1987 -1995 Kedokteran Umum, UNS1999 - 2003 S2 Kedokteran Klinis, UGM1999 – 2004 Spesialis THT-KL, UGM2009 - ..... Program Doktor FK.UGM2009 – 2012 Konsultan Onkologi Bedah Kepala Leher

1996-1999 : Dokter PTT Puskesmas , Klaten1999 : Staff di Sub Bag Onkologi-Bedah Kepala Leher IK.THT-KL FK UGM / RS. Dr. Sardjito 2006-2012 : Kodik Profesi Bag. IK.THT-KL2013 - : Sekretaris Program Studi PPDS IK.THT-KL

dr. S R Indrasari, M.Kes., Sp.THT-KL(K)Yogyakarta, 15 Juli

Jl. Bogowonto 108B Klatensrindrasari@invosa.com ; srindrasari123@gmail.com

KARSINOMA NASOFARINGS (KNF)NASOPHARYNGEAL CARCINOMA (NPC)

SUB BAGIAN ONKOLOGI BAGIAN IK. THT-KL FAKULTAS KEDOKTERAN UGM / RS DR SARDJITO

YOGYAKARTA

Why Cancer ?

The burden of Cancer

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001:51;15-36.

Penyebab utama kematian tahun 2001

MENGAPA KANKER ?

1,1

1,1

1,3

2,8

3,9

4,2

4,8

6,8

23,2

31,0

Percentage of Total Deaths, US

Heart Diseases

Cancer

Cerebrovascular Diseases

Chronic Obstructive Lung Diseases

Accidents

Pneumonia & Influenza

Diabetes Mellitus

Suicide

Nephritis

Cirrhosis of the Liver

10 besar keganasan di dunia

1 Lung Breast Lung 1,037,000

2 Stomach Colon/rectum Stomach 798,000

3 Colon/rectum Cervix uteri Breast 796,000

4 Prostate Stomach Colon/rectum 783,000

5 Liver Lung Liver 437,000

6 Mouth/pharynx Ovary Prostate 396,000

7 Esophagus Corpus uteri Cervix uteri 371,000

8 Bladder Liver Mouth/pharynx 363,000

9 Leukemia Mouth/pharynx Esophagus 316,000

10 NHL* Esophagus Bladder 261,000

Total NewRank Males Females Both Sexes Cases

*Non-Hodgkin’s lymphoma. Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:39.

Why NPC ?

The burden of NPC

Mengapa Karsinoma nasofarings ?

Keganasan no. 4 di seluruh badan No.1 dari keganasan di Kepala-Leher Insidensi cukup tinggi di Indonesia Mengenai usia produktif Penderita datang pd stadium lanjut Mortalitas tinggi

PREVALENSI / INSIDENS

CINA SELATAN

30-50 kasus*

INDONESIA (NATIVE)4.7/6.7 kasus*

MALAYSIAMALAY 1.1 kasusCHINESE 40.1(14.9) kasus SINGAPURA

CANTONESE 18.2/7.5

HOKKIEN 12.3/3.7MALAY 4.3/1.5

THAILAND4.1/1.6

HONGKONG28.5/11.2

*per 100.000/tahun

Di RS Sardjito, Yogyakarta 2007-2009

588 kasus

Tumor Nasofaring50%

Tumor Sinonasal25%

Tumor Orofaring15%

Tumor Laring7%

Tumor Telinga2%

Grafik Klasifikasi Tumor Kepala Leher Berdasarkan Letak Tumor Primer Tahun 2007-2009

