- 1. Nasopharyngeal Carcinoma N P C Mai Hai-Qiang ( ) Department
ofNPC Sun Yat-Sen University Cancer Center
2. WhatisNPC ? A very special type ofhead and neck cancer
Different from other malignancies of the upperaerodigestive tract
with regard to- Epidemiology, -Histology, -Clinical
presentationsand -Treatment strategies. 3. N P C --- Canton
Cancer
- 80% of patients with NPCare found in
- Southeast Asia, especially in southern
- China : GuangDong Province
Why is it called Canton Cancer 4. Epidemiology
- Evident geographic distribution difference
- Specific susceptible population
- Family cluster phenomenon
- Stable Incidence Rate and Men to Women Ratio: 2 ~ 3.8:1
- Differences between high and low incidence areas
5. Evident geographic distribution difference
- Highest incidence:GuangDong province.
- High incidences:Southern China
- GuangXi;HuNan; FuJian; JiangXi and Hainan.
- High incidences:S outheast Asia
- HongKong and Singapore Chinese
- ---Incidence Rate:30-50/100,000
6. Evident geographic distribution difference
- Outside of endemic areas:
- ---Incidence Rate: < 1 / 100,000
- are seen in north American Caucasians andEuropeans,
- Rare in Caucasians (white people)
7.
- -- EmigrantSouthernChineseinUSA,
- -- and the Eskimos in North America.
- Intermediate incidence North Africa: The Arabs.
- Incidence Rate: 5-10/100,000
Evident geographic distribution difference 8. ( ) 9. The High
and Relatively High NPC Incidence Areas The Arctic Ocean Pacific
Europe Asian Middle East Africa Oceania North America South America
Latin America 10. Specific susceptible population
11. Specific susceptible population North America Eskimos 12.
NPC incidence rates between Chinese immigrantsand other racial
residents in Los Angeles and Singapore 0.2 0.2 Vietnamese 0.5 0.5
Indian 2.0 6.5 Malayan 7.3 18.5 Chinese Singapore 0.3 0.2 Japanese
0.3 3.8 Philippine 2.8 9.8 Chinese 0.2 1.0 Ethiopian 0.2 0.5
CaucasianLos Angeles female maleincidencerates(/10 5 /year)
countryrace 13. NPCincidence Rate of Chinese in Sigapore(/10 5 )
4.7 14.1 FuJian 1.3 6.2 ShangHai 4.8 12.6 KeJia 6.2 18.3 ChaoZhou
11.0 29.1 Cantonese Incidence Rate of NPC MaleFemale language 14.
Death Rates in different dialectal populations in GuangDong
Province(10 5 ) 1.96 5.32 KeJia 2.89 6.18 ChaoZhou 4.32-5.84
12.08-15.96 Cantonese Death Rate of NPC MaleFemale language 15.
Family cluster phenomenon
- Family history of cancer:21.6%
- Family history of NPC:12.3%
- Statistics in GuangDong province
16.
- in Greenland were found to have a family history of cancer
among first-degree relatives
Family cluster phenomenon 17. FamousFamily maleNPC Breast Cancer
femaleNPC Male Liver Cancer 34.2%cancers 26.3% NPC 18. 4 Stable
Incidence Rate andMen to Women Ratio: 2 ~ 3.8 :1 Changes of Cancer
Incidence Rateduring 30 Years 19. 5Differences Between High andLow
Incidence Areas Two frequency age peaks: 16-19 and50-59Quickly
increase after the age of 30, and reaches thepeak between 50-59
Ageof disease onset The Low Incidence Areas The High Incidence
Areas 20. 5 Pathologydifferences between high andlow incidence
areas Type I:Well-differentiated squamous carcinoma Type
II:DifferentiatedNon-keratinising Carcinoma Type
III:Undifferentiated Non-keratinising Carcinoma WHO histological
classification of nasopharyngeal carcinoma Type I Type II Type III
21. 5Differences Between High andLow Incidence Areas Type II and
III Type II and III The Low Incidence Areas The High Incidence
Areas Well-differentiated squamous carcinoma accounts for 25%Type I
Well-differentiated squamous carcinoma accounts for 1.67% Type I
Pathology Type 22. Aetiology NPC Lung Cancer ExternalFactors
Internal Factors Internal Factors ExternalFactors 23. Aetiology NPC
EB-Virus HereditaryFactors Environmental Factors 24. Hereditary
susceptibility
- Loss of Tumor Suppressor Genes
- like: 3p13-3p25; 7p32-qter; and 9p21-22.
