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Book Details
Abstract
Global experts, in conjunction with the International Association for the Study of Lung Cancer, bring you up to date with today’s best approaches to lung cancer diagnosis, treatment, and follow-up. IASLC Thoracic Oncology, 2nd Edition, keeps you abreast of the entire scope of this fast-changing field, from epidemiology to diagnosis to treatment to advocacy. Written in a straightforward, practical style for the busy clinician, this comprehensive, multidisciplinary title is a must-have for anyone involved in the care of patients with lung cancer and other thoracic malignancies.
- Offers practical, relevant coverage of basic science, epidemiology, pulmonology, medical and radiation oncology, surgery, pathology, palliative care, nursing, and advocacy.
- Provides authoritative guidance from the IASLC – the only global organization dedicated to the study of lung cancer.
- Includes new content on molecular testing, immunotherapy, early detection, staging and the IASLC staging system, surgical resection for stage I and stage II lung cancer, and stem cells in lung cancer.
- Features a new full-color design throughout, as well as updated diagnostic algorithms.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| IFC | ES1 | ||
| IASLC Thoracic Oncology | i | ||
| IASLC Thoracic Oncology | iii | ||
| Copyright | iv | ||
| Contributors | v | ||
| Preface | xiii | ||
| Contents | xv | ||
| I -\rLung Cancer Control and Epidemiology | 1 | ||
| 1 - Classic Epidemiology of Lung Cancer | 1 | ||
| DESCRIPTIVE EPIDEMIOLOGY | 1 | ||
| RISK FACTORS | 1 | ||
| Tobacco Smoking | 1 | ||
| Differences in the Effect of Tobacco Smoking According to Histology, Gender, and Race | 2 | ||
| Secondhand Tobacco Smoke | 3 | ||
| Confounding Effects of Tobacco Smoking | 3 | ||
| Interaction Between Tobacco Smoke and Other Lung Carcinogens | 3 | ||
| Use of Smokeless Tobacco Products | 3 | ||
| Dietary Factors | 3 | ||
| Vegetables and Fruits | 3 | ||
| Meat and Other Foods | 3 | ||
| Coffee and Tea | 3 | ||
| Lipids | 4 | ||
| Carotenoids | 4 | ||
| Other Micronutrients | 4 | ||
| Isothiocyanates | 4 | ||
| Alcohol | 4 | ||
| Hormones | 4 | ||
| Anthropometric Measures | 5 | ||
| Infections | 5 | ||
| Ionizing Radiation | 5 | ||
| Occupational Exposures | 5 | ||
| Asbestos | 5 | ||
| Metals | 5 | ||
| Silica | 6 | ||
| Polycyclic Aromatic Hydrocarbons | 6 | ||
| Medical Conditions and Treatment | 6 | ||
| Indoor Air Pollution | 6 | ||
| Outdoor Air Pollution | 7 | ||
| Drinking Water Contamination | 7 | ||
| CONCLUSION | 7 | ||
| KEY REFERENCES | 7 | ||
| REFERENCES | 8.e1 | ||
| 2 - Tobacco Control and Primary Prevention | 9 | ||
| HISTORICAL CONTEXT OF THE TOBACCO EPIDEMIC | 9 | ||
| 21ST CENTURY TOBACCO-CONTROL MEASURES | 10 | ||
| Monitor Tobacco Use and Prevention Policies | 10 | ||
| Protect People From Tobacco Smoke | 11 | ||
| Offer Help to Quit Tobacco Use | 11 | ||
| Warn About the Dangers of Tobacco | 11 | ||
| Enforce Bans on Tobacco Advertising, Promotion, and Sponsorship | 12 | ||
| Raise Taxes on Tobacco | 12 | ||
| Combinations of Measures | 12 | ||
| Impact of Tobacco Control on Lung Cancer Mortality | 12 | ||
| CONCLUSION | 16 | ||
| KEY REFERENCES | 17 | ||
| REFERENCES | 17.e1 | ||
| 3 - Assessing and Treating Tobacco Use in Lung Cancer Care | 18 | ||
| WHY LUNG CANCER SPECIALISTS SHOULD HELP THEIR PATIENTS STOP TOBACCO USE | 18 | ||
| Risks of Persistent Smoking and Benefits of Cessation on Lung Cancer Outcomes | 18 | ||
| Prevalence of Persistent Smoking Among Patients With Lung Cancer | 18 | ||
| FACTORS ASSOCIATED WITH PERSISTENT SMOKING AMONG PATIENTS WITH LUNG CANCER | 19 | ||
| ASSESSING TOBACCO USE AND INTEGRATING EVIDENCE-BASED TOBACCO TREATMENT IS AN INDICATOR OF HIGH-QUALITY ONCOLOGY CARE | 19 | ||
| TREATMENT OF TOBACCO DEPENDENCE IN LUNG CANCER CARE | 19 | ||
| Guidelines for Treating Tobacco Use | 20 | ||
| Pharmacotherapy | 20 | ||
| SPECIAL CONSIDERATIONS IN TREATING TOBACCO DEPENDENCE IN PATIENTS WITH CANCER | 20 | ||
| FUTURE DIRECTIONS | 20 | ||
| CONCLUSION | 22 | ||
| KEY REFERENCES | 22 | ||
| REFERENCES | 22.e1 | ||
| 4 -\rLung Cancer in Never-Smokers: A Different Disease | 23 | ||
| EPIDEMIOLOGY OF NONSMOKING-RELATED LUNG CANCER\r | 23 | ||
| KNOWN OR SUSPECTED ETIOLOGIC FACTORS FOR LUNG CANCER IN NEVER-SMOKERS | 24 | ||
| Indoor Air Pollution | 24 | ||
| Environmental and Occupational Toxins | 24 | ||
| Human Papillomavirus | 24 | ||
| CLINICAL-PATHOLOGIC FEATURES OF LUNG CANCER IN NEVER-SMOKERS | 24 | ||
| THE GENETICS OF LUNG CANCER | 25 | ||
| MOLECULAR CHARACTERISTICS OF NONSMOKING EAST ASIAN INDIVIDUALS WITH LUNG CANCER | 25 | ||
| GENOME-WIDE MOLECULAR CHANGES | 27 | ||
| PRENEOPLASTIC CHANGES | 27 | ||
| DNA METHYLATION | 27 | ||
| CONCLUSION | 28 | ||
| KEY REFERENCES | 28 | ||
| REFERENCES | 29.e1 | ||
| 5 -\rGender-Related Differences in Lung Cancer | 30 | ||
| EPIDEMIOLOGY | 30 | ||
| United States | 30 | ||
| Europe | 32 | ||
| Asia | 33 | ||
| SUSCEPTIBILITY | 33 | ||
| Never-Smokers | 33 | ||
| Smokers | 34 | ||
| GENETIC FACTORS | 34 | ||
| FAMILY HISTORY | 35 | ||
| VIRAL FACTORS | 35 | ||
| ENVIRONMENTAL EXPOSURES, DIET, AND PREEXISTING LUNG DISEASE | 35 | ||
| Environmental Exposures | 35 | ||
| Diet | 36 | ||
| Preexisting Lung Disease | 36 | ||
| STEROID HORMONES IN LUNG CANCER | 36 | ||
| Estrogen Receptors | 36 | ||
| Aromatase | 38 | ||
| Nongenomic Estrogen Signaling and Interactions With Growth Factor Receptor Signaling Pathways | 39 | ||
| Progesterone Receptors | 40 | ||
| Implications for Lung Cancer Therapy | 40 | ||
| GENDER AS A PROGNOSTIC FACTOR IN EARLY-STAGE LUNG CANCER | 40 | ||
| PROGNOSTIC/PREDICTIVE ROLE OF GENDER IN ADVANCED DISEASE | 42 | ||
| Insights From Therapeutic Trials: NSCLC | 42 | ||
| Chemotherapy | 42 | ||
| Targeted Therapies | 43 | ||
| Insights From Therapeutic Trials: SCLC | 45 | ||
| CONCLUSION | 45 | ||
| KEY REFERENCES | 45 | ||
| REFERENCES | 45.e1 | ||
| 6 - Genetic Susceptibility to Lung Cancer | 46 | ||
| BIOLOGIC RISK FACTORS | 47 | ||
| EVIDENCE FOR FAMILIAL AGGREGATION OF LUNG CANCER | 47 | ||
| Twin Studies | 47 | ||
| Case–Control and Case–Family Cohort Studies | 47 | ||
| HIGH-RISK SYNDROMES CONFERRING AN INCREASED RISK OF LUNG CANCER | 48 | ||
| SEGREGATON ANALYSES OF LUNG AND OTHER TOBACCO-RELATED CANCERS | 48 | ||
| RARE, HIGH-PENETRANCE GENES: LINKAGE ANALYSIS OF LUNG CANCER | 49 | ||
| COMMON, LOW-PENETRANCE GENES: GENOME-WIDE ASSOCIATION STUDIES | 50 | ||
| CONCLUSION | 51 | ||
| KEY REFERENCES | 51 | ||
| REFERENCES | 51.e1 | ||
| 7 - Screening for Lung Cancer | 52 | ||
| PARTICIPANT SELECTION | 53 | ||
| Recruitment | 53 | ||
| SUMMARY OF RANDOMIZED SCREENING TRIALS | 54 | ||
| PULMONARY NODULES | 54 | ||
| Baseline Probabilistic Nodule Risk Prediction | 55 | ||
| Longitudinal Surveillance | 56 | ||
| OVERDIAGNOSIS | 56 | ||
| SMOKING CESSATION | 56 | ||
| Cost-Effectiveness | 57 | ||
| BIOMARKERS | 58 | ||
| CONCLUSION | 58 | ||
| KEY REFERENCES | 58 | ||
| REFERENCES | 58.e1 | ||
| 8 - Preclinical Biomarkers for the Early Detection of Lung Cancer | 59 | ||
| EARLY DETECTION | 59 | ||
| The Biology of Lung Carcinogenesis | 60 | ||
| Biomarker Validation | 60 | ||
| Advances in Techniques for Biomarker Discovery | 61 | ||
| Specimen Types | 61 | ||
| LUNG CANCER BIOMARKERS FOR EARLY DETECTION | 61 | ||
| Cytology | 61 | ||
| Circulating Tumor Cells and Circulating Tumor DNA | 64 | ||
| Mitochondrial DNA | 64 | ||
| Noncoding RNAs | 64 | ||
| Genetic Changes | 64 | ||
| Individual Genetic Mutations | 65 | ||
| Genomics | 65 | ||
| Gene Hypermethylation | 65 | ||
| Protein Markers | 66 | ||
| Proteomics | 66 | ||
| Autoantibodies and Tumor-Associated Antigens | 67 | ||
| Metabolomics | 67 | ||
| Volatile Organic Compounds | 67 | ||
| CONCLUSION | 68 | ||
| key references | 68 | ||
| REFERENCES | 68.e1 | ||
| 9 - Chemoprevention of Lung Cancer and Management of Early Lung Cancer | 69 | ||
| GENE SILENCING | 71 | ||
| SUSCEPTIBILITY TO LUNG CANCER AND BALANCING OF ANTAGONISTIC PATHWAYS | 71 | ||
| VITAMINS AND MICRONUTRIENTS | 72 | ||
| STATUS OF LUNG CANCER SCREENING AND ITS RELATIONSHIP TO CHEMOPREVENTION | 72 | ||
| Results of the NLST and Other Clinical Trials Are Not Equal | 74 | ||
