Geriatric Oncology

Foreword
Preface
	Reference
Acknowledgments
Contents
About the Editor
About the Section Editors
Contributors
Part I: Epidemiology and Public Health
	1 Population Trends in Aging and Cancer
		Introduction
		Bladder Cancer
		Kidney Cancer
		Prostate Cancer
		Gynecologic Cancer
		Breast Cancer
		Hematological Cancer
		Upper Gastrointestinal Cancer
		Colorectal Cancer
		References
	2 Integrating Geriatric Oncology in Public Health Planning
		Introduction
			Epidemiology in France
			Public Health Planning and Health-Care Policy in Geriatric Oncology in France
				The French National Cancer Institute (INCa)
				2003-2007 Cancer Control Plan
				2009-2013 Cancer Control Plan
				2014-2019 Cancer Control Plan
			Current Assessment
				Health-Care Modalities
				Oncogeriatrics Coordination Units (UCOGs)
			Funding
			Key Achievements and Strengths
				Collaboration Between Oncologists and Geriatricians
				Awareness of Clinical Research Importance in Geriatric Oncology
			Weak Points
				A Large Discrepancy of the Oncogeriatric Approach Between the Regions
				An Oncogeriatric Approach Limited to the Initiation of Cancer Treatment
				Performance Indicators Remain Hard to Determine
			Future Prospects
				From Oncogeriatrics to Geriatric Oncology
				Strengthened Coordination Between the Different Health-Care Professionals
				Geriatric Oncology Across the Care Pathway
				Better Access to Innovative Treatments
				Evaluation of the Geriatric Oncology Approach
				Integrating e-Health Technology
				New Forms of Financing
		Conclusion
		References
	3 Healthcare Informatics and Technology in Managing the Older Cancer Patient
		Introduction
		Rising Costs of Healthcare Among an Aging Population
		Value-Based Healthcare
		Population Health
		Predictive Modeling
		Precision Medicine
		Translational Bioinformatics
		Internet of Things
		The Smart Home
		Evolving Technology and the Use of Health Technology
		Technology and Health Technology Use Among Older Adults
		Patient-Reported Outcomes and Technology
		Assessing Cancer and Aging
		Wearable Sensors and Geriatric Assessment
		References
Part II: Biology of Aging and Cancer
	4 Role of Cell Cycle Control, Checkpoints, and DNA Repair Mechanisms in Stem Cells and Changes with Aging and Cancerogenesis
		Introduction
		Regulation of the Cell Division Cycle, Genome Maintenance, and Checkpoint Activity in Stem and Progenitor Cells
			General Overview
			Role of CDKs, Cyclins, and CKIs in HSPCs
			DNA Repair and Cell Cycle Arrest Pathways in HSPCs
			Mitotic, Decatenation, Differentiation, and Other Checkpoints
			Apoptosis and Senescence
		Alterations upon Aging and Malignant Transformation
			Changes of Cell Cycle and Checkpoint Control upon Aging
			Role of Checkpoint and DDR Deregulation in Leukemogenesis
			Treatment of Malignancies by Intervention of Checkpoint/Cell Cycle Control
		Conclusions/Directions
		Cross-References
		References
	5 Cellular Senescence and Tumor Promotion
		Introduction
		Cellular Senescence
			Induction of Cellular Senescence
			Phenotype of Senescent Cells
		From Tumor Suppression to Tumor Promotion
			Tumor Suppression
			From Wound Healing to Tumor Promotion
		Accumulation of Senescent Cells
			Aging
			Cancer Treatments
		Interfering with Senescent Cells
			Selective Induction of Cell Death
			Improvement of the Immune System
			Inhibition of the SASP
		Conclusion
		References
	6 Immunosenescence and Cancer Immunotherapy at Old Age: Basics
		Introduction
		Cancer and Aging
		Immunosenescence and Aging: Does Immunosenescence Matter for Tumorigenesis?
		What Are the Currently Used Immunotherapies, and How Might Immunosenescence Impact on Their Success?
			Regulatory T Cells (Treg)
			Innate Immunity
		Adoptive Cell Transfers
		mTOR Inhibitors
		TLR Agonists
		Immune Checkpoint Inhibitors (ICI)
		Elderly Participation in Clinical Trials
		Conclusions and Future Perspectives
		Cross-References
		References
	7 Aging and Cancer Biology
		Introduction: Aging and Cancer - Two Related Phenomena?
		Aging and Susceptibility to Carcinogenesis in Different Tissues
		Aging and Multistage Carcinogenesis
		Cellular Senescence and Carcinogenesis
		Aging and Cancer Microenvironment
		Premature Aging Promotes Carcinogenesis
		Effect of an Exposure to Environmental Carcinogens on Aging and Life Span
		DNA Damage in Aging and Carcinogenesis
		Effect of Carcinogens on the Neuroendocrine System
		Effect of Carcinogens on Carbohydrate and Lipid Metabolism
		Effect of Carcinogens on Immune System
		Carcinogens as Promoters of Spontaneous Carcinogenesis
		Effect of Geroprotectors on Aging and Carcinogenesis
		Conclusion
		References
	8 Chronic Mechanistic Target of Rapamycin Inhibition: Preventing Cancer to Delay Aging or Vice Versa?
		Introduction
		Aging Is the Principal Risk Factor for Cancer
		Caloric Restriction Prolongs Life and Healthspan
		Caloric Restriction Prevents Cancer
		mTOR Promotes Signals Through Distinct mTORC1 and mTORC2 Complexes
		Rapamycin Extends Life in Mice
		Pharmacologic mTOR Inhibition and Cancer Prevention
		mTOR Mediates Significant Immune Effects
		Immune Effects of Rapamycin in Cancer Prevention
		Cancer Prevention Effects of Other mTOR Inhibitors
		Potential mTOR-Related Targets
		Other mTOR Effects in Cancer Prevention
		Adverse Effects of mTOR Inhibitors
		Closing Thoughts
		References
	9 Calpain-Calpastatin System in Lymphoid Neoplasm of the Aged
		Introduction: Basic Characteristics of Lymphoid Malignancies
		Calpains, Calpastatin, and Their Roles in Cellular Survival, Proliferation, and Apoptosis
			Calpains: General
			Calpain Substrates
			Calpain Action on Target Proteins
			A Puzzle Regarding Calpain Activity In Vivo
			Calpains and Aging
			Complex Relations Between CCS Hyperexpression and Hyperactivity as Likely Mechanisms of Apoptosis Escape and Increased Prolife...
