Pulmonary Adenocarcinoma: Approaches to Treatment, 1e

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Pulmonary Adenocarcinoma: Approaches to Treatment
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List of Contributors
Preface
1. The Surgical Management of Pulmonary Adenocarcinoma
	INTRODUCTION
	STAGING
		Initial Staging: Imaging
		Pathologic Staging: Tissue Diagnosis for Suspected Lung Cancer
		Endobronchial and Transbronchial Biopsy
		Surgical Lung Biopsy
		Pathologic Mediastinal Assessment
	ASSESSING SURGICAL CANDIDACY
		Smoking Cessation
		Assessment of Cardiovascular Risk
		Assessment of Pulmonary Function
	SURGICAL MANAGEMENT OF LUNG CANCER
		Early-Stage Lung Cancer
		Locally Advanced Lung Cancer
		T3N1 Tumors
		N2 Disease
		T4 Tumors
		Superior Sulcus Tumors
		Oligometastatic Disease
	SURGICAL APPROACH TO LUNG CANCER
		Open Lobectomy
		Video-Assisted Thoracoscopic Surgery Lobectomy
		Robotic Lobectomy
		Uniportal and Subxiphoid Lobectomy
	IMPORTANT SURGICAL CONSIDERATIONS
		Extent of Resection
		Extent of Lymph Node Resection
	CONCLUSION
	REFERENCES
	FURTHER READING
2. Pulmonary Adenocarcinoma—Pathology and Molecular Testing
	INTRODUCTION
	HISTOLOGICAL CLASSIFICATION
	CLINICAL RELEVANCE OF ADENOCARCINOMA SUBTYPE CLASSIFICATION
		Lepidic Predominant Adenocarcinoma (Good Prognosis)
		Acinar/Papillary Predominant Adenocarcinoma (Intermediate Prognosis)
		Micropapillary and Solid Predominant Adenocarcinoma (Poor Prognosis)
		Invasive Mucinous Adenocarcinoma
	PATHOLOGICAL STAGING OF LUNG ADENOCARCINOMA—UICC/AJCC EIGHTH EDITION
	MOLECULAR CLASSIFICATION
	TRANSCRIPTOMIC CLASSIFICATIONS
		Terminal Respiratory Unit Subtype
		Proximal Inflammatory Subtype
		Proximal Proliferative Subtype
	ONCOGENIC DRIVER MUTATIONS AND MOLECULAR TESTING IN LUNG ADENOCARCINOMA
		Molecular Testing Methods
	EPIDERMAL GROWTH FACTOR RECEPTOR
		Secondary Resistance Mutations
		Activation of Bypass Pathways
		Activation of Downstream Pathways
		Histologic Transformation
		Epidermal Growth Factor Receptor Mutation Testing
			Nontargeted assays
			Targeted assays
	ANAPLASTIC LYMPHOMA KINASE
		ROS1
	ALK AND ROS1 TESTING
		Break Apart FISH Assay
		Reverse Transcription-Polymerase Chain Reaction
		Fusion Protein Detection of ALK and ROS1 by IHC
		Next-Generation Sequencing
	OTHERS DRIVER ONCOGENES
		MET
		KRAS
		BRAF
		RET
		NTRK1
		HER2
	LIQUID BIOPSIES
		Circulating Tumor Cells
		Circulating Tumor DNA
		Targeting Specific Molecular Alterations
		Targeting Multiple Molecular Alterations
		Clinical Applications
		Assessing Tumor Burden
		Characterizing Resistance Mechanisms
		Monitoring Response to Therapy
	PROGRAM DEATH LIGAND 1
		Program Death Ligand 1 Testing
	CONCLUSIONS
	REFERENCES
3. Adjuvant and Neoadjuvant Therapy in Non–Small-Cell Lung Cancer
	INTRODUCTION
	ADJUVANT CHEMOTHERAPY
	STAGE I DISEASE
	CHOICE OF CHEMOTHERAPY
	ADJUVANT RADIATION THERAPY
	NEOADJUVANT CHEMOTHERAPY
	MOLECULARLY TARGETED THERAPY
	IMMUNOTHERAPY
	NEOADJUVANT IMMUNOTHERAPY
	CONCLUSIONS AND FUTURE DIRECTIONS
	REFERENCES
4. Management of Locally Advanced Lung Cancer
	INTRODUCTION
	ANATOMY
	SCREENING
	MANIFESTATIONS
		Symptoms
		Paraneoplastic Syndromes
	WORKUP
		Imaging
		Sputum Cytology
		Mediastinoscopy
		Endobronchial Ultrasound–Guided Transbronchial Needle Aspiration
		Fiberoptic Bronchoscopy with Bronchoalveolar Lavage
	HISTOLOGY
		Adenocarcinoma
		Squamous Cell Carcinoma
		Large-Cell Lung Carcinoma
		Molecular Analysis
	STAGING (EIGHTH EDITION) (TABLES 4.3 AND 4.4)
		Pleural Invasion
	MANAGEMENT
		Smoking Cessation
	RESECTABLE LA-NSCLC
		Induction Chemotherapy
		Trimodality
	SUPERIOR SULCUS TUMORS
		Postoperative Radiation Therapy
		Radiation Alone
