Lung Cancer

Name: Lung Cancer
Brand: Wiley-Blackwell
Price: 163.99 EUR
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Jack A. Roth Waun Ki Hong Ritsuko U. Komaki(Herausgeber*in)

Wiley-Blackwell (Verlag)

4. Auflage

Erschienen am 20. März 2014

616 Seiten

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Beschreibung

The best and most concise single source for state-of-the-artdiagnosis and treatment of lung cancer -newly revised,updated, and expanded.
Lung cancer has long been the number-one cause of death from cancerevery year and the third most frequently diagnosed after breast andprostate cancers. In 2010, about 15% of all cancer diagnoses and30% of all cancer deaths were due to lung cancer. Needless to say,there is a great need for more rapid advancements in diagnosis andtreatment of this devastating disease.
Here is the comprehensively revised, updated, and expandededition of the well-established, evidence-based reference book thatdeals with the most recent advances in lung cancer prevention,screening, diagnosis, research, and treatment for the clinician.Edited and authored by leading authorities in the field, thisFourth Edition of the highly regarded Lung Cancer is betterthan ever -featuring nine new chapters along with sevenre-formatted ones that are nearly brand new in content andapproach. It covers Smoking Prevention and Cessation; MolecularProfiling; Somatic Genome Alterations in Human Lung Cancers;Management of Multi-Focal Bronchioloalveolar Carcinoma (BAC);Primary Tracheal Tumors; Predictive Tumor Biomarkers for EGFRInhibitors; Non-Small Cell and Small-Cell Lung Carcinoma; andmore.
This Fourth Edition of Lung Cancer:
* Provides the very latest research in the identification ofbiomarkers to predict a high risk for developing lung cancer- vital for implementing screening, diagnosis, and preventionstrategies
* Presents the newest lung cancer staging system, as well asupdated and cutting-edge surgical and radiation therapy techniquesthat make local tumor control more effective and less invasivewhile sparing normal tissues
* Discusses combined modality therapy and new chemotherapeuticagents which are yielding higher response rates and improvedsurvival when used in the adjuvant setting or concurrent withhighly sophisticated radiation or proton treatment
* Offers novel and emergent approaches to preventative,diagnostic, and therapeutic modalities with an emphasis on the bestevidence available from the latest studies and clinical trials
With almost half of the revised and updated content being brandnew, Lung Cancer, Fourth Edition, is an important and vitalresource for all medical professionals and students involved in thecare and treatment of those struck with this catastrophicillness.

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Inhalt

1 - Lung Cancer [Seite 3]
2 - Contents [Seite 7]
3 - Contributors [Seite 10]
4 - Preface [Seite 15]
5 - CHAPTER 1 Smoking Prevention and Cessation [Seite 17]
5.1 - Overview [Seite 17]
5.2 - Introduction [Seite 17]
5.3 - Tobacco and lung cancer [Seite 18]
5.4 - Secondhand smoke andlung cancer [Seite 19]
5.5 - Smoking among lungcancer patients [Seite 20]
5.6 - Forms of tobacco [Seite 20]
5.6.1 - Smoked tobacco [Seite 20]
5.6.2 - Smokeless tobacco [Seite 22]
5.7 - Recent developments on the tobacco market [Seite 22]
5.8 - Factors explaining tobacco use [Seite 23]
5.8.1 - Smoking initiation [Seite 23]
5.9 - Smoking prevention [Seite 23]
5.10 - Nicotine addiction [Seite 25]
5.11 - Benefits of quitting [Seite 25]
5.12 - Smoking cessation interventions [Seite 26]
5.13 - Behavioral counseling [Seite 26]
5.14 - Pharmaceutical aids for smoking cessation [Seite 28]
5.15 - Nicotine replacement therapy [Seite 33]
5.16 - Sustained-release bupropion [Seite 34]
5.17 - Varenicline [Seite 34]
5.18 - Combination therapy [Seite 35]
5.19 - Use of medications in pregnancy [Seite 35]
5.20 - Summary [Seite 35]
5.21 - References [Seite 35]
6 - CHAPTER 2 Lung Cancer Susceptibility and Risk Assessment Models [Seite 41]
6.1 - Introduction [Seite 41]
6.2 - Epidemiologic risk factors [Seite 41]
6.2.1 - Family history [Seite 41]
6.3 - Prior inflammatory diseases and disorders [Seite 42]
