Improving Outcomes in Oral Cancer (eBook)

Contents 6
1: Oral Epithelial Dysplasia 7
1.1 Introduction 7
1.2 Grading and Classification of OED 7
1.3 Clinical Presentation of OED 8
1.4 Risk Factors for OED 9
1.5 Relationship Between OED and PPOEL 10
1.6 Detection and Diagnosis 10
1.7 Human Papillomavirus and Dysplasia 11
1.8 Field Cancerization and OED 12
1.9 Malignant Transformation 12
1.10 Molecular Markers Associated with Development and Progression of OED/PPOEL 13
1.11 Management 14
1.11.1 Prevention 14
1.11.2 Surgical Management 14
1.11.3 Medical Treatments 16
1.12 Follow-Up and Recurrence After Excision or Ablation of OED 16
References 16
2: Chemoprevention in Oral Cancer 19
2.1 Introduction 19
2.2 Antimutagens 19
2.2.1 N-Acetyl-l-Cysteine 20
2.2.2 Topical Bleomycin 20
2.2.3 Polyphenols 21
2.2.3.1 Green Tea Extract 21
2.2.3.2 Curcumin 21
2.3 Antiproliferatives 21
2.3.1 Retinoids 22
2.3.2 Carotenoids 23
2.3.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) 23
2.3.4 Ligands of Peroxisome Proliferator-Activated Receptor gamma (PPAR-?) 24
2.4 Future Directions 24
2.5 Conclusions 25
References 27
3: Diagnostic Adjuncts for Screening and Surveillance in Head and Neck Cancer 29
3.1 Introduction 29
3.2 Vital Staining 30
3.2.1 Toludine Blue 30
3.2.2 Lugol’s Iodine 31
3.3 Visual Light-Based Adjuncts 31
3.3.1 Chemiluminescence 31
3.3.2 Tissue Fluorescence Imaging 32
3.4 Exfoliative-Based Techniques 33
3.4.1 Brush Biopsy 33
3.4.2 DNA-Image Cytometry 34
3.5 Molecular Biology 34
3.6 In Vivo Microscopy 35
3.7 Putting It All Together 35
3.8 Conclusion 37
References 37
4: Current Updates in Staging and Prognosis in Oral Cancer 39
4.1 Introduction 39
4.2 Changes to the American Joint Committee on Cancer (AJCC) Staging System 39
4.3 Depth of Invasion 40
4.4 Extranodal Extension 42
4.5 Resection Margins 44
4.6 Sentinel Node Biopsy 44
4.7 Other Tumor-Specific Prognostic Factors 45
4.7.1 Perineural and Lymphovascular Invasion 45
4.7.2 Human Papilloma Virus 45
4.7.3 Pattern of Invasion 46
4.7.4 Lymph Node Ratio 46
4.8 Conclusion 47
References 47
5: Surgical Factors Affecting Outcomes in Oral Squamous Cell Carcinoma 50
5.1 Introduction 50
5.2 Care Team Factors 50
5.3 Patient Factors 51
5.4 Surgical Principles 51
5.5 Management of the Primary Tumor 52
5.5.1 Mandible 52
5.5.2 Maxilla 53
5.5.3 Oral Tongue 55
5.5.4 Buccal Mucosa 56
5.5.4.1 Retromolar Trigone 56
5.5.5 Floor of Mouth 56
5.6 Evaluation of Margin Status 57
5.7 Margin Status on Frozen Section 57
5.8 Management of the Clinically Negative Neck 59
5.9 Extent of Neck Dissection 60
5.10 Sentinel Node Biopsy 61
5.11 Dental Rehabilitation 62
5.12 Adjunct Surgical Tools 63
5.13 Conclusion 64
References 64
6: Pathological Factors Affecting Outcomes in Oral Cancer 69
6.1 American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) Tumor Node Metastasis (TNM) Staging System 70
6.2 Grade 71
6.3 Perineural Invasion 77
6.4 Status of the Surgical Margins 80
6.5 Depth of Invasion 86
6.6 Status of the Cervical Lymph Nodes 88
6.7 Human Papillomavirus 91
6.8 Bone Invasion 93
6.9 Lymphovascular Invasion 95
6.10 Conclusion 97
References 97
7: Genetics of Oral Cancer 100
References 104
8: Factors Affecting Response and Survival in Radiotherapy 107
8.1 Introduction 107
8.2 Contemporary Radiation Therapy for Oral Cancer 108
8.3 Indications 111
8.4 Prognostic Factors in Radiation Therapy 111
8.5 Oxygenation 111
8.6 Tumor Volume 112
8.7 Molecular Markers 112
8.8 Timing of Radiation Therapy and Fractionation Schedule 113
8.9 Smoking and Malnutrition 113
8.10 Pathologic Factors 114
8.11 Additional Adjunctive Treatment with Chemotherapy 115