		Conclusion
		References
	10 The Biologic Interconnections Between Aging and Lymphoma
		Introduction
		Lymphomagenesis and Age: The Role of the Mutation Burden
			Lymphomagenesis Process Is Long and Implies Several Steps
			Mutations Related to B-Cell Processing
			The Mutation Burden Is Time-Dependent and Leads to Aging and Cancer
			The Epimutation Burden
			The Impact of Telomere Shortening
		Age-Related Dysfunction of Anticancer Surveillance
			Immunosenescence Links Chronic Infection to Cancer Development
			Microenvironment and Immunity Change with Age
			Senescence Modifies Tumor Cells and Their Microenvironment
			Age Induces Defects in the DNA Damage Response Pathway
		Age-Related Clonal Restriction
		Specific Entities of Lymphoma in the Elderly
			Age-Related Molecular Specificities in DLBCL
			EBV DLBCL of the Elderly
		Lymphoma, Senescence, and Therapeutic Options
		Conclusion
		References
	11 Aging of Natural Killer Cells in Acute Myeloid Leukemia
		Introduction
		Natural Killer Cells
			MHC Class I-Specific Receptors
			Non-MHC Class I-Specific Inhibitory Receptors
			Activating Receptors
		Cancer, Aging, and Immunosenescence
		NK Cells and Aging
		NK Cell Receptors and Their Ligands in Patients with Solid Tumors
		NK Cells in AML Patients
		NK Cells in Elderly AML Patients
		NK Cell-Based Immunotherapy in AML Patients
		Conclusions
		Cross-References
		References
	12 Hematopoietic Stem Cell Aging and Malignant Hemopathies
		Introduction
		Senescence: A Dual Phenomenon
		What Have We Learned from Progeroid Syndromes?
		Hematopoietic Stem Cell Aging
			Clonal Expansion of Hematopoietic Stem Cells
			Role of Epigenetics in Hematopoietic Stem Cell Aging
			Loss of Heterochromatin
		Malignancies: Not Only an Accumulation of Mutations
		Lymphomagenesis and Lymphomas
		Acute Myeloid Leukemia
		The Future
		References
	13 Mitochondria, Oxidative Stress, Cancer, and Aging
		Introduction: The Role of Mitochondria in Oxidative Stress
			Structure and Functions of Mitochondria
			Mitochondria as a Source of Reactive Oxygen Species
			Mitochondrial Stress Response
		Mitochondria and Oxidative Stress in Aging
			The Mitochondrial Free Radical Theory of Aging
			Impairment of Mitochondrial Stress Response During Aging
		Mitochondria and Oxidative Stress in Cancer
			Oncogenes, Mitochondria, and ROS: A Complex Interplay
			Mitochondrial Proteases, Oxidative Stress, and Cancer
			Mitophagy, Oxidative Stress, and Cancer
		Conclusions
		Cross-References
		References
Part III: (Patho)physiology of Aging and Cancer
	14 Normal and Abnormal Aging (General Perspective for the Oncologist)
		Introduction
		Homeostenosis
		Homeostenosis in the Aging Cardiovascular System
		Allostatic Load and Aging
		Homeostenosis and Altered Presentation of Disease in the Elderly
		Summary
		References
	15 Respiratory Organ Aging and Cancer
		Introduction
		Lung Aging
			Chronic Lung Diseases and Aging
			Chronic Lung Diseases and Frailty
		Lung Cancer and Aging
			Lung Cancer Epidemiology and Risk Factors
			Lung Cancer Screening
			Lung Cancer Diagnosis
		Non-Small Cell Lung Cancer
			Making Treatment Decisions
			Early-Stage NSCLC (Stages I and II)
			Locally Advanced NSCLC (Stage III)
			Metastatic NSCLC (Stage IV)
		Other Lung Malignancies
			Small Cell Lung Cancer
			Other Neuroendocrine Tumors, Mesothelioma, and Pulmonary Metastases
		Conclusion
		Cross-References
		References
	16 Digestive Organ Aging and Cancer
		Introduction
		Impact of Age on the Management Strategy of Digestive Cancers
			Digestive Surgery and Age
				Impact of Geriatric Evaluation in Digestive Cancer Surgery
				Impact of Surgical Treatment on Elderly Patients
				Fast-Track Surgery and Prehabilitation in Digestive Surgery for Aged Patients
			Chemotherapy and Age
		Colon Cancer
			Surgery
				Local Cancer (Stages I and II)
				Locally Advanced Stage (Stage III)
				Indication of Liver Metastasis Resection
			Adjuvant Chemotherapy
			Palliative Chemotherapy
			Targeted Therapy
		Rectal Cancer
			Treatment Management Recommendations
			Stage 0 to Stage I (T1-T2 N0 M0) Tumors
			Stage II to Stage III (T2-T4 N0-1 M0) Tumors
			Stage IV (T3-4 N2 M1): Palliative Treatments
			Surveillance
		Esophageal Cancer
			Surgery Outcomes for Older Patients
			Chemotherapy
				Neoadjuvant Chemotherapy
				Palliative Chemotherapy
			Radiotherapy
			Supportive Care
		Gastric Cancer
			Localized Stage
				Surgery
				Neoadjuvant Chemotherapy
			Metastatic Stage
				HER 2-Negative Tumors
				HER2-Positive Tumors
				Supportive Care
		Hepatocellular Carcinoma
			Curative Treatments
				Hepatectomy
				Orthotopic Liver Transplantation
				Radiofrequency Ablation
			Palliative Treatments
				Chemoembolization
				Molecular Targeted Therapy (Sorafenib)
			Conclusion
		Pancreatic Cancer
			Operable Stage
				Surgery
				Adjuvant Treatment
			Locally Advanced Stages
				Borderline
				Inoperable
			Metastatic Stage
			Supportive Care
		Conclusions
		References
	17 Musculoskeletal Aging, Sarcopenia, and Cancer
		Introduction
		Muscle Aging and Sarcopenia
			Lifestyle Factors
			Endocrine Aging
			Inflammation
			Neuromuscular Changes
			Oxidative Stress and Mitochondrial Dysfunction
		The Operational Definition of Sarcopenia
		Translation of Sarcopenia in Oncology
			Prevalence of Sarcopenia
			Different Objectives
			Different Tools
		Sarcopenia Versus Cachexia
		Interventions against Skeletal Muscle Decline in Older Persons with Cancer
			Methodological Considerations
			Physical Exercise
			Nutrition
			Pharmacological Interventions