6.4 - Diet and nutritional risk factors [Seite 43]
6.5 - Genetic susceptibility [Seite 44]
6.5.1 - Candidate gene approaches [Seite 45]
6.5.2 - Genome-wide association studies [Seite 45]
6.6 - 6p21 and 12p13 [Seite 47]
6.7 - Intermediate phenotypic assays in measuring genetic susceptibility [Seite 49]
6.7.1 - DNA damage and repair phenotypic assays [Seite 49]
6.7.2 - Cell cycle phenotypic assays [Seite 51]
6.7.3 - Phenotypic assays in apoptotic pathways [Seite 51]
6.8 - Emerging novel biomarkers for LC risk and early detection [Seite 51]
6.9 - LC risk assessment models [Seite 52]
6.9.1 - An overview of cancer risk prediction models [Seite 52]
6.10 - Concluding remarks [Seite 54]
6.11 - References [Seite 55]
7 - CHAPTER 3 Molecular Profiling [Seite 64]
7.1 - Introduction [Seite 64]
7.2 - Techniques used in molecular profiling [Seite 66]
7.3 - DNA sequencing [Seite 66]
7.4 - RNA profiling [Seite 67]
7.5 - Proteomics [Seite 69]
7.6 - Data analysis and statistics [Seite 71]
7.7 - Clinical applications [Seite 74]
7.8 - Early detection and diagnosis [Seite 74]
7.9 - Molecular subclassification and staging [Seite 75]
7.10 - Selection of therapy [Seite 76]
7.11 - Future directions and conclusions [Seite 77]
7.12 - Acknowledgments [Seite 78]
7.13 - References [Seite 78]
8 - CHAPTER 4 Somatic Genome Alterations in Human Lung Cancers [Seite 83]
8.1 - Lung cancer genetics overview [Seite 83]
8.2 - Lung adenocarcinoma genomics [Seite 84]
8.2.1 - Molecular alteration spectra of lung adenocarcinoma [Seite 84]
8.2.2 - Key genetic alterations in lung adenocarcinoma in a few selected pathways [Seite 85]
8.2.3 - Genetic correlates of sensitivity and resistance [Seite 89]
8.2.4 - Germline predisposition [Seite 89]
8.2.5 - Future directions [Seite 90]
8.3 - Lung squamous cell carcinoma genomics [Seite 90]
8.3.1 - Introduction and overview of genomic alterations of lung SqCCs [Seite 90]
8.3.2 - Somatic copy number alterations [Seite 91]
8.4 - Genomic features of small cell lung cancers [Seite 93]
8.4.1 - Previous molecular findings in SCLC [Seite 93]
8.4.2 - Large-scale genome analysis studies of SCLC [Seite 94]
8.4.3 - Biological and clinical implications of SCLC genome alterations [Seite 95]
8.5 - References [Seite 96]
9 - CHAPTER 5 Serum Proteomic Biomarkers [Seite 106]
9.1 - Natural history of lung cancer progression and potential utility for biomarkers in the clinic [Seite 106]
9.2 - The blood proteome [Seite 107]
9.3 - Proteomic discovery platforms [Seite 108]
9.4 - Proteomic approaches for discovery and validation of blood biomarkers [Seite 108]
9.5 - MALDI-TOF MS serum analysis for diagnosis [Seite 108]
9.6 - Serum proteomics for response to therapy [Seite 114]
9.7 - Strategies to address serum proteome complexity [Seite 115]
9.7.1 - Liquid chromatography (LC) tandem mass spectrometry (MS/MS) [Seite 115]
9.7.2 - Targeted proteomics using multiple reaction monitoring (LC MRM MS) [Seite 117]
9.8 - Bio-analytical validation of serum protein biomarkers [Seite 117]
9.9 - Circulating autoantibodies [Seite 118]
9.10 - Clinical validation of serum biomarkers [Seite 118]
9.10.1 - Current challenges in lung cancer biomarker development and implementation [Seite 119]
9.11 - Conclusions and future clinical implications [Seite 120]
9.12 - References [Seite 121]
10 - CHAPTER 6 Molecular Biology of Lung Preneoplasia [Seite 126]
10.1 - Introduction [Seite 126]
10.2 - Pathology of lung cancer preneoplastic lesions [Seite 127]
10.2.1 - Squamous cell carcinoma preneoplasia [Seite 127]
10.2.2 - Adenocarcinoma precursor lesions [Seite 129]
10.2.3 - Precursor lesions of neuroendocrine tumors [Seite 129]
10.3 - Molecular pathogenesis of lung cancer [Seite 130]
10.3.1 - Pathogenesis of squamous cell carcinoma [Seite 131]
10.3.2 - Pathogenesis of lung adenocarcinoma [Seite 132]
10.3.3 - Pathogenesis of SCLC [Seite 134]
10.4 - Field cancerization in lung cancer pathogenesis [Seite 134]
10.4.1 - Smoking damaged epithelium and lung field cancerization [Seite 135]
10.4.2 - Field cancerization transcriptome [Seite 135]
10.5 - Field cancerization compartmentalization [Seite 136]
10.6 - Inflammation and lung cancer [Seite 138]
10.7 - Summary and perspectives [Seite 138]
