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TEDAVSNDE GELMELER
KONYA
2003
Prof.Dr.smail Sava
Ankara niversitesi Tp
Fakltesi Gs Hastalklar
Anabilim Dal
Kadn
Akcier
Meme
Kolon/rektum
Mide
Karacier
Prostat
Serviks
zofagus
Mesane
Non-Hodgkin lenfoma
Oral kavite
Lsemi
Pankreas
Over
Bbrek
1200 1000
800
Incidence
Mortality
600
400
200
Bin
200
400
600
800
1000 1200
100,000
Kiide
erkek/kadn 60
oran
40
20
0
1930
1940
1950
1960
1970
1980
1990
AKCER KANSERLER
80
87
86
81
60
40
75
41
20
0
Dispne
Cough
Pain
Loss of Haemoptysis
appetite
ksrk
Ar
Akcier Kanseri
(Kk hcreli d)
Yass hcreli kanser(~30%)
Erkeklerde sk
Adenokarsinoma (30-50%)
Skl artmaktadr
K-ras mutasyonu sktr
Bronkoalveoler karsinom alt grubu
vardr.
Bulgular
Bronkoskopi
Sitolojik inceleme
Akcier grafisi
Bilgisayarl Tomografi
PET
Laboratuar analizler
Mediastinoskopi
Premalign
adenom
Genetik deiiklikler
Sigara
karsinojeni
Normal
epitel
Broniyal
metaplazi
Displazi
Carcinoma
in situ
Uzak organ
metastaz
Ana bron
Evre 0
Evre IA
Evre IIB
Evre IIIB
Kar taraf lenf
bezi
Evre IV
TNM
IA
T1N0M0
61
IB
T2N0M0
38
IIA
T1N1M0
34
IIB
T2N1M0 or T3N0M0
24
IIIA
T1-3N2M0 orT3N1M0
13
IIIB
T4NanyM0 or TanyN3M0
TanyNanyM1
IV
Mountain 1997
Multidisipliner Yaklam
Gs Hastalklar
Gs Cerrahisi
Medikal Onkoloji
Radyasyon Onkolojisi
Radyoloji
Patoloji
Yardmc Salk Personeli Birimleri
AKCER
KANSERLERNDE
Genel yaklam
TEDAV
Akcier Kanseri
Tedavisine Yn Veren
1) Tmrn histopatolojik tipi
Koullar
2) Hastaln evresi
3) Hastann performans durumu
Tedavi yaklamlar
(Kk hcre d akcier kanseri)
Evre I
Lobektomi veya segment / wedge resection
Cerrahi olanakszsa kratif radyoterapi
Adjuvant kemoterapi
Adjuvant radyoterapi
Evre IIIA
Sadece cerrahi
Kemoterapi +
radyoterapi / neoadjuvant tedavi
Post-operatife radyoterapi
Sadece radyoterapi
Evre IIIB
Sadece kemoterapi
Kemoterapi + radyoterapi
Sadece radyoterapi
Evre II
Lobektomi, pnmonektomi,
segment / wedge rezeksiyon
Cerrahi olanakszsa kratif
radyoterapi
Adjuvant kemoterapi
Adjuvant radyoterapi
Evre IV
Kemoterapi ( platinli ),
Yeni kemoterapi ajanlar
Radyoterapi (palyatif)
Obstrksiyon iin endobroniyal
lazer veya brakiterapi
Kk Hcre D Akcier
Kanseri
Kk Hcre D Akcier
Kanseri
CERRAH TEDAV
CERRAH TEDAV
NOPERABLTE
NEDENLER
Cerrahi Yntemler
Segmentektomi
Wedge rezeksiyon
Lobektomi (nerilen)
Bilobektomi
Pnmonektomi (kendisi bir
hastalktr)
CERRAH TEDAV
SONULARI
EVRE
I
IIA
IIB
IIIA
GENEL
pTNM
T1T2NO
T1N1
T2N1
T3N0
T3N1
N2
5 yl sakalm %
65
50
50
40
25
20
45
RADYOTERAP
Tmr Bykl ve
Radyasyon Dozuyla likili
Olarak
Sakalm*
Yazar
Evre
I
Evre I/II
Evre IIIA
Evre IIIB
<3cm 3-5 cm
Morita
25
17
Noorduk
22
0
Gouders
45 20
Martel
< 3 cm
56
26
Sibley
Armstrong
Wurschmidt
47
10
49
7
7
26
0
13
3-5cm
3-5 cm
RADYOTERAP PRATNDE
DOZLAR VE UYGULANIM
EKLLER
Doz Frak Hafta
Gy
Gn
Konvansiyonel
Split course
Hipofrak
Hiperfrak
>2
5
>2
1
1-1.3 2
CHART
1.5 3
HART
1.6 3
(CHART: Continuous hyperfractionated accelerated radiation therapy)
5-7
4-6
<5
10
2
2.5
RADYOTERAP
PREOPERATF
RADYOTERAP
POSTOPERATF
RADYOTERAP
PALYATF RADYOTERAP
Havayolu Obstrksiyonu
Hemoptizi