			Adapted Model of Care
		Conclusions
		Cross-References
		References
	18 Neurological Aging and Cancer
		Introduction
		Changes in the Brain
		Cognitive Changes
		Changes in the Peripheral Nervous System
		Changes in the Autonomous Nervous System
		Chemotherapy and Cognition
		Neurotoxicity of Anticancer Agents
		Central Neurotoxicities
		Peripheral Neurotoxicities
		Autonomic Toxicity
		Toxicity Associated with Immunotherapy
		Cross-References
		References
	19 Hematopoiesis and Aging
		Introduction
		Normal Bone Marrow Function
		The Effect of Aging on Bone Marrow Function
			Pluripotent Stem Cells (Pre-CFU-S and CFU-S)
			Committed Hematopoietic Precursors
			Progenitor Cell Cycle Kinetics
			Stem Cell Integrity
		The Effect of Aging on Stem Cell Clonality
		The Effect of Aging on Bone Marrow Stroma
		The Effect of Aging on Cytokine Production and Release
		The Effect of Aging on Immune Function
			Bone Marrow T Cells
			Bone Marrow B Cells
		Conclusions
		Cross-References
		References
	20 Pharmacology of Aging and Cancer
		Introduction
		General Pharmacotherapy Considerations in Geriatric Oncology
			Absorption
			Distribution
			Metabolism
			Elimination
			General Pharmacodynamic Principles
		Polypharmacy in Older Cancer Patients
			Definitions and Incidence of Polypharmacy
			Factors Influencing Polypharmacy in Older Cancer Patients
			Evaluating Polypharmacy and Potentially Inappropriate Medication Use
			Medications Screening Tools for the Older Cancer Patient
			Consequences of Polypharmacy in Older Cancer Patients
		Deprescribing in Older Cancer Patients
			Deprescribing Models
			Prioritizing Deprescribing Interventions
			Barriers to Deprescribing
			Outcomes Associated with Deprescribing
			The Future of Deprescribing in Geriatric Oncology
		Conclusion
		Cross-References
		References
	21 Drug Interactions in Aging and Cancer
		Introduction
		PDIs Among Older Adults with Cancer: Insights from Polypharmacy
		Risk for PDIs: How Many Medications Are Too Many?
		PDIs: Methods for Identification
		PDIs: Illustrative Examples
		PDIs and Outcomes: What Do We Know?
		PDIs in Geriatric Oncology: Future Directions
		Cross-References
		References
	22 Comorbidity in Aging and Cancer
		Introduction
		Definition of Comorbidity
		Prevalence of Comorbidity
		Measures of Comorbidity for Older Patients with Cancer
		Comorbidity and Cancer Risk
		Comorbidity and Prognosis
			Cancer Screening and Early Diagnosis
			Comorbidity and Survival Outcomes
		Comorbidity and Cancer Treatment
			Approach to Decision-Making in Older Adults with Cancer and Comorbidities
			Comorbidities and Cancer Treatment Choice
			Comorbidities and Cancer Treatment Toxicity
			Impact of Cancer Treatment on Comorbidities
		Conclusion
		References
	23 Biomarkers of Aging (With a Clinical Potential in Oncology)
		Introduction
		The Ideal Aging Biomarker
		The Ideal Frailty Biomarker for Oncology
		Classes of Biomarkers of Aging
			Cellular Markers of Inflammation
				Neutrophil-Lymphocyte Ratio (NLR)
				Lymphocyte-Monocyte Ratio (LMR)
				Platelet-Lymphocyte Ratio (PLR)
			Circulating Markers of Systemic Inflammation
				Circulating Inflammatory Markers in Oncologic Studies
			Telomere Shortening
			Cellular Senescence Markers
		Discussion
		Cross-References
		References
Part IV: Geriatric Assessment and Management in Oncology
	24 Geriatric Screening in Cancer Patients
		Introduction
		Definition of a Screening Tool
		Screening Tools in Older Patients with Cancer
			G8
			Vulnerable Elders Survey (VES)-13
			Flemish Version of the Triage Risk Screening Tool (fTRST)
			Groningen Frailty Indicator (GFI)
			Study of Osteoporotic Fractures (SOF) Index
			Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
			Fried Frailty Criteria of Physical Frailty Phenotype
			Barber Questionnaire
			Identification of Seniors at Risk (ISAR)
			Oncogeriatric Screen (OGS)
			Abbreviated Comprehensive Geriatric Assessment (aCGA)
			Gerhematolim
			Senior Adult Oncology Program 2 (SAOP2)
			Functional Tests as Screening Tool
			Use of Screening Tools in Daily Practice
		Discussion
		References
	25 Comprehensive Geriatric Assessment (CGA) for Cancer Patients
		Introduction
		Domains
			Cognition
				Tools for the Assessment of Cognition
			Function
				Performance Status
				Falls
				Physical Function
			Comorbidity
				Measurement of Comorbidity
			Nutrition
			Psychosocial Status
				Social Isolation
				Depression
				Distress
			Medications and Polypharmacy
		Benefits of CGA
		Methods of Administering a CGA
			Clinician Interview
			Self-administered
			Snail Mail Surveys
			Email/Electronic
		Conclusions
		Cross-References
		References
	26 Frailty in Cancer Patients
		Introduction
		Case Vignette
		Definition and Identification of Frailty in Cancer Patients
		Frailty Tools and Screening
		Data Regarding Frailty in Oncology
		Other Clinical Implications of Identifying Frailty in a Patient with Cancer
		How to Manage Frailty in Older Cancer Patients
		Summary
		Cross-References
		References
	27 Geriatric Interventions in Oncology
		Introduction
		Geriatric Assessment in the Oncology Setting
		GA with Management Interventions
		GA with Management Interventions in Oncology Care
		Cross-References
		References
	28 Organizing the Clinical Integration of Geriatrics and Oncology
		Introduction
		Conceptual Models of Integration
		Working Examples of Integration
			USA and Canada
			Latin America
			France
				The Oncogeriatric Coordinations Units (UCOG)
				University Training
				Training as Part of Continuing Professional Development (CPD)