10.8 - References [Seite 139]
11 - CHAPTER 7 Detection and Treatment of Preneoplastic Lesions [Seite 145]
11.1 - Introduction [Seite 145]
11.2 - Detection of preneoplastic lesions in central airways [Seite 145]
11.2.1 - Principles of biophotonic imaging [Seite 145]
11.2.2 - Autofluorescence bronchoscopy (AFB) [Seite 146]
11.2.3 - Narrow band imaging (NBI) [Seite 147]
11.2.4 - Optical coherence tomography (OCT) [Seite 147]
11.3 - Indications for autofluorescence bronchoscopy [Seite 149]
11.3.1 - Evaluation of patients with abnormal sputum cytology [Seite 149]
11.3.2 - Evaluation of patients with suspected, known or previously completely resected lung cancer [Seite 149]
11.4 - Assessment of patients with early central lung cancer prior to endobronchial therapy [Seite 150]
11.5 - Surveillance of bronchial intraepithelial neoplasia [Seite 150]
11.6 - Detection of preneoplastic lesions in peripheral lung [Seite 151]
11.7 - Treatment of preinvasive bronchial lesions [Seite 152]
11.8 - Endobronchial therapies [Seite 153]
11.8.1 - Photodynamic therapy (PDT) [Seite 153]
11.8.2 - Electrocautery [Seite 153]
11.8.3 - Cryotherapy [Seite 154]
11.8.4 - Brachytherapy [Seite 154]
11.8.5 - Follow-up after endobronchial treatment [Seite 154]
11.9 - References [Seite 154]
12 - CHAPTER 8 Pathology of Adenocarcinoma [Seite 160]
12.1 - Introduction [Seite 160]
12.2 - Adenocarcinoma classification in resected specimens [Seite 161]
12.2.1 - Preinvasive lesions [Seite 161]
12.3 - Invasive adenocarcinoma [Seite 165]
12.3.1 - Adenocarcinoma variants [Seite 165]
12.3.2 - Prognosis of adenocarcinoma subtypes in resected specimens [Seite 165]
12.3.3 - TNM staging: impact of 2011 adenocarcinoma classification [Seite 167]
12.4 - Adenocarcinoma classification in small biopsies and cytology [Seite 168]
12.5 - References [Seite 170]
13 - CHAPTER 9 Management of Multifocal Bronchioloalveolar Carcinoma (BAC) [Seite 174]
13.1 - Introduction [Seite 174]
13.2 - Heterogeneity in the presentation with advanced BAC [Seite 175]
13.3 - Evaluating Multifocal BAC [Seite 175]
13.3.1 - Symptomatology [Seite 176]
13.3.2 - Natural history and imaging findings [Seite 176]
13.4 - Interventions to manage multifocal BAC [Seite 177]
13.4.1 - Is the multifocal disease encompassed within a single lobe or lung? [Seite 177]
13.4.2 - Is the patient symptomatic, or is there any progression at a clinically significant rate? [Seite 179]
13.4.3 - If there is evidence of progression at a clinically significant pace, is this a unifocal (or arguably "oligo-focal") or multifocal process? [Seite 179]
13.5 - Approach to unifocal progression in the setting of multifocal disease [Seite 180]
13.6 - Palliative surgery [Seite 181]
13.7 - Systemic therapy for multifocal BAC [Seite 181]
13.8 - Bronchorrhea [Seite 185]
13.9 - Conclusions [Seite 186]
13.10 - References [Seite 187]
14 - CHAPTER 10 Radiology and Lung Cancer Screening [Seite 192]
14.1 - Introduction [Seite 192]
14.2 - Concept of screening [Seite 192]
14.3 - Bias [Seite 193]
14.4 - Historical perspectives [Seite 193]
14.4.1 - Radiographic screening [Seite 194]
14.4.2 - Computed tomography screening [Seite 194]
14.5 - The National Lung Screening Trial [Seite 195]
14.5.1 - Trial design [Seite 195]
14.5.2 - Participant cohort [Seite 196]
14.5.3 - Results [Seite 196]
14.6 - Ongoing lung cancer screening trials and programs [Seite 197]
14.7 - Lung cancer screening recommendations in the US [Seite 197]
14.8 - Nodule detection and management [Seite 198]
14.9 - Risks of LDCT screening [Seite 201]
14.9.1 - Risks of radiation [Seite 201]
14.9.2 - Psychological and procedural risks [Seite 202]
14.10 - Cost effectiveness of LDCT screening [Seite 202]
14.11 - Lung cancer screening and smoking cessation [Seite 202]
14.12 - Translation from trial to practice [Seite 202]
14.12.1 - Recruitment [Seite 202]
14.12.2 - Academic center to community hospital [Seite 203]
14.13 - Conclusion [Seite 203]
14.14 - References [Seite 203]
15 - CHAPTER 11 Imaging Lung Cancer [Seite 207]
15.1 - Introduction [Seite 207]
15.2 - Imaging of the primary tumor (T) [Seite 207]
15.3 - Imaging of regional lymphnodes (N) [Seite 208]
15.4 - Imaging of distant metastasis (M) [Seite 211]
15.5 - Conclusion [Seite 215]
