New CT criteria for nodal staging in non-small cell lung cancer Satoshi Kudo, Kazuhiro Imai, Kouichi Ishiyama, Manabu Hashimoto, Hajime Saito, Satoru Motoyama, Yusuke Sato, Shinogu Takashima, Katsuyuki Murata, Yoshihiro Minamiya PII: DOI: Reference:
S0899-7071(14)00054-0 doi: 10.1016/j.clinimag.2014.02.008 JCT 7575
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
5 December 2013 25 January 2014 10 February 2014
Please cite this article as: Kudo Satoshi, Imai Kazuhiro, Ishiyama Kouichi, Hashimoto Manabu, Saito Hajime, Motoyama Satoru, Sato Yusuke, Takashima Shinogu, Murata Katsuyuki, Minamiya Yoshihiro, New CT criteria for nodal staging in non-small cell lung cancer, Journal of Clinical Imaging (2014), doi: 10.1016/j.clinimag.2014.02.008
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Title: New CT Criteria for Nodal Staging in Non-Small Cell Lung Cancer
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Satoshi Kudo1, Kazuhiro Imai1, Kouichi Ishiyama2, Manabu Hashimoto2, Hajime Saito1, Satoru Motoyama1, Yusuke Sato1, Shinogu Takashima1, Katsuyuki Murata3, and Yoshihiro Minamiya1 1 Department of General Thoracic Surgery (and Breast & Endocrine Surgery), of Integrated Medicine, Division of Radiology and Radiation Medicine, 3 Department of Environmental Health Sciences, Akita University Graduate School of Medicine, 1-1-1 Hondo Akita City 010-8543, Japan
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2 Department
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Running Title: New CT Criteria for Nodal Staging in NSCLC Disclosures: The authors have no financial conflict of interest. Word Count of text (excluding references): 3155 words, abstract: 237 words, concise abstract 86 words, 2 figures, 4 Table, 32 references.
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Kazuhiro Imai, MD PhD (Corresponding author) Department of General Thoracic Surgery (and Breast & Endocrine Surgery), Akita University Graduate School of Medicine 1-1-1 Hondo, Akita City 010-8543, Japan Telephone: +81-18-884-6132 Fax: +81-18-836-2615
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E-mail: [email protected]
Abstract Objective: The purpose of our study was to develop a simple noninvasive technique for nodal staging using routine preoperative CT. Materials and Methods: The institutional review board approved this retrospective study, and written informed
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consent to perform the initial and follow-up CT studies was obtained from all patients.
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Preoperative CT findings (n=218 patients with resectable non-small cell lung cancer)
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and pathological diagnoses after surgical resection were evaluated. Using CT images, lymph node section area, circumference and lesion attenuation values (LAVs) were
caliper software.
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drawn freehand, and the short axis (SA) and long axis (LA) were measured using Receiver operating characteristic (ROC) curves were then used to
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analyze the section area, circumference and LAVs. Results:
Based on ROC curves, two cut-off values, lymph node section area >30 mm2 and circumference >25 mm, showed greater sensitivity for nodal staging than the
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conventional criterion of lymph node SA ≥10 mm, or the LA, SA/LA ratio or LAVs.
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Using lymph node section area >30 mm2 for diagnosis, the sensitivity, specificity and accuracy of nodal staging were 90.5%, 56.3% and 58.3%, respectively.
Using lymph
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Conclusion:
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node circumference >25 mm, the values were 76.2%, 70.4% and 70.8%, respectively.
Lymph node section area >30 mm2 and circumference >25 mm can serve as supportive criteria used by radiologists and surgeons to determine nodal staging.
If these CT
criteria are met, use of a more sensitive procedure such as positron emission tomography or mediastinoscopy is recommended.
Concise abstract CT is used routinely during preoperative management of lung cancer.
Based on
receiver operating characteristic analyses, the cut-off values for surface area, circumference, the short axis / the long axis ratio and lesion attenuation values for
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diagnosis of lymph node metastasis were 30 mm2, 25 mm, 0.65 and 50 Hounsfield units, Our findings indicate that a lymph node surface area >30 mm2 and
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respectively.
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circumference >25 mm are supportive criteria that can be used by radiologists and
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thoracic surgeons to determine nodal staging and surgical indications.
Keywords
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computed tomography; lung cancer; lymph node; metastasis
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Introduction
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Lung cancer accounts for the largest number of cancer-related deaths among both men and women, worldwide [1–4]. It is estimated that, in 2010, 116,750 men and
from the disease [2].
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105,770 women were diagnosed with lung cancer, and 157,300 men and women died Nonetheless, when non-small cell lung cancer (NSCLC) is
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treated surgically at an early stage (Stage I or II), patients have a favorable prognosis [3] [4]. Surgical resection is therefore the accepted standard of care for patients with NSCLC. However, only about 25% of NSCLC patients are eligible for surgery [5],
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and once the surgical candidates are selected, mediastinal staging is mandatory because up to 50% of these patients have regional metastasis [6]. Patients with advanced lung
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cancer, especially N2 lymph node metastasis, are treated non-surgically using multiple technique therapy, whereas patients with distant metastasis at diagnosis often receive
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palliative chemotherapy to improve their quality of life [7].
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The various diagnostic techniques and procedures used for preoperative staging of NSCLC include computed tomography (CT), magnetic resonance imaging (MRI), bronchoscopy, mediastinoscopy, thoracoscopy and 18F-2-deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET).
Among these, chest CT is currently the
most sensitive and specific imaging method for assessing focal and diffuse lung disease, including lung cancer.
Moreover, spiral CT enables multiplanar and three-dimensional
display of structures and visualization of pulmonary and systemic vessels at a level of detail that is comparable to conventional angiography [8]. Consequently, the vast majority of lung cancer patients undergo only chest CT. This is despite the fact that although CT scan is useful in determining the characteristics of the primary tumor, in
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some cases the evaluation of invasion to pleura, mediastinum and chest wall is limited,
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and that accurate mediastinal staging is crucial for determining the best approach to
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treating lung cancers [9, 10]. Thus, while CT offers useful information for staging patients with NSCLC, the accuracy of CT staging is imperfect [11, 12].
This
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highlights the importance of knowing the capabilities and limitations of a diagnostic technique when triaging patients for therapy or further diagnostic testing.
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Evaluation of nodal status using CT is limited because CT provides only presumptive evidence of metastatic disease, which is interpreted on the basis of size criteria. Traditionally, lymph node metastasis is diagnosed when the short axis (SA) of a node is
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10 mm or larger on axial images [9, 11, 12], but malignant lymph nodes may be smaller than 10 mm, which explains the limited sensitivity of conventional CT (~57%) [13].
