Transcript Prezentace aplikace PowerPoint

Bronchogenic
carcinoma
Prof. MUDr. Miloslav Marel, CSc.
Pulm. Depth. of the 1st Medical
Faculty of Charles University, Prague
What is Lung Cancer?
• An estimated 219,440 people diagnosed in the
United States in 2009
• The leading cause of cancer death among men and
women
• Begins when cells in the lung grow out of control
and form a tumor
• There are two main types of lung cancer: nonsmall cell and small cell
What is the Function of the
Lungs?
• The lungs consist of five
lobes, three in the right lung
and two in the left lung
• Most cells in the lung are
epithelial cells, which line
the airways and produce
mucus, which lubricates and
protects the lungs
• The main function of the
lungs is to allow oxygen
from the air to enter the
bloodstream for delivery to
the rest of the body
Lung Cancer
Global situation in the world
•
•
•
•
The leading cause of cancer death in both
women and men in USA, Canada and China
997 000 death in men and 333 000 death in
women in the world in 2000
An increase of adenocarcinoma
12,3 % of all malignant tumors , 30% of cancer
related death
Lung Cancer
Global situation in the world
European Union
29% of cancer death in men
9% in women
The highest incidence in the world
New Orleans 105/100 000 in men
New Zeland 73/100 000 in women
Incidence of tumors in the Czech
Republic in the years 2003 and 2005
2003
2005
• Men
32 551
36 823 tumors
1.skin tumors
166/100 000 (8269) 173/100 000 (8676)
2. lung cancer 92,5/100 000 (4 596) 92,8/100 000 (4632)
3. colon-rectum 91,9/100 000 ( 4567) 95,1/100 000 (4746)
4. tu prostatae
68,3/100 000 (3728)
97,1/100 000 (4846)
• Women
1. skin tumors
2. tu breast
3. colon-rectum
4. tu uterus
5. lung cancer
6. tu ovarium
31 974
152/100 000 (7961)
102,7/100 000 ( 5784)
63,3/100 000 (3306)
52,3/100 000 (2698)
26,7/100 000 (1399)
25,3/100 000 ( 1323)
34 626 tumors
153/100 000 (7999)
105,5/100 000 (5533)
61,7/100 000 (3236)
33,2/100 000 (1739)
30,8/100 000 (1617)
22,7/100 000 (1192)
Incidence of lung cancer in the
Czech republic 1970 -2005
(n/100 000)
year
1970 1980
men
89,4
women 7,7
1990
2003
2004
2005
100,2 99,6
92,1
94,3
92,8
11
26,5
29,9
30,8
15,9
Incidence and mortality on LC in
men and women in 1985-2005
Evolution of incidence of tumors
in men
C16-stomach
C19-21 rektosigma
C18- colon
C32laryngx C33-34 lung
C25 pancreas
C61prostata C67 vesica urina
C43 melanom
C91-95 hemoblastosy
C64-68- kidney
Evolution of incidence of tumors
in women :
C16-stomach
C19-21 rektosigma
C18- colon
C33-34 lung
C23-4gall-bladder
C50 breast C53cervix.u.
C43 melanom
C56-7 ovarium C91-95 hemoblastoses
C54 corpus uteri
Incidence of lung cancer according age
groups
2003
• Men till 49 years
191
50-59
1106
60-69
1525
70-79
1382
older
386
• Women till 49 years:
50-59
60-69
70-79
older
%
4,2
24,1
33,2
30,1
8,4
92
6,6
301 21,7
347 25
470 33,9
177 12,8
2005
%
177 3,8
1028 22,2
1610 34,8
1406 30,4
411
8,8
78
358
441
480
256
4,8
22,2
27,3
29,8
15,9 ;;
Incidence of LC in regions in CR to
100 000 inhabitants (2005)
• region
•
•
•
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•
•
•
•
•
•
•
•
•
Praha
Středočeský kraj
Jihočeský kraj
Plzeňský kraj
Karlovarský kraj
Ústecký kraj
Liberec
Hradec Králové
Pardubice
Vysočina
Jihomoravský kraj
Olomoucký kraj
Zlín
Moravskoslezský
men n/100 000
95
100
98
109
105
117
93
85
96
92
77
79
62
92
women n/100 000
49
35
29
34
51
42
40
20
26
17
24
24
13
24
Incidence of lung cancer to 100 000 men ( 2001 - 2005)
and the maps of CR with radioactive risk
Mortality on tumors in the 2005 in
men in the CR – LC 1. place
Mortality on tumors in women in the
year 2005 – LC 4. place
Evolution of mortality on LC in
CR
1940
Men
Women
abs. number abs. number
426
134
Men
n/100000
12,1
Women
n/100000
3,7
1960
3145
386
66,8
7,8
1980
5100
638
101,8
12,0
2000
4480
1246
89,6
23,6
2004
4346
1343
87,4
25,7
2005
4166
1370
83,5
26,1
•
Standardizated mortality to diag. C33,C34 to 100 000 women in CR and abroad
•
•
•
•
•
•
•
•
•
•
•
•
Country
Austria
Czech Republic
Finland
Hungary
Ireland
Lithuania
Norway
Poland
Romania
Russian F.
Ukraine
•
Standardizated mortality to diag. C33,C34 to 100 000 men in CR and abroad
•
•
•
•
•
•
•
•
•
•
•
•
Country
Austria
Czech Republic
Finland
Hungary
Ireland
Lithuania
Norway
Poland
Romania
Russian F.
Ukraine
2000
17
18
12
30
29
8
23
18
11
9
8
2000
54
90
52
115
59
78
45
99
65
87
72
2001
16
19
12
30
25
9
24
19
11
9
8
2001
54
86
51
114
56
81
46
100
65
84
69
2002
18
18
12
32
26
7
23
20
11
9
7
2002
55
84
49
112
54
80
49
101
66
82
67
2003
17
19
13
33
27
9
24
20
12
8
7
2003
53
81
48
115
56
79
47
97
65
80
64
2004
18
19
12
33
28
8
25
19
11
8
7
2004
51
82
46
114
53
76
46
96
65
78
63
2005
17
19
13
31
28
8
26
21
12
8
7
2005
50
77
46
103
50
74
44
95
68
77
61
Standardizated mortality to diag. C33,C34 to 100 000 inhabitants in CR and abroad ( UZIS
2008)
Country
2000
2001
2002
2003
2004
2005
Austria
33
32
33
32
32
31
Czech Republic
49
48
46
45
46
44
Finland
28
28
27
27
26
27
Hungary
65
65
65
66
66
61
Ireland
42
39
38
40
39
38
Lithuania
35
37
35
36
35
34
Norway
33
33
34
34
34
34
Poland
52
52
53
52
51
51
Romania
36
36
36
36
36
37
Russian Federation
39
37
36
35
35
34
Ukraine
33
32
31
30
29
28
Lung Cancer
Situation in the Czech Republic
• 5709 deaths in 2000 (80 deaths of TB),
5536
in 2005
• Incidence in men 93/100 000, in women
31/100 000 in 2005
• Stable figures in men, linear increase
in women
• Leading cause of cancer death in
men,
4. in women (breast, uterus-ovarium, colon)
• Change in the ratio men : women from
17/1 (in 1970) to 3/1 (in 2004)
What are the Risk Factors for Lung
Cancer?
