Radiotherapy of Liver Cancer

Description

Preface Contents Part I: Basic Science in Radiotherapy of Liver Cancer 1: Principle of Cancer Radiotherapy 1.1 Introduction 1.2 External Beam Radiotherapy 1.3 Mechanisms and Effects of Radiotherapy on Cancer and Normal Cells 1.4 Preparatory Process Before Radiotherapy 1.5 Immobilization, Motion Management, Image Acquisition, and Target Volume Delineation 1.6 Simulation and Image Acquisition 1.7 Treatment Planning and Optimization 1.8 Pretreatment Setup Verification and Radiotherapy Delivery 1.9 Recent Advances in Radiotherapy for Liver Cancer 1.10 Transarterial Radioembolization 1.11 Further Technological Advances of Radiotherapy for Liver Cancer 1.12 Conclusion References 2: Radiobiology of the Liver 2.1 Whole Liver Radiation Therapy (RT) 2.2 Partial Liver RT 2.3 Hypofractionation/Stereotactic Body Radiation Therapy (SBRT) 2.4 Radiation-Induced Liver Disease (RILD) 2.5 Non-classic RILD 2.6 Laboratory Investigations 2.6.1 Imaging of Liver Injury 2.6.2 Therapeutic Approaches for RILD 2.6.3 Future Directions 2.6.3.1 Cell Transplantation to Ameliorate RILD 2.6.3.2 Radiation as an Immunomodulatory Drug for In Situ Tumor Vaccination References 3: Imaging Anatomy for the Radiation Oncologist 3.1 Cross-Sectional Imaging Protocol 3.1.1 Computed Tomography (CT) 3.1.2 Magnetic Resonance Imaging (MRI) 3.2 Imaging Anatomy of the Liver 3.2.1 Liver Segmental Anatomy 3.2.2 Lymphatic Drainage of the Liver 3.2.3 Anatomy of the Bile Duct 3.2.4 Luminal Organs at Risk: Hollow Viscus 3.3 Practical Considerations in the Evaluation of Tumor Extent 3.3.1 Arterioportal Shunt 3.3.2 Malignant Portal Vein Thrombosis 3.3.3 Intraductal Growing HCC 3.3.4 Intrahepatic Metastasis 3.3.5 Post-Locoregional Treatment Imaging References 4: Functional Assessment of Liver for Radiation Oncologist 4.1 Radiotherapy-Induced Liver Disease (RILD) 4.2 General Liver Biochemical and Function Test 4.3 Child-Turcotte-Pugh (CTP) Score 4.4 Model for End-Stage Liver Disease (MELD) Score 4.5 Albumin-Bilirubin (ALBI) Score 4.6 Indocyanine Green (ICG) Clearance Test References 5: Antiviral Therapy in Liver Cancer 5.1 Introduction 5.2 Hepatitis B Virus 5.2.1 Antiviral Agents for HBV 5.2.2 Role of Antiviral Therapy to Reduce Risk of Developing Liver Cancer 5.2.3 Role of Antiviral Therapy to Prevent Recurrence in Liver Cancer 5.2.4 Effect of Antiviral Therapy on Prognosis of Liver Cancer 5.2.5 Prophylactic Antiviral Therapy 5.3 Hepatitis C Virus 5.3.1 Antiviral Agents for HCV 5.3.2 Role of Antiviral Therapy to Reduce Risk of Developing Liver Cancer 5.3.3 Role of Antiviral Therapy to Prevent Recurrence in Liver Cancer 5.3.4 Effect of Antiviral Therapy on Prognosis of Liver Cancer 5.3.5 Prophylactic Antiviral Therapy 5.4 Conclusion References Part II: Technologies and Techniques in Radiotherapy of Liver Cancer 6: Technological Advances in Radiotherapy 6.1 Introduction 6.2 Conformal Radiotherapy 6.3 Image-Guided Radiotherapy Technology 6.3.1 Target Delineation 6.3.2 Respiratory Motion Management 6.3.3 Tumor Surrogates and Setup Verification 6.4 Conformal Avoidance 6.5 Stereotactic Ablative Body Radiotherapy 6.6 MR Linac-Based Radiotherapy 6.7 Proton Beam Therapy 6.7.1 Passively Scattered