Vena Kava Sperior Sendromu
Kemik metastazlar
Spinal kord kompresyonu
Beyin metastaz
Toraks Radyoterapi
Toksisitesi
KEMOTERAP
Cevap
rinotecan
fosfamide
Paclitaxel
Docetaxel
Gemcitabine
Cisplatin
Mitomycin C
Vinorelbine
Vindesine
Doxorubicin
Topotecan
Etoposide
oran (%)
27
26
26
26
21
20
20
20
17
13
13
11
KEMOTERAP
KEMOTERAP
PROGNOSTK
KRTERLER
KEMOTERAP
KEMOTERAP
KEMOTERAP
Cisplatin Kombine Sakalm p
( 1 yl sa) KT
( 1 yl )
Wozniak
6ay +Vinorelbine
8 ay 0.0018
Sandler
32w+Gemcitabine 39 w
0.008
Gatzemeier 35w+Paclitaxel
37 w >0.05
Von Pawel
28w+Tiripazamine 35 w 0.008
emalar
(%)
Ortalama
sakalm
(ay)
1-yl
sakalm
(%)
cevap
Le Chevalier
1994
Vindesine/cisplatin
Vinorelbine/cisplatin
19.0
30.0*
7.4
9.2*
28
36
Bonomi
1996
Etoposide/cisplatin
Paclitaxel (135)/cisplatin
Paclitaxel (250)/cisplatin/GCSF
12.0
26.5*
32.1*
7.7
9.6
10.0
31.6
36.9
39.1
Crino
1998
Mitomycin/ifosfamide/cisplatin
Gemcitabine/cisplatin
28
40*
8.8
8.1
Belani
1998
Etoposide/cisplatin
Paclitaxel/carboplatin
14.0
21.6
8.3
8.3
35
35
Cardenal
1999
Etoposide/cisplatin
Gemcitabine/cisplatin
21.9
40.6*
7.2
8.7
26
32
*p<0.05;
emalar
Tmr
cevab
Ortalama
sakalm
(ay)
1-yl
sakalm
(%)
Kelly
2001
28
25
8
8
36
38
Schiller
2002
21
22
17
17
7.8
8.1
7.4
8.1
31
36
31
34
Fossella
2001
10.9
9.1
10
47
38
42
Kelly et al 2001
Schiller et al 2002
Fossella 2001
0.8
Ortalama
sakalm(ay)
1-yl sakalm
(%)
0.6
0.4
Docetaxel
75 mg/m2
7.5
Best
supportive
care
4.6
37
12
0.2
Log rank: p=0.01
0.0
0
12
15
18
21
Ay
Shepherd et al 2000
GEMCITABINE
N
71
Gemcitabine
1-8-15 (1000)
vs
Cisplatin (100)+
Etoposide(80)
75
*p > 0.05
%15
7.6 ay *
GEMCITABINE
N
sakalm
Cisplatin 262
vs
Gemcitabine+
Cisplatin 260
*p <0.05
Cevap
Ort.ya
%9
7.6 ay
%28
9 ay *
%39*
%31
1 yl
Evre IIIB ve IV
ECOG PS 0-2
Chemonaive
nceden RT almam
Randomize
LOKAL LER
HASTALIKTA KOMBNE
Evre III hastalarda primer hastalk RT ile kontrol
TEDAV
edilirken, gizli mikrometastazlarn KT ile kontrol
Sakalm
Ortalama
2 yl
5 yl
7 yl
CT+TRT
13.7 ay
%26
%17
%13
TRT
9.6 ay
%13
%6
%6
LOKAL LER
HASTALIKTA KOMBNE
TEDAV
Sakalm
Ortalama
2 yl
5 yl
KT+TRT
15.2 ay
%35.5
% 9.7
KT
14.7 ay
% 9.4
% 3.1
KOMBNE TEDAVDE
RADYOTERAP ZAMANI
Sakalm
Ardk
Ortalama
1 yl
2 yl
3 yl
5 yl
E zamanl
16.5 ay
%64.1
%34.6
%22.3
%15.8
13.3 ay
%54.8
%27.4
%14.7
%8.9
KK HCREL AKCER
KANSER
Extensive
Tek bir hemitoraksn
dna kan, snrl
hastalk tesinde
Uzak metastasis
Limited
Tek bir hemitoraksa
ve/veya mediasten ve
supraklavikuler
nodllere snrl
Prognostik Faktrler
Hastaln evresi
Snrl hastalk/Yaygn hastalk
Hastann performans
Serum LDH dzeyi
Plazma albmin ve sodyum dzeyi
Prognoz
70
60
Stage distribution
5-year relative survival
Hastalar
50
(%)
40
30
20
10
0
Localised
Regional
Snrl
Distant
Unstaged
Yaygn
Ries et al 2001
KK HCREL AKCER
KANSER SINIRLI HASTALIK
KK HCREL AKCER
KANSER SINIRLI HASTALIK
Snrl hastalk :
Kombine kemoterapi ve Gs
radyoterapisi
KT + RT n=1111
Meta-analiz (13 alma)
Sakalm 100
(%)
80
sadece KT n=992
60
40
20
0
0
Yllar
p=0.001
Pignon et al 1992
KK HCREL AKCER
KANSER SINIRLI HASTALIK
Cevaplanmam sorular;
Radyoterapi ne zaman ?
