แนวทางการตรวจวินิจฉัยและรักษาโรคมะเร็งปอด 2558

1
(2)

( 2)
ISBN
1,200
129
268/1610400
:0 2202 68002237
:0 2644 9097
978-974-422-788-1
37310700
.0 2424 8715.0 2879 7082
2558
ClinicalpracticeGuideline

1
Non-SmallCellLungCancer(NSCLC)
2
SmallCellLungCancer(SCLC)
25
(Categoriesofconsensus)
32
33
51
61

70
TargetedTherapy
SmallCellLungCancer(SCLC) 93
TargetedTherapy

100
126
Non-Small Cell Lung Cancer (NSCLC)
Pathology review
H&P (include
performance
status + weight
loss)
Chest x-ray
CT chest and upper
abdomen, including
adrenals
CBC, platelets
Chemistry profile
Smoking cessation
counseling
CT Chest
Peripheral = Outer third of lung
Central = inner two thirds of lung
b IIB III
(, , )
Non-Small
Cell Lung
Cancer
(NSCLC)
12
14
16
17
17
18
Separate pulmonary nodule(s)

(Stage IIB, IIA, IV)
Multiple lung cancers
Stage IIIBb (T1-3, N3) mediastinal CT positive
Contralateral (lymph nodes 1 cm ) or
palpable supraclavicular lymph nodes
Stage IIIBb (T4 extension, N2-3) on CT
Stage IV (M1a) (pleural or pericardial effusion)
Stage IV (M1b)
Solitary metastasis with resectable lung lesion
18
Stage IIIAb (T1-3, N2)
Stage IV (M1b) disseminated metastases
Stage IIBb (T3 invasion, N0);

Stage IIIAb (T4 extension, N0-1; T3, N1)
Stage I, peripherala (T2a, N0); centrala (T1ab-T2a, N0);

Stage II (T1ab-T2ab, N1; T2b, N0); stage IIB (T3,N0)
Mediastinal CT negative (lymph nodes < 1 cm)
Stage IA, peripherala (T1ab, N0)

Mediastinal CT negative (lymph nodes < 1 cm)
1.1 Non-Small Cell Lung Cancer
If clinically indicated
12
**
Stage IB
(peripheral T2a,N0)
Stage I
(central T1ab-T2a, N0)
Stage II
(T1ab-2ab, N1; T2b, N0)
Stage IIB
(T3,N0)
Stage IA
(peripheral T1ab, N0)
Positive
mediastinal
node
Bronchoscopy
Brain MRI/CT* (Stage II only)
Bone scan*
FNA
Mediastinal LN examination**
Bronchoscopy
FNA
Mediastinal LN
examination**
Negative
mediastinal
node
Positive
mediastinal
node
Negative
mediastinal
node
Definitive RT including stereotactic

ablative radiotherapy (SABR)
Medically
inoperable
Medically
inoperable
Operable
See Adjuvant
Treatment
See Stage IIIA or Stage IIIB
Surgical resection+systematic
See Adjuvant
mediastinal LN dissection or
Treatment
sampling
Consider adjuvant
Definitive RT
N0
Including SABR chemotherapy for
high-risk stages IB-II
Definitive
N1
chemoradiation
See Stage IIIA or Stage IIIB
Surgical resection +systematic

mediastinal LN dissection
or sampling
Operable
R1
Margins positive
Margins negative (R0)n
Margins positive
Chemoradiationj (sequence or concurrent)

Concurrent chemoradiationj
R2n
Chemotherapy
Or
Sequential chemotherapy + RTj (N2 only)
Reresection + chemotherapy
or
Concurrent chemoradiationj
R1n
R2n
or
Chemoradiationj (sequential or concurrent)
Chemotherapy

n
Reresection (preferred) chemotherapy

or
RTj Chemotherapy (chemotheraphy for stage IIA)
Observe
or
Chemotherapy for the high-risk patients
Reresection (preferred)
or
RTj
Observe
Margins positive (R1, R2)n
Margins positive (R1, R2)n
R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

62
Stage IIIA (T1-3, N2; T3, N1)
Stage IIB (T3, N0; T2b,N1)
Stage IIA (T1ab-T2a, N1)
Stage IIA (T2b, N0)
Stage IB (T2a, N0);
Stage IA (T1ab, N0)
if clinically indicated
Stage IIB (T3 invasion, N0)

Stage IIIA (T4 extension,
N0-1; T3, N1)
Bronchoscopy
Brain MRI/CT*
Plain Film or Bone scan
FNA
Mediastinal LN
examination
11
11
16
10
Proximal airway
or mediastinum
Metastatic disease
Unresectable disease
10
Chest wall
Superior sulcus tumor
Unresectable
Possibly
resectable
62
Superior
Sulcus tumor
(T4 extension, N0-1)
Superior
Sulcus tumor
(T3 invasion, N0-1)
Definitive concurrent
Chemoradiationj
Preoperative
concurrent
chemoradiationj
Preoperative
concurrent
chemoradiationj
Surgical
Reevaluation
Unresectable
Resectable
Complete definitive RTj

+ chemotherapy
Surgery +
chemotherapy
Surgery +
chemotherapy
10
Concurrent
chemoradiationj
or
Chemothetapy
or
Surgery (preferred)
Surgeryj
(preferred)
Margins
positive
Margins
Negative (R0)n
R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

62
Chest wall
Proximal airway,
or mediastinum
(T3 invasion, N0-1
Resection T4
extension, N0-1)
Margins positive
(R1, R2)n
Margins
Negative (R0)n
R2n
R1n
Reresection
Observe
or
Concurrent chemoradiation
or
Chemoradiationj (sequential or
concurrent)
Chemotherapy
11
Bronchoscopy
Mediastinal LN
examinationc
Brain MRI/CT
Plain film or
Bone scan
Bronchoscopy
Mediastinal LN
examinationc
Brain MRI/CT*
Plain film or
Bone scan
Mediastinoscopy, EBUS EUS option

If clinically indicated
Separate pulmonary
nodule(s)
(Stage IIIB, IIIA, IV)
Stage IIIA
(T1-3, N2)
Extrathoracic
metastatic disease
Stage IV (N0, M1a):

Contralateral lung
(solitary nodule)
Separate pulmonary
Nodule(s), same lobe (T3, N0)
Or ipsilateral non-primary
Lobe(T4, N0)
20
14
14
16
16
N3 nodes positive
Metastatic disease
13
13
N2 nodes positive
N2, N3 nodes negative
12
Brain MRI
or CT
PET/CT
scan,h
if not
previously
done
(preferred)
Brain MRI
or CT
PET/CT
scan,h
if not
previously
done
(preferred)
Surgeryi,S
Systemic
See treatment for metastasis

solitary site ( 20) or
distant disease ( 21)
Positive
Surveillance
solitary site ( 18) or

RTj (if not given)

chemotherapy
See treatment for metastasis
See Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D)

See Chemotherapy regimens Used with Radiation Therapy (NSCL-E)
e R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual
tumor.
s Patients likely to receive adjuvant chemotherapy may be treated with induction
chemotherapy as an alternative.
chemotherapyj,m
Concurrent
Chemoradiationj,m
R2n
Surveillance
Surveillance
Surgeryi chemotherapyk (category 2B)

RTj (if not given)
Chemoradiationj
(sequentialk or concurrentm)
R1n
Local
See treatment for metastasis solitary site

( 20) or distant disease ( 21)
Progression
No apparent
progression
Negative for
M1 disease
Positive
Negative for
M1 disease
Definitive
concurrent
chemoradiationj,m
(category 1)
Or
Induction
Chemochetherapyk
RTj
Medically
inoperable
Margins
positiven
See treatment
according to clinical
stage (NSCL-2)
N2
Sequential chemotherapyk
(category 1) + RT
Resectable
Margins
negativen (R0n)
16
Surgical resection
+ systematic
mediastinal LN
dissection or
sampling
N0-1
Adjuvant treatment
Initial treatment
Positive PET/CT scan findings for distant disease need pathologic or other radiologic
confirmation. If PET/CT scan is positive in the mediastatinum, lymph node status
needs pathologic confirmation.
i See Principles of Surgical Therapy (NSCL-B)
j See Principles of Radiation Therapy (NSCL-C)
T3
(invasion),
N2 nodes
positive
T1-2,
T3(7 cm),
N2 nodes
positivei
T1-3, N0-1
(including
T3 with
multiple
nodule in
same lobe)
Mediastinal biopsy
Findings
13
Treat as two primary lung

Tumors if both curable
Chest CT with contrast

PET-CT scan (if not
previously done)h
Brain MRI
Suspected multiple
Lung cancers (based on
the presence of biopsypreven synchronous
lesions or history of
lung cancer)t,u
Surveillance
Concurrent chemoradiationj,m
R2n
Pathologic
mediastinal lymph
node evaluationg
N0-1
N2-3
See initial treatment

( 20)
See Systemic Therapy for

Metastatic Disease
( 20)
See Systemic Therapy for Metastatic Disease

( 20)
See Chemotherapy regimens Used with Radiation Therapy (NSCL-E)

R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual
tumor.
t
Lesions with different cell types (eg, squamous cell carcinoma, adenocarcinoma)
may be different primary tumors. This analysis may be limited by small biopsy
samples. However, lesions of the same cell type are not nessarily metastases.
u For guidance regarding the evaluation, workup, and management of subsolid pulmo
nary nodules, please see the diagnostic evaluation of a nodule suspicious for lung
cancer(DIAG-1)

No disease
outside
of chest
Methods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS,

and CT-guided biopsy
h Positive PET/CT scan findings for distant disease need pathologic or other radiologic
k See Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D)
Surveillance
Chemoradiationj
(sequentialk or concurrentm)
R1n
See Evaluation
Surveillance
Sequential chemotherapyk
(category 1) + RTj
Disease outside
of chest
Margins
positiven
Stage IV (N0, M1a):

Contraleteral lung
(solitary nodule)
N2
Surveillance
Adjuvant treatment
Chemotherapyk
Margins negative
(R0)n
Surgeryi
N0-1
Separate pulmonary
nodule(s), same lobe
(T3, N0) or ipsilateral
non- primary lobe (T4, N0)
Clinical presentation
14
Symptomatic
Asymptomatic
Solitary lesion
(metachronous
disease)
Multiple
lesions
High risk of
becoming
symptomaticv
Low risk of
becoming
symptomaticv
Defnitive
Local therapy
not possible
Definitive
Local therapy
possible
Observation
Initial treatment
See Systemic
Therapy for
Metastatic Disease
( 20)
Consider palliative
chemotherapy
local palliative
therapy
Parenchymal
sparing
Resection
(preferred)i,w
or Radiationj
or Ablation
Surveillance
See Principles of Surgical Therapy (NSCL-B)

