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Lung Cancer (2008) xxx, xxxxxx

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/lungcan

Recommendations for optimal use of imaging

studies to clinically stage mediastinal lymph
nodes in non-small-cell lung cancer patients
Bryan A. Whitson, Shawn S. Groth, Michael A. Maddaus
University of Minnesota Department of Surgery, Division of Thoracic and Foregut Surgery,
MMC 207, 420 Delaware St. SE, Minneapolis, MN 55455, United States
Received 15 May 2007; received in revised form 27 November 2007; accepted 16 December 2007

KEYWORDS
Non-small-cell lung
cancer;
Lymph nodes;
Staging;
Mediastinum;
Computed
tomography;
Positron emission
tomography

Summary Appropriate clinical staging of mediastinal lymph nodes in non-small-cell lung cancer (NSCLC) patients has important therapeutic and prognostic implications. Because of the
wide variations in practice patterns among community and academic physicians, we reviewed
the literature so that we could provide evidence-based recommendations on the use of imaging
studies in the pretreatment clinical staging of NSCLC patients. We concluded that the most
sensitive and accurate method of noninvasive mediastinal nodal staging is a positron emission
tomography/computed tomography fusion scan; we believe this tool should be a component
of clinical staging of all NSCLC patients. Given insufcient sensitivity with currently available
imaging studies, mediastinal nodal staging should also include histologic evaluation.
2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Accurate mediastinal lymph node (MLN) staging in nonsmall-cell lung cancer (NSCLC) patients has important
therapeutic and prognostic implications [1,2]. Though imaging studies play an important role in the clinical staging of
the mediastinum, their use varies widely among community
and academic physicians [36].
Chest roentograms and computed tomography (CT) scans
are widely used for clinical MLN staging in NSCLC patients
[36]. However, positron emission tomography (PET), which

offers superior sensitivity and specicity as compared to CT,

is used infrequently (026.4%) for clinical staging of NSCLC
patients [47]. Sporadic use of PET may be due, in part,
to its lack of widespread availability at the time the justreferenced surveys were conducted. However, its sporadic
use may also be due to a lack of physician education with
regard to the evidence favoring PET. Given the implications
of inaccurate clinical staging, we reviewed the literature so
that we could provide evidence-based recommendations on
the optimal use of imaging studies for clinical MLN staging.

2. Methods

Corresponding author. Tel.: +1 612 624 9461;

fax: +1 612 625 9657.
E-mail address: madda001@umn.edu (M.A. Maddaus).

For our literature search, we used the PubMed database

(www.pubmed.gov) of the National Library of Medicine and

0169-5002/$ see front matter 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.lungcan.2007.12.019

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
doi:10.1016/j.lungcan.2007.12.019

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B.A. Whitson et al.

Table 1

2.2. CT

Statistical formulae denitions

Descriptor

Formula

Sensitivity
Specicity
Negative
predictive
value
Positive
predictive
value
Accuracy

true positives
true positives+false negatives
true negatives
true negatives+false positives
true negatives
true negatives+false negatives

true positives
true positives+false positives

true negatives+true positives

true positives+false positives+true negatives+false negatives

the National Institutes of Health. To identify relevant studies, we utilized the following keywords and medical subject
headings: non-small-cell lung cancer, lymph node, mediastinum, evaluation, staging, imaging, chest roentogram,
X-ray, magnetic resonance imaging (MRI), CT, and PET. We
excluded case reports and articles focusing on disease other
than NSCLC.
In order to adequately compare imaging modalities in
terms of their clinical efcacy, we utilized ve biostatistical descriptors: sensitivity, specicity, negative predictive
value (NPV), positive predictive value (PPV), and accuracy.
The formulae for calculating these descriptors are detailed
in Table 1. Sensitivity, or the rate of true positives, describes
how effective a screening test is. Specicity, or the rate of
true negatives, describes the adequacy of a conrmatory
test. The NPV and the PPV allow one to ascertain how a
negative or positive test, respectively, correlates with the
actual, true result. Finally, the accuracy describes how well
a test identies true-positive and true-negative results.