| Meeting or Exceeding the Favorable Outcomes Reported in the NLST | 75 | ||
| SCREENING INTERVAL AND SELECTION OF CANDIDATES | 75 | ||
| OPPORTUNITIES TO IMPROVE LDCT SCREENING | 75 | ||
| IMPROVEMENTS IN THE APPROACH TO SCREENING AND LDCT IMAGING | 76 | ||
| CHANGES IN NODULE EVALUATION AND DIAGNOSTIC WORKUP | 76 | ||
| FURTHER OPPORTUNITIES ASSOCIATED WITH LDCT SCREENING | 76 | ||
| CHEMOPREVENTION TRIALS | 76 | ||
| Primary Chemoprevention | 77 | ||
| Secondary Chemoprevention | 77 | ||
| Linkage Chemoprevention and Future Research | 79 | ||
| FUTURE STRATEGIES | 80 | ||
| CONCLUSION | 80 | ||
| KEY REFERENCES | 80 | ||
| REFERENCES | 81.e1 | ||
| II -\rLung Cancer Molecular Carcinogenesis | 82 | ||
| 10 - Copy Number Abnormalities and Gene Fusions in Lung Cancer: Present and Developing Technologies | 82 | ||
| GENETIC INSTABILITY IN LUNG CANCER | 82 | ||
| Microsatellite Instability | 82 | ||
| Aneuploidy and CIN | 83 | ||
| AMPLIFICATION AS A MECHANISM OF ONCOGENESIS | 84 | ||
| EGFR Amplification | 84 | ||
| ERBB2 Amplification | 84 | ||
| MET Amplification | 85 | ||
| PIK3CA Amplification | 85 | ||
| FGFR1 Amplification | 86 | ||
| STRUCTURAL CHANGES LEADING TO ONCOGENESIS BY GENE FUSIONS | 86 | ||
| ALK Fusion | 86 | ||
| ROS1 Fusion | 89 | ||
| RET Fusion | 91 | ||
| Other Fusions | 93 | ||
| CONCLUSION | 93 | ||
| KEY REFERENCES | 93 | ||
| REFERENCES | 94.e1 | ||
| 11 - Mutational Events in Lung Cancer: Present and Developing Technologies | 95 | ||
| OVERVIEW OF GENOMIC TECHNOLOGIES | 95 | ||
| First-Generation Sequencing | 95 | ||
| Next-Generation Sequencing | 96 | ||
| APPLICATIONS OF NEXT-GENERATION SEQUENCING | 96 | ||
| Whole-Genome Sequencing | 96 | ||
| Whole-Exome and Targeted Gene Sequencing | 97 | ||
| Transcriptome | 97 | ||
| Epigenome | 97 | ||
| COMPREHENSIVE GENOMIC STUDIES USING NGS IN LUNG CANCER | 98 | ||
| Nonsmall Cell Lung Cancer | 98 | ||
| Small Cell Lung Cancer | 98 | ||
| EMERGING TECHNOLOGIES: THIRD-GENERATION SEQUENCING | 101 | ||
| SEQUENCING IN SUBOPTIMAL SAMPLES | 101 | ||
| Formalin-Fixed Samples | 101 | ||
| Cytology Samples | 101 | ||
| Liquid Biopsies | 102 | ||
| FUTURE DIRECTIONS | 103 | ||
| KEY REFERENCES | 103 | ||
| REFERENCES | 103.e1 | ||
| 12 - Epigenetic Events in Lung Cancer: Chromatin Remodeling and DNA Methylation | 104 | ||
| GENETIC AND EPIGENETIC INTERACTIONS | 105 | ||
| HISTONE MODIFICATIONS AND THEIR ROLE IN LUNG CANCER | 105 | ||
| CHROMATIN REMODELING COMPLEXES | 108 | ||
| Genetic Alterations at SWI/SNF Chromatin Remodeling Factors in Lung Cancer | 109 | ||
| Functional Consequences of Abnormalities in Chromatin Remodelers and Other Epigenetic Modifiers in Lung Cancer Development | 110 | ||
| DNA METHYLATION | 110 | ||
| DNA HYPOMETHYLATION IN LUNG CANCER | 111 | ||
| DNA Hypermethylation in Lung Cancer: Functional Implications | 111 | ||
| DNA Hypermethylation in Lung Cancer: Application to Marker Development | 114 | ||
| Detection of DNA Methylation Markers in Body Fluids | 114 | ||
| EPIGENETIC THERAPY FOR LUNG CANCER | 115 | ||
| CONCLUSION | 116 | ||
| KEY REFERENCES | 116 | ||
| e1REFERENCES | 116.e1 | ||
| 13 - Stem Cells and Lung Cancer: In Vitro and In Vivo Studies | 117 | ||
| NORMAL LUNG | 117 | ||
| NONSMALL CELL LUNG CANCER | 117 | ||
| Adenocarcinoma and the Cells of Origin | 117 | ||
| Isolation of a CD133-Positive Stem-Like Population in Lung Cancer | 117 | ||
| The Cell of Origin in Conditional Oncogene-Driven Adenocarcinoma | 118 | ||
| Loss of PTEN Expands the BASC Pool | 118 | ||
| Maintenance of Stem Cell Populations: Notch and Wnt Signaling | 118 | ||
| Squamous Cell Lung Carcinoma | 119 | ||
| SMALL CELL LUNG CANCER | 119 | ||
| Neuroendocrine Airway Epithelia and the Origin of Small Cell Lung Cancers | 119 | ||
| Neuroendocrine Hedgehog Signaling Mediates Airway Repair and SCLC | 119 | ||
| Tumor Heterogeneity and SCLC | 119 | ||
| CONCLUSION | 119 | ||
| KEY REFERENCES | 120 | ||
| REFERENCES | 120.e1 | ||
| 14 - Microenvironment and Lung Cancer | 121 | ||
| LUNG CARCINOGENESIS | 121 | ||
| THE DEVELOPING LUNG TUMOR MICROENVIRONMENT | 122 | ||
| TME Field Component: Adjacent Histologically Normal-Appearing Epithelium | 122 | ||
| TME Cellular and Soluble Components: Immune Effector Cells and Cell-Secreted Inflammatory Mediators | 122 | ||
| TME Structural Component: Stroma | 123 | ||
| PROTOTYPICAL CELL TYPES COMPRISING THE CELLULAR COMPONENT OF THE DEVELOPING LUNG TUMOR MICROENVIRONMENT | 123 | ||
| Cytotoxic and Helper T Cells | 123 | ||
| T Regulatory Cells | 123 | ||
| Dendritic Cells | 124 | ||
| PROTOTYPICAL CELL-SECRETED PRODUCTS COMPRISING THE SOLUBLE COMPONENT OF THE DEVELOPING LUNG TUMOR MICROENVIRONMENT | 125 | ||
| Interleukin-2 | 125 | ||
| Interleukin-6 | 125 | ||
| Transforming Growth Factor-β | 125 | ||
| RECENT ATTEMPTS TO MOLECULARLY DEFINE THE FIELD COMPONENT OF THE LUNG TUMOR MICROENVIRONMENT | 125 | ||
| CONCLUSION | 127 | ||
| KEY REFERENCES | 127 | ||
| REFERENCES | 128.e1 | ||
| 15 - MicroRNAs as Biomarkers for Lung Cancer | 129 | ||
| THE IMPORTANCE OF MICRORNAS IN LUNG CANCER | 129 | ||
| Implications of miRNAs in the Diagnosis of Lung Cancer | 129 | ||
| MicroRNAs as Prognostic Biomarkers for Lung Cancer | 132 | ||
| The Role of miRNAs in the Response to Treatment | 134 | ||
| FUTURE PERSPECTIVES | 136 | ||
| KEY REFERENCES | 136 | ||
| REFERENCES | 136.e1 | ||
| III -\rImmunology | 137 | ||
| 16 - Humoral and Cellular Immune Dysregulation and Lung Cancer | 137 | ||
| SUPPRESSION OF THE ANTIGEN-PRESENTING MACHINERY | 137 | ||
| TUMOR-DERIVED SOLUBLE FACTORS | 140 | ||
| Interleukin-10 | 140 | ||
| Transforming Growth Factor-β | 140 | ||
| TUMOR-INFILTRATING T LYMPHOCYTES | 140 | ||
| MYELOID-DERIVED SUPPRESSOR CELLS | 141 | ||
| CIGARETTE SMOKING AND IMMUNE DYSFUNCTION | 142 | ||
| CONCLUSION | 142 | ||
| KEY REFERENCES | 142 | ||
| REFERENCES | 142.e1 | ||
| IV -\rPathology | 143 | ||
| 17 - Classic Anatomic Pathology and Lung Cancer | 143 | ||
| NONSMALL CELL LUNG CARCINOMA | 143 | ||
| Adenocarcinoma | 143 | ||
| Atypical Adenomatous Hyperplasia | 145 | ||
| Adenocarcinoma in Situ | 145 | ||
| Minimally Invasive Carcinoma | 145 | ||
| Invasive Adenocarcinoma | 146 | ||
| Lepidic Predominant Invasive Adenocarcinoma. This subtype consists of a proliferation of bland type II or Clara cells growing al... | 147 | ||
| Acinar Predominant Invasive Adenocarcinoma. This subtype shows a major component of glands that are round to oval with a central... | 147 | ||
| Papillary Predominant Adenocarcinoma. This subtype shows a major component of a growth of glandular cells along central fibrovas... | 147 | ||
| Micropapillary Predominant Adenocarcinoma. This subtype has tumor cells growing in papillary tufts or florets that lack fibrovas... | 147 | ||
| Solid Predominant Invasive Adenocarcinoma. The solid subtype with mucin production consists of a major component of polygonal tu... | 147 | ||
| Variants of Invasive Adenocarcinoma | 147 | ||
| Invasive Mucinous Adenocarcinoma. Multiple studies have shown major differences in clinical, radiologic, pathologic, and genetic... | 147 | ||
| Colloid Adenocarcinoma. This subtype shows abundant extracellular mucin in pools, which distend the alveolar spaces and destroy ... | 147 | ||
| Fetal Adenocarcinoma. This subtype consists of complex glandular structures composed of glycogen-rich, nonciliated cells resembl... | 147 | ||
| Primary Pulmonary Adenocarcinoma With Enteric Differ | 147 | ||
| Immunohistochemistry of Adenocarcinomas | 148 | ||
| Histologic and Molecular Correlations | 148 | ||
| Impact of the New Classification on Tumor, Node, Metastasis Staging | 148 | ||
| Small Biopsy and Cytology Samples | 149 | ||
| Squamous Cell Carcinoma | 150 | ||
| Preinvasive Lesions | 150 | ||
| Early Invasive Squamous Cell Carcinoma | 150 | ||
| Invasive Squamous Cell Carcinoma | 150 | ||
| Keratinizing and Nonkeratinizing Squamous Cell Car | 150 | ||
| Immunohistochemistry of Squamous Cell Carcinoma. Squamous cell carcinoma has traditionally been defined as a tumor that shows ke... | 151 | ||
| Basaloid Carcinoma. Basaloid carcinoma is a variant of squamous cell carcinoma (Fig. 17.7). This is a poorly differentiated tumo... | 152 | ||
