Estadiaje CA Pulmon

CHEST Supplement
journal.publications.chestnet.org CHEST / 143 / 5 / MAY 2013 SUPPLEMENT e191S

DIAGNOSIS AND MANAGEMENT OF LUNG CANCER, 3RD ED: ACCP GUIDELINES
S
tage classication is an essential part of the approach
to patients with cancer, and there are many things
we would like to get from a stage classication. The
primary purpose of the classication is to consistently
describe the anatomic extent of disease, thus providing
a common, consistent language. The anatomic extent
of the tumor has a major impact on which treatment
we choose and what the outcome will be. However, it
is important to recognize that the stage classication
does not by itself completely dene the prognosis
(which depends on multiple factors, eg, comorbidi-
ties, performance status, treatment given) or serve as
a treatment algorithm (which is driven by data from
clinical trials and treatment selection criteria). Efforts
to develop a comprehensive prognostic index system
are under way.
Stage classication is founded on the TNM system,
which dates back to 1944. Furthermore, the method
of staging is classied as clinical stage (denoted by the
prex c) and pathologic stage (denoted by the prex p).
Clinical stage is determined using all information
available prior to any treatment, and pathologic stage
is determined after a resection. The extent of clin-
ical staging can vary from a clinical evaluation alone
(history and physical examination) to extensive imaging
(CT and PET scans) or invasive staging techniques.
It must be emphasized that a surgical staging proce-
dure (eg, mediastinoscopy) is still part of clinical stag-
ing because surgical resection as a treatment has not
taken place.
The current Lung Cancer Stage Classication system is the seventh edition, which took effect in
January 2010. This article reviews the denitions for the TNM descriptors and the stage grouping
in this system. CHEST 2013; 143(5)(Suppl):e191Se210S
Abbreviations: AAH 5 atypical adenomatous hyperplasia; ACCP 5 American College of Chest Physicians; AJCC 5
American Joint Committee on Cancer; BAC 5 bronchioloalveolar carcinoma; GGO 5 ground glass opacity; IASLC 5 Inter-
national Association for the Study of Lung Cancer; ITC 5 isolated tumor cell; UICC 5 Union Internationale Contre le
Cancer
The Stage Classication of Lung Cancer
Diagnosis and Management of Lung Cancer,
3rd ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines
Frank C. Detterbeck , MD , FCCP ; Pieter E. Postmus , MD , PhD , FCCP ;
and Lynn T. Tanoue , MD , FCCP
Manuscript received September 24, 2012; revision accepted
November 30, 2012.
Afliations: From the Yale University School of Medicine
(Dr Detterbeck), New Haven, CT; Department of Pulmonary Dis-
eases (Dr Postmus), VU University Medical Center, Amsterdam,
The Netherlands; and Section of Pulmonary and Critical Care Med-
icine (Dr Tanoue), Yale School of Medicine, New Haven, CT.
Funding/Sponsors: The overall process for the development of
these guidelines, including matters pertaining to funding and con-
icts of interest, are described in the methodology article.
1
The
development of this guideline was supported primarily by the
American College of Chest Physicians. The lung cancer guidelines
conference was supported in part by a grant from the Lung Can-
cer Research Foundation. The publication and dissemination of
the guidelines was supported in part by a 2009 independent edu-
cational grant from Boehringer Ingelheim Pharmaceuticals, Inc.
COI grids reecting the conicts of interest that were current as
of the date of the conference and voting are posted in the online
supplementary materials.
Disclaimer: American College of Chest Physicians guidelines are
intended for general information only, are not medical advice, and
do not replace professional medical care and physician advice,
which always should be sought for any medical condition. The
complete disclaimer for this guideline can be accessed at http://
dx.doi.org/10.1378/chest.1435S1.
Correspondence to: Frank C. Detterbeck, MD, FCCP, Yale
School of Medicine, 330 Cedar St, PO Box 208062, New Haven,
CT 06520-8062; e-mail: frank.detterbeck@yale.edu
2013 American College of Chest Physicians . Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.12-2354
Downloaded From: http://journal.publications.chestnet.org/ by Rafael Durand on 05/31/2013
e192S The Stage Classication of Lung Cancer Diagnosis
central location) and were, therefore, placed within
this group.
The size of a tumor is dened as the greatest dimen-
sion, but how this is determined is not addressed by
AJCC, UICC, or IASLC. The ACCP panel suggests
that for consistency, this measurement be done on
an axial CT image using lung windows during inspira-
tion whenever possible (c stage); for p stage, we sug-
gest the greatest dimension (in any direction) of the
specimen xed after ination or of the unxed spec-
imen (xation causes about 20% shrinkage).
15
Further
issues arise with semisolid or ground glass opac-
ities (GGOs), which have not been addressed by the
AJCC or UICC. One can measure the solid or the
ground glass component with either mediastinal or
lung windows on a CT image. Emerging data sug-
gest that the size of the solid (invasive) component
is of greater prognostic value than the ground glass
(lepidic) component.
16-22
The ACCP panel suggests
recording the size of both the GGO and the solid
component on lung windows (or the percent solid
by area) for c stage and both the entire tumor (includ-
ing lepidic portions) and the invasive component for
p stage.
14
This suggestion is consistent with a recent
UICC supplement handbook.
5

2.2 Invasion
There were insufcient numbers of patients for
whom reliable data were available to investigate the
validity of other traditional T2, T3, or T4 descriptors
(visceral pleural invasion, central location within a
lobar or mainstem bronchus, partial or complete atel-
ectasis, direct invasion of particular structures, etc).
These traditional denitions were retained even though
they could not be conrmed because there were no
data to suggest that they are not valid.
Invasion beyond the elastic layer of the pleura is
dened as T2, including invasion into an adjacent
lobe. Elastin stains should be used whenever there is
ambiguity.
23
T3 includes invasion into the parietal
or mediastinal pleura or the parietal pericardium.
T4 includes invasion of the visceral (inner) pericar-
dial surface and the intrapericardial pulmonary artery
and pulmonary veins. Involvement of either the intra-
pericardial or extrapericardial vena cava or aorta
is considered T4. We suggest that involvement of
the azygous vein be classied as T3 because it is
not counted among the great vessels (but this is not
addressed by IASLC, AJCC, or UICC).
A Pancoast tumor is classied as T4 if there is
unequivocal involvement of C8 or higher nerve roots,
cords of the brachial plexus, subclavian vessels, verte-
bral bodies, lamina, or spinal canal. The tumor is clas-
sied as T3 if it involves only thoracic nerve roots
(eg, T1 or T2 nerve roots).
The Union Internationale Contre le Cancer (UICC)
and the American Joint Committee on Cancer (AJCC)
are the ofcial bodies that dene, review periodically,
and rene the stage classication systems. The cur-
rent seventh edition of the lung cancer staging sys-
tem was based on a major initiative undertaken by
the International Association for the Study of Lung
Cancer (IASLC). This 12-year project increased the
patient base from 5,319 (collected over several decades
predominantly at one institution) to . 100,000 (from
around the world, all cases diagnosed between 1990
and 2000).
In validating where to make a distinction between
one stage descriptor or group and another, the IASLC
required that consistent differences in prognosis had
to be seen in data sets from different continents, data-
base types, clinical and pathologic staging, and his-
tologic subtypes.
2
Furthermore, external validation
against large databases was done. The statistical anal-
ysis was quite sophisticated; in all, the current classi-
cation is a quantum leap forward that is unequalled
by any other cancer site. However, although the data-
base was large and involved many institutions from
20 countries, the distribution of cases was not uni-
form. Certain patient subgroups came predominantly
from one region or one type of database and were
treated in many different ways, and the IASLC data-
base did not report treatment-specic outcomes.
1.0 Methods
This article addresses the ofcial Lung Cancer Stage Classi-
cation system. Therefore, the primary sources of information
were the AJCC and UICC staging manuals.
3-5
These sources were
supplemented by the publications of the IASLC International
Staging Committee, which provided the basis for the AJCC/UICC
classication,
2,6-12
as well as American College of Chest Physicians
(ACCP) publications that reviewed and discussed details of the
classication.
13,14

2.0 T Descriptor
2.1 Size
A detailed analysis of tumor size by the IASLC
staging committee conrmed that 3 cm was signi-
cant as a cut point; thus, the denition of T1 vs T2
was retained. In addition, signicant cut points were
identied at 2, 5, and 7 cm. Therefore, subgroups were
dened for T1 (T1a and T1b) and T2 (T2a and T2b)
as shown in Figure 1 . The survival differences between
each size subgroup were highly statistically signi-
cant in pathologically staged patients; among clini-
cally staged patients, the trends were consistent but
not always signicant (probably because of a more
limited data set). Tumors . 7 cm led to survival that
tracked with other definitions of T3 (ie, invasion,
suggests that only unambiguous mediastinal fat involve-
ment be used as a criterion for T4 status (eg, exten-
sive replacement by tumor on CT scan); otherwise,
the lower T3 classication should be chosen.
14

3.0 N Descriptor
Analysis of the prognostic inuence of the N descrip-
tor resoundingly supported the traditional cate goriza-
tion of N0, N1, N2, and N3; therefore, these denitions
were carried forward ( Fig 1 ).
8
Direct extension of
a primary tumor into a node is classied as nodal
involvement. Station 1 nodes are classied as supra-
clavicular nodes, which include the low cervical
nodes, caudal to the lower margin of the cricoid (N3).
Left-side recurrent laryngeal nerve paralysis is clas-
sied as T4 when directly invaded by the primary
tumor but as N2 when invaded by nodal disease. Sim-
ilarly, inltration of the superior vena cava, trachea, or
esophagus by the primary tumor is defined as T4
but as N2 or N3 when inltration emanates from the
lymph nodes.
Difculties arise in the classication of mediastinal
invasion. Although mediastinal pleural invasion is clas-
sied as T3, mediastinal fat invasion is T4, and pari-
etal pericardial invasion is T3. Because there is usually
some fat between the mediastinal pleura and the
pericardium, this classication is confusing. Further-
more, differentiation between hilar fat (considered T2)
and mediastinal fat (T4) is difcult. The ACCP panel
Figure 1. [Sections 2.0, 3.0, 6.2] Denitions for TNM descriptors. Adapted with permission from Detterbeck et al.
13