		Postoperative Chemoradiation
		Adjuvant Chemotherapy
	UNRESECTABLE LA-NSCLC
		Radiation Alone
		Sequential Chemoradiation
		Sequential and Concurrent Chemoradiotherapy
		Consolidation Chemotherapy
	TARGETED THERAPIES
		Epidermal Growth Factor Receptor
		Cetuximab
		Gefitinib
		Erlotinib
		Bevacizumab and Thalidomide
		Anaplastic Lymphoma Kinase
	IMMUNOTHERAPY
		Programmed Death Ligand 1
		Combining Immunotherapy and Radiotherapy
	RADIOTHERAPY
		Dose
	VOLUMES
		Gross Tumor Volume
		Clinical Target Volume
		Planned Target Volume
	MODALITIES
		Photons: 2-D, 3-D, and Intensity-Modulated Radiotherapy Planning
		Protons
		Carbon Ions
	REFERENCES
5. First-Line Therapy for Wild-Type Patients
	CHEMOTHERAPY
	DURATION OF CHEMOTHERAPY
	BEVACIZUMAB
	MAINTENANCE THERAPY
	IMMUNOTHERAPY
	ELDERLY PATIENTS
	IMPAIRED PERFORMANCE STATUS
	CONCLUSIONS
	REFERENCES
6. Lung Adenocarcinoma: Second-Line Treatment
	INTRODUCTION
	CYTOTOXIC CHEMOTHERAPY–MONOTHERAPY
		Docetaxel
		Pemetrexed
		Other Cytotoxic Agents
	COMBINATION CHEMOTHERAPY
	TARGETED AGENTS
		Epidermal Growth Factor Receptor
		Vascular Endothelial Growth Factor
		Mitogen-Activated Protein Kinase Kinase
	IMMUNOTHERAPY
		Nivolumab
		Pembrolizumab
		Atezolizumab
	CONCLUSION
	REFERENCES
7. Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer
	EPIDEMIOLOGY
	DIAGNOSIS
	TREATMENT
		First- and Second- Generation EGFR TKIs
	ACQUIRED RESISTANCE TO FIRST- AND SECOND-GENERATION TKIS AND THE DEVELOPMENT OF THIRD-GENERATION EGFR TKIS
	CYTOTOXIC CHEMOTHERAPY
	IMMUNE THERAPY
	ADJUVANT THERAPY
	TREATMENT BEYOND PROGRESSION AND OLIGOPROGRESSIVE DISEASE
	CNS METASTASES
	SMALL-CELL LUNG CANCER TRANSFORMATION
	EXON 20 INSERTION MUTATIONS
	TREATMENT OF SELECTED TKI TOXICITIES
	SUMMARY OF CURRENT TREATMENT RECOMMENDATIONS
	FUTURE DIRECTIONS
	REFERENCES
8. Approach to Anaplastic Lymphoma Kinase (ALK) Gene Rearranged Non–Small Cell Lung Cancer (NSCLC)
	INTRODUCTION
	CLINICAL FEATURES OF ANAPLASTIC LYMPHOMA KINASE POSITIVE NON–SMALL CELL LUNG CANCER
	TESTING FOR ANAPLASTIC LYMPHOMA KINASE
	APPROACH TO ADVANCED-STAGE ANAPLASTIC LYMPHOMA KINASE PATIENT
	CRIZOTINIB
	NEXT-GENERATION ALK INHIBITORS IN CRIZOTINIB-TREATED PATIENTS
	NEXT-GENERATION ALK TKIS AS FRONT-LINE THERAPY
	ALECTINIB
	AF-001JP
	JALEX (TABLE 8.3)
	ALEX (TABLE 8.3)
	SUMMARY OF ALEX AND JALEX
	CERITINIB
	OTHER DRUGS
	RESISTANCE TO NEXT-GENERATION ALK INHIBITORS
	SEQUENCE OF ALK INHIBITORS (FIGS. 8.1 AND 8.2)
	NON-ALK-DIRECTED THERAPY
	CENTRAL NERVOUS SYSTEM METASTASES
	MANAGEMENT OF PATIENTS WITH OLIGOMETASTATIC DISEASE
	EARLY-STAGE AND LOCALLY ADVANCED ALK POSITIVE NSCLC
	FUTURE DIRECTIONS
	REFERENCES
9. Targeted Therapy in Non–Small-Cell Lung Cancer (Beyond Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase)
	INTRODUCTION
	ROS1
	BRAF
	MESENCHYMAL–EPITHELIAL TRANSITION
	RET
	HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2
	NEUROTROPHIN TYROSINE RECEPTOR KINASE–MUTATED NSCLC
	CONCLUSIONS
	REFERENCES
10. Treatment of Pulmonary Adenocarcinoma With Immune Checkpoint Inhibitors
	INTRODUCTION
	PREVIOUSLY TREATED ADVANCED NON–SMALL CELL LUNG CANCER
	TREATMENT-NAÏVE ADVANCED NON–SMALL CELL LUNG CANCER
		Early Phase Studies in Treatment-Naïve NSCLC
		Randomized Phase III Studies in Treatment-Naïve NSCLC
		Combination of Chemotherapy and Checkpoint Inhibition
	UNRESECTABLE STAGE III NON–SMALL CELL LUNG CANCER
		Combination of Radiation and Immunotherapy
	SAFETY AND MANAGEMENT OF TOXICITY
	BIOMARKERS
		Clinicopathologic Markers
			Smoking status
			EGFR Status
		PD-L1 Expression
		Tumor Mutation Burden
		T-Effector Gene Signature Expression
	TREATMENT DURATION
	ONGOING STUDIES/FUTURE DIRECTIONS
	REFERENCES
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W