Cost-effectiveness of MRI and PET imaging for the evaluation of axillary lymph node metastases in early stage breast cancer

Background

UK guidelines for breast cancer recommend axillary nodal assessment via surgical methods such as sentinel lymph node biopsy (SLNB). However, these procedures are associated with adverse effects such as lymphoedema. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are non-invasive imaging techniques. The aim of this study is to evaluate the cost-effectiveness of MRI and PET compared with SLNB for assessment of axillary lymph node metastases in newly-diagnosed early stage breast cancer patients in the UK.

Methods

An individual patient discrete-event simulation model was developed in SIMUL8^® to estimate the lifetime costs and benefits of replacing SLNB with MRI or PET, or adding MRI or PET before SLNB. Effectiveness outcomes were derived from a recent systematic review; patient utilities and resource use data were sourced from the literature.

Results

Based on our analysis the baseline SLNB strategy is dominated by the strategies of replacing SLNB with either MRI or PET. The strategy of replacing SLNB with MRI has the highest total quality-adjusted life years (QALYs) and lowest total costs. However, clinical evidence for MRI is based on a limited number of small studies and replacing SLNB with MRI or PET leads to more false-positive and false-negative cases. The strategy of adding MRI before SLNB is cost-effective, but subject to greater uncertainty.

Conclusions

Based on this analysis the most cost-effective strategy is to replace SLNB with MRI. However, further large studies using up-to-date techniques are required to obtain more accurate data on the sensitivity and specificity of MRI.     

^18F-FDGPET／CT诊断乳腺癌及其腋窝淋巴结转移的价值评价

目的探讨^18F-脱氧葡萄糖（^18F-FDG）在诊断乳腺癌及腋窝淋巴结转移的价值。方法对34例乳腺癌患者的乳腺病灶（以健侧为对照）及腋窝淋巴结^18F-FDGPET／CT显像结果进行定性分析和半定量分析,结合病理结果,计算两种方法诊断的灵敏度、特异度、准确性。两种方法诊断与病理诊断行一致性检验。对乳腺病灶恶性组及对照组组间最大标准化摄取值（SUVmax）均数的比较采用两独立样本t检验。结果两组间SUVmax均数比较显示：恶性组^18F-FDG摄取高于对照组,差异有统计学意义（P=0．00）。1例为大汗腺导管内癌,系原位癌,对^18F-FDG摄取不明显,PET／CT图像上未见明显结节影,目测显示0级,SUVmax为1．5。该例病灶微小,小于PET／CT5～8mm的分辨率,造成定性和半定量分析均漏诊。18F-FDGPET／CT定性分析诊断乳腺癌的灵敏度、特异度、准确性分别为97．7％、100．0％、97．9％;半定量分析以suVmax2．0时,诊断乳腺癌的灵敏度、特异度、准确性为佳,分别为93．2％、100．0％、93．6％。定性分析与病理诊断的一致性极好,Kappa值为0．85,半定量分析与病理诊断有较好一致性,Kappa值为0．64。在腋窝淋巴结转移的诊断上,定性分析的诊断灵敏度、特异度、准确性分别为55．9％、96．1％、90．1％,半定量分析（以文献SUVmax1．8为标准）的诊断灵敏度、特异度、准确性分别为45．8％、97．0％、89．3％。两种分析诊断与病理诊均较好一致性,Kappa值分别为0．57（定性分析）和0．51（半定量分析）。结论^18F-FDGPET／CT诊断乳腺恶性病灶时,以SUVmax2．0为临界值进行半定量分析诊断具有较好的诊断价值;在诊断腋窝淋巴结转移方面,定性分析和半定量分析与病理诊均有较好的一致性。     

18F—FDGPET／CT在非小细胞肺癌纵隔淋巴结转移上的诊断价值

目的探讨PET／CT在非小细胞肺癌纵隔淋巴结转移上的诊断价值。方法对33例术前行全身18F—FDGPET／CT检查发现肺内病灶,并行根治性手术及系统纵隔淋巴结清扫患者的PET／CT图像进行分析,记录淋巴结短径、CT值、SUVmax等,同时对患者的图像进行视觉分析,应用PET／CT综合分析法对纵隔内淋巴结进行诊断,并与病理结果对照。结果常规CT法对纵隔内淋巴结诊断的准确率为84．1％,常规PET法诊断的准确率为82．8％,常规PET／CT法对纵隔内淋巴结诊断的准确率为91．7％,PET／CT综合分析法的诊断准确率为95．2％,只有5例良性淋巴结误诊为恶性。8例肺癌伴纵隔或肺门淋巴结转移,其中5例肺癌病灶位于肺野内带。结论18F—FDGPET／CT综合分析法对纵隔淋巴结诊断的准确率较高,优于常规CT、常规PET以及常规PET／CT法（）（2=15．1,P〈0．05）;肺癌病灶位于肺野内带者较易发生纵隔或肺门淋巴结的转移。     

