Clinical ophthalmic oncology : retinoblastoma

Description

Preface Acknowledgments Contents Contributors 1: Retinoblastoma: Evaluation and Diagnosis Historical Background Clinical Presentation Misdiagnosis Stepwise Evaluation for Retinoblastoma History Initial Examination Ophthalmic Ultrasonography Examination Under Anesthesia External Examination Anterior Segment Examination Posterior Segment Examination Ancillary Testing Photography Fluorescein Angiography Ophthalmic Ultrasonography Ultrasound Biomicroscopy Electroretinogram Neuroimaging Counseling References 2: Differential Diagnosis of Leukocoria Introduction Retinoblastoma Clinical Presentation Demographics/History Diagnosis Coats’ Disease Clinical Presentation Demographics Diagnosis PHPV/PFV Clinical Presentation Demographics Diagnosis Astrocytic Hamartoma Clinical Presentation Demographics Diagnosis Toxocariasis Clinical Presentation Demographics Diagnosis ROP (Retinopathy of Prematurity) Clinical Presentation Demographics Diagnosis Hereditary Retinal Syndromes FEVR (Familial Exudative Vitreoretinopathy) Norrie’s Disease Incontinentia Pigmenti Coloboma References 3: Retinoblastoma: Staging and Grouping Introduction Unique Aspects of Retinoblastoma Reese-Ellsworth Classification International Classification of Retinoblastoma Staging the Patient Background Pre-IIRC Staging Systems St. Jude’s Hospital Staging Children’s Cooperative Group (CCG) Classification Grabowski-Abramson Classification International Retinoblastoma Classification: Staging System Stage 0 Stage I Stage II Stage III Stage IV Possible Future Improvements Grouping the Eye Disease Background International Intraocular Retinoblastoma Classification: Grouping System Group A Group B Group C Group D Group E International Classification of Retinoblastoma (ICRB) and Other Clinical Classifications: Why the Inconsistencies Matter Possible Future Improvements Improved Prediction of Vision Salvage Probability in Each Group Allowing Intraocular Grouping to Change in Case of Disease Progression Clinical Application of International Retinoblastoma Classification Moving Toward a New TNM System for Retinoblastoma: AJCC 8th Ed Summary References 4: Retinoblastoma: Incidence and Etiologic Factors Introduction Familial Retinoblastoma Sporadic Heritable Retinoblastoma Nonheritable Retinoblastoma Variations in Incidence Unilateral and Bilateral Retinoblastoma Expression of Incidence Geographic Variation in Incidence North America Europe Central and South America Asia Africa Oceania Gender Variation in Incidence Comment on Data Interpretation Conflicting Results Quality of Data and Subpopulations Models Based on Scandinavian Birth Cohorts and Birth Rate Etiology: Risk Factors for Sporadic Heritable Retinoblastoma Parental Risk Factors Etiological Factors for Nonheritable Retinoblastoma Environmental Exposure Maternal Diet and/or Vitamin Intake During Pregnancy In Vitro Fertilization (IVF) Inactivation of pRb Through Viral Complexes Future Directions Summary References 5: Retinoblastoma: An International Perspective Introduction Incidence Clinical Features Presenting Signs of Retinoblastoma in Developing Countries Extraocular Retinoblastoma at Presentation Delayed Diagnosis Patient-Related Factors Physician-Related Factors Socioeconomic Factors Survival Survival with Retinoblastoma Is Lower in the Developing Countries Steps to Improve Survival Public Awareness Programs Professional Education Programs Screening for Retinoblastoma Minimizing Treatment Refusal Socioeconomic Development Treatment Challenges in Developing Countries The Challenge of Conservative Therapy The Challenge of Adjuvant Therapy The Challenge of Treatment of Overt Extraocular Disease Developments that Provide Hope for the Future Creation of Cooperative Groups International Collaborative Efforts Summary References 6: