KARSINOMA

BRONKOGENIK
Dr. Hermawan Chrisdiono, Sp.P
RSUD Unit Swadana Pare
Des 2007

KARSINOMA
BRONKOGENIK

BATASAN :
TUMOR GANAS
PARU PRIMER
YANG BERASAL
DARI SALURAN
NAFAS

TYPES OF LUNG
CANCER
Non-Small

Cell (NSCLC)

80%

Adenocarcinoma

40-50%

Squamous Cell

20-30%

Large

5-10%

Small

Cell (SCLC)

15-20%

STEP

A mistakes happens
in the cell

STEP

the mistakes
add up

STEP 2 WEAPONS
Cancer Prevention

STEP 3 WEAPONS
Anti Growth

Cell Suicide

STEP

the cells turn

cancerous

STEP

STEP 3 WEAPONS
Immune Booster

Microradiation

the tumors
appetite grows

STEP 4
WEAPONS
Antiangiogenesis

STEP

the cancer spreads

STEP 4 AND 5 WEAPONS

Surgery

Chemotherapy

Radiation

WHO :
LEVELS of PREVENTION
PRIMER : PREVENSI ELIMINASI /
BLOCKING KARSINOGEN
SEKUNDER : DIAGNOSA DINI
TERTIER : TERAPI KURATIF
QUARTER : PENANGANAN PALIATIF

LEVELS of PREV in
NSCLC

II

III

IV

CARCINOGEN
AVOIDANCE

EARLY
DIAGNOSIS

CURE

PALLIATION &
SUPPORTIVE

+++

++

DIAGNOSA DINI ??

DX DINI dgn TUJUAN : SURVIVAL ??

IMAGING: 5 mm3 = 32 x TUMOR DBL(s)

(1 cm3 = 10^9 SEL)

KEMATIAN : 40 x TUMOR DBL(s)
80 % PERJALANAN PENYAKIT
OPERASI pd STAD I 5 yrs surv. 40-60 %
PREVENSI !!!

SURVIVAL
Stage
Ia
Ib
II a
II b
III a
III b
IV

5 yrs survival
61 %
37 %
34 %
24 %
13 %
5%
1%

RELATIONSHIP
TOBACCO LUNG CA
TUMOR SUBTYPE
SQ.CELL CA

%
> 95 %

SMALL CELL CA

90 %

LARGE CELL CA

80 %

ADENO CA

70 %

PATOFISIOLOGI

EKSOGEN :
PAPARAN KARSINOGEN ROKOK

ENDOGEN :
KEPEKAAN FAKTOR HOST

GENETIK

a.l.: p53 TUMOR SUPPRESSOR GENE

80-90 % CA PARU PEROKOK

99.99 % PEROKOK TIDAK KENA CA PARU

HUB. ROKOK CA. PARU

ASOSIASI KAUSAL
BUKAN HUB. SEBAB
AKIBAT

KIAT
STOP MEROKOK
SEKALIGUS ( COLD TURKEY)
TANPA TAPERING
TANPA PINDAH LOW TAR /
FILTER
VS WITHDRAWAL NIKOTIN
SUBSTITUSI
VS PENINGKATAN BB

VS PSIKOLOGIS

SOCIAL
PRESSURE

NICOTINE WITHDRAWAL

PHARMACO
THERAPY

NICOTINE SUBSTITUTION:
Average duration 7 WKS

BUPROPION:
Anti depressant : approved for smoking
cessation (FDA) 1997
Pregnancy : approved ( FDA : B)
Contra indication : predilection for seizures

Nicotine substitutes
NON nicotine substitutes

Bupropion : FDA approval (+)

Nortryptilene NO FDA approval
Clonidine : NO FDA approval

TATA LAKSANA

KECURIGAAN :

LAKI : ratio LK / W = 5:1

USIA > 40 TH : 84.2 % (Sby)
PEROKOK : > 80 %
PAPARAN INDUSTRI
GEJALA KLINIK :

BATUK >2 Mgg,

BATUK DARAH,
SESAK,
BB TURUN > 4kg/6bln

EXPERTISE
DOKTER
UMUM

KONFIRMASI /
SKRINING
X-RAY
(+)

X-RAY
(-)

CYTOLOGY
(+)

CYTOLOGY
(-)

A/B/C
RUJUK
D : SKRINING ULANG BL INDIKASI
TETAP ADA / 4-6 bln

TINDAKAN pd RUJUKAN
ENDOSKOPI
BIOPSI

( OPEN / FINE
NEEDLE
ASPIRATION)
SPESIALIS
CT SCAN / MRI
TUMOR MARKER.

