Global Perspectives in Ocular Oncology

Description

Eye cancers vary in presentation depending upon geographic location and access to healthcare. Global Perspectives in Ocular Oncology offers an international platform for leading ocular oncologists and multidisciplinary specialists to highlight worldwide strengths and solutions to the challenges in treating eye cancer. The goal of the book is to provide a universal view on the management of adult and pediatric tumors affecting the eye and ocular adnexa.  A range of topics pertinent to the global community have been included. Organized into seven distinct sections, this book covers international collaborations and initiatives, technology and innovations, and novel treatment strategies. In addition, it provides a glimpse into the future of the specialty. The emphasis on sharing perspectives as well as the global and multidisciplinary framework of the book are unique to the market. This work will appeal to a variety of audiences including ocular oncologists and ophthalmic subspecialists, oncologists and other specialists, optometrists, geneticists, allied medical professionals, and trainees entering these disciplines. Foreword Preface Acknowledgments Contents Contributors Part I: The Power of Collaboration Working Together: Specialty Interest Groups with Global Presence 1 Introduction 2 Young Physicians in Training or Early Years in Ocular Oncology 3 Women in Ocular Oncology 4 Patient-Centered Clinical and Research Collaborations: One Retinoblastoma World—World Eye Cancer Hope References Children’s Oncology Group Trials in Retinoblastoma 1 Introduction 2 ARET 0332 3 ARET 0331 4 ARET 0231 5 ARET 0321 6 ARET 12P1 7 Epidemiological Studies 7.1 Future Studies References Worldwide Analysis: The Global Presentation of Retinoblastoma 1 Introduction 2 A Global Perspective of Disease Burden 3 Symptoms Leading to Referral 4 Symptoms at Time of Diagnosis at Retinoblastoma Centers 5 Sex, Gender, and Retinoblastoma 6 Age at Time of Diagnosis 7 Tumor Staging 8 Familial History and Bilateral Retinoblastoma 9 Travel Burden 10 Bridging the Gap 11 Conclusion References International Collaborations for Characterizing Ocular Adnexal Lymphoma 1 Introduction 2 Why International Multicenter Registry-Based Studies? 2.1 Investigating Rare Diseases 2.2 Investigating Diseases with Rarity of Adverse Outcomes 2.3 Validating Staging Systems 2.4 Comparing Patient Populations 2.5 Improving the Dissemination of Research 3 Conducting International Multicenter Registry-Based Studies 3.1 Obtaining Ethical Approvals 3.2 Funding the Project 3.3 Forming an International Registry Database 3.4 Choosing a Database Platform 3.5 Collecting Data 3.6 Analyzing Data 3.7 Publication of the Results 3.8 General Challenges 4 What Is Next for International Research Collaboration? References Big Data: The IRIS® Registry for Ocular Oncology 1 Introduction 2 Large Data Sets in Ocular Oncology 3 The Intelligence Research in Sight (IRIS®) Registry 4 The IRIS® Registry and Ocular Oncology 5 Strategies for Growth References Part II: Multidisciplinary Perspectives Intravenous Chemotherapy for Retinoblastoma: A Pediatric Oncologist’s Perspective 1 Introduction 2 General Principles of Cancer Chemotherapy 3 General Mechanisms of Action 4 Individual Mechanisms of Action and Unique Toxicities in Agents Commonly Used to Treat Retinoblastoma 4.1 Carboplatin 4.2 Etoposide 4.3 Vincristine 4.4 Doxorubicin 4.5 Cyclophosphamide 4.6 Topotecan 5 