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Numerous studies have used the ≥10 mm node size criterion and images acquired with up to fourth-generation CT scanners to assess the ability of CT to accurately detect
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mediastinal lymph node metastasis.
The reported accuracies vary widely, ranging
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from 75% to 83% [14]. According to a surgically verified meta-analysis of CT for the mediastinal staging of NSCLC, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the technique are 33%-75%, 66%-90%, 64%-79%, 46%-55% and 68%-85%, respectively [15].
Two other
meta-analyses concluded that no additional significant advances were to be expected from CT, and meta-analytic comparison of PET and CT concluded that PET was significantly more accurate than CT for characterization of mediastinal lymph nodes [14, 16]. The main disadvantage of CT is that it only depicts the size and shape of the nodes; it does not depict the actual tumor involvement. As a result, the presence of micrometastasis in small nodes may lead to false-negatives, and large nodes may
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contain only inflammatory cells, leading to false-positives.
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In our earlier retrospective report [17], we examined 1.25 mm-5 mm thin slice images
staging based on lymph node size.
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obtained with chest CT from resectable NSCLC patients and reported new criteria for The sensitivity, specificity, and accuracy in our
SA was ≥ 9mm.
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study were 56.3%, 92.1%, and 88.1%, respectively, when the LA was ≥ 13 mm and the And the sensitivity, specificity and accuracy were 75.0%, 74.7% and
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74.7%, respectively, when the long axis (LA) was ≥13 mm or the SA was ≥9 mm. These values were superior to those obtained using the conventional criterion (node size ≥10 mm), and the findings suggested that if the lymph node LA is ≥13 mm, a more
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sensitive procedure, such as PET or invasive mediastinoscopy, should be recommended. The purpose of the present study was to develop a simple noninvasive technique for
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nodal staging using routine preoperative CT.
Patients
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Materials and Methods
The institutional review board approved this retrospective study.
In addition,
written informed consent to perform the initial and follow-up CT studies was obtained from all patients.
CT findings and pathological records for patients treated between
January 2009 and July 2012 were retrospectively reviewed. Selected for study were cases that included preoperative 1.25-mm axial section slices obtained with CT and lymph node measurements depicted as a single lesion. exploratory thoracotomy were excluded.
Any cases involving
One pathological Stage IV patient was
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performed radical lobectomy because of single brain metastasis.
In total, 218 patients
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who had undergone major pulmonary resections for NSCLC were enrolled in the study.
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All lymph nodes in the mediastinum/hilum of the patients were measured.
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patients’ characteristics are listed in Table 1.
The
Conventional Criteria and Classification of Lymph Node Metastasis using CT
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For evaluation using CT, tumor size, lymph nodes and staging were classified based on the location (i.e., mediastinal or hilar) and the 7th edition of the Union Internationale Contre le Cancer (UICC)-TNM staging system [18]. The conventional criterion used
images [9, 12, 19].
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for determining lymph node metastasis on CT was a SA of 10 mm or larger on axial An expert radiologist evaluated lymph nodes metastasis using CT In addition, an
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imaging based on the conventional criteria before the present study.
expert thoracic surgeon evaluated randomly selected lymph nodes for metastasis based
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on a criterion of lymph node LA ≥13 mm [17].
CT Measurements of Lymph Node SA, LA, Section area, Circumference, and LAVs Chest imaging was performed using a CT scanner (Light Speed VCT, GE Healthcare, Milwaukee, Wis); the scanning parameters were 120 kVp and auto mA.
In each
patient, 80 mL of contrast material (Iopamiron, 350 mg iodine per mL; Bayer Schering, Berlin, Germany) was administered intravenously at a rate of 4 mL/s.
CT images were
then obtained as 5.0-1.25-mm axial sections at 0.625-mm intervals using a high-spatial-frequency algorithm.
All images were displayed at window settings for
lung (center, −700 Hounsfield units (HU); width, 1800 HU) and soft tissue (center, 45 HU; width, 320 HU). Using the CT images at the same settings as were used for
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conventional image reading, the section area, circumference, and LAVs of the lymph
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nodes were drawn freehand, and the SA and LA of the lymph nodes were measured
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using caliper software (Figure 1). The single lymph node image that provided all of these values was used for analysis, and the SA/LA ratio was calculated.
Lengths of the
expressed in square millimeters.
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SA and LA and the circumference are all expressed in millimeters. Section area is LAVs is expressed in HU.
For all resected patients
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with NSCLC, three of the authors, including an experienced radiologist, each separately evaluated the CT images while blinded to the lymph node SA, LA, section area, circumference and LAVs.
All CT images were measured by measurers, who were However, precise correspondence between lymph
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unaware of clinical information.
nodes on imaging and at surgery is a difficult problem if several lymph nodes were So, all lymph nodes on CT were measured in each node
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sampled in the same station.
station and the longest node by measuring the SA was selected in the present study.
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Two observers were told the purpose of the study was to compare methods for
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distinguishing lymph node metastasis on CT images, and that 705 lesions were included in the study; no information was given regarding the stage of the malignancy or lymph node metastasis.
Surgery In general, NSCLC was treated with segmentectomy or lobectomy plus systematic nodal dissection. Even in cases of extensive nodal involvement, complete resection was attempted. Complete resection was defined as both macroscopic and microscopic tumor-free margins.
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Pathological Evaluation
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Two independent pathologists evaluated samples of dissected tissue. All dissected
hematoxylin-eosin staining.
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tumors and lymph nodes were sectioned and examined conventionally using Lymph node metastasis was judged in each node station.
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If there are one or more metastatic nodes in the station, we judged that a lymph node on
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CT imaging was malignant.
Statistics
Group data were expressed as means ± standard deviation.
Differences between the
measured parameters of metastatic and non-metastatic lymph nodes were examined
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using the Welch’s t test. The ROC curves were used to determine the cut-off values
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that yielded the highest combined sensitivity and specificity with respect to distinguishing metastatic lymph nodes. The areas under ROC curves (AUC) were
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compared using the method described by Hanley and McNeil [20]. The sensitivity,
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specificity, PPV, NPV, accuracy and AUC were all calculated using standard formulas with a 2 × 2 table of the collected data. considered significant.
For all tests, values of p < 0.05 were
JMP IN 8.0.2 software (SAS Institute, Cary, NC, USA) was
used for all statistical evaluations and for drawing the ROC curves.
