What is all about cancer and how to face he (or she)? 慈濟綜合醫院 高瑞和

Transcription

1 What is all about cancer and how to face he (or she)? 慈濟綜合醫院 高瑞和

2 Agenda 1. What is cancer? 2. How to diagnose and treat it? 3. How to develop new cancer therapy? 4. Is cancer preventable? 5. How to survive cancer?

3 What is cancer?

4 Disease Extrinsic: Life: bacteria, virus, fungus, worm Still: chemical, physical Intrinsic Congenital Organ failure Aging Cancer

5 What is cancer? Genetic disease Evolutional point of view Disease point of view Major threatening to human kind

6 Cancer Evolution Ecosystem Somatic evolution Darwinian evolution: natural selection

7

8 Why cancer exists? Single cell organism: selfish cell Multicellular organism Cancer is throwback to selfish cell Atavism: Cancer recreates aspects of life on earth before a billion years ago!!! Paul Davis

9

10 100 年十大死因統計 全國花蓮縣慈濟醫院 排名死亡原因百分比死亡原因百分比死亡原因百分比 1 惡性腫瘤 27.99% 惡性腫瘤 23.55% 惡性腫瘤 36.33% 2 心臟疾病 10.86% 心臟疾病 ( 高血壓性疾病除外 ) 10.47% 病毒及細菌性肺炎 15.45% 3 腦血管疾病 7.12% 腦血管疾病 7.72% 心臟疾病 7.10% 4 糖尿病 5.97% 肺炎 6.94% 腦血管疾病 6.26% 5 病毒及細菌性肺炎 5.95% 事故傷害 6.43% 慢性肝病及肝硬化 5.01% 6 事故傷害 4.42% 糖尿病 6.40% 7 慢性下呼吸道疾病 (COPD) 顱內損傷, 神經及脊髓損傷 3.55% 3.94% 慢性肝病及肝硬化 4.84% 細菌性疾病 2.51% 8 慢性肝病及肝硬化 3.39% 慢性下呼吸道疾病 4.39% 慢性下呼吸道疾病 (COPD) 2.09% 9 高血壓性疾病 3.05% 高血壓性疾病 4.13% 固體及液體所致之肺炎 2.09% 10 腎炎 腎病症候群及腎病變 2.87% 腎炎 腎病症候群及腎病變 2.81% 高血壓性腎臟疾病 1.67% 資料來源 : 行政院衛生署 ( 公告日期為 101 年 6 月 ) 10

11

12 Cancer is a genetic disease Oncogen Anti-oncogen: tumor suppressor gene Genetic instability Mismatch repair system Epigenetic

13

14

15

16 Genetic alterations Point mutation Sequence deletion Amplification Chromosome changes Epigenetic changes

17

18

19

20

21

22

23 The Hallmarks of Cancer 1. Self-sufficiency in growth signals 2. Insensitivity to antigrowth signals 3. Evasion of apoptosis 4. Limitless replicative potential 5. Sustained angiogenesis 6. Tissue invasion and metastasis. Hanahan, D.; Weinberg, R. (2000). Cell 100 (1): 57 70

24

25

26

27 How to diagnose and treat it?

28

29

30

31 Diagnosis of Cancer Physical examination Image studies: x-ray, CT, MRI, PET Blood tests Pathology

32 Plain X ray CT MRI

33

34

35

36

37 Normal prostate tissue Prostate cancer H.E staining

38

39

40 Evolution of Cancer Therapy 1894 Radical mastectomy 1946 Nitrogen Mustard treating lymphoma 1957 Co60 radiation 1961 Linear accelerator, combination chemotherapy 1979 Bone marrow transplantation 1988 Differentiation therapy 1998 Monoclonal antibody therapy 1999 Molecular therapy

41 Cancer Treatment Modality 1. Surgery 2. Radiation therapy 3. Chemotherapy 4. Hormonal therapy 5. Immunotherapy 6. Differentiation therapy 7. Monoclonal antibody therapy 8. Molecular therapy Multimodality therapy Target therapy: 7 & 8