| Immunohistochemistry of Basaloid Carcinoma. Basaloid carci | 153 | ||
| Adenosquamous Carcinoma | 153 | ||
| Immunohistochemistry of Adenosquamous Carcinoma | 153 | ||
| Sarcomatoid Carcinoma | 154 | ||
| Pleomorphic, Spindle, and Giant Cell Carcinomas | 154 | ||
| Carcinosarcoma | 154 | ||
| Pulmonary Blastoma | 154 | ||
| Immunohistochemistry of Sarcomatoid Carcinoma | 154 | ||
| Large Cell Carcinoma | 154 | ||
| Immunohistochemistry of Large Cell Carcinoma | 154 | ||
| NEUROENDOCRINE TUMORS | 155 | ||
| Carcinoid Tumors | 155 | ||
| Immunohistochemistry of Carcinoid Tumors | 156 | ||
| Large Cell Neuroendocrine Carcinoma | 157 | ||
| Immunohistochemistry of LCNEC | 157 | ||
| Small Cell Lung Cancer | 157 | ||
| Immunohistochemistry of SCLC | 157 | ||
| OTHER UNCLASSIFIED TUMORS | 158 | ||
| Lymphoepithelioma-Like Carcinoma | 158 | ||
| NUT Carcinoma | 158 | ||
| SALIVARY GLAND–TYPE TUMORS | 158 | ||
| USE OF IMMUNOHISTOCHEMISTRY FOR LUNG CANCER DIAGNOSIS | 158 | ||
| PATHOLOGY SAMPLES FOR MOLECULAR TESTING | 160 | ||
| CYTOLOGIC ANALYSIS OF LUNG CANCER | 160 | ||
| Cytologic Methods | 160 | ||
| Sputum Smears | 160 | ||
| Smears Prepared by Bronchial Scraping, Brushing, or Washing | 160 | ||
| Fine-Needle Aspiration Samples | 160 | ||
| Pleural Fluid or Washing Materials | 160 | ||
| Liquid-Based Cytology | 160 | ||
| Special Staining and Immunocytochemistry of Cytology Specimens | 161 | ||
| Molecular Analysis of Cytology Specimens | 161 | ||
| Cytologic Characteristics of Each Histologic Type of Lung Cancer | 161 | ||
| Adenocarcinoma | 161 | ||
| Squamous Cell Carcinoma | 162 | ||
| Small Cell Lung Cancer | 162 | ||
| CONCLUSION | 162 | ||
| KEY REFERENCES | 162 | ||
| REFERENCES | 163.e1 | ||
| 18 - Molecular Testing in Lung Cancer | 164 | ||
| GENETIC ABNORMALITIES IN LUNG CANCER | 164 | ||
| ASSAY PLATFORMS IN MOLECULAR TESTING | 165 | ||
| Protein Expression | 165 | ||
| Gene Mutations | 165 | ||
| Changes in Gene Structure and Copy Number | 166 | ||
| TISSUE REQUIREMENTS FOR MOLECULAR TESTING | 167 | ||
| Preanalytic Factors | 167 | ||
| Sample Processing and Analysis | 168 | ||
| SAMPLE AVAILABILITY AND PRIORITIZATION OF BIOMARKERS FOR TESTING | 168 | ||
| CURRENTLY RECOMMENDED PREDICTIVE BIOMARKERS IN LUNG CANCER | 169 | ||
| EGFR Mutations for EGFR TKI Therapy | 169 | ||
| EGFR Mutations to Be Tested | 169 | ||
| Assays Used for Testing | 170 | ||
| Other Potential Biomarkers for EGFR TKI Sensitivity | 171 | ||
| Other Biomarkers of Resistance to EGFR TKIs | 171 | ||
| Patients Who Should Have Testing | 171 | ||
| When Testing Should Be Done | 172 | ||
| Tumor Site to Be Used for Testing | 172 | ||
| Clinical Recommendations for EGFR Testing | 172 | ||
| ALK Rearrangement: A Predictor of Response to ALK Inhibitors | 172 | ||
| Assays Used for Testing | 173 | ||
| Patients Who Should Have Testing | 174 | ||
| When Testing Should Be Done | 174 | ||
| Tumor Site to Be Tested | 174 | ||
| Clinical Recommendations for ALK Testing | 175 | ||
| POTENTIAL NEW MOLECULAR MARKERS FOR THE FUTURE | 175 | ||
| Prognostic Markers | 175 | ||
| Other Predictive Biomarkers | 175 | ||
| CONCLUSION | 176 | ||
| KEY REFERENCES | 176 | ||
| REFERENCES | 177.e1 | ||
| 19 - Management of Small Histologic and Cytologic Specimens in the Molecular Era | 178 | ||
| CORE-NEEDLE BIOPSY VERSUS FINE-NEEDLE ASPIRATION | 179 | ||
| Navigational Bronchoscopy for Sample Collection | 179 | ||
| RAPID ONSITE EVALUATION | 179 | ||
| Advantages | 179 | ||
| Disadvantages | 180 | ||
| Algorithm for Processing Small Samples | 180 | ||
| MANAGING SMALL SAMPLES WITHOUT RAPID ONSITE EVALUATION | 180 | ||
| OPTIMIZATION AND TRIAGE | 180 | ||
| Optimization | 180 | ||
| Slide Preparation for Fine-Needle Aspirate | 180 | ||
| Touch Preparation for Core-Needle Biopsy Specimens | 182 | ||
| Processing Core-Needle Biopsy Specimensand Cell Blocks | 182 | ||
| Immunohistochemistry | 182 | ||
| Molecular Testing | 183 | ||
| Adding Radiography for Evaluation of Adenocarcinomas | 183 | ||
| Triage | 183 | ||
| Carcinomas | 183 | ||
| Lymphoproliferative Disorders | 184 | ||
| Infectious Processes and Granulomas | 184 | ||
| CYTOLOGIC PREPARATIONS | 184 | ||
| Diff-Quik Stain | 184 | ||
| Papanicolaou Stain | 184 | ||
| Liquid-Based Preparations | 184 | ||
| Fixation and Considerations for Ancillary Testing | 185 | ||
| Cell Blocks | 185 | ||
| CONCLUSION | 185 | ||
| KEY REFERENCES | 185 | ||
| REFERENCES | 185.e1 | ||
| V -\rClinical and Radiologic Presentation of Lung Cancer | 186 | ||
| 20 - Clinical Presentation and Prognostic Factors in Lung Cancer | 186 | ||
| SYMPTOMS AND SIGNS OF LOCAL TUMOR GROWTH | 186 | ||
| Cough | 186 | ||
| Hemoptysis | 187 | ||
| Chest Pain | 187 | ||
| Dyspnea, Stridor, Wheezing | 187 | ||
| SYMPTOMS AND SIGNS OF INVASIVE LOCAL–REGIONAL OR INTRATHORACIC SPREAD | 187 | ||
| Hoarseness | 187 | ||
| Pleural Effusion | 188 | ||
| Pericardial Effusion | 188 | ||
| Superior Vena Cava Syndrome | 188 | ||
| Pancoast Syndrome | 189 | ||
| Dysphagia | 189 | ||
| Diaphragmatic Paralysis | 189 | ||
| SYMPTOMS AND SIGNS OF METASTATIC SPREAD | 189 | ||
| Bone Metastases | 189 | ||
| Brain Metastases | 190 | ||
| Spinal Cord Metastases or Spinal Compression | 190 | ||
| Liver and Adrenal Gland Metastases | 190 | ||
| Other Metastatic Sites | 191 | ||
| PARANEOPLASTIC SYNDROMES | 191 | ||
| Dermatologic or Musculoskeletal Disorders | 191 | ||
| Hypertrophic Pulmonary Osteoarthropathy and Digital Clubbing | 191 | ||
| Rare Skin Disorders | 191 | ||
| Dermatomyositis | 191 | ||
| Polymyositis | 191 | ||
| Endocrine and Metabolic Phenomena | 192 | ||
| Syndrome of Inappropriate Antidiuretic Hormone Secretion | 192 | ||
| Cushing Syndrome | 192 | ||
| Carcinoid Syndrome | 192 | ||
| Hypercalcemia | 192 | ||
| Blood Disorders | 193 | ||
| Anemia | 193 | ||
| Leukocytosis | 193 | ||
| Thrombocytosis | 193 | ||
| Hypercoagulation States | 193 | ||
| Deep Venous Thrombosis and Thromboembolism | 193 | ||
| Disseminated Intravascular Coagulopathy | 193 | ||
| Thrombotic Microangiopathy | 193 | ||
| Paraneoplastic Neurologic Syndromes | 193 | ||
| Subacute Cerebellar Degeneration. Subacute cerebellar degeneration presents with rapidly developing cerebellar symptoms such as ... | 194 | ||
| Encephalomyelitis. Encephalomyelitis is characterized by simultaneous dysfunction at various levels of the central nervous syste... | 194 | ||
| Peripheral Nervous System | 194 | ||
| SystemSensory Neuropathy | 194 | ||
| Autonomic Neuropathy. Autonomic neuropathy may be subacute over weeks and involves the sympathetic, parasympathetic, and enteric... | 194 | ||
| Cancer-Associated Retinopathy. Cancer-associated retinopathy in SCLC is thought to be caused by damage to the retinal photorecep... | 194 | ||
| CLINICAL AND MOLECULAR PROGNOSTICATION OF LUNG CANCER | 194 | ||
| Clinical Factors | 194 | ||
| Age | 194 | ||
| Performance Status | 195 | ||
| Smoking Status | 195 | ||
| Gender | 195 | ||
| Histology | 195 | ||
| PET Imaging | 195 | ||
| Molecular Factors | 195 | ||
| Nucleotide Excision Repair System | 195 | ||
| Excision Repair Cross-Complementation Group 1. Excision | 195 | ||
| Ribonucleotide Reductase Messenger 1. Ribonucleotide reductase messenger 1 (RRM1) is a component of ribonucleotide reductase and... | 195 | ||
| Oncogenes and Tumor Suppressor Genes | 196 | ||
| Protein Kinases | 196 | ||
| Anaplastic Lymphoma Kinase. In 2007, Soda et al.202 identified the echinoderm microtubule-associated protein like 4 (EML4)-ALK f... | 196 | ||
| Fibroblast Growth Factor Receptor 1. Fibroblast growth factor receptor (FGFR) belongs to the super-family of receptor tyrosine k... | 196 | ||
| Tumor Cell Proliferation | 196 | ||
| Gene Expression Arrays | 196 | ||
| Epigenetics | 197 | ||
| Proteomic Analysis | 197 | ||
| MicroRNA | 197 | ||
| CONCLUSION | 197 | ||
| KEY REFERENCES | 197 | ||
| REFERENCES | 198.e1 | ||
| 21 - Conventional Imaging of Lung Cancer | 199 | ||
| RADIOLOGIC PRESENTATION OF LUNG CANCER | 199 | ||
| SOLITARY PULMONARY NODULE CHARACTERIZATION | 199 | ||
| Size | 200 | ||
| Density | 200 | ||
| Ground-Glass Opacity | 200 | ||
| Enhancement | 201 | ||
| Borders | 201 | ||
| Shape | 201 | ||
| Calcification | 201 | ||
| Adipose Content | 201 | ||
