Retinoblastoma

by Rodriguez-galindo, Carlos; Wilson, Matthew W.

• ISBN13: 9780387890715
• ISBN10: 0387890718
• Edition: 1st
• Format: Hardcover
• Copyright: 2010-03-09
• Publisher: Springer Verlag

Summary

Treatment of retinoblastoma has evolved at a significant speed over the last two decades; ocular salvage approaches are now at the core of modern treatments, and assessment of visual and functional outcomes has become a priority. New discoveries in retinoblastoma biology are leading the way to the development of targeted therapies that could revolutionize our current approaches to the treatment. In this book, experts address all the important aspects of research and therapy - from biology to epidemiology to treatment. Retinoblastoma will provide a single source for the diagnosis and care of children with this malignancy.

Table of Contents

Biology of Retinoblastoma
Landmark Discoveries in Cancer Genetics	p. 1
The Retinoblastoma Paradox	p. 2
Secondary Genetic Lesions in Retinoblastoma	p. 3
Preclinical Models of Retinoblastoma	p. 5
Improving Retinoblastoma Treatment with Preclinical Studies	p. 7
Cell of Origin for Retinoblastoma	p. 7
Conclusions	p. 8
References	p. 8
Epidemiology
Introduction	p. 11
Incidence	p. 12
Population Differences in Incidence	p. 12
Variation Within Countries: Subpopulations with Higher Incidence	p. 14
Gender Differences	p. 15
Biologic Underpinnings of Epidemiologic Studies on Retinoblastoma	p. 15
Potential Hypotheses	p. 16
Parental Occupations	p. 16
Parental Age	p. 16
In Vitro Fertilization (IVF)	p. 17
UV Exposure	p. 17
Nonoccupational Parental Exposures	p. 18
Diet	p. 18
Viral Agents	p. 19
Diagnostic Interval	p. 19
Screening and Media Campaigns	p. 20
Summary	p. 20
References	p. 21
Clinical Features, Diagnosis, Pathology
Introduction	p. 25
Initial Presentation	p. 25
Clinical History	p. 26
Initial Examination	p. 27
Differential Diagnosis	p. 27
Examination Under Anesthesia	p. 28
Fine Needle Aspiration Biopsy	p. 30
Grouping and Staging of Retinoblastoma	p. 30
Pathology	p. 30
Histologic Features	p. 32
Extraocular Extension, Metastasis, and Prognostic Factors	p. 33
Metastasis	p. 36
Prognostic Factors for Metastasis	p. 37
Trilateral Retinoblastoma and Other Tumors	p. 37
Processing of Eyes with Retinoblastoma for Histopathologic Examination	p. 38
References	p. 39
Genetics of Retinoblastoma and Genetic Counseling
Introduction	p. 41
Molecular Genetic Progression of Retinoblastoma	p. 41
The RB1 Gene, Protein, and Function	p. 42
Cell of Origin	p. 42
Transient Arrest: Senescence Halts Retinoma	p. 43
Post-RB1 Progressive Events	p. 43
Genomic Gain of 1q: KIF14	p. 43
Genomic Gain of 6p: DEK and E2F3	p. 44
Genomic Gain of 2p: NMYC	p. 44
Genomic Loss of 16q: CDH11	p. 44
Deregulation of Apoptosis: Loss of Expression of p75NTR	p. 45
Murine Models of Retinoblastoma	p. 45
RB1 Knockout Mouse Models	p. 45
Viral Oncoprotein-induced Murine Retinoblastoma	p. 45
Conditional RB1 Knockout Murine Retinoblastoma Models	p. 46
Limitations of Mouse Models	p. 46
Summary: A Model of Retinoblastoma Development	p. 46
Genetic Counseling	p. 46
Heritability of Retinoblastoma	p. 46
Role of Environmental Factors	p. 48
Molecular Genetic Testing	p. 48
RB1 Test Strategies	p. 48
Sporadic Bilateral or Familial Retinoblastoma	p. 48
Sporadic Unilateral Retinoblastoma	p. 49
Prenatal Testing	p. 49
RB1 Mutation Identification	p. 49
Missense Mutations	p. 49