Proton Therapy 6.7.2 Intensity-Modulated Proton Therapy 6.8 Carbon Ion Radiation Therapy 6.8.1 Biological Effects of CIRT 6.8.2 Modeling, Prescribing, and Reporting CIRT 6.8.3 Clinical Attributes of CIRT for HCC 6.8.3.1 Dose Conformality 6.8.3.2 Hypofractionation 6.8.3.3 Dose Escalation 6.9 Conclusions References 7: Basics of Ablative Radiotherapy: The Background Knowledge Necessary to Practicing Stereotactic Body Radiotherapy for Hepatocellular Carcinoma 7.1 Introduction 7.2 Materials and Methods 7.3 Results 7.3.1 Epidemiology, Risk Factors, Guidelines, and Treatment Options 7.3.2 SBRT Patient Selection, Outcomes, and Comparative Studies 7.3.3 SBRT Target Delineation, Treatment Planning, and Medical Physics Considerations 7.3.3.1 Target Definition and Delineation 7.3.3.2 Breathing Motion 7.3.3.3 Treatment Planning 7.3.3.4 Treatment Unit 7.4 Discussion References 8: Image-Guided Radiotherapy 8.1 Introduction 8.2 Imaging for Radiation Treatment Planning 8.2.1 Simulation 8.2.2 Defining Treatment Volumes 8.2.3 Quantification of Motion 8.3 Motion Management 8.4 Rationale for Image-Guided Radiation Therapy (IGRT) 8.5 IGRT Technologies 8.5.1 Pre-IGRT Preparation 8.5.2 Orthogonal X-Ray Projection Imaging and Fluoroscopy 8.5.3 MV Volumetric Image Guidance 8.5.4 In-room CT 8.5.5 Cone-Beam CT (CBCT) 8.5.6 MR-Guided Radiation Therapy (MRgRT) 8.6 Conclusions References 9: Particle Beam Radiotherapy 9.1 Introduction 9.2 Physical Characteristics of Proton Beams 9.3 Biological Characteristics 9.4 History of Particle Beam Therapy 9.5 Techniques in Proton Therapy 9.5.1 Passive Scattered Proton Therapy 9.5.2 Spot Scanning Therapy 9.5.3 Intensity-Modulated Proton Therapy (IMPT) 9.6 Proton Therapy for HCC 9.6.1 Local Control 9.6.2 Survival 9.6.3 Adverse Effects 9.6.4 Efficacy of PBT for HCC 9.7 Treatment Factors in Proton Therapy 9.7.1 Liver Function and Coexisting Disease 9.7.2 Tumor Size 9.7.3 Tumor Location and Protocol 9.7.4 Portal Vein Tumor Thrombosis (PVTT) and Inferior Vena Cava Tumor Thrombosis (IVCTT) 9.7.5 Re-irradiation 9.8 Carbon Ion Radiotherapy 9.9 Summary References 10: Internal Radiotherapy Using Radionuclides 10.1 Introduction 10.2 Therapeutic Radionuclides: Iodine-131, Yttrium-90, Holmium-166, Rhenium-188 10.3 Patient Selection and Evidence for Y-90 SIRT in Hepatic Malignancies 10.4 Hepatic Angiography: Interventional Radiology Techniques and Procedure 10.5 Radiation Simulation Study: MAA Scintigraphy 10.6 Dose Activity Prescription and Predictive Dosimetry 10.7 Post-treatment Imaging: Bremsstrahlung SPECT/CT and Y-90 PET/CT Imaging 10.8 Side Effects of SIRT 10.9 Miscellaneous Radionuclide Treatment of Liver Cancer: Peptide Receptor Radionuclide Therapy (PRRT) 10.10 Use of Adjunct External Beam Radiotherapy with SIRT 10.11 Conclusion References Part III: Radiotherapeutic Strategies in Liver Cancer 11: Therapeutic Guidelines for Patients with Liver Cancer from the Perspective of Radiation Oncologists 11.1 Introduction 11.2 Landmark Guidelines from International Associations 11.3 Guidelines from National Associations 11.4 Appraisal of Guidelines 11.5 Summary and Conclusions References 12: Ablative Radiation Therapy for Early Hepatocellular Carcinoma 12.1 Treatment of