• Tobacco and secondhand smoke
• Asbestos
• Radon
• Most people who develop lung cancer today
have either stopped smoking years earlier or
have never smoked
Lung cancer epidemic = Smoking epidemic
• LC incidence follows the smoking
incidence with the latency of 20-30 years
• USA smokers in 1965 - 42%,
in 1995 - 25%
(men)
• WHO
in 1998 47% men and 12% women
are smokers in the world
•
Smoking related LC - 83-94% in men,
57-80% in women
Kubík A aj., Čas Lek čes.,138, 10,310-315
Smoking and other risk
factors
• Smoking caused lung cancer in 94%
men and 52% women (Kubík et al:
Cancer, 1995, 7, 2452-60)
• CR: 40 % men and 25 % women in th
age 30 - 60 years are smokers (UZIS
ČR 2004)
• 10 – 18 % of smokers will suffer from
lung cancer
• coincidence with chronic lung diseases
• genetic predisposition
• cumulative effect of risks !!
Mortality on LC in Australia
Mortality in Netherlandes to 100 000
inhabitants
Lung cancer is the 3th most frequent TU diagnosed in EU
year 2000: 243,600 newly diagnosed cases of LC
Ratio men to women 4:1.
Highest incidence for men is in Hungary, Poland and Belgium for
women in Denmark, Hungary and UK
Morfo
Epid.
Ca
ČR
FN M
1985
90
97
55 %
52 %
51 %
98-00
02
01-3
51 %
49 %
2005
49%
37 %
I.TRN
Brno
ČB
Aden
ca
ČR
FN M
04-7
29%
50%
59%
13 %
17 %
19 %
20 %
26%
23%
34 %
28%
I.TRN
Brno
ČB
Small
ca
ČR
FN M
19%
14%
23 %
23 %
23 %
23%
22 %
18 %
18 %
.TRN
Brno
ČB
Nedif– ČR
. ca
FN M
I.TRN
Brno
ČB
24%
27%
23%
9%
8%
7%
7%
7%
5%
11 %
19%
4%
4%
Diagnostics and therapy-men
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•
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•
•
•
•
2003
2005
histology verific.
CR
72,6%
76%
higest
Plzeň.k.
90% JHM 89,1%
lowest
HK
53% HK 55,5%
til 3 weeks dgn
62,6%
66,9%
over 6 weeks
10,6%
8,2%
I. TNM
11,6%
12,4%
II. TNM
8,5%
7,4%
III. TNM
32,2%
28,1%
IV. TNM
47,7%
52,1%
Surgical th.
10,8%
11,4%
higest surgery in OlO
16,5%
PHA 15%
RT
22%
23,9%
CHT
32,1%,
35,3%
not treated
44,5%,
41,1%
mostly in Prague
60% KAR.V. 52,2%
Diagnostics and therapy - women
•
•
•
•
•
•
•
•
•
•
•
2003
2005
histology verification ČR
69,0%
73,7%
higest
OLO
86,7% OLO
89,7%
lowest
HK
56%
HK
56,1%
up to 3 weeks dgn
61%
61,7%
dgn over 6 weeks
12,2%
10%
I. TNM
10,3%
13,2%
II. TNM
6,9%
6,1%
III. TNM
27%
26,9%
IV. TNM
55,8%
53,8%
Surgery th.
10,1%
13,2%
mostly in PAR 17,6%
PAR 22,4%
RT
18,5%
21,5%
CHT
31%
32,3%
not treated
47%
44,8%
most in Prague
64%
SČK 56,6%
Patients with LC in TNM stages I a II and
the types of therapy in CR 1980 - 2005
1980
TNM I a II
39 % m, 28 % w
Resection of TU
7,0 %
radioterapy (RT)
chemoterapye (CHT)
26 %
18 %
1996
24 %
2005
19,8% m, 19,3 % w
8,3 % 11,4 % m, 13,2% ž
21 %
22 %
abs. number of pts, = 100 % n = 5606
n= 6346
23 %
34 %
n= 6236
5 year survival of diagnosed in the
1980 - 84 and 1996 - 2000
1980-84
• Men in I. and II. st. TNM
8,5%
in
III. a IV. st.
1,7%
all stages
4,4%
96-2000
22 %
4,1 %
7,1% (8,7%)
• Women all stages
7,9%
9,7% (11,5%)
• EU 5year survival: men 10% women 11%
• USA „ „
: men 12% women 17%
Epidemiological conclusions
• decreasing incidence of LC in men, plateau point of incidence of
women is nearing…hopefully
• problems - high incidence of LC in men
- late diagnostics
- operability only 11,4% in men and 13,2 in women
- in 2003 5995 new cases , died 5568 !!
- number of „ NO therapy“ didnt change in the past 20 years
• pozitive data
- we did not reached the highest EU incidence in women
- increased 5 year survival
- higher level of verification of LC
- lower late diagnosed pts over 6 weeks
•
Patogenezis, pathology
• Ciliated cells fade away – multiplication of bazal cells – hyperplasy
and metaplasy of multilayer epidermoid epithel – loss of polarity –
atypical nuclei - abnormal mitózes – dysplasie mild, moderate,
severe - proliferation of the cells - ca in situ
• field cancerization x progenitor cell
• reverzibility of changes
• histology
– Small cell ca – agresive, frequent metastases
– spindlecells - metastases later, typical cauliflower shape-karfiol
– adenocarcinoma - gland type, cave metastases
and periferal leasions ….bronchioalveolar ca
– nedifferentiated – largecells ca
Pathology- 2
• Development of cancer in the mucosa up to 15 years
• doubling time
• death - 1 kg tumoros mass
doubling timeí
years to diagnozes
• Small cell ca
29 days
2,8
squamous ca
88 days
8,4
adenoca
161 days
15,4
• central, peripheral
Metastases to - liver, suprarenal glands, bone, brain
• Direct invasion
• lymphatica
• hematogenes
to death
3,2
9,6
17,6
Symptoms of lung cancer








cough
weight loss
dyspnoe
haemoptysis
bone pain, clubbing
fever
Vena cava syndrome
recurrent laryngeal palsy
75%
68%
60%
20-35%
25%
15-20%
4%
5%
What are the Symptoms of Lung
Cancer?
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•
•
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•
•
•
•
Fatigue (tiredness)
Cough
Shortness of breath
Chest pain
Loss of appetite
Coughing up phlegm
Hemoptysis (coughing up blood)
If cancer has spread, symptoms include bone pain,
difficulty breathing, abdominal or back pain, headache,
weakness, and speech difficulties
Paraneoplastic syndrome
Endocrine syndromes
• Cushing´s sy (ACTH) 2-7%, SCLC 30-50%,
• Nonmetastatic hypercalcemia - squamous
ca 15%
• Inappropriate antidiuretic hormone in
SCLC , hyponatremia, urine osmolarity
over 500 mOsm.kg-1
• Gynecomastia (HCG)
Paraneoplastic syndrome
Neurological syndrome
• Symptoms peripheral neuropathy,
encephalomyelitis
• Lambert Eaton myasthenic syndrome
Cutaneous
• Erythema gyratum repens, acanthosis nigrans
Haematological
• microcytic anemia in 20%, haemostatic
disturbance
Clubbing
Anorexia, nausea, vomiting
How is Lung Cancer Diagnosed?