2.1. Clinical staging of MLNs: radiographic

techniques
In the initial evaluation of lung cancer, posterioranterior
and lateral chest roentograms are valuable. However,
because of their poor sensitivity (less than 50%) [8], chest
roentograms are an inadequate method to screen for NSCLC
MLN metastasis, in the absence of obvious, bulky mediastinal
adenopathy [9,10]. Unless the patient is not a candidate for
surgery or for denitive chemoradiation therapy, additional
imaging studies are required.

Table 2

Because of its relatively widespread availability and its

superior sensitivity, specicity and diagnostic accuracy, as
compared with plain lms (Tables 2 and 3), CT is the most
widely used imaging modality for MLN staging for NSCLC
patients in the United States [4]. Despite its advantages as
compared with chest roentograms, CT relies on an inaccurate (<70%) method to differentiate benign from malignant
MLNs: the size of the LN. The criterion of 1 cm is generally
used to differentiate potentially malignant MLNs (more than
1 cm in diameter) from benign MLNs (less than 1 cm in diameter). Using this paradigm, the false-positive rate of CT in the
diagnosis of MLN metastasis is 1020% [11]; this rate is even
higher in patients with central T3 lesions, central adenocarcinomas, or left upper lobe lesions [12]. More importantly,
the false-negative rate is more than 10% [11]. If CT alone
was used to screen for MLN metastasis, patients with falsenegative results would be denied optimal treatment for their
cancer.
In an observational study in which NSCLC patients underwent CT and subsequently thoracotomy for tumor resection
and pathologic staging, MLN size was poorly correlated with
the presence of malignancy. MLNs harboring malignant disease were not signicantly different in size than those
containing benign disease. MLNs less than 1 cm in diameter
contained malignant pathology 15% of the time, while MLNs
larger than 1 cm were not infrequently (43%) associated with
benign disease processes [13]. Because of the limitations of
CT in staging MLNs, functional imaging has emerged as a
valuable adjunct.

2.3. PET and PET/CT

In January of 1998 the Centers for Medicare and Medicaid Services (CMS) approved the use and reimbursement of
18
FDG-PET for the initial staging of NSCLC. In July 2001, this
coverage was extended to diagnosis, staging, and restaging
[14]. In addition, the NCCN advocates that PET imaging plays
a role in the staging and diagnostic management of every
stage of NSCLC disease [15]. While the anecdotal experience at tertiary and quaternary treatment centers is that a
large percentage majority of patients receive 18 FDG-PET or
PET/CT fusion scans, the data available describing community clinical practice reveal lower utilization rates (026.4%)
[47].

Radiographic modalities for mediastinal lymph node staging [8,1623,38,4043,45,47]

Chest roentogram
CT
FDG-PET
Choline-PET
FDG-PET and CT
FDG-PET/CT fusion
MRI

Sensitivity (%)

Specicity (%)

NPV (%)

PPV (%)

Accuracy (%)

45
1984
5096
100
81
6094
6471

78
4999
7797
97
94
8594
4891

78
7084
4591

45
3162
4480

4360

5699

68
5694
4596
96
88
7896
6183

CT: computed tomography, FDG: uorodeoxyglucose, PET: positron emission tomography, MRI: magnetic resonance imaging, NPV: negative
predictive value, PPV: positive predictive value.

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
doi:10.1016/j.lungcan.2007.12.019

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Table 3

Individual study results

Modality

Lead author

Year

Sensitivity
(%)

Specicity
(%)

NPV (%)

PPV (%)

Accuracy
(%)

Chest roentogram

Patterson [8]

1987

71

81

43

79

46

57

CT

Martini [47]
Patterson [8]
Webb [45]
Bury [16]
Egri [18]
Magnani [40]
Gupta [20]
Hara [38]
Luketich [21]
Cerfolio 17]
Fritscher-Ravens
[19]
Antochc [67]
Shim [68]
Birim [23]
Tourney [42]

1985
1987
1991
1996
1998
1999
2000
2000
2001
2003
2003

34
84
155
50
316
28
54
29
40
400
33

87
71
52
72

79
89
64
81

84

79

82
82
65

68

84

66
68
19
50
43
57

79
65
99
71
75
74

83
82

60
47

84

31

2003
2005
2005
2007

19
106
Meta-analysis
105

70
70
59
84

59
69
78
61

77

56

Bury [16]
Magnani [40]
Hara [38]
Gupta [20]
Luketich [21]
Cerfolio [17]
Fritscher-Ravens
[19]
Antoch [67]
Cerfolio [41]
Halpern [22]
Birim [23]
Lee [43]