General Toxicities of Cytotoxic Chemotherapy Regimens 6 Intravenous Chemotherapy Regimens for Intraocular Retinoblastoma 7 Chemoreduction 8 Adjuvant Chemotherapy 9 Treatment of Extraocular Retinoblastoma 10 Metastatic Disease 11 Pineoblastoma (Trilateral RB) 12 Summary References Intra-arterial Chemotherapy for Retinoblastoma: A Team Effort 1 Introduction 2 IAC Objective 3 Indications 3.1 Bridge Chemotherapy 3.2 Tandem Therapy 3.3 Rescue Therapy 4 Contraindications 5 Protocol Treatment 5.1 Customized Treatment 5.2 IAC Technique 5.3 Principal Chemotherapeutic Agents 6 Retinoblastoma Regression Pattern 7 Complications 7.1 Ocular and Periocular Side Effects 7.2 Systemic Side Effects 7.3 Procedure-Related Complications 8 IAC: Advantages and Disadvantages 8.1 Advantages 8.2 Disadvantages 9 Conclusions References Treatment Algorithms for Intraocular Retinoblastoma: An Ocular Oncologist’s Perspective 1 Introduction 2 Primary Therapy 2.1 Unilateral Retinoblastoma 2.2 Bilateral Retinoblastoma 2.3 Intravitreal Melphalan (IVM) During Primary Therapy 2.4 Infants 3 Secondary Therapy 3.1 Vitreous Seeding 3.2 Retinal Recurrence in a Unilateral Patient 3.3 Retinal Recurrence in a Bilateral Patient 4 Treatment Complications 4.1 IAC Complications 4.2 Intravitreal Melphalan Injections for Vitreous Seeding (IVM) 4.3 Systemic Chemotherapy (CEV) 5 Metastatic Risk After IAC and CEV References Treatment for Primary Vitreoretinal Lymphoma: The Neuro-Oncologist’s View 1 Introduction and Nomenclature 2 Epidemiology 3 Prognostic Factors 4 Clinical Presentation 5 Diagnosis and Pathophysiology 6 Treatment 6.1 Local Therapy 6.2 Ocular Radiation Therapy 6.3 Intravitreal Therapy 6.4 Systemic Chemotherapy 7 Combined Systemic and Local Treatment 8 High-Dose Chemotherapy (HDT) and Autologous Stem Cell Transplant (ASCT) 9 Emerging Therapies 9.1 BTK Inhibitors 9.2 Immunomodulatory Drugs 10 Perspective References Advances in Imaging in Ocular Oncology: A Radiologist’s Perspective 1 Introduction 2 Radiological Imaging Techniques in Ocular Oncology 3 Imaging in the Initial Workup for Ocular Tumors: Diagnosis and Staging 3.1 Radiological Imaging Aiding diagnosis in a Child with Suspected Retinoblastoma 3.2 Imaging for Tumor Staging in Retinoblastoma 3.3 Imaging for Diagnosis of Uveal Melanoma 3.4 Imaging for Tumor Staging in Uveal Melanoma 3.5 Imaging of Other Intraocular Tumors 4 Prognosis and Treatment Follow-Up 5 Detection of Associated Brain Tumors in Retinoblastoma 6 Imaging as Screening Tool in Ocular Oncology 7 Future Perspectives References Systemic and Genetic Associations of Ocular and Ocular Adnexal Neoplasms References A Singular View: The Ocularist’s Role in Eye Loss Restoration and Rehabilitation 1 The Fourth “O” in Eye Care: Ocularists 2 Introduction 3 The Main Visual Challenges of Monocularity 4 Visual Field Loss 5 Areas of Visual Field Limitation 6 Solutions to Visual Field Limitations 7 Reconstruction Following Eye Loss 8 The Ocularist’s Work 9 Conclusion References Part III: Current Concepts in Ocular Oncology Guidelines and Recommendations for Retinoblastoma Screening 1 Introduction 2 Genetic Testing 3 Risks for Each Individual Depend on Genetic Testing and Clinical Presentation 4 Screening Protocols 5 Examination Under Anesthesia Versus Non-Sedated Office Examination 6 Risks of Developing Retinoblastoma in the Absence of Genetic Testing 7 Conclusion References Orbital and Metastatic Retinoblastoma: Conquests and Challenges 1 Introduction 2 Orbital