• Because almost all patients will have a tumor in the lung, a chest
x-ray or CT scan of the chest is performed
• The diagnosis must be confirmed with a biopsy or cytology
• The location(s) of all sites of cancer is determined by additional
CT scans, PET (positron emission tomography) scans, and MRI
(magnetic resonance imaging)
• It is important to find out if cancer started in the lung or
somewhere else in the body. Cancer arising in other parts of the
body can spread to the lung as well- metastases
Diagnosis of lung cancer
•
•
•
•
•
•
•
•
•
•
•
screening method does not exists
passive approach – waiting for symptoms
personal history and physical examination,
performance status
pulmonary function tests- air flow limitation
sputum cytology, chest X ray, chest CT scan
bronchoscopy (TBNA, brush, forceps biopsy....),
cytology, histology
autofluorescence, EBUS
transparietal fine needle lung biopsy
PET, bone scan, mediastinoscopy (?)
thoracoscopy
operability ???
Staging of lung cancer
prognosis
therapy
NSCLC – SCLC
The rules for TNM staging
•
•
•
•
T- tumor T0,T1-4,
N - lymphonodes N0, N1-3
M – metastases M0, M1
clinical cTNM vs pathological pTNM ( based on
surgical and pathological examination)
• cTNM – therapeutical options, pTNM - prognosis
• According established T-, N-, M- are tumors
divided to the stages. The stage should be fixed in
the documentation and should not to be changed
Bronchogenic carcinoma-TNM
• TX- malignant cells in sputum but no X-ray and
bronchoscopical findings
• T0- no evidence of lung cancer
• Tis - ca in situ
• T1< 3 cm, not in the main bronchus
• T2> 3 cm, involving main bronchus, > 2 cm distal
to the carina, visceral pleura, atelectasis or
pneumonia in part of the lung (T2 also if the size is
≤ 3 cm if any non-size-based descriptor were
present)
Bronchogenic carcinoma-TNM
• T3 - chest wall, diaphragm, main bronchus
< 2 cm from carina but without involvement
of it, mediastinal pleura, atelectasis,
pneumonia in the entire lung
• T4 – any size with invading to the
mediastinum, heart, great vessels, trachea or
satelite tumor/s in the same lobe, malignant
pleural or pericardial effusion
Bronchogenic carcinoma-TNM
• NX – N cannot be assessed
• N0 – No regional lymph node metastasis
• N1 – ipsilateral peribronchial,
intrapulmonary, hilar (code
10-14) also infiltrated directly
by tumor
• N2 – ipsilateral mediastinal
and/or subcarinal (code 1-9)
• N3 – contralateral mediastinal,
hilar, ipsi/ contralateral scalene
or supraclavicular (contralateral
1-10)
Bronchogenic carcinoma-TNM
• MX - M cannot be assesed
• M0 – no distant metastasis
• M1 – distant metastasis or other tumor nodule
in other ipsi/contralateral lobes
Stage I Non-Small Cell Lung
Cancer
• Cancer is found only
in the lung
• Surgical removal
recommended
• Radiation therapy
and/or chemotherapy
may also be used
Stage II Non-Small Cell Lung
Cancer
• The cancer has spread to
lymph nodes in the lung
• Treatment is surgery to
remove the tumor and
nearby lymph nodes
• Chemotherapy
recommended; radiation
therapy sometimes given
after chemotherapy
Stage III Non-Small Cell Lung
Cancer
• The cancer has spread to the
lymph nodes located in the center
of the chest, outside the lung
• Stage IIIA cancer has spread to
lymph nodes in the chest, on the
same side where the cancer
originated
• Stage IIIB cancer has spread to
lymph nodes on the opposite side
of the chest, under the collarbone,
or the pleura (lining of the chest
cavity)
• Surgery or radiation therapy with
chemotherapy recommended for
stage IIIA
• Chemotherapy and sometimes
radiation therapy recommended
for stage IIIB
Stage IV Non-Small Cell Lung
Cancer
• The cancer has spread to
different lobes of the lung or
to other organs, such as the
brain, bones, and liver
• Stage IV non-small cell lung
cancer is treated with
chemotherapy
• More information can be
found in the What to Know:
ASCO’s Guideline on
Advanced Lung Cancer
Other characteristic of tumors
•
•
G- histopathological grading
GX not assesed
G1 well differentiated
G2 middle grade of differentiation
G3 poorly differentiated
G4 non differentiated
Resection of tumor under 2 cm in 160 pts with stage I TNM. In every pts were
checked clinicopathological features : sex, age, smoking habits, CEA, and
histopathological grade.
• Results: pts with poorly differentiated carcinomas showed significantly unfavorable
survival p< 0,001 compared with pts with well-moderately differentiated
carcinomas. Kobayashi N et al: J Thorac Oncol 2007, September,2(9):808-12
• R- residual tumor after treatment
RX residual tumor not evaluated
R0 without residual tumor
R1 microscopic residue of tumor
R2 macroscopic residue of tumor
The stages of BCA
•
•
•
•
•
•
Occult BCA
Stage 0
Stage IA
Stage IB
Stage IIA
Stage IIB
TX
N0
Tis
N0
T1
N0
T2
N0
T1
N1
T2 N1
T3
N0
• Stage IIIA
T1,2 N2
T3
N1,2
• Stage IIIB
any T N3
T4 any N
• Stage IV
any T any N
( 6th version of TNM staging )
M0
M0
M0
M0
M0
M0
MO
M0
M0
M0
M0
M1
IA
I
1
IIA
2
IIIA
3
Lung Cancer Staging
• Staging is a way of describing a cancer, such as
the size of a tumor and if or where it has spread
• Staging is the most important tool doctors have to
determine a patient’s prognosis
• The type of treatment a person receives depends
on the stage of the cancer
• Staging is different for non-small cell lung cancer
and small cell lung cancer
• Recurrent cancer is cancer that comes back after
treatment
Small Cell Lung Cancer: All Stages
• Classified as limited stage (confined to one area of
the chest) or extensive stage (not confined to one
area of the chest)
• Patients with limited stage small cell lung cancer
are best treated with simultaneous radiation
therapy and chemotherapy
• Patients with extensive stage small cell lung
cancer are treated with chemotherapy
• In patients whose tumors have shrunk after
chemotherapy, preventive radiation therapy to the
head cuts the risk that the cancer will spread to the
brain and extends patients’ the lives
Small cell lung cancer
• TNM classification may be useful for SCLC too ! Shepherd FA et al,
J Thorac Oncol, 2007,1067-77
• Veterans Administration Lung Cancer Group (VALG)+
IASLC:
• Limited disease – one hemithorax:
- with/without ipsi- and/or contralateral N
or supraclavicular lymphonodes
- with/without ipsilateral pleural effusion
regardless malignant or paramalignant (TNM IA-IIIB)
• Extensive disease - more extensive than described above (
TNM IV )
Survival according TNM stages
Mountain, 1997, Naruke 1988
cTNM
n
n
687
5 year pTNM
surv. %
61 65 pIA
511
5 year
surv. %
67 76
cIA
cIB
1189
38 42
pIB
549
57 57
cIIA
29
34
pIIA
76
55
cIIB
357
24
pIIB
375
39
cIIIA
511
13
pIIIA
399
23
cIIIB
1030
5
cIV
1427
1
The changes of the TNM stage frequency in the
sets of pts in the last 40 years
n
TNM I% TNM II%
• Czech republic:
1983
1985
1995
1998
2005
5784
5718
6658
6083
6249
• Study population
1961- 1972 I.TRN Prague
1980-1985 Beroun
1984-87 SRN-Rohrbach
1997- 1999 Sweden
1998-2003- TRN Motol
2000-2003 Brno
2004-2007 I.TRN
465
30
157
16
1758 15
364
18
1024 237/16
373
115/6
353
187/11
20
20
16
11
12
19
18
14
8
8
33
20
10
1,5
5
71/6
41/3
TNM III%
TNM IV%
30
29
33
31
28
31
33
37
50
52
18
26
4118/23
3810/28
4015/25
4618/28
3813/25
19
38
34
42,5
32
36
40
Therapy in Nonsmall cell LC
• I st TNM – surgery (or RT in inoperability)
• II st. TNM – surgery (or CHT/RT in inoperability)
• III A TNM – surgery, or neoadjuvant CHT 2-3 cycles
gemcitabin-cis platina followed by surgery or RT/CHT