乳腺癌腋窝淋巴结声像图联合免疫组织化学与淋巴结转移的相关性研究

背景与目的：乳腺癌腋窝淋巴结转移对于乳腺癌患者的预后及治疗方案的选择有重要的指导意义。本研究旨在探讨乳腺癌腋窝淋巴结声像图表现联合免疫组织化学与腋窝淋巴结转移的相关性。方法：回顾性分析应用超声检出的366例乳腺癌患者共计728枚腋窝淋巴结的声像图表现,采用单因素分析、多因素logistic回归及受试者工作特征(receiver operating characteristic,ROC)曲线分析的方法,分别检验乳腺癌腋窝淋巴结皮质最大厚度、长短径之比、皮髓质之比和淋巴结血流特征,联合乳腺癌术后免疫组织化学结果,研究其与病理学腋窝淋巴结转移的相关性。结果：依据单因素分析,腋窝淋巴结皮质最大厚度、长短径之比、血流特征以及乳腺癌病灶p53的阳性表达率与淋巴结转移有关(P<0.05)。依据多因素分析及ROC分析,腋窝淋巴结皮质最大厚度是判定腋窝淋巴结转移的最佳指标。腋窝淋巴结皮质最大厚度大于3 mm的患者,其乳腺癌病灶的p53阳性表达率(42.78%)明显高于皮质最大厚度小于等于3 mm的患者(25.82%),差异有统计学意义(P<0.01)。结论：乳腺癌腋窝淋巴结声像图表现联合免疫组织化学评价腋窝淋巴结转移,对乳腺癌的临床诊疗方法选择具有重要价值。     

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.     

Comparative efficacy of positron emission tomography and ultrasonography in preoperative evaluation of axillary lymph node metastases in breast cancer

PURPOSE: In primary breast cancer, axillary nodal status is the most powerful predictive factor of recurrence. However, axillary lymph node dissection may cause surgical complications. If preoperative evaluation of axillary lymph node metastases is possible, unnecessary axillary lymph node dissections can be avoided. The purpose of this study was to evaluate the efficacy of positron emission tomography (PET) on detection of axillary lymph node metastases in breast cancer. METHODS: PET scans of the axilla were obtained in 32 patients with primary breast cancer. All patients fasted for at least 4 hours before the examination. After transmission scans for attenuation correction were performed, emission scans after intravenous injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) were obtained. RESULTS: Overall accuracy of PET alone, ultrasonography alone, and in combination in the detection of axillary metastases were 82%, 79%, and 85% respectively. CONCLUSION: There were no significant differences between PET, ultrasonography, and PET in combination with ultrasonography regarding sensitivity, specificity and accuracy in the detection of axillary metastases.     

Factors influencing axillary lymph node metastasis in invasive breast cancer

Purpose: To explore the relationship between auxiliary lymph node metastasis and clinical features, andto identify the factors that affect metastasis occurrence. Methods: A total of 164 cases of primary breastcancer were selected to investigate features such as age, concomitant chronic disease and pathologic diagnosis.Immunohistochemistry was used to detect the expression of the estrogen receptor (ER) and CerbB-2. Logisticregression was employed to analyze the factors that affect the incidence of lymph node metastases. Results: Theincidence of lymph node metastases was 46.3% among elderly patients with breast cancer. Based on logisticregression, chronic disease, scale of tumor, age, and ER expression affected the occurrence of lymph nodemetastases; the ORs were 3.05, 2.18, 0.34, and 3.83, respectively. Between different pathologic diagnoses andthe risk factors, the OR scores were 12.7 and 8.02, respectively, for aggressive ductal carcinoma and aggressivelobular carcinoma auxiliary lymph node metastases. Conclusion: The incidence of lymph node metastases isaffected by chronic disease, scale of tumor, age, ER expression and pathologic diagnosis.     