See Principles of Radiation Therapy (NSCL-C)
v Lesions at low risk of becoming symptomatic can be observed (eg. Small subsolid nodules with slow growth). However, if lesion(s) becomes symptomatic or becomes high risk
for producing symptoms (eg. subsolid nodules with accelerating growth or increasing solid component or increasing FDG uptake, even while small), treatment should be considered.
w Lung-sparing resection is preferred, but tumor distribution and institutional expertise should guide individual treatment planning
Multiple lung
cancers
Clinical
presentation
15
PFTs (if not previously done)

PET/CT scanh (if not previously
done)
Brain MRI or CT
Pathologic comfirmation of N3
disease by either:
Mediastinoscopy
Supraclavicular lymph node
biopsy
Thoracoscpy
Needle biopsy
Mediastinotomy
EUS biopsy
EBUS biopsy
Pretreatment evaluation
chemoradiationj,m,q
(category 1)
See Treatment for Metastasis
solitary site ( 18) or distant
disease ( 19)
Metastatic disease
See initial treatment for

stage I-IIIA
N3 positive
N3 negative
Initial treatment
Positive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastatinum, lymph node status needs
pathologic confirmation.
m See Chemotherapy regimens Used with Radiation Therapy (NSCL-E)
q If full-dose chemotherapy is not given concurrently with RT as initial treatment, give addition 2 cycles of full-dose chemotherapy.
Stage IIIB
(T1-3, N3)
Clinical
assesment
16
Thoracentesis or
Pericardiocentesis
thoracoscopy
thoracentesis indeterminate
While most pleural effusions associated with lung cancer are due to tumor, there are a
few patients in whom multiple cytopathologic examinations of pleural fluid are
negative for tumor and fluids is non-bloody and not an exudates. When these elements
and clinical judgement dictate that the effusion is not related to the tumor, the effusion
should be excluded as a staging element. Pericardial effusion is classified using the
same criteria.
x
Positivex
See treatment for Metastasis

Solitary site ( 18) or
Distant disease ( 19)
Chemoradiationj,m,q
(category 1)
Chemoradiationj,m,q
(category 1)
Local therapy if necessary (eg,

plearadesis, ambulatory small
catheter drainage, pericardial
window) + treatment for stage IV
disease solitary site ( 18) or
Ipsilateral
mediastinal
node positive
(T4, N2)
See treatment for stage IIIA
See treatment according to

TNM stage
Metastatic disease
Contralateral
mediastinal
node positive
(T4, N3)
Contralateral
mediastinal
node negative
Ipsilateral
mediastinal
node negative
(T4, N0-1)
Negativex
PFTs (if not previously done)

PET/CT scanh (if not previously done)
Brain MRI
Pathologic comfirmation of N3
disease by either:
Mediastinoscopy
Supraclavicular lymph node biopsy
Thoracoscpy
Needle biopsy
Mediastinotomy
EUS biopsy
EBUS biopsy
Positive PET/CT scan findings for distant disease need pathologic or other radiologic
m See Chemotherapy regimens Used with Radiation Therapy (NSCL-E)
q If full-dose chemotherapy is not given concurrently with RT as initial treatment, give
addition 2 cycles of full-dose chemotherapy.
Stage IV, M1a:

Pleural or
pericardial
effusion
Stage IIIBz
(T4 extension,
N2-3)
17
Adrenal
Brainy
Pathologic
Diagnosis
by needle
or resection
Local therapy for adrenal

lesionz (if lung lesion curable,
based on T and N stage)
(category 2B)aa
or
See systemic therapy for
metastasis disease ( 20)
Surgical resectioni,
Followed by whole brain
RTj (WBRT) (category 1)
Or stereotactic
radiosurgeryj (SRS)
or
SRS + WBRTj
(category 1 for one metastasis)
Or
SRSj alone
T1-2, N2;
T3, N1-2;
Any T, N3;
T4, Any N
T1-2,
N0-1;
T3, N0
Surgical
resection of
lung lesioni or
SABR of lung
lesion
Chemotherapybb
See systemic therapy

for metastatic disease
( 20)
Surgical resection
of lung lesioni
or
Stereotactic
Ablative
radiotherapyj
(SABR) of lung
Lesion
or
Chemotherapybb
aa Pateints with N2 disease have a poor prognosis and systemic therapy should be con
Methods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS,
and CT-guided biopsy
sidered.
h Positive PET/CT scan findings for distant disease need pathologic or other radiologic bb See system therapy for advances or metastatic disease (NSCL-F)
y See NCCN Guidelines for Central Nervous System cancers.
z May include adrenalectomy or RT (including SABR).
Stage IV,
M1b:
Solitary
site
Pathologic
mediastinoscopy
lymph node
evaluationg
Bronchoscopy
Brain MRI or CT
PET/CT scanh
(if not previously
done)
18
Physical exam +
chest x-ray every
3-4 mo for 2 y, then
every 6 mo for 3 y
then annually
Low dose spiral
chest CT annually
(optional)
Smoking cessation
counseling
Distant
metastases
Locoregional
recurrence
External-beam RT
Stent
Resectable
recurrence
Superior vena
cava (SVC)
obstruction
20
20
Disseminated
metastasis
Evidence of
disseminated
disease
No evidence
of
disseminated
disease
Solitary
metastasis
+ orthopedic stabilization
if risk of fracture
Palliative external-beam RT
Diffuse brain
Metastasis
Symptomatic
bony
metastasis
Localized
Symptoms
Severe
hemoptysis
Reresection
External-beam RT
External-beam RT
Brachytherapy
Laser
Photodynamic therapy
Embolization
Surgery
Laser/stent/other sugery
Brachytherapy

External-beam RT
Endobronchial
obstruction
20
20
Observation
or
Systemic
chemotherapy
19
101
Stage IV /
Metastatic
Disease
Eatablish histologic subtype

with adequate tissue for
molecular testinga (if
consider targeted therapy)
Smoking cessation
counseling
Integrate palliative care
Squamous cell
carcinoma
Adenocarcinoma
Large cell carcinoma
NSCLC not otherwise
specified (NOS)
Consider
EGFR and/or
ALK testings
Sensitive EGFR
mutation and
ALK negative or
Unknown/not
testing
ALK positive
Sensitive EGFR
mutation positive
22
22
21
21
20
ALK inhibitora
- Crizotinib
Chemotherapy
targeted therapy 71
ALK
positive
Sensitizing
EGFR
Mutation
Positive
EGFR TKIsa
- Erlotinib
- Gefitinib
- Afatinib
Systemic
Brain
Progression
Systemic
Brain
24
Progression
FIRST-LINE THERAPY
Multiple
lesions
Isolated
lesion
22
Multiple
lesions
22
Continue ALK inhibitor
Consider local therapy/

WBRT and
Continue EGFR TKI
Consider local therapy/

WBRT and
Isolated
lesion
21
Performance
status 3,4
Best supportive
care
Chemotherapy
(category1)
Course 1-2
Tumor
response
Evaluation
Course 3-4
Response or
Stable disease
Progression
71
k Performance status (PS) 2 PS 0-1
Systemic
Chemotherapyj
and/or
supportive care
Performance
status 0-2k
Relapse
continue to 4- 6
cycles
Response
Stable disease
Progression
23
23
23
22
Best
supportive
care
ALK inhibitor
( ALK positive
)
Progression
Performance
status 0-2k
Performance
status 3-4
ALK inhibitor
( ALK positive
)
EGFR TKI
(
adenocarcinoma
)
Best
supportive
care
71
k Performance status (PS)2 PS 0-1
Performance
status 3-4
Performance
status 0-2k
EGFR TKI
(
adenocarcinoma
)
Second-line
chemotherapyj
()
Progressive disease
Progression
Clinical
trial
Performance
status 0-2
Best
supportive
care
23
Sputum cytology
positive;
chest x-ray and
CT negative
Bronchoscopy
Negative
Tis
T1-3
Rebronchoscope
Rebronchoscope
Endobronchial ablation: Laser

Surgical resection
Brachytherapy
Photodynamic therapy
24
Small cell Lung cancer (SCLC)
25
H&P
Pathology review
Chest x-ray
Chest/liver/adrenal CT
Head MRI CT*
Bone scan
CBC, platelets
Electrolytes, liver function tests
(LFT)
BUN, creatinine
Smoking cessation counseling
and intervention
Extensive
stage
Limited
stage

(1) Limited disease: disease confined to the ipsilateral hemithorax within a single rediation port.
(2) Extensive disease: disease beyond ipsilateral hemithorax or malignant pleural effusion or obvious metastatic disease.
* If clinically indicated
Small cell or
combined small
cell/non-small cell
lung cancer on
biopsy
or
cytology of primary or
metastatic site
2.1 Small Cell Lung Cancer
29
27
26
Bone radiographs of areas

showing uptake or
abnormalities on bone scan
If pleural effusion is seen in

chest x-ray, thoracentesis is
recommended, if
thoracentesis inconclusive,
consider thoracoscopy
Thoracentesis,
bone studies
consistent with
malignancy
Limited disease
extensive-stage disease
( 29)
28
Pleural effusions exudate

Pleural effusion
Limited
stage
27
94
e 62
Limited disease
Chemotherapyd or RTe
Chemotherapyd
Concurrent RT(category 1)
Good performance
status
Poor performance
status due to
comorbidity
28
Plain-film x-rays
of bone scan
abnormalities of
weight-bearing
areas
Extensive stage with

brain metastases
Extensive stage +
localized
symptomatic
sites
Extensive stage
without localized
symptomatic
sited or brain
metastases
Spinal cord
compression
SVC syndrome
Lobar obstruction
Bone metastases
Performance
status (PS) 3-4
Severely

debilitated
94
f Sequential radiotherapy to thorax in selected patients with low-bulk metastatic disease and CR or near CR after systemic therapy.
Extensive
stage
Whole-brain RT followed by
chemotherapy, unless immediate
systemic therapy is required
If asymptomatic, may administer
RT after chemotherapy
RT+ Chemotherapyd
Chemotherapyd
Individualized therapy
including supportive care
regimens
Combination chemotherapyd,f
including supportive care
regimens
29
Primary
progressive
disease
Partial response
Complete response
or radiation
scarring on chest
imaging studies or
10% of original
mass on CT scan
Limited disease:
PCIg (category 1)
Extensive
disease: PCIg
31
64
At every visit: H&P,

chest imaging,
bloodwork as clinically

indicated
New pulmonary nodule after 2y
follow-up should initiate work-up
for potential new primary
Smoking cessation
intervention
After recovery from primary

therapy:
Oncology follow-up visits
every 2-3 mo during year 1,
every 3-4 mo during year
2-3, every 4-6 mo during
year 4-5, then annually
PCI: PCI Complete response Chemotherapy 24-36 Gy ( 30 Gy 15 fractions,

