Cita Herawati Murjantyo

ENT DEPT

DHARMAIS CANCER

CENTRE HOSPITAL

INTRODUCTION :

INDONESIA :NPC – ENT 1st

ALL OF CANCER – IVth

EARLY STAGE DIFFICULT !!

- NO SPESIFIC SYMPTOM

- PHYSICAL EXT. NOT VISIBLE

- NASOPHARYNX :

THE TRANSITIONAL ZONE BETWEEN NASAL CAVITY & OROPHARYNX :

“ANATOMICAL BLIND SPOT”

1. LUMEN / NASOPHARYNX

CHAMBER

2. RETROPHRYNX

3. PARAPHARYNX

4. INTRACRANICAL

5. PARANASAL SINUS

6. DISTANT METASTATIC

12

3

4555

MONGOLOID RACE : SOUTHERN

CHINESE, HONGKONG, VIETNAMESE, THAIS, MALAYS, INDONESIANS.

INDONESIA : RSCM 100 NEW CASES / YEAR RSHS 60 UJUNG PANDANG 25 PALEMBANG 25 DENPASAR 15 PADANG 11 DHARMAIS HOSPITAL 70

Sumber : Instalasi Rekam Medis & Admission RSKD

No. DIAGNOSA ICD-X JUMLAH

1 BREAST C501 – C509 1661

2 CERVIX C530 – C539 708

3 BRONCHUS & LUNG C340 – C349 390

4 PHARYNX C100 – C148 380

5 COLORECTUM C180 –C209 353

6 LYMPH NODES C770 – C779 320

7 LEUKIMIA C420 – C424 270

8 OVARY C569 223

9 THYROID GLAND C739 183

10 HEPAR C220 – C221 170

10 BESAR KANKER TERSERING RS KANKER DHARMAIS

RAWAT JALAN (KASUS BARU) TAHUN 2005 - 2007

Sumber : Instalasi Rekam Medis & Admission RSKD

No. DIAGNOSA ICD-X JUMLAH

1 BREAST C501 – C509 227

2 PHARYNX C100 – C148 264

3 COLORECTUM C180 – C209 203

4 LYMPH NODES C770 – C779 191

5 LEUKIMIA C420 –C424 151

6 HEPAR C220 – C221 126

7 ORAL CAVITY C000 – C609 78

8 PROSTATE GLAND C619 60

9 SKIN C440 – C449 58

10 SOFT TISSUE C490 – C499 55

10 BESAR KANKER TERSERING RS KANKER DHARMAIS

RAWAT JALAN (KASUS BARU) MALE TAHUN 2005 - 2007

Etiology

Epstein-Barr Virus (EBV)- 100% association with NPC

- Elevated high titer of EBV-EA, VCA for early diagnosis

Enviromental factors- Salted fish, nitrosamine, N-nitrosodimethyamine

- Herbal medicines: promoter and initiator in plants

Genetic factors- Somatic changes:

activation of oncogenes and inactivation of tumor suppressor genes

- Heritable genetic changes:

Susceptibility genes in high risk family (familial aggregation and

immigration)

Agent/Factors Implication

Epstein-Barr virus

Chemical-Tobacco

Drugs

Plant Products

Diet

Raised antibody

Viral genome in tumor cells

Cigarette smoking

Chinese herbal medicine

EBV activating properties/co-factors

Salted fish

Preserved vegetables, fermented food stuff

Nitrosamines & nitro-precursors

Tunisian preserved spice meat and stewing base

Agent/Factors ImplicationCooking Habits

Religious Practice

Occupation

Household smoke and fumes

Incense and joss stick smoke

Industrial fumes and chemicals

Metal smelting

Formaldehyde

Wood dust

1. EPISTAXIS & NASORESPIRATORY SYMPTOMS

- BLOOD STAINED, NASAL MUCUS & SALIVA(POST NASAL DRIP)

- EPISTAXIS / NOSE BLEEDING

- NOSE BLOCKAGE

2. TINITUS & AURAL SYMPTOMS

- OTITIS MEDIA WITH EFFUSION

- TINNITUS

- OTALGIA

- DISCOMFORT EAR

3. NEUROLOGICAL PALSIES

- DOUBLE VISION (+ + +) N III, IV, VI, V (LACERUM FORM.)