				Research
			Other European Countries
			Israel
			Australasia
				Australia
				Singapore
		Possible Models in Different Situations and Settings
			Different Situations
				Geriatric Oncologist
				Geriatric Consultation
				Geriatric Oncology Team Collaboration with the Treating Clinical Oncologist or Shared Care Model
			Different Settings
				Cases with Interdisciplinary Approach Needed
				Timing
				Place
		Suggestions/Recommendations for Starting a Geriatric Oncology Program
		References
	29 Predictive Tools for Older Cancer Patient Management
		Introduction
			Chemotherapy Toxicity Predictive Tools in Older Cancer Patients
				The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) Score
				The Cancer and Aging Research Group (CARG) Chemotherapy Toxicity Assessment
			Predicting the Risk of Perioperative Complications
		Frailty Identifying Tools
		Predictive Tools for Life Expectancy
		Future Needs
		Conclusions
		Cross-References
		References
Part V: Heme Malignancies
	30 Myelodysplastic Syndrome
		Introduction
		Epidemiology
		Etiology
		Diagnosis
		Differential Diagnosis
		Classification
			French-American-British (FAB) Classification
			Original WHO Classification
			2008 Revised WHO Classification
			2016 Revised WHO Classification
		Clonal Hematopoiesis of Indeterminate Potential
		Pathogenesis
		5q Minus Syndrome
		Clinical Presentation
		Risk Stratification Models
			The International Prognostic Scoring System
			The Revised IPSS
			The Global MD Anderson Model
			Other Risk Models
			Comorbidities and Frailty in MDS
		Molecular Alterations
		Management of MDS: Low, High, and Intermediate Risk
			Low-Risk
				Low-Risk Patients with Isolated del(5q) Syndrome
				Low-Risk Patients Without Isolated del(5q) Syndrome
			High-Risk
				High-Risk, Transplant Ineligible
				High-Risk, Transplant Eligible
				Relapsed/Refractory Disease
			Intermediate-Risk R-IPSS
		The Role of Allogeneic Stem Cell Transplant
		Therapies on the Horizon
		References
	31 Acute Myeloid Leukemia in Older Adults
		Introduction
		Epidemiology
		Diagnosis and Risk Stratification
		Outcome and Treatment Disparity by Age
		Age-Related Changes in Tumor Biology
		Treatment
			Induction Chemotherapy
			Lower-Intensity Treatments
			Extrapolating Clinical Trial Data
		Post-remission Therapy
		Acute Promyelocytic Leukemia (APL)
		Individualizing Therapeutic Decisions
			Risk Prediction Models
			Assessing Fitness: A Role for Geriatric Assessment
			Quality of Life, Survivorship, and Communication
		Future Strategies
		References
	32 Chronic Lymphocytic Leukemia in Older Adults
		Introduction
		Disease Features in Older Adults with CLL
		Aging Features in Older Adults with CLL
		Management of Older Adults with CLL
			Diagnosis
			Prognostication
			Indication for Treatment
			Choice of Front-Line Treatment
			Choice of Further-Line Treatment
		Conclusion
		References
	33 Chronic Myelogenous Leukemia and Myeloproliferative Disorders in Older Adults
		Introduction
		Chronic Myeloid Leukemia
			Epidemiology
			Presentation
			Diagnosis
			Treatment
		Philadelphia-Negative Chronic Myeloproliferative Neoplasms
			Polycythemia Vera
			Essential Thrombocythemia
			Primary Myelofibrosis
		Age and Comorbidities
			Age and Polypharmacy in CML Older Patients
			Age and Quality of Life in CML Older Patients
			Real-World Patients Versus Clinical Data Trial
		Conclusion
		Cross-References
		References
	34 Multiple Myeloma in Older Adults
		Introduction
		Diagnosis of Multiple Myeloma
			Laboratory Testing
			Anemia
			Renal Dysfunction
			Radiographic Imaging
			Hypercalcemia
			Monoclonal Proteins and Light Chains
			Beta 2 Microglobulin (β2M)
			Lactate Dehydrogenase (LDH)
			Bone Marrow Evaluation and Cytogenetics
		Staging
			Durie-Salmon Staging System (DSS)
			International Staging System (ISS)
			Revised-International Staging System (R-ISS)
		Treatment Stratification
			Transplant Ineligible Therapy for MM in the Older Adult
				Melphalan-Based Therapy
				Immunomodulatory Drugs (IMiD)-Based Therapy
				Bortezomib-Based Therapy
				Next Generation Therapy
			Autologous Stem Cell Transplant in Older Adult with MM
		Risk Stratification
			Geriatric Assessment in Multiple Myeloma
		Cross-References
		References
	35 Low-Grade Lymphomas (Other than CLL/SLL) in Older Patients
		Introduction
		Indolent Lymphomas in Older Patients: The Impact of Age
		The Comprehensive Geriatric Assessment: A Useful Tool for Evaluating Elderly Patients
		Diagnostic and Therapeutic Management of Elderly Patients with Low-Grade Lymphomas
			Marginal Zone Lymphoma (MZL)
				Splenic Marginal Zone Lymphoma
				Extranodal Marginal Zone Lymphoma
				Nodal Marginal Zone Lymphoma
			Follicular Lymphoma
			Lymphoplasmacytic Lymphoma and Waldenström´s Macroglobulinemia
		Conclusions
		Cross-References
		References
	36 Diffuse Large B-Cell Lymphomas in Older Adults
		Introduction
		Demographics and Staging in Older DLBCL Patients
		Prognostic Factors
		Comorbidities in Elderly Patients
		Comprehensive Geriatric Assessment and Measures of Frailty
		Supportive Care Issues in the Elderly
		Initial Therapy of DLBCL in the Elderly
		Treatment Approaches for Limited Stage Disease or Bulky Disease
		Maintenance Therapy
		Management of Relapsed/Refractory DLBCL in the Elderly
		Therapy of DLBCL in the Elderly - Conclusions
		References
	37 The Evolving Role of Transplant for Older Adults
		Introduction
		Allogeneic Transplantation
			What Is the Effect of Increasing Age on Allogeneic Hematopoietic Stem Cell Transplant (alloHCT) Outcomes?