36 Gy 18 fractions, 25 Gy 10 fractions, 24 Gy 8 fractions) Lower fraction regimens (1.8-2.0 Gy/fraction) multiple comor
bidities, poor performance status
Chest x-ray
Head MRI or CT, if
prophylactic cranial
irradiation (PCI) to be
given
Other imaging
studies, to assess
prior sited of
involvement, as

clinically indicated
CBC, platelets
Electrolytes, LFTs,
BUN, creatinine
30
Continue until
maximal benefit or
refractory to
therapy or
development of
unacceptable
toxicity
Palliative symptom management, including localized RT

or
Clinical trial
or
Second-line chemotherapyd (PS 0-2)
94
Primary
progressive
disease
Relapse
Second-line
chemotherapyd
or
Clinical trial
or
Best supportive
care
Clinical trial
or
Best supportive care
31
32
(Categoriesofconsensus)
2(strengthofevidence)
(consensus)
1
1
2A
2B
3
1:(randomized
clinicaltrialmeta-analysis)
2A:1
(phaseIIcohort
retrospectivestudies)
2B:12A

2B
1
3:
32
randomizedtrial
3
-----------------------------------------------------------------------------------------------
1.
2.
3.
33
34
510-20
10(1)(2)
..25502552
(estimatedincidencerate)26.2
11.5
2.31

8090 8-20
10202.5
(Passivesmoker)(3)
90
10
91512
(3)
35
-
2
12(4)
radon
-
asbestos,metals(arsenic,chromium,
nickel),ionizingradiationpolycyclicaromatic
-
Idiopathicinterstitialpulmonaryfibrosis
adenocarcinomasarcoidosis
3 adenocarcinoma
(Chronicobstructivepulmonarydisease;COPD)
1. Non-smallcelllungcancer(NSCLC)75-80
90(5)NSCLC
1.1 Squamouscellcarcinoma
1.2 Adenocarcinoma
1.3 Largecellcarcinoma
1.4 Adenosquamouscellcarcinoma
36
2. Smallcelllungcancer(SCLC)10

(centralairway)(6)
squamous
cellcarcinomasmallcellcarcinoma
trachea
60
2
40
(%)
45-75
8-68
37-58
27-57
27-49
2-18
37
(peripheralairway)
adenocarcinomalargecell
parietalpleura
(Distancemetastasis)
smallcelllargecell
Paraneoplasticsyndrome
Paraneoplasticsyndrome

smallcellneuroendocrinecell
polypeptideproteinhormone
Syndromeofinappropriatesecretionofantidiuretichormone(SIADH)
ADHsmallcell
carcinomasodium,ureaosmolarity
osmolarity1-69smallcellcarcinoma
sodium2580
3
Ectopicadrenocorticotrophichormone
smallcellcarcinomacarcinoidtumor30
ACTH Cushingsyndrome
ACTH
38
Hypercalcemia
6squamouscell
parathyroidhormonelikepeptide
coma
Gynecomastia
squamouscell1
Hyperthyroidism
squamouscellcarcinoma
Neuromyopathies
LambertEatonmyasthenicsyndrome70
smallcellreflex
electrophysiologyacetylcholine
28
Fingerclubbing
10-30squamouscell
adenocarcinoma
Hypertrophicpulmonaryosteoarthropathy
fingerclubbingperiostitis,arthropathy
thymiccarcinoma,
chronicmyeloidleukemia,thyroidcarcinoma,Hodgkinsdisease,adenocarcinoma
esophagusbronchialcarcinoidtumor Cyanoticcongenital
heartdisease,pleuralfibroma,Gravesdisease,esophagealachalasia,portalcirrhosis,
inflammatoryboweldisease,leiomyomaesophagus,cysticfibrosis
(DiagnosticApproachofLungCancer)
3
39
3 (DiagnosticApproachofLungCancer)
Abnormal CXR
and/or
Clinically suspected
previous CXR
Suspected Lung Cancer
negative CXR with

Clinically suspected
distant metastasis
pleural effusion
tissue diagnosis
pleural tapping
for cell cytology
pleural biopsy
inaccessable
mediastinal
involvement
- bronchoscopy with TBNA/

- TTNA/
- mediastinoscopy
accessable
negative
(2 times)
biopsy
consider tissue
form primary
lesion
lung cancer
diagnosis
positive
negative
thoracotomy
Investigation for
cause of pleural
effusion
lung cancer
diagnosis
SPN*
size 3 cm
central
SPN*
size < 3 cm
peripheral
sputum cytology
and/or
bronchoscopy
Lung lesion of
mass
uncertain
- TTNA
- bronchoscopy
high risk**
surgical
candidate
positive
negative
Yes
Low risk**
No
- TTNA
- bronchoscopy
operable and
surgical candidate
No
Yes
re-evaluate
benign
positive
negative
Yes
suspected for
TB(7)
Rx TB
CAT 1
Reassess
CXR 3,6 m
Follow up
3,6,12,24 m
No
Yes
growth
thoracotomy
thoracotomy
Lung cancer diagnosis
No
Follow up
3,6,12,24 m
40
TTNATransthoracicNeedleAspiration
TBNATransbronchialNeedleAspiration
SPNSolitaryPulmonaryNodule
3
**Highrisk,Lowrisk
Lungnodule
1.50(8)2
2
(%)
35-39
3
40-49
15
50-59
43
>50
60
<5mm.
1
5-9mm.
2-6
8-20mm
18
>20mm
>50

2.emphysema(9)
3.(9)2
4.spiculated
coronaradiata(10)
5.calcificationbenignlesioneccentric
6.upperlobe(9)
41
(11)
ProbabilityofMalignancy=ex/(1+ex)
X=-6.8272+(0.0391xage)+(0.7917xsmoke)+(1.3388xcancer)+(0.1274x
diameter)+(1.0407xspiculation)+(0.7838xlocation)
e=baseofnaturallogarithms
age=
smoke=1(=0)
cancer=1extra-thoraciccancer>5(=0)
diameter=
speculation=1spicules(=0)
location=1upperlobe(=0)
1.
2. thoracicsurgeons,thoracic
radiologistspulmonologists
3.
(11)
4. Fluorodeoxyglucose(FDG)avidityonPETimaging (PETscan)
PETscan
positivePETscanstandardized
uptakevalue(SUV)baselinemediastinalbloodpool
PETscan
5.
6. 1 2
42

preoperativestagingpostoperativestaging
(12,13)
Non-smallcelllungcancer(NSCLC)
TheInternationalsystemforstaginglungcancer
TNMsystem(T=tumor,N=regionalnodes,M=metastasis)
423
5 61
1A1 4
3 TNMstagingsystemforlungcancer(7thedition)
Primarytumor(T)
T1
Tumor3cmdiameter,surroundedbylungorvisceralpleura,without
invasion moreproximalthanlobarbronchus
T1a
Tumor2cmindiameter
T1b
Tumor>2cmbut3cmindiameter
T2
Tumor>3cmbut7cm,ortumorwithanyofthefollowingfeatures:
Involvesmainbronchus,2cmdistaltocarina
Invadesvisceralpleura
Associatedwithatelectasisorobstructivepneumonitisthatextends
tothehilar regionbutdoesnotinvolvetheentirelung
T2a
Tumor>3cmbut5cm
T2b
Tumor>5cmbut7cm
T3
Tumor>7cmoranyofthefollowing:
Directlyinvadesanyofthefollowing:chestwall,diaphragm,phrenic
nerve,mediastinalpleura,parietalpericardium,mainbronchus<2cm
from carina (withoutinvolvementofcarina)
Atelectasisorobstructivepneumonitisoftheentirelung
Separatetumornodulesinthesamelobe
43
T4
Tumorofanysizethatinvadesthemediastinum,heart,greatvessels,
trachea,recurrentlaryngealnerve,esophagus,vertebralbody,carina,orwith
separate tumornodulesinadifferentipsilaterallobe
Regionallymphnodes(N)
N0
Noregionallymphnodemetastases
N1
Metastasisinipsilateralperibronchialand/oripsilateralhilarlymphnodes and
intrapulmonarynodes,includinginvolvementbydirectextension
N2
Metastasisinipsilateralmediastinaland/orsubcarinallymphnode(s)
N3
Metastasisincontralateralmediastinal,contralateralhilar,ipsilateralor
contralateralscalene,orsupraclavicularlymphnode(s)
Distantmetastasis(M)
M0
Nodistantmetastasis
M1
Distantmetastasis
M1a
Separatetumornodule(s)inacontralaterallobe;tumorwithpleuralnodules
ormalignantpleuralorpericardialeffusion
M1b
Distantmetastasis(inextrathoracicorgans)
Stagegroupings
StageIA T1a-T1b
N0
M0
StageIB T2a
N0
M0
StageIIA T1a,T1b,T2a
N1
M0
T2b
N0
M0
StageIIB T2b
N1
M0
T3
N0
M0
Stage
T1a,T1b,T2a,T2b
N2
M0
IIIA
T3
N1,N2
M0
T4
N0,N1
M0
Stage
T4
N2
M0
IIIB
AnyT
N3
M0
StageIV AnyT
AnyN
M1aorM1b

Adaptedfrom:GoldstrawP,CrowleyJ,ChanskyK,etal.TheIASLCLungCancer
StagingProject:ProposalsfortherevisionoftheTNMstagegroupsintheforthcoming
(seventh)editionoftheTNMclassificationofmalignanttumours.JThoracOncol2007;
2:706-14.
44
4
4 StagingofLungCancer
Lung CA
Clinical, CXR, lab
NSCLC
SCLC
All
CT chest included upper abdomen

Bronchoscopy
- CT chest
Brain MRI/CT
- US/abdominal CT
Plain film or bone scan
- CT or MRI brain if
symptomatic
- Bone scan if suspected
bone metastasis
suspected distant
metastasis
confirm (M1)
Suspected mediastinal
lymphadenopathy
EBUS/EUS/Mediastinoscopy/
TTNA/VATS
supraclavicular
cervical L.N. +
confirm
N = 0-3
stage IV
Clinical finding
AnyT N3
Stage I
Stage II
Stage IIIa
Stage IIIb
stae III B
limited stage
extensive stage
45
1.(Primarytumor,Tstage)
Tstage
1.1 postero-anteriorviewlateralview

(central)
(Periphery)
1.2 ComputedTomographyofchest(CTChest)mediastinum
morbidity
mediastinum
mediastinum
CT 20-87
mediastinum
6963-72
1.3 MagneticResonanceImaging(MRI)MRICT
mediastinumMRI
CTMRI90
86
SuperiorsulcustumorsMRI
mediastinum
1.4 Positron-EmissionTomography(PETscan)PETscan[18F]
fluorodeoxyglucose
positronelectronlightpulse
lightsensitivecrystalPETscanPETscan
46
1.4.1 PETscanhypermetabolic
lesionsnormometabolicbenignlesions
CTscan(14)
1.4.2 PETscan