1996
1999
2000
2000
2001
2003
2003

50
28
29
54
40
400
33

90
67
75
96
67
71
73

86
84
97
93
79
77
83

86
89

90
67

98

86

91

44

2003
2004
2005
2005
2007

20
129
36
Meta-analysis
336

89
62
50
83
61

89
97
77
92
94

94
98
80

80
42
45

89
93
69

92

69

89

Choline-PET

Hara [38]

2000

29

100

97

FDG-PET and CT

Magnani [40]
Fritscher-Ravens
[19]
Magnani [40]
Antoch [67]
Cerfolio [41]
Shim [68]
Halpern [22]
Tourney [42]
Lee [43]

1999
2003

28
33

67
81

95
94

86

75

86
88

1999
2003
2004
2005
2005
2007
2007

28
26
129
106
36
105
336

78
89
64
85
60
84
86

95
94
94
84
85
84
81

90
94
99

88
89
49

85
85
95

60

89
93
96
84
78

56

82

Martini [47]
Patterson [8]
Webb [45]

1985
1987
1991

34
84
155

87
71
48

68
91
64

84

82

76
83
61

FDG-PET

FDG-PET/CT fusion

MRI

71
75
61
94
68
68
67
63
69

79
96
94
78
76
79

96

CT: computed tomography, FDG: uorodeoxyglucose, PET: positron emission tomography, MRI: magnetic resonance imaging, NPV: negative
predictive value, PPV: positive predictive value.

PET enables detection of MLNs with abnormally high functional activity (e.g., tumor metastases), a feature that CT
lacks. Because of this advantage and because of the limitations of using size criteria with CT to diagnose tumor
metastases, PET has superior sensitivity, specicity, accuracy, NPV, and PPV in staging the mediastinum as compared
with CT and chest roentograms (Tables 2 and 3) [1623].

The most commonly utilized radiotracer in PET is

18-uorodeoxyglucose (18 FDG), which detects foci of abnormally high glucose metabolism. The standardized uptake
value (SUV), the measure of metabolic activity detected by
PET, is directly related to the degree of metabolic activity within a tissue focus or within an organ and provides
predictive information regarding treatment response and

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
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survival [2426]. The maximum SUV (maxSUV) in a region

of interest (ROI) has been adopted as an approach to characterize metabolically active lesions. The formula for the
SUV is [2729]:
SUV =

mean ROI activity (MBq/mL)

dose (MBq)/Body weight (kg)

As one can see, the SUV is normalized by body weight.

The clinical utility of PET is related to the SUV. However,
in the utilization of the SUV, the evaluation relies somewhat
on the kinetics of the radiotracer involved (18 FGD and 11 Ccholine in this review) and the compartments of distribution
of the radiotracer for accurate modeling of the effects. The
amount of the radiotracer, the aliquots in which it is administered, and the rate of administration are all key factors in
the time and duration of steady state values. Additionally,
radiotracer can be distributed in the serum, fat, muscle, and
potential tumor volumes [27,29].
The metabolic rate of glucose (MRglu ) metabolism is a
measure of the glucose metabolism within tissues. In gen-

eral, the SUV calculations do not take into account the

volumes of distribution [29]. It has been proposed that
following changes in MRglu may be a more accurate clinical response indicator than volumetric averages would be.
MRglu s importance is in the SUV calculation, where SUV is
the tumor activity per dose injected per body mass. SUV is
proportional to MRglu [30,31]. The serum glucose levels can
inuence SUV levels in background tissue as elevated serum
glucose preferentially drives glucose and [18] FDG into adipose tissues. In attempts to circumvent this phenomenon,
dual time point imaging and evaluations are performed to
follow washout in tissues of less biologic interest (adipose)
[27].
Traditionally, clinicians and radiologists have designated
a maxSUV of 2.5 as the upper limit of normal in an attempt to
minimize the chance of false-negative results [28,32,33]. In
an attempt to improve the diagnostic validity of PET scans,
several researchers have challenged this dogma, advocating the use of higher normal limit for SUV (>4.5 [20] and
>5.3 [28]). Bryant et al. compared the PET/CT results of
397 NSCLC patients (143 of which had pathologically proven

Fig. 1 American Thoracic Society Regional Lymph Node Stations. Chest. Online by Mountain and Dresler. Copyright 1997 by Am
College of Chest Physicians. Reproduced with permission of Am College of Chest Physicians in the format Journal via Copyright
Clearance Center. [66].