• Adjuvant CHT in resected IB-IIIA
• N2 found at surgery – adjuvant RT
• III B TNM – concomitant CHT( navelbin - platina)/RT , or
only paliative RT
• IV st TNM wrong status – symptomatic therapy, good status
CHT ( gemcitabin a carboplat.) or paliative RT
Therapy in Small Cell Lung
Cancer
• Limited disease: good general condition - CHT ( cis platin
+ etoposide) and concomitant normo/ hyperfractionated
radiotherapy (RT) from 1.cycle 45-55Gy
• I stage surgery and adj CHT,
• LD SCLC wrong general status, polymorbidity, sequence
CHT-5 cycles/RT up to 60 Gy
• Extensive diseases – 6x CHT ( etoposid-carboplatin)
• Relaps till 3 months - other CHT ( gemcitabin, taxany,
ifosf. , topotecan aj.)
• Relaps over 3 months the same CHT as in 1.line
How is Lung Cancer Treated?
• Treatment depends on the stage and type of lung cancer
• Surgery
• Radiation therapy
• Chemotherapy (options include a combination of drugs)
• Targeted therapy
• Lung cancer is usually treated with a combination of therapies
Cancer Treatment: Surgery
• The tumor and the nearby lymph nodes in
the chest are typically removed to offer the
best chance for cure
• For non-small cell lung cancer, a lobectomy
(removal of the entire lobe where the tumor
is located), has shown to be most effective
• Surgery may not be possible in some
patients
Cancer Treatment: Adjuvant Therapy
• Treatment given after surgery to lower the
risk of the cancer returning
• May include chemotherapy, radiation
therapy, and targeted therapy
• More information may be found in the
What to Know: ASCO’s Guideline on
Adjuvant Treatment for Lung Cancer
Cancer Treatment: Radiation Therapy
• The use of high-energy x-rays to destroy cancer cells
• Side effects include fatigue, malaise (feeling unwell), loss
of appetite, and skin irritation at the treatment site
• Radiation pneumonitis is the irritation and inflammation of
the lung; occurs in 15% of patients
• It is important that the radiation treatments avoid the
healthy parts of the lung
Cancer Treatment: Chemotherapy
• Use of drugs to kill cancer cells
• A combination of medications is often used
• May be prescribed before or after surgery, or
before, during, or after radiation therapy
• Can improve survival and lessen lung cancer
symptoms in all patients, even those with
widespread lung cancer
Cancer Treatment: Targeted Therapy
• Treats lung cancer by stopping the action of abnormal proteins that cause cells
to grow and divide out of control
• Bevacizumab (Avastin) prevents the formation of new blood vessels, which help
feed the growth and spread of a tumor; given with chemotherapy
• Erlotinib (Tarceva) approved for locally advanced and metastatic non-small cell
lung cancer
• Cetuximab (Erbitux) (monocklonal AB IgG1, which bind to receptor of
epidermal growth factor (EGFR). Cetuximab is highly specific with higher
afinity to this receptor than - epidermal growth factor (EGF) and transforming
growth factor alfa (TGF-alfa)) may be given with chemotherapy in situations
where bevacizumab may be unsafe
The Role of Clinical Trials for the
Treatment of Lung Cancer
• Clinical trials are research studies involving people
• They test new treatment and prevention methods to determine whether they
are safe, effective, and better than the standard treatment
• The purpose of a clinical trial is to answer a specific medical question in a
highly structured, controlled process
• Clinical trials can evaluate methods of cancer prevention, screening,
diagnosis, treatment, and/or quality of life
Clinical Trials: Patient Safety
• Informed consent: participants should understand
why they are being offered entry into a clinical
trial and the potential benefits and risks; informed
consent is an ongoing process
• Participation is always voluntary, and patients can
leave the trial at any time
• Other safeguards exist to ensure ongoing patient
safety
Clinical Trials: Phases
• Phase I trials determine the safety and dose of a new treatment in a
small group of people
• Phase II trials provide more detail about the safety of the new
treatment and determine how well it works for treating a specific
type of cancer
• Phase III trials take a new treatment that has shown promising
results when used to treat a small number of patients with cancer
and compare it with the standard treatment for that disease; phase
III trials involve a large number of patients
Clinical Trials Resources
• Coalition of Cancer Cooperative Groups
(www.CancerTrialsHelp.org)
• CenterWatch (www.centerwatch.com)
• National Cancer Institute
(www.cancer.gov/clinical_trials)
• EmergingMed (www.emergingmed.com)
Living With Lung Cancer
• Many people with lung cancer feel that they will
not receive as much support or help from people
around them because they believe others will think
that their behavior caused the disease
• Doctors and other members of the health care
team can help patients and families cope with a
diagnosis of lung cancer
• Patients can take comfort knowing that the
advances being made in the diagnosis and
treatment of lung cancer will provide more and
more patients with a chance for cure
Coping with Side Effects
• Side effects are treatable; talk with the doctor or nurse
• Fatigue is a common, treatable side effect
• Pain is treatable; non-narcotic pain-relievers are
available
• Antiemetic drugs can reduce or prevent nausea and
vomiting
• Medications and extra oxygen can improve breathing
• Radiation therapy or surgery can be used to treat
metastases that are causing pain or other symptoms
• For more information, visit www.cancer.net/sideeffects
After Treatment
• Patients with lung cancer face the risk of cancer growing back or the
development of a new lung cancer. All patients must follow up with
their doctors for regular x-rays, scans, and check-ups
• Quitting smoking helps recovery and health. Patients who have
developed lung cancer who then stop live longer. It is never too late to
stop smoking
• Many survivors are at high risk for heart disease, stroke, emphysema,
and chronic bronchitis; some cancer treatments increase this risk
• Walking for 15 to 30 minutes each day can improve lung and heart
functioning
Where to Find More Information
Cancer.Net Guide to Lung Cancer
(www.cancer.net/lung)
•
•
•
•
•
•
Overview
Medical Illustrations
Risk Factors
Symptoms
Diagnosis
Staging With
Illustrations
• Treatment
• Clinical Trials
• Living With Lung
Cancer
• Side Effects
• After Treatment
• Current Research
• Questions to Ask the
Doctor
• Patient Information
Resources
Cancer.Net (www.cancer.net)
• Comprehensive, oncologist-approved cancer
information
• Guides to more than 120 types of cancer and
cancer-related syndromes
• Coping resources
• Survivorship information
• Cancer information in Spanish
• Weekly feature articles
• The latest cancer news
• For patient information resources, please call 888651-3038
Adjuvant Chemotherapy and
Adjuvant Radiation Therapy for
Stages I-IIIA Resectable Non-Small
Cell Lung Cancer Guideline
Cancer Care Ontario and American
Society of Clinical Oncology
Introduction
• The Cancer Care Ontario (CCO) Program in Evidencebased Care (PEBC) and the American Society of Clinical
Oncology (ASCO) convened an expert panel in August
2006 to review the evidence and draft recommendations
on the role of adjuvant chemotherapy and adjuvant
radiation therapy for completely resected stages I-IIIA
non-small cell lung cancer (NSCLC).