N0N1N2N3PETscansensitivity
specificity8992CT scan
sensitivityspecificity 65 80
(14)PETscannegativepredictivevalue
positivepredictivevalue
PETscanpositivePETscan
positive
1.4.3 Whole
bodyPETscansensitivityCTscan(15,16)
PETscan
highglucoseuptakeMRI
CTbrain
- PETscanpositive
(infectionorinflammation)
- PETscan(false-negativePETscan)
(smallnodule,nonsolidnoduleorground-glassopacity
[GGO]), (lowtumoravidityforFDG
adenocarcinomainsitubronchoalveolarcarcinoma
carcinoidtumor)
PETscan
PETscan
1.5 (Bronchoscopy)
carina
carina
47
2.(Nstage)

mediastinum
mediastinum
1
5010
PETscanuptake
mediastinoscopy
2.1 (Bronchoscopy)
(Transbronchialneedleaspirationbiopsy:TBNA
Transtrachealneedleaspirationbiopsy:TTNA)
invasive

mediastinum89

Endobronchialultrasoundguidedtransbronchialneedleaspiration
(EBUS- TBNA) 1
2.2 (Esophagoscopy)
Transesophagealendoscopicultrasonographicguidance
forfine-needleaspiration(EUS-FNA)
mediastinum89

2.3 Mediastinoscopygoldstandard
mediastinum
48
2.4
3.
3.1

3.2
CTscanupperabdomenultrasound
3.3
3.4
benign
adenoma
Smallcelllungcancer(SCLC)
Limiteddisease (Ipsilateral
hemithorax)
Extensivedisease
49
mediastinum
upperabdomen
(T)(N)
(M)
NSCLCTNM
AmericanJointCommitteeonCancer(AJCC)5
4
4 5NSCLCTNM(13)
TNMClassification
5(%)
0
Carcinomainsitu
NR
IA
T1N0M0
61
IB
T2N0M0
38
IIA
T1N1M0
34
IIB
T2N1M0orT3N0M0
24
IIIA
T1-3N2M0orT3N1M0
13
IIIB
T4AnyNM0orAnyTN3M0
5
IV
AnyTAnyNM1
1

50
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individualdatafor25,676,887patientsfrom279population-basedregistriesin67countries(CONCORD-2).
Lancet.2015;385:977-1010.
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2007-2009.Bangkok,Thailand;2013.
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today.JNatlCancerInst1981;66:11911308.
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laboratorytestsandparaneoplasticsyndromes.Chest2003;123:97s-104s.
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Managementoftuberculosis:ModifiedWHOmodulesofmanagingtuberculosisatdistrictlevel.:
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theguidelines.Chest2003;123:147s-49s.
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15. BuryT,DowlatiA,PaulusP,etal.Whole-body18FDGpositronemissiontomographyinthestagingof
non-smallcelllungcancer.EurRespirJ1997;10:2529-34.
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tomographyinlungcancer.AnnThoracSurg1998;66:886-92.
-----------------------------------------------------------------------------------------------
1.

2.
51
52
Non-smallcelllungcancer(NSCLC)
1.
-TNMStagingedition6edition7edition
2010 1 (upstage)
(downstage)
-CTPET/CT60
-
(mediastinallymphnodeexaminationmediastinalstaging)
53
Transbronchialneedleaspirationbiopsy(TBNA)
Endobronchialultrasoundguided-TBNA(EBUS-TBNA)
Endoscopicultrasound(EUS)
Mediastinoscopy(conventionalandextended)
Anteriormediastinotomy(Chamberlainprocedure)
Video-assistedthoracicsurgery(VATS)
-anatomicpulmonaryresection
-sublobarresection(segmentectomywedgeresection)
-(margin)2
-N1N2
-
(frozensection)N2positivemarginpositive/unfree
lobectomy
-sublobarresection(limitedresection)
-lobectomy
-(peripheralnodule)2
-PureAIShistology
-groundglassappearance 50CT
-longdoublingtime(400)
-orificeofbronchus(proximaltumor)
sleevelobectomy(pneumonectomy)negative/
freemargin
-VATSopen
thoracotomy
-N1N2N2
3completelymphnodedissection
-formalipsilateralmediastinallymphnodedissection
IIIA(N2)
-Completeresection(R0) freemarginsystematic
nodedissectionsamplinghighestmediastinalnodenegativefortumor
54
-Incompleteresectionresectedmarginpositive
node positivepleuralorpericardialeffusionsR1:
microscopically positiveresectionR2:macroscopicresidualtumor
-oncologistpathologicstageII
2.NSCLC1(stageI)
StageIA T1a-T1bN0M0
StageIB T2aN0M0
curativelungresectionsystematiclymphnodedissection
sampling mediastinallymphnode
examination mediastinallymphnode
CTscan1 5-15(1.2 )
T1a-T1bN0M0(stageIA)postoperativeadjuvantchemotherapy
(3)unfreesurgicalmarginadjuvant
radiation
T2aN0M0(stageIB) postoperative
adjuvantchemotherapy(4-6) 4
adjuvantchemotherapy(6)
(7)
3.NSCLCII(stageII)
StageIIA T1a-T1bN1M0

T2aN1M0

T2bN0M0
StageIIB T2bN1M0
curativelungresectionsystematiclymphnodedissections
mediastinallymphnodeexaminationpostoperative
adjuvanttherapy27(3.10)
(7)
StageIIB T3N0M0
N1
55
N2negative
-(extentofchestwallinvasion)
-(completenessofresection)
-(regionalnodemetastases)
CTscanN2nodemediastinal
lymphnodeexamination(mediastinalstaging)
-N2nodenegativecurativeenblocchestwallandlung
resectionwithsystematiclymphnodedissection(11)
-N2nodepositivestageIIIA
4.NSCLCIIIA(stageIIIA)
T1a-T3N2M0(IIIAN2)
T3N1M0
T4N0-N1M0
mediastinallymphnodeexamination
truepathologicalN21
CTscan 70 (12) mediastinallymphnode
examinationN2negativestageIIN2positive
4.3
mediastinallymphnodeexamination
CTchest
IIIAN24
4.1 IIIA1(postoperative)N2positivepathology
adjuvantchemotherapyradiation
4.2 IIIA2(intraoperative)N2positive2
4.1.1 (resectable)N2postitive
(singlestationN2) (lungresectionwith
systematiclymphnodedissections)chemo-radiation
4.1.2 (unresectable)
(extracapsularextension)chemo-radiation
56
4.3 IIIA3(preoperative)N2positive imaging(CTscan,

PET/CT)mediastinallymphnodeexaminationpre-opchemotherapy
RTdefinitivechemotherapy/RT(13,14,15,16)

4.4 IIIA4(bulkyN2)N2imagingmediastinal
lymphnodeexaminationtrueN2N2positive/
(neo-adjuvantchemo/chemo-radiation)CTchest

5.NSCLCIIIB(stageIIIB)
T1-T4N3M0
T4N2M0
6.NSCLC4(stageIV)
AnyTAnyNM1a-M1b
6.1 (synchronouspresentation)
sterotacticradiation
(T1-3,N0-1),N2nodenegative
sterotacticradiation
(11,23)
6.2 (synchronouspresentation)

(T1-3,N0-1),N2nodenegative
(24)
57
7.Superiorsulcustumor(Pancoasttumor)
(11)N2mediastinal
lymphnodeexaminationN2N3
involvement(25)
vertebralbody ,subclavianvessel
Hornersyndromesympatheticganglion

22527(25)
(completeresection-R0)
92 (localrecurrence)33(26)
8.Synchronoussecondprimarylungcancer
2
moleculargeneticcharacteristics 60N2involvement
synchronoussecondprimarylungcancer
T4mediastinallymphnodeexamination
(27)
9.Metachronoussecondprimarylungcancer
2
2-4(11,28)520(11)
T1536(11)
10.
(marginpositiveR1,R2)(35)
StageIA(T1abN0) (re-resection) (preferred)
StageIB(T2aN0)StageIIA(T2bN0)
StageIIA(T1ab-T2aN1)StageIIB(T3N0,T2bN1)
+
StageIIIA(T1-3N2,T3N1)+
58
Smallcelllungcancer(SCLC)
SCLC
T1N0(29,30,31)
SCLC
1.SCLCT1-2N0
(32,33)20-25SCLC
(localrecurrence)(34)
2.SCLCII
(33,34)
3.5-17SCLCsynchronoussecondprimarylesion
SCLC(secondprimarylesion)(33,34)
59
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-----------------------------------------------------------------------------------------------
1.

2.
3.
61
62
NationalComprehensiveCancerNetwork,Clinical
PracticeGuidelinesinOncology(1,15)
Non-smallcellcarcinoma
3
(Resectablegroup), (Unresectablegroup)
(Marginallyresectablegroup)
(Resectablegroup)
1.
(medicalinoperable)
60(Gray;Gy)6-7
56%
65(Gray;Gy)(
10-252)
(1-3)SBRT(Hypofractionation,Ablativedoseradiotherapy)T1-2N0M0
387-92 (4,5)
50
=2A(1)
2.
(positivemargin)
N2
(6-8,)
63

456065(Gray;Gy)4
7(1,6,9)
=2B(1)positivemargin
=2A(1)N2

(
N1,N2Mediastinum3)
(1)
(1,6,10)
(Unresectablegroup)
(locallyadvanced)
60(Gray;Gy)6-7
(1,7)
(Concomitanttreatment)
336
(Sequentialtreatment)
(1,7,8)
=1(1)
(Marginallyresectablegroup)
(locallyadvanced)

(Neoadjuvanttreatment)()
IIIA(N2)

Unresectable()
=1(1)
64
(Neoadjuvanttherapy)
(1,12-16)
(Palliativegroup)(1)
3
Palliativetreatment
(Hypo-
fractionation)
30(Gray;Gy)2,20(Gray;Gy)
1
SuperiorsulcusPancoasttumor
non-smallcellapex
1brachialplexusHornorssyndrome
,,
40-60(Gray;Gy)
4-7
=2A(1)
(1,17,18)
=1(1)
Smallcellcarcinoma

limiteddisease
30
65
9
510
Extensivedisease
(17-19)
=1(19)
50(Gray;Gy)5-6
60(Gray;Gy)1.5(Gray;Gy)245(Gray;Gy)(19,20)
Extensivedisease
30(Gray;Gy)2(21)(National
ComprehensiveCancerNetwork)
Palliativeradiotherapy
non-smallcell
(ProphylacticCranialIrradiation)
bloodbrainbarrier
smallcelllimitedextensive
35
=1(19)
25(Gray;Gy)1030(Gray;Gy)
10-15(19,20,22)
non-smallcell
SuperiorVenaCavaObstruction
SuperiorVenaCavaObstruction
3-4(Gray;Gy)
66
3-4
72
(23)shunt
(Externalbeamradiotherapy)
mediastinum

3
(3dimensionalconformalradiotherapy)
2(2dimensionalradiotherapy)
(24)

4(4dimensionalconformalradiotherapy)

Image-GuidedRadiationTherapy(IGRT)(CTscan,
MRI,PET-CT)
(24)

(Intensity-ModulatedRadiotherapy,IMRT)(VolumetricModulated
ArcRadiotherapy,VMAT) (Tomotherapy),
(SterotacticBodyRadiotherapy,SBRT)
67
3(24)
SBRT(Hypofractionation,Ablativedoseradiotherapy)non-smallcelllungcancer
(25,26)
35(Gray;Gy)1 ,20(Gray;Gy)3 ,10(Gray;Gy)
5 10
(StereotacticRadiosurgery,SRS)
(1)(15,18
24(Gray;Gy)1)(27)
(Brachytherapy)
Bronchoscopy(Irridium192)
EndobronchialIntraluminalBrachytherapy
(28)
68
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70
Non-SmallCellLungCancer
(NSCLC) TargetedTherapy
-----------------------------------------------------------------------------------------------
1.
2.
3.
4.