Results CT was used to measure 192 hilar lymph nodes and 513 mediastinal lymph nodes. The SA, LA, section area, circumference and LAVs of the metastatic lymph nodes were always significantly larger than those of the non-metastatic nodes (Table 2).
To
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determine the cut-off values that yielded the highest combined sensitivity and
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specificity with respect to distinguishing metastatic from non-metastatic lymph nodes,
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conventional ROC curves were used to analyze the measured parameters (Figure 2). From these analyses, we determined the cut-off values for section area, circumference,
HU, respectively.
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SA/LA ratio and LAVs for lymph node metastasis to be 30 mm2, 25 mm, 0.65 and 50 The thresholds obtained from the ROC curves as well as the
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sensitivity, specificity, PPV, NPV and accuracy are all summarized in Table 3. A section area cut-off value of >30 mm2 or a circumference cut-off of >25 mm best distinguished between metastatic and non-metastatic lymph nodes.
When the SA
cut-off value of ≥10 mm was used for diagnosis of lymph node metastasis, the
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sensitivity, specificity, PPV, NPV, and accuracy were 28.6% (12 of 42), 98.0% (650 of
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663), 48.0% (12 of 25), 95.6% (650 of 680), and 93.9% (662 of 705), respectively. When the LA cut-off value of ≥13 mm was used for diagnosis, the sensitivity, specificity,
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PPV, NPV, and accuracy were 45.2% (19 of 42), 91.1% (604 of 663), 24.4% (19 of 78),
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96.3% (604 of 627), and 88.4% (623 of 705), respectively. When the section area cut-off value of >30 mm2 was used for diagnosis, the sensitivity, specificity, PPV, NPV, accuracy and AUC were 90.5% (38 of 42), 56.3% (373 of 663), 11.6% (38 of 328), 98.9% (373 of 377), 58.3% (411 of 705) and 0.813, respectively.
When the
circumference cut-off value of >25 mm was used for diagnosis, the values were 76.2% (32 of 42), 70.4% (467 of 663), 14.0% (32 of 228), 97.9% (467 of 477), 70.8% (499 of 705) and 0.812, respectively.
This represents a substantial improvement over the
sensitivity obtained by radiologists using the conventional criteria, as well as over the values reported in our earlier retrospective review. Table 4a shows the sensitivity, specificity, PPV, NPV and accuracy for diagnosis when the section area of a mediastinal
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or hilar lymph node is greater than 30 mm2. The values for mediastinal nodes were
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87.5% (14 of 16), 61.6% (306 of 497), 6.8% (14 of 205), 99.4% (306 of 308) and 62.4%
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(320 of 513), respectively, while the values for hilar nodes were 87.0% (20 of 23), 45.8% (76 of 166), 18.2% (20 of 110), 96.2% (76 of 79) and 50.8% (96 of 189), Table 4b shows the sensitivity, specificity, PPV, NPV, accuracy for
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respectively.
diagnosis when the circumference of a mediastinal or hilar lymph node is greater than
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25 mm. The values for mediastinal nodes were 81.8% (13 of 16), 72.2% (359 of 497), 8.6% (13 of 151), 99.2% (359 of 362) and 72.5% (372 of 513), respectively, while the values for hilar nodes were 73.9% (17 of 23), 65.7% (109 of 166), 23.0% (17 of 74),
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94.8% (109 of 115) and 66.7% (126 of 189), respectively.
Discussion
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Our findings indicate that a lymph node section area >30 mm2 or a circumference >25
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mm can be effective criteria for use by radiologists and thoracic surgeons to determine nodal staging and surgical indications. Using those cut off values, we achieved greater sensitivity than was achieved by experienced radiologists using conventional criteria. Accurate clinical staging of the mediastinal lymph nodes is essential for determining the best approach to treatment, therapeutic options and prognoses.
From our experience
with CT, we suggest that if a lymph node section area is >30 mm2 or the circumference is >25 mm, a more sensitive procedure, such as PET or mediastinoscopy, is indicated. Many have used an SA cutoff value of ≥10 mm to demonstrate the accuracy of CT for nodal staging in lung cancer.
It is noteworthy, however, that malignant lymph nodes
may be smaller than 10 mm. This explains the limited sensitivity and specificity of CT
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[14, 16, 17, 21–23]. The main disadvantage of CT is that it only depicts the size and
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shape of the nodes; it does not depict the actual tumor involvement. Consequently, the
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presence of micrometastasis in small nodes may lead to false-negatives, and large nodes may contain only inflammatory cells, leading to false-positives. Furthermore, the vast
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majority of patients undergo only chest CT, although CT is notoriously inaccurate for T and N staging in many situations, and accurate mediastinal staging is crucial for
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determining the best approach to treatment in lung cancer [9, 10]. The sensitivity, specificity and accuracy for diagnosis were 87.5%, 61.6%, 62.4%, respectively when the section area of a mediastinal lymph node was greater than 30 mm2, and were 81.8%,
greater than 25 mm.
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72.2%, 72.5%, respectively, when the circumference of a mediastinal lymph node was Use of these criteria to determine mediastinal lymph node
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metastasis provides a greater degree of sensitivity and more accurate nodal staging than do conventional criteria.
Moreover, the mean LAVs of metastatic lymph nodes on
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enhanced CT images (57.6 ± 16.9 HU) were significantly greater than those of
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non-metastatic lymph nodes. However, the sensitivity, specificity and accuracy of LAVs were low and not available to determine nodal staging.
Nonetheless, the
absence of LAVs 30 mm2 or circumference >25 mm) is that the PPV is lower than was achieved using SA ≥10 mm or LA ≥13 mm. This is because the number of metastatic lymph nodes in the resected NSCLC patients was only 0.03% (99 of 3228 dissected lymph nodes).
When the prevalence of preclinical
disease is low, the PPV will also be low, even when using a test with high sensitivity and specificity. To increase the PPV of the new criteria, a program could target those
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at high risk of developing the lymph node metastasis, based on considerations such as For example, the new
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the presence of a large lung tumor and progressive T staging.
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criteria (section area >30 mm2 or circumference >25 mm) would be recommended for NSCLC patients showing lymph node uptake of FDG on PET/CT, as that is a
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population with a higher prevalence of lymph node metastasis.
Another limitation is
that the section area and circumference were drawn freehand, and the inter and intra However, the time that takes to obtain the
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observer variability was not evaluated.
section area and circumference is about 3-5 seconds. We believe that the time using new procedure in the present study is not significant difference in comparison with the conventional measurement of the short axis for lymph nodes.
