Gastrointestinal Oncology (eBook)

Dr. Blanke has been the Provincial Head for Systemic Therapy, as well as the Chief of Medical Oncology at the University of British Columbia, since 2008. Professor Blanke has an international reputation in treatment and research of colorectal cancers and gastrointestinal stromal tumours. He has a particular interest in new drug development and currently chairs the North American phase III Intergroup trial of chemotherapy plus bevacizumab or cetuximab in advanced colorectal cancer (co-principal investigator), and the National Cancer Institute-designated GIST Research Task Force. Dr. Blanke attended medical school at Northwestern University in Chicago, and hre underwent additional internal medicine and oncology training at the Gundersen Medical Foundation (Wisconsin) and Indiana University (Indiana), serving as chief resident and chief fellow at the latter institutions. Dr. Blanke is the author of more than 130 manuscripts and 20 book chapters, and he has presented at more than 170 conferences, including the Plenary Session of the 2001 American Society of Clinical Oncology meeting. He has received multiple research, teaching, and service awards. Claus Rödel (born 3.2.66) graduated from Erlangen Medical School in 1994. He achieved the medical speciality degree in Radiation Therapy in 2002. He was attending physician at the Department of Radiation Therapy at the University of Erlangen until 2006. In 2007, he was appointed Director and Chair of the Department of Radiotherapy and Oncology at the University of Frankfurt. Since April 2008, he also serves as Clinical Director of the Comprehensive Cancer Center of the University Hospital of Frankfurt. His main scienitific interests focus on combined modality treatment, including targeted therapies, for organ preservation for patients with rectal and bladder cancer, as well as molecular prediction of tumor response and radiation-induced apoptosis. His scientific work has been honoured with the Herman-Holthusen Award of the German Society of Radiation Oncologist (DEGRO) in 2004, and with the ARO Award of the German Cancer Society in 2005. Since 2007, he serves as editorial board of "Strahlentherapie und Onkologie". Mark S. Talamonti, M.D. is Clinical Professor of Surgery at the University of Chicago Pritzker School of Medicine and Chairman of the Department of Surgery at NorthShore University HealthSystem. Following graduation from Northwestern University Medical School in 1983, Dr. Talamonti completed a residency in General Surgery At Northwestern and then a fellowship in Surgical Oncology in the Department of Surgery at the University of Texas, MD Anderson Cancer Center in Houston. While at the MD Anderson Cancer Center, Dr. Talamonti developed his research interests in combined modality clinical trials for patients with gastrointestinal malignancies. Dr. Talamonti’s clinical expertise focuses on the area of gastrointestinal surgical oncology with specific interests in pancreas and gastric cancers. He has served as the principal investigator or co-investigator on two recent Intergroup Trials examining the role of combined chemotherapy with external beam radiation therapy as neoadjuvant strategies prior to Whipple procedures for potentially resectable pancreatic cancers. In addition, Dr. Talamonti has served as a clinical investigator on several multimodality trials examining outcomes following neoadjuvant therapy for gastroesophageal junction cancers. His most recent work with the American College of Surgeons National Cancer Database has helped define quality metrics and surgical standards for patients with pancreatic cancer. Dr. Talamonti is the author of over 120 peer reviewed scientific publications, as well as 25 book chapters. He serves on the Editorial Board for the Annals of Surgical Oncology and the Journal of Surgical Oncology. He is a member of many surgical societies including the Society of Surgical Oncology, the Society of University Surgeons and the American Surgical Association. Dr. Talamonti has been honored with numerous teaching awards and has been honored for his dedication and compassion in the care of patients with cancer and life threatening illnesses.