Frameshift and Nonsense Mutations	p. 50
Aberrant Splicing	p. 50
Epigenetic Mutations	p. 50
Translocations and Gross Deletions	p. 50
Penetrance of Retinoblastoma	p. 51
Mosaicism	p. 51
Parent of Origin Effect	p. 51
Conclusions and Significance	p. 51
Glossary	p. 52
References	p. 52
Radiation Therapy in the Management of Retinoblastoma
Introduction	p. 55
Treatment Methods	p. 56
Extraocular and High-Risk Retinoblastoma	p. 60
Secondary Malignant Tumors	p. 61
Nonmalignant Side Effects from Radiation Therapy	p. 63
Controversies in the Management of Retinoblastoma	p. 63
Recommendations	p. 64
References	p. 64
Chemotherapy in the Management of Retinoblastoma
Introduction	p. 67
Ocular Pharmacokinetics	p. 68
Ocular Drug Transporters	p. 69
Chemotherapy in the Treatment of Intraocular Retinoblastoma	p. 69
Unilateral Retinoblastoma	p. 69
Bilateral Retinoblastoma	p. 70
New Tumor Formation on Chemotherapy	p. 72
Therapy-Related Leukemia	p. 73
Periocular Administration of Chemotherapy	p. 73
Mechanisms for Transscleral Drug Delivery	p. 73
Periocular Chemotherapy in Retinoblastoma	p. 75
Intravitreal and Intrarterial Chemotherapy for Intraocular Retinoblastoma	p. 77
Treatment of Extraocular Retinoblastoma	p. 77
Orbital and Locoregional Retinoblastoma	p. 77
Metastatic Retinoblastoma	p. 78
Translational Research and Emergent Therapies in Retinoblastoma	p. 79
Specific Agents	p. 81
Vincristine	p. 81
Carboplatin	p. 81
Etoposide (VP-16)	p. 82
Doxorubicin	p. 82
Cyclophosphamide	p. 83
Cisplatin	p. 84
Topotecan	p. 85
Thiotepa	p. 85
References	p. 86
Treatment of Intraocular Retinoblastoma
Introduction	p. 91
Primary Treatments	p. 91
Focal Therapies	p. 94
Emerging Treatments	p. 99
Conclusion	p. 99
References	p. 99
Treatment of Extraocular and Metastatic Retinoblastoma
Introduction	p. 103
Patients with High Risk Intraocular Disease	p. 104
Choroidal Invasion	p. 105
Optic Nerve Invasion	p. 105
Patients with Microscopic Residual Disease after Enucleation	p. 106
Trans-Scleral Invasion	p. 107
Future Directions	p. 108
Orbital and Locoregional Disease	p. 108
Orbital Relapse	p. 109
Special Situations	p. 110
Metastatic Disease	p. 111
Stage 4a: Metastatic Disease Without CNS Involvement	p. 111
Stage 4b: Distant Metastatic Disease with CNS Involvement	p. 112
Future Research	p. 112
References	p. 113
Second Malignancies and Other Long Term Effects in Retinoblastoma Survivors
Introduction	p. 115
Second Malignancies	p. 115
Osteosarcoma	p. 117
Soft Tissue Sarcomas	p. 119
Skin Cancers	p. 120
Lung Cancer and Other Common Cancers of Adulthood	p. 120
Hematologic Malignancies	p. 121
Trilateral Retinoblastoma	p. 121
Other Long Term effects	p. 123
Orbital Growth and Facial Asymmetry	p. 123
Visual Outcome	p. 123
Cognitive and Functional Development of Patients with Retinoblastoma	p. 123
Other Late Effects	p. 124
References	p. 124
Visual Rehabilitation
Introduction	p. 127
Spectacles	p. 127
Patching or Pharmacologic Penalization	p. 129
Cataract Surgery	p. 129
Strabismus Surgery	p. 131
Low Vision	p. 131
Conclusion	p. 132
References	p. 132
Retinoblastoma in Developing Countries
Introduction	p. 133
Delayed Diagnosis	p. 134
Causes of Delayed Diagnosis	p. 135
Preventing Late Diagnosis	p. 135
Special Problems in the Treatment of Retinoblastoma in Less Developed Countries	p. 137
Resources to Address this Global Problem	p. 138
References	p. 140
Appendix	p. 143
Subject Index	p. 153
Table of Contents provided by Ingram. All Rights Reserved.