Download Lung cancer

Lung cancer
ร.ศ.น.พ. ธีรวิทย์ พันธุ์ชยั เพชร
ภาควิชาศัลยศาสตร์
คณะแพทยศาสตร์ศิริราชพยาบาล
M
International variation in
age-standardized lung cancer
incidence rates per 100,000
population in 2002
new case=1.35 m
dead = 1.18 m
F
5 year relative survival
M<14%, F<18%
Youlden et al. (J Thorac Oncol. 2008;3: 819–831)
World Age-adjusted Incidence Rates for
Most Common Sites in Men
Lung
34.9
Stomach
21.5
Prostate
21.2
Colorectal
19.1
Liver
15
Esophagus
10.8
Bladder
10
Lymphoma
6.7
Oral cavity
6.4
Larynx
5.5
0
10
20
30
Incidence rates (per 100,000)
40
World Age-adjusted Incidence Rates for
Most Common Sites in Women
Breast
35.7
Cervix
16.2
Colorectal
14.4
Lung
11.1
Stomach
10.4
Ovary
6.5
Uterus
6.4
Liver
5.5
Lymphoma
4.8
Esophagus
4.5
0
10
20
30
Incidence rates (per 100,000)
40
World Age-adjusted Death Rates for Most
Common Sites in Men
Lung
31.4
Stomach
15.6
Liver
14.4
Colorectal
9.8
Esophagus
8.8
Prostate
8
Pancreas
4.3
Leukemia
3.9
Bladder
3.8
Lymphoma
3.6
0
10
20
30
Death rates (per 100,000)
40
World Age-adjusted Death Rates for Most
Common Sites in Women
Breast
12.5
Lung
9.5
Cervix
8
Stomach
7.8
Colorectal
7.6
Liver
5.5
Ovary
3.8
Esophagus
3.7
Pancreas
3.3
Leukemia
2.8
0
5
10
Death rates (per 100,000)
15
Estimated New Cancer Cases and Deaths by Sex, United States, 2012.
Estimated new cases and deaths from lung cancer ( USA)
New cases: 219,440.
Deaths: 159,390.
5-year relative survival rate (1995 – 2001)= 15.7%.
Local recurrence =49%
Regional metastasis = 16%
Distant metastasis = 2%
(American Cancer Society.: Cancer Facts and Figures 2009)
LUNG CANCER
Risk
factors—smoking
Smoking
has been implicated in:
• 80% of lung cancer deaths in men
• 75% of lung cancer deaths in women
• 17% of lung cancer cases in nonsmokers
• 28% of all cancer deaths
35-year old male who smokes 25 cigarettes per day:
• 13% risk of dying from lung cancer before age 75
• 10% risk of dying from coronary disease
• 28% risk of dying from smoking-related disease
American Cancer Society. Cancer Facts & Figures–2001
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 6th ed. 2001;925-983.
LUNG CANCER
Risk factors other than smoking
• Asbestos
• Radon (from mining or indoor exposure)
• Other “occupational carcinogens”
Chloromethyl ether
Chromium
Nickel
Arsenic
• Diet (vitamins A, C, E, -carotene deficiencies)
• Genetic/familial factors
Figlin RA, et al. Cancer Treatment. 1995;385-413.
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 6th ed. 2001;925-983.
NCCN guideline on lung cancer
screenining
(version 1.2012)
• Risk factors for lung cancer
• Recommend high-risk for screening
• Evaluation & follow-up of nodules
• Accuracy of LDCT & image modalities
• Benefits & Risks of screening
Lung cancers screening : Risk asessments
a) encourage quit smoke
b) high radon exposure
c) lung carcinogen:
asbestos, arsenic, nickel,
beryllium, cadmium, chromium, sillica
diesel fumes
d) lung cancer, lymphomas, cancers of
head & neck, smoking-related cancers
e) Second hand smoke: variable exposure:
It is not independent risk factor for lung
cancer screening.
Recommendation for lung cancer screening
High risk:
# Age 55-74 y and >30 pack
LDCT= Spiral(herical) Lowdose computed tomography
100-120kVP & 40-60mAs
year history of smoking and
smoking cessation < 15 y
(category 1)
# Age > 50 y and >20 pack
year history of smoking and
one of additional risk
factors(other than secondhand smoke)
(category 2B)
Additional risk factors:
cancer history,
lung disease history,
family history of lung cancer,
radon exposure,
occupational exposure
Risk status
Routine lung cancer screening is not recommended.
f evaluated mediastinum or lymph node prefered standard dose CT with contrast.
g benign pathern: calcification, fat in nodule, feathure suggested inflammatory process, multiple nodules
m new nodule > 3 mm in mean diameter
l rapid increase in size suspeced inflammatory process.
n PET/CT for lesion greater than 8 mm.