5.
6.
71
TargetedTherapy
non-smallcelllungcancer(NSCLC) ( I
IIIIIA
(1)
adjuvantchemotherapy
neoadjuvantchemotherapyNSCLC
NSCLCIII IIIA
(N2T3-4 IIIB
chemoradiation
NSCLCIV
IV
performancestatus(PS)0-2
1.NSCLCI[IA(T1N0M0),
IB(T2N0M0)]
1.1 AdjuvantchemotherapyNSCLCI
randomizedcontroltrialcisplatin-basedchemotherapy
I-IIImeta-analysisadjuvantchemotherapy
adjuvantchemotherapy(2-5)
adjuvantchemotherapyIB
randomizedphaseIIIadjuvantchemotherapyUFT
I IB 5 (6)
InternationalAdjuvantLungCancerTrial(IALT)cisplatin-based
chemotherapyNSCLCI-III5 (44.5%vs.40%,
P<0.03)(7)adjuvantchemotherapyvinorelbinecisplatin
NSCLC IBIIJBR10 (8) NSCLC I-III
AdjuvantNavelbineInternationalTrialistAssociation(ANITA) (9) adjuvant
chemotherapyIALT
72
7.5
(HR0.91,95%CI,0.81-1.02;P=0.10) (10)
JBR.109.3(11)

IB(AJCC6thedition)CALGB9633
paciltaxelcarboplatin(observation)
(12)
IB(HR=0.83;
95%CI0.64-1.08,P=0.12)4adjuvant
chemotherapy(HR=0.69;95%CI0.48-0.99,
p=0.043)(13)subgroupanalysisJBR10ANITAI
vinorelbinecisplatinIIIII
(8,9)
randomizedstudyadjuvantchemotherapy
I,IIIIIAcisplatin-basedchemotherapyAdjuvantLungProject
Study(14)TheBigLungTrial(15)Adjuvantchemotherapy
meta-analysisadjuvantchemotherapyadjuvant
chemotherapycisplatin-basedchemotherapyUFT
(16,17)
adjuvantchemotherapyNSCLCIA(T1N0M0)
1
adjuvantchemotherapyNSCLCIB(T2aN0M0)
T4
2B
1.2 NeoadjuvantchemotherapyNSCLCI
NeoadjuvantchemotherapyI
IIIIIA(18-21) Depierre(15)
neoadjuvantchemotherapyIB II
MRCLU22/EORTC08012multicenterrandomizedtrial
neoadjuvantchemotherapystageI,II,III(down-staging)
31%(22)NATCH
73
neoadjuvantchemotherapy,adjuvantchemotherapyI,II
T3N1( T2N0) carboplatin paclitaxel
(disease-freesurvival)
(23)
neoadjuvantchemotherapyNSCLCI
2A
2.NSCLCII
[IIA(T2bN0M0,T1-2aN1M0),IIB(T2bN1M0,T3N0M0)]
AdjuvantchemotherapyNSCLCIIrandomizedcontroltrial
meta-analysis(2,5,14,15)
adjuvantchemotherapycisplatin-basedchemotherapy(7)vinorelbinecisplatin(8,9)
meta-analysis
adjuvantchemotherapy(16,17)
adjuvantchemotherapyNSCLCII
1
2.2NeoadjuvantchemotherapyNSCLCIII
neoadjuvantchemotherapy (18-21)

adjuvantchemotherapySWOGS9900
IB-IIIA(IB/IIA)neoadjuvantchemotherapycarboplatin
paclitaxel (24)
ScagliottiIB-IIIAneoadjuvantchemotherapy
cisplatingemcitabine
IIB/IIIA(25)
neoadjuvantchemotherapyNSCLCII
2A
74
3.NSCLCIII
IIIIIIAIIIBIIIA
T3N1,T4N0-1 mediastinallymphnodesprimary
tumor(N2)T1-3N2N2(incidentalpotential
resectableN2)(bulkyN2)
IIIB N3T4N2-3 N3
NSCLCIII
3
1T3N1M0 N2disease
N2diseaseincidentalN2
2IIIAN2diseaseCTscan
(potentialresectableN2disease)
3locallyadvanceddiseaseunresectableIIIA bulkyN2
diseaseIIIBN3disease
3.11IIIA:T3N1M0incidentalN2disease
3.1.1Adjuvantchemotherapy
randomizedcontroltrialNSCLCI,
II,IIIadjuvantchemotherapyvinorelbinecisplatin(9)meta-analysis
adjuvantchemotherapy(16,17)adjuvantchemotherapy
IALT
cisplatin
(10)
adjuvantchemotherapyNSCLCIIIA
1
3.1.2Adjuvantcombinationchemoradiotherapy
adjuvantradiotherapylocalrecurrence
(26-28)chemotherapyradiation
(29-31)
75
adjuvantchemoradiationNSCLCIIIA(
positivemargin)
1
3.2 2 IIIA:PotentiallyresectableN2disease
3.2.1Neoadjuvantchemotherapy
neoadjuvantchemotherapy
micrometastasissurgicalseeding
Rosell(32)Roth(33)
60neoadjuvantchemotherapy
Depierre(18)I,II
IIIAsubsetanalysisN0,N1
neoadjuvantchemotherapy IIIA92
chemotherapy-surgery75
3
neoadjuvantchemotherapy
debulking
IIIApotentiallyresectable
Neoadjuvantchemotherapy
2A
3.2.2Concurrentchemoradiotherapy
SouthwestOncologyGroup(34)Bueno(35)
chemoradiotherapy
inductiontherapy(median
survival10months,5-yearsurvival9%)(complete
pathologicclearingofresidualdiseases)
concurrentchemoradiotherapyresidualnodaldiseases( biopsy)
Rusch(36)phaseIIIstudy(Intergroup
0139,RTOG9309)IIIA(N2)inductionchemoradiotherapy
2adjuvantchemotherapy
76
progressionfreesurvival
overallsurvival2
IIIAperformancestatus(PS)
inductionchemoradiotherapy
2A
3.33LocallyadvanceddiseaseIIIA(BulkyN2)IIIB(N3)
3.3.1Combinedchemotherapywithradiation(sequentialchemotherapy
followedbyradiation)cisplatin-basedcombination.
CALGB (37) sequentialchemotherapyfollowedbyradiotherapy(CT/RT)
radiotherapy(RT)CT/RT2
5RT (2-year=26%vs.13%and5-year=13%vs.6%).
LeChevalier(38)
meta-analysis3(5,39,40)locallyadvanced,unresectable
NSCLC platinum-basedchemotherapy
ECOGPS0-1
3.3.2Concurrentchemotherapyandradiotherapy
concurrentCT/RTsequentialCT/RT(41)
320concurrentsequential2-yearsurvival
34.6%vs.27.4%5-yearsurvival15.8%vs.8.8%
RTOGstudy(42)phaseIIItrialconcurrenttherapy
sequentialtherapyconcurrentCT/RTmediansurvivalsequential CT/
RT1714.6Frenchcooperativegroup(43)
mediansurvivalconcurrentCT/RT1513.82-year
survival35%23%concurrentCT/RTgrade3-4
esophagitis26%concurrentCT/RTPS0-1
concurrentCR/RT
consolidationchemotherapydocetaxelconcurrent
chemoradiation randomizedtrial
77
HoosierOncologyGroup(HOG)randomizedIIIAIIIB
concurrentchemoradiationdocetaxel3cyclesobservation
consolidationdocetaxel
consolidationobservation(44)
3.3.3InductionchemotherapyconcurrentchemoradiationCALGB
39801Vokes (45)randomized IIIB induction
chemotherapycarboplatinpaclitaxel2cyclesconcurrentchemoradiation
66Gy carboplatinpaclitaxel
concurrentchemoradiation2
1.UnresectableIIIA(BulkyN2)IIIB(N3)
PS0-1concurrentchemoradiationsequentialchemotherapyradiation
chemotherapyplatinum-basedconsolidationchemotherapy
docetaxelchemoradiation
1
2.1PS>2
2A
4.NSCLCIV
randomizedtrialsmeta-analysisNSCLC
IVPS01
bestsupportivecare(BSC) (5,46-48)platinum-based
chemotherapy27BSC(HR0.73;95%Cl0.63-0.85,
p<0.001)(5)
newgenerationpaclitaxel,vinorelbine,docetaxel,gemcitabinepemet
rexedNSCLCIV
cisplatincarboplatinprospectiverandomizedstudyNSCLC
IIIIVcisplatinpaclitaxel,gemcitabinecisplatin,
docetaxelcisplatinpaclitaxelcarboplatin
(49)SouthwestOncologyGroup
paclitaxelcarboplatinvinorelbinecisplatin
advancedNSCLC(IIIBmalignantpleuraleffusionIV)
78
2(50)
platinum(cisplatincarboplatin)1
advancedNSCLC
3(tripletchemotherapy)
2(doubletchemotherapy) (51)
pemetrexedcisplatingemcitabinecisplatin
(pre-plannedanalysis)pemetrexed
cisplatingemcitabinecisplatin
adenocarcinomalargecellcarcinoma
gemcitabinecisplatin squamouscellcarcinoma(52)
pemetrexedadvancedNSCLCsquamouscellcarcinoma
PSNSCLCIVPS2
PS0-1(49,53-55)
NSCLC(>70)platinum-based
chemotherapyPS70(56-57)
vinorelbineBSC
BSC(58-59)vinorelbine
gemcitabine2vinorelbinegemcitabine
2 (60)
carboplatinpaclitaxel
gemcitabinevinorelbineadvancedNSCLC70-89
(72)PS0-1(61)3PS2
non-squamouscellcarcinomacarboplatinpemetrexed
pemetrexed(62)
PS
mitomycin/vinblastine/cisplatin(MVP)36
(63)Socinski (64)
79
carboplatinpacliltaxel4
4
4