Gastrointestinal Oncology 2
Preface 4
Contents 5
1: Imaging in Gastrointestinal Cancer 7
1.1 Introduction 7
1.2 Screening 7
1.2.1 Colon Cancer Screening 8
1.2.2 Diagnosis and Staging 9
1.2.3 PET Imaging: The Basics 9
1.2.4 PET in Staging GI Cancers 11
1.3 Monitoring Response to Treatment 14
1.3.1 Use of FDG-PET in Monitoring Early Response to Treatment 15
1.3.1.1 Esophageal Cancer 15
1.3.1.2 Colorectal Cancer 16
1.3.1.3 GI Stromal Tumors 18
1.4 Surveillance 19
1.4.1 Surveillance After Potentially Curative Resection 19
1.5 Summary 20
References 21
2: Interventional Gastrointestinal Oncology 27
2.1 Endoscopic Mucosal Resection 27
2.2 Endoscopic Submucosal Dissection 30
2.3 Endoscopic Ultrasound 32
2.3.1 Pancreatic Adenocarcinoma 32
2.3.2 Pancreatic Cystic Lesions 33
2.3.3 Hepatobiliary Neoplasms 35
2.3.4 Submucosal Gastrointestinal Lesions 35
2.3.5 Gastric Cancer 36
2.3.6 Esophageal Neoplasms 36
2.3.7 Colorectal Carcinoma 37
2.3.8 Lung Malignancy 37
2.3.9 Therapeutic Applications of EUS-FNA 38
2.3.9.1 Celiac Plexus Blockade 38
2.3.9.2 EUS-Guided Pancreatico-Biliary Access/Drainage 38
2.3.9.3 EUS-Guided Fine Needle Injection 39
2.4 Endoscopic Management of Malignant Gastrointestinal Obstruction 39
2.4.1 Malignant Esophageal Obstruction 39
2.4.2 Malignant Gastro-Duodenal Obstruction 41
2.4.3 Malignant Colorectal Obstruction 41
2.4.4 Malignant Biliary Obstruction 42
2.5 Conclusion 43
References 44
3: Practical Gastrointestinal Oncology Correlative Science 48
3.1 The Molecular Bases of Gastrointestinal Cancer 48
3.2 Molecular Pathways of Colorectal Carcinoma 49
3.2.1 Chromosomal Instability Pathway 50
3.2.2 Microsatellite Instability Pathway 50
3.2.2.1 Specific Genetic Alterations in the MIS Pathway 51
3.2.2.2 Practical Applications of MSI Testing 51
3.3 Molecular Alterations in GI Cancers with Current Clinical Applications 54
3.3.1 KRAS 54
3.3.1.1 Practical Applications of KRAS Mutational Analysis 55
3.3.2 Allelic Imbalance in 18q 56
3.3.3 Other Molecular Abnormalities 56
3.4 Molecular Testing in Other GI Cancers 56
3.5 Summary of Recommendations for Molecular Testing in GI Carcinomas 57
3.6 Gastrointestinal Stromal Tumor (GIST) 57
3.6.1 Pathology 57
3.7 Oncogenic Kinase Mutations in GISTs 58
3.8 Molecular Classification of GISTs 59
3.8.1 GIST Variants 60
3.9 Kinase Genotype and Treatment with Imatinib Mesylate 61
3.9.1 Adjuvant Imatinib and Kinase Genotype 61
3.10 Imatinib Resistance 62
3.10.1 Sunitinib 62
3.10.2 Other Tyrosine Kinase Inhibitors 62
3.11 Recommendations for GIST Genotyping 63
3.12 Summary 63
References 64
4: Esophageal Cancer 72
4.1 Epidemiology 72
4.2 Etiologic Factors 73
4.2.1 Squamous Cell Cancer 73
4.2.2 Adenocarcinoma 74
4.3 Classification and Pathology 75
4.3.1 Squamous Cell Carcinoma 75
4.3.2 Adenocarcinoma 76
4.3.3 Precancerous Lesions 76
4.3.4 Differential Pathologic Diagnosis 76
4.3.5 Specific Histotypes 76