*These subgroup labels are not dened in the IASLC publications
7-10
but are added here to facilitate a clear discussion.
In the greatest dimension.
T2 tumors with these features are classied as T2a if 5 cm.
The uncommon supercial spreading tumor in central airways is classied as T1.
Pleural effusions are excluded that are cytologically negative, nonbloody, transudative, and clinically judged not to be due to cancer.
survival than those with pathologic multizone N2
involvement (5-year survival, 34% vs 20%; P , .001).
In fact, the survival curves of patients with pathologic
multizone N1 and single-zone N2 involvement were
almost superimposed.
8
However, the prognostic impact
of the number of pathologic nodal zones involved
could not be validated within T-stage categories and
by geographical region, type of databases, or clinical
staging because the number of patients in the subsets
was too small.
8
Therefore, the IASLC staging com-
mittee decided against subdivision of N categories.
The prognostic impact of nodal involvement by direct
extension of a primary tumor also could not be vali-
dated through the IASLC database because of insuf-
cient sample sizes but was retained because it is
consistent with general UICC and AJCC rules.
3.1 Node Map
The IASLC node map is shown in Figures 3 and 4 .
Important features include better denition of the
subcarinal zone as extending down to the level of
origin of the left lower lobe and right middle lobe
bronchus.
24
The border between left- and right-side
paratracheal nodes is the left lateral border of the tra-
chea (not the midline). The 4R nodal area extends
from the lower border of the left innominate vein to
the lower border of the azygous vein; the 4L nodal
region extends from the level of the top of the aortic
arch to the upper border of the left-side pulmonary
artery medial to the ligamentum. The level 2 regions
extend from the border of level 4 to the upper border
of the manubrium in the midline. The supraclavicu-
lar nodes extend from the lower border of the clavi-
cles to the lower border of the cricoid. Further details
and denitions of all the node stations can be found
in Rusch et al.
24

3.2 Criteria for Pathologic N Assessment
The following comments apply to nodal staging at
the time of resection. Issues regarding clinical (pre-
treatment) staging are discussed in section 7.0 of this
article, Type of Stage Classication.
A general AJCC/UICC recommendation is that at
least six lymph nodes/stations be sampled for patho-
logic node staging. The IASLC manual recommends
that three mediastinal (including level 7) and three
N1 nodes/stations be sampled. Whether the number
is supposed to apply to node stations or individual
nodes is undened. Moreover, the pathologist cannot
distinguish six nodal fragments from six separate
nodes (unless the surgeon is meticulous in how nodes
and fragments are labeled and submitted). However,
the IASLC staging committee encourages systematic
intraoperative node assessment as recommended by
clinical guidelines.
25,26

Extrathoracic node involvement is designated as M1b
(eg, a positive axillary node).
Further analyses were done to explore whether
particular node stations within an N category had
any particular impact. No such relationship could be
identied ( Fig 2 ).
8
Specically, there was no differ-
ence in survival among patients with involvement of
only peripheral N1 nodes or hilar N1 nodes, and no
difference based on which N2 nodal stations were
involved. This was true globally as well as within geo-
graphic regions. Survival among patients with pN2
right upper lobe tumors with and without N1 involve-
ment (skip metastases) was not different, although
there was a slight difference among such patients
with a left upper lobe tumor.
8

The IASLC staging committee developed a new
node map
24
to overcome ambiguities arising from dis-
crepancies between previous node maps in use in dif-
ferent geographic regions. Furthermore, the committee
dened several nodal zones as follows: a supraclavic-
ular zone (station 1), an upper zone (stations 2-4), an
aortopulmonary zone (stations 5 and 6), a subcari-
nal zone (station 7), a lower zone (stations 8 and 9),
a hilar zone (stations 10 and 11), and a peripheral zone
(stations 12-14). There were no differences in prog-
nosis among involvement of different nodal zones
within the N1 or N2 category. Specically, there was
no difference between patients with a left upper lobe
tumor and involvement of nodes only in station 5 and
6 and patients with a tumor in a different lobe and
involvement of another single N2 nodal zone.
8

The number of involved nodal zones appeared to
have a prognostic impact. Patients with pathologic
single-zone N1 involvement had better survival than
those with pathologic multizone N1 involvement (5-year
survival, 48% vs 35%; P , .09). Similarly, patients
with pathologic single-zone N2 involvement had bet ter
Figure 2. [Section 3.0] Median survival (mo) of patients in the
International Association for the Study of Lung Cancer database with
single lymph node zone involvement.
8
NS 5 not signicant.
Furthermore, the denition of number of nodes/sta-
tions needed for pathologic staging by IASLC and
AJCC is confusing. If all nodes are negative, the tumor
is dened as pN0, regardless of the number sam-
pled, yet if some are positive, it is implied that only
cN status be used if fewer than six nodes/stations
were sampled. To avoid this awkward inconsistency,
the ACCP panel endorses the suggestion
14
that when-
ever fewer than six nodes/stations are sampled at
resection, the tumor is classied as pN0, pN1, or pN2
with the uncertainty descriptor [eg, pN0(un)], as is
described in section 8.0 of this article, Additional
Descriptors. This descriptor has been suggested by
IASLC for further testing relative to the complete-
ness of resection (R) classication; however, extrapo-
lation to address an inconsistency in the formal rules
Figure 3. [Section 3.1] The International Association for the Study of Lung Cancer lymph node map,
including the proposed grouping of lymph node stations into zones for the purposes of prognostic anal-
yses. Ao 5 aorta; Eso 5 esophagus; L 5 left side; mPA 5 main pulmonary artery; R 5 right side; SVC 5
superior vena cava; T 5 trachea. Reproduced with permission from Rusch et al.
24

regarding the denition of pN status seems reason-
able to the panel.
Biopsy of only one sentinel node is considered
adequate and is denoted as pN0(sn) if ndings are
negative and pN1-3(sn) if positive, reecting the level
of the sentinel node. However, sentinel node iden-
tication in lung cancer is variable and not widely
practiced.
27-29

4.0 M Descriptor
The new stage classication system no longer rec-
ognizes the term MX because clinical staging infor-
mation is always available. A history and physical
examination are critical parts of clinical staging and
often are very reliable without further imaging or
biopsy.
The presence of distant metastases is classied as
M1b.
9
Slightly worse survival was seen in patients
with multiple vs a solitary distant metastasis (median
survival, 5 months vs 6 months; 1 year survival, 20%
vs 23%; P 5 0,006).
9
No differences were noted by
the site of a solitary distant metastasis except slightly
shorter survival for a solitary brain metastasis. How-
ever, the data set was too limited for adequate valida-
tion, and further subdivision of the M1b category was
not undertaken.
9

Pleural (or pericardial) involvement (either mul-
tiple implants or a malignant effusion) is classied as
M1a because of slightly better survival than for dis-
tant metastatic sites and worse survival than for other
categories of T4.
9
These prognostic differences were
highly statistically signicant and held up to inter-
nal validation (across database types and geographic
Figure 4. [Section 3.1] A-F, Illustrations of how the International Association for the Study of Lung Cancer
lymph node map can be applied to clinical staging by CT scan in axial (A-C), coronal (D), and sagittal
(E, F) views. A and B, The border between the right- and left-side paratracheal region is shown. Az 5 azy-
gous vein; InV 5 innominate vein; LLLB 5 left lower lobe bronchus; Lt 5 left; MB 5 mainstem bron-
chus; PA 5 pulmonary artery; Rt 5 right; SCA 5 subclavian artery; SPV 5 superior pulmonary vein. See
Figure 2 legend for expansion of other abbreviations . Reproduced with permission from Rusch et al.
24

regions) as well as external validation (ie, the Surveil-
lance Epidemiology and End Results [SEER] database).
9

The IASLC, AJCC, and UICC manuals are confus-
ing about whether M1a applies to only the ipsilateral
pleura or also to the contralateral pleura
14
; the ACCP
panel suggests that it apply to both.
5.0 Stage Grouping
The IASLC staging committee dened stage group-
ings ( Figs 5, 6 ). Despite the recognition of many new
subdivisions of the T and M descriptors, the stage
grouping has no new subdivisions. However, the def-
inition of the stage groups has become more com-
plex because of the additional T and M descrip tor
subgroups. An online tool to manage the complexity
and to assist in on-the-spot denition of a tumors
stage is available at http://staginglungcancer.org.
30

Illustrations of the TNM categories and subcate-
gories included within each stage group are shown
in Figures 7 to 9 .
6.0 Additional Tumor Nodules and
Multiple Primary Lung Cancers
The classication of patients with additional tumor
nodules has created confusion largely related to a lack
of appreciation of distinctly different categories of
such nodules. Applying a classication system intended
for one category to a different group has the potential
to lead to suboptimal treatment and outcomes.
The rst category involves patients with a newly
found lung cancer who have another (small) nodule
detected by imaging. The majority (about 75%) of
additional pulmonary nodules seen on CT imaging in
patients with potentially operable cI to cIIIa primary
lung cancer are benign (see Evaluation of Individuals
With Pulmonary Nodules: When Is It Lung Can-
cer? by Gould et al
31
in the ACCP Lung Cancer
Guidelines).
32-35
An expert panel (ie, a multidisciplinary
tumor board that includes chest radiology, thoracic
surgery, and pulmonary medicine) usually can arrive
at a strong consensus about most of these lesions.
36