34
metanalysis4-6
(PFS)
(65)
IVPS0-1
PS2
PS
(maintenancetherapy)advancedNSCLC
(inductiontherapy)4-62
continuationmaintenancetherapyswitch
maintenancetherapy
maintenancetherapypemetrexed
3PARAMOUNT (66)JMEN (67) pemetrexedcontinuous
maintenancetherapyswitchmaintenancetherapy
pemetrexedbevacizumabcontinuation
maintenancetherapy
bevacizumab(68,69)
docetaxel(70)erlotinib(71,72)switchmaintenancetherapygemcitabine (72,73)
continuationmaintenancetherapy

maintenancetherapy(observation)4-6
advancedNSCLC
(treatmentfreeperiod),maintenancetherapy
2
pemetrexed,EGFR
80
maintenancetherapy
maintenancetherapyPS2pemetrexed
non-squamoushistology
second-linechemotherapy
PSPS0-1PS2randomizedphaseIII
docetaxelBSCdocetaxel
BSC(74)pemetrexed
docetaxel (75)
pemetrexed
docetaxel(76)
pemetrexedadvancedNSCLCpemetrexed
non-squamouscellcarcinomasquamouscellcarcinoma
pemetrexedpemetrexed
squamouscellcarcinomamoleculartargetedtherapy
advancedNSCLCEpidermalgrowthfactorreceptor(EGFR)tyrosinekinaseinhibitors
(TKIs),AnaplasticLymphomaKinase(ALK)inhibitor,bevacizumabcetuximab
EGFRcisplatinvinorelbine
(77)

EGFRTKIs3erlotinib,gefitinibafatinib
(predictivebiomarker)EGFRTKIs
NSCLC platinum-basedchemotherapy
9.6-19 (78-80)erlotinib
advancedNSCLCerlotinib
(6.7vs.4.7,p=0.001)
(2.23vs.1.84,p<0.001)(81)
gefitinib
NSCLCgefitinib
(5.6vs.5.1,p=0.11)(82)preplannedsubsetanalyses
gefitinib(9.5vs.5.5,p=0.010)
(83)IPASSgefitinib
carboplatinpaclitaxeladvancedNSCLCadenocarcinoma
81
(non-orlightsmoking)gefitinib
EGFR
3559

gefitinib
(84)
EGFRTKIsplatinumdoublet
advancedNSCLCEGFRgefitinib
erlotinibafatinibEGFRTKIs
(85-89)advancedNSCLCTAILOR
EGFR docetaxel
erlotinib(p=0.05) (90) EGFR
(biomarker)EGFRTKIsfirstline
EGFRTKIsEGFR
EGFREGFRTKIs
EGFREGFRTKIs
adenocarcinomaadenocarcinoma
EGFRadenocarcinomasquamouscell
carcinomaEGFRTKIsadvanced NSCLC
(91,92) EGFRTKI
progressivedisease(brainmetastasis)
(solitarylesion)EGFR
TKIEGFRTKI
ALKinhibitor advancedNSCLC
crizotinibALKrearrangementFISH82
57(93)locallyadvancedmetastatic
ALKpositiveNSCLCplatinumcrizotinib
docetaxelpemetrexed crizotinib
(7.73.0)(94)
advancedAIKpositiveNSCLCcrizotinib
82
(95)crizotinibadvancedNSCLC
ALKrearrangementFISH
ALKrearrangementALKrearrangement
7NSCLC(94)
(immunohistochemistry)
FISH(96-98)ALKrearrangementadenocarcinoma
EGFR
(mutuallyexclusive)ALK
adenocarcinoma
moleculartargetedtherapy
advancedNSCLCnon-squamouscellcarcinoma
bevacizumabmonoclonalantibodyvascular
endothelialgrowthfactor(VEGF) (anti-
angiogenesis)paclitaxel/carboplatin
2.3(99)AVAILstudybevacizumab
cisplatin/gemcitabineadvancedrecurrent
non-squamousNSCLCbrainmetastasisprogression-freesurvival,response
rate,responseduration
(100)
1. (NSCLC)IVperformancestatus01
1.1 platinum(platinumdoublets)
1
1.2 platinum pemetrexed
(NSCLC)non-squamous

2B
1.3 (platinumdoublet)bevacizumab(NSCLC)
non-squamous
2B
83
2.(NSCLC)IVperformancestatus2
2A
1
4.(NSCLC)IV
4-6
2A
5. (NSCLC) IV EGFR
EGFRTKIserlotinib,gefitinibafatinib
5.1 (first-linetreatment)

1
5.2 (second-orlaterlinetreatment)

2A(erlotinibgefitinib)

2B(afatinib)
targetedtherapy
6.1 Docetaxel
1
6.2 Pemetrexed(NSCLC)non-squamous
2A
6.3 Erlotinib

2A
6.4 Gefitinib

2A
7.(NSCLC)IVALKrearrangementFISH
crizotinib
7.1 (first-linetreatment)

1
7.2 (second-orlaterlinetreatment)

1
84
5.adjuvantchemotherapy
PE
Regimens
Cisplatin/Vinorelbine
Agents
cisplatin
Dose
80mg/m2,day1
etoposide
100mg/m2ondays1-3
(every21daysfor4cycles)
cisplatin
50mg/m2onday1and8
vinorelbine
25mg/m2ondays1,8,15,22
cisplatin
100mg/m2onday1
vinorelbine
30mg/m2ondays1,8,15,22
cisplatin
75-80mg/m2onday1
vinorelbine
25-30mg/m2ondays1,8
6.chemoradiation
PE
Cb/Pac
Regimens
Agents
cisplatin
Dose
50mg/m2,day1,8,29,36
etoposide
Carboplatin
50mg/m2ondays1-5,29-33
AUC2wkly
Paclitaxel
50mg/m2wkly
85
7.AdvancedNSCLC
Regimens
PE(101)
Agents
Cisplatin
etoposide
CarboP(49)
carboplatin
paclitaxel
CD(49)
cisplatin
docetaxel
CV(50)
cisplatin
vinorelbine
CG(49)
cisplatin
gemcitabine
Cis/Pem(52)
Cisplatin
Pemetrexed
docetaxel
Docetaxel(66)
(second-line)
Pemetrexed(67)
(second-line)

pemetrexed
Dose
75mg/m2,day1
100mg/m2,days1-3
every3weeks
AUC6,day1
225mg/m2over3h,d1
every3weeks
75mg/m2,day1
75mg/m2,day1
every3weeks
100mg/m2,day1
25mg/m2/week
every4weeks
100mg/m2,day1
1000mg/m2,days1,8,15
every4weeks
75mg/m2,day1
500mg/m2,day1
75mg/m2,day1
every3weeks
500mg/m2,day1
every3weeks
ORR/survival
15%/274d
17%/8.1m
17%/7.4m
28%/8m
22%/8.1m
30.6%/10.3m
7.1%/7m
9.1%/8.3m
1. carboplatinAUC5-6,day1cisplatin
cisplatinhydration,
,
2. cisplatin75-100mg/m2
3. paclitaxel175-225mg/m2
86
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93
SmallCellLungCancer (SCLC)
TargetedTherapy
-----------------------------------------------------------------------------------------------
1.
2.
3.
4.

5.
6.
94
(ClinicalPracticeGuidelineforChemotherapyinPatientswith
SmallCellLungCancer(SCLC))
(SmallcelllungcancerSCLC)
(non-smallcelllungcancerNSCLC)14%
(1)
SCLCneuroendocrine
(extensivedisease)
(localizeddisease)VALungStudyGroup
(localizeddisease)
)
(extensivedisease)/
)(2)
(PS3-4)(extensivedisease)
LDH(3)SCLC

(2-5%) (TNMStage1)(4)
localizeddisease
(concurrentthoracicchemoradiotherapy)(5,6)
NationalCancerInstituteofCanada
(7)
(1)extensivedisease
extensivedisease
(wholebrainradiotherapy)
localizeddiseaseextensivedisease
(PRCR) prophylacticcranialirradiation
(non-smallcell
lungcancer)
(First-linetherapy)
95
EP(etoposide/cisplatin)
limiteddiseaseEP
alkylatingagentanthracycline(8)meta-analysis
carboplatincisplatin
(9)(1)
irinotecan/cisplatin
EP(12.89.4,p=.002)(10)

irinotecan/cisplatin(11,12)
carboplatin/Irinotecancarboplatin/etoposidecarboplatin/Irinotecan
(8.57.1,p=0.04)(13)(2A
Irinotecanetoposidefirst-linecombinationwithplatinum)
limiteddiseaseEP 70-90
extensivedisease
60-7014-20
limiteddisease9-11extensivedisease
alkylatingagent
(cyclophosphamide)/anthracycline(doxorubicinepirubicin)
EPEPpaclitaxel
EP
maintenancetreatmentoraletoposideEP
4-6
EPEP
(14)
SCLC

etoposideplatinumetoposide
(PS0-2)(15,16)carboplatin/etoposide
carboplatinAUC5etoposide (17)
( 1)
96
(Second-linetherapy)
SCLC
4-5
(PS0-2)
3(10%)
(refractoryresistantdisease)3
(sensitivedisease)25
EP
3-6CAV
CAVtopotecan

