Comparison of normal tissue dose with three-dimensional conformal techniques for breast cancer irradiation including the internal mammary nodes

PURPOSE: To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with three commonly used strategies, by analyzing the dose to the heart and other organs at risk. METHODS AND MATERIALS: Four different three-dimensional conformal dose plans were created for 30 breast cancer patients. The IMN were enclosed with the Para Mixed technique by a widened mediolateral tangent photon beam and an anterior electron beam, with the Patched technique by an anterior electron beam, with the Standard technique by an anterior photon and electron beam, and with the PWT technique by partially wide tangents. All techniques were optimized for conformality and produced equally adequate target coverage. RESULTS: Heart dose was lowest with the Para Mixed and Patched technique for all patients and with the PWT technique for right-sided treatment only. Lung dose was highest with the PWT, lowest with the Patched, and intermediate with the Para Mixed and Standard techniques. Skin dose was highest with the Patched, lowest with the PWT, and intermediate with the Para Mixed and the Standard techniques. The Para Mixed technique resulted in a 13-Gy lower dose in an overlap area, and the PWT technique was the only technique that incorporated considerable volumes of the contralateral breast. CONCLUSION: The Para Mixed technique yielded the overall best results. No other technique resulted in a lower heart dose. Lung and skin were equally spared instead of one of them being compromised, and the contralateral breast was avoided.     

乳腺癌内乳区淋巴结照射研究进展

乳腺癌内乳区淋巴结照射能够降低局部和远处复发并改善患者的生存,NCCN指南也在内乳区淋巴结照射方面进行了相应的更新,但由于内乳区淋巴结照射造成的心肺损伤不容忽视,因此需要提供更为准确的个体化内乳区放疗指征。内乳区前哨淋巴结活检能够以微创的方法评估内乳区淋巴结的转移情况,为内乳区淋巴结照射提供准确的放疗指征,使乳腺癌患者获得更大的生存获益。本文主要从内乳区放疗获益、不良反应控制及内乳区前哨淋巴结活检指导放疗的探讨等方面进行了综述。     

Parasternal lymphoscintigraphy: implications for the treatment planning of internal mammary lymph nodes in breast cancer

Parasternal lymphoscintigraphy is an easily performed technique for visualizing and accurately determining thethree dimensional location of internal mammary lymph nodes. Sixty-eight women with primary or locally recurrent breast cancer underwent parasternal lymphoscintigraphy before treatment planning. The mean depth and lateral position of the internal mammary nodes were 1.8. ± 0.9 cm and 2.4 ± 0.9 cm respectively. Thirteen per cent of the nodes would have been undertreated by the standard tangential technique used at our institution. Six of 15 patients whose treatment plans were examined retrospectively had at least 1 lymph node undertreated by the standard tangential tec hnique. Thus, although standard tangential portals provide adequate coverage for the internal mammary lymph nodes in a majority of patients, parasternal lymphoscintigraphy can insure complete coverage of this lymph node group.     

乳腺癌内乳淋巴结预防性照射的Meta分析

目的 Meta分析乳腺癌患者内乳淋巴结预防性照射的疗效。方法 计算机检索中国知网、万方医学网、中国生物医学文献数据库、PubMed、EMBASE、Web of science。纳入比较以内乳淋巴结照射与否为干预措施的临床对照研究,按照Newcastle-Ottawa Scale量表进行纳入文献的质量评价。采用RevMan5.3软件和Stata14软件进行Meta分析。结果 共纳入11篇原始文献,13181例患者进行Meta分析。与内乳未照射患者相比,内乳照射患者 5年总生存未见改变(P=0.490)。通过以患者治疗日期以及入组人群风险程度为划分标准进行亚组分析显示,于 2000年后治疗和入组条件为Ⅱ-Ⅲ期(N+、T3-T4期)高风险患者内乳照射后 5年总生存明显提高(P=0.003、0.006)。与内乳未照射患者相比,内乳照射明显提高患者 5年无瘤生存(P<0.001)。结论 在现代放疗技术下,乳腺癌内乳淋巴引流区照射提高了患者无瘤生存率,并且可能会对Ⅱ-Ⅲ期(N+、T3-T4期)高风险乳腺癌患者带来总生存益处。     

Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy

Purpose The selective treatment of internal mammary lymph nodes (IMNs) in breast cancer is controversial. The purpose of this research was to determine the subpopulation patients with high risk of internal mammary lymph nodes metastasis who received extended radical mastectomy without any preoperative treatment from 1956 to 2003 in China. Patients and methods 1,679 Chinese patients were underwent extended radical mastectomy (ERM) between 1956 and 2003. Four individual variables were selected (tumor site, tumor size, the number of ALNs involvement, patient age),then classified by following standards: tumor site(lateral, central, medial),tumor size(T1:≤2 cm; T2:2 < T ≤ 5 cm, T3:>5 cm), ALNs(0,1–3,4–6, ≥7), age(≤35 y, 36–50 y, >50 y). Chi-square and binary logistic regression were used to analysis relationship of these variable and IMMs. Results The four individual variables were significantly associated with IMNs metastasis using univariate analysis. However, three individual variables except for tumor size independently impact the IMNs metastasis using multivariate analysis. The incidence of IMNs metastasis in patients with 4–6 and ≥7 positive ALNs was 28.1%, 41.5%. Within subgroup patients with medial tumor and positive ALNs, the incidence of IMNs metastasis was 23.6% for patients with 1–3 positive ALNs, and 47.5% for 4–6 positive ALNs, 38.7% for patients with ≥7 positive ALNs. The incidence of IMNs metastasis was 25.4% for patients with T3 tumor and younger than 35 y. Conclusion Patients with following conditions had high risk of IMNS metastasis: (1) patients with 4 or more positive ALNs. (2) patients with medial tumor and positive ALNs.(3) patients with T3 tumor and younger than 35 y. (4) patients with T2 tumor and positive ALNs.(5) patients with T2 tumor and medial tumor .The incidences of IMNS metastasis for those patients were more than 20%.     

Dose to lung in primary breast irradiation

Using anatomic data derived from computerized tomography (CT) scans of the torso, the volume of lung irradiated during primary breast treatment has been measured for a variety of irradiation techniques. Two-field tangential plans which are angled into lung to treat also the internal mammary nodes have been compared to three-field plans which include a separate internal mammary field (IMF). The volume of lung achieving high dose (greater than 3000 rad) is similar in both techniques when photons only are used. Electron beam treatment of the IMF is successful in lowering the lung dose. Additional treatment plans that angle the IMF parallel to the tangential fields may offer some theoretical advantage.     

乳腺癌术后内乳淋巴结的放疗

内乳淋巴结属于乳腺淋巴引流的第一站淋巴结,在乳腺癌的发生、发展过程中扮演着重要角色.临床上对内乳淋巴结是否行放疗还有很大争议.目前认为,对于早期患者,内乳淋巴结照射的疗效并不明确.而对腋窝淋巴结阳性、内侧象限或中央区病变患者,术后对内乳淋巴结进行放疗具有一定的价值.     

Adjuvant radiotherapy in operable breast cancer: Correlation between dose in internal mammary nodes and prognosis

In a controlled clinical trial preoperative radiotherapy was compared to modified radical mastectomy followed either by no further treatment or by postoperative radiotherapy. The total number of patients was 960; 654 of these had a follow-up time of more than five years. The patients who were irradiated preoperatively, had a significantly better survival rate than the patients who were treated with surgery only (p = 0.05); however, this was not true for those irradiated postoperatively. The radiation dose in the ipsilateral internal mammary nodes was, on the average, lower with the postoperative treatment technique than with the preoperative technique. This difference in dose-distribution in the internal mammary nodes is analyzed. The result of the study indicates that adequate local treatment may increase survival in a subgroup of patients.     

乳腺癌前哨淋巴结和非前哨淋巴结转移的影响因素分析

目的 探讨影响乳腺癌前哨淋巴结和非前哨淋巴结转移的相关因素.方法 回顾性分析2010年7月至2011年8月收治的、行前哨淋巴活检的283例女性乳腺癌患者的临床资料.结果 单因素分析结果显示,患者年龄、是否绝经、肿瘤大小、病理类型和脉管瘤栓均与前哨淋巴结转移(SLNM)有关(均P＜0.05);年龄、恶性肿瘤家族史、绝经情况、局部切除术、示踪技术、前哨淋巴结阳性、肿瘤大小、病理类型、分化程度、雌激素受体(ER)阳性、孕激素受体阳性、人表皮生长因子受体2阳性数目、脉管瘤栓和Ki-67≥15％等均与非前哨淋巴结转移无关(均P＞0.05).Logistic回归分析结果显示,患者年龄、肿瘤大小和脉管瘤栓均与SLNM有关(均P＜0.05).结论 患者年龄、肿瘤大小和脉管瘤栓是影响SLNM的独立因素,其中年龄是保护因素.而病理类型、病理分级和ER状态是否与SLNM有关存在争议.     

Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation

Purpose

To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of left-sided breast cancer including the regional lymph nodes.

Materials and methods

For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared.

Results

Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose (D_mean,heart) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial D_mean,heart (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the D_mean,heart further when D_mean,heart was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy).

Conclusions

VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When D_mean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast.     

胸腔镜内乳淋巴结清扫:一种针对乳腺癌内乳淋巴结的分期技术(英文)

Objective  

The aim of our study was to investigate the feasibility and safety of thoracoscopic internal mammary lymphadenectomy as a method to refine and thereby improve nodal staging in breast cancer.     

乳腺癌内乳区淋巴结转移研究进展

 内乳区淋巴结的转移状况是乳腺癌的独立预后指标,也是乳腺癌分期的重要依据之一。内乳区淋巴结转移的患者预后较差。内乳区淋巴结的总体转移率为18 %～33 %,仅有内乳区淋巴结转移而无腋窝淋巴结转移的发生率为2 %～11 %,其转移受腋窝淋巴结状况、患者年龄、原发肿瘤的位置和特点等多因素影响。随着前哨淋巴结活检技术的不断发展,内乳区前哨淋巴结活检术可能以最小的风险评估内乳区淋巴结状况,并进一步完善乳腺癌的淋巴结分期,有助于为患者制定更为准确的个体化治疗方案。     

Prevalence of extracapsular extension in metastatic sentinel lymph nodes in breast cancer

IntroductionAxillary lymph node involvement is recognized as a key prognostic factor for invasive breast cancer. Retrospective analyzes have shown that extracapsular extension (ECE) is correlated with negative prognostic factors in this neoplasia.Objectiveto evaluate the measurement of ECE and its relationship with the number of affected non-sentinel lymph nodes, as well as to investigate the association between ECE with other clinical and pathological prognostic factors.MethodsThis is a cross-sectional observational study carried out from January 2015 to June 2019, at the Breast Surgical Oncology service of Liga Contra o Cancer (LIGA), in Natal, Brazil. A total of 150 patients were included in the study and were divided into three groups: absence of ECE, ECE less than or equal to 2 mm and ECE greater than 2 mm.ResultsThe mean age was 58 years for the group with ECE and 57 years for the group without ECE. Most of the patients were mixed race (66.7%), had no family history of breast cancer (64%) and underwent quadrantectomy (64.5%). Regarding the characteristics of the disease, most presented a histological report compatible with Invasive Carcinoma of the non-special type (IC NST) (87.5%), histological grade II (52.7%), negative Lymphovascular invasion (LVI) (52.7%), Tumor Size T1 (<2.0 cm) (52%) and Luminal B molecular subtype (36.7%). Regarding sentinel lymph nodes: 103 patients (68.7%) had ECE and 1 positive sentinel lymph node was identified in most cases. There was a statistically significant association between the presence of ECE and of being mixed race (p = 0.03), between ECE and LVI (p = 0.05) and between ECE and a greater number of positive non-sentinel lymph nodes (p < 0.001).ConclusionOur study showed that ECE> 2 mm is associated with increased axillary nodal load compared to groups without ECE and ECE ≤ 2 mm in sentinel node biopsy in patients who met the Z0011 criteria.     

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer.     

Clinical significance of internal mammary lymph node metastasis for breast cancer: Analysis of 337 breast cancer patients

Purpose

Internal mammary nodes (IMNs) is a major pathway of lymphatic drainage for breast cancer, apart from axillary lymph node (ALN). However, owing to lack of a feasible and safe biopsy method, management of IMNs is still controversial in breast surgery.