| Cavitation | 201 | ||
| Multiplicity | 202 | ||
| Location | 202 | ||
| IMAGING WITH CHEST RADIOGRAPHS | 202 | ||
| Technical Factors | 203 | ||
| Blind Spots on Radiography | 203 | ||
| Characteristics of Lung Cancers Missed on Radiography | 204 | ||
| Use of Special Radiographic Views | 204 | ||
| New Technology in Radiography | 204 | ||
| Computer-Aided Detection | 204 | ||
| Dual-Energy Subtraction Radiography | 204 | ||
| IMAGING WITH CT | 205 | ||
| Blind Spots on CT | 206 | ||
| Characteristics of Lung Cancers Missed on CT | 206 | ||
| New Technology in CT | 206 | ||
| Computer-Aided Detection | 206 | ||
| Maximum Intensity Projection | 206 | ||
| USE OF CT IN STAGING OF LUNG CANCERS | 206 | ||
| Tumor (T) Descriptors | 207 | ||
| Direct Invasion of the Pleura | 207 | ||
| Direct Invasion of the Mediastinum | 208 | ||
| Satellite Nodules | 208 | ||
| Postobstructive Collapse or Pneumonitis | 209 | ||
| Lymph Node (N) Descriptors | 209 | ||
| Metastasis (M) Descriptors | 210 | ||
| Adrenal Gland Imaging | 210 | ||
| Liver Imaging | 210 | ||
| Bone Imaging | 210 | ||
| Brain Imaging | 210 | ||
| IMAGE-GUIDED BIOPSY | 210 | ||
| CT IMAGING OF RESPONSE TO THERAPY | 211 | ||
| Chemotherapy | 211 | ||
| Radiotherapy | 211 | ||
| Surgical Resection | 213 | ||
| IMAGING OF EMERGENT CONDITIONS IN LUNG CANCER | 213 | ||
| Pulmonary Embolism | 213 | ||
| Superior Vena Cava Syndrome | 214 | ||
| Central Airway Obstruction | 214 | ||
| IMAGING WITH MRI | 214 | ||
| Identification of Pulmonary Nodules | 214 | ||
| Characterization of Pulmonary Nodules | 214 | ||
| USE OF MRI IN STAGING OF LUNG CANCER | 215 | ||
| T Descriptors | 215 | ||
| N Descriptors | 216 | ||
| M Descriptors | 216 | ||
| MRI OF RESPONSE TO THERAPY | 217 | ||
| CONCLUSION | 217 | ||
| KEY REFERENCES | 218 | ||
| REFERENCES | 218.e1 | ||
| 22 - Positron Emission Tomography Imaging of Lung Cancer | 219 | ||
| STAGING OF LUNG CANCER | 219 | ||
| Size, Location, and Locoregional Invasion (T Descriptor) | 219 | ||
| Regional Lymph Nodes (N Descriptor) | 219 | ||
| Distant Metastasis | 221 | ||
| PROGNOSIS | 223 | ||
| THERAPEUTIC RESPONSE | 226 | ||
| FDG-PET–CT FOR RADIATION TREATMENT PLANNING AND ADAPTIVE PLANNING | 227 | ||
| Novel Tracers | 228 | ||
| CONCLUSION | 231 | ||
| KEY REFERENCES | 232 | ||
| REFERENCES | 232.e1 | ||
| VI -\rDiagnosis and Staging of Lung Cancer | 233 | ||
| 23 - Diagnostic Workup for Suspected Lung Cancer Confined to the Chest | 233 | ||
| CLINICAL FEATURES | 233 | ||
| HISTORY | 234 | ||
| IMAGING FEATURES AND DIAGNOSTIC ACCURACY | 235 | ||
| DIAGNOSTIC APPROACH FOR ESTABLISHING A DEFINITIVE DIAGNOSIS AND STAGING | 236 | ||
| Endoscopic Techniques for Diagnosis and Staging | 237 | ||
| Flexible Bronchoscopy | 237 | ||
| EBUS Fine-Needle Aspiration | 237 | ||
| EUS Needle Aspiration | 237 | ||
| Combined EBUS and EUS Needle Aspiration | 238 | ||
| TTNA and Core Biopsy | 239 | ||
| CONCLUSION | 239 | ||
| KEY REFERENCES | 239 | ||
| REFERENCES | 240.e1 | ||
| 24 - Preoperative and Intraoperative Invasive Staging of the Mediastinum | 241 | ||
| LYMPH NODE ANATOMY OF THE MEDIASTINUM AND THE IASLC LYMPH NODE MAP | 241 | ||
| LYMPH NODE STATIONS AND CHOICE OF STAGING TECHNIQUE | 241 | ||
| INDICATIONS FOR INVASIVE MEDIASTINAL STAGING | 242 | ||
| DEFINITIONS OF MEDIASTINAL LYMPH NODE STAGING | 244 | ||
| REQUIRED LYMPH NODE STATIONS FOR INVASIVE STAGING | 245 | ||
| CHOICE OF STAGING TECHNIQUE | 245 | ||
| INVASIVE/SURGICAL STAGING TECHNIQUES | 245 | ||
| Mediastinoscopy | 245 | ||
| Definition | 245 | ||
| Technique | 245 | ||
| Results | 246 | ||
| Complications | 246 | ||
| Limitations | 246 | ||
| Parasternal Mediastinotomy | 246 | ||
| Definition | 246 | ||
| Indicatio\\ns | 246 | ||
| Technique | 246 | ||
| VII -\rSurgical Management of Lung Cancer | 265 | ||
| 26 - Preoperative Functional Evaluation of the Surgical Candidate | 265 | ||
| EVALUATION OF COMORBIDITY | 265 | ||
| ESTIMATION OF CARDIAC RISK | 266 | ||
| PREDICTED POSTOPERATIVE FORCED EXPIRATORY VOLUME IN 1 SECOND | 267 | ||
| CARBON MONOXIDE LUNG DIFFUSION CAPACITY | 267 | ||
| VIDEO-ASSISTED THORACOSCOPIC SURGERY | 268 | ||
| EXERCISE TESTING | 268 | ||
| Low-Technology Tests | 268 | ||
| 6-Minute Walking Test | 268 | ||
| Shuttle Walk Test | 268 | ||
| Stair-Climbing Test | 269 | ||
| Cardiopulmonary Exercise Test | 269 | ||
| ALGORITHMS | 270 | ||
| SMOKING CESSATION | 270 | ||
| PULMONARY REHABILITATION | 271 | ||
| CONCLUSION | 271 | ||
| KEY REFERENCES | 272 | ||
| REFERENCES | 273.e1 | ||
| 27 - Results of Video-Assisted Techniques for Resection of Lung Cancer | 274 | ||
| DEFINITIONS | 274 | ||
| Patient Selection | 274 | ||
| OUTCOMES: COMPARISON OF VATS AND OPEN LOBECTOMY | 275 | ||
| Short-Term Outcomes | 275 | ||
| Long-Term Outcomes | 276 | ||
| Specific Issues | 280 | ||
| Node Dissection/Staging N1 and N2 | 280 | ||
| Ability to Tolerate Adjuvant Chemotherapy | 281 | ||
| Learning Curve | 281 | ||
| Robotic Versus VATS Lobectomy | 281 | ||
| DISCUSSION | 281 | ||
| CONCLUSION | 281 | ||
| KEY REFERENCES | 281 | ||
| REFERENCES | 282.e1 | ||
| 28 - Robotic Surgery: Techniques and Results for Resection of Lung Cancer | 283 | ||
| DEFINITIONS | 283 | ||
| HISTORY OF SURGICAL ROBOTICS | 283 | ||
| ROBOTIC LOBECTOMY: TECHNICAL ASPECTS | 284 | ||
| Operating Room Configuration | 284 | ||
| Console | 284 | ||
| Robot/Bed | 284 | ||
| Surgical Team | 284 | ||
| Patient Positioning | 285 | ||
| Port Placement/Docking | 285 | ||
| Sequence of Port Placement | 285 | ||
| Mediastinal Lymph Node Dissection | 286 | ||
| Right Side | 286 | ||
| Left Side | 286 | ||
| General Concepts | 286 | ||
| OUTCOMES | 288 | ||
| Short-Term Results | 288 | ||
| Long-Term Results | 288 | ||
| CONCLUSION | 288 | ||
| REFERENCES | 288.e1 | ||
| 29 - Extent of Surgical Resection for Stage I and II Lung Cancer | 289 | ||
| OVERVIEW OF THE EVOLUTION OF LUNG CANCER SURGERY | 289 | ||
| RESULTS OF SURGICAL RESECTION FOR STAGE I AND II LUNG CANCER | 290 | ||
| POSSIBILITY OF SUBLOBAR, LIMITED RESECTION FOR STAGE I AND II LUNG CANCER | 291 | ||
| Technical and Pathologic Considerations | 291 | ||
| Oncologic Considerations | 292 | ||
| CONCLUSION | 294 | ||
| KEY REFERENCES | 294 | ||
| REFERENCES | 294.e1 | ||
| 30 - Extended Resections for Lung Cancer: Chest Wall and Pancoast Tumors | 295 | ||
| CHEST WALL TUMORS | 295 | ||
| General Principles | 295 | ||
| Staging | 295 | ||
| Surgical Resection | 296 | ||
| Results and Long-Term Survival | 296 | ||
| PANCOAST TUMORS | 298 | ||
| Historical Background | 298 | ||
| Anatomic Definition | 298 | ||
| Pretreatment Evaluation | 298 | ||
| Multimodality Treatment | 298 | ||
| Technical Approaches to Resection | 300 | ||
| Posterior (Paulson) Approach | 300 | ||
| Resection of Vertebral Body and Epidural Tumors | 301 | ||
| Anterior Approaches | 301 | ||
| CONCLUSION | 302 | ||
| KEY REFERENCES | 303 | ||
| REFERENCES | 303.e1 | ||
| 31 - Extended Resections for Lung Cancer: Bronchovascular Sleeve Resections | 304 | ||
| HISTORY AND SURGICAL OUTCOMES OF BRONCHOVASCULAR SLEEVE RESECTION | 304 | ||
| Bronchial Sleeve Resection | 304 | ||
| Pulmonary Artery Angioplasty | 304 | ||
| HEALING OF THE ANASTOMOTIC SITE AFTER BRONCHIAL SLEEVE RESECTION | 304 | ||
| SURGICAL TECHNIQUES AND CONTROVERSIES REGARDING BRONCHIAL SLEEVE RESECTIONS | 305 | ||
| Suturing Method: Interrupted or Continuous? | 305 | ||
| Suturing Layers: Through-and-Through or Submucosal Suture? | 305 | ||
| Type of Anastomosis: Telescope or End-To-End? | 305 | ||
| Type of Sleeve Resection: Wedge or Conventional? | 306 | ||
| Bronchial Anastomosis: Wrap or No Wrap? | 306 | ||
| SURGICAL TECHNIQUES AND CONTROVERSIES REGARDING PULMONARY ARTERY ANGIOPLASTY | 306 | ||
| Pulmonary Artery Resections and Reconstructions: Tangential Resection or Sleeve Resection? | 306 | ||
| Tangential Resection | 306 | ||
| Sleeve Resection | 307 | ||
| Which Should Be Reconstructed First in a Double Sleeve Resection: The Bronchial or Vascular Anastomosis? | 307 | ||
| Postoperative Anticoagulant Therapy: Necessary or Unnecessary? | 307 | ||
| CONCLUSION | 307 | ||
| KEY REFERENCES | 307 | ||
| REFERENCES | 307.e1 | ||
| 32 -\rMultiple Nodules: Management of Synchronous and Metachronous Lung Cancers | 308 | ||