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
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5
ity of choline transmembrane transporters, the metabolism
of choline via choline kinase, and the rate of cell membrane synthesis are all increased in tumor cells; accordingly,
increased 11 C-choline activity is indicative of tumor proliferation [37]. In a prospective comparative study of 29
patients who underwent 18 FDG-PET as well as 11 C-cholinePET followed by surgical resection and MLN dissection,
11
C-choline-PET provided greater sensitivity (100%) than
18
FDG-PET (75%) [38]. In that study, the 11 C-choline-PET
was able to identify small disease not seen on traditional
18
FDG-PET. Additional trials are needed to validate its
use.
In the study by Hara et al. (above) [38] and their followup of 97 patients [37], the potential utility of 11 C-cholinePET was laid out. This utility is that with the 11 C-cholinePET, the maxSUV of the metastatic lesion was similar to that
of the primary, while the 18 FGD-PET was not. This effect
could allow for less false-positive results, but has yet to be
validated.
Not all investigators have espoused the clinical utility
of the maxSUV. In Vesselle et al.s prospective study of
208 patients of whom 103 underwent resection, the use
of the maxSUV or the volumetric average of the maxSUV,
did not correlate with overall survival or recurrence in
univariate analysis. In this analysis, only pathologic stage
correlated with survival and recurrence [39]. This is one
counter-viewpoint of the utility of maxSUV in clinical prognostication.
The combination of CT and PET amalgamates the
advantages of each technique, thereby enhancing the sensitivity, specicity, and accuracy of either CT or PET alone
(Tables 2 and 3) [19]. Integrated PET/CT fusion scans,
as compared with either test alone or with both tests
performed sequentially, offers a superior balance of the sensitivity, specicity, accuracy, NPV, and PPV (Tables 2 and 3)
[22,40,41].

N2 disease) with their pathologic stages. Using a receiver

operator characteristic curve analysis, they demonstrated
that a maximum SUV of 5.3 optimized the sensitivity (91%),
specicity (88%), and accuracy (92%) of PET [28]. Until more
data are available supporting the use of a higher maximum
SUV cut-off, 2.5 should be used.
Despite its advantages, PET has a distinct limitation as a
screening tool for MLN metastasis: its sensitivity for detecting tumor metastasis varies depending on the lymph nodes
location within the mediastinum. Though PET has excellent
sensitivity (8099%) in detecting metastasis to American
Thoracic Society MLN stations 4R, 4L, 10R, and 10L (Fig. 1),
its sensitivity at other MLN stations (e.g., stations 5, 6, 7,
8R, and 8L) is poor (2960%) [17]. In addition to a high falsenegative rate with screening for metastases at certain MLN
stations, false-positive results can and do occur. Therefore,
in general, treatment decisions should not be based on PET
results alone; a tissue diagnosis is required.
With the use of PET imaging, false positives can occur any
time there is tissue present which is abnormally metabolically active. The increased SUV of tissue corresponds with
glucose utilization and is not entirely specic to malignant
processes. For this reason, false-positive PET images have
been described in the setting of infection, benign disease
and chronic inammatory processes (e.g., sarcoidosis, amyloidosis), and residual inammation after local treatment
effects (e.g., following surgery, chemotherapy, or radiation)
[29,3436].
Though FDG is the most widely utilized PET metabolite,
11
C-choline is emerging as a potential superior alternative.
Choline, an organic compound that is a critical component
of cell membranes, of cholinergic neurotransmitters, and
of biosynthesis pathways, is taken up by cells via a transmembrane transport protein. Once inside the cell, choline
is ultimately metabolized into phosphatidylcholine, which is
then integrated into the extracellular membrane. The activ-