			Consideration of Treatment Alternatives: TransplantVersus Nontransplant Therapy
			Assessing Candidacy for alloHCT: Disease-Specific Factors
				Disease Prognosis
				Disease Control
			Assessing Candidacy for alloHT: Patient-Specific Factors
				Chronologic Age
				Performance Status
				Comorbidity
				Functional Status and Geriatric Assessment (GA)
			Donor Considerations
			Allogeneic Transplant: Case Studies
		Autologous Transplant
			Multiple Myeloma
				Effect of Increasing Age on Autologous Transplant Outcomes:
				Autologous Transplant Versus Other Therapy
				Determining Treatment Tolerance and Transplant Eligibility
			Non-Hodgkin Lymphoma
		Cross-References
		References
Part VI: Solid Tumors
	38 Early-Stage Breast Cancer in Older Adults
		Introduction
		Surgery
			Surgery to the Breast
			Surgery to the Axilla
			Other Factors to Consider and Future Directions
		Radiotherapy
			Radiotherapy Omission
			Innovations
		Systemic Treatment
			Endocrine Therapy
			Chemotherapy
			Anti-HER2 Treatments
			Neoadjuvant Strategy
		Cross-References
		References
	39 Systemic Treatment of Metastatic Breast Cancer in Older Adults
		Introduction
		Special Treatment Considerations in Older Adults with Metastatic Breast Cancer
		Systemic Treatment Options and Clinical Evidence
			Treatment of Choice for Older Women with Hormone Receptor-Positive Metastatic Breast Cancer
			Treatment of Choice for Older Women with Hormone Receptor-Negative, Triple-Negative, Hormone Refractory, or Rapidly Progressiv...
			Treatment of Choice for Older Women with HER2-Positive Disease
		Conclusion
		Cross-References
		References
	40 Prostate Cancer: Management in Elderly Men Population in 2017
		Introduction
		Clinical Presentation
		Diagnosis, Staging, and Prognostic Factors
			Diagnosis
			Staging Procedures
			Prognostic Factors
		Health Status Evaluation in Senior Adults
			Evaluation of Health Status
			Cognitive Screening
			Simplified Geriatric Evaluation
			Patient Staging and Treatment Strategy After Geriatric Evaluation
		Treatment of Localized Disease
			Introduction
			Deferred Treatment (Watchful Waiting, Active Surveillance)
			Radical Prostatectomy
			External Beam Radiotherapy
			Androgen Deprivation Therapy (ADT)
			Minimally Invasive Therapies
		Treatment of Advanced Disease
			Metastatic Hormone-Naïve Prostate Cancer
			Castration-Resistant Prostate Cancer (CRPC)
			Endocrine Therapy
			Chemotherapy
			Radiotherapy, Radiopharmaceuticals, and Bone-Targeted Therapy
			Vaccine (Sipuleucel-T)
			Choosing the Right Treatment and Sequencing
			Palliative Care
		Conclusion
		Cross-References
		References
	41 Bladder Cancer in Older Adults
		Introduction
		Clinical Presentation
		Etiology and Risk Factors, Pathology, Natural History, and Tumor Biology
			Etiology and Risk Factors
			Pathology
		Diagnosis, Staging, and Prognostic
			Diagnosis: Imaging, Cystoscopy, and Urinary Cytopathology
			Staging
			Prognosis of BC
		Geriatric Assessments (GA)
		Treatments
			Treatment of BC
			Treatment of NMIBC
				Transurethral Resection of Bladder Tumor (TURBT)
				Intravesical Therapies
			Treatment of MIBC
				Surgical Treatment
					Radical Cystectomy (RC)
					Surgical Alternatives to Radical Cystectomy
						Radical TURBT Only
						Partial Cystectomy +/- Lymphadenectomy
				Nonsurgical Treatments/Organ-Sparing Treatments
					Radio-Chemotherapy
					Metastatic Bladder Cancer/Palliative Treatments
					New Drugs
		Follow-Up
			NMIBC
			MIBC
				After Optimal Treatment
				Palliative Treatment
		Cross-References
		References
	42 Kidney Cancer in Older Adults
		Introduction
		Renal Cell Carcinoma in the Older Adults
		Unique Issues Affecting Older Adults with RCC
			Physiology of Aging and Treatment Implications
			Decision-Making and Treatment Goals
			Treatment Compliance
		The Role of Geriatric Assessment (GA) in Older RCC Patients
		Localized Renal Cell Carcinoma in Older Adults
			Surgical Resection
			Adjuvant Systemic Therapies
			Ablation Therapies
			Active Surveillance
		Metastatic Renal Cell Carcinoma in the Older Adult
			Clear Cell mRCC
				Role of Cytoreductive Nephrectomy
				Systemic Therapies
				Active Surveillance
			Non-clear Cell RCC
		Guidelines
		Summary
		Cross-References
		References
	43 Colorectal Cancer in Older Adults: Systemic Treatments
		Introduction
		Geriatric Evaluation in Colorectal Cancer
		Adjuvant Chemotherapy After R0 Resected Colon Cancer
			Stage III
			Stage II
		Specificities for Rectal Cancer
		Palliative Chemotherapy in Metastatic Patients
			Evaluation of Chemotherapy for Treatment of mCRC in Elderly Patients
			Evaluation of Targeted Therapy for the Treatment of mCRC in Elderly Patients
		Cross-References
		References
	44 Colorectal Cancer in Older Adults: Surgical Issues
		Introduction
		What Do Surgeons Want To Know?