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N staging using PET/CT is better than with PET or CT alone [21-25]. The benefit of
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PET/CT for N staging appears to lie in the moderate increases in specificity and PPV, which stems from the improved accuracy of the anatomical information [24, 25]. In a
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prospective comparison of the abilities of CT and PET/CT to detect malignant nodes,
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the sensitivity, specificity and accuracy of CT were 70%, 69% and 69%, respectively, while those of PET-CT were 85%, 84% and 84% [24]. It was also found that the post-test probability for N2 disease was 5% among patients with lymph nodes measuring 10-15 mm on CT and having a negative FDG-PET result.
This suggests
these patients should be scheduled for thoracotomy because the yield from mediastinoscopy will be very low. On the other hand, for patients with lymph nodes measuring >16 mm on CT and a negative FDG-PET result, the post-test probability for N2 disease was 21%, suggesting unnecessary thoracotomies could be prevented in these patients by first scheduling a mediastinoscopy.
Taken together, these findings indicate
the utility of FDG-PET for diagnosing lymph node metastasis is limited because
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standard uptake values for FDG-PET are affected by lymph node size [26].
Other
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limitations on FDG-PET for evaluation of lymph nodes are false-positives due to uptake
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of FDG into sites of inflammation and granulomatous disease (e.g., tuberculosis, aspergillosis and sarcoidosis), leading to a reduction in specificity, and false-negatives
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for very small tumors or those with low FDG uptake (e.g., low-metabolism tumors such as bronchioloalveolar carcinomas and carcinoid tumors).
The addition of FDG-PET
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scanning to the conventional work-up has reportedly changed management in 20%-30% of patients with NSCLC, mostly by upstaging the disease [27, 28].
Further
investigation will be needed to more precisely define the relation between SA, LA,
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section area and circumference on CT and FDG uptake on PET. Recent advances in CT technology have allowed investigation of novel methods
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for the evaluation of lung cancers including volumetry, perfusion analysis, dual-energy applications and computer-aided detection [29].
Three-dimensional (3D) volumetric
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measurements are moreaccurate and reproducible than two-dimensional measurements
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and are increasingly used in lung cancer screening programs [30] [31] [32]. Takahashi et al. reported optimal 76% accuracy was obtained with a criterion of 3D volume of >1282 mm3 or CT values of >103 HU for the 30 mm2 or circumference >25 mm, we achieved a higher performance level than is
are supportive criteria that can be used by radiologists and thoracic surgeons to If these CT criteria are met, use of a
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determine nodal staging and surgical indications.
more sensitive procedure such as positron emission tomography or mediastinoscopy is
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recommended.
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[27] Weng E, Tran L, Rege S, Safa A, Sadeghi A, Juillard G, Mark R, Santiago S, Brown C, Mandelkern M. Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol 2000; 23(1):47–52. [28] Changlai SP, Tsai SC, Chou MC, Ho YJ, Kao CH. Whole body 18 F-2-deoxyglucose positron emission tomography to restage non-small cell lung cancer. Oncol Rep 2001;8(2): 337–339. [29] Lee WK, Lau EW, Chin K, Sedlaczek O, Steinke K. Modern diagnostic and therapeutic interventional radiology in lung cancer. J Thorac Dis. 2013;5(Suppl 5):S511–S523. [30] Fabel M, von Tengg-Kobligk H, Giesel FL, Bornemann L, Dicken V, Kopp-Schneider A, Moser C, Delorme S, Kauczor HU. Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV--a feasibility study. Eur Radiol. 2008;18(6):1114–1122. [31] Wang Y, de Bock GH, van Klaveren RJ, van Ooyen P, Tukker W, Zhao Y, Dorrius MD, Proença RV, Post WJ, Oudkerk M. Volumetric measurement of pulmonary nodules at low-dose chest CT: effect of reconstruction setting on measurement variability. Eur Radiol. 2010;20(5):1180–1187. [32] Takahashi Y, Takashima S, Hakucho T, Miyake C, Morimoto D, Jiang BH,
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Numasaki H, Tomita Y, Nakanishi K, Higashiyama M. Diagnosis of regional node metastases in lung cancer with computer-aided 3D measurement of the volume and CT-attenuation values of lymph nodes. Acad Radiol. 2013;20(6):740–745.
Figure 1
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Figure Legends
Measurement of lymph nodes on CT images.
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The long and short axes, section area, circumference and lesion attenuation values of lymph nodes were measured on the computer screen using caliper software. (a) Example of a mediastinal lymph node
Figure 2
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(b) Example of a hilar lymph node
Receiver operating characteristic (ROC) curves for detection of lymph
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node metastasis using CT.
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Panels a-d depict the ROC curves for section area, circumference, SA/LA ratio, and lesion attenuation values for all lymph nodes.
The thresholds obtained based on the
ROC curves for sensitivity, specificity, positive predictive value, negative predictive value and accuracy are summarized in Table 3.
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Figure 1b
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Figure 2b
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Figure 2
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N0 N1 N2 N0 N1 N2
192 14 12 181 22 15
(mm) Mean Range Type adeno squamous others Dissected lymph node Met (+) Met (–)
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Tumor size
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Tumor location RUL RML
RLL LUL LLL RUML RMLL RUMLL LULL Pathological stage IA IB
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80
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pN status
Female
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Nodal status cN status
218 69.4±9.60 67.0±10.2 138
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No. of patients Age Male Female Sex Male
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Table 1. Patient characteristics
29.9 ± 19.3 4 – 120 162 43 13 3327 99 3228
IIA IIB IIIA IIIB IV
64 15 55 51 26 2 1 1 3 115 47 17 17 18 2 2
RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; adeno, adenocarcinoma; squamous, squamous cell carcinoma
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Measurement of the LA, SA, surface area, circumference, SA/LA ratio,
and LAVs of metastatic lymph nodes
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Table 2.
Mets (+) 42
Mets (–) 663
SA (mm)
8.27 ± 3.81
4.97 ± 1.95
< 0.001
LA (mm) Surface area (mm2) Circumference (mm) SA/LA ratio LAVs (HU)
12.6 ± 4.32 81.2 ± 68.5 34.3 ± 12.5 0.66 ± 0.14 57.6 ± 16.9
8.11 ± 3.09 32.3 ± 23.4 21.9 ± 8.00 0.64 ± 0.31 45.7 ± 28.3
< 0.001 < 0.001 < 0.001 0.602 30 mm2 90.5 56.3 11.6 98.9
Circumference >25 mm 76.2 70.4 14.0 97.9
SA/LA ratio >0.65 52.4 60.6 7.8 95.3
LAVs >50 HU 73.8 52.0 8.9 96.9
Accuracy (%)
93.9
88.4
58.3
70.8
60.1
53.3
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Method
PPV, positive predictive value; NPV, negative predictive value; SA, short axis; LA, long axis; LAVs; lesion attenuation values;
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Diagnosis of mediastinal or hilar lymph node metastasis based on
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Table 4a.