Tumor Nasofaring Tumor Sinonasal Tumor Orofaring Tumor Laring Carcinoma Auricula

191

76

49

40

8

93

67

35

26

Grafik Klasifikasi Tumor Kepala Leher Berdasarkan Jenis Kelamin Tahun 2007-2009

Laki-laki Perempuan

5-14

15-24

25-34

35-44

45-54

55-64

65-74

75-84

4-14

15-25

26-36

37-47

48-58

59-69

70-80

81-91

7-17

18-28

29-39

40-50

51-61

62-72

73-83

12-24

25-37

38-50

51-63

64-76

77-89

18-27

28-37

38-47

48-57

58-67

68-77

78-87

Tumor Nasofaring Tumor Sinonasal Tumor Orofaring Tumor Laring Tumor Telinga

27

24

58

107

51

29

6 311

17

30

40

27

13

2 15

11

2024

20

3 2 5 4

1811

2 3 1 0 1 3 4 2

Grafik Tumor Kepala Leher Berdasarkan Umur Tahun 2007-2009

What is NPC ?

DefinitionCause & Risk factors

Symptoms & signs

Apa yg disebut dg KNF ?

Advanced stage

Stad awal : Tdk spesifik (tinnitus, blood stained

discharge)

Stad lanjut: metast, cranial nerves involvements

ETIOLOGI & FAKTOR RISIKO

Epstein-Barr virus

NPCEthnicity

Diet(“smoke”)

(Immuno)genetic factors

Gender

Herbal Drugs/

oils

Environmentalfactors

PATOLOGI ANATOMI

WHO; 1978:Type 1: Keratinizing SCCType 2: Non Keratinizing SCCType 3: Undifferentiated

GEJALA & TANDA ---ANATOMI

GEJALA KLINIS

Cefalgia

Diplopia Ophtalmoplegia Lagophtalmus

Obstruksi hidung Sekret + darah Anosmia Blood

stained discharge PND Trismus Disfagia Gangguan

pengecap Atrofi palatum mole Parese parsial lidah

Limfadenopati colli

Rasa penuh di telinga Tinnitus , Otalgia

Tuli konduktif unilateral Perforasi , OME

AWAL LANJUT

ALIRAN KGB LEHER

DIAGNOSIS

Anamnesis Pemeriksaan Fisik THT Rinoskopi Anterior &

Posterior Endoskopi: Rigid/ Fiber nasopharyngolaryngoscopy

BIOPSI

Pemeriksaan Penunjang

CT Scan: * Perluasan tumor * Superior: destruksi tulang, densitas jaringan lunak

MRI: * Resolusi tinggi * Superior: residual/reccurent, inflamasi,

fibrosis * Keterlibatan sum tul,perineural, intracranial

Penentuan Stadium Tumor Primary Tumor

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor confined to the nasopharynx

T2 Tumor extends to soft tissuesT2a: Tumor extends to the oropharynx and/or nasal cavity without parapharyngeal extension* T2b: Any tumor with parapharyngeal extension*

T3 Tumor invades bony structures and/or paranasal sinuses

T4 Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space

T1Tumor terbatas pada nasofarings, menyebabkan

penebalan / asimetri mukosa

T2aPerluasan ke orofarings atau kavum nasi

T2bKeterlibatan spasium para farings

T3Keterlibatan sinus paranasal atau tulang

T4Intrakranial, hipofarings, orbita

Penentuan Stadium Tumor Lymph Node

Nx Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Unilateral metastasis in lymph node(s), not more than 6 cm in greatest dimension, above the supraclavicular fossa*

N2 Bilateral metastasis in lymph node(s), not more than 6 cm in greatest dimension, above the supraclavicular fossa*

N3 Metastasis in a lymph node(s)* larger than 6 cm and/or to supraclavicular fossa N3a: Larger than 6 cm N3b: Extension to the supraclavicular fossa**

* [Note: Midline nodes are considered ipsilateral nodes.]** [Note: Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described in the Ho-stage classification for nasopharyngeal cancer. It is defined by three points: (1) the superior margin of the sternal end of the clavicle; (2) the superior margin of the lateral end of the clavicle; and, (3) the point where the neck meets the shoulder. Note that this would include caudal portions of Levels IV and V. All cases with lymph nodes (whole or part) in the fossa are considered N3b.]