Retinoblastoma 2.1 Definition and Classification 2.2 Routes of Spread 2.3 Clinical Features 2.4 Diagnostic Evaluation 2.5 Treatment 2.5.1 Management Algorithm 2.6 Radiotherapy 3 Metastatic Retinoblastoma 3.1 Risk Factors for Metastatic Disease 3.2 Management 3.2.1 Management Algorithm for Metastatic Disease 4 Challenges and Future Directions References Metastatic Behavior of Uveal Melanoma: From Biology to Treatment 1 Introduction 2 Risk Factors for Metastasis 3 Genetic Background 4 Metastasis and Liver Tropism 5 Management of Metastatic Disease in Uveal Melanoma 5.1 Disease Staging and Nomograms 5.1.1 TNM Classification 5.1.2 Helsinki University Hospital Working Formulation 5.1.3 International Rare Cancers Initiative (IRCI) Ocular Melanoma Study 5.1.4 Nomograms 5.2 Best Supportive Care 5.3 Systemic Chemotherapy 5.4 Locoregional Therapies 5.4.1 Transarterial Chemoembolization 5.4.2 Isolated/Percutaneous Hepatic Perfusion 5.4.3 Hepatic Intra-Arterial Chemotherapy 5.4.4 Immunoembolization 5.4.5 Radioembolization 5.4.6 Surgical Resection 5.5 Immunotherapy References Intra-vitreal Chemotherapy for Vitreoretinal Lymphoma 1 Introduction 2 Intra-vitreal Chemotherapy 2.1 Intra-vitreal Methotrexate 2.2 Intra-vitreal Rituximab 2.3 Other Drugs for Intra-vitreal Chemotherapy 2.4 Investigational Drugs for Intra-vitreal Injections 3 Summary References Update on Uveal Lymphoma 1 Introduction 2 Historical Perspective 3 Clinical Features 3.1 Primary Choroidal Lymphoma 3.2 Secondary Choroidal Lymphoma 3.3 Iris Lymphoma 4 Diagnostic Testing 4.1 Biopsy 4.2 Ultrasonography 4.3 Optical Coherence Tomography 4.4 Angiography 5 Differential Diagnosis 6 Pathology 7 Treatment 7.1 Primary Uveal Lymphoma 7.2 Secondary Uveal Lymphoma References Topical Chemotherapy for Ocular Surface Squamous Neoplasia 1 Introduction 2 Interferon α-2b 2.1 Description 2.2 Usage and Efficacy 2.3 Dosage and Administration 2.4 Adverse Effects 2.5 Cost 3 5-Fluorouracil 3.1 Description 3.2 Usage and Efficacy 3.3 Dosage and Administration 3.4 Adverse Effects 3.5 Cost 4 Mitomycin C 4.1 Description 4.2 Usage and Efficacy 4.3 Dosage and Administration 4.4 Adverse Effects 4.5 Cost 5 Retinoic Acid 5.1 Description 5.2 Usage and Efficacy 5.3 Dosage and Administration 5.4 Adverse Effects 5.5 Cost 6 Anti-Vascular Endothelial Growth Factor Agents 6.1 Description 6.2 Usage and Efficacy 6.3 Dosage and Administration 6.4 Adverse Effects 6.5 Cost 7 Aloe Vera 7.1 Description 7.2 Usage and Efficacy 7.3 Dosage and Administration 7.4 Adverse Effects 7.5 Cost 8 Cidofovir 8.1 Description 8.2 Usage and Efficacy 8.3 Dosage and Administration 8.4 Adverse Effects 8.5 Cost 9 Conclusion References Surgical Management of Ocular Surface Squamous Neoplasia 1 Introduction 2 Clinical Assessment 3 Surgical Management of OSSN 3.1 Conjunctival OSSN 4 Surgical Technique for Conjunctival OSSN 4.1 Excision of Lesion 4.2 Cryotherapy 5 Closure of Conjunctival Defect 5.1 Corneal OSSN 6 Surgical Technique for Corneal OSSN 6.1 Eyelid and Anterior Orbital Involvement 7 Post-Operative Management References Part IV: Tools, Technology, and Innovations Genomics: Past, Present, and Future 1 Retinoblastoma: The Prototypic Genetic Cancer 1.1 The Retinoblastoma Tumor Suppressor 1.2 Genotype-Phenotype Correlations 1.2.1 Penetrance and Expressivity 1.2.2 Mosaicism 1.3 Cell Cycle Regulation by the Retinoblastoma Protein 1.4 Tumorigenesis: M1, M2, M3, and Beyond 2 Where Are We Now? 2.1 Retinoblastoma Staging: “H Status” 2.2 Screening