Early HCC 12.1.1 The Significance of Surveillance in Early HCC Detection 12.1.2 Early HCC that Should Be Treated 12.2 The Role of SBRT as a Curative Local Therapy 12.2.1 SBRT as an Ablative Therapy 12.2.2 Local Control of SBRT and Other Local Therapies 12.2.3 Survival after SBRT and Other Local Therapies 12.2.4 SBRT as a Definitive Treatment for Small HCC 12.2.5 Ongoing Trials Involving SBRT for HCC 12.3 Optimal Prescribed Doses 12.3.1 Dose-Response in HCC 12.3.2 Dose Prescription in Consideration of Liver Preservation 12.4 SBRT in Special Situations and Future Directions References 13: Transarterial Chemoembolization Plus External Beam Radiotherapy 13.1 Transarteral Chemoembolization 13.2 The Weakness of TACE 13.3 The Benefit of Combining TACE and RT 13.4 Approaches for Combining RT and TACE 13.5 Clinical Evidences of Combining RT with TACE 13.6 Special Consideration 13.6.1 Portal-Vein Tumor Thrombosis 13.6.2 Optimal Timing of RT After TACE 13.6.3 Optimal Dose of RT After TACE 13.7 Treatment-Associated Complications References 14: Definitive Radiotherapy for Locally Advanced Hepatocellular Carcinoma 14.1 Introduction 14.2 Macroscopic Vascular Invasion 14.3 Rationale of External Beam Radiotherapy for Macroscopic Vascular Invasion 14.4 Clinical Outcomes of Radiotherapy for HCC with Macroscopic Vascular Invasion 14.4.1 Pilot Study in the Initial Stage 14.4.2 The Results of External Beam Radiotherapy Alone 14.4.3 Emergence of the Combined Radiotherapy with Transarterial Treatments 14.4.4 Comparison Studies on the Management of HCC with Macroscopic Vascular Invasion 14.4.4.1 Treatment Combinations with and Without Radiotherapy 14.4.4.2 TACE and Radiotherapy Combination Versus TACE 14.4.4.3 Concurrent Radiotherapy with HAIC Versus HAIC Alone 14.4.4.4 Study Including Hepatic Resection as a Primary Treatment 14.4.4.5 Combined TACE and Radiotherapy Versus Sorafenib 14.5 Additional Considerations 14.5.1 Definition of the Target Volume During Radiotherapy Planning 14.5.2 Radiotherapy-Related Toxicities 14.5.3 Future Directions in Combination with New Immunotherapy and Systemic Therapies 14.6 Conclusions References 15: Neoadjuvant Radiotherapy Converting to Curative Resection 15.1 Introduction 15.2 How to Assess Resectability in HCC 15.3 Neoadjuvant RT in Locally Advanced HCC 15.4 Curative Resection After Downstaging RT 15.5 Conclusions References 16: Bridging Therapy for Liver Transplantation 16.1 Introduction 16.2 Bridge to Transplant Therapies for Hepatocellular Carcinoma 16.3 Clinical Evidence of Radiotherapy as a Bridge to Transplant Therapy 16.4 Radiotherapy Compared to Other Bridge to Transplant Therapies 16.5 Toxicity 16.6 Radiology - Pathology Correlation After Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma 16.7 Special Considerations for Stereotactic Body Radiation Therapy Planning 16.8 Future Directions 16.9 Summary References 17: Palliative Radiotherapy 17.1 Radiotherapy for Treating HCC with Venous Tumor Thrombi 17.1.1 Survival of HCC Patients with PV and/or IVC Tumor Thrombi Treated with 2- or 3-Dimensional Conformal RT Versus no RT 17.1.2 Combined TACE and 3-Dimensional Conformal RT 17.1.2.1 Retrospective Studies 17.1.2.2 Prospective Randomized Studies 