| DIFFERENTIATING MPLCs FROM METASTATICDISEASE | 308 | ||
| MPLCs in the Lung Cancer Staging System | 309 | ||
| Synchronous Primary Lung Cancers | 309 | ||
| Patient Evaluation | 309 | ||
| Surgical Resection and Outcome | 309 | ||
| Metachronous Primary Lung Cancers | 310 | ||
| Incidence | 310 | ||
| Evaluation | 310 | ||
| Surgical Resection and Outcome | 310 | ||
| Metachronous Tumors Following Pneumonectomy | 311 | ||
| Stereotactic Body Radiotherapy | 311 | ||
| EVIDENCE-BASED PRACTICE GUIDELINES | 312 | ||
| CONCLUSION | 313 | ||
| KEY REFERENCES | 313 | ||
| REFERENCES | 313.e1 | ||
| 33 - Surgical Management of Patients Considered Marginally Resectable | 314 | ||
| WHICH PATIENTS ARE CONSIDERED MARGINALLY RESECTABLE? | 314 | ||
| ROLE OF SUBLOBAR RESECTION IN THE TREATMENT OF NONSMALL CELL LUNG CANCER | 314 | ||
| IMPACT OF SUBLOBAR RESECTION ON LUNG FUNCTION AND MORBIDITY | 315 | ||
| VIDEO-ASSISTED THORACOSCOPIC SURGERY | 316 | ||
| SUBLOBAR RESECTION VERSUS OTHER LOCAL THERAPIES | 316 | ||
| Optimization of Oncologic Outcomes With Sublobar Resection | 316 | ||
| CONCLUSION | 316 | ||
| KEY REFERENCES | 317 | ||
| REFERENCES | 317.e1 | ||
| VIII -\rRadiotherapeutic Management of Lung Cancer | 318 | ||
| 34 - Technical Requirements for Lung Cancer Radiotherapy | 318 | ||
| RADIOTHERAPY EQUIPMENT | 320 | ||
| Imaging and Simulation Systems | 320 | ||
| 2-D Simulation | 320 | ||
| Computed Tomography | 320 | ||
| Positron Emission Tomography | 320 | ||
| Magnetic Resonance Imaging | 321 | ||
| Immobilization | 321 | ||
| Treatment Planning Systems | 321 | ||
| Target and Normal Tissue Delineation | 321 | ||
| Dose Calculation for Lung Cancer Radiotherapy | 322 | ||
| Photon Transport Correction Methods | 322 | ||
| Superposition/Convolution Methods | 322 | ||
| Monte Carlo Methods | 323 | ||
| Finite-Element Methods | 323 | ||
| Treatment Delivery Systems | 323 | ||
| Linear Accelerator | 323 | ||
| Cobalt Therapy Systems | 324 | ||
| Hadron Therapy Systems | 324 | ||
| TREATMENT DELIVERY FOR NONSMALL CELL LUNG CANCER | 324 | ||
| 2-D Planning Simulation | 324 | ||
| Conformal Radiotherapy: 3-D Conformal Radiotherapy, IMRT, and VMAT | 324 | ||
| Hadron Therapy | 326 | ||
| Delivery of Conformal Radiotherapy: Image-Guided Radiotherapy | 326 | ||
| MOTION MANAGEMENT | 326 | ||
| QUALITY ASSURANCE FOR LUNG CANCER RADIOTHERAPY | 327 | ||
| FUTURE DIRECTIONS IN LUNG CANCER RADIOTHERAPY | 328 | ||
| Early Stage Lung Cancer and Pulmonary Metastases | 328 | ||
| Locally Advanced Lung Cancer | 328 | ||
| Individualizing Treatment | 328 | ||
| Technical Advances in Radiotherapy Planning and Imaging | 328 | ||
| CONCLUSION | 328 | ||
| KEY REFERENCES | 328 | ||
| REFERENCES | 329.e1 | ||
| 35 - Radiobiology of Lung Cancer | 330 | ||
| RADIOBIOLOGIC BASIS OF CONVENTIONALLY FRACTIONATED RADIOTHERAPY | 330 | ||
| DNA: The Critical Target for the Biologic Effects of Radiation Damage | 330 | ||
| The Linear–Quadratic Model | 330 | ||
| The Four Rs of Radiobiology | 331 | ||
| Repair | 331 | ||
| Reassortment | 331 | ||
| Reoxygenation | 331 | ||
| Repopulation | 331 | ||
| Summary | 331 | ||
| Biologically Effective Dose (BED) | 331 | ||
| ALTERNATIVE FRACTIONATION SCHEDULES AND DOSE ESCALATION | 332 | ||
| Hyperfractionated Radiation Therapy in Lung Cancer | 332 | ||
| Clinical Applications of Hyperfractionation | 332 | ||
| Summary | 332 | ||
| Accelerated Fractionation Schedules in Lung Cancer | 333 | ||
| Clinical Applications of Accelerated Fractionation | 333 | ||
| Modestly Hypofractionated Radiation Schedules | 333 | ||
| Summary | 333 | ||
| STEREOTACTIC ABLATIVE RADIOTHERAPY | 334 | ||
| Radiobiology of Stereotactic Ablative Radiotherapy | 334 | ||
| The Linear–Quadratic Model | 334 | ||
| Universal Survival Curve | 334 | ||
| Effects of SABR: New Mechanisms of Cell Killing? | 334 | ||
| MODIFICATION OF RADIATION RESPONSE | 334 | ||
| Chemotherapy | 334 | ||
| Clinical Application: Radiation-Dose Escalation in the Setting of Concurrent Chemotherapy | 334 | ||
| Addressing Tumor Hypoxia | 335 | ||
| Hypoxic Cell Radiosensitizers | 335 | ||
| Hypoxic Cytotoxins | 335 | ||
| Future Directions | 335 | ||
| BIOMARKERS PREDICTIVE OF RADIATION RESPONSE | 335 | ||
| CONCLUSION | 336 | ||
| KEY REFERENCES | 336 | ||
| REFERENCES | 336.e1 | ||
| 36 - Patient Selection for Radiotherapy | 337 | ||
| PATIENT-RELATED FACTORS | 337 | ||
| Performance Status | 337 | ||
| Lung Function | 337 | ||
| Comorbidities | 338 | ||
| Age and Frailty | 338 | ||
| Concurrent Medication (Other Than Chemotherapy) | 338 | ||
| Molecular Factors | 338 | ||
| Smoking Status | 339 | ||
| Nutrition | 339 | ||
| Fatigue and Physical Activity | 339 | ||
| Repeat Radiation | 339 | ||
| TUMOR-RELATED FACTORS | 339 | ||
| Radiated Volume and Toxicity | 340 | ||
| F-2-Deoxy-d-Glucose Uptake | 340 | ||
| Computed Tomography and Positron Emission Tomography Metrics | 341 | ||
| Mutation Status | 341 | ||
| CONCLUSION | 341 | ||
| KEY REFERENCES | 341 | ||
| REFERENCES | 341.e1 | ||
| 37 - Stage I Nonsmall Cell Lung Cancer and Oligometastatic Disease | 342 | ||
| SABR: BACKGROUND AND DEFINITIONS | 342 | ||
| SABR Protocol Development, Implementation, and Quality Assurance | 343 | ||
| CLINICAL ASSESSMENT | 343 | ||
| Diagnosis and Staging Before SABR | 343 | ||
| TECHNICAL OVERVIEW FOR RADIATION ONCOLOGISTS | 344 | ||
| Target Volume Definition and Treatment Planning | 344 | ||
| Target Volume Concept and Motion Management Strategy | 344 | ||
| Dose Fractionation and Prescription | 344 | ||
| Treatment Planning | 344 | ||
| Patient Immobilization and Set-Up | 345 | ||
| CLINICAL RESULTS OF SABR | 345 | ||
| Toxicity | 346 | ||
| SABR FOR CENTRAL LESIONS | 347 | ||
| FOLLOW-UP AFTER SABR | 347 | ||
| SALVAGE THERAPIES | 349 | ||
| REPRODUCIBILITY OF SABR RESULTS | 349 | ||
| ALTERNATIVES TO SABR FOR EARLY-STAGE NSCLC | 349 | ||
| OLIGOMETASTASES FROM LUNG CANCER | 350 | ||
| IMMUNE EFFECTS OF SABR FOR OLIGOMETASTASES | 351 | ||
| CLINICAL RESULTS OF SABR FOR OLIGOMETASTASES | 351 | ||
| Adrenal Gland | 351 | ||
| Liver | 351 | ||
| Lymph Nodes | 351 | ||
| Vertebrae | 352 | ||
| Multiple Organs | 353 | ||
| CONCLUSION | 353 | ||
| KEY REFERENCES | 353 | ||
| REFERENCES | 354.e1 | ||
| 38 - Ablation Options for Localized Nonsmall Cell Lung Cancer | 355 | ||
| MECHANISM OF ACTION OF ABLATION TECHNIQUES | 355 | ||
| Radiofrequency Ablation | 355 | ||
| Microwave Ablation | 355 | ||
| Cryoablation | 356 | ||
| Irreversible Electroporation | 356 | ||
| TECHNICAL FACTORS INFLUENCING SIZE OF THE ABLATION ZONE | 357 | ||
| Probe Characteristics | 357 | ||
| Tissue Characteristics | 357 | ||
| Heat Sink | 358 | ||
| INDICATIONS FOR THERMAL ABLATION | 358 | ||
| COMPLICATIONS OF THERMAL ABLATION | 359 | ||
| REPORTED OUTCOMES OF THERMAL ABLATION | 359 | ||
| Survival and Recurrence | 359 | ||
| Surveillance | 359 | ||
| TREATMENT CONSIDERATIONS | 360 | ||
| Identifying the Ideal Candidate for Ablation | 360 | ||
| Immunologic Effects | 361 | ||
| Thermal Ablation in Combination With Adjunctive Therapies | 361 | ||
| CONCLUSION | 362 | ||
| KEY REFERENCES | 362 | ||
| REFERENCES | 362.e1 | ||
| 39 - Radiotherapy for Locally Advanced Nonsmall Cell Lung Cancer Including Combined Modality | 363 | ||
| RADIOTHERAPY DOSE AND FRACTIONATION | 363 | ||
| Dose | 363 | ||
| Altered Fractionation Schedules | 364 | ||
| Hypofractionation | 364 | ||
| CHEMORADIATION THERAPY | 364 | ||
| Role of Chemotherapy | 365 | ||
| Sequential and Concurrent Therapy | 365 | ||
| Chemotherapy Drug Combinations | 366 | ||
| Induction and Consolidation Therapy | 367 | ||
| Chemoradiation Therapy for Older Individuals | 367 | ||
| MOLECULARLY TARGETED THERAPEUTIC AGENTS | 368 | ||
| Epidermal Growth Factor Receptor | 368 | ||
| Antiangiogenesis Agents | 369 | ||
| Anaplastic Lymphoma Kinase Inhibitors | 369 | ||
| Immune Checkpoint Inhibitors (PD-1/PD-L-1) | 369 | ||
| LOCOREGIONAL TREATMENT WITH SURGERY OR RADIOTHERAPY | 369 | ||
| Randomized Trials of Surgery | 369 | ||
| Advantages and Disadvantages of Surgery | 371 | ||
| Considerations for Choosing Surgery or Radiotherapy | 371 | ||
| BRAIN METASTASES AND PROPHYLACTIC CRANIAL RADIATION | 372 | ||
| OUTCOME MEASUREMENTS | 373 | ||