Although rm data are lacking, experience suggests
that the judgment is seldom wrong when such an
informed review deems an additional nodule to most
likely be benign.
36

A second category involves patients with an advanced
primary cancer (most often also with nodal involve-
ment) who have several pulmonary nodules or a single
pulmonary nodule and other sites that appear typ-
ical for distant metastases. Again, the judgment of
a tumor board that the additional nodules in such a
presentation represent metastatic disease is rarely
called into question by the subsequent course of the
dis ease (although specic data documenting this
are lacking).
6.1 Second Primary Lung Cancers
Occasionally, patients with a typical clinical presen-
tation of a lung cancer (ie, a solid, spiculated mass in
a patient with lung cancer risk factors) also exhibit a
second lesion with such a typical appearance (either
synchronously or metachronously). In fact, the inci-
dence of a second primary lung cancer has been con-
sistently found to be approximately 1.5% to 2% per
patient per year.
37-47
Traditionally, this group has been
dened by a clinical team guided by criteria devel-
oped empirically by Martini and Melamed
48
in 1975
Figure 5. [Section 5.0] Stage groups according to TNM
descriptor and subgroups. Reproduced with permission from
Detterbeck et al.
13

Figure 6. [Section 5.0] TNM elements included in stage groups.
Adapted with permission from Detterbeck et al.
13

*Percentage of patients in IASLC database according to best stage
(rounded to nearest integer).
10
and more recently rened by the ACCP using indi-
rect data ( Fig 10 ).
34,49
The majority of tumors clas-
sied in this way have been of the same histologic
type,
37,41,42,50-61
which is logical because the etiology of
both cancers is likely the same (ie, genetic predispo-
sition, environmental exposures). Furthermore, similar
survival results have consistently been found whether
the histologic type is the same or different,
51-55,58,60-66

suggesting that the traditional denition of second
primary lung cancers based on clinical features (as
opposed to one based only on different histology) is
generally correct.
The IASLC staging committee puts the responsi-
bility of identifying second primary lung cancers
squarely on the pathologist.
6
However, dening sec-
ond primary lung cancers primarily by histologic fea-
tures is problematic for several reasons. First, this
deviates from the denition that has been in use,
thereby dening patients differently moving forward
than what was done in the IASLC database. Second,
this creates tremendous pressure to use genetic and
morphologic characteristics that are not yet standard-
ized or validated. Finally, pathologic assessment has
primarily involved resected specimens, yet clinical
Figure 7. [Section 5.0] Graphic illustration of stages 0, I, and II. Reproduced with permission from
Detterbeck et al.
13

management necessitates a preoperative denition. The
applicability of postoperative data to limited biopsy
specimens is poorly dened.
Differentiation of adenocarcinomas (in resected
specimens) by the percentage of morphologic pat-
terns (eg, acinar, papillary) has been proposed.
16,19,22,66-70

Denition of second primary lung cancers by genetic
characteristics has produced conicting results so
far.
71-77
How valid these measures are in differenti-
ating a second primary lung cancer from a metastasis
requires further study, and whether these techniques
can be applied to small biopsy specimens is unclear.
The AJCC, UICC, and IASLC rules are confusing
with regard to stage classication. The IASLC stated
that multiple synchronous primary tumors should
be staged separately.
6
However, the next sentence
states, The highest T category and stage of disease
should be assigned and the multiplicity of the num-
ber of tumors should be indicated in parenthesis,
e.g. T2(m) or T2(5).
6
It seems contradictory that sepa-
rate staging can be achieved by combining all tumors
under one TNM designation. The AJCC spec ied that
this multiple tumor classication T(m) applies to tumors
of the same histology,
4
but the IASLC implied that
Figure 8. [Section 5.0] Graphic illustration of stages IIIA and IIIB. Reproduced with permission from
Detterbeck et al.
13

the T(m) NM classication be used even with differ-
ent histologic types.
6
The UICC 2010 manual did not
comment on this,
3
but the 2012 supplement manual
stated, A tumor in the same organ with a different
histologic type is counted as a new tumor.
5
Finally,
the AJCC manual stated that in simultaneous bilat-
eral cancers in paired organs, the tumors are classied
separately as independent tumors in different organs,
4

with essentially the same wording used by UICC and
IASLC.
3,6
Whether this means a TNM designation for
each one or for both together is not explained. Fur-
thermore, there is confusion about whether the lungs
are considered together as one organ or two paired
organs (unclear in AJCC but clearly listed as a paired
single organ by UICC).
3,4

Therefore, the ACCP panel endorses the sugges-
tion that second primary lung cancers be dened by
an experienced multidisciplinary team,
14
using collec-
tive judgment and considering all information (including
the imaging, risk factors, suspicion of distant dissem-
ination, and the pathologists condence given the
available specimens). A careful evaluation for distant
and mediastinal metastases is strongly recommended
(see the articles Methods for Staging Non-small Cell
Lung Cancer by Silvestri et al
78
and Treatment of
Small Cell Lung Cancer by Jett et al
79
in the ACCP
Lung Cancer Guidelines). A regional dedicated tho-
racic oncology team should be consulted if not avail-
able locally.
In addition, with the hope that this will reduce con-
fusion, the ACCP panel recommends that when two
lung cancers with a typical appearance (solid, spicu-
lated, or lobulated) are deemed to be synchronous
primary cancers, they be classied with a TNM descrip-
tor for each tumor. The combined T(m) classication
should be reserved for multifocal tumors (usually
more than two) that typically have a GGO appear-
ance (as discussed in section 6.3 ).
6.2 Additional Pulmonary Tumor Nodules
The IASLC database contains cases of lung cancer
with additional pulmonary tumor nodules of cancer,
accounting for a small portion (2.5%) of the database.
Second primary lung cancers and metastatic disease
(M1) were specically excluded from this category;
however, there is no information regarding how the
contributing centers dened such additional nodule
cases beyond this.
Because of similar relative survival differences,
these nodules were classied within the T3, T4, and
M1a descriptor cohorts if they were located in the
same lobe, an ipsilaterally different lobe, or the con-
tralateral lung, respectively (ie, T3
Satell
, T4
Ipsi Nod
, and
M1a
Contr Nod
in Fig 1 ). Because of conicting deni-
tions in the IASLC and AJCC manuals, it is unclear
whether the additional tumor nodule designation is
meant to apply only to lesions that can be recog-
nized grossly or also to lesions detected solely by the
pathologist.
4-6

It has been suggested that the IASLC stage classi-
cation of additional pulmonary tumor nodules T(m)
be used for patients with a dominant classic lung can-
cer (ie, solid, spiculated) who have an additional nod-
ule with similar radiographic and histologic features.
14

The ACCP panel endorses this denition and suggests
Figure 9. [Section 5.0] Graphic illustration of stage IV. Repro-
duced with permission from Detterbeck et al.
13

Figure 10. [Section 6.1] Denition of multiple primary lung
cancers.
that the additional nodule classication also applies to
lesions that are not clinically apparent. It is not clear
that this denition matches the cases included in the
IASLC database. The database may have included
some multifocal, predominantly GGO lesions because
this cohort included mostly cases from Asia
2
(where
such tumors appear to becoming more common),
80,81

although the fact that the IASLC database includes
only cases from 1990 to 2000 probably diminishes
this effect because the detection of GGO lesions
appears to have been less common during this period.
It is important to note that the IASLC database
does not clearly dene the prognosis of patients with
additional nodules that are encountered clinically today.
First, the denitions used in the IASLC database for
this cohort are unclear. Second, the prognosis varies
signicantly among geographic regions and types of
databases. Finally, treatment was not accounted for
in the analysis yet varied markedly (96% and 88% of
T3
Satell
and T4
Ipsi Nod
, respectively, were managed sur-
gically vs 2% of M1a
Contr Nod
).
2,7,9
In fact, patients with
additional tumor nodules who underwent resection
exhibited good 5-year survival (45% for T3
Satell
N0 M0
R0, 48% for pT4
Ipsi Nod
N0 M0 R0).
7

6.3 Multiple (Multifocal) Lung Cancers
Multifocal disease is well recognized for bronchi-
oloalveolar carcinoma (BAC)
82-84
; however, because
the term BAC was used in different ways, its use has
been abandoned.
19
Although the term BAC has been
retired, patients are still seen with multiple foci of such
tumors. The spectrum of lesions that were included
under the rubric of BAC included newly dened his-
tologic entities (ie, adenocarcinoma in situ, mini-
mally invasive adenocarcinoma, lepidic predominant
adenocarcinoma)
19
; the nature and relationship of these
lesions to one another is not yet well understood.
19,21,83-90