Based on Genetic Risk 2.3 Prenatal Diagnosis for Familial Retinoblastoma 2.4 Molecular Testing Strategies for Retinoblastoma 2.4.1 Global Partnerships 2.5 Molecular Markers of Metastasis 2.6 Aqueous Humor: A Liquid Biopsy 3 The Future of Retinoblastoma Genomics 3.1 Expanding the Role of Aqueous Cell-Free DNA 3.1.1 Diagnosis 3.1.2 Prognosis 3.2 Non-Invasive Prenatal Diagnosis 3.3 Targeted Therapies 3.4 Molecular Surveillance for Second Cancers 4 Uveal Melanoma: A Genetic Comparison References Application of Deep Learning Models in the Evaluation of Histopathology of Uveal Melanoma 1 Introduction 2 Uveal Melanoma 3 Artificial Intelligence 4 Possible Solutions Through Software in Uveal Melanoma Diagnostics 5 Conclusion References Developing Prognostic Tools for Estimating Risk of Metastatic Death and Non-Metastatic Death in Individuals with Choroidal Melanoma 1 Introduction 2 LUMPO III 2.1 Access 2.2 Data Input 2.3 Output 2.4 Data Collection 2.5 LUMPO Model 2.6 Internal Validation 2.7 External Validation 3 Prognostic Tables 4 Clinical Impact of LUMPO 5 Conclusions References Applications of Plaque Brachytherapy in Anterior Segment Ocular Tumors: A Clinical Review 1 Introduction 2 Pterygium 3 Conjunctival Melanoma 4 Ocular Surface Squamous Neoplasia 4.1 Plaque Brachytherapy 5 Iris Melanoma 5.1 Iris Melanoma Primary Treatment 6 Epicorneal Plaque Surgery 7 Ciliary Body Melanoma 8 American Brachytherapy Society Consensus Guidelines 9 Limitations of Plaque Brachytherapy 10 Summary References The Role of Telemedicine in Ocular Oncology 1 Introduction 2 Definitions and Types of Telemedicine 3 Telemedicine Can Alleviate Health-Care Access Disparities 4 Teleophthalmology 5 Telemedicine and Ocular Oncology 6 Telemedicine and Ocular Oncology: São Paulo Experience 7 Barriers to Overcome for Teleophthalmology 8 Conclusions References Harnessing the Power of Artificial Intelligence 1 Introduction 2 Applications of AI in Ocular Oncology 2.1 AI-Assisted Diagnosis 3 Prognosis 4 Management Decisions 5 Future Perspectives References Developing Animal Models in Ocular Oncology 1 Introduction 2 Retinoblastoma 2.1 Transgenic Models 2.2 Genetically Modified and Knockout (KO) Models 2.3 Xenograft Models 3 Uveal Melanoma 3.1 Xenograft Models 3.1.1 Hamsters 3.1.2 Rats 3.1.3 Rabbits 3.1.4 Mice 3.2 Transgenic Models and Knock-Out/In Models 4 Adenoid Cystic Carcinoma 5 Animal Models Exploring Interventional Pathways 6 Conclusion References Part V: Novel Treatment Strategies Iris Melanoma: Advanced Surgical Techniques 1 Introduction 2 Biopsy Techniques 2.1 Fine-Needle Aspiration Biopsy 2.1.1 Technique 2.1.2 Instrumentation 2.1.3 Indications 2.1.4 Limitations 2.1.5 Complications 2.1.6 Conclusions 2.2 Cutter Biopsy 2.3 Forceps 2.4 Punch Biopsy 2.5 Cannula Aspiration 3 Excisional Techniques 3.1 Standard Iridectomy 3.1.1 Technique 3.2 Small Incision Iridectomy 3.3 Iridocyclectomy 3.3.1 Anteroposterior Approach 3.3.2 Posteroanterior Approach 4 Block Resection 5 Outcomes 6 Conclusions References The MOLES Acronym and Scoring System for Estimating Likelihood of Malignancy in Melanocytic Choroidal Tumors 1 Introduction 2 Pathophysiology 3 Clinical Signs 3.1 Ophthalmoscopy and Color Photography 3.2 Autofluorescence Imaging 3.3 Optical Coherence Tomography (OCT) 3.4 Ultrasonography (US) 3.5 Fluorescein and Indocyanine-Green Angiography 4 MOLES Acronym 4.1 Mushroom Shape 4.2 Orange Pigment 4.3 Large Size 4.4 Enlargement 4.5 Subretinal Fluid 4.6 Omitted Features 5 Moles