- TRIGEMINAL NEURALGIA

- VOICE & SWALLOWING CAN BE AFFECTED (N. IX, X, XI, XII, JUGULARE FORM)

4. CERVICAL LYMPHADENOPATHY

- EARLY LYMPHATIC SPREAD

EARLY DIAGNOSIS : IMPORTANT !!

EARLY SYMPTOMS :– BLOOD STAINED MUCUS– EUSTC.TUBE BLOCKAGE

• OTHER SYMPTOMS MAY BE :A LUMP IN THE NECKNOSEBLEEDSMUFFLED HEARINGRINGING IN THE EAR HEADACHEDOUBLE VISION

∞ COLDS/

SINUSITIS

Number of patients

27

9

9

6

18

4

Neck Mass

Symptoms / Sign

Neck Mass + Epistaxis

Others

Epistaxis

Neck Mass + Ear Fullness

/ Tinitus

Neck Mass + Epistaxis + Ear Disorder

Others = Diplopi / Cephalgi

NASOPHARYNX

POST OR RHINOSCOPY

POST OR RHINOSCOPY + CATHETER

NASOENDOSCOPY/NASOPHARYNGOSCOPY

LOCAL ANESTHETIA

GENERAL ANESTHETIC (SPESIFIC CIRCUMTANCES)

THE GOLD STANDART

WHO : Type I - Squamous cell carcinoma

Type II - Non keratinizing carcinoma

Type III - Undifferentiated carcinoma

• CT Scan (MRI)

• USG – distant metast

• Bone scans – distant metast

• EBV serology

IgA anti VCA (viral carsid antigen)

IgA anti EA (early antigen)

IgA anti EBNA (nuclear antigen)

Serological screening in endemic region

Conjunction with nasoendoscopy & radiological evaluation

Pretreatment staging

1. Nasoparyngeal

tumor biopsy

2. Chest radiograph

3. Plane radiograph

of skull and

nasopharynx

4. CT scan of

nasopharynx

5. Fibreoptic

endoscopic

examination

6. Clinical assesment

for level and size

of cervical lymph

nodal metastases

(if any)

7. Liver ultrasound

8. Bone 99m

Tc-scintigram

9. Fine needle

aspiration of

doubtful cervical

lymph nodes

No

distans

metastasi

s (M0)

Distant metastasis (M1)

Bulky cervical

N1-N3 (≥ 4

cm in

maximal

diameter)

Negative

cervical

nodes N0

Parapharyngeal boost

Local

residual

disease for

T1 or T2n

Pretreatmen

t bulky

parapharyng

eal disease

(T2p and

T3p)ERT*

Neoadjuvant

chemotherap

y

ICT ⁺

Palliative treatment

Non-bulky

cervical

nodes N1-

N3 (<4 cm in

maximal

diameter)

NPC Diagram

Stg I T1 N0 M0

T2 N0 M0

External Rad.6000cgy(30x)

Brachyterapy4-6 x 300cgy+

Radiosentisizer- Cisplatin 20-25- Giemsar 200

Stg IIB T3 N0 M0

T1 N1 M0ChemoradStg III

Rad.ext 6000BrachyTx 4-6x300

Cisplatin 40mg/m2/mggDocetaxel 25mg/m2/mggPaclitaxel 90mg/m2/mgg

Stg IV T4 N0 M0 ChemoradRad.ext 6600 - 7000

Cisplatin 40mg/m2/mggDocetaxel 25mg/m2/mggPaclitaxel 90mg/m2/mgg

Stg IV T1-3 N3 M0 NeoAdjuvan

Taxotere 20-25mg/m2/mgg

Cisplatin 40mg/m2/mgg

5 FU 1000mg/m2/mgg

T4 N3 M0

every 3 weeks 4 cyclescontinue :