4.3.6 Lymphatic Spread 77
4.3.7 Distant Metastases 77
4.3.8 Anatomic Classification 78
4.4 Symptoms 78
4.5 Clinical Diagnostics 80
4.6 Preoperative Risk Assessment 81
4.7 Indications and Selection of Treatment Modalities 83
4.8 Endoscopic Therapy 83
4.9 Surgical Therapy 84
4.9.1 Procedures 84
4.9.2 Perioperative Morbidity and Mortality 87
4.9.3 Long-Term Surgical Outcome 88
4.10 Perioperative Treatment 89
4.10.1 Neoadjuvant Radiation 89
4.10.2 Neoadjuvant Chemotherapy 90
4.10.3 Neoadjuvant Chemoradiation 90
4.10.4 Quality of Life 91
4.10.5 Treatment Protocols 92
4.10.5.1 Chemotherapy 92
4.10.5.2 Chemoradiation 92
4.10.6 Response Evaluation and Response Prediction 93
4.11 Definitive Chemoradiotherapy 94
4.11.1 Randomized Studies 94
4.11.2 Chemoradiation vs. Surgery 95
4.12 Treatment of Metastatic Disease 95
4.12.1 Chemotherapy 95
4.12.2 Local Treatment 97
References 98
5: Gastric Cancer 106
5.1 Epidemiology 106
5.2 Etiology 107
5.3 Environmental Risks and Prevention 108
5.3.1 Genetic Risk 109
5.4 Diagnosis and Workup 110
5.5 Staging 111
5.6 Surgical Treatment 111
5.6.1 Extent of Organ Resection (Subtotal vs. Total Gastrectomy and Margins) 113
5.6.2 Endoscopic Mucosal Resection (EMR) 113
5.6.3 Lymphadenectomy and “D-Level” Trials 114
5.6.4 “Low Maruyama Index” Lymphadenectomy is Associated with Improved Survival 116
5.7 Radiotherapy 118
5.7.1 Palliative Radiotherapy 118
5.7.2 Role of Radiotherapy in Potentially Curative Gastric Cancer 118
5.7.2.1 Patterns of Failure 118
5.7.3 Postoperative Adjuvant Radiation 120
5.7.4 Local Unresectable/Postoperative Residual Local Disease 121
5.7.5 Definitive Radiochemotherapy 121
5.7.6 Neoadjuvant Chemotherapy for Locally Unresectable Gastric Cancer 122
5.7.7 Preoperative Radiotherapy with/without Chemotherapy 123
5.8 Systemic Therapy in Advanced Disease 125
5.8.1 Single-Agent Chemotherapy 126
5.8.2 Combination Chemotherapy 126
5.8.3 Nitrosourea Combinations 126
5.8.4 Mitomycin Regimens 127
5.8.5 5-Fluorouracil, Doxorubicin, Leucovorin, and Methotrexate 129
5.8.6 Cisplatin-Based Combinations 129
5.8.7 Taxane-Based Regimen 130
5.8.8 Irinotecan-Based Therapy 130
5.8.9 Epirubicin-Based Combinations 131
5.8.10 Chemotherapy vs. Best Supportive Care 131
5.8.11 Targeted Therapy 132
5.8.12 Monoclonal Antibodies and Tyrosine Kinase Inhibitors 133
5.8.13 Chemotherapy in Resectable Gastric Cancer 133
5.8.14 Supportive Care 135
5.9 Conclusion 135
References 136
6: Gastrointestinal Stromal Tumors 144
6.1 Epidemiology 144
6.1.1 Demographics 144
6.1.2 Special Types and Associations 145
6.1.2.1 Pediatric GIST 145
6.1.2.2 Familial GIST 146
6.1.2.3 Syndromic GIST 146
6.1.2.4 Other Associations 146
6.2 Pathology 147
6.2.1 Gross Pathology 147
6.2.2 Light Microscopy 147
6.2.2.1 Morphology 147
6.2.2.2 Immunohistochemistry 148
CD117 148
CD34 149
PDGFR 150
Protein Kinase C Theta 150
DOG-1 150
6.2.2.3 Other Markers 151
6.2.3 Electron Microscopy 151