Score 5.1 Mushroom Shape 5.2 Orange Pigment 5.3 Large Size 5.4 Enlargement 5.5 Subretinal Fluid 5.6 Multivariable Scoring 6 Tumor Categorization 7 Other Diagnosis Aids 7.1 TFSOM-DIM 7.2 DOCTOR GASS 8 Validation 9 Impact on Clinical Practice 10 Conclusions References Novel Therapies for Choroidal Melanoma 1 Introduction 2 Current Treatments for Choroidal Melanoma 2.1 Enucleation Versus Radiation Therapy 2.2 Side Effects of Radiation Therapy 2.3 Future of Treatment for Choroidal Melanoma 3 AU-011 Technology and Preclinical Trials 4 Clinical Trials 4.1 Intravitreal Treatment 4.2 Suprachoroidal Treatment 5 Conclusions References Novel Treatment Strategies for Malignant Anterior Segment Tumors 1 Introduction 2 Conjunctival Melanoma 2.1 Targeted Molecular Therapy with Selective BRAF/MEK Inhibitors 2.2 Immunotherapy with Checkpoint Inhibitors 3 Conjunctival Squamous Cell Carcinoma 3.1 Immunotherapy with Immune Checkpoint Inhibitors 4 Conjunctival Lymphoma 4.1 Intralesional Rituximab Injections 5 Iris Lymphoma 5.1 Intralesional Rituximab Injections 6 Iris Melanoma 6.1 Small-Incision Guarded Hydroaspiration of Small Iris Melanomas 7 Conclusion References Recent Developments in the Management of Orbital and Periocular Neoplasms 1 Eyelid and Periocular Melanoma 1.1 Sentinel Node Biopsy for Conjunctival and Periocular Melanomas 1.2 Targeted and Immunotherapy for Periocular Melanomas 1.2.1 Targeted Therapies 1.2.2 Immune Checkpoint Inhibitors 2 Eyelid and Periocular Squamous Cell Carcinoma 2.1 Epidermal Growth Factor Receptor (EGFR) Inhibitors for Locally Advanced Periocular SCC 2.2 Immune Checkpoint Inhibitors for Locally Advanced or Metastatic Periocular SCC 3 Eyelid and Periocular Basal Cell Carcinoma 3.1 Sonic Hedgehog Inhibitors 3.2 Immune Checkpoint Inhibitors for Locally Advanced BCC 4 Ocular Adnexal Lymphoma 4.1 Ultra-Low-Dose External Beam Radiation Therapy 4.2 Rituximab-Based Chemotherapy Regimens (R-CHOP, Rituximab, cyclophosphamide, vincristine sulfate, and prednisone (R-CVP), R-Bendamustine) for High-Grade OAL or Low-Grade OAL with Extraocular Sites of Involvement 5 Lacrimal Gland Carcinoma 5.1 Eye-Sparing Surgery and Adjuvant Radiotherapy 5.2 Neoadjuvant Intra-Arterial Chemotherapy for Adenoid Cystic Carcinoma References Proton Beam Irradiation: Expanding Indications 1 Introduction 2 Light Field Technique 3 Conjunctival Melanoma 3.1 Case 4 Choroidal Hemangioma 4.1 Case 5 Retinal Hemangioblastoma 5.1 Case 6 Choroidal Metastasis 6.1 Case 7 Conclusion References The Rise in Immunotherapy and Associated Ocular Toxicities 1 Introduction 2 General Principles 3 Immunotherapy Considerations 4 Pathogenesis of ICI 5 Clinical Manifestations of ICI Toxicities 5.1 Eyelids, Eyebrows, and Eyelashes 5.1.1 Blepharitis and Meibomian Gland Dysfunction (MGD) 5.1.2 Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) 5.2 Conjunctiva and Sclera 5.2.1 Conjunctivitis 5.2.2 Sclera 5.2.3 Episcleritis 5.2.4 Scleritis 5.3 Cornea and Tear Film 5.3.1 Dry Eye Syndrome 5.3.2 Corneal Epithelial Defects, Keratitis, and Corneal Melts 5.4 Cataracts 5.5 Uveitis 5.5.1 Anterior Uveitis 5.5.2 Intermediate Uveitis 5.5.3 Posterior Uveitis and Panuveitis 5.5.4 Vogt-Koyanagi-Harada (VKH)-Like Syndrome 5.5.5 Uveal Effusion 5.6 Retina and Vitreous 5.6.1 Retinal Tears and Detachments 5.6.2 Macular Edema 5.6.3 Choroidal Neovascularization 5.6.4 Other 5.7 Neuro-ophthalmology 5.7.1 Optic Nerve Edema and Neuropathy 5.7.2 Optic Neuritis 5.8 Orbital Inflammation 5.8.1 Thyroid Eye Disease 5.8.2 Orbital Myositis 5.8.3 Myasthenia Gravis 5.8.4 Giant Cell Arteritis 5.9 Glaucoma 5.9.1 Hypotony 6 Patient Education and Multidisciplinary Approach 7 Conclusion References Part VI: Healthcare Barriers Worldwide: Meeting the Challenge Awareness, Advocacy, and the Volunteer Sector 1 Introduction 2 Improving Awareness of the Potential Significance of These Signs is Imperative 2.1 Leukocoria 2.2 Strabismus 2.3 Who Should Be Targeted? 