GAMBARAN KLINIK
INTRA-PULMONAL

INTRA - TORAKAL
EKSTRA - PULMONAL

GANGG.MUCUCIL
ULSERASI
OBSTRUKSI
RADANG

MEDIASTINAL
INVOLVEMENT

GEJALA
EKSTRA-TORAKAL
NON - METASTATIK
NEUROMUSK.
ENDOKRIN
JAR.IKAT & TLG
VASKULER

METASTATIK

GEJALA INTRAPULMONAL

BATUK LAMA / BERULANG : 70-90%

BATUK DARAH
: 6 - 51%
NYERI DADA
: 42-67%
SESAK NAFAS
:
58%
MEKANISME :
GANGG.GERAKAN SILIA, ULSERASI
MUKOSA, RADANG BERULANG,
OBSTRUKSI SAL.NAFAS

INTRATORAKAL
EKSTRAPULMONAL
PENYEBARAN TUMOR KE
MEDIASTINUM :
N.FRENIKUS :---->DIAFR.
N.REKURENS :---->CH.VOCALIS
S.SIMPATIK :---->Sindr.HORNER
ESOFAGUS :----> DISFAGI
V.CAVA SUP. :----> Sindr.V.C.SUP.
JANTUNG
:----> Gg.FUNGSI

EKSTRA PULM. NON

METASTATIK
NEUROMUSKULER:

Myo / Neuro / Encephalopathia

ENDOKRIN

& METABOLIK:

Syndr. Cushing / IADH / Karsinoid

gynecomastia / hyperpigmentasi
JAR.IKAT

dan TULANG:

Clubbing fingers
VASKULER & HEMATOLOGIK
Anemia / purpurae / thrombo-phlebitis

METASTATIK
EKSTRAPULMONAL
SATU-SATUNYA TUMOR

yang
mampu LANGSUNG AKSES ke
SIRKULASI ARTERIIL
terutama :
OTAK, HATI dan TULANG

RSUD.
DR.SOETOMO
hanya 1.5 % kanker paru
merupakan kandidat operasi pada
saat diagnosa
Pada fase lanjut :

QUALITY of LIFE

umumnya lebih

penting dari

LENGTH of SURVIVAL

DATA RSUD DR.SOETOMO

BATUK
: 85 %
SESAK NAFAS : 72 %
PENURUNAN BB
: 53.1 %
NYERI DADA : 42.4 %
BATUK DARAH : 23.3 %
JARI TABUH
: 23.2 %
DISFONI : 15.1 %
SVCS
: 10.9 %

Major signs and symptoms

of
LUNG CANCER
Patients 100
(%)
80
60
40
20
0
Dyspnea

Cough

Pain

Loss of Hemoptysis
appetite

Baseline major presenting symptoms

Hollen et al 1999

SESAK
PREV. 29-74%, tergnt: JENIS & STADIA
ETIOLOGI:
PENYAKIT PENYERTA a.l.:
PPOK, ASMA, DEKOMP.,ANEMI dsb

KOMPLIKASI / PENY.SUPERIMPOSED a.l.:

INFEKSI, EMBOLI PARU, ATELEKTASIS,
PNEMOTORAKS, EFUSI PLERA dsb

KANKER PARU nya sendiri

IATROGENIK a.l.:
akibat RADIASI, akibat KEMOTERAPI (misalnya
FIBROSIS o.k.BLEO.) , akibat PEMBEDAHAN

FARMAKOLOGIK
BRONKODIL.
STEROID

RADIASI

R.STIMULAN

OKSIGEN

R.DEPRESS.

SESAK

FISIOTERAPI

KEMO

KHUSUS: stent

BATUK
FREKW. : + 83 % KANKER PARU
PATOFISIOLOGI:

PRODUKSI MUKUS BERLEBIH

INHALASI BENDA ASING / TERSELAK
STIMULASI ABN. PUSAT BATUK

PRINSIP PENANGANAN:
KAUSAL
Faktor REVERSIBEL
SIMPTOMATIS
SUPORTIF
V/S

INFEKSI

OBSTRUKSI
STEROID
SUPRESAN
NEBUL.ANEST
FISIOTx

ANTIBIOT.
SUPRESAN
EKSPEKT.
FISIOTx

BATUK
REFLUKS ESOF.

ASPIRASI

POSISI TEGAK
ANTI REFL.