topotecan(18)(1topotecansecond-linetreatmentfor
platinum-refractory SCLC)
topotecan1.5mg/m2/d 5
1.25mg/m2/d
1.5mg/m2/d
1.0mg/m2/d(19)topotecan
(26
14)(20)amrubicintopotecan
topotecan(21)
topotecangrade3-4neutropenia
70-90 topotecan
4mg/m2(22,23)
grade3-4neutropenia(19-22%)
paclitaxel,docetaxel,vinorelbine,gemcitabine,temozolomide(24)
3
topotecan
97
:LD-SCLC
Regimens
Agents
Dose
ORR/survival
(25)
2
PE
cisplatin
60mg/m ,day1
87%/19m
etoposide
120mg/m2*,days1-3
every3weeks
*
100mg/m2
CarboE(26)
carboplatin
AUC6**,day1
76%/17.5m
2
etoposide
100mg/m ,days1-3
every3weeks
**
AUC=5
:ED-SCLC
Regimens
Agents
Dose
ORR/survival
PE(27)
cisplatin
80mg/m2,day1
22CR%/11.4m
etoposide
80mg/m2**,days1-3
every3weeks
(28)
CAV
cyclophosphamide 1,000mg/m2,day1
__/31wks
doxorubicin
50mg/m2,day1
vincristine
1.4mg/m2,day1*
every3weeks
(10)
Irinotecan/cisplatin Irinotecan
60mg/m2,days1,8,15
84.4%/12.8m
cisplatin
60mg/m2,day1
every3weeks
Topotecan(18)
Topotecan(IV) 1.5mg/m2/d,days1-5
4mg/m2/week, 12weeks(22,23)
*Maximumtotaldose,2mgperinjection.
carboplatinAUC5-6,day1cisplatin
cisplatinhydration,,
98
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24:4539-4544
2. MickeP,FaldumA,MetzT,etal.Stagingsmallcelllungcancer:VeteransAdministrationLungStudyGroup
versusInternationalAssociationfortheStudyofLungCancerwhatlimitslimiteddiseaseLungCancer2002;
37:271-276
3. AlbainKS,CrowleyJJ,LeBlancM,LivingstonRB.Determinantsofimprovedoutcomeinsmall-celllungcancer:
ananalysisofthe2580-patientSoutwestOncologyGroupdatabase.JClinOncol1990;8:1563-1574
4. YuJB,DeckerRH,DetterbeckFC,WilsonLD.Surveillance,epidemiologic,andendresultsevaluationoftherole
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6. WardeP,PayneD.Doesthoracicirradiationimprovesurvivalandlocalcontrolinlimited-stagesmallcell
carcinomaofthelung?Ameta-analysis.JClinOncol1992;10:890-895
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oflimited-stagesmall-celllungcancer.TheNationalCancerInstituteofCanadaClinicalTrialsGroup.JClinOncol
1993:11:336-344
8. SundstromS,BremnesRM,KaasaS,etal.Cisplatinandetoposideregimenissuperiortocyclophosphamide,
epirubicin,andvincristineregimeninsmall-celllungcancer:resultsfromarandomizedphaseIIItrialwith
5yearsfollow-up.JClinOncol2002;20:4665-4672.
9. RossiA,DiMaioM,ChiodiniP,etal.Carboplatioorcisplatin-basedchemotherapyinfirst-linetreatment
ofsmall-celllungcancer:theCOCISmeta-analysisofindividualpatientdata.JClinOncol2012;30:1692-1698
10. NodaK,NishiwakiY,KawaharaM,etal.Irinotecanpluscisplatincomparedwithetoposidepluscisplatinfor
extensivesmall-celllungcancerNEnglJMed2002;346:85-91
11. LaraPN,Jr.,NataleR,CrowleyJetal.PhaseIIItrialofirinotecan/cisplatincomparedwithetoposide/cisplatin
inextensive-stagesmall-celllungcancer:clinicalandpharmacogenomicresultsfromSWOGS0124.JClinOncol
2009;27:2530-2535
12. HannaN,BunnPA,Jr,LangerC,etal.RandomizedphaseIIItrialcomparingirinotecan/cisplatinwithetoposide/
cispatininpatientswithpreviouslyuntreatedextensive-stagediseasesmall-celllungcancer10.1200/
JCO.2005.04.8595.JClinOncol2006;24:2038-2043
13. HermesA,BergmanB,BremnesR,etal.Irinotecanpluscarboplatinversusoraletoposiedpluscarboplatinin
extersivesmall-celllungcancer:arandomizedphaseIIItrial.JClinOncol2008;26:4261-4267
14. WolfM,TebbeS,FinkT.Firstlinechemotherapyinmetastaticsmallcelllungcancer(SCLC).LungCancer2004
(Suppl.2)S223-S234
15. GirlingDJ.Comparisonoforaletoposideandstandardintravenousmultidrugchemotherapyforsmall-celllung
cancer:astoppedmulticenterrandomizedtrial.MedicalresearchCouncilLungCancerWorkingParty.Lancet
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randomizedcomparisonwithintravenouschemotherapy.JNatlCancerInst1997;89:577-580
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patientswithsmall-celllungcancer.InternMed2001;40:603-606
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18. vonPawelJ,SchillerJH,ShepherdFA,etal.Topotecanversuscyclophosphamide,doxorubicin,andvincristine
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cancer. EurRespirJ2006;27:1183-1189.
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JClinOncol1989;7(4):450-6.
100
-----------------------------------------------------------------------------------------------
1.
2.

3.

4.
5.
6.
7.

101
1. (bronchoalveolarlavage,BAL) (bronchialwashing,
BW)30 4-6
24 50%ethanol (finaldilution
25%ethanol)Saccomannofixative
1:1
- centrifugetube1500-2000
10
- supernatantPasteurpipettepellet
-
bloodsmear
- 95%ethanol
(wetfixed) 30
- Saccomannosfixative
- 4
2.(pleuraleffusion)
heparin1:1000fibrin
(4-6)72

- centrifugetubepipette
fibin
- centrifugetube1500-2000
10
102
- supernatantphosphatebuffersaline(PBS)
5
- Pasteurpipetteresuspendpellet
centrifugetube15
- 51500-2000
- supernatantPasteurpipettepellet
-
bloodsmear
- 4
- cellblock
forceps
sample pack cassette 10% neutral buffered formalin (NBF) 4-6
fluid cell block 2
1. phosphate buffered saline (PBS)
1.1 fluid 50 conical vial 3500 rpm 5
supernatant
1.2 PBS 20 3500 rpm 10 supernatant
1.3 1.2
1.4 Pellet sample
pack cassette 10% NBF 4-6
2. Nalthan Alcohol Fixative Solution (NAFS)
40% formaldehyde 1 + 95% Ethanol 9 (40% formaldehyde : 95%
ethanol = 1:9)
2.1 fluid 25-50 4000 rpm 6 supernatant

2.2 NAFS 45
2.3 4000 rpm 6 supernatant
2.4 pellet cassette 80% Ethanol processor
103
Fluid
BAL, BW
Fresh
(within 30 min)
Pleural fluid
1:1, 50% ethanol, or

1:1, Saccamanno fixative
Store in refrigerator within 72 hours
Centrifuge
1500-2000rpm,10min
Smear(4slides)
Immediatelywetfixed
andleft30minthenairdried
Centrifuge
1500-2000rpm,10min
Centrifuge,#1
1500-2000rpm,10min
Smear(4slides)
discardsupernatant
+
PBSfinalvolume5ml
Air-dried
Centrifuge,#2 1500-2000rpm,5min
PathologyLab
Smear(4slides)
PathologyLab
104
3.Fineneedleaspiration(Directlungtap,Wangsneedleaspiration)
Bronchialbrushing 95%ethanol (wetfixed)
30
4.biopsy:
request
0.1-0.2 10%NBF(
exudates
)
5.
,--(lobectomy)
(pneumonectomy),(segment)

10%NBF2
(24)formalin(10%NBF)
200-500(bronchialmargin)
formalin
1. centrallesion
2. peripherallesionpleuralsurface
pleuralsurfaceretraction
10%NBF2
10%NBF
formalin
105
1. (Cytologyreport):
1.1
-
-(bronchoalveolarlavageBAL)(bronchial
washingBW)
-Bronchialbrushing
-(pleuralfluid)
-directlungtap(DLT)needleaspiration
-Cellblock
1.2 Adequacy (Inadequate
fordiagnosis)
1.3 GuidelinesofthePapanicolaousocietyofCytopathology
fortheExaminationofCytologicSpecimensObtainedfromtheRespiratory
Tract
FNA5
1) nondiagnoticspecimen
2) specificbenignlesionsbenigntumor,inflammatory
processes,infectiousagents
3) atypicalcellspresent,probablybenign
4) atypical,suspiciousformalignancy
5) malignancypresenthistologictypecarcinoma

2.(Surgicalpathologyreport)
2.1biopsy

NSCLCSCLCadenocarcinoma
NSCLC52paraffinblocks
106
non-smallcelllungcarcinoma(NSCLC)
(smallbiopsy)
/
(targetedtherapy)adenocarcinoma(ADC)squamouscellcarcinoma(SQCC)

(wellormoderatedifferentiation)
glandularformation,papillarypatternlepidic
patternADCintercellularbridgeskeratinpearlSQCC(1a)
(poordifferentiation)
H&Estainedslide
ADC(molecularstudy)
targetedtherapy
NSCLC(1)
1(welltomoderatedifferentiation)
ADC SQCC
ADCgrowthpattern(1b-d)ADClepidic
patternInvasivecomponentcannotbeexcluded
mucinoustallcolumnar
mucinousADCADCSQCC
NSCLC,nototherwisespecified(NOS)
2
2NSCLC,NOSimmunohistochemicalstain(TTF-1,p40p63CK5/6)mucicarminestain
immunohistochemicalstain1
ADCTTF-1/mucicarmineNSCLC,
favorADC (supportedbyspecialstains)(2)
107
SQCCp63/
CK5/6 TTF-1mucicarmine NSCLC,favorSQCC
(supportedbyspecialstains)(3)TTF-1p40
p63/CK5/6NSCLC,NOS
(comment)adenosquamouscarcinoma
NSCLC,NOS
3ADC
classicADC,NSCLC,favorADC,NSCLC,NOSNSCLC, NOS,
possibleadenosquamouscarcinoma
immunohistochemical
stain 100
TTF-1ADC
cloneTTF-1clone8G7G3/1
ADC cloneSPT24SQCC(1)
(Ref:MatosoA,SinghK,JacobR,GreavesWO,TaveresR,NobleL,etal.
Comparisonofthyroidtranscriptionfactor-1expressionby2monoclonalantibodiesin
pulmonaryandnonpulmonaryprimarytumors.ApplImmunohistochemMol
Morphol.2010;18(2):142-9.)
108
1 NSCLC(IASLC/ATS/
ERSclassificationforlungadenocarcinoma,2011)
NE morphology, large cells,

NE IHC+
NE morphology, small cells, no
nucleoli, NE IHC+,TTF-1 +/-,
CK+
Keratinization, pearls
and/or intercellular bridges
STEP 1
POSITIVE BIOPSY (FOB,
TBBx,Core, SLBx)
POSITIVE CYTOLOGY
(effusion, aspirate, washings
brushings)
Histology: Lepidic, papillary, and/or
acinar architecture(s)
Cytology: 3-D arrangements, delicate
foamy/ vacuolated (translucent)
cytoplasm,
Fine nuclear chromatin and often
prominent nucleoli
Nuclei are often eccentrically situated
Classic morphology:
ADC
ADC marker
and/or
Mucin +ve;
SQCC
marker -ve
(or weak in
same cells)
NSCLC,
?LCNEC
SCLC,
Classic Morphology:
SQCC
No clear ADC or
SQCC morphology:
NSCLC-NOS
NSCLC, favor SQCC
STEP 2
Apply ancillary panel of
One SQCC and one ADC marker
+/OR Mucin
IHC -ve and