These factors have led to confusion about how to
classify multifocal disease, which is exacerbated by
wording in the stage classication manuals that can
be interpreted in different ways. Such multifocal
tumors (ie, what would formerly have been called
multifocal BAC) currently are variably classied as
multiple distant metastases, synchronous second pri-
mary cancers, and additional nodules. A more uni-
form classication is needed, or the data collected
will be uninterpretable.
The ACCP panel endorses the suggestion that the
T(m) designation be used for patients with multifocal
lung cancer, meaning patients with several GGO
lesions that are malignant or contain numerous small
foci.
14
The AJCC and UICC rules suggest that mul-
tiple simultaneous tumors be classied by the highest
T stage of one focus with the number of tumors in
parentheses.
3,4
For example, a patient with four GGO
lesions all measuring , 2 cm would be classied as
having T1a(4) disease. In this classication category,
the N and M designations apply to all the multi-
ple tumor foci. The T(m) designation should only be
applied to lesions that are either proven or strongly
suspected to be malignant, that is, not atypical adeno-
matous hyperplasia (AAH) lesions. This appears to
be consistent with the intent of the T(m) designation
according to the IASLC manual, which specically
mentions the common occurrence of multiple foci
of BAC tumors.
The ACCP panel denes multifocal lung cancers as
multiple GGO lesions, which may, however, develop
a solid component.
62,83,87,91,92
There may be a few
or many lesions.
92
We include patients with such a
malignant GGO lesion (either suspected or proven)
and other small GGO lesions that are likely AAH
because data suggest that AAH is a precursor to such
tumors.
21,83-89,93,94
Including such patients also sat-
ises the need for a clinically applicable denition.
At the other end of the spectrum are patients with an
inltrative pattern of disease conned to a partic-
ular area (segment or lobe) or appearing diffusely in
the lung parenchyma (also called pneumonic type
of adenocarcinoma).
62,95,96
These lesions should also
be included among multifocal cancers.
Multifocal cancers appear to have a decreased propen-
sity for nodal or systemic spread and an increased pro-
pensity to develop additional pulmonary foci.
62,83,87,91,97

This feature seems to t with what was intended by
the T(m) nomenclature, which designates multiple
tumors in the T descriptor but maintains a composite
N and M designation that applies to all the multiple
tumors in aggregate. Further study of this form of
lung cancer is needed. Nevertheless, adoption of a
classication nomenclature, even if imperfect, will
facilitate such research by more precisely identifying
a specic and homogeneous population.
7.0 Type of Stage Classification
The main stage classication types are clinical and
pathologic ( Fig 11 ). According to the AJCC manual,
4

clinical stage (pretreatment classication) encom-
passes any information obtainedbefore initiation
of denitive treatment, incorporating symptoms and
Figure 11. [Section 7.0] Types of staging assessments.
physical examination; imaging; endoscopy; biopsy;
and surgical staging procedures, including explora-
tion. The pathologic stage (postsurgical classication)
includes information from the clinical stage supple-
mented by information obtainedthrough completion
of denitive surgery.
4
Other stage classication types
( Fig 11 ) include restaging after induction treatment
(designated yc or yp), staging when recurrence develops
(designated by r), or staging at autopsy (designated
by a). Although pathologic stage is more accurate,
clinical stage is what is available when treatment
decisions are made.
Complexity arises because the AJCC allows clin-
ical and pathologic classication to be applied to indi-
vidual T, N, and M descriptors and allows use of
individual pT and pN descriptors outside the setting
of (intended) surgical resection.
4
This creates confu-
sion because procedures explicitly classied as clin-
ical staging nevertheless yield results that can dene
a pT or pN descriptor, and the overall classication
can be a mixture of clinical or pathologic individual T,
N, and M descriptors. Note that the UICC and IASLC
do not recognize this individual p designation out-
side the setting of a surgical resection (or attempted
resection).
Denition of pT status outside the setting of
attempted resection requires biopsy specimen proof
of invasion to conrm the highest T category. Practi-
cally speaking, such a clinical determination of pT is
rare but might include biopsy specimen proof of cari-
nal involvement (or potentially an excisional wedge
resection specimen that denes the largest tumor
dimension yet was not intended as a therapeutic pro-
cedure). The designation of pM can be used when
there is biopsy specimen proof of a distant (or pleu-
ral/pericardial) metastasis; however, a pM0 designa-
tion does not exist, even if a biopsy is done (only cM0).
AJCC denition of pN outside the setting of
attempted resection is particularly problematic.
98,99

This requires one of the following: (1) biopsy spec-
imen proof of N3; (2) all nodes with negative biopsy
specimen ndings, regardless of number sampled
(presumably at least 1); (3) any microscopic evalu-
ation of nodes if pT status is dened; or (4) a sentinel
node biopsy specimen and denition of pT status.
Thus, although endobronchial ultrasound or medi-
astinoscopy explicitly comprise clinical staging, the
result can be viewed as dening a pN status.
Complex rules govern assignment of an overall clin-
ical or pathologic designation to a mixture of indi-
vidual descriptors (eg, cT1pN3cM1, pT2cN0cM1,
cT2cN0pM1). In the absence of resection, the overall
classication is pathologic if (1) an M1 biopsy spec-
imen nding is positive (ie, cTcNpM1), (2) an N3
biopsy specimen nding (the highest N category) is
positive (ie, cTpN3cM0), or (3) the T stage is con-
rmed by biopsy specimen and nodal involvement
at any level is conrmed (ie, pT1-4pN1-3cM0). All other
combinations of cT, pT, cN, pN, and cM dene an over-
all clinical stage. The denition is awkward in a non-
resectional setting because pN0 is unacceptable for
dening overall pathologic stage (eg, pT1-4pN1-3cM0
is classied as pathologic, whereas pT1-4pN0cM0
is clinical). Presumably, these rules pertain only to
patients with unresected lesions; otherwise, clinical
staging would apply to all with N0, even if resected,
including a complete lymphadenectomy.
The AJCC staging rules are ambiguous and appear
to allow for several approaches. The approach that
avoids the confusion and ambiguity arising from the
others is to restrict pathologic staging to the postresec-
tion stage (or rarely an aborted resection with exten-
sive biopsy specimens). Pretreatment staging remains
clinical; if such staging involves biopsy specimens,
the UICC rules allow for the use of cT, cN, or cM
along with a certainty factor classication (eg, cN2C3)
rather than pT or pN. The C designation is described
in the next section and summarized in Figure 12 .
This approach is suggested by the ACCP panel.
8.0 Additional Descriptors
8.1 Certainty Factor
The UICC has dened an optional C factor ( Fig 12 )
to denote the extent of investigation performed to
establish the stage designation (ie, clinical evaluation,
imaging and needle aspiration, surgical staging, resec-
tion). This factor can be applied to the entire stage
or to individual T, N, and M descriptors. This factor
carries the misleading name of certainty , implying
that certainty is related primarily to the specic tech-
nique, whereas in reality, the clinical setting is most
important (eg, a normal mediastinum on PET scan
has a false-negative rate of , 5% for peripheral cI
tumors vs about 25% for central tumors).
100,101
Fur-
thermore, the thoroughness of staging procedures var-
ies greatly.
102

8.2 Completeness of Resection
The completeness of resection (radicality) is more
clearly dened in the new system ( Fig 12 ). A positive
margin includes nodal margins and positive pleural
or pericardial uid cytology. According to sugges-
tive individual studies, several new classications
will be tested, including pleural or pericardial lavage
cytology, highest mediastinal node involvement, or
nodal classication based on a limited assessment.
Additional descriptors have been developed for the
depth of visceral pleural invasion, chest wall invasion,
lymphatic and vascular invasion, and the number of
nodal zones involved.
14

tion and should be coded as N0 (or M0), regard-
less of node level harboring the ITCs [eg, pN0(i 1 ),
pN0(mol 1 )]. The prognostic value of ITCs has been
inconsistent.
104-109

9.0 Applicability to Different
Lung Cancer Types
The seventh edition of the Lung Cancer Stage
Classication is applicable to all major types of pri-
mary lung cancer. The system was developed based
on non-small cell lung cancer; however, validation
studies in patients with small cell lung cancer
11
and
carcinoid tumors
12
have demonstrated that the de-
nitions are also of value in these cohorts. Therefore,
8.3 Minimal Disease
Sophisticated immunohistochemical and genetic
techniques permit detection of very small tumor
deposits ( Fig 12 ). A micrometastasis as dened by
the UICC and AJCC
3,4
is 0.2 to 2 mm in size and
usually is detected by routine hematoxylin and eosin
staining; typically, mitoses and invasion are seen.
103

Such micrometastases in nodes or distant sites are
counted as positive and denoted by the symbol (mi)
[eg cN1(mi), pN2(mi)]. However, the prognostic impact
was not evaluated in the IASLC staging analysis.
Isolated tumor cells (ITCs) are small clumps of
tumor cells ( , 0.2 mm), typically without mitoses or
vascular or lymphatic invasion. ITCs within nodes (or
distant sites) are not counted in the stage classica-
Figure 12. [Sections 7.0, 8.0] Additional descriptors.
The classication can also be applied to distant metastatic sites (M0). Nonmorphologic techniques include DNA or RNA analysis or ow cytometry.
CXR 5 chest radiograph; ITC 5 isolated tumor cell.

a
In greatest dimension.
the stage classication should be applied to patients
with these tumors as well.
10.0 Discussion
The purpose of the stage classication system is
to provide a nomenclature to describe the anatomic
extent of disease. In the past, the descriptors and
groupings have been based largely on what seemed
to be logical; in the current seventh edition, this is
based on extensive statistical analysis. The basis for
deciding that a particular cut point or denition was a
good criterion to distinguish one group from another
was a difference in prognosis between the groups
that was consistent in multiple subset analyses (geo-

Figure 13. [Section 10.0] Median survival (mo) of the clinical
T descriptor cohort (cN0, cM0) in the International Association for
the Study of Lung Cancer database according to the geographic
region and database type. Aus 5 Australia; Clin 5 clinical.
2

Figure 14. [Section 10.0] Median survival (mo) of the clinical N
descriptor cohort (cT Any , cM0) in the International Association
for the Study of Lung Cancer database according to the geo-
graphic region and database type. See Figure 13 legend for expan-
sion of abbreviations.
2