• CCO originally published guidelines in 1997 and
updated them in 2004-2006.
• Both CCO-PEBC and ASCO conducted external reviews
of the current guidelines.
2007 Recommendations for Adjuvant
Treatment of Stages I-IIIA NSCLC
Clinical Questions
1. What is the benefit in terms of overall survival of
adjuvant chemotherapy in patients with
completely resected stages I – IIIA non-small cell
lung cancer?
2. What is the benefit in terms of overall survival of
adjuvant radiation therapy in patients with
completely resected stages I – IIIA non-small cell
lung cancer?
3. What roles should adjuvant chemotherapy and
adjuvant radiation therapy play in completely
resected stages I – IIIA non-small cell lung
cancer?
2007 Recommendations for Adjuvant Treatment of
Stages I-IIIA NSCLC
Adjuvant Cisplatin-Based Chemotherapy
• Stage IA: Adjuvant chemotherapy is not recommended
• Stage IB: Adjuvant cisplatin-based chemotherapy is not
recommended for routine use.
• Stage IIA: Adjuvant cisplatin-based chemotherapy is
recommended.
• Stage IIB: Adjuvant cisplatin-based chemotherapy is
recommended.
• Stage IIIA: Adjuvant cisplatin-based chemotherapy is
recommended.
• The use of adjuvant chemotherapy regimens that include alkylating
agents is not recommended as these agents have been found to be
detrimental to survival.
 Recommendations apply only to completely
resected tumors.
Recommended Dose:
Adjuvant Chemotherapy for Stages IIA-IIIA
NSCLC
Cisplatin-Vinorelbine
• Cisplatin: 50 mg/m2 on days 1 and 8 every four weeks
for four cycles, and
• Vinorelbine: 25 mg/m2 weekly for 16 weeks for four
cycles
• Considerations:
– Convenience for patients
– Patients’ resource constraints
– The use of one cisplatin-based chemotherapy
regimen consistently in order to ensure familiarity
and optimize patient safety
2007 Recommendations for Adjuvant Treatment of
Stages I-IIIA NSCLC:
Adjuvant Radiotherapy
• Stages IA/B and IIA/B: Adjuvant radiation is not
recommended.
• Stage IIIA: Adjuvant radiation therapy is not
recommended for routine use because of the lack
of prospective, randomized clinical trial data
evaluating its efficacy. A clinical trial is underway
to determine the advisability of its routine use.
Recommendations apply only to completely
resected tumors.
2007 Recommendations for Adjuvant Treatment of
Stages I-IIIA NSCLC
Special Considerations
• Patients with poor performance status
• Patients with advanced age
Strategies to Improve Doctor-Patient
Communication
• Therapeutic nihilism towards adjuvant chemotherapy
for stages II-III NSCLC should now be abandoned
• Recognize that unique issues face people with lung
cancer
• Offer a session devoted solely to discussing patient’s
prognosis and the risks and benefits of adjuvant
chemotherapy
**This section is consensus-based, rather than evidence-based
Strategies to Improve Doctor-Patient
Communication
• Patients with cancer generally prefer shareddecision making
• Present patients with individualized descriptions
of their risks and benefits
• Graphs included in guideline to help physicians
communicate the absolute risk and benefit of
adjuvant chemotherapy for the various stages of
NSCLC
**This section is consensus-based, rather than evidencebased
Strategies to Improve Doctor-Patient
Communication, cont’d
• With the physician providing immediate guidance
and interpretation, a graph may help patients achieve
a better understanding of absolute risk and benefit.
• Graphical Representations*
• Source: LACE meta-analysis
• Using LACE data to estimate absolute benefit,
adjuvant chemotherapy raises 5-year survival from
64% to 67% for stage IB NSCLC, from 39% to 49%
for stage II NSCLC, and from 26% to 39% for stage
Strategies to Improve Doctor-Patient
Communication, cont’d
•Graphs separate patient sample into groups:
–Those who die within 5 years whether they receive
chemotherapy or not (white)
–Those who live without receiving chemotherapy (yellow)
–Those who live because of chemotherapy (green)
Stage I
Stage II
Stage III
*
Notes: The figures are a graphical representation of patient survival probabilities at 5 years: the
combined yellow and green areas represents the survival probability for the treatment group (S a) (the
yellow represents the survival probability for untreated patients (S c), green represents the absolute risk
reduction (Sa-Sc), i.e., the “extra” survival achieved by therapy), the white area represent the mortality
probability in patients (1-Sa). The statistical uncertainty in these probabilities is not depicted in the
figures. Calculations for these figures included data on untreated patients from the ANITA trial
because these data were not available in the LACE abstract. *Includes the three trials that included
only stage IB, does not include two trials open for stages IA and IB.
Selective Review of Molecular
Markers in NSCLC
• Panel undertook selective review of the literature
pertaining to seven molecular markers
• The majority were investigated for their possible
ability to predict cisplatin resistance
• Currently there is a lack of conclusive evidence
showing that any marker is significantly related to
clinical outcome
Summary
Not Recommended
Recommended
Stage IA
•Adjuvant chemotherapy
•Adjuvant radiation therapy
•Alkylating agents
Stage IB
•Adjuvant cisplatin-based chemotherapy on a
routine basis
•Adjuvant carboplatin-based chemotherapy
•Adjuvant radiation therapy
•Alkylating agents
Stage IIA
•Adjuvant carboplatin-based chemotherapy
•Adjuvant radiation therapy
•Alkylating agents
•Adjuvant cisplatin-based chemotherapy
Stage IIB
•Adjuvant carboplatin-based chemotherapy
•Adjuvant radiation therapy
•Alkylating agents
•Adjuvant cisplatin-based chemotherapy
Stage IIIA
•Adjuvant carboplatin-based chemotherapy
•Adjuvant radiation therapy for routine use
•Alkylating agents
•Adjuvant cisplatin-based chemotherapy
Additional ASCO Resources
• The full text of the guideline, this slide set, a Decision Aid
Tool*, and additional resources are available at:
http://www.asco.org/guidelines/adjuvantnsclc
• A Patient Guide on Adjuvant Treatment for Lung Cancer can
be found at http://www.cancer.net
• *A version of Adjuvant! has been produced to make estimates of NSCLC
patient outcomes with and without adjuvant therapy (1,2,3). We have for the
publication of these guidelines produced our own version of such a tool.