ChemoradExternal Rad. + BrachyTx

-Cisplatin 40mg/m2/mgg-5FU oral 100mg 1-2hour before

Stg IV T1-4 N3 M1 Full dose

Response Cisplatin + 5FU – 3 sesi

Response

Response continue until 6 cycles

Response 2nd line chemotx

2nd line : CarboplatinTaxan (docetaxel 75mg/m2/3mmg

Paclituxel 175.200mg/m2/3mmg)

Salvation Surgery

Reccurant local Hemimaxilectomy swing

Mid facial degloving

Transpalatal app

Regional lymphnodes : Neck dissection

DISTANT METASTASIS

FAILED OF CURED

TO RELIEVE SYMPTOMS & IMPROVE QUALITY

OF LIFE

TO LIVE LONGER & LIVE COMFORTABLY

NOT JUST MEAN PAINKILLERS & ANTI

SICKNESS DRUGS

CHEMOTHERAPY

RADIOTHERAPY

SURGICALCAN ALL BE USED

BENEFIT OF CHEMOTHERAPY

LOCOREGIONAL TUMOUR CONTROL

CONTROL OF PAIN

RESTORATION OF SWALLOWING & APPETITE

IMPROVEMENT OF WEIGHT LOSS & FATIGUE

INCREASED DISEASE – FREE SURVIVAL

PALLIATIVE RADIOTHERAPY

USEFUL FOR METASTASES IN BONE,BRAIN &

SKIN

RELIEVING BLEEDING

RELIEVING PRESSURE SYMPTOM SUCH AS PAIN

OR OBSTRUCTION CAUSEDTHE BULK OF

TUMOR

SURGERY FOR PALLIATION :

DEBULKING : LESION MUST BE RESECTABLE

MUST BE RECONSTRUCTIVE TO FUNCTION LEVEL

PATIENT MUST BE AGREE, FULL INFORMATION

LOSS OF FUNCTION

POTENTIAL MUTILATION/ COMPLICATION

CONTROL OF HEMORRHAGE

PAIN CONTROL :

INFRA TEMPORAL FOSSA : MANDIBULAR

NEURALGIA, TRISMUS, TEMPORAL PAIN

NEURALGIAS IN DISTRIBUTION OF N.X & XI

NUTRITIONAL PROBLEM :

DIFFICULTY IN MASTICATION : PAIN, DRY

MOUTH, XEROSTOMIA

POOR ORAL HYGIENE

PROGRESSIVE LOCAL DISEASE

CHRONIC NAUSEA

CHANGES IN TASTE

ASPIRATION

DYSPNEA :

UPPER AIRWAY OBSTRUCTION:

HUMIDIFIED AIR TO REDUCE STICKY

TRACHEOSTOMY

SUPERIOR VENA CAVA OBSTRUCTION :

RADIOTHERAPY

LUNG METASTASE : SYMPTOMATIC TREATMENT

PULMONARY EMBOLI

BRONCHOPNEUMONI

TX Primary tumor unable to be assessed

T0 No primary tumor detected

T1 Confined to nasopharynx

T2a Tumor extend to nasal cavity, oropharynx

T2b Tumor extend to parapharyngeal space

T3 Tumor involves sinuses, orbit, skull base, hypopharynx or bony erosion

T4 Intracranial involvement, cranial nerve palsy

N0 No nodal involvement

N1 Nodes confined to ipsilateral neck, not greater than 3cm

N2 Ipsilateral node greater than 3cm but not greater than 6cm, bilateral nodes or contra lateral nodes