6.2.4 Molecular Biology and Mutational Analysis 152
6.2.4.1 KIT 152
6.2.4.2 PDGFR 153
6.2.4.3 IGF-1 153
6.2.4.4 BRaf V600E 153
6.2.4.5 Other 154
6.2.5 Behavior and Prognosis 154
6.2.5.1 Patterns of Metastasis 154
6.2.5.2 Prediction of Behavior 154
6.3 Diagnosis and Staging 156
6.3.1 Clinical Presentation 156
6.3.2 Investigations 156
6.4 Clinical Management 157
6.4.1 Surgical Management 157
6.4.1.1 Resectable Primary GIST 157
6.4.1.2 Borderline Resectable Disease 158
6.4.1.3 Surgery for Recurrence 158
6.4.2 Medical Management 159
6.4.2.1 Chemotherapy 159
6.4.2.2 Imatinib mesylate (Glivec, Gleevec, (STI571) Novartis) 159
6.4.2.3 Toxicity of Imatinib 161
6.4.2.4 Dosing of Imatinib Mesylate 162
6.4.2.5 Duration of Imatinib Therapy 163
6.4.2.6 Management of Progression on Imatinib 163
6.4.2.7 Sunitinib (Sutent (SU11248) Pfizer) 164
6.4.3 Assessing Response to Therapy 165
6.4.4 Radiotherapy 166
6.4.5 Adjuvant Therapy for Resected Gastrointestinal Stromal Tumor 167
6.4.6 Neoadjuvant Therapy for Locally Advanced GISTs 168
6.4.7 Other Agents in Development 169
6.4.7.1 Nilotinib (AMN107, Tasigna, Novartis) 169
6.4.7.2 Sorafenib (BAY 43 1006, Nexavar, Bayer) 170
6.4.7.3 Retaspimycin Hydrochloride (IPI-504, Infinity Pharmaceuticals) 170
6.4.7.4 Everolimus (RAD001, Afinitor, Novartis) 170
6.4.7.5 Motesanib Diphosphate (AMG706, Amgen) 171
6.5 Conclusion 171
References 172
7: Multimodality Management of Localized and Borderline Resectable Pancreatic Adenocarcinoma 178
7.1 Introduction 178
7.2 Clinical Staging and Preoperative Management 179
7.3 Principles of Surgical Management and Current Controversies 183
7.3.1 Extent of Regional Lymphadenectomy 184
7.3.2 Role of Vascular Resection 184
7.3.3 Standard Gastrectomy vs. Pyloric-Preserving Whipple 186
7.3.4 Techniques for Pancreatic Reconstruction 187
7.3.5 Surgical Morbidity and Mortality 188
7.4 Adjuvant Therapy for Pancreatic Adenocarcinoma 189
7.5 Neoadjuvant Therapy for Localized and Borderline Resectable Pancreas Cancer 196
7.5.1 Resectable Disease 197
7.5.2 Borderline Resectable Strategies 199
7.6 Summary 201
References 202
8: Unresectable Pancreatic Cancer 209
8.1 Introduction 209
8.2 Locally Advanced Pancreatic Cancer 210
8.2.1 Radiation and Chemoradiotherapy 210
8.2.2 Different Chemoradiotherapy Protocols 211
8.2.2.1 Radiotherapy Protocols 211
8.2.2.2 Chemotherapy Given Concurrently 211
8.2.3 Chemotherapy Alone 212
8.2.4 Chemotherapy Followed by Chemoradiotherapy 214
8.2.5 Targeted Therapy 214
8.2.6 Summary and Future Directions 215
8.3 Metastatic Pancreatic Cancer 216
8.3.1 Chemotherapy 216
8.3.2 Targeted Therapy 218
8.3.3 Second-Line Therapy 221
8.3.4 Summary and Future Directions 222
8.4 Summary 223
References 223
9: Liver Cancer 229
9.1 Introduction 229
9.2 Epidemiology and Risk Factors 229
9.3 Clinical Presentation 230
9.4 Liver Disease and HCC 231
9.5 Diagnosis and Staging 232