1) Ravdin PM, Davis GJ. Prognosis of patients with resected non-small cell
lung cancer: Impact of clinical and pathologic variables. Lung Cancer. 2006
May;52(2):207-12.
2) A computer program designed to assist in NSCLC adjuvant therapy
decision making. P. M. Ravdin Abstract - No. 7230. 2006 ASCO Annual
Meeting
3) www.adjuvantonline.com
ASCO Guidelines
It is important to realize that many management questions have not been
comprehensively addressed in randomized trials and guidelines cannot always
account for individual variation among patients. A guideline is not intended to
supplant physician judgment with respect to particular patients or special clinical
situations and cannot be considered inclusive of all proper methods of care or
exclusive of other treatments reasonably directed at obtaining the same results.
Accordingly, ASCO considers adherence to this guideline to be voluntary, with
the ultimate determination regarding its application to be made by the physician
in light of each patient’s individual circumstances. In addition, the guideline
describes administration of therapies in clinical practice; it cannot be assumed to
apply to interventions performed in the context of clinical trials, given that clinical
studies are designed to test innovative and novel therapies in a disease and
setting for which better therapy is needed. Because guideline development
involves a review and synthesis of the latest literature, a practice guideline also
serves to identify important questions for further research and those settings in
which investigational therapy should be considered.
• Stage IV NSCLC
• Therapy
• ASCO recommendation
2009 Recommendations
First-Line Chemotherapy
• Recommendation A1. Evidence
supports the use of chemotherapy in
patients with stage IV* non-small cell
lung cancer with ECOG/Zubrod
performance status 0, 1, and possibly 2.
*Stage IV as defined by the International Association for the
Study of Lung Cancer (IASLC) Lung Cancer Staging Project, for
the 7th Edition of the TNM Classification of Malignant Tumors
{Goldstraw P, J Thorac Onc , 2007}
2009 Recommendations
First-Line Chemotherapy
• Recommendation A2. In patients with performance
status 0 or 1, evidence supports using a combination
of two cytotoxic drugs for first-line therapy. Platinum
combinations are preferred over nonplatinum
combinations because they are superior in response
rate, and marginally superior in overall survival.
Nonplatinum therapy combinations are reasonable in
patients who have contraindications to platinum
therapy. Recommendations A8 and A9 address
whether to add bevacizumab or cetuximab to first-line
cytotoxic therapy.
2009 Recommendations
First-Line Chemotherapy
• Recommendation A3. Available data support the use of
single-agent chemotherapy in patients with a
performance status of 2. Data are insufficient to make a
recommendation for or against using a combination of
two cytotoxic drugs in patients with performance status
2.
• Recommendation A4. The evidence does not support the
selection of a specific first-line chemotherapy drug or
combination based on age alone.
2009 Recommendations
First-Line Chemotherapy
• Recommendation A5. The choice of either cisplatin
or carboplatin is acceptable. Drugs that may be
combined with platinum include the third-generation
cytotoxic drugs docetaxel, gemcitabine, irinotecan,
paclitaxel, pemetrexed, and vinorelbine. The
evidence suggests that cisplatin combinations have a
higher response rate than carboplatin and may
improve survival when combined with thirdgeneration agents. Carboplatin is less likely to cause
nausea, nephrotoxicity, and neurotoxicity than
cisplatin, but more likely to cause thrombocytopenia.
2009 Recommendations
First-Line Chemotherapy
• Recommendation A6. In patients with stage IV
NSCLC, first-line cytotoxic chemotherapy should be
stopped at disease progression or after four cycles in
patients whose disease is not responding to treatment.
Two-drug cytotoxic combinations should be
administered for no more than six cycles. For
patients who have stable disease or who respond to
first-line therapy, evidence does not support the
continuation of cytotoxic chemotherapy until disease
progression, or the initiation of a different
chemotherapy prior to disease progression.
2009 Recommendations
First-Line Chemotherapy
• Recommendation A7. In unselected patients,
erlotinib or gefitinib should not be used in
combination with cytotoxic chemotherapy as first-line
therapy. In unselected patients, evidence is
insufficient to recommend single-agent erlotinib or
gefitinib as first-line therapy. The first-line use of
gefitinib may be recommended for patients with
activating EGFR mutations. If EGFR mutation status
is negative, or unknown, then cytotoxic chemotherapy
is preferred (see Recommendation A2).
2009 Recommendations
First-Line Chemotherapy
• Recommendation A8. Based on the results of one large phase
III randomized controlled trial, the Update Committee
recommends the addition of bevacizumab, 15 mg/kg every
three weeks, to carboplatin-paclitaxel, except for those
patients with squamous cell carcinoma histologic type, brain
metastases, clinically significant hemoptysis, inadequate organ
function, ECOG performance status >1, therapeutic
anticoagulation, clinically significant cardiovascular disease,
or medically uncontrolled hypertension. (Based on exclusion
criteria for Sandler et al. registration trial) Bevacizumab may
be continued, as tolerated, until disease progression.
2009 Recommendations
First-Line Chemotherapy
• Recommendation A9. Based on the results of one large
phase III randomized controlled trial, clinicians may
consider the addition of cetuximab to cisplatin-vinorelbine
in first-line therapy in patients with an EGFR positive
tumor as measured by immunohistochemistry. Cetuximab
may be continued, as tolerated, until disease progression.
2009 Recommendations
Second-Line Chemotherapy
• Recommendation B1. Docetaxel, erlotinib,
gefitinib, or pemetrexed is acceptable as secondline therapy for patients with advanced non-small
cell lung cancer with adequate performance
status when the disease has progressed during or
after first-line, platinum-based therapy.
• Recommendation B2. The evidence does not
support the selection of a specific second-line
chemotherapy drug or combination based on age
alone.
2009 Recommendations
Third-Line Chemotherapy
• Recommendation C1. When disease progresses on or
after second-line chemotherapy, treatment with
erlotinib may be recommended as third-line therapy
for patients with performance status 0 to 3 who have
not received prior erlotinib or gefitinib.
• Recommendation C2. The data are not sufficient to
make a recommendation for or against using a
cytotoxic drug as third-line therapy. These patients
should consider clinical trials, experimental
treatment, and best supportive care.
2009 Recommendations
Molecular Analysis
• Recommendation D1. Evidence is insufficient to
recommend the routine use of molecular markers to select
systemic treatment in patients with metastatic NSCLC.
• Recommendation D2. In order to obtain tissue for more
accurate histologic classification or for investigational
purposes, the Update Committee supports reasonable efforts
to obtain more tissue than what is contained in a routine
cytology specimen.