15.6 - References [Seite 215]
16 - CHAPTER 12 Staging of the Mediastinum [Seite 218]
16.1 - Introduction [Seite 218]
16.2 - Imaging [Seite 218]
16.3 - Endoscopic evaluation [Seite 219]
16.4 - Mediastinoscopy [Seite 221]
16.4.1 - Anterior mediastinotomy, extended cervical mediastinoscopy, thoracoscopy and re-do mediatinoscopy [Seite 223]
16.5 - Video Assisted Mediastinal Lymphadenectomy (VAMLA) - a staging procedure? [Seite 224]
16.6 - Discussion [Seite 224]
16.7 - References [Seite 227]
17 - CHAPTER 13 Management of the Solitary Pulmonary Nodule [Seite 230]
17.1 - Introduction [Seite 230]
17.2 - Prevalence of lung nodules [Seite 230]
17.3 - Risk of malignancy [Seite 231]
17.3.1 - Clinical features [Seite 231]
17.3.2 - Radiographic features [Seite 231]
17.4 - Management [Seite 232]
17.4.1 - Patient preference and shared decision-making [Seite 232]
17.4.2 - Management plan [Seite 232]
17.4.3 - Low probability [Seite 232]
17.4.4 - Intermediate probability [Seite 233]
17.4.5 - High probability [Seite 235]
17.5 - Conclusion [Seite 237]
17.6 - References [Seite 237]
18 - CHAPTER 14 Minimally Invasive Resections for Lung Cancer [Seite 240]
18.1 - Introduction [Seite 240]
18.2 - Postoperative pain [Seite 242]
18.3 - Estimated blood loss and chest tube duration [Seite 242]
18.4 - Postoperative independence and return to pre-operative function [Seite 243]
18.5 - Pulmonary function [Seite 243]
18.6 - Operative time and length of stay [Seite 245]
18.7 - Cost-effectiveness [Seite 245]
18.8 - Administration of adjuvant chemotherapy [Seite 246]
18.9 - Complications [Seite 248]
18.10 - Special circumstances [Seite 248]
18.10.1 - Reoperation [Seite 248]
18.10.2 - Barriers to adoption [Seite 248]
18.10.3 - Thoracoscopic segmentectomy [Seite 248]
18.10.4 - Thoracoscopic pneumonectomy [Seite 249]
18.10.5 - Thoracoscopic bronchoplasty [Seite 249]
18.10.6 - Thoracoscopic chest wall resections [Seite 249]
18.10.7 - Thoracoscopic lymphadenectomy [Seite 249]
18.10.8 - Robotic-assisted lobectomy [Seite 249]
18.11 - Conclusions [Seite 249]
18.12 - References [Seite 250]
19 - CHAPTER 15 Extended Resections for Lung Cancer [Seite 252]
19.1 - Introduction [Seite 252]
19.2 - General principles for all extended resections [Seite 252]
19.3 - Chest wall invasion [Seite 254]
19.4 - Superior sulcus tumor resection [Seite 258]
19.5 - Vertebral body involvement [Seite 259]
19.6 - Diaphragm Involvement [Seite 261]
19.7 - Phrenic nerve involvement [Seite 261]
19.8 - Recurrent laryngeal nerve involvement [Seite 262]
19.9 - Pericardium [Seite 262]
19.10 - Heart and great vessels [Seite 263]
19.11 - Trachea [Seite 265]
19.12 - Surgical perspectives for synchronous tumors [Seite 265]
19.13 - Summary [Seite 266]
19.14 - References [Seite 266]
20 - CHAPTER 16 Bronchoscopic Interventions for Lung Cancer [Seite 269]
20.1 - Introduction [Seite 269]
20.2 - Central airway disease in lung cancer amenable to bronchoscopic treatment [Seite 269]
20.3 - Mechanical bronchoscopic interventions in lung cancer [Seite 271]
20.4 - Thermal bronchoscopic interventions in lung cancer [Seite 274]
20.5 - Nonthermal, nonmechanical bronchoscopic interventions in lung cancer [Seite 277]
20.6 - Conclusion [Seite 279]
20.7 - References [Seite 279]
21 - CHAPTER 17 Primary Tracheal Tumors [Seite 283]
21.1 - Epidemiology [Seite 283]
21.2 - Anatomy and physiology [Seite 283]
21.3 - Symptoms [Seite 284]
21.4 - Diagnosis and staging [Seite 284]
21.5 - Tumor pathology and classification [Seite 286]
21.6 - Management [Seite 288]
21.7 - Surgical techniques [Seite 290]
21.8 - Prognosis [Seite 292]
21.9 - Conclusion [Seite 292]
21.10 - References [Seite 292]
22 - CHAPTER 18 Adjuvant Chemotherapy Following Surgery for Lung Cancer [Seite 294]
22.1 - Introduction [Seite 294]
22.2 - Clinical trials of adjuvant chemotherapy [Seite 294]
22.2.1 - Japanese Clinical Oncology Group Trial 9304 [Seite 295]
22.2.2 - Adjuvant Lung Project Italy [Seite 296]
22.2.3 - International Adjuvant Lung Cancer Trial [Seite 296]
22.2.4 - Big Lung Trial [Seite 297]
22.2.5 - JBR.10 Trial [Seite 298]
22.2.6 - Adjuvant Navelbine International Trialist's Association Study [Seite 298]
22.2.7 - Cancer and Leukemia Group B-9633 [Seite 299]