Figure 15. [Section 10.0] Treatment given (as percentage of
total) in NCDB (2004-2007) to patients with non-small cell lung
cancer (n 5 22,044) whose stage grouping shifted from the desig-
nation in the sixth to the seventh edition of the Lung Cancer Stage
Classication system. Ch 5 chemotherapy; ChRT 5 chemoradio-
therapy; ChRT-S 5 chemoradiotherapy then surgery; Ch-S 5 che-
motherapy then surgery; NCDB 5 National Cancer Database; No
Tmt 5 no treatment; RT 5 radiotherapy; S 5 surgery alone; S-Ch 5
surgery then chemotherapy; S-ChRT 5 surgery then chemoradio-
therapy; S-RT 5 surgery then radiotherapy. See Figure 4 legend
for expansion of other abbreviations. Reproduced with permis-
sion from Boffa et al.
110

graphic, histologic, database type, time period, clinical
or pathologic) as well as in external validation (ie, Sur-
veillance Epidemiology and End Results database).
Thus, prognosis was used as a tool in the analysis,
and differences in prognosis were the end points of
analysis.
How do we use the staging nomenclature? A clin-
ical need is to select the optimal treatment of patients,
and the anatomic extent of disease is certainly a major
factor in the treatment selection. However, we cannot
expect the stage classication to serve as a treatment
algorithm. First, many other factors affect the treat-
ment selection, including functional status, comor-
bidities, histology, and personal factors. Second, the
criterion used to separate or group patients was not
whether current guidelines recommended treatment
that was the same or different . Finally, progress in
dening optimal treatment should be continuous and
informed by the results of clinical trials. Stage classi-
cation is relatively static, updated every 7 or 8 years
when a new edition is produced. Thus, the stage
classication is useful in describing one factor related
to choosing a treatment strategy and in assessing
whether the results of a clinical trial may be applicable
to a particular patient, but it does not by itself dene
a treatment approach.
Another clinical need is to dene prognosis. Again,
the anatomic extent of disease is an important factor
that contributes to prognosis. However, there are
many other prognostic factors, including those related
to the tumor, patient, treatment, and clinical and social
setting. There is a need for a prognostication tool that
takes these factors into account, and it is often sug-
gested that the stage classication be modied to include
other factors (eg, shifting stage grouping up or down
depending on patient age or other factors). However,
prognostication is extremely complex, and such an
approach is overly simplistic. For example, certain
factors may be highly signicant if a particular treat-
ment is given but have little relevance in other set-
tings. Therefore, acknowledging only a few prognostic
factors and adjusting the TNM stage would be insuf-
cient to dene prognosis yet could tremendously
complicate use of the TNM system; it is best to sepa-
rate prognostication from anatomic disease descrip-
tion and allow time for development of a sophisticated
prognostication tool.
We need to be careful in applying prognostic data
from the IASLC database. It is true that this database
is the largest available and denes prognosis for patients
with a certain anatomic extent of disease from around
the world, but there were marked differences in pro-
gnosis in different geographic regions and by data-
base type ( Figs 13, 14 ), and which region or database
type was better varied between T and N categories. It
is not clear why prognosis varied so much; no consis-
tent factor has been identied, although many have
Figure 16. [Section 11.0] ACCP suggestions to avoid ambiguities in the IASLC, UICC, and AJCC stage classication systems.
ACCP 5 American College of Chest Physicians; AJCC 5 American Joint Committee on Cancer; GGO 5 ground glass opacity; IASLC 5 International
Association for the Study of Lung Cancer; UICC 5 Union Internationale Contre le Cancer.

a
Explicitly dened by AJCC or UICC, listed here nevertheless because of common lack of awareness of this.