2.4 Damned If You Do, Damned If You Don’t 2.5 Awareness Amongst Healthcare Providers 2.6 Retinoblastoma Awareness Campaigns: A Global Study 2.7 Sustainability of Awareness Programmes 2.8 Awareness of Survivors: Late Effects of Treatment, Risk of Second Primary Cancers and Family Planning or Surveillance of Their Children 3 Advocacy, Volunteering and Retinoblastoma 3.1 Advocates Working Together 3.2 Where Would We Be Without Volunteers? 3.3 A Final Word… References Overcoming Challenges in the Delivery of Care: The Thailand Story 1 Introduction 2 Ocular Oncology in Thailand 3 Our Experiences 4 Retinoblastoma in Thailand 5 Retinoblastoma in our Center 6 Staging of Retinoblastoma 7 Treatment of Retinoblastoma 8 Genetic Testing 9 Three-Dimensional Organoid Model 10 Future Challenges and Plans 11 Uveal Melanoma 12 Uveal Metastases 13 Hemangioma 14 Retinal Vasoproliferative Tumor 15 Conclusion References Building a Retinoblastoma Service in China References Retinoblastoma, the African Context 1 Introduction: Retinoblastoma Worldwide 2 Retinoblastoma in Africa 2.1 The Burden 2.2 Clinical Presentation, Risk Factors for Late Disease Presentation and Poor Patient Outcome 3 Retinoblastoma Treatment in Africa 4 Cost of Treatment of Retinoblastoma 5 National Retinoblastoma Strategies and Twinning Programme 6 Research on Retinoblastoma in Africa 7 The Way Forward 8 Conclusion References The Brazilian Experience: The Retinoblastoma Awareness Campaign 1 Introduction 2 Early Diagnosis 3 Campaign for Early Diagnosis and Educational Actions 4 Conclusion References Part VII: Reflections Creating a Science Project: Advice from Personal Experience 1 Introduction 2 A Case 3 A Diagnostic Series 4 Retrospective and Prospective Data Collection 5 Translational Studies 6 Functional Studies 7 In Vivo Experiments 8 Prospective Studies 9 Setting Up Collaborations 10 Collaborative Studies 11 Visibility 12 Education: Nature Reviews Uveal Melanoma 13 Outreach 14 Conclusion References Ocular Oncology Practice During the COVID-19 Pandemic 1 Introduction 2 Clinic Evaluations 3 Screening and Triage 4 Check-In and Checkout 5 Waiting Rooms 6 Electronic Medical Record 7 Multimodal Imaging 8 Intravitreal and Laser Therapy 9 Clinic Flow and Patient Focus 10 Universal Precautions 11 High Risk of SARS-CoV-2 Patients 12 Operation Room Safety Protocols 13 Radiation Oncology Guidelines 14 Disease-Specific Recommendations 15 Conclusion References Pearls from a Mentor and Legend in Ophthalmic Pathology and Oncology 1 Introduction 2 Study the Work of Others with Different Perspectives, Apply and Modify such Knowledge to One’s Own Area of Investigation, and Share with New Audiences 3 Physicians and Scientists Should Study What They Love, Even if It Does Not Fit the Mold, and… 3.1 …Even If One Takes an Unconventional Path or Studies an Unusual Combination of Fields 3.2 …Even If It Is Not a Popular, Lucrative or Field-Changing Topic 4 Be a Lifelong Learner 5 Choose Collaborators and Mentees Wisely and Champion Them References Index