22.2.8 - Pooled analyses of adjuvant chemotherapy trials [Seite 299]
22.3 - Selection of patients to receive adjuvant chemotherapy [Seite 300]
22.3.1 - Stage II and III disease [Seite 300]
22.3.2 - Stage IA disease [Seite 300]
22.3.3 - Stage IB disease [Seite 300]
22.3.4 - Elderly patients [Seite 301]
22.3.5 - Patients with poor performance status [Seite 301]
22.4 - Selection of adjuvant chemotherapy regimen [Seite 301]
22.4.1 - Cisplatin versus carboplatin [Seite 301]
22.4.2 - Choice of a second agent [Seite 301]
22.5 - Unanswered questions [Seite 302]
22.5.1 - Predictive and prognostic biomarkers [Seite 302]
22.5.2 - Use of targeted therapies with adjuvant chemotherapy [Seite 302]
22.6 - Summary of recommendations [Seite 302]
22.7 - References [Seite 303]
23 - CHAPTER 19 Neoadjuvant Chemotherapy for Resectable Non-Small Cell Lung Cancer [Seite 306]
23.1 - Introduction [Seite 306]
23.2 - Phase II trials in resectable stage III disease [Seite 307]
23.3 - Phase II trials in earlier stage disease [Seite 310]
23.4 - Randomized phase II and phase III trials [Seite 311]
23.5 - Meta-analyses of neoadjuvant chemotherapy [Seite 315]
23.6 - Impact on surgical morbidity and mortality [Seite 316]
23.7 - Surrogate efficacy endpoints in neoadjuvant trials [Seite 317]
23.8 - Window of opportunity trials [Seite 318]
23.9 - Conclusions [Seite 320]
23.10 - References [Seite 321]
24 - CHAPTER 20 Image-Guided Radiation Therapy [Seite 325]
24.1 - Introduction [Seite 325]
24.2 - Conventional versus CT-based simulation [Seite 326]
24.3 - PET and PET-CT in radiation treatment planning [Seite 326]
24.4 - Tumor motion [Seite 328]
24.5 - Image guided radiation therapy [Seite 329]
24.6 - Cone-beam CT [Seite 329]
24.7 - Tomotherapy [Seite 330]
24.8 - Markers and respiratory gating [Seite 330]
24.9 - Orthogonal kV X-rays [Seite 331]
24.10 - In-room CT [Seite 331]
24.11 - The role of image guidance in stereotactic body radiotherapy (SBRT) [Seite 332]
24.12 - Conclusions [Seite 332]
24.13 - References [Seite 332]
25 - CHAPTER 21 Stereotactic Ablative Radiotherapy for Lung Cancer [Seite 336]
25.1 - Introduction [Seite 336]
25.2 - History of SABR [Seite 337]
25.3 - Radiobiology of SABR tumor biology [Seite 338]
25.4 - Normal tissue biology and tolerance [Seite 339]
25.5 - Defining SABR [Seite 340]
25.6 - Immobilization and target motion issues related to SABR [Seite 341]
25.7 - Physics and dosimetry of SABR [Seite 341]
25.8 - Treatment experience in non-small cell lung cancer [Seite 343]
25.8.1 - Medically inoperable stage I patients [Seite 343]
25.8.2 - Operable stage I patients [Seite 347]
25.9 - SABR for lung cancer metastases, multiple primary lung tumors, and recurrent lung cancer [Seite 348]
25.10 - Summary [Seite 349]
25.11 - References [Seite 349]
26 - CHAPTER 22 Proton Therapy [Seite 354]
26.1 - Introduction [Seite 354]
26.2 - Relative biologic effectiveness and biological research on protons [Seite 355]
26.3 - Rationale for proton therapy [Seite 356]
26.4 - Proton treatment planning and delivery [Seite 357]
26.4.1 - Physical characteristics of proton beams [Seite 357]
26.4.2 - Passive scattering systems [Seite 357]
26.4.3 - Dynamic spot scanning systems [Seite 359]
26.4.4 - Planning proton therapy versus photon therapy [Seite 360]
26.4.5 - Image-guided proton delivery [Seite 362]
26.4.6 - Tumor motion considerations [Seite 362]
26.4.7 - Adaptive proton therapy [Seite 363]
26.5 - Normal-tissue doses from proton therapy versus other forms of radiation therapy [Seite 363]
26.5.1 - Protons produce lower normal tissue doses than 3D CRT, IMRT, or SBRT [Seite 363]
26.5.2 - Clinical trials [Seite 365]
26.6 - References [Seite 366]
27 - CHAPTER 23 Combinations of Radiation Therapy and Chemotherapy for Non-small Cell and Small-Cell Lung Carcinoma [Seite 369]
27.1 - Introduction [Seite 369]
27.2 - Rationale for combining radiation therapy and chemotherapy [Seite 369]
27.3 - Sequential chemotherapy and radiation therapy [Seite 370]
27.4 - Concurrent chemotherapy and radiation therapy [Seite 372]
27.5 - Sequential versus concurrent chemoradiation therapy [Seite 372]
27.6 - Concurrent chemoradiation therapy followed by surgical resection [Seite 373]
