This document discusses nasopharyngeal carcinoma (NPC), including: 1) NPC is the 4th most common cancer and number 1 head and neck cancer in Indonesia, with high incidence rates in Southeast Asia. 2) Risk factors for NPC include Epstein-Barr virus, genetic factors, diet, environment, and ethnicity. 3) Symptoms of early NPC are non-specific but advanced NPC involves cranial nerves and lymph node metastasis. 4) Treatment protocols at RS Sardjito hospital for advanced NPC include chemotherapy and radiotherapy (Protocol I), or with additional brachytherapy (Protocol II), with Protocol II showing improved survival rates.

1. dr. S R Indrasari, M.Kes., Sp.THT-KL(K)
Yogyakarta, 15 Juli
1987 -1995
1999 - 2003
1999 – 2004
2009 - .....
2009 – 2012
Kedokteran Umum, UNS
S2 Kedokteran Klinis, UGM
Spesialis THT-KL, UGM
Program Doktor FK.UGM
Konsultan Onkologi Bedah
Kepala Leher
1996-1999 : Dokter PTT Puskesmas , Klaten
1999
: Staff di Sub Bag Onkologi-Bedah Kepala Leher
IK.THT-KL FK UGM / RS. Dr. Sardjito
2006-2012 : Kodik Profesi Bag. IK.THT-KL
2013 : Sekretaris Program Studi PPDS IK.THT-KL
Jl. Bogowonto 108B Klaten
srindrasari@invosa.com ; srindrasari123@gmail.com

2. KARSINOMA NASOFARINGS (KNF)
NASOPHARYNGEAL CARCINOMA (NPC)
SUB BAGIAN ONKOLOGI BAGIAN IK. THT-KL
FAKULTAS KEDOKTERAN UGM / RS DR SARDJITO
YOGYAKARTA

3. Why Cancer ?
The burden of Cancer

4. MENGAPA KANKER ?
Penyebab utama kematian tahun 2001
Percentage of Total Deaths, US
31,0
Heart Diseases
Cancer
23,2
6,8
Cerebrovascular Diseases
4,8
Chronic Obstructive Lung Diseases
Accidents
4,2
Pneumonia & Influenza
3,9
Diabetes Mellitus
2,8
Suicide
1,3
Nephritis
1,1
Cirrhosis of the Liver
1,1
Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001:51;15-36.

5. 10 besar keganasan di dunia
Rank
Males
Females
Both Sexes
1
Lung
Breast
Lung
2
3
4
5
6
7
8
9
10
Stomach
Colon/rectum
Prostate
Liver
Mouth/pharynx
Esophagus
Bladder
Leukemia
NHL*
Colon/rectum
Cervix uteri
Stomach
Lung
Ovary
Corpus uteri
Liver
Mouth/pharynx
Esophagus
Stomach
Breast
Colon/rectum
Liver
Prostate
Cervix uteri
Mouth/pharynx
Esophagus
Bladder
*Non-Hodgkin’s lymphoma.
Total New
Cases
1,037,000
798,000
796,000
783,000
437,000
396,000
371,000
363,000
316,000
261,000
Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:39.

6. Why NPC ?
The burden of NPC

7. 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

8. PREVALENSI / INSIDENS
CINA SELATAN
30-50 kasus*
INDONESIA
(NATIVE)
4.7/6.7 kasus*
MALAYSIA
MALAY 1.1 kasus
CHINESE 40.1(14.9) kasus
SINGAPURA
CANTONESE 18.2/7.5
HOKKIEN 12.3/3.7
MALAY 4.3/1.5
*per 100.000/tahun
THAILAND
4.1/1.6
HONGKONG
28.5/11.2

10. Di RS Sardjito, Yogyakarta 2007-2009
Grafik Klasifikasi Tumor Kepala Leher
Berdasarkan Letak Tumor Primer Tahun 2007-2009
Tumor Telinga
2%
Tumor Laring
8%
Tumor Orofaring
15%
Tumor Nasofaring
50%
Tumor Sinonasal
25%
588 kasus

11. Grafik Klasifikasi Tumor Kepala Leher
Berdasarkan Jenis Kelamin Tahun 2007-2009
Laki-laki
Perempuan
191
93
76
67
49
35
40
2
Tumor Nasofaring
Tumor Sinonasal
Tumor Orofaring
Tumor Laring
8
6
Carcinoma Auricula