Risks/Benefits of lung cancer screening
WHO histologic classification of Lung Cancer
(1999)
• Preinvasive lesion
Squamous dysplasia/carcinoma in situ
Atypical adenomatous hyperplasia
Diffus idiopathic pulm.neuroendocrine cell hyperplasia
• Invasive malignant
Squamous cell (papillary, clear cell, small cell, basaloid) (30%)
Small cell (combined SCLC) (15-20%)
Adenocarcinoma (acinar, papillary, bronchioloalveolar, solid with mucin
formation, mucinous, signet ring, clear cell) (30-50%)
Large cell (neuroendocrine, basaloid, lymphoepithelioma-like, clear cell,
large cell with rhabdoid phenotype) (5-10%)
Adenosquamous (1.5%)
Carcinomas with pleomorphic, sarcomatoid, or sarcomatous
elements(spindle,giant cell, carcinosarcoma, pulm. Blastoma)
Carcinoid tumor (typical,atypical) (1%)
Carcinomas of salvary gland type (mucoepidermoid, adenoid cystic)(0.1%)
Unclassified carcinoma
International Association for the Study of Lung Cancer/American Thoracic Society/European
Respiratory Society classification of lung adenocarcinoma in resection specimens
Pre-invasive lesions
Invasive adenocarcinoma
• Atypical adenomatous hyperplasia(AAH) • Lepidic predominant
• Adenocarcinoma in situ
(formerly nonmucinous BAC pattern,
(≤3 cm formerly BAC) =AIS
with >5 mm invasion)
Nonmucinous
• Acinar predominant
Mucinous
• Papillary predominant
Mixed mucinous/nonmucinous
• Micropapillary predominant
Minimally invasive adenocarcinoma
• Solid predominant with mucin
(≤3 cm lepidic predominant tumour,
production
with ≤5 mm invasion) = MIA
• Variants of invasive adenocarcinoma
Nonmucinous
Mucinous
Mixed mucinous/nonmucinous
Invasive mucinous adenocarcinoma
(formerly mucinous BAC)
Colloid
Fetal (low and high grade)
Enteric
SCLC: Staging
• Limited Stage
tumor involvement of one lung, the
mediastinum and ipsilateral and/or
contralateral supraclavicular lymph nodes
or disease that can be encompassed in a
single radiotherapy port.
• Extensive Stage
SMALL CELL LUNG CANCER
Survival by stage
Median Survival –
Untreated Patients
(wk)
Median Survival –
Treated Patients
(mo)
5-Year Survival
(%)
12
14-20
10%-20%
5
8-12
3%-5%
Limited disease
Extensive disease
Ihde DC, et al. Cancer: Principles & Practice of Oncology. 1997;911-948.
Lassen U, et al. Cancer Treatment. 1995;414-420.
Soriano AF, et al. Current Cancer Therapeutics. 1998;177-191.
NSCLC
Survival for Resected Patients (TMN staging 1986)
Stage
Descriptors
5-yr Survival%
I
T1-2 N0 M0
60 – 80
II
T1-2 N1M0
25 – 50
IIIA
T3 N0-1 M0
T1-3 N2 M0
25 – 40
10 – 30
IIIB
Any T4 or
Any M3 M0
<5
IV
Any M1
<5
Staging (1997)
TNM Subset
5-year survival
Clinical staging
Pathologic staging
IA
T1N0M0
61%
67%
IB
T2N0M0
38%
57%
IIA
T1N1M0
34%
55%
IIB
T2N1M0
T3N0Mo
IIIA
T1-3N2M0
IIIB
IV
24%
22%
39%
38%
13%
23%
T3N1M0
9%
25%
T4N0-2M0
7%
<10%
T1-4N3M0
3%
Any T Any N M1
1%
IASLC: analysis: NSCLC 68,463,SCLC 13,032 from 1990-2000……New Lung cancer staging 2010
New lung cancer staging system(AJCC and UICC2010 )
for
NSCLC, SCLC Carcinoid tumors
•
•
•
•
•
T1 ….. T1a (≤2 cm in size) & T1b (>2–3 cm)
T2 …...T2a (>3–5 cm in size) & T2b (>5–7 cm)
T2 (>7 cm in size) …..T3.