17.1.3 Combined EBRT and Chemotherapy 17.1.4 Neoadjuvant RT 17.1.5 EBRT for IVC Tumor Thrombosis 17.1.6 Image-Guided Intensity Modulated RT 17.1.7 Prognostic Factors 17.1.8 RT Techniques 17.2 Lymph Node Metastases 17.2.1 Introduction 17.2.2 Efficacy of EBRT 17.2.3 Prognostic Factors 17.2.4 RT Techniques 17.3 EBRT for Non-lymphatic Extrahepatic Metastasis 17.3.1 Bone and Soft Tissue Metastasis 17.3.1.1 Diagnosis of Bone Metastases from HCC 17.3.1.2 Clinical Features of BM from HCC 17.3.1.3 Treatment of BM from HCC Surgery RFA TACE Internal RT Bisphosphonates Analgesic Medications EBRT 17.3.1.4 Efficacy of EBRT Effectiveness of EBRT for BM from HCC Efficacy of EBRT for BM Following Liver Transplantation for HCC Differentiating Between Needle Tract Seeding and BM in Patients with Soft-Tissue Masses Comparison Between Conventional Fractionation and Hypofractionated RT for BM from HCC 17.3.1.5 Prognostic Factors 17.3.1.6 RT Techniques 17.3.2 Adrenal Gland Metastases 17.3.2.1 Introduction 17.3.2.2 RT Effects 17.3.2.3 Prognostic Factors 17.3.2.4 RT Techniques 17.3.3 Pulmonary Metastases from HCC 17.3.3.1 Introduction 17.3.3.2 Treatment Surgical Resection Interventional Therapy Molecular Targeted Therapy Chemotherapy Microwave Ablation or RFA EBRT 17.3.3.3 RT Effects 17.3.3.4 RT Techniques 17.3.4 Brain metastasis 17.3.4.1 Characteristics of Brain Metastasis from HCC 17.3.4.2 Management of Brain Metastasis from HCC Single Intracranial Metastasis Multiple Intracranial Metastases 17.3.4.3 Prognostic Factors 17.3.5 Peritoneal Implantation of HCC 17.3.6 Rare Types of Metastases 17.4 Typical Cases: Description and Discussion 17.4.1 Case 1 17.4.1.1 Description 17.4.1.2 Discussion Does RT Decrease Mortality of Patients with HCC Who Have Abdominal LNM? What Dosage Can Be Delivered to Abdominal LNM? Can RT Improve Survival in Patients with HCC Who Have PV or IVC Tumor Thrombi? What Dosage Can Be Delivered to PV and/or IVC Tumor Thrombi? Does RT Shrink Adrenal Metastatic HCC Lesions? Is IGRT Superior to Non-IGRT for Overall Survival and Local Control? Why Was the Tumor in the Left Hepatic Lobe Not Treated with a Third Course of RT? 17.4.2 Case 2 17.4.2.1 Case Description 17.4.2.2 Discussion Diagnosis Treatments What Is the Indication for RT? What Is the Goal of RT? What Is the Treatment Volume? What Is the Planned Treatment Technique? What Is the Planned Treatment Dose? What Types of Treatment Could Be Combined with RT to Improve Patient Outcomes? References Part IV: Specific Issues 18: Multidisciplinary Team Approaches for the Management of Hepatocellular Carcinoma 18.1 Introduction 18.2 What Is the Hurdle of Current Systemic Therapy? 18.3 Can Combination Therapy Overcome the Hurdle of Current Systemic Therapy? 