12. Grafik Tumor Kepala Leher Berdasarkan Umur
Tahun 2007-2009
107
58
51
40
Tumor Nasofaring
Tumor Sinonasal
20
18
Tumor Orofaring
Tumor Laring
3
Tumor Telinga
4
78-87
1
68-77
0
58-67
38-47
1
48-57
3
28-37
2
18-27
2
11
4
77-89
5
25-37
12-24
73-83
51-61
3
64-76
11
40-50
1
29-39
7-17
81-91
70-80
59-69
48-58
37-47
26-36
2
5
18-28
3
15-25
4-14
75-84
65-74
55-64
45-54
6
35-44
15-24
5-14
2
25-34
7
13
11
24
51-63
20
17
38-50
27
62-72
30
29
24
2

13. What is NPC ?
Definition
Cause & Risk factors
Symptoms & signs

15. Apa yg disebut dg KNF ?
Stad awal : Tdk spesifik (tinnitus, blood stained
discharge)
Stad lanjut: metast, cranial nerves involvements
Advanced stage

16. ETIOLOGI & FAKTOR RISIKO
Epstein-Barr virus
(“smoke”)
(Immuno)genetic
factors
Diet
NPC
Environmental
factors
Gender
Ethnicity
Herbal
Drugs/
oils

17. PATOLOGI ANATOMI
WHO; 1978:
Type 1: Keratinizing SCC
Type 2: Non Keratinizing SCC
Type 3: Undifferentiated

18. GEJALA & TANDA ---ANATOMI

19. Cefalgia
Rasa penuh di telinga
Tinnitus , Otalgia
Diplopia
Ophtalmoplegia
Lagophtalmus
Tuli konduktif unilateral
Perforasi , OME
GEJALA
KLINIS
Obstruksi
hidung Sekret +
darah Anosmia
Blood stained
discharge
PND
Limfadenopati
colli
Trismus Disfagia
Gangguan pengecap
Atrofi palatum mole
Parese parsial lidah

20. ALIRAN KGB LEHER

21. DIAGNOSIS
 Anamnesis
 Pemeriksaan Fisik THT
 Rinoskopi Anterior &
Posterior
 Endoskopi: Rigid/ Fiber
nasopharyngolaryngoscopy
 BIOPSI

22. 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

23. 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 tissues
T2a: 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

24. T1
Tumor terbatas pada nasofarings, menyebabkan
penebalan / asimetri mukosa

25. T2a
Perluasan ke orofarings atau kavum nasi

26. T2b
Keterlibatan spasium para farings

27. T3
Keterlibatan sinus paranasal atau tulang

28. T4
Intrakranial, hipofarings, orbita

29. 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.]

30. AJCC Stage Grouping
Distant Metastasis
MX
Distant metastasis cannot be assessed
Stage 0
Tis, N0, M0
M0
No distant metastasis
Stage I
T1, N0, M0
M1
Distant metastasis
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

31. Survival Rates
Stage
Relative Survival Rates
5-year
10-year
I
78%
62%
II
64%
52%
III
60%
46%
IV
47%
37%

32. PENATALAKSANAAN
Stadium I & II
•Radioterapi
Stadium III, IVa & b
•Kemoradiasi
Stadium IVc
•Kemoterapi

33. N
P
C
THT
Pemeriksaan klinis
Endoskopi
Biopsi nasofarings
Radiologi
CT scan kepala coronal extended
Foto thorak
USG upper abd
DIAGNOSIS
THT
Catat hasil PA
Ambil darah utk serologi
Brushing nasofarings
Staging: Stad. awal / Stad.lanjut
M
A
N
A
G
E
M
E
N
T
Stad.awal
Stad.lanjut
TERAPI
Radioterapi
Radiasi eksternal 70 Gy
+
Brachitherapy
THT
Pemeriksaan klinis
& endoskopi
THT
Endoskopi
Biopsi nasofarings
CT scan kepala coronal extended
Ambil darah utk serologi
Brushing nasofarings
THT
Endoskopi
Swab nasofarings / kp. biopsi
Brushing nasofarings
Ambil darah utk serologi
Tulip
Kemoterapi Cisplatin & 5FU
3 siklus
EVALUASI
Tulip
Pemeriksaan klinis
Ambil darah utk serologi
Radioterapi
Pemeriksaan klinis
Ambil darah utk serologi
FOLLOW UP

34. Potentially DO
Diagnosis
Early
stage
Advanced
stage
Radiotherapy
Chemotherapy
2
weeks
12 weeks
Radiotherapy
12
weeks
Response Assessment
Follow-up