Surface area >30 mm2
Surface area >30 mm2
87.5 61.6 62.4
Diagnosis of mediastinal or hilar lymph node metastasis based on
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circumference >25 mm
Method
87.0 45.8 50.8
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Table 4b.
Hilum
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Sensitivity (%) Specificity (%) Accuracy (%)
Mediastinum
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Method
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surface area >30 mm2
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Sensitivity (%) Specificity (%) Accuracy (%)
Mediastinum
Hilum
Circumference >25 mm 81.3 72.2 72.5
Circumference >25 mm 73.9 65.7 66.7
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S0899-7071(14)00054-0 doi: 10.1016/j.clinimag.2014.02.008 JCT 7575
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
5 December 2013 25 January 2014 10 February 2014
Please cite this article as: Kudo Satoshi, Imai Kazuhiro, Ishiyama Kouichi, Hashimoto Manabu, Saito Hajime, Motoyama Satoru, Sato Yusuke, Takashima Shinogu, Murata Katsuyuki, Minamiya Yoshihiro, New CT criteria for nodal staging in non-small cell lung cancer, Journal of Clinical Imaging (2014), doi: 10.1016/j.clinimag.2014.02.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title: New CT Criteria for Nodal Staging in Non-Small Cell Lung Cancer
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Satoshi Kudo1, Kazuhiro Imai1, Kouichi Ishiyama2, Manabu Hashimoto2, Hajime Saito1, Satoru Motoyama1, Yusuke Sato1, Shinogu Takashima1, Katsuyuki Murata3, and Yoshihiro Minamiya1 1 Department of General Thoracic Surgery (and Breast & Endocrine Surgery), of Integrated Medicine, Division of Radiology and Radiation Medicine, 3 Department of Environmental Health Sciences, Akita University Graduate School of Medicine, 1-1-1 Hondo Akita City 010-8543, Japan
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2 Department
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Running Title: New CT Criteria for Nodal Staging in NSCLC Disclosures: The authors have no financial conflict of interest. Word Count of text (excluding references): 3155 words, abstract: 237 words, concise abstract 86 words, 2 figures, 4 Table, 32 references.
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Kazuhiro Imai, MD PhD (Corresponding author) Department of General Thoracic Surgery (and Breast & Endocrine Surgery), Akita University Graduate School of Medicine 1-1-1 Hondo, Akita City 010-8543, Japan Telephone: +81-18-884-6132 Fax: +81-18-836-2615
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E-mail: [email protected]
Abstract Objective: The purpose of our study was to develop a simple noninvasive technique for nodal staging using routine preoperative CT. Materials and Methods: The institutional review board approved this retrospective study, and written informed
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consent to perform the initial and follow-up CT studies was obtained from all patients.
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Preoperative CT findings (n=218 patients with resectable non-small cell lung cancer)
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and pathological diagnoses after surgical resection were evaluated. Using CT images, lymph node section area, circumference and lesion attenuation values (LAVs) were
caliper software.
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drawn freehand, and the short axis (SA) and long axis (LA) were measured using Receiver operating characteristic (ROC) curves were then used to
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analyze the section area, circumference and LAVs. Results:
Based on ROC curves, two cut-off values, lymph node section area >30 mm2 and circumference >25 mm, showed greater sensitivity for nodal staging than the
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conventional criterion of lymph node SA ≥10 mm, or the LA, SA/LA ratio or LAVs.
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Using lymph node section area >30 mm2 for diagnosis, the sensitivity, specificity and accuracy of nodal staging were 90.5%, 56.3% and 58.3%, respectively.
Using lymph
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Conclusion:
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node circumference >25 mm, the values were 76.2%, 70.4% and 70.8%, respectively.
Lymph node section area >30 mm2 and circumference >25 mm can serve as supportive criteria used by radiologists and surgeons to determine nodal staging.
If these CT
criteria are met, use of a more sensitive procedure such as positron emission tomography or mediastinoscopy is recommended.
Concise abstract CT is used routinely during preoperative management of lung cancer.
Based on
receiver operating characteristic analyses, the cut-off values for surface area, circumference, the short axis / the long axis ratio and lesion attenuation values for
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diagnosis of lymph node metastasis were 30 mm2, 25 mm, 0.65 and 50 Hounsfield units, Our findings indicate that a lymph node surface area >30 mm2 and
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respectively.
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circumference >25 mm are supportive criteria that can be used by radiologists and
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thoracic surgeons to determine nodal staging and surgical indications.
Keywords
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computed tomography; lung cancer; lymph node; metastasis
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Introduction
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Lung cancer accounts for the largest number of cancer-related deaths among both men and women, worldwide [1–4]. It is estimated that, in 2010, 116,750 men and
from the disease [2].
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105,770 women were diagnosed with lung cancer, and 157,300 men and women died Nonetheless, when non-small cell lung cancer (NSCLC) is
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treated surgically at an early stage (Stage I or II), patients have a favorable prognosis [3] [4]. Surgical resection is therefore the accepted standard of care for patients with NSCLC. However, only about 25% of NSCLC patients are eligible for surgery [5],
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and once the surgical candidates are selected, mediastinal staging is mandatory because up to 50% of these patients have regional metastasis [6]. Patients with advanced lung
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cancer, especially N2 lymph node metastasis, are treated non-surgically using multiple technique therapy, whereas patients with distant metastasis at diagnosis often receive
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palliative chemotherapy to improve their quality of life [7].
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The various diagnostic techniques and procedures used for preoperative staging of NSCLC include computed tomography (CT), magnetic resonance imaging (MRI), bronchoscopy, mediastinoscopy, thoracoscopy and 18F-2-deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET).
Among these, chest CT is currently the
most sensitive and specific imaging method for assessing focal and diffuse lung disease, including lung cancer.
Moreover, spiral CT enables multiplanar and three-dimensional
display of structures and visualization of pulmonary and systemic vessels at a level of detail that is comparable to conventional angiography [8]. Consequently, the vast majority of lung cancer patients undergo only chest CT. This is despite the fact that although CT scan is useful in determining the characteristics of the primary tumor, in
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some cases the evaluation of invasion to pleura, mediastinum and chest wall is limited,
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and that accurate mediastinal staging is crucial for determining the best approach to
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treating lung cancers [9, 10]. Thus, while CT offers useful information for staging patients with NSCLC, the accuracy of CT staging is imperfect [11, 12].