ANTI-KHOL
NEB.ANEST

BATUK DARAH

SELALU PATOLOGIK
JARANG ASFIKSIA atau EKSANGUINASI
STRESS : MENGINGATKAN akan
KANKERNYA serta PROGRESIFITAS
FREKW. KANKER PARU 47 - 70 %
PENANGANAN :
SUPRESI BATUK
HEMOSTATIK v/s OOZING KAPILER
KEMOTERAPI, RADIASI dan LASER

TNM DEFINITION in

NSCLC

T PRIMARY TUMOR
TX

RO / FOB VISUALIZATION (-); MALIGN.CELLS in BRONCHIAL

SECRETIONS (+)

T0

NO EVIDENCE OF PRIMARY TUMOR

TIS

CARCINOMA INSITU

T-1

< 3 cm, SURROUNDED BY LUNG or VISCERAL PL; w.o.

INVASION PROX to a LOBAR BR.

T-2

T-3

DIRECT

T-4

INVASION

cm or INVADES VISC.PL or ATELECT(+) or

OBSTRUCT.PNEUMONITIS extending TO HILAR, but < ENTIRE
LUNG
. FOB > 2 cm from CARINA
EXTENSION into CHEST WALL; DIAPHR.,
MEDIAST.PL, PERICARDIUM, PANCOAST, w.o. INVOLVING
HEART, GREAT VESSELS, TRACHEA, CORP.VERT.
FOB < 2 cm from CARINA
of MEDIAST INVOLVING ABOVE STRUCTURES
MALIGNANT PL.EFFUSION

TNM DEFINITIONS in NSCLC

N NODAL INVOLVEMENT
N-0

REGIONAL LY.ND (-)

N-1

LY ND PERIBRONCHIAL / IPSILATERAL
HILAR(+)

N-2

LY ND IPSILATERAL MEDIAST;
SUBCARINAL(+)

N-3

LY ND CONTRALATERAL MEDIAST / HILAR;

SCALENE / SUPRA CLAV (+)

TNM DEFINITIONS in
NSCLC
M DISTANT METASTASIS
M-0

NO (KNOWN) DISTANT METASTASIS

M-1

DISTANT METASTASIS (+)

RECOMMENDATION : SPECIAL CASE

PERICARDIAL EFF.
T-4
N.PHRENICUS

:
:

STAGING SCLC DBL

AMAT
CEPAT

LIMITED

EXTENSIVE

BATAS :
SUDAH / BELUM TERLAMPAUI
IPSILATERAL HILAR NODES

TX NON SURGICAL
CHEMO SURV
; CURE(-)

PENENTUAN
MODALITAS TERAPI
HISTO PATH
SURGERY
CHEMO / &
RADIASI
HORMONAL
BIOLOGICAL
RESPONSE
MODIFIER (BMR)
GENE TX

NSCLC
SURGICAL
CASE
CURATIVE?
PALLIATIVE

SCLC
NON
SURGICAL
MAIN
THERAPY

TERAPI

UMUM : 5 MODALITAS TERAPI

1. PEMBEDAHAN
2. SITOSTATIKA
WHO
3. RADIASI
4. HORMONAL
(NSCLC)
5. IMUNOLOGIK

EXPERIMENTAL

SURGICAL OPTION:
MAJOR CONSIDERATIONS
FITNESS for
SURGERY
1. AGE
2. PULM.FUNCTION
3.CARDIOVASC.FITNESS
4. NUTRITION &
PERFORMANCE
STATUS

OPERABILITY
1. DIAGNOSIS &
STAGING
2. ADJUVANT THX.
3. SURG.PROCEDURES
AVAILABLE
4. LOCALLY
ADV.DISEASE
5. SMALL C.L.C.

TNM

STAGING
NSCLC

N-0

N-1

N-2

N-3

T-1

IA

II A

III A

III B

T-2

IB

II B

III A

III B

T-3

II B

III A

III A

III B

T-4

III B

III B

III B

III B

ALL M-1 = IV

OPERABLE

KEMOTERAPI
PERSYARATAN :
PERFORMANCE :