N3 Ipsilateral node greater than 6cm, supraclavicular nodes

M0 No distant metastasis

M1 Distant metastasis (includes mediastinal nodes)

Stage I T1 N0 M0

Stage II T2 N0 M0, T1 N1 M0, T2 N0M0

Stage III T3 N0 M0, T3 N1 M0, T1 N2 M0, T2 N2 M0

Stage IV T4 N0 M0, any T N3 M0,any T any N M1

Sumber : Instalasi Rekam Medis & Admission RSKD

No. DIAGNOSA ICD-X JUMLAH

1 BREAST C501 – C509 1637

2 CERVIX UTERI C530 – C539 700

3 OVARY C569 221

4 COLORECTUM C180 – C209 147

5 THYROID GLAND C739 138

6 LYMPH NODES C770 – C779 127

7 LEUKIMIA C420 – C424 119

8 PHARYNX C100 – C148 114

9 BRONCHUS & LUNG C340 – C349 112

10 CORPUS UTERI C540 – C549 100

10 BESAR KANKER TERSERING RUMAH SAKIT

“DHARMAIS” RAWAT JALAN (KASUS BARU) FEMALE

TAHUN 2005 - 2007

History and Examination

Normal looking

NP

Other

Tretment

Repeat

Biopsy

(LA/GA

)

Treatment

Other

DiagnosisDiagnosis

Uncertain

NPC

Proven

Biopsy NP

(LA)

Obvious Tumour

Biopsy

NP

(GA)

Radiologicall

y Suspicious

Unexplaine

d SOM

Suspicious

Neck Node

Persistentl

y Raised

IgA

Clinically

SuspiciousClinicaly

not

Suspicious

FNA

Cytology

Biopsy NP (GA) +/-

PanendoscopyOther Treatment

Squamous Cell or

Undifferentiared Carcinoma

Other

Diagnosis

Treatment

SOM = Serous otitis

media LA = Local

anaesthesia

GA = General

anaesthesia

NP = Nasopharynx

FNA = Fine-needle

aspiration

Stage classification

Ho’s (1978) Huang’s (1985)

T-Stage T1 NP Only T2 T2n Nasal fossa

T20 Oropharynx T2p Parapharyngeal region

T3 T3a Bone involvement below the base of the skull including floor of the sphenoid sinus

T3b Base of the skull T3c Cranial nerve(s) palsy T3d Orbits, larygopharynx (hypopharynx) or

infratemporal fossa

T Ts Primary soft tissue tumour only Tb basal skull destruction evident on radiographs Tn cranical nerve involvement Tc direct invasion to the adjecent brain evident

on CT scan (newly added item)

N-Stage N0 No nodes N1 Node(s) above skin crease at laryngeal

cartilageN2 Node(s) below skin crease but above

supraclavicular fossa N3 Supraclavicular node(s)

N Cervival lymph node N0 No palpable node N1 Unilateral (ipsilateral) small lymph nodes with

total diameter ≤ 5cm N2 Bilateral (contralateral) large lymph nodes

with total diameter > 5cm

M-Stage N0 Nb distant metastase M1 Distant metastaces

M Distant metastasis evident clinically M M0 No distant metastasis

M1 Clinically evident distant metastasis beyond cervical lymph node involvement

Stage Grouping

I TIN0 II T2 and/or N1 III T3 and/or N2IV N3 (any T) V M1

I TsN0M0 (prymary soft tissue only) II TsN1M0 or TbN0-1M0 (any condition with N1

and /or Tb) III TsN2M0 or TbN2M0 or TnN0-2M0 or TcN0-2M0

or TcN0-2M0 or TbnN0-2M0 or TbcN0-2M0 or TbncN0-2M0 (any condition involving N2 or Tn or TC or more combinations)

IV M1 (any of the above conditions with distant metastasis evident clinically)

Tabel. 3 Stage NPC

Stage classification

Changsha (1983) UICC (1987)