			Role of Screening Tools in a Busy Surgical Practice
			Role of the Standard of Care in Older Fit Patients
				Laparoscopy
				Enhanced Recovery
				Adjuvant Chemotherapy in Older Patients with Stage III Colorectal Cancer
			Undertreatment Versus Customized-Conservative Treatment in Older Patients with Rectal Cancer
		What Do Patients Want to Know?
			The Role of Patient-Reported Outcome Measures
		What Do Hospital Administrations Want to Know?
			Costs and Perception of Surgical Oncology Versus Medical Oncology
			What Is the Value of Health Care: Outcomes That Matter to Patients/Cost per Patient Ratio
		Conclusions
		Summary
		Cross-References
		References
	45 Multidisciplinary Management of Liver, Pancreatic, and Gastric Malignancies in Older Adults
		Introduction and Background
		Liver Malignancies
			Liver Resection and Special Considerations
			Hepatocellular Carcinoma
				Diagnosis
				Resection
				Transplant
				Ablation
				Hepatic Arterial Embolization
				Systemic Therapy - Sorafenib
			Cholangiocarcinoma
			Colorectal Liver Metastasis
				Resection
				Chemotherapy
					Neoadjuvant Therapy
					Conversion Therapy
					Adjuvant Therapy
		Pancreatic Cancer
			Staging
			Surgical Resection in Elderly Patients
			Chemotherapy in Elderly Patients
				Metastatic Disease
				Adjuvant Treatment
				Neoadjuvant Treatment
			Elderly Patients and Clinical Trials
		Gastric Cancer
			Surgery
				Extent of Resection in the Elderly
			Perioperative Therapy
			Adjuvant Radiation Therapy
			Metastatic Gastric Cancer in the Elderly
		Conclusion
		Cross-References
		References
	46 Head and Neck Tumors in Older Adults: Systemic Treatments and Combination with Local Strategies
		Introduction
		Systemic Treatment in Curative Intent
			Systemic Treatments for Locally Advanced (LA) HNC Patients
			Postoperative Radio(Chemo)Therapy
			Induction Chemotherapy
			Supportive Care
		Systemic Treatment in Palliative Intent: Recurrent and/or Metastatic (R/M) HNC Patients
			First-Line Therapy
				Fit Elderly HNC Patients
				Unfit Elderly HNC Patients
			Second-Line and More Systemic Treatment
		Conclusion
		Cross-References
		References
	47 Ovarian Cancer in the Older Woman
		Introduction
		Geriatric Assessment
			Background
			Presurgery Assessment
			Prechemotherapy Assessment
		Chemotherapy
			Background
			Chemotherapy: First Line
			Neoadjuvant Chemotherapy (NACT)
			Intraperitoneal Chemotherapy
			Chemotherapy for Recurrent Disease
			Targeted Agents
		Surgery
		Conclusion/Future Directions
		References
	48 Lung Cancer in Older Adults: Local Treatment
		Introduction
		Surgery for Early Stage Lung Cancer
		Stereotactic Radiotherapy for Early Stage Lung Cancer
		Deciding Between Surgery and Radiotherapy
		Treatment of Locally Advanced Disease
		Small-Cell Lung Cancer
		Conclusions
		References
	49 Lung Cancer in Older Adults: Systemic Treatment
		Introduction
		Specific Factors Helping Therapeutic Medical Decision in Elderly Patients with Lung Cancer?
		Representativity of Elderly Patients in Clinical Trials
		Systemic Treatment in Small Cell Lung Cancer
		Systemic Treatment in NSCLC
			Adjuvant Chemotherapy
			Locally Advanced NSCLC
			Systemic Treatment in Stage IV Disease
				Chemotherapy
				Targeted Therapies
				Immunotherapy
		Conclusion
		Cross-References
		References
	50 CNS Tumors in Older Adults
		Introduction
		History, Clinical Presentation, and Clinical Findings
		Diagnostic Strategies
		Primary Brain Tumors
			Gliomas
			Meningiomas
			Primary CNS Lymphoma (PCNSL)
			Brain and Leptomeningeal Metastases
			Symptomatic and Supportive Therapy and Palliative Care
		Outlook
		References
Part VII: Patient Care Issues
	51 Principles of Cancer Surgery in Older Adults
		Introduction
		What Do Elderly People with Cancer Want? The Challenge of Communicating, Patients´ Perspectives, and Quality of Life
		Preoperative Evaluation and Multidisciplinary Decision-Making
		Surgical Planning (Not Only Picking a Calendar Date)
			Prehabilitation
			Minimally Invasive Surgery
			Enhanced Recovery Programs
		Old Assumptions about Surgery and Poor Cancer Prognosis
			Pancreatic Cancer
			Stage IV Colorectal Cancer with Liver Metastasis
		Conservative Treatment Versus Undertreatment
			Breast Cancer
			Rectal Cancer
			Ovarian Cancer
			Lung Cancer
		Palliation of Symptoms: The Sooner the Better
		Cross-References
		References
	52 Principles of Radiation Therapy in Older Adults
		Introduction
		Neoadjuvant Radiotherapy
		Definitive Radiation Therapy
		Adjuvant Radiation
		Palliative Radiation
		Future Directions
		Conclusion
		Cross-References
		References
	53 Principles of Chemotherapy in Older Adults
		Introduction
		Geriatric Assessment in Oncology
		Physiology of Aging and Drug Therapy
		Research
		Pharmacokinetic Evaluation in Older Patients
		Clinical Trial Design
		Chemotherapy: Pharmacology
			Alkylating Agents
			Melphalan
			Cyclophosphamide
			Bendamustine
			Fluoropyrimidines
				Studies Suggesting an Effect of Age on Toxicity
				Studies Suggesting that Age Is Not Determinant of Toxicity
			Capecitabine
			Platinum Compounds
				Oxaliplatin
				Cisplatin
				Carboplatin
			Anthracyclines
				Liposomal Anthracyclines
			Antimicrotubule Agents (Spindle Poisons) in Elderly Cancer Patients
				Vinca Alkaloids
			Taxanes: Paclitaxel and Docetaxel