18.4 Multidisciplinary Team Approach to Patients with HCC 18.5 Localized Concurrent Chemoradiation Therapy for Locally Advanced HCC 18.6 Summary and Conclusion References 19: Response Evaluation After Radiotherapy 19.1 Histopathological Changes After Liver Radiotherapy 19.1.1 Changes in the Liver Parenchyma 19.1.2 Changes in the Tumor Tissue 19.2 Image Response Evaluation Criteria 19.3 Image Evaluation Tools 19.4 Imaging Changes 19.4.1 Tumor Imaging Changes 19.4.2 Liver Parenchyma Imaging Changes 19.5 Potential Pitfalls in Tumor Response Evaluation 19.6 Conclusion References 20: Liver Hypertrophy Following Radiotherapy 20.1 Portal Vein Ligation or Embolism to Achieve an Adequate Future Liver Remnant 20.2 Liver Hypertrophy Following Internal Radiotherapy 20.3 Liver Hypertrophy Following External Beam Radiotherapy (EBRT) 20.4 Summary and Conclusions References 21: Hepatic Dysfunction Following Radiotherapy and Management 21.1 Introduction 21.1.1 Radiation-Induced Liver Disease 21.1.1.1 Pathogenesis of RILD 21.1.1.2 Classification of RILD 21.1.2 Hepatic Dysfunction Following Radiation Therapy 21.1.2.1 Ascites 21.1.2.2 Diuretics 21.1.2.3 Measures to Maintain Blood Pressure 21.1.2.4 Therapeutic Paracentesis 21.1.2.5 Management of Refractory Ascites 21.1.3 Spontaneous Bacterial Peritonitis 21.1.4 Jaundice 21.1.4.1 Management of Jaundice 21.1.5 Portal Hypertension and Variceal Hemorrhage 21.1.5.1 Management of Acute Esophageal Variceal Bleeding 21.1.5.2 Prevention of Rebleeding of Esophageal Varices 21.1.6 Hepatorenal Syndrome 21.1.6.1 Drug Therapy 21.1.6.2 TIPS 21.1.6.3 Renal Replacement Therapy 21.1.6.4 Liver Transplantation 21.1.7 Hepatic Encephalopathy 21.1.7.1 Diagnosis of HE 21.1.7.2 Treatment of HE 21.1.7.3 Prevention of HE 21.2 Conclusions References 22: Lymphopenia Following Radiotherapy for Hepatocellular Carcinoma 22.1 The Radiosensitivity of Lymphocytes 22.2 Factors Associated with Radiation-Induced Lymphopenia 22.3 Radiation-Induced Lymphopenia and Treatment Outcome 22.4 Radiation-Induced Lymphopenia and Immune System 22.5 Chronicity of Radiation-Induced Lymphopenia 22.6 Liver Cancer and Radiation-Induced Lymphopenia 22.7 Recommendations to Reduce the Development of Radiation-Induced Lymphopenia 22.8 Prospects References 23: Perspectives of Radiotherapy in Immuno-oncology Era 23.1 Immune Environment of Liver 23.1.1 Special Immune Environment of Liver 23.1.2 Immune Dysfunction of HCC 23.1.3 Immune-Related Tumor Microenvironment 23.2 Immunotherapy in HCC 23.2.1 The Limitation of Treatment in HCC 23.2.2 Evolving Immunotherapy in HCC 23.2.3 Current Status of Immunotherapy in HCC 23.2.4 The Concerns of Immunotherapy in HCC 23.3 The Integration of Radiotherapy in Immunotherapy 23.3.1 Radiation and Immune Response 23.3.2 Radiation and Immune-Related TME 23.3.3 Abscopal Effect with RT 23.3.4 The Impact of RT Dose and Fractionation on Immune Modulation 23.3.5 Clinical Trial on Combined RT and Immunotherapy in Non-HCC Cancers 23.4 Experimental Model of RT and Immunotherapy in HCC 23.4.1 The Limitation of RT and the Need of Combined RT and Immunotherapy in HCC 23.4.2 Preclinical Experiments of RT and Immunotherapy in HCC 23.4.3 NK Cell and MHC I Chain-Related Protein A/B 23.4.4 Personalized Peptide Vaccination 23.4.5 Interleukin 12 23.4.6 Histone Deacetylase Inhibitor 23.4.7 Glucocorticoid-Induced Tumor Necrosis Factor Receptor 23.4.8 T Cell Immunoglobulin and Mucin-Domain Containing Molecule-3 23.5 Perspectives in the Combination of RT and Immunotherapy to HCC 23.5.1 Completed, Ongoing, and Upcoming Clinical Studies on the Use of Combined RT and Immunotherapy in HCC Patients 23.5.2 A Future Scope of RT in Immuno-oncology Era for HCC References