Mucin -ve
NSCLC, favor ADC
SQCC marker +ve

ADC marker -ve/or
Mucin -ve
ADC marker or Mucin +ve;

as well as SQCC marker +ve
in different cells
NSCLC NOS
Molecular analysis:
e.g. EGFR mutation
NSCLC, NOS,
possible
adenosquamous ca
STEP 3
If tumor tissue inadequate for molecular testing,
discuss need for further sampling - back to Step 1
109
TTF-1*
p40*orp63*
immunohistochemistry
NSCLC,favoradenocarcinoma
+# (focal or diffuse)
+ (focal or diffuse)
NSCLC,favorsquamouscell carcinoma
+**
NSCLC,favorsquamouscell carcinoma
+**
NSCLC,NOS
1 immunohistochemicalstain(WHOclassificationof
number of the lung, pleura, thymus and heart, 2015)
*TTF-1p63
p40 squamous
differentiation p63 adenocarcinoma
1/3 p40 TTF-1
#adenocarcinomaTTF-1 p40 / p63
(same population)
**p40 / p63 SQCC
(moderate)(diffuse)
(patchy)(weak)ADC
NSCLC,NOS
110
Neuroendocrinetumor
PathologyofSmallcelllungcancer(SCLC)
Histologictype
TC
AC
LCNEC
SCLC
NEmorphology
yes
yes
yes
TypicalsmallcellCA
Nuclearpleomorphism minimal
yes
yes
yes,<3-4Lymphocytes
Distinctnucleoti
no
maybe
yes
no
Mitosis/2mm2
<2
2-10
>10
>10
Necrosis
no
yes,minimal
yes
yes,pronounced
Shape
R,O,S
R,O,S
R,O,P
R,O,S;N/Cincreased
Other
Crushartifact,mold,Azz
Histologictype:TC=typicalcarcinoid,AC=atypicalcarcinoid,LCNEC=largecellneuroendocrinecarcinoma,SCLC=smallcelllungcarcinoma,ND=neuroendocrinedifferentiation
Cellularshapes:R-round,O-oval,S-Spindle,P-polygonal.
Other:Azz=Azzopardiseffect
Histologictype
Chomogranin
Synaptophysin
TTF-1
Ki-67
CD56
ImmunohistochemistryforSCLCdiagnosis
TC
AC
LCNEC
SCLC
Diffuse
Lessdiffuse Average30%
vary
80-100%case
80%case
40-60%case
Diffuse
Lessdiffuse Average45%
vary
80-100%case
80%case
40-80%case
0-35%case
40-70%case
50-95%case
<10%
>25%
Diffuse
usuallydiffuse
111
2.2SurgicalSpecimenguidelineCAP
check list(7)
112
113
114
115
116
117
LUNG CANCER
WORK AID
Patient Name:
Hospital #:
Case #:
Diagnosis:
Procedure:
Major airway resection
Wedge resection
Segmentectomy
Other:
Included Sites:
Left upper lobe
Lingula
Left lower lobe
Lobectomy
Bilobectomy
Pneumonectomy
Not Specified
Right upper lobe

Right middle lobe
Right lower lobe
Mainstem bronchus
Other:
Specimen integrity: Intact

Tumor Site:
Left upper lobe
Lingula
Left lower lobe
Disrupted
Mainstem bronchus
Other:
Right upper lobe

Right middle lobe
Right lower lobe
Tumor Size:
Histologic Type:
Non-small cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenocarcinoma
Mucinous adenocarcinoma

Treatment Effect: (Required only if applicable)

> than 10% residual viable tumor
Cannot be determined
< 10% residual viable tumor
Not applicable
Lymph Nodes:
Node Group
Positive
Extracapuslar
Large cell carcinoma

Adenosquamous carcinoma
Giant cell carcinoma
Carcinosarcoma
Typical carcinoid
Atypical carcinoid
Pathologic Staging: (Descriptors: m-multiple, r-recurrent, y-post tx)

m
Comments:
Tumor Extension:
Diaphragm
Phrenic nerve
Mediastinal pleura
Parietal pericardium
Mediastinum (incl. heart, great

vessels, recurrent laryngeal nerve,
Parietal pleura

trachea, esophagus)

Vertebral body
Chest Wall
Other:
Margins:
Margin
Total
Multifocal, different ipsilateral lobe(s)

Synchronous carcinomas
Other:
Main bronchus
< 2 cm from carina
2 cm or more from carina
Inolving carina
Visceral pleuraV
Negative Equivocal Positive
Lymph-vascular invasion:
cm
(in greatest dimension)
Tumor Focality:
Unifocal
Multifocal, same lobe
Cannot be determined
Indeterminate
Negative
Closest *distance (mm)
Positive
pT
pN
pM
118
SynopticReportExample
Carcinomaofthelung
Specimentype:

Lung,leftupperlobe
Procedure:

Lobectomy
Specimenintegrity:
Intact
Tumorsite:

Upperlobe
Tumorsize:

1.7x1.5x1.2cm
Tumorfocality:

Unifocal
Histologictype:

Squamouscellcarcinoma
Visceralpleuralinvasion:
Notidentified
Directtumorextensionintoextrapulmonarystructures:Notapplicable
Bronchialmargin:

Uninvolvedbyinvasivecarcinoma
Vascularmargin:

Uninvolvedbyinvasivecarcinoma
Parenchymal(stapled)margin: Notapplicable
Parietalpleuralmargin:
Notapplicable
Chestwallmargin:
Notapplicable
Otherattachedtissuemargin: Notapplicable
Distancetoclosestmargin: 4.2cmfromvascularmargin
Neoadjuvanttreatmenteffect: Notapplicable
Lymph-vascularinvasion:
Notidentified
Pathologicstaging(pTNM):
Primarytumor:

Regionallymphnodes:
Numberexamined:
Numberinvolved:

pT1a
pN0
5
0
119
2.3(Nodesampling)
1.Partialnodesampling:3Carina
2.Systemicnodesampling:>3
anthracosis fat issue
(mattedonenode)
2.4(Moleculartesting)
adenocarcinomasquamouscellcarcinoma
paraffin
1. EGFRexon19exon21
DNA
biopsy 100/
T790Mexon20
Immunohistochemistryantibodyexon19deletion exon21
L858R
2. ALKfusiongene Immunohistochemistry
antibodyD5F35A4antibody positivecriteria
D5F3 2+/3+criteria5A4Abcam
ALKBreakApartFISHprotocol
120
121
122
123

1SQCCkeratinformation
intercellularbridge(a),ADC
(growthpattern)
acinarpattern(b),(fibrovascular
core)papillarypattern(c)
lepidicpattern(d)
2NSCLC,favorADC(supportedbyspecialstains)
solidpattern
ADCSQCCmucicarmine()TTF-1 p63
CK5/6ADC
124
3NSCLC,favorSQCC(supportedbyspecialstains)
solidpattern3p63CK5/6 mucin
TTF-1 SQCC
4Smallcellcarcinoma(SCLC)
125
1. TravisW.D,BrambillaE.,Muller-HermelinkH.K.,HarrisC.C.(eds.):WorldHealthOrganizationClassification
of Tumors.PathologyandGeneticsofTumorsofSofttissueandBone.IARCPress:Lyon2002.
2. LesterS.ManualofSurgicalPathology.2ndedition.ElsevierInc.:ChurchillLivingstone,Philadelphia2006.
3. ColbyT.V.,KossM.N.andTravisW.D.:Atlasoftumorpathology.Tumorsofthelowerrespiratorytract.
AFIP:WashingD.C.1995.
4. KumarV.,AbbasA.KandNelsonF.(eds):RobbinsandCotranpathologicbasisofdisease.7thedition.Elsevier
Inc. :Internationaledition:Saunders.Philadelphia2005.
5. NCCN,ClinicalpracticeguidelinesinOncology2008.Smallcelllungcancer.
6. NCCN,ClinicalpracticeguidelinesinOncology2008.Non-smallcelllungcancer
7. ButnorK.J.,BeasleyM.B.,CagleP.T.,GrunbergSM,KongFM,MarchevskyA,OkbyNT,RoggliVL,SusterS,
TazelaarHD,TravisWD.ArchPatholLabMed.:Protocolfortheexaminationofspecimensfrompatientswith
primarynon-smallcellcarcinoma,smallcellcarcinoma,orcarcinoidtumorofthelung.2009.

126
127

1.
2. (PeerReviewer)
3. (Diagnosis)
4. (Surgery)
5. (Radiotherapy)
6. (Chemotherapy)
7. (Pathology)
1.
1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.
14.

15.

128
16.

17.
18.
19.

20.

21.

22.
23.

2.(PeerReviewer)
1.

2.

3.
4.
5.
3.(Diagnosis)
1.
2.

3.
4.(Surgery)
1.
2.
129
5.(Radiotherapy)
1.

2.
3.
6.(Chemotherapy)
1.
2.
3.
4.

5.

6.

7.(Pathology)
1.
2.

3.

4.
5.
6.
7.

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1

Non-Small Cell Lung Cancer (NSCLC)

Separate pulmonary nodule(s)

Stage IIIAb (T1-3, N2)

Stage IV (M1b) disseminated metastases

Stage IIBb (T3 invasion, N0);

Stage I, peripherala (T2a, N0); centrala (T1ab-T2a, N0);

Stage IA, peripherala (T1ab, N0)

1.1 Non-Small Cell Lung Cancer

Definitive RT including stereotactic

See Stage IIIA or Stage IIIB

See Stage IIIA or Stage IIIB

Surgical resection +systematic

1.2 Non-Small Cell Lung Cancer

Margins negative (R0)n

Chemoradiationj (sequence or concurrent)

Margins negative (R0)n

Reresection (preferred) chemotherapy

Margins positive (R1, R2)n

Margins negative (R0)n

Margins positive (R1, R2)n

Margins negative (R0)n

R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

Stage IIIA (T1-3, N2; T3, N1)

Stage IIB (T3, N0; T2b,N1)

Stage IIA (T1ab-T2a, N1)

Stage IIA (T2b, N0)

Stage IB (T2a, N0);

Stage IA (T1ab, N0)

1.3 Non-Small Cell Lung Cancer

Stage IIB (T3 invasion, N0)

Superior sulcus tumor

1.4 Non-Small Cell Lung Cancer

1.5 Non-Small Cell Lung Cancer

Complete definitive RTj

R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

1.6 Non-Small Cell Lung Cancer

Mediastinoscopy, EBUS EUS option

Stage IV (N0, M1a):

N2, N3 nodes negative

1.7 Non-Small Cell Lung Cancer

See treatment for metastasis

solitary site ( 18) or

RTj (if not given)

See Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D)

Surgeryi chemotherapyk (category 2B)

See treatment for metastasis solitary site

1.8 Non-Small Cell Lung Cancer

Treat as two primary lung

Chest CT with contrast

See initial treatment

See Systemic Therapy for

See Systemic Therapy for Metastatic Disease

See Chemotherapy regimens Used with Radiation Therapy (NSCL-E)

Methods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS,

Stage IV (N0, M1a):

1.9 Non-Small Cell Lung Cancer

See Principles of Surgical Therapy (NSCL-B)

1.10 Non-Small Cell Lung Cancer