				Paclitaxel
				Docetaxel
			Purine Analogs
				Fludarabine
				Cytarabine
				Gemcitabine
				Pemetrexed
			Camptothecins
				Topotecan
				Irinotecan
				Etoposide
		Conclusion
		Cross-References
		References
	54 Principles of Cancer Targeted Therapy in Older Adults
		Introduction
		The Use of Target Agents in Older Patients
			Non-Small Cell Lung Cancer
				Bevacizumab
				Erlotinib
				Gefitinib
				Afatinib
				Crizotinib
				Nintedanib
				Ramucirumab
				Nivolumab
			Breast Cancer
				Trastuzumab
				Pertuzumab
				Trastuzumab Emtansine
				Lapatinib
			Colorectal Cancer
				Bevacizumab
				Panitumumab
				Cetuximab
				Aflibercept
				Regorafenib
			Renal Cell Carcinoma
				Sunitinib
				Axitinib
				Pazopanib
				Sorafenib
				Temsirolimus
				Everolimus
				Cabozantinib
				Nivolumab
			Melanoma
				Vemurafenib and Dabrafenib
				Ipilimumab
				Nivolumab
			Hepatocellular Carcinoma
				Sorafenib
			Gastric Cancer
				Trastuzumab
				Ramucirumab
		Cross-References
		References
	55 Pain Management in Older Cancer Patients
		Introduction
			Multidimensional Assessment of Pain in Geriatric Oncology
				Severity of the Pain
				Location and Pathophysiological Characteristics
				Particular Medical, Psycho-Behavioral, and Social Characteristics of the Patient
				Assessment of the Anticipated Efficacy of Treatment
			Pain Management in Geriatric Oncology
				Etiological Treatment
				Analgesic Drug Treatments
				Co-analgesics
				Complementary Approaches, Physical Measures, and Holistic Management
		Conclusion
		References
	56 Digestive Symptoms Control and Nutrition Issues in Older Cancer Patients
		Introduction
		Digestive Symptoms Management
			Nausea and Vomiting (Based on Roila et al. 2016)
			Diarrhea (Based on Bossi et al. 2018)
			Constipation (Based on Larkin et al. 2018)
			Stomatitis/Mucositis (Based on Peterson et al. 2015)
			Nutrition Issues in Elderly Patients (Based on Arends et al. 2017)
		Cross-References
		References
	57 Exercise and the Older Cancer Survivor
		Introduction
		Physiological Toxicities
		Patient-Reported Toxicities
		Exercise as Therapy for the Older Cancer Patient
		Exercise and Biological Mechanisms Involved in the Pathophysiology of Toxicities
		Exercise Guidelines for Older Cancer Patients and Survivors
		Exercise Prescription for Older Cancer Patients and Survivors
		Exercise Professionals
			Managing Risk and Contraindications for Exercise Professionals Working with Older Cancer Patients
		Conclusion
		References
	58 Geriatric Oncology in Tropical and Developing Countries
		Introduction
		Geography and Demography
			Geography of the Most Important Countries
			Population in Tropical, Low- and Lower-Middle-Income Countries (TLLMICs)
		Health Expenditure
		Aging in the World and Aging in TLLMICs
		Cancer in TLLMICs
			Incidence and Characteristics in the Whole Patient Population
			Incidence and Characteristics in the Elderly Patient Population
		Elderly Cancer Patient Health Status in TLLMICs
			Comorbidities
			Dependence
			Nutritional Status
			Cognitive and Thymic Impairments
			Socioeconomic Status
			Geriatric Assessment Tools
			Geriatric Series Published in TLLMICs
			Geriatric Oncology Series Published in TLLMICs
		Diagnostics in Elderly Patients
			Delay to Cancer Diagnostics in TLLMICs
			The Reasons to Explain Cancer Diagnostic Delay
			Health Status Evaluation
		Therapeutic Tools
			Palliative Treatments
			Surgery
			Radiotherapy
			Medical Treatments
		Perspectives of Management Optimization
			To Develop Interventions That Are Highly Effective, Cost-Effective, and Resource-Level Appropriate
			To Develop Geriatric Oncology in This Setting
			It Is Important to Include Information and Transcultural Mediation in These Objectives
		Conclusion
		Cross-References
		References
	59 Integrating Geriatric Oncology into Clinical Pathways and Guidelines
		Introduction
			Cancer Burden in the Elderly
			Complexity of Older Cancer Patients
			Comprehensive Geriatric Assessment
			Lack of External Validity of the Current Evidence
		Integration of Geriatric Oncology into Clinical Pathways
			Models of Care in Geriatric Oncology
			Survivorship Care of Elderly Cancer Patients
		Integration of Geriatric Oncology into Disease-Specific Guidelines
		References
	60 Decision Making and Safety Issues in Older Cancer Patients
		Introduction
		Screening/Prevention
		Assessment
		Management
		Chemotherapy Safety
		Cancer Trials
		End-of-Life Care
		Surgery
		Radiotherapy
		Healthcare Professionals Treatment Decision Making
		Cognition
		Cross-References
		References
	61 Improving Communications with Older Cancer Patients
		Introduction
		Demographic Shifts in Health Care
		Culture, Worldview, and Effective Communication
		Impact of Effective Patient-Provider Communications
		Factors That Influence Culturally Effective Communication
			Intersectionality
			Acculturation
		Essentials of Communications to Promote Effective Patient-Provider Relationship
		Creating a Patient-Centric Environment for Learning
		Preferred Methods of Learning and Communication Technologies
			Preferred Methods
			Mobile Technologies
		Language and Health Literacy
			Language
			Health Literacy
				Health Literacy Universal Precautions
				Assessing Health Literacy
			Deconstructing Information to Improve Communication