Retinoblastoma Tumorigenesis Introduction Retinoblastoma Cell of Origin Events in Retinoblastoma Progression Retinoblastoma Genomics Recurrent Chromosomal Abnormalities in Retinoblastoma Escaping Death and Promoting Clonal Expansion: p53 Pathway in Retinoblastoma Retinoblastoma Epigenomics miRNAs DNA Methylation Uncommon RB Genesis 13q Syndrome MYCN Amplification (Chromosome 2p) Chromothripsis Preclinical Models of Retinoblastoma Clinical Implications References 7: Animal Models in Retinoblastoma Research Background Models of Retinoblastoma Early Adenoviral Models Genetic Models of Retinoblastoma Rb1/p53/p107 Knockout Mouse Model LHβTAG Mouse Model Cell of Origin and Validity of Mouse Models Xenograft Models of Retinoblastoma Location of Xenograft Choice of Xenografted Tissue Preventing Rejection of the Xenograft by the Immune System Immunocompromised and Immunologically Naïve Hosts Pharmacological Exogenous Immunosuppression to Facilitate Xeno-engraftment Preclinical Animal Models to Assess Pharmacokinetics and Toxicity Models of Intravitreal Chemotherapy Models of Periocular Chemotherapy Models of Intravenous Chemotherapy Models of Intra-arterial Chemotherapy Porcine Models Nonhuman Primate (NHP) Models Rabbit Models Animal Models to Test Therapeutic Efficacy Against Retinoblastoma Intravenous Models Considerations Combination Periocular/Systemic Therapy Intravitreal Models Considerations Intra-arterial Model Considerations References 8: Retinocytoma or Retinoma Introduction Etiology and Pathogenesis Clinical Features and Diagnosis Characteristics Diagnostic Evaluation Fluorescein Angiography Ultrasonography Optical Coherence Tomography (OCT) Histopathology Differential Diagnosis Retinoblastoma Astrocytic Hamartoma Myelinated Nerve Fibers Treatment and Follow-Up References 9: Retinoblastoma: Genetic Counseling and Testing Introduction Background Who Is the Patient in Genetic Counseling? Who Should Be Referred for Genetic Counseling and Testing? The Role of the Genetic Counselor Preparing the Family/Patient for Genetic Counseling The Pedigree and Family History Confounding Factors Chromosome 13q14 Deletions Mosaicism Low-Penetrance Mutations and Variable Expressivity Evolving Phenotypes and Changing Pedigrees The Isolated Case of Unilateral Retinoblastoma Prenatal Diagnosis The Limits of Technology and Non-informative Results Mutation Detection The Future in DNA Testing for Retinoblastoma RB1+/+ MYCNA Tumors Summary References 10: Retinoblastoma: Treatment Options Introduction Classification (Grouping) Intravenous Chemotherapy Treatment Parameters Concomitant Focal Therapy Efficacy Complications Periocular Chemotherapy (Injections and Exoplants) Efficacy Complications Selective Intra-arterial Chemotherapy (IAC) Efficacy Complications Intravitreal Chemotherapy Efficacy Complications Laser Therapy Treatment Parameters Efficacy Complications Cryotherapy Treatment Parameters Efficacy Complications Brachytherapy Treatment Parameters Efficacy Complications External Beam Radiotherapy Treatment Parameters Efficacy Complications Enucleation Emerging Therapies Conclusion References 11: Retinoblastoma: Focal Therapy: Laser Treatment and Cryotherapy Introduction Terminology Focal Treatment Focal Primary Treatment Chemoreduction Consolidation Treatment Photocoagulation Hyperthermia Thermotherapy Focal Primary Treatment Focal Consolidation Treatment Photocoagulation with Argon Green Laser (532 nm) Background Technique Frequency of Treatment Mechanism of Action Recommendations Photocoagulation with Red Laser (810 nm) Background Technique Frequency of Treatment Mechanism of Action Recommendation Transpupillary Thermotherapy (TTT) Transscleral Cryotherapy Background Technique Mechanism of Action Frequency of Treatment Recommendations Special Recommendations for Consolidation Therapy References 12: Retinoblastoma: Focal Therapies: Brachytherapy Introduction Brachytherapy Background Technique Mechanism of Action Frequency of Treatment Recommendations Efficacy as Primary Treatment Efficacy as Secondary Treatment Complications Conclusion References 13: Retinoblastoma: Intravenous Chemotherapy Introduction Chemotherapy Regimens Treatment of Intraocular Retinoblastoma Group A and B Eyes Group C, D, and E Eyes Special Considerations Low-Dose Chemoreduction for Infants Diagnosed with Retinoblastoma Before 6 Months of Age Drug Shortage High-Risk Pathology Treatment of Extraocular Retinoblastoma Regional Extraocular Disease: Stage II and III Metastatic Retinoblastoma Without CNS Involvement: Stage IVa Metastatic Retinoblastoma with CNS Involvement: Stage IVb Trilateral Retinoblastoma Chemotherapy Agents Treatment-Related Toxicity: Carboplatin, Etoposide, and Vincristine (CEV) References 14: Intra-ophthalmic Artery Chemotherapy for Retinoblastoma Introduction Historic Background Current Technique Current Results Visual Outcome Confounding Factors Complications Current Status Future Studies References 15: Retinoblastoma: Intravitreal Chemotherapy Introduction Background and History Vitreous Seeding Pathogenesis Clinical Features Clinical Classification, Histopathological Correlation, and Correlation to Treatment Response Chemotherapy Agents Diagnostic Evaluation, Determination of IVitC Eligibility, and Follow-Up Initial Evaluation: Criteria of Eligibility Follow-Up Evaluation of IVitC: Response Monitoring Technique Treatment Outcomes Adverse Effects Perspectives References 16: Retinoblastoma: External Beam Radiation Introduction Current Indication and Efficacy Globe Preservation Visual Acuity Side Effects and Secondary Malignancies Risk of Second Malignant Neoplasms The 1914–1984 New York/Boston Patient Series [15] The Incidence of Radiogenic Tumors Is Smaller in Other Series A 2005 Update on the 1914–1984 New York/Boston Patient Series Patient Age at Radiation Appears to Be Important Reducing Side Effects from Radiation Therapy Delay Radiation Lower the Radiation Dose Use Episcleral Plaque Brachytherapy Use New Radiation Treatment Techniques Conformal and Intensity-Modulated Radiation Therapy (IMRT) Proton Beam Radiation Therapy Current Recommendations References 17: Retinoblastoma: Enucleation Introduction Indications Box 17.1 Retinoblastoma: Indications for Enucleation Preoperative Counseling Surgical Procedure Long Optic Nerve Stump Harvest of Fresh Tumor for RB1 Testing or Other Research Uses Insertion of Orbital Implant Attention to Surgical Closure and Prevention of Implant Extrusion Postoperative Care References 18: Retinoblastoma: Evolving Therapies The History of Traditional Treatment Intra-Arterial Chemotherapy Intravitreal Chemotherapy Pars Plana Vitrectomy Surgical Approach to PPV Post-PPV Care Results of PPV for Retinoblastoma References 19: Histopathologic Features and Prognostic Factors Introduction Endophytic Growth Pattern Exophytic Growth Pattern Mixed Growth Pattern Diffuse Infiltrative Pattern Necrotic Retinoblastoma Histopathologic Features Routes of Spread Outside the Eye Optic Nerve Invasion Choroidal Invasion Hematogenous Dissemination Lymphatic Dissemination Histopathologic Factors That May Be Useful in Determining Prognosis Tumor Invasion into the Optic Nerve Tumor Invasion into the Choroid Scleral and Extrascleral Extension Tumor at Surgical Margins and in the Orbit Anterior Segment Involvement Size and Tumor Characteristics Histopathologic Features in Enucleation After Treatment Suggested Guidelines for Handling Enucleated Eyes with Retinoblastoma Limitations of Published Studies Limited Patient Numbers and Inconsistent Treatment Confounding Variables Strategies for the Future Extent of Angiogenesis in Retinoblastoma Tumors Applying Therapy Targeted to Cellular