Variability in axillary lymph node dissection for breast cancer

BACKGROUND: The axillary nodal status may influence the prognosis and the choice of adjuvant treatment of individual breast cancer patients. The variation in number of reported axillary lymph nodes and its effect on the axillary nodal stage were studied and the implications are discussed. METHODS: Between 1994 and 1997, a total of 4,806 axillary dissections for invasive breast cancers in 4,715 patients were performed in hospitals in the North-Netherlands. The factors associated with the number of reported nodes and the relation of this number with the nodal status and the number of positive nodes were studied. RESULTS: The number of reported nodes varied significantly between pathology laboratories, the median number of nodes ranged from 9 to 15, respectively. The individual hospitals explained even more variability in the number of nodes than pathology laboratories (range in median number 8-15, P < 0.0001). The number of reported nodes increased gradually during the study period. A decreasing trend was observed with older patient age. A higher number of reported nodes was associated with a markedly increased chance of finding tumor positive nodes, especially more than three nodes. The frequency of node positivity increased from 28% if less than six nodes to 54% if >/=20 nodes were examined, the percentage of tumors with >/=4 positive nodes increased from 4 to 31%. Multivariate analysis confirmed these results. CONCLUSIONS: This population-based study showed a large variation in the number of reported lymph nodes between hospitals. A more extensive surgical dissection or histopathological examination of the specimen generally resulted in a higher number of positive nodes. Although the impact of misclassification on adjuvant treatment will have varied, the impact with regard to adjuvant regional radiotherapy may have been considerable.     

临床腋淋巴结阳性乳腺癌患者行全腋窝淋巴结清扫的应用探讨

背景与目的:临床腋淋巴结阳性乳腺癌患者常规行全腋窝淋巴结清扫,本研究探讨改良根治术时采用改进L3组淋巴结清扫方式的临床应用及意义.方法:322例临床腋淋巴结阳性的乳腺癌患者中,154例采用改进的L3组淋巴结清扫方式,168例行常规Auchinclos改良根治术,对两种手术方式所用时间和术后不良反应进行比较,同时随访观察患者的无病生存率.结果:两种手术方式所用手术时间、术后不良反应差异无统计学意义(P＞0.05),行改进术式患者腋下淋巴结总数及L3组淋巴结数较常规术式多,两组差异有统计学意义(P＜0.05),L3组淋巴结未转移患者5年无病生存率为68.6％,L3组淋巴结转移患者5年无病生存率为35.7％,差异有统计学意义(P＜0.05).结论:对临床腋淋巴结阳性乳腺癌患者行L3组淋巴结清扫具有一定的临床应用价值,采用改进的淋巴结清扫方式,便于L3组淋巴结的清扫.     

早期乳腺癌腋淋巴结转移的多因素分析

目的：探讨早期乳腺癌腋淋巴结转移（ALNM）的相关因素,并对阴性腋淋巴结行角蛋白19（CK19）检测以发现微转移癌.方法：收集乳腺癌病例138例,建立数据库,用Logistic回归进行单因素和多因素分析,并对有意义的指标进行相关分析,对40例患者441枚阴性腋淋巴结再切片,用CK19行免疫组织化学染色.结果：多因素分析显示肿瘤大小、肿瘤部位、癌抗原153（CA153）、人类表皮生长因子受体-2（HER2）4个指标进入Logistic回归方程,40例患者中有3例患者的腋窝淋巴结CK19免疫组织化学染色阳性.结论：肿瘤大小、肿瘤部位、CA153和HER2为乳腺癌患者ALNM的高危因素;CK19免疫组织化学染色可发现乳腺癌腋淋巴结微转移癌.     

Primary tumour characteristics and axillary lymph node status in breast cancer.

This paper examines the correlation between axillary lymph node status and primary tumour characteristics in breast cancer and whether this can be used to select patients for axillary lymphadenectomy. The results are based on a retrospective analysis of 909 patients who underwent axillary dissection in our unit. Axillary lymph nodes containing metastases were found in 406 patients (44.7%), all with invasive carcinomas, but in none of the 37 carcinomas-in-situ. Nodal status was negative in all T1a tumours, but lymph node metastases were present in 16.3% and 35.7% of T1b and T1c tumours respectively. When histological grade was taken into account, positivity for grade I T1b and T1c tumours fell to 13.6% and 26.7% respectively. Lymph node metastases were found in 85% of patients with lymphovascular invasion in their tumours as compared to only 15.4% of those without and in 45.5% of oestrogen and progesterone receptor-positive tumours. When one or both hormone receptors were absent this figure was much higher. It appears that for T1a breast cancers axillary dissection is not necessary, whereas for T1b, T1c and grade I T2 tumours other histopathological parameters should be taken into consideration in deciding who should undergo axillary lymphadenectomy.     