T-Stage T0 Subclinical T1 One wall or corner betwen 2 walls T2 ≥ 2 walls T3 Nasal fossa, oropharynx (including

parapharyngeal region) T4 ≥ 2 features of T3

T1 One wall NP T2 ≥ 2 walls NP T3 Nasal cavity, oropharynx (including

parapharyngeal region) T4 Skull base and /or cranial nerve

N-Stage N0 No nodes N1 Mobile and /or < 3 cm above supraclavicular

fossa N2 Fixed and/or (3-8) cm and above

supraclavicular fossa N3 Supraclavicular and /or > 8cm

N0 No node N1 Single homolateral node ≤ 3cm N2 N2a single homolateral node

> 3 - ≤ 6cm N2c bilateral or contralateral nodes ≤ 6cm

N3 > 6cm node(s)

M-Stage N0 No metastase M1 Distant metastaces

N0 No metastase M1 Distant metastaces

Stage Grouping

I TIN0 II T2N0; T0-2N1 III T3N0-1; T0-3N2IV T4N0-2; T0-4N3; M1

I TIN0 II T2N0III T3N0; T1-3N1 IV T4N0-1

N2-3 (any T); M1 (any T, any N)

Tabel. 3 Stage NPC

Anamnesis :

1. GEJALA HIDUNG :

a. Ingus campur darah (sedikit) / epistaksis ringan

unilateral

b. Sumbatan hidung unilateralbilateral

c. Post nasal drip

2. GEJALA TELINGA :

a. Rasa penuh/gangguan pendengaran unilateral

menetap

b. Tinitus unilateral

c. Otalgia/Otorea unilateral

3. GEJALA LEHER :

a. Benjolan leher unilateral bilateral

4. GEJALA MATA & SYARAF :

a. Sakit kepala

b. Diplopia (N3&6)

c. Ptosis (N4)

d. Trismus (N5)

e. Parese lidah (N12)

f. Parese Saraf Otak lain

Alur Diagnosis

Penentuan

Stadium

PF Penunjang

Pemeriksaan

Pemeriksaan lengkap THT-Kepala Leher:

1. Pemeriksaan hidung & nasofaring (THT lengkap) :

a. Rinoskopi anterior & posterior

b. Nasoendoskopi/nasolaringoskopi kaku/fleksibel

2. Perhatian pada :

a. OMS, Lesi Intrakranial, Limfadenopati Servikal

3. Pemeriksaan kelenjar leher:

lokasi, ukuran, kekenyalan, mobilitas4. Pemeriksaan lesi intrakranial:

a. Gangguan gerak bola mata (Diplopia N3&6)b. Ptosis (N4)c. Trismus (N5)d. Parese lidah (N12)

AnamnesisPenunjang

Penentuan

Stadium

Alur Diagnosis

Pemeriksaan Penunjang

1. CT scan/MRI

2. Serologi:

a) IgA VCA

b) IgA EA

c) EBNA total

Tentukan Stadium :

1. Ro Toraks

2. Laboratorium:

fungsi hati, ginjal, kimia drh

3. Konsul saraf dan mata

4. USG abdm atas & bone scan

5. Audiogram

Anamnesis

& PF

Alur Diagnosis

Anamnesis :

KGB leher >>

Keluhan

hidung,telinga,

sakit kepala

kronis

PF

PENEMUAN

Kls curiga :

CT scan NF

Serologi

CT scan NF

Curiga (+)

OM Serosa

e.c. tidak

jelas

Pe IgA

KGB leher

curiga

Biopsi

NF

FNABKSS/Ca

undiff

KNF (+)

KNF(-)

ulangi

3x/eksplorasi

(-)bukan

KNF

GAMBARAN

KLINIS

WORK UP

KNF (+)