42

43 Cure or Palliative?

44

45 Surgery

46

47

48

49

50

51 Is cancer hereditary?

52

53 Pattern of Breast Cancer Incidence

54

55

56 Chemotherapy

57 Magic Bullet 我ㄧ定要發明一種定要發明一種 神奇的子彈, 讓他只射殺人體內的病源而不會傷害人體 ~ 保羅 埃利希 (Paul Ehrlich) (Paul Ehrlich ) 德國細菌學家 免疫學家 1908 年諾貝爾醫學獎

58

59

60

61 Sidney Farber (September 30, 1903 March 30, 1973) was an American pediatric pathologist. He is regarded as the father of modern chemotherapy, and after whom the Dana-Farber Cancer Institute is named.

62

63 Radiotherapy

64

65

66

67

68

69 Proton therapy

70

71

72

73

74

75 Hormonal Therapy Lancet 1896; ii: Beatson GT Bilateral oophorectomy to treat breast cancer

76 Hormone-Related Cancer Breast cancer, prostate cancer, endometrial cancer Breast cancer- estrogen Prostate cancer- androgen

77

78

79 Hormonal Therapy of Breast Cancer Surgery: bilateral oophorectomy Radiation to ablate ovarian function Drugs: Tamoxifen, Arimidex, GnRH

80 Immunotherapy Interferon: CML, melanoma Interleukin-II: renal cell carcinoma Cancer vaccine Fortified T-cell immunotherapy

81

82 APL: Acute promyelogenic leukemia

83 Differentiation Therapy Acute promyelocytic leukemia (APL), M3 t(15;17), PML-RAR transcript Blood : ME Huang et al Use of all-trans retinoid acid in the treatment of acute promyelocytic leukemia Induction with all-trans retinoid acid+anthracycline Salvage with Arsenic trioxide

84

85 清光绪帝砒霜中毒而亡

86 Sun H-D, Ma L, Hu C-X, Zhang T-D. Thirty-two cases of treating acute promyelocytic leukemia by Ailing-1 (cancer-cure-1) therapy combined with syndrome differentiation treatment of traditional chinese medicine. Chin J Comb Trad Chin Med West Med 1992; 12:

87 毒藥是毒, 還是藥?

88 Target Therapy 標靶治療

89 Monoclonal Antibody Therapy

90 Key features of MabThera CD20+ cell Chimaeric anti-cd20 MAb Activates complementmediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) Direct anti-tumour effects Human Mouse Synergistic activity with chemotherapy Sensitises chemoresistant cell lines

91

92 After anti-cd20 treatment

93 HER2 receptor provides an extracellular therapeutic target Binding site Plasma membrane Signal transduction to nucleus Tyrosine kinase activity Cytoplasm Nucleus Gene activation CELL DIVISION

94

95

96 Molecular Therapy

97 CML Disease Overview

98

99

100

101 Targets of STI571 BCR/ABL: CML C-kit: GIST PDGF receptor: hypereosinophilic syndrome

102 EGFR Expression in Human Tumours Tumours showing high EGFR expression NSCLC 40-80% Prostate 40-80% Gastric 33-74% Head and neck % Breast 14-91% Colorectal 25-77% High expression generally associated with Invasion Metastasis Late-stage disease Chemotherapy resistance Hormonal therapy resistance Poor outcome Pancreatic 30-50% Ovarian 35-70%

103 IRESSA (gefitinib): a small-molecule EGFR-TK inhibitor Extracellular Membrane Intracellular IRESSA Ligand R R K K IRESSA Orally bioavailable Selective inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK) Competitive inhibitor of ATP binding Proliferation Growth factors Chemotherapy/ radiation sensitivity Signalling D N A Apoptosis Angiogenesis Metastasis

104 CT scan of 42-year-old female with NSCLC pre- and post-treatment with IRESSA 250 mg Baseline T baseline + 5 months + 5 months L S T T Key: T=tumour L= contrast medium in liver S= stomach