• Guideline reviews evidence on the following molecular markers:
–
EGFR, KRAS, ERCC1, RRM1, VEGF
2009 Recommendations
Future Directions of Research
• Research needed with participants who:
–
–
are elderly (≥65 or ≥70)
have ECOG Performance Status ≥2 (distinguish those with PS ≥2
from NSCLC from those impaired by co-morbidities)
• Enrich trial population with participants with tumors with
recently discovered prognostic markers and clinical
characteristics e.g.:
–
–
–
–
Histology
Molecular characteristics
Number and time receiving prior therapies
With known smoking status
2009 Recommendations
Future Directions of Research
(cont’d)
• Stratify trials by the prognostic factors listed above
• Treatments which improve only PFS require greater
scrutiny for toxicity, side effects, quality of life, and cost
effectiveness
• Establish more data on biologic factors of NSCLC in
parallel with drug discovery
• Research on strategies to improve patient-clinician
communication
Encourage patients to participate in clinical research
trials at any time during the course of their disease.
Patient-Physician Communication in
NSCLC Treatment
• Research specific to NSCLC has found:
– Missed opportunities for expressing empathy
– Observantions of blaming words ( obviňování)
– Lack of discussion on prognosis (n.b. approximately 20%
of patients may not want discussion of prognostic
information)
– Lack of information-exchange and trust between patients
and clinicians of different racial/ethnic backgrounds
– Intensive training for clinicians can help, as can presence
of a caregiver at appointment(s)
Patient-Physician Communication in
NSCLC Treatment (cont’d)
• Patients with lung cancer may overestimate the
survival benefits of potentially toxic treatment
• Suggested language:
–
–
–
–
“Tell me what you know about your lung cancer?”
“How much do you want to know?”
“Sounds like what you are telling me is”
“It sounds like you were really frightened when you got
that news about the cancer.”
Patient-Physician Communication in
NSCLC Treatment (cont’d)
• Qualitative statements, e.g. “chances are you will live longer if
you take this chemotherapy versus another, or no chemotherapy.”
• Quantitative statements, e.g. “Chemotherapy will improve your
chance of being alive in one year from 10-20% up to 30-50%.”
• “Without any chemotherapy, the average person will live about 4
and a half months. With chemotherapy most will live longer and
some will live a shorter time. More recent chemotherapy trials
have shown that people live about 3 months longer than if they did
not get chemotherapy…” (Continued on next slide)
Patient-Physician Communication in
NSCLC Treatment (cont’d)
• (Continued from previous slide) “…Even with chemotherapy
,the chance of being alive at one year is about 30-50%; the
chance of dying within this year is 50-70%.”
• State at least one pessimistic aspect, e.g. “…the chance of
dying is….;”
• If asked “can you cure me?” a suggested answer is “No, I can’t,
but we have good chances of prolonging your life and keeping
you comfortable and we will always be here to help you and
your family.”
Guideline Methodology: Update
Committee Members
Christopher G. Azzoli, MD, Co-Chair
Memorial-Sloan Kettering Cancer Center
Giuseppe Giaccone, MD, Co-Chair
National Cancer Institute
Reily Smith, Patient Representative
Bakersfield, CA
John R. Strawn, MD, Patient
Representative
Timothy Aliff, MD
Houston, TX
Sherman Baker, Jr., MD
Virginia Commonwealth University - Massey
Cancer Center
Julie Brahmer, MD
Sidney Kimmel Comprehensive Cancer Center,
Johns Hopkins University
Northwest Oncology & Hematology Associates
David H. Johnson, MD, Co-Chair 2003 Vanderbilt-Ingram Cancer Center
Update and current panelist
Janessa L. Laskin, MD
British Columbia Cancer Agency
Guideline Methodology: Update
Committee Members (cont’d)
Gregory Masters, MD
Helen F. Graham Cancer Center
Daniel Milton, MD
Hematology/Oncology of Indiana, PC
Luke Nordquist, MD
William Pao, MD, PhD
David G. Pfister, MD, Co-Chair 2003
Update and current panelist
Nebraska Cancer Specialists, PC
Vanderbilt-Ingram Cancer Center
Memorial-Sloan Kettering Cancer Center
Steven Piantadosi, MD, PhD
Samuel Oschin Comprehensive Cancer
Center Institute
Joan H. Schiller, MD
University of Texas, Southwestern medical
Center
Virginia Commonwealth University Massey Cancer Center
Thomas J. Smith, MD
David Trent, MD, PhD
Virginia Cancer Center
Additional ASCO Resources
• The full text and an abridged version of the
guideline, this slide set, and a set of ClinicianPatient Decision Aids can be found at:
http://www.asco.org/guidelines/nsclc
• A patient guide, “What to Know” about this
guideline, is available at http://www.cancer.net
ASCO Guidelines
It is important to realize that many management questions have not been
comprehensively addressed in randomized trials and guidelines cannot always
account for individual variation among patients. A guideline is not intended to
supplant physician judgment with respect to particular patients or special clinical
situations and cannot be considered inclusive of all proper methods of care or
exclusive of other treatments reasonably directed at obtaining the same results.
Accordingly, ASCO considers adherence to this guideline to be voluntary, with
the ultimate determination regarding its application to be made by the physician
in light of each patient’s individual circumstances. In addition, the guideline
describes administration of therapies in clinical practice; it cannot be assumed to
apply to interventions performed in the context of clinical trials, given that clinical
studies are designed to test innovative and novel therapies in a disease and
setting for which better therapy is needed. Because guideline development
involves a review and synthesis of the latest literature, a practice guideline also
serves to identify important questions for further research and those settings in
which investigational therapy should be considered.
The problems connected with TNM
staging of BCA
• TNM IA- T ≤ 3 cm. But the survival differentiation was
found also within stage IA:
• N= 244 NSCLC, 1991-2001,
161 T1≤ 2 cm 5 y. survival 77,2%,
83 T1 ≥ 2cm, 5 y. survival 60,3%, p = 0,03.
Should be considered further substaging??
Port JP et al.,CHEST 2003, 124, 1828-33
• The current ( sixth) TNM classification from 2002 made
no changes to the previous fifth edition from 1997. This
was based only on 5319 cases from one institution
accumulated since 1975 treated predominantly surgically
Th 7th edition of TNM staging
• Is due to be published in 2009
• Based on the results of IASLC staging project started
in 1998
• Data from 46 sources, in 19 countries from 1990-2000
• N= 100 869 submitted, 81 015 were analysed,
67 725 NSCLC, 13 290 SCLC
• Recommendation:T1 will be subclassified to
T1a ≤ 2 cm and T1b ≥ 2 cm,T2 to T2a 3-5 cm,
T2b≥ 5 and ≤ 7 cm, T2 ≥ 7cm becomes a T3 descriptor
Th 7th edition of TNM staging
• Additional tumor in the same lobe will be T3(was
T4), in other ipsilateral lobe T4(was M1), in
contralateral lung M1a( This classification was
applied to 657 pts with BAC – accurately reflect
survival) Zell JA et al, J Thorac Oncol, 2007, 1078-85)
• Pleural nodule(was T4), malignant pleural and
pericardial eff..(was T4), contralateral tumor –will
be M1a, distant metastases -M1b
• Existing N descriptors were validated and no
changes are proposed
Proposed stage grouping
6.edition
New T/M
N0
N1
N2
N3
T1≤2cm
T1a
IA
IIA
IIIA
IIIB
T1 2-3 cm
T1b
IA
IIA
IIIA
IIIB
T2≤ 5cm
T2a
IB
IIA( was II B) IIIA
IIIB
T2 ≥5-7 cm
T2b
IIA (was IB)
IIB
IIIA
IIIB
T2≥7 cm
T3
IIB ( IB)
IIIA ( IIB)
IIIA
IIIB
T3 invasion
T3
IIB
IIIA
IIIA
IIIB
T4 same lobe
T3
IIB ( IIIB)
IIIA ( IIIB)
IIIA (was IIIB) IIIB
T4 extension
T4
IIIA( IIIB)
IIIA( IIIB)
IIIB
IIIB
M1 ipsil.lung
T4
IIIA ( IV)
IIIA ( IV)
IIIB ( IV)
IIIB (was IV)
T4 PE malig
M1a
IV ( IIIB)
IV ( IIIB)
IV ( IIIB)
IV ( IIIB)
M1 contral.l.