Alternan ? Ardk ? Ayn anda ?
KK HCREL AKCER
KANSER SINIRLI HASTALIK
KK HCREL AKCER
KANSER SINIRLI HASTALIK
Akut zofajitis
Sk kullanlan emalar
cisplatin/etoposide (PE)
cyclophosphamide/doxorubicin/vincristine (CAV)
cyclophosphamide/doxorubicin/etoposide (CAE)
CAV / PE
PE uluslararas standart
Carboplatin/etoposide daha az toksik
Kelly 2000
Snrl hastalk:
Proflaktik kafa nlamas
Total beyin
metastaz
(%)
80
60
40
20
0
0
12
24
36
48
60
Aylar
Arriagada et al 1995
YKSEK DOZ
KEMOTERAP
Kk hcre destekli yksek
doz kemoterapi henz
aratrma aamasndadr.
Sonular deerlendirmek
iin erkendir.
YKSEK DOZ
KEMOTERAP
Febril ntropeni
alma kolunda %28
Kontrol kolunda %57
YKSEK DOZ
KEMOTERAP
KK HCREL AKCER
KANSER YAYGIN HASTALIK
Trombositopenia*
(%)
Irinotecan/
etoposide
25
71
56
20
Paclitaxel/
carboplatin
32
25
37
9.4
Nks kk hcreli
hastalarda
Faz
III
topotecan
almas
Cevap
Tedavi
Sakalm
hasta
[say
CR
(%)]
PR
(hafta)
Topotecan
107
26 (24%)
25
CAV
104
1 (1%)
18 (18%)
24.7
Tmrn bass ;
Genel kanser etkisi (anemi, halsizlik, ar, anksiyete)
Elik eden hastalklar (KOAH, kalb yetmezlii,
nfeksiyon)
PALYATF TEDAV
Tmrn etkisi dnda
(KSRK)
nfeksiyon, reflux , astm , ACE
inh.
Tedavide;
1) Nonopioidler, lokal anestetikler
2) Opioidler (Codein, methadon )
PALYATF TEDAV
(Hemoptizi)
PALYATF TEDAV
(Postradyasyon
Radyoterapiden 6-12 hafta sonra
pnmonitis)
oluur.
PALYATF
TEDAV
Adenokarsinomada sktr.
(Lenfanjitis
karsinomatoza)
Prognoz ktdr.
Oral kortikosteroid dexamethasone
8 mg/gn, spironolakton
100mg/gn, nebulize
bronkodilatrler
noperable hastalardr.
Kk hcreli d hastalarda acil
radyoterapi gerekir.
Kk hcreli kanserde
kemoterapiyle tedavi edilebilir.
PALYATF TEDAV
noperabiliteyi gsterir.
(Malign plevral sv))
PALYATF TEDAV
(Kanser
Baz sitokinler
( TNF-, IL , IFN-) bu
kaeksisi)
PALYATF TEDAV
Halsizlik
Hastalarn %50sinde psikolojik
skntlar
Anksiyete
Depresyon (leri evrede %75)
Uykusuzluk
Panik
PARANEOPLASTK
SEMPTOMLAR
Hiperkalsemi
Hidrasyon
Bifosfonatlar
Bulant-kusma
Antiemetik tedavi
(Dopamin ve serotonin antagonistleri)
Pansitopeni
Sa dklmesi
Radyoterapi
( Mukozit, zofajit )
Korunma
Erken Tan
KOAH l hastalarda yakn takip ?