This
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highlights the importance of knowing the capabilities and limitations of a diagnostic technique when triaging patients for therapy or further diagnostic testing.
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Evaluation of nodal status using CT is limited because CT provides only presumptive evidence of metastatic disease, which is interpreted on the basis of size criteria. Traditionally, lymph node metastasis is diagnosed when the short axis (SA) of a node is
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10 mm or larger on axial images [9, 11, 12], but malignant lymph nodes may be smaller than 10 mm, which explains the limited sensitivity of conventional CT (~57%) [13].
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Numerous studies have used the ≥10 mm node size criterion and images acquired with up to fourth-generation CT scanners to assess the ability of CT to accurately detect
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mediastinal lymph node metastasis.
The reported accuracies vary widely, ranging
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from 75% to 83% [14]. According to a surgically verified meta-analysis of CT for the mediastinal staging of NSCLC, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the technique are 33%-75%, 66%-90%, 64%-79%, 46%-55% and 68%-85%, respectively [15].
Two other
meta-analyses concluded that no additional significant advances were to be expected from CT, and meta-analytic comparison of PET and CT concluded that PET was significantly more accurate than CT for characterization of mediastinal lymph nodes [14, 16]. The main disadvantage of CT is that it only depicts the size and shape of the nodes; it does not depict the actual tumor involvement. As a result, the presence of micrometastasis in small nodes may lead to false-negatives, and large nodes may
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contain only inflammatory cells, leading to false-positives.
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In our earlier retrospective report [17], we examined 1.25 mm-5 mm thin slice images
staging based on lymph node size.
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obtained with chest CT from resectable NSCLC patients and reported new criteria for The sensitivity, specificity, and accuracy in our
SA was ≥ 9mm.
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study were 56.3%, 92.1%, and 88.1%, respectively, when the LA was ≥ 13 mm and the And the sensitivity, specificity and accuracy were 75.0%, 74.7% and
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74.7%, respectively, when the long axis (LA) was ≥13 mm or the SA was ≥9 mm. These values were superior to those obtained using the conventional criterion (node size ≥10 mm), and the findings suggested that if the lymph node LA is ≥13 mm, a more
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sensitive procedure, such as PET or invasive mediastinoscopy, should be recommended. The purpose of the present study was to develop a simple noninvasive technique for
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nodal staging using routine preoperative CT.
Patients
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Materials and Methods
The institutional review board approved this retrospective study.
In addition,
written informed consent to perform the initial and follow-up CT studies was obtained from all patients.
CT findings and pathological records for patients treated between
January 2009 and July 2012 were retrospectively reviewed. Selected for study were cases that included preoperative 1.25-mm axial section slices obtained with CT and lymph node measurements depicted as a single lesion. exploratory thoracotomy were excluded.
Any cases involving
One pathological Stage IV patient was
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performed radical lobectomy because of single brain metastasis.
In total, 218 patients
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who had undergone major pulmonary resections for NSCLC were enrolled in the study.
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All lymph nodes in the mediastinum/hilum of the patients were measured.
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patients’ characteristics are listed in Table 1.
The
Conventional Criteria and Classification of Lymph Node Metastasis using CT
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For evaluation using CT, tumor size, lymph nodes and staging were classified based on the location (i.e., mediastinal or hilar) and the 7th edition of the Union Internationale Contre le Cancer (UICC)-TNM staging system [18]. The conventional criterion used
images [9, 12, 19].
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for determining lymph node metastasis on CT was a SA of 10 mm or larger on axial An expert radiologist evaluated lymph nodes metastasis using CT In addition, an
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imaging based on the conventional criteria before the present study.
expert thoracic surgeon evaluated randomly selected lymph nodes for metastasis based
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on a criterion of lymph node LA ≥13 mm [17].
CT Measurements of Lymph Node SA, LA, Section area, Circumference, and LAVs Chest imaging was performed using a CT scanner (Light Speed VCT, GE Healthcare, Milwaukee, Wis); the scanning parameters were 120 kVp and auto mA.
In each
patient, 80 mL of contrast material (Iopamiron, 350 mg iodine per mL; Bayer Schering, Berlin, Germany) was administered intravenously at a rate of 4 mL/s.
CT images were
then obtained as 5.0-1.25-mm axial sections at 0.625-mm intervals using a high-spatial-frequency algorithm.
All images were displayed at window settings for
lung (center, −700 Hounsfield units (HU); width, 1800 HU) and soft tissue (center, 45 HU; width, 320 HU). Using the CT images at the same settings as were used for
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conventional image reading, the section area, circumference, and LAVs of the lymph
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nodes were drawn freehand, and the SA and LA of the lymph nodes were measured
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using caliper software (Figure 1). The single lymph node image that provided all of these values was used for analysis, and the SA/LA ratio was calculated.
Lengths of the
expressed in square millimeters.
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SA and LA and the circumference are all expressed in millimeters. Section area is LAVs is expressed in HU.
For all resected patients
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with NSCLC, three of the authors, including an experienced radiologist, each separately evaluated the CT images while blinded to the lymph node SA, LA, section area, circumference and LAVs.
All CT images were measured by measurers, who were However, precise correspondence between lymph
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unaware of clinical information.
nodes on imaging and at surgery is a difficult problem if several lymph nodes were So, all lymph nodes on CT were measured in each node
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sampled in the same station.
station and the longest node by measuring the SA was selected in the present study.
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Two observers were told the purpose of the study was to compare methods for
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distinguishing lymph node metastasis on CT images, and that 705 lesions were included in the study; no information was given regarding the stage of the malignancy or lymph node metastasis.
Surgery In general, NSCLC was treated with segmentectomy or lobectomy plus systematic nodal dissection. Even in cases of extensive nodal involvement, complete resection was attempted. Complete resection was defined as both macroscopic and microscopic tumor-free margins.
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Pathological Evaluation
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Two independent pathologists evaluated samples of dissected tissue. All dissected
hematoxylin-eosin staining.
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tumors and lymph nodes were sectioned and examined conventionally using Lymph node metastasis was judged in each node station.
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If there are one or more metastatic nodes in the station, we judged that a lymph node on
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CT imaging was malignant.
Statistics
Group data were expressed as means ± standard deviation.