| CONCLUSION | 373 | ||
| KEY REFERENCES | 373 | ||
| REFERENCES | 373.e1 | ||
| 40 - Radiotherapy in the Management of Small Cell Lung Cancer: Thoracic Radiotherapy, Prophylactic Cranial Irradiation | 374 | ||
| TIMING QUESTION | 375 | ||
| FRACTIONATION AND DOSE | 376 | ||
| RADIATION TREATMENT VOLUMES | 377 | ||
| CHEMOTHERAPY REGIMEN COMBINED WITH RADIOTHERAPY | 378 | ||
| EXTENSIVE DISEASE: THORACIC RADIOTHERAPY | 379 | ||
| PROPHYLACTIC CRANIAL IRRADIATION | 379 | ||
| PROPHYLACTIC CRANIAL IRRADIATION IN EXTENSIVE DISEASE | 380 | ||
| KEY REFERENCES | 381 | ||
| REFERENCES | 381.e1 | ||
| 41 - Palliative Radiotherapy for Lung Cancer | 382 | ||
| PALLIATIVE RADIOTHERAPY FOR THORACIC SYMPTOMS | 382 | ||
| Indications | 383 | ||
| External-Beam Radiotherapy | 383 | ||
| Radiotherapy Planning | 383 | ||
| Radiotherapy Regimens | 383 | ||
| Side Effects | 383 | ||
| Repeat Radiation | 384 | ||
| Brachytherapy | 385 | ||
| Palliative Chemoradiation Therapy | 385 | ||
| BONE METASTASES | 385 | ||
| International Bone Metastases Consensus End Points | 385 | ||
| Indications for External-Beam Radiotherapy: Uncomplicated Bone Metastases | 386 | ||
| Impending Pathologic Fracture | 386 | ||
| Established Pathologic Fracture | 386 | ||
| Postoperative Radiotherapy | 386 | ||
| Neuropathic Pain | 386 | ||
| Quality of Life | 387 | ||
| Indications for Hemibody External-Beam Radiation | 387 | ||
| Indications for Stereotactic Radiosurgery | 388 | ||
| Side Effects of External-Beam Radiotherapy | 388 | ||
| Integration of External-Beam Radiotherapy With Other Modalities | 388 | ||
| External-Beam Radiotherapy and Minimally Invasive Techniques | 388 | ||
| External-Beam Radiotherapy and Systemic Therapy | 388 | ||
| Repeat Radiotherapy | 388 | ||
| Spinal Cord Compression | 389 | ||
| Impending Spinal Cord Compression | 389 | ||
| Established Spinal Cord Compression | 389 | ||
| Repeat Radiotherapy for Spinal Cord Compression | 389 | ||
| BRAIN METASTASES | 389 | ||
| Selection of Patients Who Are More Likely to Benefit From Treatment | 390 | ||
| Whole-Brain Radiotherapy: Dose Fractionation and Planning | 390 | ||
| Outcomes | 391 | ||
| Toxicity of WBRT | 391 | ||
| Alternative Management Approaches | 391 | ||
| Repeat Treatment | 391 | ||
| PALLIATIVE RADIOTHERAPY TO OTHER AREAS | 392 | ||
| CONCLUSION | 392 | ||
| KEY REFERENCES | 392 | ||
| REFERENCES | 392.e1 | ||
| 42 - Acute and Late Toxicities of Thoracic Radiotherapy: Pulmonary, Esophagus, and Heart | 393 | ||
| PULMONARY TOXICITY | 393 | ||
| Pathophysiology | 393 | ||
| Grading of Lung Toxicity | 393 | ||
| Changes in Pulmonary Function Tests | 394 | ||
| RADIATION PNEUMONITIS | 395 | ||
| Dosimetric Factors | 396 | ||
| Clinical Factors | 396 | ||
| Combined Dosimetric and Clinical Factors | 397 | ||
| Biomarkers | 398 | ||
| Recall Radiation Pneumonitis | 398 | ||
| Prevention and Management | 398 | ||
| Amifostine | 398 | ||
| Pentoxifylline and Vitamin E | 399 | ||
| Steroids | 399 | ||
| Angiotensin-Converting Enzyme Inhibitors | 399 | ||
| TGF-β Tyrosine Kinase Inhibitors | 399 | ||
| Treatment of Radiation Pneumonitis | 399 | ||
| ESOPHAGUS TOXICITY | 399 | ||
| Pathophysiology | 399 | ||
| Grading of Esophagus Toxicity | 399 | ||
| Radiation Esophagitis | 400 | ||
| Dosimetric Factors | 400 | ||
| Clinical Factors | 401 | ||
| Combined Dosimetric and Clinical Factors | 402 | ||
| Prevention and Management | 402 | ||
| Management | 403 | ||
| HEART | 403 | ||
| Pathophysiology | 403 | ||
| Heart Imaging Data From Irradiated Patients | 403 | ||
| Grading of Heart Toxicity | 404 | ||
| Types of Cardiovascular Toxicity | 404 | ||
| Scoring of Cardiac Toxicity | 404 | ||
| Data From Lung Cancer Patients | 405 | ||
| Data From Breast Cancer Patients | 406 | ||
| Data From Patients With Hodgkin Disease | 406 | ||
| Dosimetric Factors | 406 | ||
| Combined Modality Therapy | 407 | ||
| Pneumonitis Versus Cardiac Injury | 407 | ||
| Prevention and Management | 407 | ||
| CONCLUSION | 408 | ||
| KEY REFERENCES | 408 | ||
| REFERENCES | 408.e1 | ||
| 43 - Neurotoxicity Related to Radiotherapy and Chemotherapy for Nonsmall Cell and Small Cell Lung Cancer | 409 | ||
| NEUROTOXICITY FROM RADIOTHERAPY | 409 | ||
| Brachial Plexus | 409 | ||
| Spinal Cord | 411 | ||
| Brain | 412 | ||
| Prophylactic Cranial Radiation | 413 | ||
| Radiographic Imaging Studies | 413 | ||
| PREVENTION OF NEUROCOGNITIVE COMPLICATIONS | 414 | ||
| Chemotherapy-Induced Peripheral Neuropathy | 414 | ||
| Chemotherapy Treatments Associated With CIPN | 414 | ||
| Prevention of CIPN | 415 | ||
| Pharmacologic Therapy for CIPN | 416 | ||
| CONCLUSION | 417 | ||
| KEY REFERENCES | 417 | ||
| REFERENCES | 417.e1 | ||
| IX -\rChemotherapy and Targeted Agents for Lung Cancer | 418 | ||
| 44 -\rFrontline Systemic Therapy Options in Nonsmall Cell Lung Cancer | 418 | ||
| PROGNOSTIC FACTORS IN NONSMALL CELL LUNG CANCER | 418 | ||
| Clinical Factors | 418 | ||
| Ethnicity | 419 | ||
| Tumor Stage | 419 | ||
| Histology | 419 | ||
| Molecular Markers | 420 | ||
| TREATMENT OF ADVANCED NONSMALL CELL LUNG CANCER | 420 | ||
| Systemic Chemotherapy | 420 | ||
| Platinum Compounds | 420 | ||
| Cisplatin Versus Carboplatin | 421 | ||
| Triplets for Advanced NSCLC | 421 | ||
| Platinum-Free Versus Platinum-Based Chemotherapy | 422 | ||
| Duration of Chemotherapy | 422 | ||
| Maintenance Therapy | 422 | ||
| IMPORTANCE OF HISTOLOGY IN THE TREATMENT OF NSCLC | 423 | ||
| MANAGEMENT OF ELDERLY PATIENTS | 423 | ||
| MANAGEMENT OF PATIENTS WITH A POOR PERFORMANCE STATUS | 424 | ||
| BIOMARKERS FOR SELECTION OF CHEMOTHERAPY | 424 | ||
| COMBINATION OF TARGETED AGENTS WITH PLATINUM-BASED CHEMOTHERAPY | 425 | ||
| ANTIANGIOGENIC THERAPY | 425 | ||
| Other Antiangiogenic Agents | 426 | ||
| EPIDERMAL GROWTH FACTOR BLOCKADE IN NSCLC | 427 | ||
| EGFR Tyrosine Kinase Inhibitors | 427 | ||
| Monoclonal Antibody Against EGFR | 428 | ||
| Biomarkers for EGFR Blockade | 429 | ||
| Resistance to EGFR TKIs | 429 | ||
| ALK-REARRANGED NSCLC | 430 | ||
| MOLECULAR CHARACTERIZATION OF NSCLC | 431 | ||
| IMMUNOTHERAPY IN NSCLC | 432 | ||
| CONCLUSION | 432 | ||
| KEY REFERENCES | 432 | ||
| REFERENCES | 433.e1 | ||
| 45 - Systemic Options for Second-Line Therapy and Beyond | 434 | ||
| HISTORY | 435 | ||
| SECOND-LINE CHEMOTHERAPY | 435 | ||
| CHOICE OF CHEMOTHERAPY AGENT | 436 | ||
| SCHEDULING OF CHEMOTHERAPY | 436 | ||
| THIRD- AND SUBSEQUENT-LINE OF CHEMOTHERAPY | 437 | ||
| SECOND-LINE TREATMENT WITH MOLECULARLY TARGETED AGENTS | 437 | ||
| Gefitinib | 437 | ||
| Erlotinib | 437 | ||
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Patients With Known Wild-Type EGFR Tumors | 438 | ||
| Vascular Endothelial Growth Factor Inhibitors | 438 | ||
| NOVEL TARGETS | 439 | ||
| Second- and Third-Generation Epidermal Growth Factor Receptor Inhibitors | 439 | ||
| ANAPLASTIC LYMPHOMA KINASE | 441 | ||
| ROS1 | 442 | ||
| B-Raf Kinase | 442 | ||
| KRAS | 442 | ||
| MET | 442 | ||
| HEAT SHOCK PROTEIN 90 INHIBITORS | 443 | ||
| IMMUNE CHECKPOINT INHIBITORS | 444 | ||
| CYTOTOXIC T-LYMPOCYTE ASSOCIATED ANTIGEN 4 | 444 | ||
| Anti-Program Death 1 and Program Death 1 Ligand | 444 | ||
| CONCLUSION | 445 | ||
| KEY REFERENCES | 446 | ||
| REFERENCES | 447.e1 | ||
| 46 - Maintenance Chemotherapy for Nonsmall Cell Lung Cancer | 448 | ||
| HISTORICAL MAINTENANCE TRIALS | 448 | ||
| MODERN MAINTENANCE TRIALS | 450 | ||
| Switch Maintenance With Chemotherapy (Table 46.1) | 450 | ||
| Continuation Maintenance With Chemotherapy (Table 46.2) | 450 | ||
| Maintenance With Noncytotoxic Agents | 455 | ||
| Epidermal Growth Factor Receptor Inhibitors (Table 46.3) | 455 | ||
| Vascular Endothelial Growth Factor Targeted Agents | 460 | ||
| Immunotherapy | 461 | ||
| META-ANALYSES | 462 | ||
| COST-EFFECTIVENESS | 463 | ||
| PATIENT SELECTION | 464 | ||
| REMAINING QUESTIONS AND FUTURE STUDIES | 464 | ||
| KEY REFERENCES | 465 | ||
| REFERENCES | 465.e1 | ||
| 47 -\rPharmacogenomics in Lung Cancer: Predictive Biomarkers for Chemotherapy | 466 | ||
| TUMOR-RELATED FACTORS | 466 | ||
| Measurement of Molecular Biomarkers | 467 | ||
| Driver Mutations in Lung Adenocarcinomas | 467 | ||
| Epidermal Growth Factor Receptor | 468 | ||
| EGFR Overexpression | 468 | ||