Genetik risk faktrleri ?
Balgam sitolojisi
Molekler tmr belirteleri
Dk doz spiral CT
Positron emission tomography
Lazer-floresan endoskop (LIFE) bronkoskopi
Edell 1997
Hirsch 2001
Beyaz k
bronkoskopi grnts
LIFE
Bronkoskopi grnts
R R
Antikor
EGFR-TKI
Membran
Intraselller
EGFR-TKI
Proliferasyon
Byme faktrleri
Kemoterapi/
radyoterapi duyarll
K K
Signalling
Hcrel yaam
(anti-apoptosis)
DNA
Anjiyogenez
Metastaz
R, epidermal growth factor receptor
Tmr anjiyogenezi
Tmr
1.Anjiyogenik faktrlerin
sekresyonu
2. Ekstraselller matriksin
proteolitik paralanmas 3. Endotelyal
proliferasyon
ve g
Kapiller oalmas
4. Yeni tmr
damarlarnn oluum
Antianjiyogenik ajanlar
Thalidomide
Sponsor
ema
NCI, NCCTG
Plasebo
Carboxyamidotriazole
NCIC-Klinik
alma grubu
Plasebo
OSI-774
Docetaxel/plasebo
Docetaxel/exisulind
NCI, NCCTG,
NCIC-Klinik
alma Grubu,
SWOG
Cisplatin/etoposide/
radyoterapi/
docetaxel/plasebo
Cisplatin/etoposide/
radyoterapi/
docetaxel/ZD1839
Ligand
Pharmaceuticals
Vinorelbine/cisplatin
Vinorelbine/cisplatin/bexarotene
Hcre Alar
NCI, National Cancer Institute; NCCTG, North Central Cancer Treatment Group; SWOG,
Southwest Oncology Group
ema
Aratrlan ema
NCI, SWOG
Paclitaxel/carboplatin
Paclitaxel/carboplatin/tirapazamine
Sanofi-Synthelabo
Cisplatin/vinorelbine
Cisplatin/vinorelbine/tirapazamine
Genentech
Paclitaxel/carboplatin
Paclitaxel/carboplatin/OSI-774
ISIS Pharmaceuticals
Paclitaxel/carboplatin
Paclitaxel/carboplatin/ISIS 3521
NCI, ECOG
Paclitaxel/carboplatin/
radyoterapi
Paclitaxel/carboplatin/radyoterapi/
thalidomide
Abgenix, Immunex
Paclitaxel/carboplatin
Paclitaxel/carboplatin/ABX-EGF
AstraZeneca
Paclitaxel/carboplatin/
plasebo
Paclitaxel/carboplatin/ZD1839
AstraZeneca
Gemcitabine/cisplatin/
plasebo
Gemcitabine/cisplatin/ZD1839
NCI, National Cancer Institute; SWOG, Southwest Oncology Group; ECOG, Eastern
Cooperative Oncology Group
ema
Aratrlan ema
Paclitaxel/carboplati
n
Paclitaxel/carboplatin/bevacizumab
Paclitaxel/carboplati
n/plasebo
Paclitaxel/carboplatin/BMS-275291
Oblimersen/docetaxel
Docetaxel
NCI, National Cancer Institute; ECOG, Eastern Cooperative Oncology Group; SWOG,
Southwest Oncology Group;
ema
Hastalk
Aratrlan ema
Carboplatin/paclitaxel
evre
Snrl
Cyclophosphamide/
doxorubicin/
etoposide
Yaygn
Hastalk evre
NCI, SWOG
Gemcitabine/irinotecan
Tedavisiz,yaygn
NCI, CALGB
Paclitaxel
yaygn
NCI, NCCTG
Topotecan/paclitaxel
Nks, direnli
CCI-779
yaygn
Fenretinide
Nks
Temozolomide
Nks, ilerleyici
Chloroquinoxaline sulfonamide
Yaygn,nks
Sponsor
NCI, ECOG
NCI, Uni of Michigan
NCI, FCCC
NCI, BRI
NCI, National Cancer Institute; SWOG, Southwest Oncology Group; CALGB, Cancer and
Leukemia Group B; NCCTG, North Central Cancer Treatment Group; ECOG, Eastern
Cooperative Oncology Group; FCCC, Fox Chase Cancer Center; Beckman Research
Institute
Korunma
Eitim ve primer korunma
Sigarayla mcadele
Kemoproflaksi
retinoidler
EGFR inhibitorleri
selenyum
COX-2 inhibitorleri
Yeil ay
SONU