Isolated internal mammary sentinel lymph node metastasis in two breast cancer patients

 Lymphatic mapping with sentinel node biopsy may lead to more accurate staging of breast cancer patients. Two patients with sentinel nodes in the internal mammary node chain are described. These nodes were visualized on lymphoscintigraphy images and harvested by the surgeon. They were shown to contain tumor cells in the absence of axillary involvement. This led to upstaging and to a change in the subsequent management. Received: May 16, 2002 / Accepted: July 1, 2002 Correspondence to:S.J. Haryono     

乳房保留术后野中野正向调强全乳房照射的腋窝淋巴结剂量学研究

目的 研究早期乳腺癌患者保乳术后采用野中野正向调强技术进行单纯乳房照射时各站腋窝淋巴结剂量分布及影响因素。方法 37例乳腺癌患者保乳术后采用“野中野”技术照射乳房,在定位CT图像上勾画患侧第Ⅰ、Ⅱ、Ⅲ站和胸肌间淋巴结靶区,并勾画腋静脉,在三维放疗计划软件上逐站分析其所接受的剂量。配对t检验分析影响腋窝淋巴结剂量分布的因素。结果 在全乳PTV处方剂量50 Gy分25次情况下,第Ⅰ、Ⅱ、Ⅲ站和胸肌间淋巴结被95%处方剂量所包括体积比平均值分别为34.7%、6.1%、0.4%和39.6%,D_mean分别为30.8、15.7、5.0 Gy和28.8 Gy;腋静脉以下和以上淋巴结区域被95%处方剂量包括的体积比为45.6%和0.7%,D_mean为38.2 Gy和6.7 Gy。乳房照射野的上界距离肱骨头的距离是影响腋静脉以下淋巴结区域D_mean的唯一有意义因素(P=0.037)。结论 全乳正向调强野中野技术对腋静脉以下腋窝淋巴结的实际照射剂量是不可忽略的,必须在分析保乳术后腋窝淋巴结控制率时予以考虑。     

左侧乳腺癌保乳术后采用深吸气屏气放疗的心脏剂量学分析

目的 探究左侧乳腺癌保乳术后放疗患者采用深吸气屏气(DIBH)技术对心脏剂量的改善情况,分析可能影响心脏剂量的解剖因素。方法 前瞻性入组 15例左侧乳腺癌保乳术后行全乳放疗患者,符合呼吸控制要求。分别在自由呼吸(FB)和DIBH状态下进行2次模拟CT扫描,在DIBH图像上制定全乳放疗计划。比较FB和DIBH状态下心肺位置和体积变化以及心肺剂量差异,探究FB状态下各解剖因素与心脏剂量的相关性。对计数资料组间行非参数Wilcoxon秩和检验,双变量相关分析采用Pearson法。结果 DIBH与FB状态下心脏体积相似(P=0.773),而双肺体积明显增加(P=0.001)。心脏、冠脉左前降支、左心室、右心室和左肺 Dmean、Dmax和V5—V40均明显降低(P<0.05)。DIBH使肺体积增加越显著,心脏平均剂量下降幅度越大。FB状态下乳腺体积、心肺体积比、乳腺下界与心脏下界距离、最大心脏切缘距离分别与心脏剂量呈线性相关,其中心肺体积比、最大心脏切缘距离与心脏剂量具有独立相关性。结论 左侧乳腺癌保乳术后采用DIBH技术行全乳放疗较FB状态明显降低心肺剂量。肺体积的变化是改善心脏相对解剖位置的基础。心肺体积比、最大心脏切缘距离或许可以作为进行DIBH技术治疗的参考标准。     

Extra-axillary sentinel lymph nodes in breast cancer

Background  Extra-axillary locations are known sites of lymph node metastases in patients with carcinoma of the breast. Methods  A technique utilizing a gamma probe was used to identify hot spots representing sentinel nodes residing in either axillary or extra-axillary locations in 680 patients with operable, clinically node-negative breast cancer. All identified sentinel nodes were excised. Results  Results showed that extra-axillary hot spots were found in 6.5% of patients. This rate increased to 14.8% if patients were injected with 8.0 ml unfiltered Technetium-99m-Sulfur colloid. Extra-axillary metastatic disease was identified in 6.8% of patients with extra-axillary hot spots. In patients with extra-axillary drainage, pathologically-positive nodes were exclusive to extra-axillary sites (ie, no axillary metastases) in 4.5% of cases. Factors found to increase the likelihood of identifying extra-axillary hot spots included; an increased volume of injection, medial or central tumor locations and T3 primary tumors. Conclusion  Gamma probe-guided techniques can identify extra-axillary sentinel nodes, which are at risk for harboring metastatic disease. Removal of these nodes can be done with little morbidity and may improve staging in the individual patient.