- Human Leucocyte Antigen (HLA) and
- are possibly NPC susceptibility genes.
- NPC susceptibility genes are possibly located
- in : 4p1511-q12 area.(2002, nature)
25. EBV---Epstein Barr Virus
- a member of the herpes sub-family
- Infection of EBV is ubiquitous
- In our country, EBV Infection occurs early
- in life:90% of population have been
- infected by this virus in the age of 3-5.
- EBV can stay in the body life-long
26. EBV---Epstein Barr Virus
- Antibodies IgA titres to EBV Antigens:
- Viral Capsid Antigen ( VCA )
- Usually VCA-IgA and EA-IgA positive rate and its
- titres are much higher in NPC patients than in healthy
- people and other cancer patients
- Serve as a diagnostic marker.
- Help doctors to identify NPC patients and to do early
27. EnvironmentalFactors Nitrosamines salted fish laboratory
mice cancer of nasal cavity cancer of nasopharynx Cantonese-style
salted fish and other preserved foods 28. EnvironmentalFactors
- Extensive exposure to smoke and dust
29. (nickel sulfate) DNP( EvironmentalFactors (microelements) (
nickel) EB , (selenium) (calcium) 30. .Anatomy of Nasopharynx 31.
Soft palate the torus sphenoid sinusclivus atlasaxis
Pharyngealtonsil 32. .Anatomy of Nasopharynx lateral
pharyngealRecess(fossa ofRosenmullar) the torus ( Eustachian tube (
) nasal septumChoanae ( ) 33. lateral pharyngeal recess (Fossa of
Rosenmullar) the torus Soft palate 34. * Ascending palatine
Ascending pharyngeal -main External carotid A MaxillarySupplying
vessels 35. Maxillary 36. jugulodigastric Rouvieres lymph
nodes,Deep cervical lymph nodes, Supraclavicular lymph nodes
Lymphatic Drainage Necknodes 37. Clinical presentations
38. Symptoms 1
- NeckSymptoms:Lump in the neck 60-80%
39. jugulodigastric ( ) 40. Symptoms 2
- --Blood-stained nasal discharge (sputum ) :70%
- (tumor friction with soft palate)
- --Frequent nose bleeds (Epistaxis):37%
- (when blood vessels broken)
- --Nasal obstruction or stuffiness: 50%
- ( Is a late finding indicating that a large tumor obstructing
the posterior choanae)
41. Symptoms 3
- -- Ringing in an ear (tinnitus ) :60%
- -- Trouble hearing or hearing loss: 50%
- -- Sense of fullness or pain in the ear :
- (when tumor presses on or obstructseustachian tube )
42. Symptoms 4
- Cranial Nerve Paralysis: 45%
- VI and V cranial nerves are the most
- due to skull base erosion or cranial nerve
- irritation without bony involvement.
43. Cranial Nerves
- 2. Optic8.Vestibulocochlear
- 3. Oculomotor 9.Glossopharyngeal
- 5. Trigeminal 11.Spinal Accessory
- 6. Abducens 12.Hypoglossal
- : cervical sympathetic nerve
44. Cranial Nerve Damage
- Damaged area is in or under the exit of cranial nerves
- through bony base of skull
- cranial nervesV and VI are the most common affected
nerves.