Differences between the
measured parameters of metastatic and non-metastatic lymph nodes were examined
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using the Welch’s t test. The ROC curves were used to determine the cut-off values
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that yielded the highest combined sensitivity and specificity with respect to distinguishing metastatic lymph nodes. The areas under ROC curves (AUC) were
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compared using the method described by Hanley and McNeil [20]. The sensitivity,
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specificity, PPV, NPV, accuracy and AUC were all calculated using standard formulas with a 2 × 2 table of the collected data. considered significant.
For all tests, values of p < 0.05 were
JMP IN 8.0.2 software (SAS Institute, Cary, NC, USA) was
used for all statistical evaluations and for drawing the ROC curves.
Results CT was used to measure 192 hilar lymph nodes and 513 mediastinal lymph nodes. The SA, LA, section area, circumference and LAVs of the metastatic lymph nodes were always significantly larger than those of the non-metastatic nodes (Table 2).
To
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determine the cut-off values that yielded the highest combined sensitivity and
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specificity with respect to distinguishing metastatic from non-metastatic lymph nodes,
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conventional ROC curves were used to analyze the measured parameters (Figure 2). From these analyses, we determined the cut-off values for section area, circumference,
HU, respectively.
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SA/LA ratio and LAVs for lymph node metastasis to be 30 mm2, 25 mm, 0.65 and 50 The thresholds obtained from the ROC curves as well as the
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sensitivity, specificity, PPV, NPV and accuracy are all summarized in Table 3. A section area cut-off value of >30 mm2 or a circumference cut-off of >25 mm best distinguished between metastatic and non-metastatic lymph nodes.
When the SA
cut-off value of ≥10 mm was used for diagnosis of lymph node metastasis, the
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sensitivity, specificity, PPV, NPV, and accuracy were 28.6% (12 of 42), 98.0% (650 of
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663), 48.0% (12 of 25), 95.6% (650 of 680), and 93.9% (662 of 705), respectively. When the LA cut-off value of ≥13 mm was used for diagnosis, the sensitivity, specificity,
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PPV, NPV, and accuracy were 45.2% (19 of 42), 91.1% (604 of 663), 24.4% (19 of 78),
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96.3% (604 of 627), and 88.4% (623 of 705), respectively. When the section area cut-off value of >30 mm2 was used for diagnosis, the sensitivity, specificity, PPV, NPV, accuracy and AUC were 90.5% (38 of 42), 56.3% (373 of 663), 11.6% (38 of 328), 98.9% (373 of 377), 58.3% (411 of 705) and 0.813, respectively.
When the
circumference cut-off value of >25 mm was used for diagnosis, the values were 76.2% (32 of 42), 70.4% (467 of 663), 14.0% (32 of 228), 97.9% (467 of 477), 70.8% (499 of 705) and 0.812, respectively.
This represents a substantial improvement over the
sensitivity obtained by radiologists using the conventional criteria, as well as over the values reported in our earlier retrospective review. Table 4a shows the sensitivity, specificity, PPV, NPV and accuracy for diagnosis when the section area of a mediastinal
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or hilar lymph node is greater than 30 mm2. The values for mediastinal nodes were
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87.5% (14 of 16), 61.6% (306 of 497), 6.8% (14 of 205), 99.4% (306 of 308) and 62.4%
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(320 of 513), respectively, while the values for hilar nodes were 87.0% (20 of 23), 45.8% (76 of 166), 18.2% (20 of 110), 96.2% (76 of 79) and 50.8% (96 of 189), Table 4b shows the sensitivity, specificity, PPV, NPV, accuracy for
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respectively.
diagnosis when the circumference of a mediastinal or hilar lymph node is greater than
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25 mm. The values for mediastinal nodes were 81.8% (13 of 16), 72.2% (359 of 497), 8.6% (13 of 151), 99.2% (359 of 362) and 72.5% (372 of 513), respectively, while the values for hilar nodes were 73.9% (17 of 23), 65.7% (109 of 166), 23.0% (17 of 74),
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94.8% (109 of 115) and 66.7% (126 of 189), respectively.
Discussion
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Our findings indicate that a lymph node section area >30 mm2 or a circumference >25
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mm can be effective criteria for use by radiologists and thoracic surgeons to determine nodal staging and surgical indications. Using those cut off values, we achieved greater sensitivity than was achieved by experienced radiologists using conventional criteria. Accurate clinical staging of the mediastinal lymph nodes is essential for determining the best approach to treatment, therapeutic options and prognoses.
From our experience
with CT, we suggest that if a lymph node section area is >30 mm2 or the circumference is >25 mm, a more sensitive procedure, such as PET or mediastinoscopy, is indicated. Many have used an SA cutoff value of ≥10 mm to demonstrate the accuracy of CT for nodal staging in lung cancer.
It is noteworthy, however, that malignant lymph nodes
may be smaller than 10 mm. This explains the limited sensitivity and specificity of CT
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[14, 16, 17, 21–23]. The main disadvantage of CT is that it only depicts the size and
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shape of the nodes; it does not depict the actual tumor involvement. Consequently, the
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presence of micrometastasis in small nodes may lead to false-negatives, and large nodes may contain only inflammatory cells, leading to false-positives. Furthermore, the vast
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majority of patients undergo only chest CT, although CT is notoriously inaccurate for T and N staging in many situations, and accurate mediastinal staging is crucial for
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determining the best approach to treatment in lung cancer [9, 10]. The sensitivity, specificity and accuracy for diagnosis were 87.5%, 61.6%, 62.4%, respectively when the section area of a mediastinal lymph node was greater than 30 mm2, and were 81.8%,
greater than 25 mm.
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72.2%, 72.5%, respectively, when the circumference of a mediastinal lymph node was Use of these criteria to determine mediastinal lymph node
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metastasis provides a greater degree of sensitivity and more accurate nodal staging than do conventional criteria.
Moreover, the mean LAVs of metastatic lymph nodes on
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enhanced CT images (57.6 ± 16.9 HU) were significantly greater than those of
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non-metastatic lymph nodes. However, the sensitivity, specificity and accuracy of LAVs were low and not available to determine nodal staging.
Nonetheless, the
absence of LAVs 30 mm2 or circumference >25 mm) is that the PPV is lower than was achieved using SA ≥10 mm or LA ≥13 mm. This is because the number of metastatic lymph nodes in the resected NSCLC patients was only 0.03% (99 of 3228 dissected lymph nodes).
When the prevalence of preclinical
disease is low, the PPV will also be low, even when using a test with high sensitivity and specificity. To increase the PPV of the new criteria, a program could target those
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at high risk of developing the lymph node metastasis, based on considerations such as For example, the new
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the presence of a large lung tumor and progressive T staging.