b
Implied by AJCC or UICC.
been suggested (eg, genetic variation, such as the
frequency of epidermal growth factor receptor muta-
tions or differences in the proportion of nonsmokers
in different regions). Furthermore, the treatment
given was not accounted for or validated in the IASLC
database. A comparison of what treatment was given
in the US National Cancer Database (which does have
validated treatment data) for those cohorts whose
stage grouping changed from the sixth to the seventh
edition shows marked variation ( Fig 15 ). Therefore,
we must acknowledge that the IASLC database does
not precisely dene the prognosis for a particular
patient, and we certainly cannot assume that it has
dened the prognosis for a particular treatment
approach.
We must be particularly careful in the use of prog-
nosis to guide decisions about treatment. The fact that
survival is poor does not necessarily imply that it is
worth adding further therapy (eg, adjuvant chemo-
therapy); what we really need is data demonstrating
that additional treatment actually improves survival.
At the same time, we should not rule out a particular
approach just because (our perception of) prognosis
is poor. In the IASLC database, patients with pleural
involvement or with ipsilaterally different lobe nod-
ules who underwent resection actually had good sur-
vival (5-year survival, 31% if pT
Any
N0 M1a
Pl Dissem
R0
and 48% for pT4
Ipsi Nod
N0 M0 R0).
7
The patients who
underwent resection, of course, represent a selected
subgroup. However, these observations illustrate how
the interplay among clinical and pathologic staging,
treatment approach, and patient selection can inu-
ence our perception of similar outcomes.
Although the stage groupings are a reasonable way
to group patients and are based on a sound statistical
analysis, this does not prove that the tumor biology is
homogeneous. For example, the survival curves of
patients with T4
Inv
and T4
Ipsi Nod
tumors do not neces-
sarily track together, suggesting that there may be
biologic differences. Certainly, there are groups that
have a similar prognosis but markedly different clin-
ical characteristics (eg, stage IIIA includes patients
with N2 disease [T1-3 N2 M0], those with extensive
local invasion only [T4
Inv
N0 M0], and those with ip-
silateral additional tumor nodules [T4
Ipsi Nod
N0 M0]).
We must view stage classication as a useful tool that
may well change over time as our understanding and
treatment outcomes evolve.
11.0 Conclusion
There is no question that the IASLC staging classi-
cation is a major advance. The size of the database,
the broad international spectrum, the careful and
detailed analysis, and the internal and external val-
idation are tremendous achievements and relatively
unique among types of cancer. Inevitably, it is also
more complex, and with more rened data comes a
greater ability to discern granular details. As with any
complex system, rules that seem clear in one context
can seem awkward or conicting in another. This arti-
cle reviews the fundamental denitions as well as
suggested approaches that minimize the conicts in
those cases where ambiguous rules create confu-
sion ( Fig 16 ). A thorough understanding of the stage
classication is essential because it is fundamental
to our ability to converse clearly about patients with
cancer.
Acknowledgments
Author contributions: Dr Detterbeck had full access to all of
the data in the study and takes responsibility for the integrity of
the data and the accuracy of the data analysis.
Dr Detterbeck: contributed to the conceptual approach, review
of staging manuals, and writing of the manuscript.
Dr Postmus: contributed to the review and revisions of the manu-
script.
Dr Tanoue: contributed to the review and revisions of the manu-
script.
Financial/nonnancial disclosures: The authors have reported
to CHEST the following conicts of interest: Dr Detterbeck is a
member of the International Association for the Study of Lung
Cancer International Staging Committee and a speaker in an edu-
cational program regarding lung cancer stage classication; both
activities are funded by Lilly Oncology (Lilly USA, LLC). He has
participated on a scientic advisory panel for Oncimmune (USA)
LLC; an external grant administration board for Pzer, Inc; a mul-
ticenter study of a device for Medela; and formerly a multicenter
study of a device for DeepBreeze. Compensation for these activ-
ities is paid directly to Yale University. Drs Postmus and Tanoue
have reported that no potential conicts of interest exist with any
companies/organizations whose products or services may be dis-
cussed in this article .
Role of Sponsors: The American College of Chest Physicians
was solely responsible for the development of these guidelines.
The remaining supporters played no role in the development
process. External supporting organizations cannot recommend
panelists or topics, nor are they allowed prepublication access to
the manuscripts and recommendations. Further details on the
Conict of Interest Policy are available online at http://chestnet.
org.
Endorsements: This guideline is endorsed by the European
Society of Thoracic Surgeons, Oncology Nursing Society, American
Association for Bronchology and Interventional Pulmonology, and
the Society of Thoracic Surgeons.
Other contributions: The authors thank Ramon Rami-Porta,
MD, for his thoughtful critique during the development of this
article and review of the nal manuscript.
References
1 . Lewis SZ , Diekemper R , Addrizzo-Harris DJ . Methodology
for development of guidelines for lung cancer: diagnosis
and management of lung cancer, 3rd ed: American College
of Chest Physicians evidence-based clinical practice guide-
lines. Chest . 2013; 143 ( 5 )( suppl ): 41S - 50S .
2 . Groome PA , Bolejack V , Crowley JJ , et al ; IASLC Interna-
tional Staging Committee ; Cancer Research and Biostatis-
tics ; Observers to the Committee ; Participating Institutions .
The IASLC Lung Cancer Staging Project: validation of the
proposals for revision of the T, N, and M descriptors and
consequent stage groupings in the forthcoming (seventh)
edition of the TNM classication of malignant tumours .
J Thorac Oncol . 2007 ; 2 ( 8 ): 694 - 705 .
3 . Union Internationale Contre le Cancer. TNM Classication
of Malignant Tumors . 7th ed. Hoboken, NJ : Wiley-Blackwell ;
2009 .
4 . American Joint Committee on Cancer. AJCC Cancer Staging
Manual. 7th ed. New York, NY : Springer ; 2009 .
5 . Wittekind C , ed. TNM Supplement: A Commentary on
Uniform Use . 4th ed. London, England: John Wiley & Sons ;
2012 .
6. Goldstraw P, ed. IASLC Staging Manual in Thoracic Oncology .
Orange Park, FL: Editorial Rx Press; 2009
7 . Rami-Porta R , Ball D , Crowley J , et al ; International Staging
Committee ; Cancer Research and Biostatistics ; Observers to
the Committee ; Participating Institutions . The IASLC Lung
Cancer Staging Project: proposals for the revision of the T
descriptors in the forthcoming (seventh) edition of the TNM
classication for lung cancer . J Thorac Oncol . 2007 ; 2 ( 7 ):
593 - 602 .
8 . Rusch VW , Crowley J , Giroux DJ , et al ; International
Association for the Study of Lung Cancer International
Staging Committee ; Cancer Research and Biostatistics ;
Observers to the Committee ; Participating Institutions . The
IASLC Lung Cancer Staging Project: proposals for the revi-
sion of the N descriptors in the forthcoming seventh edition
of the TNM classication for lung cancer. J Thorac Oncol .
2007 ;2(7):603-612.
9 . Postmus PE , Brambilla E , Chansky K , et al ; International
Association for the Study of Lung Cancer International
Staging Committee ; Cancer Research and Biostatistics ;
Observers to the Committee ; Participating Institutions . The
IASLC Lung Cancer Staging Project: proposals for revision
of the M descriptors in the forthcoming (seventh) edition
of the TNM classication of lung cancer . J Thorac Oncol .
2007 ; 2 ( 8 ): 686 - 693 .
10 . Goldstraw P , Crowley J , Chansky K , et al ; International
Association for the Study of Lung Cancer International Stag-
ing Committee ; Participating Institutions . The IASLC Lung
Cancer Staging Project: proposals for the revision of the
TNM stage groupings in the forthcoming (seventh) edition
of the TNM classication of malignant tumours . J Thorac
Oncol . 2007 ; 2 ( 8 ): 706 - 714 .
11 . Shepherd FA , Crowley J , Van Houtte P , et al ; International
Association for the Study of Lung Cancer International Stag ing
Committee and Participating Institutions . The International
Association for the Study of Lung Cancer lung cancer stag-
ing project: proposals regarding the clinical staging of small
cell lung cancer in the forthcoming (seventh) edition of the
tumor, node, metastasis classication for lung cancer . J Thorac
Oncol . 2007 ; 2 ( 12 ): 1067 - 1077 .
12 . Travis WD , Giroux DJ , Chansky K , et al ; International Staging
Committee and Participating Institutions . The IASLC Lung
Cancer Staging Project: proposals for the inclusion of bron-
cho-pulmonary carcinoid tumors in the forthcoming (seventh)
edition of the TNM Classication for Lung Cancer . J Thorac
Oncol . 2008 ; 3 ( 11 ): 1213 - 1223 .
13 . Detterbeck FC , Boffa DJ , Tanoue LT . The new lung cancer
staging system . Chest . 2009 ; 136 ( 1 ): 260 - 271 .
14 . Detterbeck FC , Boffa DJ , Tanoue LT , Wilson LD . Details and
difculties regarding the new lung cancer staging system .
Chest . 2010 ; 137 ( 5 ): 1172 - 1180 .
15 . Hsu P-K , Huang H-C , Hsieh C-C , et al . Effect of formalin
xation on tumor size determination in stage I non-small
cell lung cancer . Ann Thorac Surg . 2007 ; 84 ( 6 ): 1825 - 1829 .
16 . Yim J , Zhu L-C , Chiriboga L , Watson HN , Goldberg JD ,
Moreira AL . Histologic features are important prognostic
indicators in early stages lung adenocarcinomas . Mod Pathol .
2007 ; 20 ( 2 ): 233 - 241 .
17 . Suzuki K , Yokose T , Yoshida J , et al . Prognostic signicance
