1. Nasopharyngeal Carcinoma N P C Mai Hai-Qiang ( 麦海强 ) Department of NPC Sun Yat-Sen University Cancer Center

2. What is NPC ? ★ A very special type of head and neck cancer ★ Different from other malignancies of the upper aerodigestive tract with regard to - Epidemiology, -Histology, -Clinical presentations and -Treatment strategies.

8. 中国 ( 南方六省 ) 鼻咽癌分布情况 湖 南 江 西 福 建 广 西 广 东 海南

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

11. ⑵ Specific susceptible population 特定的易感人群 North America Eskimos

12. NPC incidence rates between Chinese immigrants and 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 Caucasian Los Angeles female male incidence rates (/10 5 /year) country race

13. NPC incidence 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 Male Female 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 Male Female language

17. Famous Family ↓ □ male ■ NPC  Breast Cancer ○ female ● NPC  Male Liver Cancer 34.2% cancers 26.3% NPC ● ○ ●  ●■■■ □  □ ■ ○○ ■ □□□○ ■ □○□○□○○□□○○○□ ■ □□○ ■■ ○○ ○○□□□ ○○□□ ○□ □ ○□○□□ ○□ □○○○○□○○ □□ □○ □○ □○ ○○○ □□ □ □ ○ ○□ ○ ○○ □○ ○ ○○ ○ ○○ ● ○ ○ ● □ ■ □ ○ □ □ ○

18. 4 Stable Incidence Rate and Men to Women Ratio: 2 ~ 3.8 :1 发病率相对稳定 Changes of Cancer Incidence Rate during 30 Years

19. 5 Differences Between High and Low Incidence Areas Two frequency age peaks: 16-19 and 50-59 Quickly increase after the age of 30, and reaches the peak between 50-59 Age of disease onset The Low Incidence Areas The High Incidence Areas

20. 5 Pathology differences between high and low incidence areas Type I: Well-differentiated squamous carcinoma 角化性鳞状细胞癌 Type II: Differentiated Non-keratinising Carcinoma 分化型非角化性癌 Type III: Undifferentiated Non-keratinising Carcinoma 未分化型非角化性癌 WHO histological classification of nasopharyngeal carcinoma Type I Type II Type III

21. 5 Differences Between High and Low 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. 二、 Aetiology NPC Lung Cancer External Factors Internal Factors Internal Factors External Factors

23. 二 Aetiology NPC EB-Virus Hereditary Factors Environmental Factors

27. Environmental Factors Nitrosamines 亚硝胺 salted fish  laboratory mice  cancer of nasal cavity cancer of nasopharynx Cantonese-style salted fish and other preserved foods

29. 硫酸镍 (nickel sulfate) 小剂量 DNP( 二亚硝基哌嗪）诱发大鼠鼻咽癌的过程中起促进癌变的作用 Evironmental Factors 微量元素 (microelements) 镍 ( nickel) 激发 EB 病毒 , 并促进其抗原表达 硒 (selenium) 鼻咽癌患者硒含量偏低 钙 (calcium) 低钙区与鼻咽癌高发区分布一致

30. 三 . Anatomy of Nasopharynx

31. Soft palate the torus sphenoid sinus clivus atlas axis Pharyngeal tonsil

32. 三 . Anatomy of Nasopharynx lateral pharyngeal Recess (fossa of Rosenmullar) the torus ( 隆突） Eustachian tube ( 耳咽管 ) nasal septum 鼻中膈 Choanae ( 后鼻孔 )

33. lateral pharyngeal recess (Fossa of Rosenmullar) the torus Soft palate

34. * Ascending palatine Ascending pharyngeal - main External carotid A Maxillary Supplying vessels

35. Maxillary

36. jugulodigastric Rouviere’s lymph nodes, Deep cervical lymph nodes, Supraclavicular lymph nodes Lymphatic Drainage Neck nodes

39. jugulodigastric ( 颈静脉 二腹肌 )