27.7 - Radiation therapy [Seite 375]
27.7.1 - The importance of radiation dose in local tumor control [Seite 375]
27.7.2 - Designing the radiation volume and configuration [Seite 376]
27.7.3 - Minimizing radiation-induced toxicity to normal tissues [Seite 378]
27.7.4 - Novel radiation delivery techniques [Seite 382]
27.8 - Chemoradiation for small-celllung cancer [Seite 383]
27.9 - Sequencing of radiation and chemotherapy for limited-stage disease [Seite 383]
27.10 - Chemotherapy regimens [Seite 384]
27.11 - Radiation dose and fractionation schedule [Seite 384]
27.12 - Radiation target volumes and dose constraints [Seite 386]
27.13 - Consolidative thoracic radiation for extensive-stage disease [Seite 386]
27.14 - Prophylactic cranial irradiation [Seite 386]
27.15 - Conclusions [Seite 387]
27.16 - References [Seite 387]
28 - CHAPTER 24 Individualized Radiotherapy by Dose Escalation and Altered Fractionation in Non-small Cell Lung Cancer [Seite 395]
28.1 - Introduction [Seite 395]
28.2 - History of radiation dose escalation and altered fractionation [Seite 395]
28.3 - Advances in technology and conformality [Seite 397]
28.4 - Modern studies of dose-escalation for locally advanced disease [Seite 399]
28.5 - Individualized radiation treatment planning [Seite 401]
28.6 - Conclusions [Seite 402]
28.7 - References [Seite 402]
29 - CHAPTER 25 Molecular Target Treatment for Personalized Radiotherapy in Lung Cancer [Seite 406]
29.1 - Technologic improvements in radiation delivery enhances therapeutic ratio [Seite 406]
29.2 - Overcoming the plateau of radiation efficacy [Seite 407]
29.3 - Targeted therapy with radiotherapy: past successes and failures [Seite 407]
29.4 - Hypoxia targeting [Seite 407]
29.5 - Vascular targeting [Seite 409]
29.6 - EGFR targeting [Seite 409]
29.7 - Guidelines for incorporating novel targeted agents in combination with radiation in lung cancer [Seite 410]
29.7.1 - Potential targeted agents to combine with radiation therapy [Seite 411]
29.7.2 - DNA damage repair targeting drugs [Seite 411]
29.7.3 - Cell cycle checkpoint inhibitors [Seite 412]
29.7.4 - Signal transduction inhibitors [Seite 412]
29.7.5 - Epigenetic agents [Seite 412]
29.7.6 - HSP90 inhibitors [Seite 413]
29.8 - Considerations for bringing agents into clinical testing [Seite 414]
29.8.1 - The synthetic lethality effect with radiation [Seite 414]
29.8.2 - Prioritizing agents for clinical development [Seite 414]
29.8.3 - Preclinical studies in the disease site of interest [Seite 414]
29.8.4 - Biomarkers for patient selection [Seite 414]
29.8.5 - Design of clinical trials [Seite 415]
29.9 - Challenges and opportunities for the clinical development of targeted agents with radiation therapy [Seite 417]
29.10 - Conclusion [Seite 417]
29.11 - References [Seite 418]
30 - CHAPTER 26 EGFR Tyrosine Kinase Inhibitors and Monoclonal Antibodies: Clinical Trial Review [Seite 422]
30.1 - Background [Seite 422]
30.2 - Front-line therapy: combination anti-EGFR therapy and chemotherapy for molecularly unselected NSCLC patients [Seite 422]
30.3 - Front-line therapy: chemotherapy and intermittent anti-EGFR therapy [Seite 424]
30.4 - Front-line therapy: anti-EGFR single agent [Seite 425]
30.5 - Maintenance therapy [Seite 428]
30.6 - Salvage therapy [Seite 429]
30.7 - Other TKIs and MAbs [Seite 430]
30.8 - Conclusions [Seite 432]
30.9 - References [Seite 432]
31 - CHAPTER 27 Mechanisms of Resistance to Epidermal Growth Factor Receptor (EGFR) in Non-small Cell Lung Cancer [Seite 437]
31.1 - Introduction [Seite 437]
31.2 - Primary resistance to EGFR TKIs [Seite 438]
31.2.1 - EGFR-resistant mutations [Seite 438]
31.2.2 - KRAS and BRAF mutations [Seite 440]
31.2.3 - PIK3CA mutations and PTEN loss [Seite 440]
31.2.4 - ErbB family members: mutation and amplification [Seite 441]
31.3 - Acquired resistance to EGFR TKIs [Seite 441]
31.3.1 - Acquired EGFR mutations [Seite 441]
31.3.2 - HER2 amplification [Seite 443]
31.3.3 - MAPK1 amplification [Seite 443]
31.3.4 - MET amplification [Seite 443]
31.3.5 - HGF overexpression [Seite 444]
31.3.6 - IGF-1R signaling and other pathways [Seite 444]
31.3.7 - Histological transformation [Seite 444]
31.3.8 - Epithelial-mesenchymal transition (EMT) [Seite 444]