KARNOFFSKY > 70 = ECOG / WHO 0-1

MEMAKSAKAN KEMOTERAPI PADA
KONDISI YANG TIDAK MEMENUHI SYARAT
MEMPERCEPAT KEMUNDURAN
PENDERITA

SKALA TAMPILAN
(PERFORMANCE
SCALE)
KARNOFFSKY

WHO / ECOG

90 100
70 80
50 60

0
1
2

30 40
10 20
0 10

3
4
-

KETERANGAN
AKTIVITAS N
MASIH AKTIF dan
DAPAT MENGURUS DIRI
CUKUP AKTIF namun
KADANG PERLU
BANTUAN
KURANG AKTIF, PERLU
RAWATAN
TIDURAN, BUTUH
RAWAT INAP
TIDAK SADAR

REALITA

0.8

1.0

Survival byTreatment Group

All RandomizedCases

0.2

0.4

0.6

Cis/Paclitaxel
Cis/Gemcitabine
Cis/Docetaxel
Carbo/Paclitaxel

0.0

TREATMENT of NONSURGICAL NSCLC

THERAPEUTIC
PLATEAU / CEILING
BENEFIT:
OBJECT.RESP.RATE
: 25-40%
MEDIAN SURV : 8-10
mo
1 YR SURV RATE: 3040%

10

15
Months

20

25

30

Therapy :

A New Paradigm for the 21st Century

GENE
THX

Targeted
thx

MOLECULAR PATHWAYS OF
TUMORS
MAXIMIZING
EFFICACY
REDUCING
TOXICITY

REVOLUTION IN CANCER THX:

NON-SPECIFIC USE OF ANTI NEOPLASTIC AGENTS
SHIFT

SPECIFIC TARGETED THERAPY

EGFR SIGNALING NETWORK

EGFR activation
Survival/protection
from apoptosis

Dedifferentiation
Signalling cascade
Angiogenesis

Gene
activation
M
G2

G1

S
Cell proliferation
Metastasis: cell
migration and
invasion

ANTI-ANGIOGENESIS

ANY TUMOR > 2 mm

CANNOT SURVIVE DEPENDING
upon PASSIVE DIFFUSION of
NUTRIENTS ALONE
NEO-ANGIOGENESIS is
NEEDED

GENE THERAPY

TUMOR
WITH
IN

DELIVERING CYTOTOXIC MOLECULES or

IMMUNOSTIMULATORY FACTORS / CELLS

RATIONALE GENE THX

IMMUNOSURVEILANCE:
ABNORMAL (e.g.TUMOR) CELLS ACTIVATION of APC
DEPLOYMENT of TUMOR-SPECIFIC, CELLULAR & HUMORAL
EFFECTORS.

PROBLEM:
TUMOR CELLS :
NON- IMMUNOGENIC ( CO-STIMULATORY MOLECULES <<)
CREATE ENVIRONMENT THAT SHIELDS FROM IMMUNE SYSTEM:

PROD.of ANTAGONISTIC MEDIATORS

DOWN REGULATION of APC
INDUCTION of TOLERANCE in TUMOR SPECIFIC T CELLS

SOLUTION:
ACTIVATE IMMUNE SYSTEM RECOGNIZE & ATTACK TUMOR

DENDRITIC CELL(DC)-BASED GENETIC THERAPY:

DC and IL-7 ; DC and CCL21
ANTISENSE RNA BLOCKING TGF-beta
ADENOVIRUS MEDIATED EXPRESSION of IFN-beta

PHASE I STUDIES

CA

THE USE OF NATURAL SUBSTANCES

DERIVED FROM PLANTS OR ANIMALS,
TO STOP, REVERSE OR SLOW DOWN
MALIGNANT DISEASE TO OBTAIN A BETTER
QUALITY OF LIFE AND MEANINGFUL
SURVIVAL

BIO-PHARMACA
ACTION

CYTOTOXIC EFFECT ;
DIFFICULT / EXPENSIVE TO PROVE

IMMUNOLOGIC EFFECT
IMMUNOSTIMULATING EFFECT:

MACROPHAGE ACTIVITY
NATURAL KILLER CELL ACTIVITY
T-CELL ACTIVITY
LYMPHOKINE
IL-1 , IL-2

ANTI ANGIOGENESIS

ENHANCED

KONTROVERSI PENGOBATAN
ALTERNATIF
CURRENT MEDICAL
PRACTICE

FOCUS ON DISEASE
INSTEAD OF HEALTH
PATERNALISTIC
UNDERVALUES
SOCIAL,
PSYCHOLOGICAL &
SPIRITUAL ASPECTS

ALTERNATIVE
MEDICINE

MAY NOT ONLY BE

WASTING TIME &
EFFORT ON USELESS
REMEDIES, BUT MAY
NEGLECT EFFECTIVE
TREATMENT
NOT SCIENT.PROVEN

TERAPI ALTERNATIF /
TRADISIONIL
KOMPLIMENTER = / = ALTERNATIF
(in conjunction) v/s (instead of)
KONVENSIONIL