			Creating a Literacy Friendly Environment
		Special Topic: Role of Effective Communication in Clinical Trial Participation and Research
		Summary
		Cross-References
		References
	62 The Older Cancer Patient: Religious and Spiritual Dimensions
		Introduction
		Religion, Spirituality, and Health Care
			Definitions
			Assessment
			Effects of Religion and Spirituality on Health
			Religion, Spirituality, and Cancer
		Religion, Spirituality, Aging, and Cancer
			Aging is Dynamic
			Religion, Spirituality, and Aging
			Religion/Spirituality, Diseases, and Aging
			Religion Spirituality, Aging, and Cancer
			Religion, Spirituality, and the Caregiver of the Older Cancer Patient
		Spiritual and Religious Interventions
		Conclusions and Perspectives
		References
Part VIII: Research Methods in Geriatric Oncology
	63 Research Methods: Epidemiologic Research in Geriatric Oncology
		Introduction
		Data from Randomized Controlled Trials
			Extrapolation of Study Results to the General Older Population
		Observational Studies
			Cohort Data from Cancer Registries
			International Comparisons
			Treatment Effectiveness
			Competing Risks of Death
		References
	64 Research Methods: Translational Research in Geriatric Oncology
		Introduction
		Potential Biomarkers of Aging
			Systemic Inflammatory Markers
			Markers of Senescence
			Impact of Cancer Therapies on Biomarkers of Aging
			Conclusions
		Body Composition and Sarcopenia
			Introduction
			Sarcopenia in Oncology
			Assessing Sarcopenia
			Impact of Sarcopenia on Outcomes in Oncology
			Conclusions
		Cardiovascular Aging
			Introduction
			Assessing Cardiorespiratory Fitness
			Cardiorespiratory Fitness in Oncology
			Exercise as a Countermeasure to Improve Cardiorespiratory Fitness in Oncology
			Conclusions
		Methodology and Design Considerations
		General Conclusions
		Cross-References
		References
	65 Research Methods: Clinical Trials in Geriatric Oncology
		Introduction
		Definitions of ``Older´´ and ``Frailty´´
		Implications of Underrepresentation of Older Patients in Cancer Trials
		Suitable Endpoints in the Older Population
			Overall Survival (OS)
			Disease-Specific Survival (DSS)
			Coprimary Endpoints
			Composite Endpoints
			Treatment Failure-Free Survival and Time to Treatment Failure
			QoL-Related Endpoints
			Preservation of Functional Capacity/Independence
			Cognitive Function
			Surgical Trial Endpoints
		Improving Cancer Trial Design in Older Patients
			Age Limits
			Phase III Versus Phase II Trials
			Pharmacokinetics and Phase I Trials
			Randomized Controlled Trials, Observational Cohort Studies or Both?
				Randomized Controlled Trials (RCTs)
				Observational Cohort Studies
				Single Versus Multicenter Observational Cohort Studies
				Overcoming Bias in Observational Cohort Studies
				Expanded Access Programs
		Conclusion
		References
	66 Research Methods: Using Big Data in Geriatric Oncology
		Introduction
		Potential Uses in Geriatric Oncology
			Cancer Registries and Insurance Claims Databases
			Health and Research Informatics Databases
		Methods for Effective Big Database Digging
		Specific Research Applications and Methods
			Mutations, Gene Expression, Epigenetics
			Potential Application: Diagnostic and Targetable Mutations for Personalized Medicine
			Using HRI for Clinical Studies
			Digging for Therapeutic Use in Individual Unusual Cases
		Conclusions
		Cross-References
		References
	67 Research Methods: Systematic Reviews and Meta-analysis in Geriatric Oncology
		Introduction
		Overview of Evidence Reviews and Summaries in Geriatric Oncology
		Conducting a High Quality Systematic Review
		Evidence Summaries and Meta-analyses
		Special Considerations
			Diagnostic and Prognostic Studies
			Individual Patient Data Meta-analysis
			Survival Outcomes
		A Summary of Systematic Reviews and Meta-analyses in Geriatric Oncology
		Summary of Major Recommendations/Guidelines for Quality Appraisal or Reporting of Systematic Reviews and Meta-analyses
		Discussion
		References
	68 Research Methods: Quality of Life and Patient-Reported Outcome Research in Geriatric Oncology
		Introduction
		What Are Patient-Reported Outcomes?
		Endpoints in Clinical Research in Geriatric Oncology
		Instruments to Assess Patient-Reported Outcomes
			Health-Related Quality of Life Instruments
				The European Perspective
				The North American Perspective
				The EORTC QLQ-ELD14
			Creation of New Quality of Life Instruments
			Patient-Reported Outcome and Toxicity
		Patient-Reported Outcome/Health-Related Quality of Life and Geriatric Assessment
		Improving PRO by Using PROM
		PRO-cision Medicine
		Conclusion
		Cross-References
		References
	69 Research Methods: Outcomes and Survivorship Research in Geriatric Oncology
		Introduction
		Interaction Between Aging, Cancer, Cancer Treatment, and Their Impact on Frailty
		Measuring Frailty of Older Cancer Survivors
		Older Cancer Survivors´ Outcomes and Research
		Functional Decline
		Cancer-Related Functional Compromise
		Cognitive Decline
		Cancer-Related Cognitive Deficits
		Older Cancer Survivors and Endocrine Abnormalities
		The Psychosocial Aspects of Cancer Survivorship
		Cardiotoxicity
		The Future of Cancer Survivorship Research for Older Patients
		Methodological Challenges
		Conclusion
		Cross-References
		References
Index