Multiple tumor nodules in the same lobe = T4 ….T3
Multiple tumor nodules in the same ~ different lobe = M1 ….T4
• M1 …..M1a & M1b.
• Malignant pleural and pericardial effusions = T4 …..M1a.
• Separate tumor nodules in the contralateral lung = M1a …..M1b
*Sarcomas and other rare tumors are not included
Classification of visceral pleural invasion (VPI)
PL category
Definition
PL0
Tumor within the subpleural
parenchyma or, invading
superficially into the pleural
connective tissue below the
elastic layer.
PL1
Tumor invades beyond the elastic
layer.
T status
PL0 is not a T descriptor
and the T component
should be assigned on
other features.
Indicates
VPI
pT2
PL2
Tumor invades to visceral pleural
surface.
PL3
Tumor invades the parietal pleura.
pT3
Classification of visceral pleural invasion (VPI)
The 7th edition of the “TNM Classification of Malignant Tumors”
new lung cancer staging system(AJCC and UICC2010 )
6th ed
7th ed
T/M descriptors
N0
N1
N2
N3
T1 (=2cm)
T1a
IA
IIA
IIIA
IIIB
T1 (>2 cm =3 cm)
T1b
IA
IIA
IIIA
IIIB
T2 (>3 cm =5 cm)
T2a
IB
IIA
IIIA
IIIB
T2 (>5 cm = 7 cm)
T2b
IIA
IIB
IIIA
IIIB
IIB
IIIA
IIIA
IIIB
IIB
IIIA
IIIA
IIIB
T4 (same lobe nodules)
IIB
IIIA
IIIA
IIIB
T4 (extension)
IIIA
IIIA
IIIB
IIIB
IIIA
IIIA
IIIB
IIIB
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
T2 (>7 cm)
T3 (direct invasion)
M1 (ipsilateral nodules)
T4 (pleural effusion)
M1 (contralateral nodules)
M1 (distant)
T3
T4
M1a
M1b
Definitions of second primary, satellite nodules and metastasis
Type
Definition
Satellite nodule
MPLCs
Metastasis
Same histology
And same lobe as primary cancer
And no systemic metastasis
Same histology,
anatomically separated
Tumors in different lobes
And no N2-3 involvement
And no systemic metastasis
Same histology, temporally
separated
=4-yr interval between tumors
And no systemic metastasis from
either tumor
Different histology
Or different molecular genetic
features
Or arising separately from foci of
CIS
Same histology
With multiple systemic metastasis
Same histology, in different And presence of N2-3 involvement
lobes
Or < 2-yr interval
Diagnosis
• Sputum cytology
• Bronchoscopy
+
60-70%
central lesion +90%
mid lung lesion +50%
Peripheral lesion +25%
• TNA or FNA under fluoroscopy or CT guide
sensitivity 75-80%, specificity 100%
result possibility cancer 20-30%
Non-Invasive Staging for Lung Cancer (ACCP:2007)
mediastinal lymph node metastasis?
sensitivity
specificity
51%
74 %
85%
85%
97%
Without enlarged nodes on CT
90 %
58 %
EBUS
92 - 96 %
CT scan
PET scan
EUS-guided FNA
With enlarged nodes on CT
FDG-PET scan
False-negative ….. small tumors(<1cm)
False-positive …..benign inflammatory diseases
Unreliable for brain metastasis
For detection of mediastinal metastases:
sensitivity = 91%
specificity = 86%
For detecting distant metastases:
sensitivity = 82%
specificity = 93%
Invasive mediastinal staging
Mediastinoscopy
Anterior Mediastinotomy
(Chamberlain Procedure)
VATS
International Association for the Study of Lung Cancer
(IASLC) & European Society of Thoracic Surgeons
Systematic nodal dissection (SND): to dissect and
remove all mediastinal tissue containing the lymph
nodes within anatomic landmarks. Excision of at least
three mediastinal nodal stations, including the subcarinal
node, is recommended as a minimum requirement.
“Systematic sampling” refers to a routine biopsy of
lymph nodes at some levels of nodal station.