| EGFR Mutations | 468 | ||
| Anaplastic Lymphoma Kinase | 469 | ||
| KRAS | 469 | ||
| MET | 469 | ||
| ROS1 | 470 | ||
| ERCC1 and RRM1 | 470 | ||
| BRCA1 | 475 | ||
| Class β-Tubulin | 476 | ||
| Thymidylate Synthase | 476 | ||
| Gene Expression Profiling | 476 | ||
| HOST-RELATED FACTORS | 477 | ||
| UGT1A1*28 | 477 | ||
| CYP3A | 477 | ||
| CONCLUSION | 477 | ||
| KEY REFERENCES | 478 | ||
| REFERENCES | 478.e1 | ||
| 48 - New Targets for Therapy in Lung Cancer | 479 | ||
| KEY SIGNAL TRANSDUCTION PATHWAYS | 479 | ||
| THERAPEUTIC TARGETS | 480 | ||
| Receptor Tyrosine Kinases | 480 | ||
| Human Epidermal Growth Factor Receptor Type 2 | 480 | ||
| Human Epidermal Growth Factor Receptor Type 3 | 481 | ||
| Hepatocyte Growth Factor Receptor | 482 | ||
| Fibroblast Growth Factor Receptor | 483 | ||
| c-Ros Oncogene 1 | 483 | ||
| Rearranged During Transfection–RET | 484 | ||
| Discoidin Domain Receptors | 484 | ||
| Tyrosine-Protein Kinase Receptor UFO (AXL) and Proto-Oncogene Tyrosine-Protein Kinase (MER) | 484 | ||
| Tropomysin Receptor Kinase | 485 | ||
| Nonreceptor Targets | 485 | ||
| RAS | 485 | ||
| v-Raf Murine Sarcoma Viral Oncogene Homolog B–BRAF | 485 | ||
| Mitogen Activated Protein Kinase Kinase–MEK | 486 | ||
| Phosphoinositide 3-Kinase | 486 | ||
| Protein Kinase B–AKT | 487 | ||
| Mammalian Target of Rapamycin | 487 | ||
| Heat Shock Protein 90 | 488 | ||
| Cyclin-Dependent Kinase | 488 | ||
| CONCLUSION | 489 | ||
| KEY REFERENCES | 489 | ||
| REFERENCES | 489.e1 | ||
| 49 - Management of Toxicities of Targeted Therapies | 490 | ||
| DERMATOLOGIC SIDE EFFECTS | 491 | ||
| EGFR TKIs and Monoclonal Antibodies | 491 | ||
| Antiangiogenic Agents | 494 | ||
| GASTROINTESTINAL SIDE EFFECTS OF EGFR INHIBITORS | 496 | ||
| Mechanism of Diarrhea | 496 | ||
| Incidence and Effect of Diarrhea | 496 | ||
| Consequences and Management of Diarrhea | 497 | ||
| PULMONARY SIDE EFFECTS: INTERSTITIAL LUNG DISEASE | 497 | ||
| Mechanism of Interstitial Lung Disease | 497 | ||
| Incidence of Interstitial Lung Disease | 497 | ||
| Management of Interstitial Lung Disease | 497 | ||
| BEVACIZUMAB AND RAMUCIRUMAB SIDE EFFECTS | 498 | ||
| ANAPLASTIC LYMPHOMA KINASE INHIBITOR SIDE EFFECTS | 498 | ||
| HEAT-SHOCK PROTEIN 90 INHIBITOR SIDE EFFECTS | 498 | ||
| BRAF INHIBITOR SIDE EFFECTS | 499 | ||
| MEK INHIBITOR SIDE EFFECTS | 499 | ||
| PD1 AND PD-L1 MONOCLONAL ANTIBODY SIDE EFFECTS | 499 | ||
| ETHNIC DIFFERENCES IN SIDE EFFECTS OF TARGETED THERAPY | 500 | ||
| CONCLUSION | 500 | ||
| KEY REFERENCES | 500 | ||
| REFERENCES | 500.e1 | ||
| 50 - Immunotherapy and Lung Cancer | 501 | ||
| IMMUNOLOGIC DYSFUNCTION IN PATIENTS WITH LUNG CANCER | 501 | ||
| SUPPORTING EVIDENCE FOR THE USE OF IMMUNOTHERAPY FOR LUNG CANCER | 502 | ||
| VACCINES | 502 | ||
| Melanoma-Associated Antigen-A3 Vaccine | 502 | ||
| Mucinous Glycoprotein-1 Vaccines | 503 | ||
| Tecemotide (L-BLP25) | 503 | ||
| TG4010 Vaccine | 503 | ||
| Belagenpumatucel-L | 504 | ||
| Epidermal Growth Factor Vaccine | 504 | ||
| Racotumomab | 504 | ||
| IMMUNE CHECKPOINT INHIBITORS: AGENTS AND CLINICAL DEVELOPMENT | 504 | ||
| Checkpoint Inhibitors | 504 | ||
| Anti-PD1 and Anti-PDL1 Antibodies | 505 | ||
| Initial Phase I Studies | 506 | ||
| Nivolumab (BMS-936558, MDX-1106/ONO-4538, OPDIVO) | 506 | ||
| Pembrolizumab (MK-3475, Keytruda) | 506 | ||
| Atezolizumab (MPDL3280A, Tecentriq) | 507 | ||
| Second-Line Randomized Studies Establishing PD1/PDL1 Inhibition as a Standard of Care | 507 | ||
| Nivolumab (MDX-1108, OPDIVO) | 507 | ||
| X -\rOther Thoracic Malignancies | 536 | ||
| 53 - Malignant Mesothelioma | 536 | ||
| BIOLOGY OF MALIGNANT PLEURAL MESOTHELIOMA | 536 | ||
| Cyclin-Dependent Kinase Inhibitor 2A/Alternative Reading Frame | 536 | ||
| Neurofibromatosis Type 2 | 536 | ||
| BAP1 | 536 | ||
| DIAGNOSIS | 537 | ||
| STAGING | 537 | ||
| Laparoscopy and Thoracoscopy | 537 | ||
| Mediastinal Evaluation | 538 | ||
| BIOMARKERS | 538 | ||
| Diagnostic Biomarkers | 539 | ||
| Prognostic Biomarkers | 539 | ||
| Prognostic Imaging Biomarkers | 539 | ||
| CHEMOTHERAPY | 539 | ||
| First-Line Chemotherapy | 539 | ||
| Timing of First-Line Chemotherapy | 540 | ||
| Second-Line and Subsequent Chemotherapy | 540 | ||
| SURGERY | 541 | ||
| Palliative Surgery | 541 | ||
| Pleural Drainage | 541 | ||
| Palliative Pleurectomy | 542 | ||
| Cytoreductive Surgery | 542 | ||
| Extrapleural Pneumonectomy | 542 | ||
| Pleurectomy/Decortication | 543 | ||
| Intrapleural Therapies | 544 | ||
| IMMUNOTHERAPY FOR MESOTHELIOMA | 545 | ||
| Regulatory T Cells and Immunosuppressive Cytokines | 546 | ||
| Immune Checkpoint Inhibition | 546 | ||
| Dendritic Cell–Based Immunotherapy | 546 | ||
| Vaccination Using WT1 | 547 | ||
| Mesothelin-Targeted Therapies | 547 | ||
| SS1P | 547 | ||
| Amatuximab (MORAb-009) | 548 | ||
| Mesothelin Vaccine (CRS-207) | 548 | ||
| Mesothelin-Directed CAR Therapy | 548 | ||
| Oncolytic Viral Therapies | 548 | ||
| Gene Therapy | 549 | ||
| CONCLUSION | 549 | ||
| KEY REFERENCES | 549 | ||
| REFERENCES | 549.e1 | ||
| 54 -\rMediastinal Tumors | 550 | ||
| GERM CELL TUMORS | 550 | ||
| Benign Teratoma | 550 | ||
| Seminoma | 550 | ||
| Nonseminomatous Germ Cell Tumor | 551 | ||
| LYMPHOMA | 551 | ||
| Hodgkin Lymphoma | 551 | ||
| Non-Hodgkin Lymphoma | 552 | ||
| NEUROGENIC TUMORS | 552 | ||
| BENIGN CYSTIC MASSES | 552 | ||
| Bronchogenic Cysts | 552 | ||
| Esophageal Cysts | 552 | ||
| Pericardial Cysts | 552 | ||
| SUBSTERNAL GOITER | 552 | ||
| PARATHYROID ADENOMA | 553 | ||
| LEIOMYOMA | 553 | ||
| SURGICAL APPROACH | 553 | ||
| CONCLUSION | 554 | ||
| KEY REFERENCES | 554 | ||
| REFERENCES | 554.e1 | ||
| 55 - Neuroendocrine Tumors of the Lung Other Than Small Cell Lung Cancer | 555 | ||
| CLASSIFICATION | 555 | ||
| DIAGNOSIS | 555 | ||
| Histology | 555 | ||
| Bronchopulmonary Carcinoids | 555 | ||
| Large Cell Neuroendocrine Carcinoma | 556 | ||
| Cytology | 556 | ||
| Differential Diagnosis | 557 | ||
| Histology | 557 | ||
| Cytology | 558 | ||
| Cytokeratin Markers. High-molecular-weight cytokeratin (CK) types 1, 5, 10, and 14 (antibody clone 34E1β2) are almost solely exp... | 558 | ||
| Markers for Differentiating Atypical From Typical Carcinoid. Counting mitoses may be challenging, especially if there is crush a... | 558 | ||
| Markers for Differentiating Large Cell Neuroendocrine Carcinoma From Squamous Cell Carcinoma. In addition to high-molecular-weig... | 558 | ||
| Markers for Differentiating Large Cell Neuroendocrine Carcinoma From Adenocarcinoma. Thyroid transcription factor-1 (TTF-1), a m... | 558 | ||
| Markers for Differentiating Bronchopulmonary Carcinoid From Small Cell Lung Cancer. Ki-67 staining may be of value because SCLC ... | 558 | ||
| Markers for Differentiating Large Cell Neuroendocrine Carcinoma From Small Cell Lung Cancer. As of the time of publication, dist... | 559 | ||
| Markers for Differentiating Atypical and Typical Carcinoids From Large Cell Neuroendocrine Carcinoma. Separating atypical and ty... | 559 | ||
| Immunohistochemical on Cytology. IHC neuroendocrine markers such as chromogranin, synaptophysin, and NCAM were found to be posit... | 559 | ||
| MOLECULAR BIOLOGY | 559 | ||
| Loss of Heterozygosity | 559 | ||
| Chromosomal Aberrations | 559 | ||
| Microarray Comparison | 560 | ||
| Mutation Analysis | 560 | ||
| Pathways | 560 | ||
| CLINICAL CHARACTERISTICS | 561 | ||
| BP Carcinoids | 561 | ||
| XI -\rSymptom Management and Complications | 590 | ||
| 57 - Lung Cancer Emergencies | 590 | ||
| CENTRAL AIRWAY OBSTRUCTION | 590 | ||
| Types of Central Airway Obstruction Presenting as Emergencies | 590 | ||
| Symptoms of Lung Cancer-Related Central Airway Obstruction | 591 | ||
| Diagnosis of Central Airway Obstruction | 592 | ||
| Clinical Findings | 592 | ||
| Chest Radiographs Often Aid in Diagnosis | 592 | ||
| Flexible Bronchoscopic Examination | 593 | ||
| Evaluation of Patients | 593 | ||
| Treatment Modalities for Emergency Management of Lung Cancer–Related Central Airway Obstruction | 593 | ||
| Bronchoscopic Laser Resection | 593 | ||
| Airway Stenting | 594 | ||
| External-Beam Radiotherapy | 594 | ||
| Endobronchial Brachytherapy | 595 | ||
| Photodynamic Therapy | 595 | ||
| Cryotherapy | 595 | ||