31.3.9 - Pharmacologic interactions [Seite 444]
31.3.10 - Tumor heterogeneity [Seite 445]
31.4 - Conclusions [Seite 445]
31.5 - References [Seite 445]
32 - CHAPTER 28 Predictive Tumor Biomarkers for EGFR Inhibitors [Seite 451]
32.1 - EGFR [Seite 452]
32.1.1 - EGFR mutation [Seite 452]
32.1.2 - Sensitizing EGFR mutations [Seite 452]
32.1.3 - Resistant EGFR mutations [Seite 454]
32.1.4 - Other rare mutations [Seite 455]
32.1.5 - Role of EGFR mutations in clinical settings [Seite 456]
32.1.6 - Mutation detection methods [Seite 456]
32.1.7 - EGFR gene copy number [Seite 459]
32.1.8 - EGFR protein expression [Seite 459]
32.1.9 - Germline polymorphisms of EGFR [Seite 459]
32.1.10 - KRAS mutations [Seite 460]
32.2 - Other biomarkers [Seite 460]
32.3 - EGFR testing in the clinical setting [Seite 461]
32.4 - Perspectives for future development of the biomarkers [Seite 463]
32.5 - References [Seite 464]
33 - CHAPTER 29 Immunologic Approaches to Lung Cancer Therapy [Seite 470]
33.1 - Cancer immunotherapy [Seite 470]
33.2 - Targeting immune regulatory checkpoints for lung cancer therapy [Seite 470]
33.3 - Tumor protein and peptide vaccines [Seite 471]
33.4 - Dendritic cell vaccines [Seite 473]
33.5 - Modified tumor cell vaccines [Seite 474]
33.6 - Immune adjuvant vaccines [Seite 475]
33.7 - Gene delivery vaccines [Seite 476]
33.8 - Conclusion [Seite 476]
33.9 - References [Seite 477]
34 - CHAPTER 30 Novel and Emerging Agents in NSCLC [Seite 480]
34.1 - Introduction [Seite 480]
34.2 - Novel targeted agents [Seite 480]
34.2.1 - HSP 90 inhibitors [Seite 480]
34.2.2 - Met inhibitors/HCF inhibitors [Seite 481]
34.2.3 - MEK inhibitors [Seite 482]
34.2.4 - PI3K/AKT/mTOR pathway inhibitors [Seite 482]
34.2.5 - PARP inhibitors [Seite 484]
34.2.6 - Notch and hedgehog inhibitors [Seite 484]
34.2.7 - Mitotic inhibitors [Seite 485]
34.2.8 - Conclusion and future directions for novel targeted agents [Seite 486]
34.3 - Targeted gene therapy for lung cancer [Seite 486]
34.3.1 - p53 gene replacement [Seite 487]
34.3.2 - Clinical trials of p53 gene replacement [Seite 487]
34.3.3 - Gene replacement in combination with chemotherapy and radiation [Seite 488]
34.3.4 - Systemic gene therapy for metastases [Seite 489]
34.3.5 - Future directions for gene therapy [Seite 490]
34.4 - References [Seite 490]
35 - CHAPTER 31 Novel Clinical Trial Designs for Metastatic Lung Cancer [Seite 495]
35.1 - Introduction [Seite 495]
35.2 - Alternative endpoints in clinical trials [Seite 495]
35.3 - The need for novel trial designs [Seite 496]
35.4 - The impact of molecularly targeted agents in trial design [Seite 497]
35.5 - The BATTLE trial [Seite 498]
35.6 - Moving forward with innovative clinical trial designs [Seite 500]
35.7 - References [Seite 502]
36 - CHAPTER 32 Novel Statistical Models for NSCLC Clinical Trials [Seite 504]
36.1 - Introduction [Seite 504]
36.2 - Bayesian statistics and its relevance in clinical trials [Seite 507]
36.3 - Adaptive designs [Seite 509]
36.3.1 - Continual reassessment method (CRM) [Seite 509]
36.3.2 - Predictive probability design (PPD) [Seite 509]
36.3.3 - Biomarker stratified Bayesian adaptive randomization design (BSBARD) [Seite 510]
36.3.4 - Comparison of standard and novel designs [Seite 510]
36.3.5 - Challenges for adaptive designs [Seite 512]
36.4 - The BATTLE trial: a case study [Seite 512]
36.5 - Other novel designs [Seite 515]
36.6 - Summary [Seite 518]
36.7 - References [Seite 518]
37 - CHAPTER 33 Tumor Microenvironment, Angiogenesis Biology, and Targeted Therapy [Seite 521]
37.1 - Tumor angiogenesis [Seite 521]
37.2 - Regulation of tumor angiogenesis [Seite 522]
37.3 - Vascular endothelial growth factor receptor signaling [Seite 522]
37.4 - Fibroblast growth factor receptor signaling [Seite 523]
37.5 - Epidermal growth factor receptor signaling [Seite 523]
37.6 - Platelet derived growth factor receptor signaling [Seite 523]
37.7 - Therapeutic strategies to inhibit angiogenesis in lung cancer [Seite 524]
37.8 - VEGF targeted therapies: FDA approved agents [Seite 524]
37.9 - Combined VEGF/R and EGFR targeted therapies [Seite 525]
37.10 - Tyrosine kinase inhibitors of VEGFR pathway [Seite 525]
37.11 - Novel agents [Seite 528]