105 Studies Gefitinib in Asian chemotherapy-treated NSCLC No. of patients RR (%) RR+ SD (%) MS (months) 1-year survival (%) PFS (months) Response duration (months) Taiwan China Korea Singapore Thailand Malaysia (PR) ISEL (placebo) Chang et al, 2005/ Su et al, 2005/ Chiu et al, Guan et al, China Registration Study 3. Park et al, Lim et al, Thailand EAP 6. Malaysia EAP RR, response rate; SD, stable disease; MS, median survival; PFS, progression-free survival

106

107

108 EGFR Mutation vs Response and Survival in Asia Response rate Median survival (months) Study Centre No. of patients Mutation rate (%) Mut+ (%) Mut (%) Mut+ Mut Taiwan 1 NTUH Taiwan 2 VGH-T Korea 3 Seoul NU Japan 4 NCC Tokyo Japan 5 Aichi CCH HK 6 Chinese U China 7 Pek UMCH IDEAL 8 Global INTACT 8 Global /40* 55/39* *CT+IRESSA/CT+placebo 1. Shih et al, IJC Chou et al, CCR Han et al, JCO Takano et al, JCO Mitsudomi et al, JCO Lung et al, PAACR Mu et al, CCR Lynch et al, PASCO 2005

109 Multiple Targets

110 Multiple Targets

111 Anti-angiogenesis

112 Tumor v.s. Angiogenesis

113 The Angiogenic Switch The switch : ON OFF Activators bfgf VEGF HGF PAF NO PD-ECGF TGF-β? Inhibitors TSP-1 Platelet factor-4 NK4 Endostatin Angiostatin IL-6 IL-1 TGF-β?

114 Bevacizumab (Avastin) Humanized anti-vegf MAb Anti-angiogenesis effect Improve delivery of chemotherapeutic agent

115 N Engl J Med 2004;350:

116 Evaluation of Cancer Treatment Response rate = CR+PR Clinical benefit = CR+PR+SD Survival Life quality

117 Response Categories Complete remission (CR) WHO Disappearance of all Lesions, > 1M RECIST Disappearance of all Lesions Partial remission (PR) Stable disease (SD) At least 50% decrease In sum of all lesions No significant change At least 30% decrease in sum of LD* No significant change Progressive disease (PD) At least 25% increase or New lesion At least 20% increase in sum of LD or New lesion *LD: longest diameter

118 Survival Overall survival (OS) Disease free survival (DFS) Progression free survival Dx Tx CR recurrence death DFS OS

119 Principles of Cancer Therapy Diagnosis Staging Treatment Assessment Follow-up

120 Diagnosis Gold standard: pathologic diagnosis Can not depend on image studies or tumour markers except PSA: prostate cancer AFP: hepatoma

121 Staging Prognostic factors Treatment plan Image studies AJCC TNM system T: primary tumour N: regional lymph node M: distant metastasis Clinical vs pathologic stage

122 How to develop new cancer therapy?

123

124

125 Clinical Trial

126 To understand God s thoughts we must study statistics, for these are the measure of His purpose - Florence Nightingale

127

128

129 Is cancer preventable?

130 1. Environment 2. Food 3. Life style 4. Chemoprevention

131

132

133

134

135

136

137

138

139

140

141

142

143

144 Chemoprevention

145

146 Adapted from: Surh, Y. -J. (2003): Nature Reviews Cancer

147

148

149 Human papilloma virus vaccine prevents cervical cancer

150 Cancer screening for high risk group HBV, HCV carriers: liver cancer Smoker: lung cancer betel nut users: oral cancer Family history of breast cancer: breast cancer Sex experience of women: cervical cancer

151 Cancer Screening Pap smear in cervical cancer Mammography in breast cancer Stool occult blood in colon cancer Regular blood tests & liver echo in HBV, HCV carrier Oral inspection in smoker, betel nut user

152

153 Incidence & Mortality of Breast Cancer in UK

154

155 How to survive cancer? Seek medical help immediately with any body change Find a good doctor Correct information Second opinion Adhere to medical order Love yourself, trust your doctor, believe your God

156 Hospice care ( 安寧照顧 ) 幫助病人尊嚴的走完人生最後里程 疼痛控制 芳香治療 人性關懷 心理輔導 宗教信仰

157 靜思語 心寬 不傷人 念純 不傷己

158 Finale