.05). The results suggest that radiotherapy should be initiated early after surgery to maintain the breast recurrence rate as low as possible.     

乳腺癌保乳术后放疗疗效和美观效果

目的　观察乳腺癌保乳术后放疗的疗效和美观效果。方法　保乳术后全乳外照射和瘤床加量共10 9例,79例除应用高剂量率插植技术[T1期肿瘤用单排插植,针距为1.5cm ,T2期以上肿瘤用双排或三排插植;针距间单次剂量(DB) 10～12Gy ,靶区周边剂量为85 %DB]外,其中4 8例还经组织间插植加量放疗;30例除采用电子线常规外照射15Gy外,其中2 7例还经电子线外照加量放疗。全乳照射应用6MV直线加速器,采用双切线半野照射技术,靶区剂量为4 5～5 2Gy(平均4 8.6Gy)。采用医生评分与患者问卷方法评价美观效果。结果　5年生存率为93.8% ,局部复发率为6 .5 %。全组无放射性溃疡发生,5例出现位于插植针孔周围急性皮肤炎症。在经临床随访体检的75例中,医生打分和患者自评满意度为优的比例分别占87%和81% (P >0 .0 5 )。两组满意度医生总评为优的患者比例分别为81.2 %和85 .2 % (P >0 .0 5 )。结论　乳腺癌保乳术后放疗可降低术后复发率,并发症少。不同的瘤床加量放疗方法不影响美观满意度。     

Comparison of modulated electron radiotherapy to conventional electron boost irradiation and volumetric modulated photon arc therapy for treatment of tumour bed boost in breast cancer

Background and purpose

To compare few leaf electron collimator (FLEC)-based modulated electron radiotherapy (MERT) to conventional direct electron (DE) and volumetric modulated photon arc therapy (VMAT) for the treatment of tumour bed boost in breast cancer.

Materials and methods

Fourteen patients with breast cancer treated by lumpectomy and requiring post-operative whole breast radiotherapy with tumour bed boost were planned retrospectively using conventional DE, VMAT and FLEC-based MERT. The planning goal was to deliver 10 Gy to at least 95% of the tumour bed volume. Dosimetry parameters for all techniques were compared.

Results

Dose evaluation volume (DEV) coverage and homogeneity were best for MERT (D₉₈ = 9.77 Gy, D₂ = 11.03 Gy) followed by VMAT (D₉₈ = 9.56 Gy, D₂ = 11.07 Gy) and DE (D₉₈ = 9.81 Gy, D₂ = 11.52 Gy). Relative to the DE plans, the MERT plans predicted a reduction of 35% in mean breast dose (p < 0.05), 54% in mean lung dose (p < 0.05) and 46% in mean body dose (p < 0.05). Relative to the VMAT plans, the MERT plans predicted a reduction of 24%, 36% and 39% in mean breast dose, heart dose and body dose, respectively (p < 0.05).

Conclusions

MERT plans were a considerable improvement in dosimetry over DE boost plans. There was a dosimetric advantage in using MERT over VMAT for increased DEV conformity and low-dose sparing of healthy tissue including the integral dose; however, the cost is often an increase in the ipsilateral lung high-dose volume.     

Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: Long-term results focused on topographic pattern of locoregional relapse

Background

Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT.

Methods

A total of 335 patients with LARC [?cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed.

Results

Median follow-up was 72.6 months (range, 4–205). In multivariate analysis distal margin distance ?10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1–2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC.

Conclusions

Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.