9.6 Alpha Fetoprotein 232
9.6.1 Ultrasound 232
9.6.2 MRI 233
9.6.3 CT 233
9.6.4 Liver Biopsy 233
9.7 Staging and Prognostic Systems in HCC 234
9.8 Treatment of HCC 238
9.9 Surgical Resection 238
9.10 Liver Transplantation 242
9.11 Nonresectional Locoregional Therapies 243
9.12 Systemic Therapy 244
9.13 Growth Factors as Therapeutic Targets in Hepatocellular Carcinoma 246
9.14 Summary and Conclusions 248
References 248
10: Carcinoma of the Biliary Tract 254
10.1 Introduction 254
10.2 Gallbladder Cancer 255
10.2.1 Epidemiology and Risk Factors 255
10.2.2 Pathology of Gallbladder Cancer 256
10.2.3 Diagnosis of Gallbladder Cancer 257
10.2.4 Staging of Gallbladder Cancer 258
10.2.5 Surgical Resection of Gallbladder Cancer 258
10.2.5.1 Management of Known Gallbladder Cancer 260
10.2.5.2 Management of Incidental Gallbladder Cancer 262
10.2.6 Radiation Therapy in Gallbladder Cancer 263
10.2.6.1 Adjuvant Radiation Therapy for Gallbladder Cancer 263
10.2.6.2 Radiation Therapy for Unresectable Gallbladder Cancer 264
10.3 Carcinoma of the Extrahepatic Bile Duct 265
10.3.1 Epidemiology and Risk Factors 265
10.3.2 Pathology of Extrahepatic Bile Duct Cancer 266
10.3.3 Diagnosis of Extrahepatic Bile Duct Cancer 266
10.3.4 Staging Extrahepatic Bile Duct Cancer 267
10.3.5 Surgical Resection of Extrahepatic Bile Duct Cancer 268
10.3.6 Radiation Therapy in Bile Duct Cancer 271
10.3.6.1 Adjuvant Radiation Therapy for Perihilar Cholangiocarcinomas 271
10.3.6.2 Neoadjuvant Radiation Therapy for Cholangiocarcinomas 272
10.3.6.3 Radiation Therapy for Unresectable Cholangiocarcinoma 273
10.4 Intrahepatic Cholangiocarcinoma 275
10.4.1 Epidemiology and Risk Factors 275
10.4.2 Pathology of Intrahepatic Cholangiocarcinoma 275
10.4.3 Diagnosis of Intrahepatic Cholangiocarcinoma 276
10.4.4 Staging of Intrahepatic Cholangiocarcinoma 277
10.4.5 Surgical Resection of Intrahepatic Cholangiocarcinoma 279
10.4.6 Radiation Therapy for Intrahepatic Cholangiocarcinoma 280
10.5 Systemic Therapy in Biliary Cancers 280
10.5.1 Metastatic Disease 280
10.5.1.1 Early Chemotherapy Studies 281
10.5.1.2 The Newer Chemotherapy Agents 282
10.5.1.3 Targeted Therapies 285
10.5.2 Adjuvant Systemic Therapy 286
10.6 Conclusions and Future Work 287
References 288
11: Neuroendocrine Cancers 303
11.1 Introduction 304
11.2 Epidemiology 304
11.3 Prognosis 305
11.4 Pathogenesis and Molecular Biology 305
11.5 Pathologic Classification 307
11.6 Clinical Presentation of NETs and Diagnostic Work Up 308
11.6.1 Neuroendocrine Tumor Laboratory Tests and Markers 308
11.6.2 Imaging 309
11.6.2.1 Endoscopy 309
11.6.2.2 Computed Tomography and Magnetic Resonance Imaging 309
11.6.2.3 OctreoScan 310
11.6.2.4 Positron Emission Tomography (PET) 310
11.6.2.5 Other Nuclear Scintigraphy Techniques 310
11.7 Carcinoid Clinical Behavior by Site 310
11.7.1 Gastric Carcinoid 310
11.7.2 Small Intestine Carcinoid 311