(+) TRADISIONIL

REASONING :
HAK OTONOMI PENDERITA
ADV. PATIENT :RETAINING CONTROL
ADV. DR.: RETAINING PAT.TRUST

Integrative medicine

WHY TAKE
HERBALS

TO FEEL BETTER
SEARCHING FOR A CURE TAKE
WHATEVER YOU CAN GET
ACCESS IS EASY
ANECDOTES / TESTIMONIAL FROM
FRIENDS POWERFUL PERSUADERS
SUBJECTIVE RESPONSES (PAIN /
FATIQUE etc) 1/3 PLACEBO EFFECT
EST. 7 83 % CANCER PTS (INDUSTRIALIZED C.)
INDONESIA approx. 95 %

CAUTION
ANYTHING THAT
HAS
PHARMACOLOGICAL
ACTIVITY,
CARRIES THE RISK OF

TOXICITY

IMMUNE SYSTEM
STIMULATION
IL-4, IL5

COULD
BE DETRIMENTAL

T cell
precursor

(IL3, IL6-10, IL14)

B cell

TH2 cell

TH1 cell
MHC class I
COULD
BE BENE
FICIAL

cytokines

TC cell

NK cell

IMMUNOSURVEILANCE

THERAPEUTIC
PRIORITIES
SUPPORTIVE

PALLIATIVE
V.S. REVERSIBLE FACTORS

V.S. CAUSAL FACTORS

SEQUENTIAL / SIMULTANEOUS

PRIMARY CARE GOAL

CURE LIFE
IMPACT on DISEASE
ACCEPTABLE ADV. EFF.

ERADICATE

MAJOR

PROLONGING
PALLIATIVE

PALLIATIVE
(SUPPORTIVE)

ARREST
PROGRESSION

AVOID
COMPLICATIONS

MOD - MAJOR

WIN

ATTITUDE

SYMPTOMATIC

NONE - MINOR

FIGHT

ACCEPT

CPR

YES

PROBABLY

PROB.NO

HOSPICE

NO

NO

PROBABLY

SYMPTOM RELIEF

SECONDARY

SUPPORT for FAMILY

YES

YES

YES

ADV.CARE PLANNING

YES

YES

YES

BEREAVEMENT SUPPORT

NO

SOMETIMES

USUALLY

BALANCED

PRIMARY

NOTE: WHO NEITHER LIFE PROLONGING OR

HASTENING DEATH

HASIL META ANALISA ATAS SURVIVAL DARI KELOMPOK KEMOTERAPI

DIBANDING BEST SUPPORTIVE CARE
( 6 RCT, N khemo = 341, N BSC = 294 )
100 l
l
90 l
l
S
80 l
U
l________75
R
70 l
l
V
l
l
________ KEMOTERAPI
I
60 l..........60..l
................BEST SUPPORTIVE
V
l
l_________54
CARE
A
50 l
:
l
L
l
:
l
40 l
:
l
l
:...........34..l__________34
%
30 l
:
l
l
:...............24____________22
20 l
.......................:15
l
10 l
l
0 L__________________________________________
3
6
9
12 bulan
di kutib dari Grilli R.dkk (1993)

MEDIAN PROLONGATION of SURVIVAL

7 wks

GOAL of
PALLIATIVE CARE
SYMPTOM PALLIATION
IMPROVING QUALITY of LIFE
PROLONGING LIFE for some period
enabling the patient to ACCOMPLISH
CERTAIN OBJECTIVES before death
(median prolong.surv 6 wks (v.s.BSC))

IN TERMINAL STAGE, TIME IS MEASURED

IN MOMENTS - NOT MONTHS

CANCER
Is an

ILLNES
S
Not

NOT

DEATH
SENTENCE
A

DIMENSIONS
Of

HOPE

Hope to die in dignity

INFORMATION
DO NOT
GIVE
FALSE
HOPE
THE RIGHT TO
INFORMATION
CONCERNING
THEMSELVES

DO NOT
DESTROY
HOPE
OBLIGATION TO
PRESERVE BOTH
PHYSICAL &
EMOTIONAL
WELL-BEING

FINAL OBJECTIVE
Might not lengthen
survival,
B U T increase their

QUALITY OF LIFE
Attaining
A
Meaningful
survival

Time flies