of the size of central brosis in peripheral adenocarcinoma
of the lung . Ann Thorac Surg . 2000 ; 69 ( 3 ): 893 - 897 .
18 . Maeshima AM , Niki T , Maeshima A , Yamada T , Kondo H ,
Matsuno Y . Modied scar grade: a prognostic indicator in
small peripheral lung adenocarcinoma . Cancer . 2002 ; 95 ( 12 ):
2546 - 2554 .
19 . Travis W , Brambilla E , Noguchi M , et al . The new IASLC/
ATS/ERS international multidisciplinary lung adenocarcinoma
classication. Paper presented at: 13th World Conference
on Lung Cancer; August 4, 2009; San Francisco, CA.
20 . Yokose T , Suzuki K , Nagai K , Nishiwaki Y , Sasaki S , Ochiai A .
Favorable and unfavorable morphological prognostic factors
in peripheral adenocarcinoma of the lung 3 cm or less in
diameter . Lung Cancer . 2000 ; 29 ( 3 ): 179 - 188 .
21 . Kerr KM . Pulmonary adenocarcinomas: classication and
reporting . Histopathology . 2009 ; 54 ( 1 ): 12 - 27 .
22 . Yoshizawa A , Motoi N , Riely GJ , et al . Impact of proposed
IASLC/ATS/ERS classication of lung adenocarcinoma:
prognostic subgroups and implications for further revision
of staging based on analysis of 514 stage I cases . Mod Pathol .
2011 ; 24 ( 5 ): 653 - 664 .
23 . Travis WDMD , Brambilla EMD , Rami-Porta RMD , et al ;
International Staging Committee. Visceral pleural invasion:
pathologic criteria and use of elastic stains: proposal for the
7th edition of the TNM classication for lung cancer. J Thorac
Oncol . 2008 ;3(12):1384-1390.
24 . Rusch V , Asamura H , Watanabe H , Giroux DJ, Rami-Porta R,
Goldstraw P; Members of IASLC Staging Committee. The
IASLC Lung Cancer Staging Project: a proposal for a new
international lymph node map in the forthcoming 7th edi-
tion of the TNM classication for lung cancer. J Thorac
Oncol . 2009 ;4(5):568-577.
25 . Detterbeck F , Jantz M , Wallace M , Vansteenkiste J, Silvestri
GA; American College of Chest Physicians. Invasive medi-
astinal staging of lung cancer: ACCP evidence based clinical
practice guidelines (2nd edition). Chest . 2007 ;132(suppl
3):202S-220S.
26 . Lardinois D , De Leyn P , Van Schil P , et al . ESTS guidelines
for intraoperative lymph node staging in non-small cell lung
cancer . Eur J Cardiothorac Surg . 2006 ; 30 ( 5 ): 787 - 792 .
27 . Liptay MJMD , Damico TAMD , Nwogu CMD , et al ; Thoracic
Surgery Subcommittee of the Cancer and Leukemia Group
B . Intraoperative sentinel node mapping with technitium-99
in lung cancer: results of CALGB 140203 multicenter phase
II trial . J Thorac Oncol . 2009 ; 4 ( 2 ): 198 - 202 .
28 . Rzyman W , Hagen OM , Dziadziuszko R , et al . Intraoperative,
radio-guided sentinel lymph node mapping in 110 nonsmall
cell lung cancer patients . Ann Thorac Surg . 2006 ; 82 ( 1 ):
237 - 242 .
29 . Ono T , Minamiya Y , Ito M , et al . Sentinel node mapping
and micrometastasis in patients with clinical stage IA non-
small cell lung cancer . Interact Cardiovasc Thorac Surg .
2009 ; 9 ( 4 ): 659 - 661 .
30 . Kim AW , Johnson KM , Detterbeck FC . The lung cancer
stage page: there when you need itstaginglungcancer.org .
Chest . 2012 ; 141 ( 3 ): 581 - 586 .
31 . Gould MK , Donington J , Lynch WR , et al. Evaluation of
individuals with pulmonary nodules: when is it lung cancer?
diagnosis and management of lung cancer, 3rd ed: American
College of Chest Physicians evidence-based clinical practice
guidelines. Chest . 2013; 143 ( 5 )( suppl ): e93S - e120S .
32 . Keogan MT , Tung KT , Kaplan DK , Goldstraw PJ , Hansell DM .
The signicance of pulmonary nodules detected on CT stag-
ing for lung cancer . Clin Radiol . 1993 ; 48 ( 2 ): 94 - 96 .
54 . Verhagen AFTM , Tavilla G , van de Wal HJCM , Cox AL , Lacquet
LK . Multiple primary lung cancers . Thorac Cardiovasc Surg .
1994 ; 42 ( 1 ): 40 - 44 .
55 . Adebonojo SA , Moritz DM , Danby CA . The results of modern
surgical therapy for multiple primary lung cancers . Chest .
1997 ; 112 ( 3 ): 693 - 701 .
56 . Okada M , Tsubota N , Yoshimura M , Miyamoto Y . Operative
approach for multiple primary lung carcinomas . J Thorac
Cardiovasc Surg . 1998 ; 115 ( 4 ): 836 - 840 .
57 . Wu SC , Lin ZQ , Xu CW , Koo KS , Huang OL , Xie DQ .
Multiple primary lung cancers . Chest . 1987 ; 92 ( 5 ): 892 - 896 .
58 . De Leyn P, Moons J , Vansteenkiste J , et al . Survival after resec-
tion of synchronous bilateral lung cancer . Eur J Cardiothorac
Surg . 2008 ; 34 ( 6 ): 1215 - 1222 .
59 . Lee JG , Lee CY , Kim DJ , Chung KY , Park IK . Non-small
cell lung cancer with ipsilateral pulmonary metastases: prog-
nosis analysis and staging assessment . Eur J Cardiothorac
Surg . 2008 ; 33 ( 3 ): 480 - 484 .
60 . Riquet M , Cazes A , Pfeuty K , et al . Multiple lung cancers
prognosis: what about histology? Ann Thorac Surg . 2008 ;
86 ( 3 ): 921 - 926 .
61 . Rostad H , Strand TE , Naalsund A , Norstein J . Resected
synchronous primary malignant lung tumors: a population-
based study . Ann Thorac Surg . 2008 ; 85 ( 1 ): 204 - 209 .
62 . Battafarano RJ , Meyers BF , Guthrie TJ , Cooper JD , Patterson
GA . Surgical resection of multifocal non-small cell lung can-
cer is associated with prolonged survival . Ann Thorac Surg .
2002 ; 74 ( 4 ): 988 - 993 .
63 . Detterbeck FC , Jones DR , Funkhouser WK Jr . Satellite
nodules and multiple primary cancers . In: Detterbeck FC ,
Rivera MP , Socinski MA , et al , eds. Diagnosis and Treatment
of Lung Cancer: an Evidence-Based Guide for the Practicing
Clinician . Philadelphia, PA : W. B. Saunders ; 2001 : 437 - 449 .
64 . Battafarano RJ , Force SD , Meyers BF , et al . Benets of re-
section for metachronous lung cancer . J Thorac Cardiovasc
Surg . 2004 ; 127 ( 3 ): 836 - 842 .
65 . Lee BE , Port JL , Stiles BM , et al . TNM stage is the most
important determinant of survival in metachronous lung
cancer . Ann Thorac Surg . 2009 ; 88 ( 4 ): 1100 - 1105 .
66 . Finley DJ , Yoshizawa A , Travis W , et al . Predictors of out-
comes after surgical treatment of synchronous primary lung
cancers . J Thorac Oncol . 2010 ; 5 ( 2 ): 197 - 205 .
67 . Motoi N , Szoke J , Riely GJ , et al . Lung adenocarcinoma:
modication of the 2004 WHO mixed subtype to include the
major histologic subtype suggests correlations between pap-
illary and micropapillary adenocarcinoma subtypes, EGFR
mutations and gene expression analysis . Am J Surg Pathol .
2008 ; 32 ( 6 ): 810 - 827 .
68 . Russell PA , Wainer Z , Wright GM , Daniels M , Conron
M , Williams RA . Does lung adenocarcinoma subtype pre-
dict patient survival? A clinicopathologic study based on
the new International Association for the Study of Lung
Cancer/American Thoracic Society/European Respiratory
Society international multidisciplinary lung adenocarcinoma
classication . J Thorac Oncol . 2011 ; 6 ( 9 ): 1496 - 1504 .
69 . Sica G , Yoshizawa A , Sima CS , et al . A grading system of
lung adenocarcinomas based on histologic pattern is pre-
dictive of disease recurrence in stage I tumors . Am J Surg
Pathol . 2010 ; 34 ( 8 ): 1155 - 1162 .
70 . Warth A , Muley T , Meister M , et al . The novel histologic
International Association for the Study of Lung Cancer/Amer ican
Thoracic Society/European Respiratory Society classication
system of lung adenocarcinoma is a stage-independent pre-
dictor of survival . J Clin Oncol . 2012 ; 30 ( 13 ): 1438 - 1446 .
71 . Wang X , Wang M , MacLennan GT , et al . Evidence for com-
mon clonal origin of multifocal lung cancers . J Natl Cancer
Inst . 2009 ; 101 ( 8 ): 560 - 570 .
33 . Kunitoh H , Eguchi K , Yamada K , et al . Intrapulmonary sub-
lesions detected before surgery in patients with lung cancer .
Cancer . 1992 ; 70 ( 7 ): 1876 - 1879 .
34 . Shen KR , Meyers BF , Larner JM , Jones DR; American College
of Chest Physicians. Special treatment issues in lung cancer:
ACCP evidence-based clinical practice guidelines (2nd edi-
tion). Chest . 2007 ;132(3):290S-305S.
35 . Cerfolio RJ , Bryant AS . Is palpation of the nonresected
pulmonary lobe(s) required for patients with non-small cell
lung cancer? A prospective study . J Thorac Cardiovasc Surg .
2008 ; 135 ( 2 ): 261 - 268 .
36 . Swensen SJ , Silverstein MD , Edell ES , et al . Solitary pulmo-
nary nodules: clinical prediction model versus physicians .
Mayo Clin Proc . 1999 ; 74 ( 4 ): 319 - 329 .
37 . Antakli T , Schaefer RF , Rutherford JE , Read RC . Second
primary lung cancer . Ann Thorac Surg . 1995 ; 59 ( 4 ): 863 - 866 .
38 . Thomas PA Jr , Rubinstein L ; The Lung Cancer Study Group .
Malignant disease appearing late after operation for T1 N0
non-small-cell lung cancer . J Thorac Cardiovasc Surg . 1993 ;
106 ( 6 ): 1053 - 1058 .
39 . Pastorino U , Infante M , Maioli M , et al . Adjuvant treat-
ment of stage I lung cancer with high-dose vitamin A . J Clin
Oncol . 1993 ; 11 ( 7 ): 1216 - 1222 .
40 . Martini N , Bains MS , Burt ME , et al . Incidence of local
recurrence and second primary tumors in resected stage I
lung cancer . J Thorac Cardiovasc Surg . 1995 ; 109 ( 1 ): 120 - 129 .
41 . Ribet M , Dambron P . Multiple primary lung cancers . Eur J
Cardiothorac Surg . 1995 ; 9 ( 5 ): 231 - 236 .
42 . Van Meerbeeck J , Weyler J , Thibaut A , et al . Second pri-
mary lung cancer in Flanders: frequency, clinical presen-
tation, treatment and prognosis . Lung Cancer . 1996 ; 15 ( 3 ):
281 - 295 .
43 . Levi F , Randimbison L , Te V-C , La Vecchia C . Second
primary cancers in patients with lung carcinoma . Cancer .
1999 ; 86 ( 1 ): 186 - 190 .
44 . Tockman MS , Mulshine JL , Piantadosi S , et al . Prospective
detection of preclinical lung cancer: results from two studies
of heterogeneous ribonucleoprotein A2/B1 overexpression .
Clin Cancer Res . 1997 ; 3 (12 pt 1): 2237-2246 .
45 . Ginsberg RJ , Rubinstein LV ; Lung Cancer Study Group .
Randomized trial of lobectomy versus limited resection
for T1 N0 non-small cell lung cancer . Ann Thorac Surg .
1995 ; 60 ( 3 ): 615 - 622 .
46 . Pairolero PC , Williams DE , Bergstralh EJ , Piehler JM ,
Bernatz PE , Payne WS . Postsurgical stage I bronchogenic
carcinoma: morbid implications of recurrent disease . Ann