45. Exit of cranial nerves through bony base of skull Middle
cranial fossa Posterior cranial fossa 46. Exit of cranial nerves
through bony base of skull Optic foramen:II Cribriform plate:I
Superior orbital fissure:III, IV, V 1 , VI 47. Exit of cranial
nerves through bony base of skull Hypoglossal canal:XII Foramen
rotundum: V 2 Foramen ovale:V 3 Internal auditory meatus:VII, VIII
Jugular foramen:IX, X, XI 48. Optic foramen :II Superior orbital
fissure :III, IV, V 1 VI Foramen rotundum :V 2 Foramen ovale :V 3
(Middle cranial fossa ) Internal auditory meatus :VII, VIII Jugular
foramen :IX, X, XI Hypoglossal canal :XII (Posterior cranial fossa
) Exit of cranial nerves through bony base of skull 49. Cranial
nerves III-VI are affected within theCavernous sinus III IV V 1 VIV
2 (Situated beside sella turcica) 50. Cavernous sinus (Situated
beside sella turcica) 51. Cavernous sinus 52. ParapharyngealSpace
Processus styloideus 53. Processus styloideus 54. Parapharyngeal
Space 55. Parapharyngeal Space involvement 56. Nerves IX-XII are
primarily affected in the Parapharyngeal Space below the skull
base
- : cervical sympathetic nerve
57. Symptoms of commonly affected cranial nerves
- (failure of accommodation)
58. Unilateralptosis oculomotor nerveparalysis 59.
- (pons) (masticatory muscles)
- Difficulty opening the mouth(trismus)
Symptoms of commonly affected cranial nerves 60.
- Numbness in the face or facial paresthesia
- disappearance of corneal reflex
Symptoms of commonly affected cranial nerves 61. V1 V2 V3 62.
(jaw tilt) ptosis) CN III V VI (+) 63.
- ( ) lateral rectus muscle
- failure of abduction), double vision: diplopia
Symptoms of commonly affected cranial nerves 64. 65. CN VI XII +
Horner s + tongue lateralized toaffected side upon protrusion
failure of abduction 66.
- * (soft palate depression)
- * 1/3 (deficiency of taste sensation ofposterior third of the
tongue)
Symptoms of commonly affected cranial nerves 67.
Symptoms of commonly affected cranial nerves 68.
- * (tongue lateralized to affected side upon protrusion) (tongue
atrophy)
Symptoms of commonly affected cranial nerves 69. N 70.
DiagnosisCTscan endoscopy laboratory 71. Procedure of diagnosis
- Take a complete medical history
- Noting all symptoms and risk factors.
- Clinical examination of NP:
- Indirect mirror examinationor
- direct fibroscopic examination
- Clinical examination of neck mass
- EBV Serology :VCA-IgA; EA-IgA; EBV-DNaseAb
- Imaging : CT or MRI of NP and neck
72. Indirect mirror examination 73. With a forcep Rarely used
Inconvenient 74. Direct transnasal endoscopic examination
Widelyused 75. Anatomic Types NodularFungatingSubmucosalInverting
UlceratingMixed 76. Imaging Study
- Help to make the correct diagnosis
- Help To know the disease stage
- Help to determine the target volume of
- Help to evaluate the treatment results
77. Imaging Study 78. Imaging Study 79. Imaging Study 80.
Imaging Study 81. MRI of NP---- better than CT 82. MRI of NP----
better than CT MRI is more sensitive thanCT in detecting tumors of
the nasopharynx and its possible spread to nearby tissues or lymph
nodes. 83. More examination To find Metastasis
- to identify lung metastasis
- to find liver metastasis.
- ECT of bones: Radionuclide bone scan
- Using very small amounts of radioactive
- material to determine whether the cancer
84. PET(positron emission tomography)
- This test creates an image of the body using an injection of a
substance, such as glucose (sugar), in a low dose, radioactive
form.
- Since it is new, the benefit of PET scanning is not clearly
proven, but some doctors may recommend it to look for cancers that
cannot be identified by other scans or tests.