Pathways in the Metastatic Process A Cooperative Group Clinical Trial Conclusions References 20: Orbital Retinoblastoma: Diagnosis and Management Definition Incidence Clinical Features Classification Primary Orbital Retinoblastoma Secondary Orbital Retinoblastoma Accidental Orbital Retinoblastoma Overt Orbital Retinoblastoma Microscopic Orbital Retinoblastoma Evaluation and Investigations Management Follow-Up Future Perspectives Conclusion References 21: Retinoblastoma: Metastatic Disease Introduction Clinical Features Diagnostic Evaluation Differential Diagnosis Treatment and Prognosis Isolated Orbital Retinoblastoma Regional Extraocular Retinoblastoma Distant Metastatic Retinoblastoma Without CNS Involvement (Stage 4a) Conventional-Dose Chemotherapy Plus Radiation Therapy Case Reports of High-Dose Chemotherapy with ASCR Outcomes Using a Protocol of High-Dose Chemotherapy with ASCR Confirmatory Case Series COG ARET0321 for Patients with Stage 4a Disease Distant Metastatic Disease with CNS Involvement (Stage 4b) COG ARET0321 for Patients with CNS Involvement Future Research References 22: Non-ocular Tumors and Other Long-Term Complications Introduction Pathogenesis Genetic Susceptibility Effects of Radiation Therapy Three Subsets of Patients Increased Incidence Timing of the Radiation Therapy Age of Onset Location Types of Second Malignant Neoplasms Radiation-Associated Solid Tumors Alkylating Agent and Topoisomerase II Inhibitor-Related Acute Myeloid Leukemia and Myelodysplastic Syndrome Incidence Clinical Features Treatment Prevention Screening Prognosis Visual Complications After Completion of Therapy Cataract Amblyopia Strabismus References 23: Trilateral Retinoblastoma Introduction Incidence Clinical Presentation Screening Prognosis Treatment References 24: Screening Children at Risk for Retinoblastoma Introduction Background Risk Stratification and Genetics Screening Recommendations Conclusions References 25: Children’s Oncology Group (COG) Trials for Retinoblastoma Introduction Larger Role for Pediatric Oncology Establishment of the Children’s Oncology Group (COG) Major Biologic Questions About the RB1 Pathway Formation of a COG Committee on Retinoblastoma Five COG Retinoblastoma Protocols COG ARET 0332: A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy (The Histopathologic Risk Factor Protocol) Aims Background Study Methods Statistical Considerations Protocol Update COG ARET 0331: Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma (The Group B Protocol) Aims Background Study Methods Statistical Considerations Conclusion COG ARET 0231: A Single-Arm Trial of Systemic and Subtenon Chemotherapy for Groups C and D Intraocular Retinoblastoma (The Group C/D Protocol) Aims Background Study Methods Statistical Considerations Protocol Update COG ARET 0321: A Trial of Intensive Multimodality Therapy for Extraocular Retinoblastoma (The Extraocular Disease Protocol) Aims Background Study Methods Statistical Considerations Protocol Update ARET 12P1: A Multi-institutional Feasibility Study of Intra-arterial Chemotherapy Given in the Ophthalmic Artery of Children with Retinoblastoma (The Intra-arterial Chemotherapy Protocol) Aims Background Study Design Protocol Update Conclusion References 26: Social Aspects, Advocacy and Organizations Introduction Social Determinants and Retinoblastoma First Lag Time: Detection of Symptom to Seeking Care Second Lag Time: Presentation at Primary Health Clinic to Referral to Ophthalmologist Access and Availability of Quality Care Treatment Refusal, Noncompliance and Abandonment Consequences for Patients Addressing Social Determinants in Retinoblastoma Transdisciplinary Research Advocacy Organizations and Approaches Global Collaborations, Projects and Committees Non-governmental Organizations, Charities and Parent Groups Conclusion References Index