35. KNF di RS Sardjito
Kasus baru bertambah (1992= 48 ; 1993 = 59 ; 1994 = 63 )
Penderita KNF di THT (Mei ‘03 - Nov ’06) = 446 penderita
Th 2007=103, th 2008=73, th 2009=108
Laki : Wanita = 297:149 (2:1)
Management: Protocol I ( 4 cycles CT + ERT)
Protocol II ( 3 cycles CT + ERT + BT)
Protocol III – Concurrent Chemoradiation
Area
Age Proportion
50.00%
5%
4%
5%
40.00%
Luar Jawa
Jawa Timur
Jawa Barat
Jawa Tengah
86%
30.00%
Series1
20.00%
10.00%
0.00%
10-30 y.o
31-50 y.o
51-70 y.o
>70 y.o

36. Sardjito’s standard therapy protocols
(Advanced stage)
Protocol I:
Chemotherapy :
Neoadjuvant.
CisPlatinum : 80 mgr/m2 body surface
5 Fu : 800 mgr/m2 body surface
4 cycles
Radiotherapy :
Cobalt 60
6600 – 7000 cGy

37. Protocol II:
Chemotherapy :
–Neoadjuvant.
–CisPlatinum : 100 mgr/m2 body
surface
–5 Fu : 1000 mgr/m2 body surface
3 cycles.
Radiotherapy :
–Cobalt 60
6600-7000 Cgy
Brachytherapy:
–1200 cGy/3 days
Protocol III:
Concurrent chemoradiotherapy

38. Protocol I vs Protocol II
Survival analysis
log rank=8,60; p=0,003
1.0
.9
.8
.7
terapi
LMP 2
.6
.5
Brachy (+)
< 2.7=5:5
.4
Cencored 25
< 2.7-censored
.3
=24
.2
Brachy (-):14
>= 2.7=14
Censored
12
.1
>= 2.7-censored
0.0
=13
0
10
20
30
40
50
60
70
80
Follow-up (bulan)
n=56, stad. III dan IV non metastasis

39. Protocol III
n=23, Stad. III & IV non metastasis
Overall Survival
1.0
Overal Survival
.8
.6
.4
.2
Survival Function
0.0
Censored
0
5
10
15
20
25
30
Time (months)
Overall survival is 86.95% median follow up of 12 month

40. 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

41. Principle of Photodynamic therapy (PDT)
administration
therapy
96 h
12
9
photosensitizer
3
6
photosensitizer + light + O2
laser
Non thermal
illumination
of target
volume
cell death

42. PDT
Survival analysis
n=25, rekurens/residu
1.0
.9
2005-2008
.8
Cum Survival
.7
.6
.5
.4
.3
.2
Survival Function
.1
0.0
Censored
0
5
10
15
20
25
30
35
40
Follow Up (Months)
Event: Died and recurrence
42

43. PDT, 2011 n=36
5 –year overall survival: 65.5

44.  Advanced stage diseases need longer treatment
time  potentially DO !
 In advanced diseases, treatment results are poor
Important !
Diagnosis in early stage
NO DELAY !!

45. Delay in the diagnosis & treatment of NPC:
Patient delay
Profesional delay:
Gagal mengidentifikasi gejala & tanda kecurigaan kanker
System delay:
Waktu yg diperlukan utk mendpt pelayanan kesehatan primer / RS
Waktu yg diperlukan utk referal ke pelayanan tertier

46. EARLY DIAGNOSIS
AWARENESS
(of symptoms and
signs)

47. Stadium dini
Stadium lanjut

48. KNF
vs
Clinical Symptom

51. Cefalgia
Rasa penuh di telinga
Tinnitus Otalgia
Diplopia
Ophtalmoplegia
Lagophtalmus
Tuli konduktif
unilateral Perforasi
OME
GEJALA
KLINIS
Obstruksi
hidung Sekret +
darah Anosmia
Blood stained
discharge
PND
Limfadenopati
collie
Trismus Disfagia
Gangguan pengecap
Atrofi palatum mole
Parese parsial lidah

52. Peran Serologi EBV pd KNF ?
Serology
Indonesia Singapore
Hongkong
IgA anti VCA
Sensitivity %
Specificity %
73,33% 95,00%
83,33% 80-90%
93,00%
IgA anti EA
Sensitivity %
Specificity%
98,67%
63,67%
76,00%
>95%
Skreening faktor risiko, bukan diagnosis !!!

53. Early diagnosis- “difficult”
Tumor
: non specific symptoms
sub mucosal
Medical expert : low index of suspiciousness
technical exam of nasopharynx

54. 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.

55. Skreening penderita dengan risiko
Pd umumnya tdk berhasil krn:
 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
Schantz SP, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;797-860.

56. UPAYA PENCEGAHAN
Jaga 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

57. 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