85. PET/CT 86. PET/CT 87. PET/CT 88. Pathological study
- The diagnosis can be made only after the
- biopsy of the nasopharyngeal tumor
- Neck nodes biopsy isdone only when the
- biopsy of the nasopharyngeal tumor is
89. Clinical Types of NPC Ascending Type -----Type of Cranial
Nerves damage Descending Type -----Type of Lymphatic Metastasis
MixedType Metastasis Type: 90. Ascending Type(Type of Cranial
Nerves) Damages ofII III IV V cranial Nervesand/or skull baseBut No
lymph node Metastasis 91. Descending Type (Type of Lymphatic
Metastasis)
92. MixedType
- +damage ofcranial Nervesand/or cranial base
93. Metastasis Type: 1.Bone 2.Liver 3.Lung 4.Other: abdominal
nodes 94. Metastasis of NPC
- Bone is the most commonly affected area
- ( pelvis vertebral column; ribs; extremities)
- Liver is the second most common affected area
- Lung is the another common affected area
95. PET/CT: dorsal vertebra lumbar vertebra 96. 97. Lung
metastasis Liver metastasis 98. Differentiated diagnosis
- Median Necrotic Granuloma (NK/T lymphoma)
- Chordoma;craniopharyngioma
99. Differential Diagnosis Adenoids 100. Differential Diagnosis
Median Necrotic Granuloma tuberculosis 101. Fibroangioma 102.
Clinical staging
- How large is the primary tumor
- Has the tumor spread to the lymph nodes?
- Has the cancer spread to other parts of the body?
103. NPC 92 Clinical Classification 104. T staging
- T1: tumor limited to the nasopharynx.
- T2: tumor involving nasal cavity, oropharynx, soft
- palate, and parapharyngeal space. Extension
- T3: tumor extension overSO-line , involving either
anterior
- or posterior cranial nerves, base of skull
- pterygoprocesse zone, pterygopalatine fossa.
- T4: tumor involving both anterior and posterior
- cranial nerves, paranasal sinus, cavernous sinus,
- orbit, infratemporal fossa, and direct invasion of
- first and second cervical vertebrae
105. N - MStaging
- N1: Upper neck nodes < 4cm, mobile
- N2: Lower neck nodes or nodes 4~7cm;
- N3: Node >7cm or supraclavicular node,or
M0: no metastasis M1: metastasis 106. Treatment Option
Radiotherapy:Radical Chemotherapy:Adjuvant Operation:Complementary
107. Treatmentprotocol -- stratifiedtherapy Radiotherapy Induction
or Concomitant Adjuvant chemotherapy Radiotherapy Induction or
Adjuvant chemotherapy N2-3 Radiotherapy Induction or Concomitant
chemotherapy RadiotherapyN0-1 T3-4 T1-2 108. Brachytherapyis most
often used to manage cancers that have recurred (come back) after
treatment. It may also be used to treat the small original tumor.
Intensity Modulated Radiation Therapy (IMRT) A new method of
external radiation, known for delivering more effective doses of
radiation while reducing the damage to healthy cells, thus causing
fewer side effects. Stereotactic radiosurgerydelivers radiation
therapy precisely to the tumor using a machine called agamma knife
. This can be used to treat tumors that have invaded the base of
the skull, or tumors that have recurred at the base of the brain or
skull. 109. 80 110. 90 LN (Ia) 111. 112. Radiotherapy:Radical 113.
90 114. From Bucci, M. K. et al.CA Cancer J Clin 2005;55:117-134.
21 115. IMRT 116. IMRT 117. External beam radiation -
complications
- Endocrine disorders hypopituitarism hypothyroidism,
hypothalamic disfunction
- Soft tissue fibrosis including trismus
- temporal lobe necrosis;peripheral nerve damages(nerve
atrophy).
118. Chemotherapy: combined
- : Neo-adjuvant chemotherapy
- Concomitant Chemoradiotherapy
119. Protocols of chemotherapy
- PF: DDP+5-Futhe first line
120. 5-year survival of 351 cases aftercombined stratified
therapy (92classification) 22% 50% 76% 90% Radiotherapy only (411
cases) 40.2% 62.3% 80% 95% Combined Therapy (351 cases) IVa III II
I stage 121. Surgery-- for selected patients
- (when radiation therapy is contraindicated)
122. 123. thanks for your attention !