Diagnosis of axillary lymph node metastases in patients with breast cancer

Summary The diagnosis of axillary (AX) metastases remains a challenge in the management of breast cancer and is a subject of controversy. Clinical node staging clearly is limited in the assessment of AX lymph nodes. AX mammography, ultrasonography, and computed tomography (CT) do not provide histologic information. Although nuclear magnetic resonance imaging may have considerable value in the diagnosis of AX metastases, it does not detect micrometastases. The use of biologic markers in the assessment of AX metastases remains a subject of investigation. On the other hand, biopsy of selected AX nodes or tissue with examination of histology or cytology generally would not identify a significant percentage of patients with AX node involvement. Sentinel lymph node biopsy, however, might be potentially useful for assessing AX metastases, although it remains investigational. In order to simplify diagnosis and reduce morbidity and mortality, alternatives to AX dissection must be sought and imaging and staging modalities refined. We present a review of the literature pertaining to the diagnosis of AX metastases in patients with breast cancer and a discussion of some current areas of controversy.     

Intraoperative assessment of axillary lymph node metastases in operable breast cancer

The diagnostic value of intraoperative histologic examination of frozen sections of axillary lymph nodes was investigated in 243 patients with operable breast cancer. One to six hard or enlarged axillary nodes were sampled from the axillary pad which was derived from a partial axillary dissection (including level 1 and 2 nodes). Half of these nodes were histologically examined using frozen sections during surgery. After a total axillary dissection, both the axillary nodes in the partial axillary dissection and the nodes dissected at level 3 were histologically examined on permanent section. A mean of four nodes were sampled (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60). Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients with positive axillary lymph nodes. In the patients in whom the axillary involvement was not identified by axillary sampling, however, the extent of axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary dissection may be justified for patients in whom axillary involvement is not found on frozen section of nodes from axillary sampling, whereas a total axillary dissection should be performed for patients in whom axillary involvement is found by these procedures.     

Recent advances in non-invasive axillary staging for breast cancer

Nodal staging in breast cancer is a key predictor of prognosis and directs subsequent adjuvant therapy. This article addresses current modalities of nodal staging in breast cancer but focuses on promising non-invasive alternatives for staging the axilla.     

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.     

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.     

Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a triage test in breast cancer staging

Introduction Axillary node fine needle aspiration cytology (FNAC) has the potential to triage women with operable breast cancer to initial nodal surgical procedure. Because of variability in the reported accuracy of this test its role and clinical utility in pre-operative staging remains controversial. Methods We retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all consecutive clinically T1–2 N0–1 breast cancers that had undergone this test (491 biopsies). We included subjects with clinically or sonographically indeterminate or suspicious nodes. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). Results Sensitivity of node FNAC was 72.6% (67.3–77.9) and specificity was 95.7% (92.5–98.8) for all cases, sensitivity was lower at 64.6% (59.3–70.0) if inadequate cytology was included as a negative result. FNAC sensitivity was highest in women with clinically suspicious nodes [92.5% (88.2–96.7)] and lowest in women with sonographically abnormal and clinically negative nodes [50.0% (41.3–58.7)]. Specificity was high in both groups, 81.2% (54.5–96.0) and 97.2% (94.6–99.9), respectively. The false-negative rate was 15.3% (12.1–18.5), the false-positive rate was 1.4% (0.4–2.5), and the inadequacy rate was 10.8% (8.0–13.5). The likelihood of node FNAC being positive was significantly associated with tumour grade and stage, and the number of nodes involved with metastases. Discussion Our data show that axillary FNAC has moderate sensitivity (which varies according to selection criteria for the test) and consistently high specificity, is associated with low inadequacy and very few false positives. We estimate that its use would have improved triage to initial nodal procedure in about one quarter of our cases. If one accepts the premise that initial surgical staging of the axilla should be based on all information available through pre-operative diagnosis, then axillary FNAC should be adopted routinely into clinical practice.     

FDG PET对非小细胞肺癌纵隔淋巴结分期的价值

目的 评价FDGPET显像对非小细胞肺癌(NSCLC)纵隔淋巴结分期的价值。方法 对70例经病理证实为NSCLC的病例进行FDGPET显像，以纵隔淋巴结FDG摄取增高及SUV≥2．5作为阳性判断标准，进行纵隔淋巴结分期，并与CT结果比较。结果 PET对纵隔淋巴结转移诊断的灵敏度、特异性和准确率分别为100％、93％和94％。且阳性淋巴结数目和部位与病理结果完全符合，使12例术前临床分期得以纠正。CT的灵敏度、特异性和准确率分别为70％、77％和76％。结论 PET对NSCLC纵隔淋巴结的准确分期有很高的应用价值，有助于指导临床治疗方案的制定。