Penentuan Stadium Tumor Distant Metastasis

MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis

AJCC Stage Grouping

Stage 0 Tis, N0, M0

Stage I T1, N0, M0

Stage IIA T2a, N0, M0

Stage IIB T1, N1, M0 T2, N1, M0 T2a, N1, M0 T2b, N0, M0 T2b, N1, M0

Stage III T1, N2, M0 T2a, N2, M0 T2b, N2, M0 T3, N0, M0 T3, N1, M0 T3, N2, M0

Stage IV A T4, N0, M0 T4, N1, M0 T4, N2, M0

Stage IV B Any T, N3, M0

Stage IV C Any T, any N, M1

Survival RatesStage Relative Survival Rates

5-year 10-year

I 78% 62%

II 64% 52%

III 60% 46%

IV 47% 37%

PENATALAKSANAAN•Radioterapi

Stadium I & II

•Kemoradiasi

Stadium III, IVa & b

•Kemoterapi

Stadium IVc

Stad.awal

RadiologiCT scan kepala coronal

extendedFoto thorak

USG upper abd

THTPemeriksaan klinis

EndoskopiBiopsi nasofarings

Stad.lanjut

THTCatat hasil PA

Ambil darah utk serologiBrushing nasofarings

Staging: Stad. awal / Stad.lanjut

RadioterapiRadiasi eksternal 70 Gy

+Brachitherapy

TulipKemoterapi Cisplatin &

5FU 3 siklus

THTPemeriksaan klinis

& endoskopi

THTEndoskopi

Biopsi nasofaringsCT scan kepala coronal extended

Ambil darah utk serologiBrushing nasofarings

TulipPemeriksaan klinis

Ambil darah utk serologi

THTEndoskopi

Swab nasofarings / kp. biopsiBrushing nasofarings

Ambil darah utk serologi

RadioterapiPemeriksaan klinis

Ambil darah utk serologi

DIAGNOSIS

TERAPI

EVALUASI

FOLLOW UP

NP

C

MANAGEMENT

2

weeks

Potentially DO Diagnosis

Early stage

Advanced stage

Radiotherapy Chemotherapy

Radiotherapy

Response Assessment

Follow-up

12 weeks

12 weeks

Kasus baru bertambah (1992= 48 ; 1993 = 59 ; 1994 = 63 ) Penderita KNF di THT (Mei ‘03 - Nov ’06) = 446 penderitaTh 2007=103, th 2008=73, th 2009=108Laki : Wanita = 297:149 (2:1)

Management: Protocol I ( 4 cycles CT + ERT) Protocol II ( 3 cycles CT + ERT + BT) Protocol III – Concurrent Chemoradiation

KNF di RS Sardjito

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

10-30 y.o 31-50 y.o 51-70 y.o >70 y.o

Age Proportion

Series1

Area

5% 4% 5%

86%

Luar Jawa

Jawa Timur

Jawa Barat

Jawa Tengah

Sardjito’s standard therapy protocols(Advanced stage)

Protocol I:

Chemotherapy :Neoadjuvant.CisPlatinum : 80 mgr/m2 body surface5 Fu : 800 mgr/m2 body surface 4 cycles

Radiotherapy :Cobalt 606600 – 7000 cGy

Protocol II:

Chemotherapy :–Neoadjuvant.–CisPlatinum : 100 mgr/m2 body

surface–5 Fu : 1000 mgr/m2 body surface

3 cycles.Radiotherapy :

–Cobalt 606600-7000 Cgy

Brachytherapy:–1200 cGy/3 days

Protocol III: Concurrent chemoradiotherapy

log rank=8,60; p=0,003

Follow-up (bulan)

80706050403020100

Ang

ka K

etah

anan

Hid

up1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

LMP 2

< 2.7=5

< 2.7-censored

=24

>= 2.7=14

>= 2.7-censored

=13

terapi

Brachy (+) :5

Brachy (-):14

Censored12

Cencored 25

n=56, stad. III dan IV non metastasis

Protocol I vs Protocol II

Survival analysis

Overall Survival

Time (months)