Lymphatic drainage of the lung
Lardinois D, De Leyn P, Van Schil P, et al. ESTS guidelines for intraoperative lymph node
staging in non-small cell lung cancer. EurJ Cardiothorac Surg 2006;30:787–792.
Performance Status
Eastern Cooperative Oncology Group/ Zubrod Scale
0=minimal symptoms; fully functional
1= symptomatic; able to carry out all ordinary tasks
2= < or = 50% waking hours in bed
3= 50% waking hours in bed
4= bedridden; often moribund
Principles of surgical therapy of lung cancer
• Anatomic pulmonary resection
• Sublobar resection:
segmentectomy & wedged excision:
margin>2 cm.or > size of the nodule
N1-2 sampling if technical feasible(add no risk)
for poor lung reserve or major co-morbid
Peripheral nodule<2cm. With:
Pure AIS
Nodule has 50% ground glass on CT
a long doubling time(>400d) from Imaging
Principles of surgical therapy of NSCLC
• VATS approach is acceptable. (no compromise standard
oncologic & dissection principles)
• Lung sparing anatomic resection(sleeve lobectomy
preferred over pneumonectomy) if complete resection.
• Enbloc resection for T3(extention) & T4 local invasion if
potential complete resection.
• Pathology:close or positive margin:risk of local
recurrence
• N1-2 dissection(minimal three N2 sampling or complete
dissection)
Principles of surgical therapy of NSCLC
• Complete resection:
systemic dissection or sampling
free margin
no extracapsular nodal extension
highiest mediastinal node negative
• Incomplete resection:
margin positive,
extracapsular nodal extension
unremoved positive nodes
positive pleural or pericardial effusions
• R0 = complete resection
• R1 = microscopic positive resection
• R2 = macroscopic residaul tumors
Post NSCLC resection
management
• Pathologic stage II or greater:
should be referred to medical oncologist for
evaluation.
• Consider referral to medical oncologist for
resected stageIB.
• Consider referral to radiation oncologist for
resected stageIIIA.
The role of surgery in stageIIIA (N2 dis).
• ?N2…Radiologic & invasive staging before Rx.
• EUS/EBUS before Rx
• Intraop. Occult N2: standard resection.
• Mediastinoscopy before planned resection
• Single node size < 3 cm may considered resection.
• PET/CT for restaging after induction therapy.
• Negative mediastinum after neoadjuvant Rx: better prognosis
• After neoadjuvant Rx:evaluation of the mediastinum
Radiographic methods ..unreliable
EBUS(+/-EUS) for pre treatment evaluation
Remediastinoscopy is difficult & lower accuracy.
Reserve mediastinoscopy for nodal restaging
Principles of surgical therapy of SCLC
• Stage I, SCLC < 5% of all SCLC
• Staging > IB, do not benefit from surgery.
• Stage I should undergo standard evaluation &
invasive mediastinal staging before surgery.
• PCI(Prophylatic cranial irradiation) can improve
disease-free & overall survival.
• PCI is not recommended in poor performance
status & impaired mental function.
Standard evauation= CT chest,upper abdomen,brain imaging,PET/CT
Postop.complete resection: without nodal metastasis …potop. Chemotherapy.
with nodal metastasis…concurrent chemo-radiation.
Early stage Lung cancer:
severe dysplasia,
carcinoma in situ (CIS),
carcinoma in sputum cytology(normal CXR)
Treatment: Photodynamic therapy under
autofluorescent bronchoscopy guide
Superficial squamous cell carcinoma who are not
surgical candidates
Treatment: photodynamic therapy,
electrocautery,
cryotherapy,
brachytherapy
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
clinical stage I and II NSCLC
surgical resection:
conventional surgical resection,
lobectomy or greater resection (1A)
comorbid disease or decreased pulmonary
function, sublobar resection is recommended (1B)
stage I and II NSCLC, it is recommended
that intraoperative systematic mediastinal
lymph node sampling or dissection be performed for accurate pathologic staging. (1B)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
stage I NSCLC the use of VATS by surgeons
experienced in these techniques is an acceptable
alternative to open thoracotomy.(1B)
centrally or locally advanced NSCLC in whom a
complete resection can be achieved with either technique, sleeve lobectomy is recommended over
pneumonectomy.(1B)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
completely resected stage IA NSCLC, the use of
adjuvant chemotherapy is not recommended for
routine use outside the setting of a clinical trial.(1A)
completely resected stage IB NSCLC, the use of
adjuvant chemotherapy is not recommended for
routine use. (1B)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
In NSCLC patients with N2 disease identified
preoperatively (IIIA), induction therapy followed by
surgery is not recommended except as part of a clinical
trial.(1C)
Post induction chemoradiotherapy for stageIIIA,N2 dis.