Table 4

Modalities for tissue conrmation of diagnosis

Station

Mediastinoscopy

TEMLA
[69,70]

2R
2L
3
4R
4L
5
6
7
8
9
10R
10L
11R
11L

Chamberlain
procedure [71]

TB-FNA
[72]

EBUS-FNA
[72]

EUS-FNA
[73]

VATSa

Thoracotomya

EUS: endoscopic ultrasound, EBUS: endobronchial ultrasound, FNA: ne needle aspiration, TB: transbronchial (without ultrasound),
TEMLA: transcervical extended mediastinal lymphadenectomy, VATS: video assisted thoracoscopic surgery.
a MLN sampling without parenchymal resection.
b Only anterior MLN are accessible from this station.
c Only proximal MLN are accessible from this station.

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
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In a prospective study, 52 NSCLC patients were evaluated by CT and by integrated PET/CT prior to pathologic
tumor staging. PET/CT fusion scans demonstrated superior
specicity (85%) as compared with CT alone (61%); their
sensitivities, however, were similar (84%) [42]. In a single institution retrospective review of 336 NSCLC patients,
PET/CT fusion had a signicantly better sensitivity (85.7%)
as compared with 18 FDG-PET alone (61.1%). However, as
compared with 18 FDG-PET performed individually, PET/CT
fusion studies were associated with an improved specicity
(80.6% versus 94.3%), PPV (55.8% versus 68.8%), and accuracy (81.7% versus 88.6%) [43].
Because of the benets of the combination of CT and PET,
the current National Comprehensive Cancer Network (NCCN)
Clinical Practice Guidelines in Oncology state that both CT
and PET should be part of the initial and pretreatment evaluations of NSCLC patients [15]. If a PET/CT fusion study is
not available, PET and CT should be performed sequentially.

2.4. MRI
As compared with CT, magnetic resonance imaging (MRI)
has two additional advantages: (1) multi-planar imaging,
another means of evaluating MLNs that are difcult to assess
on axial images, and (2) enhanced ability to distinguish blood
vessels from LNs, which may be helpful in cases where CT
is equivocal [44]. However, like CT, MRI relies on anatomic
features (principally diameter) to diagnose MLN metastasis.
Furthermore, MRI, as compared with CT, is a less sensitive means of detecting calcication (an indicator of benign

disease) and has poorer spatial resolution [44]. In part,

because of these limitations, MRIs sensitivity, specicity,
and accuracy are similar to those of CT in detecting MLN
metastasis [8,4548] (Tables 2 and 3). Consequently, the
use of standard anatomic MRI for staging the mediastinum is
currently limited to cases where CT ndings are indeterminate. However, emerging MRI techniques, such as short-time
inversion-recovery turbo spin-echo MRI [49] and physiologic
MRI with iron oxide [44,5052], may offer an enhanced
capacity to detect MLN metastasis in the future.

3. Cost of imaging modalities

The cost associated with these various imaging modalities
can be signicant. The more contemporary techniques are
more costly. In several international studies of cost utilization, CT has been uniformly less expensive than PET (all in
US dollar equivalents unless otherwise stated). In the Canadian system, the cost of a chest CT is $290, while a PET
is $1029 [53]. In Japan, the cost of a chest CT is $129 and
that of PET is $669700 [54,55]. In Australia, a chest CT is
$400 and PET is $1200 [56]. In Germany, a chest CT costs
583 EUR while a PET is 1227 EUR (range, 6271827) [57]. In
the United States, CPT code 71551 (MRI of the chest with IV
contrast) is reimbursed by CMS at $451.91; CPT code 71260
(CT of the chest with IV contrast) is reimbursed at $303.32.
The standard relative value units of a PET are not published
and allow for variation between systems [58]. Given the
increased cost associated with PET over CT and MRI, the
clinical efcacy of PET imaging needs to be superior.

Fig. 2 Typical diagnostic algorithm for the preoperative evaluation of a non-small-cell lung cancer patient in order to accurately
stage the mediastinal lymph nodes. PET positron emission tomography, CT computed tomography, MLN mediastinal lymph
node.

Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
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3.1. Pathologic staging of MLNs

4. Recommendations

Clinical staging with the currently available imaging studies

(i.e., CT, MRI, and PET) is an insufcient method on which to
base treatment decisions. A large, multi-institutional, cooperative group trial of 502 NSCLC patients demonstrated a
38.3% false-negative rate with clinical staging with CT as
compared with pathologic staging [59]. Had these patients
not been appropriately staged by histologic evaluation of
MLNs, they likely would have received suboptimal cancer
treatment. Currently, MRI offers no advantage over CT or
PET. Though PET/CT fusion scans are the most sensitive and
accurate radiographic means of screening for MLN metastasis [22,40,41], false-positive and false-negative results
can and do occur. PET-negative MLNs may contain occult
micrometastatic disease while PET-positive MLNs may harbor
hypermetabolic benign infectious or inammatory processes
[20,28]. Because of the limitations of these imaging studies,
an accurate MLN evaluation must include histologic assessment of MLN tissue.

To optimize the care of and outcomes for NSCLC patients

through more accurate clinical staging, educational programs are needed to distribute evidence-based practice
guidelines to both community and academic physicians. In
light of our review, we offer the following evidence-based
recommendations:

3.2. Tissue conrmation of diagnosis

In the current era of high-resolution fusion PET/CT scans
and increasingly experienced radiologists, some authors
have argued that pathologic evaluation of MLNs (i.e., mediastinoscopy) prior to tumor resection can be averted in
the setting of a negative PET/CT study [60]. Because
false-negative and false-positive results are common (about
10% of studies) [20,28,42,43], we do not advocate this
approach for most patients. A conrmatory tissue diagnosis is needed in nearly all cases. Knowledge of the American
Thoracic Society MLN stations (Fig. 1) and the anatomic limitations of the available modalities to obtain MLN tissue
(Table 4) are essential to developing and implementing an
effective diagnostic algorithm. In the evaluation of NSCLC
patients, consideration needs to be both the anatomic
location of the MLN in question and the expertise of the
physicians at a particular institution. At the University
of Minnesota, we routinely perform an integrated PET/CT
scan followed by a histologic MLN assessment, regardless of the imaging results (Fig. 2). In the setting of a
negative PET/CT fusion scan, our patients undergo mediastinoscopy; if the mediastinoscopy is negative, patients
proceed to denitive tumor resection and complete MLN
dissection in order to provide accurate staging [6164]. If
a MLN is positive on PET/CT, an endobronchial ultrasound
(EBUS)-guided ne needle aspiration (FNA), an endoscopic
ultrasound (EUS)-guided FNA, an anterior parasternal mediastinotomy (Chamberlain procedure), or a MLN biopsy via
video-assisted thoracoscopic surgery (VATS) is performed
depending on the anatomic location of the MLN in question (Table 4). Because of the potential for false-negative
results, patients who have a negative EBUS-FNA or EUS-FNA
undergo mediastinoscopy or VATS for conrmation. Because
our thoracic surgeons are also experienced minimally invasive surgeons, we do not routinely perform MLN biopsies via
a thoracotomy. A thorough review of the accuracy and diagnostic yield of the modalities listed in Table 4 is beyond
the scope of this manuscript but is available elsewhere
[65].

A chest roentogram alone is not adequate.

MRI has a limited role in staging NSCLC.
PET/CT fusion scans, the most sensitive imaging technique, should be used in the clinical staging of NSCLC
patients whenever possible.
If fusion scans are not available, CT and PET scans should
be performed separately.
A maximum SUV of 2.5 should be utilized as a cut-off for
suspicious MLN.
Pathologic evaluation of tissue should be performed in
all patients who are considered potential candidates for
denitive chemoradiation therapy or for surgical resection. Decisions should not be based on clinical staging by
imaging alone.

Conict of interest statement

None of the authors have any nancial or personal relationship conicts of interest to disclose.

Acknowledgment
The authors would like to acknowledge Mary Knatterud,
Ph.D., for her editorial assistance with this manuscript.

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Please cite this article in press as: Whitson BA, et al., Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients, Lung Cancer (2008),
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