8.12 Conclusion 115
References 115
9: Novel and Emerging Chemotherapeutic Agents in Head and Neck Cancer 118
9.1 Introduction 118
9.2 Systemic Therapy for Locoregionally Advanced Disease 118
9.3 Chemotherapy Regimens for Locoregionally Advanced Disease 119
9.4 Treatment Regimens for Recurrent Metastatic Disease in Previously Untreated Patients 119
9.5 Epidermal Growth Factor Receptor (EGFR)-Targeted Therapy 120
9.5.1 Monoclonal Antibodies (mAb) Against EGFR 120
9.5.1.1 Cetuximab 120
9.5.1.2 Panitumumab 121
9.5.1.3 Zalutumumab 121
9.5.1.4 Nimotuzumab 121
9.5.2 Tyrosine Kinase Inhibitors (TKI) Against EGFR 121
9.5.2.1 Gefitinib 121
9.5.2.2 Erlotinib 121
9.5.2.3 Lapatinib 122
9.5.2.4 Afatinib 122
9.5.2.5 Dacomitinib 122
9.6 Vascular Endothelial Growth Factor Receptor (VEGFR)-Directed Therapies 122
9.6.1 Monoclonal Antibodies (mAb) Against the VEGFR 122
9.6.1.1 Bevacizumab 122
9.6.2 Tyrosine Kinase Inhibitors (TKIs) Against VEGFR 122
9.6.2.1 Sorafenib 122
9.6.2.2 Sunitinib 123
9.6.2.3 Vandetanib 123
9.7 P13K/AKT/mTOR Pathway Inhibitors 123
9.8 Palbociclib 123
9.9 Immune Checkpoint Inhibitors 123
9.10 Oligometastatic Disease 124
9.11 Drug Resistance 124
9.12 Conclusions and Future Directions 125
References 125
10: Immunotherapy in Oral Cancer: A Fourth Dimension of Cancer Treatment 130
10.1 The Immune System in Head and Neck Cancer 130
10.2 A New Standard of Care in Recurrent or Metastatic Head and Neck Cancer 132
10.2.1 PD-1 Inhibitors 132
10.3 Additional Checkpoint Inhibitors 134
10.3.1 PD-L1 134
10.3.2 CTLA-4 135
10.3.3 TIM-3 136
10.3.4 LAG-3 136
10.3.5 TIGIT 136
10.4 Combinations of Checkpoint Inhibitors 137
10.5 Costimulatory Agonists 138
10.5.1 CD28 Superfamily 138
10.5.2 Tumor Necrosis Factor (TNF) Receptor Superfamily 138
10.6 Cytokines 141
10.7 Targeting the Innate Immune System 142
10.7.1 TLR Agonists 142
10.7.2 STING Agonists 143
10.8 Vaccines 144
10.9 Adoptive Cell Therapy 146
10.10 Oncolytic Viruses 146
10.11 The Role of Conventional Therapies in Activating the Immune System 147
10.12 Conclusions 150
References 150
11: Recurrent Oral Cancer and Salvage Options 156
11.1 Introduction 156
11.2 Recurrent Disease of the Oral Cavity: General Considerations 156
11.3 Surgical Salvage 158
11.4 Radiation Therapy for Salvage 160
11.5 Systemic Therapy and Immunotherapy 162
11.6 Summary 163
References 163
12: Oral Reconstruction 166
12.1 General Considerations 166
12.2 Reconstruction of the Lips 166
12.2.1 A Timeline of Lip Reconstruction Techniques 167
12.3 Reconstruction of the Vermillion 167
12.4 Lower Lip Reconstruction 167
12.4.1 Defects Less Than 50% 167
12.4.2 Defects Greater Than 50% 168
12.4.2.1 Karapandzic Flap 168
12.4.2.2 Lip Switch Flaps 168
12.4.3 Subtotal Defects 168
12.4.3.1 Cheek Advancement Flaps 168
12.4.3.2 Gate Flap 169
12.4.4 Upper Lip 169
12.4.4.1 Primary Closure 169
12.4.4.2 Abbe Flap 169
12.4.4.3 Perialar Crescenteric Advancement 169
12.4.4.4 Reverse Karapandzic 169
12.4.5 Commissuroplasty 170
12.4.6 Total Lip Defects 170
12.5 Buccal Mucosa and Cheek 171
12.6 Floor of Mouth 172
12.7 Tongue Reconstruction 173
12.7.1 Primary Closure 173
12.7.2 Pedicled Flap Reconstruction 173
12.7.3 Free Flap Reconstruction 173
12.8 Mandibular Reconstruction 174
12.8.1 Classification of Defects 174
12.8.2 Soft Tissue Reconstruction 174
12.8.3 Hard Tissue Reconstruction 175
12.9 Palatal and Maxillary Defects 176
References 178
13: Predicting Quality of Life (QoL) of Oral Cancer 181
13.1 Introduction 181
13.2 Quality of Life (QoL) 181
13.3 Glossectomy and Reconstruction 182
13.4 Maxillectomy 183
13.5 Dental Implants 184
13.6 The Patient 185
13.7 Conclusion 186
References 186