302520151050

Ove

ral S

urv

iva

l1.0

.8

.6

.4

.2

0.0

Survival Function

Censored

Overall survival is 86.95% median follow up of 12 month

n=23, Stad. III & IV non metastasis

Protocol III

Photodynamic Therapy in Recurrent or Residual Disease of Nasopharyngeal

Carcinoma After Standard Therapy in Sardjito Hospital Yogyakarta:

5-year Experience 

Sagung Rai Indrasari1, Camelia Herdini1, Bambang Hariwiyanto1, Tan IB2

administration

photosensitizer

laser

therapy

96 h

12

6

9 3

Non thermal illumination

of target volume

Principle of Photodynamic therapy (PDT)

photosensitizer + light + O2

cell death

42

Follow Up (Months)

4035302520151050

Cu

m S

urv

iva

l1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

Survival Function

Censored

Survival analysis

Event: Died and recurrence

n=25, rekurens/residu

2005-2008

PDT

5 –year overall survival: 65.5

PDT, 2011 n=36

Advanced stage diseases need longer treatment

time potentially DO !

In advanced diseases, treatment results are poor

Important !

Diagnosis in early stage

NO DELAY !!

Delay in the diagnosis & treatment of NPC:Patient delayProfesional delay:

Gagal mengidentifikasi gejala & tanda kecurigaan kanker

System delay:Waktu yg diperlukan utk mendpt pelayanan

kesehatan primer / RSWaktu yg diperlukan utk referal ke pelayanan

tertier

EARLY DIAGNOSISAWARENESS

(of symptoms and signs)

Stadium dini Stadium lanjut

KNFvs

Clinical Symptom

GEJALA KLINIS

Cefalgia

Diplopia Ophtalmoplegia Lagophtalmus

Obstruksi hidung Sekret + darah Anosmia Blood

stained discharge PND Trismus Disfagia Gangguan

pengecap Atrofi palatum mole Parese parsial lidah

Limfadenopati collie

Rasa penuh di telinga Tinnitus Otalgia

Tuli konduktif unilateral Perforasi OME

AWAL LANJUT

Peran Serologi EBV pd KNF ?

Serology

Indonesia

Singapore Hongkon

gIgA anti VCASensitivity %Specificity %

IgA anti EASensitivity %Specificity%

73,33% 83,33%

98,67% 63,67%

95,00%80-90%

>95%

93,00%

76,00%

Skreening faktor risiko, bukan diagnosis !!!

Early diagnosis- “difficult”

Tumor : non specific symptoms sub mucosal

Medical expert : low index of suspiciousness technical exam of nasopharynx

Deteksi dini pada penderita dg faktor risiko

Annual physical examination Special attention to upper aerodigestive

tract and neck with digital examination of oral cavity

Referral for evaluation of unexplained symptoms

Follow-up for patient with risk factor

Stupp R, Vokes EE. Current Cancer Therapeutics. 3rd ed. 1998;165.

Skreening penderita dengan risiko

Rendahnya tingkat partisipasi penderita berisiko dlm program skreening

Kondisi subklinis/tanpa gejala yg lama

Faktor waktu dan perlu edukasi di seting di pelayanan kesehatan primer

Pd umumnya tdk berhasil krn:

Schantz SP, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;797-860.

UPAYA PENCEGAHANJaga daya tahan tubuh

Cegah ISPA

Skrining pasien risiko tinggi

Kurangi makanan dengan pengawet

Kurangi pemakaian alat rumah tangga yang mengandung karsinogen

Hindari rokok (aktif + pasif), terutama di sekitar anak-anak

KEYPOINTS

•KNF kasus terbanyak di kepala leher

•Stadium dini prognosis lebih baik

•Skrining pasien risiko tinggi

•Rekuren terjadi < 1 tahun

•Follow up rutin: KEHARUSAN

•Program kewaspadaan

TERIMA KASIH