11.7.3 Appendiceal Carcinoid 311
11.7.4 Rectal Carcinoid 311
11.8 Clinical Features of Islet Cell Tumors 312
11.8.1 Insulinomas 312
11.8.2 Gastrinomas 312
11.8.3 Glucagonomas 313
11.8.4 Somatostatinoma 313
11.8.5 VIPoma 313
11.8.6 Pancreatic Polypeptidomas 314
11.9 Carcinoid Syndrome, Carcinoid Heart Disease, and Carcinoid Crisis 314
11.9.1 Carcinoid Syndrome 314
11.9.2 Carcinoid Heart Disease 315
11.9.3 Carcinoid Crisis 315
11.10 General Approach to Treatment of Localized and Advanced Neuroendocrine Tumors 315
11.11 Treatment of Resectable Neuroendocrine Tumors 316
11.12 Treatment of Advanced Neuroendocrine Tumors 318
11.12.1 Surgical Resection of Hepatic Metastases 318
11.12.2 Somatostatin Analogs 318
11.12.3 Biotherapy 319
11.12.4 Hepatic Artery Embolization and Hepatic Artery Chemoembolization 319
11.12.5 Radiofrequency Ablation 320
11.12.6 Additional Symptom Control Methods 321
11.12.7 Chemotherapy 321
11.12.7.1 Effectiveness of Chemotherapy in Carcinoids 321
11.12.7.2 Effectiveness of Chemotherapy Islet Cell Carcinomas 321
11.12.8 Biochemotherapy 321
11.12.9 Peptide Receptor Radionuclide Therapy 321
11.12.10 Targeted Therapy 322
11.13 Conclusion 323
References 323
12: Colon Cancer 327
12.1 Introduction 327
12.2 Pathogenesis, Pathology and Prognosis 327
12.3 Risk Factors for Colon Cancer 329
12.3.1 Inherited Predisposition 329
12.3.2 Inflammatory Bowel Disease 331
12.3.3 Acquired Risk Factors 331
12.4 Screening 332
12.4.1 Fecal Occult Blood Test 333
12.4.2 Fecal Immunochemistry Tests 334
12.4.3 Barium Enema 334
12.4.4 CT Colonography 334
12.4.5 Flexible Sigmoidoscopy 335
12.4.6 Colonoscopy 336
12.4.7 Current Screening Recommendations 336
12.5 Staging 336
12.6 Clinical Management 338
12.6.1 Malignant Polyps 338
12.6.2 Early-Stage Colon Cancer (Stage I–III Disease) 341
12.6.2.1 Surgical Management of the Primary Tumor 341
Surgical Procedures for Colon Cancer 341
Lymphadenectomy 342
Laparoscopic Surgery 345
12.6.3 Radiotherapy Considerations in Resected High-Risk Colon Cancer 345
12.6.4 Adjuvant Chemotherapy for Resected High-Risk Colon Cancer 347
12.6.4.1 5-FU Monotherapy 347
12.6.4.2 5-FU and Oxaliplatin 348
12.6.4.3 Negative Trials in Adjuvant Colon Cancer 348
12.6.4.4 Considerations in Stage II Colon Cancer 349
12.6.4.5 Adjuvant Therapy in the Elderly 350
12.6.5 Advanced Colon Cancer (Stage IV Disease) 351
12.6.5.1 Management of the Primary Tumor in Metastatic Colon Cancer 351
12.6.5.2 Locoregional Management of Liver-Limited Metastatic Colon Cancer 352
12.6.5.3 Stereotactic Body Radiotherapy 358
12.6.6 Unresectable Metastatic Disease 359
12.6.6.1 Radiotherapy Considerations to Palliate Advanced Unresectable Disease 359
12.6.6.2 Systemic Therapy for Advanced Unresectable Colon Cancer 360
First and Second-Line Chemotherapy 360
First and Second-Line Targeted Therapies in Advanced Disease 362
Bevacizumab 362
Cetuximab and Panitumumab 364