Thorac Surg . 1984 ; 38 ( 4 ): 331 - 338 .
47 . Saito Y , Sato M , Sagawa M , et al . Multicentricity in resected
occult bronchogenic squamous cell carcinoma . Ann Thorac
Surg . 1994 ; 57 ( 5 ): 1200 - 1205 .
48 . Martini N , Melamed MR . Multiple primary lung cancers .
J Thorac Cardiovasc Surg . 1975 ; 70 ( 4 ): 606 - 612 .
49 . Detterbeck FC , Jones DR , Kernstine KH , Naunheim KS ;
American College of Physicians . Lung cancer. Special treat-
ment issues . Chest . 2003 ; 123 (suppl 1 ): 244S - 258S .
50 . van Bodegom PC , Wagenaar SS , Corrin B , Baak JP, Berkel J ,
Vanderschueren RG . Second primary lung cancer: impor-
tance of long term follow up . Thorax . 1989 ; 44 ( 10 ): 788 - 793 .
51 . Mathisen DJ , Jensik RJ , Faber LP , Kittle CF . Survival fol-
lowing resection for second and third primary lung cancers .
J Thorac Cardiovasc Surg . 1984 ; 88 ( 4 ): 502 - 510 .
52 . Deschamps C , Pairolero PC , Trastek VF , Payne WS . Multiple
primary lung cancers. Results of surgical treatment . J Thorac
Cardiovasc Surg . 1990 ; 99 ( 5 ): 769 - 777 .
53 . Rosengart TK , Martini N , Ghosn P , Burt M . Multiple pri-
mary lung carcinomas: prognosis and treatment . Ann Thorac
Surg . 1991 ; 52 ( 4 ): 773 - 778 .
88 . Sakuma Y , Matsukuma S , Yoshihara M , et al . Epidermal
growth factor receptor gene mutations in atypical adenoma-
tous hyperplasias of the lung . Mod Pathol . 2007 ; 20 ( 9 ): 967 - 973 .
89 . Takashima S , Maruyama Y , Hasegawa M , et al . CT nd-
ings and progression of small peripheral lung neoplasms
having a replacement growth pattern . AJR Am J Roentgenol .
2003 ; 180 ( 3 ): 817 - 826 .
90 . Kitamura H , Kameda Y , Nakamura N , et al . Atypical ade-
nomatous hyperplasia and bronchoalveolar lung carcinoma.
Analysis by morphometry and the expressions of p53 and carci-
noembryonic antigen . Am J Surg Pathol . 1996 ; 20 ( 5 ): 553 - 562 .
91 . Trousse D , Barlesi F , Loundou A , et al . Synchronous mul-
tiple primary lung cancer: an increasing clinical occurrence
requiring multidisciplinary management . J Thorac Cardiovasc
Surg . 2007 ; 133 ( 5 ): 1193 - 1200 .
92 . Kim HK , Choi YS , Kim J , Shim YM , Lee KS , Kim K . Management
of multiple pure ground-glass opacity lesions in patients
with bronchioloalveolar carcinoma . J Thorac Oncol . 2010 ;
5 ( 2 ): 206 - 210 .
93 . Miller RR , Nelems B , Evans KG , Mller NL , Ostrow DN .
Glandular neoplasia of the lung. A proposed analogy to
colonic tumors . Cancer . 1988 ; 61 ( 5 ): 1009 - 1014 .
94 . Ullmann R , Bongiovanni M , Halbwedl I , et al . Is high-grade
adenomatous hyperplasia an early bronchioloalveolar ade-
nocarcinoma? J Pathol . 2003 ; 201 ( 3 ): 371 - 376 .
95 . Wislez M , Massiani M-A , Milleron B , et al . Clinical char-
acteristics of pneumonic-type adenocarcinoma of the lung .
Chest . 2003 ; 123 ( 6 ): 1868 - 1877 .
96 . Akira M , Atagi S , Kawahara M , Iuchi K , Johkoh T . High-
resolution CT ndings of diffuse bronchioloalveolar carci-
noma in 38 patients . AJR Am J Roentgenol . 1999 ; 173 ( 6 ):
1623 - 1629 .
97 . Park JH , Lee KS , Kim JH , et al . Malignant pure pulmo-
nary ground-glass opacity nodules: prognostic implications .
Korean J Radiol . 2009 ; 10 ( 1 ): 12 - 20 .
98 . Lpez-Encuentra A , Duque-Medina JL , Rami-Porta R .
Persistent confusion on the clinical and pathologic nodal
staging in lung cancer . J Thorac Oncol . 2010 ; 5 ( 2 ): 285 - 286 .
99 . Rami-Porta R , Lpez-Encuentra A , Duque-Medina JL .
Cau tion! The latest AJCCs rules for lung cancer classica-
tion differ from the latest UICCs . Lung Cancer . 2004 ; 43 ( 3 ):
361 - 362 .
100 . Detterbeck FC . Integration of mediastinal staging techniques
for lung cancer . Semin Thorac Cardiovasc Surg . 2007 ; 19 ( 3 ):
217 - 224 .
101 . Silvestri G , Gould MK , Margolis ML , et al ; American College
of Chest Physicians. Noninvasive staging of non-small cell
lung cancer: ACCP evidenced-based clinical practice guide-
lines (2nd edition). Chest . 2007 ;132(suppl 3):178S-201S.
102 . Detterbeck F , Puchalski J , Rubinowitz A , Cheng D . Classi-
cation of the thoroughness of mediastinal staging of lung
cancer . Chest . 2010 ; 137 ( 2 ): 436 - 442 .
103 . Hermanek P , Hutter RVP , Sobin LH , Wittekind C . Inter-
national Union Against Cancer. Classication of isolated tumor
cells and micrometastasis . Cancer . 1999 ; 86 ( 12 ): 2668 - 2673 .
104 . Osaki T , Oyama T , Gu C-D , et al . Prognostic impact of micro-
metastatic tumor cells in the lymph nodes and bone marrow
of patients with completely resected stage I non-small-cell
lung cancer . J Clin Oncol . 2002 ; 20 ( 13 ): 2930 - 2936 .
105 . Wu J , Ohta Y , Minato H , et al . Nodal occult metastasis in
patients with peripheral lung adenocarcinoma of 2.0 cm or
less in diameter . Ann Thorac Surg . 2001 ; 71 ( 6 ): 1772 - 1777 .
106 . Le Pimpec-Barthes F , Danel C , Lacave R , et al . Association of
CK19 mRNA detection of occult cancer cells in mediastinal
lymph nodes in non-small cell lung carcinoma and high risk
of early recurrence . Eur J Cancer . 2005 ; 41 ( 2 ): 306 - 312 .
72 . Hiroshima K , Toyozaki T , Kohno H , Ohwada H , Fujisawa
T . Synchronous and metachronous lung carcinomas: molec-
ular evidence for multicentricity . Pathol Int . 1998 ; 48 ( 11 ):
869 - 876 .
73 . Huang J , Behrens C , Wistuba I , Gazdar AF , Jagirdar J . Molec-
ular analysis of synchronous and metachronous tumors of
the lung: impact on management and prognosis . Ann Diagn
Pathol . 2001 ; 5 ( 6 ): 321 - 329 .
74 . Dacic SMDP , Ionescu DNMD , Finkelstein SMD , Yousem
SA . Patterns of allelic loss of synchronous adenocarcinomas
of the lung . Am J Surg Pathol . 2005 ; 29 ( 7 ): 897 - 902 .
75 . Chang Y-L , Wu C-T , Lin S-C , Hsiao CF , Jou YS , Lee YC .
Clonality and prognostic implications of p53 and epidermal
growth factor receptor somatic aberrations in multiple pri-
mary lung cancers . Clin Cancer Res . 2007 ; 13 ( 1 ): 52 - 58 .
76 . Girard ND , Deshpande C , Lau C , et al . Comprehensive his-
tologic assessment helps to differentiate multiple lung pri-
mary nonsmall cell carcinomas from metastases . Am J Surg
Pathol . 2009 ; 33 ( 12 ): 1752 - 1764 .
77 . Girard N , Ostrovnaya I , Lau C , et al . Genomic and mutational
proling to assess clonal relationships between multiple
non-small cell lung cancers . Clin Cancer Res . 2009 ; 15 ( 16 ):
5184 - 5190 .
78 . Silvestri GA , Gonzalez AV , Jantz MA , et al. Methods for
staging non-small cell lung cancer: diagnosis and manage-
ment of lung cancer, 3rd ed: American College of Chest
Physicians evidence-based clinical practice guidelines. Chest .
2013; 143 ( 5 )( suppl ): e211S - e250S .
79 . Jett JR , Schild SE , Kesler KA , Kalemkerian GP . Treatment
of small cell lung cancer: diagnosis and management of
lung cancer, 3rd ed: American College of Chest Physicians
evidence-based clinical practice guidelines. Chest . 2013;
143 ( 5 )( suppl ): e400S - e419S .
80 . Asamura H , Goya T , Koshiishi Y , et al ; Japanese Joint
Committee of Lung Cancer Registry . A Japanese Lung
Cancer Registry study: prognosis of 13,010 resected lung
cancers . J Thorac Oncol . 2008 ; 3 ( 1 ): 46 - 52 .
81 . Sawabata N , Miyaoka E , Asamura H , et al ; Japanese Joint
Committee for Lung Cancer Registration . Japanese lung
cancer registry study of 11,663 surgical cases in 2004: demo-
graphic and prognosis changes over decade . J Thorac Oncol .
2011 ; 6 ( 7 ): 1229 - 1235 .
82 . Arenberg D; American College of Chest Physicians . Bronchi-
oloalveolar lung cancer: ACCP evidence-based clinical
practice guidelines (2nd edition). Chest. 2007 ;132(suppl 3):
306S-313S.
83 . Gareld DH , Cadranel JL , Wislez M , Franklin WA , Hirsch
FR . The bronchioloalveolar carcinoma and peripheral adeno-
carcinoma spectrum of diseases . J Thorac Oncol . 2006 ; 1 ( 4 ):
344 - 359 .
84 . Detterbeck FC , Jones DR , Funkhouser WK Jr . Bronchi-
oloalveolar carcinoma . In: Detterbeck FC , Rivera MP ,
Socinski MA , et al , eds. Diagnosis and Treatment of Lung
Cancer: An Evidence-Based Guide for the Practicing Clinician .
Philadelphia, PA : W. B. Saunders ; 2001 : 394 - 407 .
85 . Kakinuma R , Ohmatsu H , Kaneko M , et al . Progression of
focal pure ground-glass opacity detected by low-dose helical
computed tomography screening for lung cancer . J Comput
Assist Tomogr . 2004 ; 28 ( 1 ): 17 - 23 .
86 . Nakata M , Sawada S , Yamashita M , et al . Surgical treat-
ments for multiple primary adenocarcinoma of the lung .
Ann Thorac Surg . 2004 ; 78 ( 4 ): 1194 - 1199 .
87 . Travis WD , Garg K , Franklin WA , et al . Evolving concepts
in the pathology and computed tomography imaging of lung
adenocarcinoma and bronchioloalveolar carcinoma . J Clin
Oncol . 2005 ; 23 ( 14 ): 3279 - 3287 .
109 . Marchevsky AM , Qiao J-H , Krajisnik S , Mirocha JM ,
McKenna RJ . The prognostic signicance of intranodal iso-
lated tumor cells and micrometastases in patients with non-
small cell carcinoma of the lung . J Thorac Cardiovasc Surg .
2003 ; 126 ( 2 ): 551 - 557 .
110 . Boffa D , Detterbeck F , Smith E , et al . Should the 7th edition
of the lung cancer stage classication system change treatment
algorithms in NSCLC? J Thorac Oncol . 2010 ;5(11):1779-1783.
107 . Nosotti M , Falleni M , Palleschi A , et al . Quantitative real-
time polymerase chain reaction detection of lymph node
lung cancer micrometastasis using carcinoembryonic antigen
marker . Chest . 2005 ; 128 ( 3 ): 1539 - 1544 .
108 . Maddaus M , Wang X , Vollmer R , et al . CALGB 9761: A pro-
spective analysis of IHC and PCR based detection of occult
metastatic disease in stage I NSCLC. J Clin Oncol , ASCO
Annual Proceedings Part I . 2006 ;24(18s):7030.

Estadiaje CA Pulmon

Caricato da

Informazioni sul documento

Descrizione originale:

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Estadiaje CA Pulmon

Caricato da

Copyright:

Formati disponibili

CHEST Supplement

journal.publications.chestnet.org CHEST / 143 / 5 / MAY 2013 SUPPLEMENT e191S

Potrebbero piacerti anche