Hasil PA WHO

Pemeriksaan 3 hr

STAGING

Staging persiapan

terapi

Stadium I

Stadium II

Stadium III

Stadium IV

PENEMUAN

STAGING TERAPI FOLLOW UP

Stadium IT1 N0 M0

Stadium IIAT2a N0 M0

Radiasi ekst 60 Gy + brakiterapi 4-6 x

3 Gy

PR : cisplatin + 5 FU

TR : cisplatin + 5FU + Docetaxel +

atau Carboplatin + Docetaxel +

gemcitabin

Rekurensi : < 1 thn Kemoterapi

> 1 thn Kemoradiasi

Thn I : setiap 1-2 bln

Thn II: setiap 2-3 bln

Thn III: setiap 4-6 bln

Thn IV & V : setiap 12 bln

Setiap follow up:

Anamnesis & PF

Nasofaringoskopi

Setiap 6 bln ( th.I & II)

Lab, Rö toraks, CT scan NF

Seromarker, Bonescan

USG abdomen

Biopsi ulang stlh 6 bln/thn 1

Rehabilitasi

minggu ke-2 stlh radiasi

Radiasi ekst 60 Gy + brakiterapi 4-6 x

3 Gy

PR : cisplatin + 5 FU

TR : cisplatin + 5FU + Docetaxel atau

Carboplatin + Docetaxel +

gemcitabin

Rekurensi : < 1 thn Kemoterapi

> 1 thn Kemoradiasi

Stadium IIBT1 N1 M0

T2a N1 M0

T2b N0-1 M0

Radiasi ekst 60 Gy + brakiterapi 4-6 x

3 Gy + kemoterapi

PR : cisplatin + 5 FU

TR : cisplatin + 5 FU + Docetaxel atau

Carboplatin + Docetaxel +

gemcitabin

Rekurensi : < 1 thn Kemoterapi

> 1 thn Kemoradiasi

Thn I : setiap 1-2 bln

Thn II: setiap 2-3 bln

Thn III: setiap 4-6 bln

Thn IV & V : setiap 12 bln

Setiap follow up:

Anamnesis & PF

Nasofaringoskopi

Setiap 6 bln ( thn.I & II )

Lab, Rö toraks, CT scan NF

Seromarker, Bonescan

USG abdomen

Biopsi ulang stlh 6 bln/thn 1

Rehabilitasi

minggu ke-2 stlh radiasi

Stadium IIIT1 N2 M0

T2a N2 M0

T2b N2 M0

T3 N0-2M0

Neoadjuvan + kemoradiasi

Reseksi KGB bl primer bersih

Bila T3 CT scan u/ radiasi

Bila N2 CT scan u/ booster KGB

5-10 x 2 Gy

STAGING TERAPI FOLLOW UP

STAGING

Stadium IIIT1 N2 M0

T2a N2 M0

T2b N2 M0

T3 N0-2M0

Stadium IVaT4 N0-3 M0

T berapa

pun, N3, M0

Stadium IVbT berapa pun,

N berapa

pun, M1

Thn I : setiap 1-2 bln

Thn II: setiap 2-3 bln

Thn III: setiap 4-6 bln

Thn IV & V : setiap 12 bln

Setiap follow up:

Anamnesis & PF

Nasofaringoskopi

Setiap 6 bln ( th. I & II )

Lab, Rö toraks, CT scan NF

Seromarker, Bonescan

USG abdomen

Biopsi ulang stlh 6 bln/thn 1

Rehabilitasi

minggu ke-2 stlh radiasi

TERAPI FOLLOW UP

Neoadjuvan + radiasi

Reseksi KGB bl primer bersih

Bila T3 CT scan u/ radiasi

Bila N2 CT scan u/ booster KGB 5-

10 x 2 Gy

Neoadjuvan + radiasi 60 Gy

Bila penekanan saraf mata (+)

Radioterapi cito

Neoadjuvan + radiasi paliatif

40-60 Gy

Untuk lokasi tumor pd weight bearing

boneradioterapi dahulu