37.12 - Vascular disrupting agents (VDAs) [Seite 528]
37.13 - Antiangiogenic therapy in SCLC [Seite 529]
37.14 - Biomarkers of response to antiangiogenic therapy [Seite 530]
37.14.1 - High blood pressure [Seite 531]
37.14.2 - Circulating cytokines [Seite 531]
37.14.3 - VEGF single nucleotide polymorphisms (SNPs) [Seite 532]
37.14.4 - Other biomarkers [Seite 532]
37.15 - Tumor resistance to antiangiogenic therapies [Seite 532]
37.16 - Conclusion [Seite 533]
37.17 - References [Seite 534]
38 - CHAPTER 34 Anti-angiogenic Agents in Metastatic NSCLC [Seite 543]
38.1 - Introduction [Seite 543]
38.2 - Monoclonal antibodies to VEGF/VEGFR [Seite 543]
38.2.1 - Bevacizumab [Seite 543]
38.2.2 - Ramucirumab [Seite 546]
38.3 - Small molecule tyrosine kinase inhibitors [Seite 546]
38.3.1 - Sorafenib [Seite 547]
38.3.2 - Sunitinib [Seite 548]
38.3.3 - Pazopanib [Seite 548]
38.3.4 - Vandetanib [Seite 548]
38.3.5 - Cediranib [Seite 549]
38.3.6 - Motesanib [Seite 549]
38.3.7 - Axitinib [Seite 549]
38.3.8 - BIBF 1120 [Seite 549]
38.3.9 - Cabozantinib [Seite 550]
38.4 - Vascular disrupting agents [Seite 550]
38.5 - Other anti-angiogenic therapies [Seite 550]
38.5.1 - Aflibercept [Seite 550]
38.6 - Biomarkers for anti-angiogenic therapies [Seite 551]
38.7 - Conclusion [Seite 552]
38.8 - References [Seite 552]
39 - CHAPTER 35 Targeting ALK Rearrangements [Seite 557]
39.1 - Introduction [Seite 557]
39.2 - The molecular biology of native ALK [Seite 557]
39.3 - EML4-ALK: role in molecular pathogenesis [Seite 558]
39.4 - Clinicopathologic features of patients with ALK rearrangements [Seite 559]
39.5 - Prognostic implications of ALK rearrangements [Seite 560]
39.6 - Diagnostic testing for ALK rearrangements [Seite 560]
39.6.1 - ALK FISH [Seite 560]
39.6.2 - RT-PCR [Seite 561]
39.6.3 - Immunohistochemistry [Seite 561]
39.7 - ALK Inhibitors: Crizotinib [Seite 562]
39.7.1 - Clinical efficacy [Seite 562]
39.7.2 - Safety profile [Seite 564]
39.8 - Acquired resistance to crizotinib [Seite 564]
39.9 - Other systemic therapies [Seite 565]
39.10 - Future directions [Seite 565]
39.10.1 - Next generation ALK inhibitors [Seite 565]
39.10.2 - Heat shock protein 90 inhibitors [Seite 566]
39.11 - Conclusion [Seite 566]
39.12 - References [Seite 567]
40 - CHAPTER 36 Non-small Cell Lung Cancers (NSCLC) with Mutations in BRAF [Seite 573]
40.1 - Introduction [Seite 573]
40.2 - Biology of BRAF mutant malignancies [Seite 573]
40.3 - Molecular pathogenesis and frequency of BRAF mutations in human malignancies [Seite 574]
40.4 - BRAF V600E mutant melanomas and colorectal cancers [Seite 574]
40.5 - BRAF mutant NSCLC [Seite 575]
40.5.1 - Diagnosis of BRAF mutations [Seite 575]
40.5.2 - Clinical characteristics of BRAF mutated NSCLC [Seite 575]
40.5.3 - The treatment of V600E BRAF mutant NSCLC [Seite 575]
40.5.4 - The non-V600E BRAF mutants [Seite 576]
40.5.5 - BRAF inactivating mutations [Seite 576]
40.6 - Mechanisms of resistance to BRAF inhibitors [Seite 576]
40.7 - Summary [Seite 577]
40.8 - References [Seite 577]
41 - CHAPTER 37 Prognostic and Predictive Biomarker Signatures [Seite 580]
41.1 - Introduction [Seite 580]
41.2 - Prognostic biomarker signatures [Seite 581]
41.3 - Predictive biomarker signatures [Seite 583]
41.4 - Future directions [Seite 584]
41.5 - References [Seite 584]
42 - CHAPTER 38 Brain Metastasis from Lung Cancer [Seite 588]
42.1 - Introduction [Seite 588]
42.2 - Pathophysiology of brain metastasis [Seite 588]
42.3 - Treatment options [Seite 589]
42.3.1 - Surgical resection [Seite 589]
42.4 - Stereotactic radiosurgery [Seite 589]
42.5 - Whole-brain radiation therapy [Seite 590]
42.6 - WBRT as primary therapy for gross disease [Seite 590]
42.7 - WBRT as an adjuvant after local therapy [Seite 592]
42.7.1 - WBRT after surgery [Seite 592]
42.8 - WBRT after stereotactic radiosurgery [Seite 593]
42.9 - Prophylactic cranial irradiation [Seite 594]
42.10 - Toxicity of radiation to the brain [Seite 597]
42.11 - Biomarkers in non-small cell lung cancer and brain metastases [Seite 598]
42.12 - Conclusions [Seite 599]
42.13 - References [Seite 599]
43 - Index [Seite 607]
44 - Supplemental Images [Seite 619]

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