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 视神经孔 : II ☺ Superior orbital fissure 眶上裂 : III, IV, V 1 ， VI ☺ Foramen rotundum 圆孔 : V 2 ☺ Foramen ovale 卵圆孔 : V 3 (Middle cranial fossa 中颅窝 ) ☺ Internal auditory meatus 内耳门 : VII, VIII ☺ Jugular foramen 颈静脉孔 : IX, X, XI ☺ Hypoglossal canal 舌下神经孔 : XII (Posterior cranial fossa 后颅窝 ) Exit of cranial nerves through bony base of skull

49. Cranial nerves III-VI are affected within the Cavernous sinus 破裂孔 III IV V 1 VI V 2 (Situated beside sella turcica)

50. Cavernous sinus 破裂孔 (Situated beside sella turcica)

51. Cavernous sinus

52. Parapharyngeal Space 茎突 Processus styloideus

53. 茎突 Processus styloideus

54. Parapharyngeal Space

55. Parapharyngeal Space involvement

58. Unilateral ptosis oculomotor nerve paralysis

61. V1 V2 V3

62. (jaw tilt) （ ptosis) CN ： III 、 V 、 VI (+)

64. 面神经损伤 （周围性面瘫）

65. CN ： VI 、 XII （ + ） Horner ’s （ + ） tongue lateralized to affected side upon protrusion 舌肌萎缩，伸舌偏向患侧 failure of abduction 内斜视

69. 颅 N 损害 涕 血 鼻 塞 外展障碍 耳鸣、听力↓ 伸舌右歪舌肌萎缩 头痛

70. 五 Diagnosis CT scan endoscopy laboratory

72. Indirect mirror examination

73. With a forcep 钳子 Rarely used Inconvenient

74. Direct transnasal endoscopic examination Widely used

75. Anatomic Types Nodular Fungating Submucosal Inverting Ulcerating Mixed 菜 花 型 结 节 型 粘 膜 下 型 浸 润 型 溃 疡 型 混 合 型

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 than CT in detecting tumors of the nasopharynx and its possible spread to nearby tissues or lymph nodes.

85. PET/CT

86. PET/CT 鼻咽部病灶

87. PET/CT

89. 六 Clinical Types of NPC ▲ Ascending Type 上行性 ----- Type of Cranial Nerves damage ▲ Descending Type 下行性 ----- Type of Lymphatic Metastasis ▲ Mixed Type 混合性 ▲ Metastasis Type: 转移性

90. Ascending Type (Type of Cranial Nerves) Damages of II 、 III 、 IV 、 V cranial Nerves and/or skull base But No lymph node Metastasis ！

93. Metastasis Type: 1.Bone 2.Liver 3.Lung 4.Other: abdominal nodes

95. PET/CT: dorsal vertebra lumbar vertebra

97. Lung metastasis Liver metastasis

99. 八 Differential Diagnosis Adenoids 成人腺样体增生 鼻咽腺样体 成人淋巴组织增生 鼻咽扁桃体增生

100. Differential Diagnosis Median Necrotic Granuloma tuberculosis 鼻咽结核 中线坏死性肉芽肿

101. 青年男性多见 Fibroangioma

103. 九 NPC ’92 Clinical Classification

106. Treatment Option ★ Radiotherapy: Radical （根治手段） ★ Chemotherapy: Adjuvant ★ Operation: Complementary

107. Treatment protocol -- stratified therapy Radiotherapy ＋ Induction or Concomitant ＋ Adjuvant chemotherapy Radiotherapy ＋ Induction or Adjuvant chemotherapy N2-3 Radiotherapy ＋ Induction or Concomitant chemotherapy Radiotherapy N0-1 T3-4 T1-2

108. Brachytherapy is 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 radiosurgery delivers radiation therapy precisely to the tumor using a machine called a gamma 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 年代的方法

110. 90 年代放射治疗 眼 鼻咽 口腔 大脑 脑干 鼻 LN 照射区 铅 挡 块 模拟定位照片和复位照片，示照射范围 (Ia)

111. 铅挡块

112. Radiotherapy: Radical

113. 90 年代放射治疗

114. 常规放射治疗 调强放射治疗 From Bucci, M. K. et al. CA Cancer J Clin 2005;55:117-134. 21 世纪放射治疗

115. 多页光栅 IMRT

116. IMRT 剂量分布图

120. 5-year survival of 351 cases after combined 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

123. thanks for your attention !