M1a
IV
IV
IV
IV
M1 distant
M1b
IV
IV
IV
IV
FIGURE 2. Overall survival, expressed as median survival time (MST) and 5-year
survival, by clinical stage using the sixth edition of TNM (A) and proposed International
Association of the Study of Lung Cancer recommendations (B).
Advantage of the new proposed
TNM staging
• Better delineates the early stages ( overlap between IB
and IIA)
• Provide with better distinction between IIA and IIB
• New system may better identify pts with tumor of
different size with differing prognoses
• Reflect different prognosis between those with spread
within the thorax and those with metastases to distant
sites
Solitary lesions - Coin lesion
• asymptomatic pacient finding „ by chance“ or by screening
( 5 year survival in T1 NO MO is 80 - 100 %)
• X ray, CT signs of benign - rounded shape, sharp edge,
calcification
• benign - granulom - tuberculoma, cryptococosis,
blastomykosis
– absces, pneumonie, hamartoma
– bronchogen cyst,, pl. infarctus, br. adenom
– A -V aneurysma, reumatic nodule
• over 50 year are 50 % malignant , 10 % meta
!!!comparison with older X ray !!! To verify or
removed ????
Other lung tumors
• carcinoids – „bronchial adenoma“ today is one of the 9
subtypes of LC
– „semimalignant“, production of vasoactive amins – APUD but
today belong to LC subtype
– bronchial obstruction
– 1 / 3 hemoptysis
– local removing acceptable, or standard surgery
• atypic carcinoids more malignant
• adenoid cystic carcinom - cylindrom- high 5year survival
• papilomas
• mesenchym benign tu - hamartoma, chondroma, lipoma,
leiomyoma
Other chest tumors - 2
Pleura - malignant mesothelioma - asbestos diffuse form
- benign fibromesotelioma - demarcate
Mediastinum - thymus, lymphoms, neurinoms,
thyreoid gland
Bronchogenic cysts,
Meta of lung cancer
Differential diagnosis
•
•
•
•
•
metastatic disease
other tumors – Hodgkin l., mesothelioma, thymoma
benign tumors
pleural effusion
nontumorous masses
tuberculoma
pneumonia – lung absces
sarcoidosis
aspergiloma
pulmonary emboli
Screening ???
• 3 USA and 1 Czechoslovak study
chest Xray + sputum cytology
no effect on mortality
• biomarkers ?
• molecular genetics ?
• high risk population ?
• low dose spiral CT ?
Screening ???
low dose spiral CT ?
Sone 0,48 % LC cases in screened group
Jett 1,5 %
Henschke 2,7%
80-90% operability of screened cases
Lung Cancer and Early Detection
• No tests are recommended for screening the
general population
• A low-dose helical computerized
tomography (CT or CAT) scan is currently
being studied for this purpose
Treatment in the Czech Republic
1985-2005
surgical treatment
10,4% - 11,4% in men
9,4 % - 13,2% in women
radiotherapy
26% in 1985 - 23%in 2005
chemotherapy
20,7% in 1985 – 34% in 2005
no treatment
47% in 1985 - 42% in 2005
Interventional bronchoscopy
• currative intent
• paliative intent
Interventional bronchoscopy
Situation in the Czech Republic
• Nd -YAG laser 10x
• stenting 8x
• brachytherapy 9x
• autofluorescence 4x Life, 1x SAFE
• EBUS 4x
• photodynamic therapy - 0
• cryotherapy 2x
• argon-plasma coagulation - 2
• endobronchial drug and gene therapy - 0
Endobronchial therapy
• paliative intend
• Stenting by Dynamic „ Freitag“ stent
• Standard Dumon silikon stent
• Personal experience from 1991
Bolliger CT, Mathur PN, Marel, M. et al:
ERS/ATS statement on interventional
pulmonology Eur Respir J. 2002 Feb , 356-73
Contribution of BRS to
diagnosis
• BRS finding: direct Tu changes
indirect tu changes
normal findings
BRS not done
BRS findings in 353 „our“ pts
• The whole set:
•
•
•
•
direct Tu changes at BRS
indirect Tu changes
normal findings
BRS not done
35%
26%
20%
19%
BRS findings in central and
peripheral types of LC
•
•
•
•
•
Central type
direct changes BRS in
indirect
normal findings
not done
•
•
•
•
•
Peripheral type
direct changes BRS in
indirect
normal findings
not done in
52%
25%
6%
17%
15%
27%
37%
21%
p< 0,00001
BRS findings and other
features
• In smokers more direct TU changes (41%)
vs in
nonsmokers and exsmokers (27% resp. 26%), p<0,03
• in adenoca less direct tu changes in BRS (19%) than in
other types (p<0,013)
• In SCLC most direct tu changes 66%
• We resected :
9% pts with direct tu changes
17% pts with indirect tu changes
40% pts with normal BRS finding
BRS and verification
•
•
•
•
•
BRS findings:
Direct tumor changes
35%
Indirect tumor changes
26%
Normal BRS
20%
Brs not done
19%
verification at BRS
95,3%
55%
22,8%
0%
Operability of LC during 1970 - 1990
in three departments of University Hospitals
in the Czech Republic
1970 Velesl
255
21%
17/1,0
1980 Velesl
229
23%
12/1,0
1990 Velesl
207
18%
9/1,0
1998 Motol
1999 Motol
2000 Motol
2001 Motol
04-7 I.TRN
136
130
149
177
353
23%
24%
25%
28%
18%
1,8/1,0
2/1,0
2/1,0
1,75/1,0
2:01
Type of surgery in 64 LC patients
In the 1st Pulmonary Department
University Hospital Prague
2004-7
Type of operation
Lobectomy
Pneumonectomy
Bilobectomy
Wedge resection
Explor.thoracotomy
Total
N
51
6
2
1
4
64
%
80%
9%
3%
1%
7%
100%
Conclusions
• The situation throughout the world is unsatisfactory
• Non smoking society - is it a reality of Eastern Europe
and world?
• Earlier diagnosis
• New:
autofluorescence bronchoscopy, EBUS, TBNA,
electromagnetic navigation
active approach to the disease
screening of LC ??
in CR best possibility may be low dose spiral CT
in the world biomarkers, genetic changes,
low dose spiral CT
• it is realistic to await a new „revolutionary drug„???
•
•
Thank you
for your
attention