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criteria (section area >30 mm2 or circumference >25 mm) would be recommended for NSCLC patients showing lymph node uptake of FDG on PET/CT, as that is a
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population with a higher prevalence of lymph node metastasis.
Another limitation is
that the section area and circumference were drawn freehand, and the inter and intra However, the time that takes to obtain the
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observer variability was not evaluated.
section area and circumference is about 3-5 seconds. We believe that the time using new procedure in the present study is not significant difference in comparison with the conventional measurement of the short axis for lymph nodes.
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N staging using PET/CT is better than with PET or CT alone [21-25]. The benefit of
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PET/CT for N staging appears to lie in the moderate increases in specificity and PPV, which stems from the improved accuracy of the anatomical information [24, 25]. In a
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prospective comparison of the abilities of CT and PET/CT to detect malignant nodes,
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the sensitivity, specificity and accuracy of CT were 70%, 69% and 69%, respectively, while those of PET-CT were 85%, 84% and 84% [24]. It was also found that the post-test probability for N2 disease was 5% among patients with lymph nodes measuring 10-15 mm on CT and having a negative FDG-PET result.
This suggests
these patients should be scheduled for thoracotomy because the yield from mediastinoscopy will be very low. On the other hand, for patients with lymph nodes measuring >16 mm on CT and a negative FDG-PET result, the post-test probability for N2 disease was 21%, suggesting unnecessary thoracotomies could be prevented in these patients by first scheduling a mediastinoscopy.
Taken together, these findings indicate
the utility of FDG-PET for diagnosing lymph node metastasis is limited because
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standard uptake values for FDG-PET are affected by lymph node size [26].
Other
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limitations on FDG-PET for evaluation of lymph nodes are false-positives due to uptake
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of FDG into sites of inflammation and granulomatous disease (e.g., tuberculosis, aspergillosis and sarcoidosis), leading to a reduction in specificity, and false-negatives
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for very small tumors or those with low FDG uptake (e.g., low-metabolism tumors such as bronchioloalveolar carcinomas and carcinoid tumors).
The addition of FDG-PET
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scanning to the conventional work-up has reportedly changed management in 20%-30% of patients with NSCLC, mostly by upstaging the disease [27, 28].
Further
investigation will be needed to more precisely define the relation between SA, LA,
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section area and circumference on CT and FDG uptake on PET. Recent advances in CT technology have allowed investigation of novel methods
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for the evaluation of lung cancers including volumetry, perfusion analysis, dual-energy applications and computer-aided detection [29].
Three-dimensional (3D) volumetric
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measurements are moreaccurate and reproducible than two-dimensional measurements
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and are increasingly used in lung cancer screening programs [30] [31] [32]. Takahashi et al. reported optimal 76% accuracy was obtained with a criterion of 3D volume of >1282 mm3 or CT values of >103 HU for the 30 mm2 or circumference >25 mm, we achieved a higher performance level than is
are supportive criteria that can be used by radiologists and thoracic surgeons to If these CT criteria are met, use of a
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determine nodal staging and surgical indications.
more sensitive procedure such as positron emission tomography or mediastinoscopy is
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recommended.
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References [1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55(2):74–108. [2] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61(2):69–90.
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Figure Legends
Measurement of lymph nodes on CT images.
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The long and short axes, section area, circumference and lesion attenuation values of lymph nodes were measured on the computer screen using caliper software. (a) Example of a mediastinal lymph node
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(b) Example of a hilar lymph node
Receiver operating characteristic (ROC) curves for detection of lymph
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node metastasis using CT.
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Panels a-d depict the ROC curves for section area, circumference, SA/LA ratio, and lesion attenuation values for all lymph nodes.
The thresholds obtained based on the
ROC curves for sensitivity, specificity, positive predictive value, negative predictive value and accuracy are summarized in Table 3.
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Figure 1b
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Figure 2b
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Figure 2
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N0 N1 N2 N0 N1 N2
192 14 12 181 22 15
(mm) Mean Range Type adeno squamous others Dissected lymph node Met (+) Met (–)
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Tumor size
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Tumor location RUL RML
RLL LUL LLL RUML RMLL RUMLL LULL Pathological stage IA IB
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80
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pN status
Female
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Nodal status cN status
218 69.4±9.60 67.0±10.2 138
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No. of patients Age Male Female Sex Male
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Table 1. Patient characteristics
29.9 ± 19.3 4 – 120 162 43 13 3327 99 3228
IIA IIB IIIA IIIB IV
64 15 55 51 26 2 1 1 3 115 47 17 17 18 2 2
RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; adeno, adenocarcinoma; squamous, squamous cell carcinoma
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Measurement of the LA, SA, surface area, circumference, SA/LA ratio,
and LAVs of metastatic lymph nodes
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Table 2.
Mets (+) 42
Mets (–) 663
SA (mm)
8.27 ± 3.81
4.97 ± 1.95
< 0.001
LA (mm) Surface area (mm2) Circumference (mm) SA/LA ratio LAVs (HU)
12.6 ± 4.32 81.2 ± 68.5 34.3 ± 12.5 0.66 ± 0.14 57.6 ± 16.9
8.11 ± 3.09 32.3 ± 23.4 21.9 ± 8.00 0.64 ± 0.31 45.7 ± 28.3
< 0.001 < 0.001 < 0.001 0.602 30 mm2 90.5 56.3 11.6 98.9
Circumference >25 mm 76.2 70.4 14.0 97.9
SA/LA ratio >0.65 52.4 60.6 7.8 95.3
LAVs >50 HU 73.8 52.0 8.9 96.9
Accuracy (%)
93.9
88.4
58.3
70.8
60.1
53.3
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Method
PPV, positive predictive value; NPV, negative predictive value; SA, short axis; LA, long axis; LAVs; lesion attenuation values;
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Diagnosis of mediastinal or hilar lymph node metastasis based on
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Table 4a.
Surface area >30 mm2
Surface area >30 mm2
87.5 61.6 62.4
Diagnosis of mediastinal or hilar lymph node metastasis based on
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circumference >25 mm
Method
87.0 45.8 50.8
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Table 4b.
Hilum
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Sensitivity (%) Specificity (%) Accuracy (%)
Mediastinum
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Method
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surface area >30 mm2
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Sensitivity (%) Specificity (%) Accuracy (%)
Mediastinum
Hilum
Circumference >25 mm 81.3 72.2 72.5
Circumference >25 mm 73.9 65.7 66.7
25