12.6.7 Management of Chemotherapy-Refractory Disease 364
References 366
13: Rectal Cancer 380
13.1 Introduction 380
13.2 Epidemiology 381
13.3 Etiology 381
13.4 Prevention and Early Detection 382
13.4.1 Primary Prevention 382
13.4.2 Screening for Early Detection 383
13.5 Clinical Manifestations 383
13.6 Diagnostic Evaluation and Imaging 383
13.6.1 Pretreatment Staging 383
13.6.2 Imaging After Radio(Chemo)therapy 387
13.7 Pathology 388
13.7.1 Anatomy and Pathway of Spread 388
13.7.2 Histopathology 389
13.7.3 TNM Classification System 389
13.7.4 Circumferential Resection Margin 393
13.7.5 Recording of Surgical Quality 394
13.7.6 Tumor Regression 395
13.8 Surgery 395
13.8.1 Local Excision: pT1-Low Risk Rectal Cancer 395
13.8.2 Standard Resection (Including Total Mesorectal Excision): High-Risk pT1- and pT2-Rectal Cancer 397
13.8.3 Surgical Treatment in Locally Advanced Rectal Cancer (UICC Stages II and III) 397
13.8.4 Partial Mesorectal Excision 399
13.8.5 Total Pelvic Exenteration 401
13.9 Radiotherapy and Chemotherapy 401
13.9.1 Randomized Trials of Postoperative CRT 402
13.9.2 Randomized Trials to Optimize 5-FU-Based Postoperative CRT 402
13.9.3 Preoperative Radiation 405
13.9.4 Randomized Trials to Optimize the Sequence 406
13.9.5 Concomitant Chemotherapy with Preoperative RT? 408
13.9.6 Adjuvant Chemotherapy After Neoadjuvant RT/CRT 409
13.9.7 Integrating Combination Chemotherapy into the Combined Modality Program 410
13.9.8 Integrating Targeted Agents into the Combined Modality Program 412
13.9.9 Treatment Toxicity and Quality of Life 414
13.10 Future Perspectives 416
References 418
14: Anal Cancer 423
14.1 Incidence 423
14.2 Aetiology and Risk Factors 425
14.3 Pathology and Biology 425
14.4 Intra-Epithelial Neoplasia 425
14.5 Histological Types 426
14.6 Tumour Grade 426
14.7 Anatomy 426
14.8 Lymphatic Drainage 427
14.9 Presentation 427
14.10 Staging and Risk Assessment 427
14.11 Pre-Treatment Assessment 428
14.12 Radiological Staging 428
14.13 Other Investigations/Procedures 429
14.14 Predictive Factors 429
14.15 Prognostic Factors 430
14.16 Biological Markers 430
14.17 Tumour Markers 431
14.18 Surgery as Primary Treatment for Anal Cancer 432
14.19 Non-Surgical Treatment 432
14.20 T1/T2 Tumours 436
14.21 The Use of Radiation Alone 436
14.22 The Boost 437
14.23 Treatment for Late Stage (T3/T4) 437
14.24 Neoadjuvant Chemotherapy 438
14.25 Consolidation Chemotherapy 439
14.26 Biological Agents 439
14.27 Radiotherapy Technique and Treatment Fields 439
14.28 Post-Operative Adjuvant Treatment 440
14.29 Toxicity and Supportive Care During Radiotherapy 440
14.30 Patterns of Relapse 441
14.31 Chemoradiotherapy Salvage 441
14.32 Surgical Salvage 441
14.33 Treatment of Recurrent and/or Metastatic Anal Cancer 442
14.34 Late Sequelae 442
14.35 Follow-Up and Surveillance 442
14.36 Conclusions 443
14.37 Guidelines 443
14.38 Reviews 444
References 444
Index 451