Pneumonectomy is not recommended.(1B)
Incomplete resection of stageIIIA,N2 dis.
Postoperative platinum-based chemoradiotherapy is
recommended. (1C)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
In selected patients with clinical T4N0-1 NSCLC due to
satellite tumor nodule(s) in the same lobe, Surgery is
not recommended if there is N2 involvement.. (1C)
StageIIIB,T4(satellite)N0, no mediastinal or distant
metastasis:
Lobectomy is the recommended.(1B)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
Pancoast tumor with mediastinal nodes or distant
metastasis is contraindicated to resection.(1C)
Potential resectable, nonmetastatic Pancoast tumor
with good PS
Preop. concurrent chemoradiotherapy is recommended
prior to resection.(1B)
Complete or incomplete resected Pancoast tumor:
postoperative radiotherapy is not recommended
because of no survival benefit.(2C)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
Intraoperative found a second cancer in a different lobe,
resection of each lesion is recommended.(1C)
Metachronous NSCLC with mediastinal nodes
metastasis is a contraindication to resection.(1C)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
Isolated brain metastasis with mediastinal nodes involvement is
a contraindication to resection. (1C)
In resectable N0,1 or previously complete resected primary
NSCLC with isolated brain metastasis:
Resection or radiosurgical ablation of an isolated brain
metastasis is recommended.(1C)
After curative resection of an isolated brain metastasis,
adjuvant whole-brain radiotherapy is suggested.(2B)
After curative resections of both the isolated brain metastasis
and the primary tumor, adjuvant chemotherapy may be
considered.(2C)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
Isolated adrenal metastasis with mediastinal nodes
metastasis is a contraindication to resection.(1C)
In resectable N0,1 primary NSCLC, with isolated adrenal
metastasis:
Resection of both primary tumor and adrenal metastasis
is recommended.(1C)
Isolated adrenal metastasis in previously complete
resected primary NSCLC and disease-free interval is > 6
months:
Resection of an isolated adrenal metastasis is
recommended.(1C)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
In suspected BAC who are good surgical candidates
and CT shows a pure ground-glass appearance:
Sublobar resection may be appropriate if intraoperative
pathologic confirms pure BAC without evidence of
invasion, and surgical margins are free of disease.(1B)
In stage I,SCLC who are being considered for curative
resection:
Invasive mediastinal staging and extrathoracic imaging
(head CT/MRI, abdominal CT plus bone scan) followed
by a platinum-based chemotherapy should be offered.
(1A)
Diagnosis and Management of Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)2007
A Consensus Statement of ISMICS 2007
Video-Assisted Thoracic Surgery for Lung Cancer Resection
1. VATS can be recommended to reduce overall postoperative
complications ( IIa, level A ).
2. VATS can be recommended to reduce pain and overall
functionality over the short term ( IIa, level B ).
3. VATS can be recommended to improve delivery of adjuvant
chemotherapy delivery ( IIa, level B ).
4. VATS can be recommended for lobectomy in clinical stage I and
II NSCLC patients, with no proven difference in stage-specific
5-year survival compared with open thoracotomy ( IIb, level B
).
Robert J. Downey, Davy Cheng,Kemp Kernstine,Rex Stanbridge,Hani Shennib,Randall Wolf,Toshiya
Ohtsuka,Ralph Schmid,David Waller, Hiran Fernando,Anthony Yim,and Janet Martin (Innovations 2007;2: 293–
302)
VATS versus Open Thoracotomy: A Comparison
THORACOTOMY
VATS
Size of incision
10-14 inches
approx. 1 inch
Average hospital stay
10-12 days
Less than 2 days
Return to work/normal routine
6-8 weeks
7-10 days
Major Complications
30 percent
less than 5 percent
Less postop. Pain
Shorten hospiyal stay
Rapidly recover
Cosmetic
Minimal trauma immunological advantage
Simultaneous
Stapling lobectomy
The Valley Hospital
New Jersy
Open? or VATS?
Multiple or Single port VATS?
Rib spreading or Not?