| Argon Plasma Coagulation | 596 | ||
| Covered Self-Expanding Metal Stents | 596 | ||
| Bronchoscopic Balloon Dilatation | 596 | ||
| Expected Outcomes of Emergency Bronchoscopic Management of Central Airway Obstruction | 596 | ||
| MASSIVE HEMOPTYSIS | 596 | ||
| Definition | 597 | ||
| Etiology of Hemoptysis | 597 | ||
| Vascular Source of Bleeding | 597 | ||
| Clinical Assessment, Initial Resuscitation, and Stabilization | 598 | ||
| Approach to Diagnosis | 599 | ||
| Computed Tomography | 599 | ||
| Bronchoscopy | 599 | ||
| Treatment | 599 | ||
| Bronchoscopy | 600 | ||
| Endovascular Embolization | 600 | ||
| Surgery | 602 | ||
| Outcomes | 602 | ||
| MASSIVE PLEURAL EFFUSIONS | 602 | ||
| Pleural Physiology | 602 | ||
| Etiology and Pathogenesis | 602 | ||
| Clinical Presentation | 603 | ||
| Initial Management | 603 | ||
| Initial Presentation | 603 | ||
| Initial Therapeutic Intervention | 603 | ||
| Subsequent Management | 606 | ||
| Additional Chest Imaging | 606 | ||
| Pleural Fluid Analysis | 606 | ||
| Histologic Analysis | 606 | ||
| More Definitive Management | 606 | ||
| Medical Thoracoscopy and Video-Assisted Thoracoscopic Surgery | 606 | ||
| Serial Thoracentesis | 606 | ||
| Pleurodesis and Indwelling Pleural Catheter | 606 | ||
| CONCLUSION | 607 | ||
| KEY REFERENCES | 607 | ||
| REFERENCES | 607.e1 | ||
| 58 - The Role of Palliative Care in Lung Cancer | 608 | ||
| DEFINITION OF PALLIATIVE CARE | 608 | ||
| PHILOSOPHICAL DIFFERENCES BETWEEN ONCOLOGY AND PALLIATIVE CARE | 608 | ||
| WHY PALLIATIVE CARE IS NEEDED EARLY IN THE MANAGEMENT OF ADVANCED LUNG CANCER | 609 | ||
| Symptoms | 609 | ||
| Communication | 610 | ||
| BENEFITS OF EARLY INTEGRATION OF PALLIATIVE CARE INTO ONCOLOGY | 612 | ||
| Symptom Management, Prognostic Information, and Hope | 612 | ||
| Communication, Quality of Life, and Patient-Related Outcomes | 612 | ||
| Rehabilitation | 612 | ||
| Health-Care Economics | 612 | ||
| Survival | 613 | ||
| STUDIES DOCUMENTING BENEFITS TO INTEGRATING PALLIATIVE CARE INTO CANCER CARE | 613 | ||
| BARRIERS TO INTEGRATING PALLIATIVE CARE INTO CANCER CARE | 613 | ||
| END-OF-LIFE CARE | 614 | ||
| ASSESSING SYMPTOMS AND QUALITY OF LIFE IN LUNG CANCER | 614 | ||
| MANAGING LUNG CANCER SYMPTOMS | 615 | ||
| Fatigue | 615 | ||
| Dyspnea | 616 | ||
| Cough | 616 | ||
| Cachexia and Anorexia | 617 | ||
| Pain | 617 | ||
| LUNG CANCER AND THE INTENSIVE CARE UNIT | 618 | ||
| LUNG CANCER AND CARDIOPULMONARY RESUSCITATION | 618 | ||
| CONCLUSION | 618 | ||
| KEY REFERENCES | 619 | ||
| REFERENCES | 619.e1 | ||
| XII -\rClinical Trials | 620 | ||
| 59 - Clinical Trial Methodology in Lung Cancer: Study Design and End-Point Considerations | 620 | ||
| EARLY PHASE TRIALS | 621 | ||
| PHASE II TRIALS | 622 | ||
| End-Point Considerations | 622 | ||
| Randomized and Single-Arm Designs | 623 | ||
| Assessing Biomarker-Based Subgroups: Design Considerations | 623 | ||
| Adaptive Designs | 624 | ||
| PHASE II/III AND PHASE III TRIALS | 624 | ||
| Traditional Designs | 624 | ||
| Noninferiority Designs | 624 | ||
| Phase II/III Designs | 625 | ||
| Biomarker-Based Trial Designs | 626 | ||
| Trial Designs for Rare Tumors | 626 | ||
| CONCLUSION | 626 | ||
| KEY REFERENCES | 627 | ||
| REFERENCES | 627.e1 | ||
| 60 - How to Promote and Organize Clinical Research in Lung Cancer | 628 | ||
| HOW TO ORGANIZE CLINICAL TRIALS IN LUNG CANCER | 628 | ||
| Issues | 628 | ||
| Definition of Lung Cancer Today | 628 | ||
| Expectations for Quick Progress and Impact on Financial Issues | 628 | ||
| Selection of Hypotheses for Clinical Trials and Impact of Biomarkers on Design | 629 | ||
| National, Multinational, and International Cooperation or Competition | 629 | ||
| Possible Solutions | 629 | ||
| New Designs for Modern Clinical Trials | 629 | ||
| New Designs: Mixing Avatar Models and Clinical Trials | 631 | ||
| Cooperation and Networks | 631 | ||
| Regulatory Issues | 632 | ||
| Financial Issues | 632 | ||
| HOW TO PROMOTE CLINICAL TRIALS | 633 | ||
| Issues | 633 | ||
| Goal and Philosophy of Different Systems | 633 | ||
| Increasing Difficulty of Conducting Clinical Trials | 633 | ||
| Time and Effort | 633 | ||
| Patient Education | 633 | ||
| Possible Solutions | 633 | ||
| Train Physicians Early and Continuously | 633 | ||
| Simplify Regulation | 634 | ||
| CONCLUSION | 634 | ||
| KEY REFERENCES | 634 | ||
| REFERENCES | 634.e1 | ||
| XIII -\rThoracic Oncology Advocacy | 635 | ||
| 61 - The Role of Advocacy Groups in Lung Cancer | 635 | ||
| LUNG CANCER ADVOCACY GROUPS | 635 | ||
| CHALLENGES IN LUNG CANCER ADVOCACY | 635 | ||
| Lack of Advocates | 635 | ||
| Stigma Surrounding the Association With Tobacco | 635 | ||
| Low Public Profile | 636 | ||
| LUNG CANCER ADVOCACY GROUP ACTIVITY | 636 | ||
| Integrated Tobacco Control Programs | 636 | ||
| Increased Funding for Lung Cancer Research | 636 | ||
| Increased Number of People With Lung Cancer Enrolled in Clinical Trials | 636 | ||
| Earlier Diagnosis | 636 | ||
| Equitable Access to Best-Practices Treatment and Care | 637 | ||
| High-Quality Data | 637 | ||
| Help for People With Lung Cancer and Their Families | 637 | ||
| LUNG CANCER ADVOCACY STRATEGIES | 637 | ||
| Use of Mass Media, Including New Social Media | 637 | ||
| Public Awareness Campaigns | 637 | ||
| Political Lobbying | 638 | ||
| Informing and Influencing Health Services Providers | 638 | ||
| CONCLUSION | 638 | ||
| KEY REFERENCES | 638 | ||
| REFERENCES | 638.e1 | ||
| 62 - The Role of Health Services Research in Improving the Outcomes for Patients With Lung Cancer | 639 | ||
| HOW CAN HEALTH SERVICES RESEARCH IMPROVE THE OUTCOMES FOR PATIENTS WITH LUNG CANCER? | 639 | ||
| THE THREE DIMENSIONS OF HEALTH SYSTEM PERFORMANCE | 639 | ||
| Health-Care Accessibility | 640 | ||
| Quality in Health Care | 640 | ||
| Efficiency in Health Care | 640 | ||
| STANDARDS FOR THE CARE OF INDIVIDUAL PATIENTS | 640 | ||
| Guidelines for the Care of Individual Patients With Lung Cancer | 641 | ||
| Challenges to the Development and Application of Practice Guidelines | 641 | ||
| Variation in Patient Values | 641 | ||
| Biologic Heterogeneity | 641 | ||
| Do Guidelines Guide Practice? | 641 | ||
| Does Adherence to Guidelines Improve Outcomes in the General Population? | 642 | ||
| QUALITY STANDARDS FOR CANCER TREATMENT PROGRAMS | 643 | ||
| General Quality Standards | 643 | ||
| Multidisciplinary Team Management | 643 | ||
| Multidisciplinary Team Management of Lung Cancer | 643 | ||
| Modality-Specific Quality Standards for Cancer Programs | 645 | ||
| Standards for Acceptable Patient Volumes for Cancer Programs | 645 | ||
| STANDARDS FOR THE ACCESSIBILITY OF CANCER MANAGEMENT PROGRAMS | 646 | ||
| Standards for Waiting Times | 646 | ||
| Standards for Rates of Treatment Utilization | 646 | ||
| Evidence-Based Requirements Analysis | 646 | ||
| Criterion-Based Benchmarking | 646 | ||
| BARRIERS TO THE OPTIMAL CARE OF PATIENTS WITH LUNG CANCER | 647 | ||
| Classification of Barriers to Optimal Care | 647 | ||
| Barriers to Optimal Care: Case Studies From High-Income Countries | 647 | ||
| Barriers to Optimal Care in Low- and Middle-Income Countries | 648 | ||
| Do Variations in Patterns of Care Affect the Outcomes of Lung Cancer? | 648 | ||
| CONCLUSION | 649 | ||
| KEY REFERENCES | 649 | ||
| REFERENCES | 650.e1 | ||
| Diagnostic Algorithms | 651 | ||
| INITIAL EVALUATION | 651 | ||
| History and Physical | 651 | ||
| Radiographic Evaluation | 652 | ||
| Invasive Diagnosis | 652 | ||
| PATHOLOGIC CLASSIFICATION OF LUNG CANCER | 653 | ||
| Tumor Histology | 653 | ||
| Molecular Classification | 654 | ||
| Repeat Biopsy for Acquired Resistance | 655 | ||
| Molecular Diagnostic Platforms | 655 | ||
| FUTURE CONSIDERATIONS | 657 | ||
| CONCLUSION | 657 | ||
| KEY REFERENCES | 657 | ||
| REFERENCES | 658.e1 | ||
| Index | 659 | ||
| A | 659 | ||
| B | 661 | ||
| C | 662 | ||
| D | 664 | ||
| E | 665 | ||
| F | 666 | ||
| G | 667 | ||
| H | 667 | ||
| I | 668 | ||
| J | 669 | ||
| K | 669 | ||
| L | 669 | ||
| M | 672 | ||
| N | 674 | ||
| O | 675 | ||
| P | 676 | ||
| Q | 678 | ||
| R | 678 | ||
| S | 680 | ||
| T | 682 | ||
| U | 684 | ||
| V | 684 | ||
| W | 685 | ||
| X | 685 | ||
| Z | 685 | ||
| IBC\r | ES2 |