Damage vs. morbidity, in lung, 601–602
Dasatinib (BMS-354825), 745
DC101 plus radiotherapy, 198t, 199
4D-CT/intensity-modulated radiotherapy
(IMRT), 629–630, 630f
Death-associated protein kinase (DAPK)
methylation, 154
Death rates
lung cancer, gender on, 355
U.S. cancer
female, 3, 4f, 4t
male, 3, 4f
Deep vein thrombosis
in NSCLC, 336–337
in SCLC, 348
Deforolimus (AP-23573), 741
Deforolimus (AP-23573) plus radiotherapy,
on cell cycle, 197
Dendritic cells (DCs), 753
definition of, 174
in lung cancer, 174
Dendritic cell vaccines, 753, 755t, 756t,
760
Depression, in lung cancer patients,
332–333
Dermatologic conditions
in NSCLC, 336, 336t
in SCLC, 346t, 348
Dermatomyositis
in NSCLC, 336
in SCLC, 348
Desmoplasia, in adenocarcinoma, 305
Detection, early. See Early detection
Dexamethasone, for radiotherapy risk
reduction, 631
Dexosomes, 755t, 756t, 760
Diesel exhaust, lung cancer from, 37
Diet, 47. See also Nutrition
as chemoprevention, 215
on incidence, 13–14
on incidence, gender and, 356
Diffuse alveolar damage (DAD), 252–253
Diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia
(DIPNECH), 302, 971, 973
Digital clubbing
in NSCLC, 336
in SCLC, 346t, 348
Dirofilariasis (Dirofilaria immitis), 252
DNA-based genome-wide search, for
aberrant copy number, 266
DNA-based markers
in blood, 267
in sputum, 269
DNA-based methylation markers, 266
DNA damage, 62
DNA hypermethylation, 100–107, 786
of CpG islands, 97, 100, 154
detection of, in bodily fluids, 102t–103t,
101–103
functional implications of, 104–106, 105f
histone modifications in, 106–107
markers and loci for, 100f, 101, 102t
INDEX 989
in NSCLC, 100–101
of promoter CpG islands, 104
reversal of, 106
studies for functional characterization of,
100, 100f
DNA methylation, 66, 96–98. See also
Epigenetic changes
aberrant, in blood, 267
in cancer (CpG islands), 97, 97f
in CpG dinucleotides, 96–97
hypermethylation in, 100–107 ( See also
DNA hypermethylation)
hypomethylation in, 97–98
marker detection in remote media in, 97,
102t–103t
of MGMT, 95–96
in molecular prognostication, 154–155
by MSP in sputa, 269
study of, 97
tumor-acquired, 61t
DNA methylation inhibitors, 95, 107
DNA repair capacity, 267, 689
DNA repair gene hypermethylation, 95–96, 96f
Docetaxel
biomarkers for resistance to, 688
mechanism of action of, 688
for NSCLC
advanced, 646–647, 646t, 648t
as second-line chemotherapy
dose and schedule of administration
of, 671–672, 672t
evidence for, 669–671, 670t, 671f
plus platinating agent, 741–742
plus radiotherapy on cell cycle, 194t,
195–196
for SCLC, 847, 848t
Docetaxel-cisplatin, for recurrent/refractory
NSCLC, 675
Docetaxel-gemcitabine, for recurrent/ refractory
NSCLC, 675–676, 675t
Docetaxel-irinotecan, for recurrent/refractory
NSCLC, 674, 675t
Docetaxel-vandetanib, 744
Docetaxel-vinflunine, for recurrent/refractory
NSCLC, 674
Doppler optical coherence tomography
(DOCT), 259
Dose. See specific therapies
Dose and fractionation, radiotherapy, 558–560
calculation of
Monte Carlo (SM), 558
superposition/convolution (SC), 558
tissue heterogeneity correction in, 558
normal-tissue dose constraints in, 561–562
for NSCLC, 558–560
adjuvant radiation with resected
NSCLC, 558
altered fractionation, 560
inoperable or unresectable NSCLC,
558–559
treatment duration, 559–560
for SCLC, 560
time-corrected biologically effective dose
(tBERD), 559
Dose–volume histograms (DVH), 556, 556f
Dose–volume relationships, in radiotherapyrelated
lung damage, 618
assessing regional lung function in
CT density, 618, 618f
FDG-PET, 619, 619f
SPECT, 619
quantification of, 619–621, 620f, 621f
Doxorubicin, for malignant mesothelioma,
953
Dumon silicon Y stent, 894, 894f
Dynamic Y stent, 894–895, 895f
Dysphagia, in NSCLC, 330
Dyspnea, in NSCLC, 329, 329t
E
Early detection
biomarkers for, 219–220
bronchoscopy for, 257–262 ( See also
Bronchoscopy, for early
detection)
evolving screening modalities of, 265–271
airway-based markers, 267–271
bronchoscopically procured, for
DNA/RNA/protein analyses,
267–268, 268f
exhaled breath, for volatile small
compounds, 269–271, 270f
sputum-based cytology, 269
sputum, DNA methylation by MSP
in, 269
sputum, for DNA-based markers, 269
sputum, for protein-based markers, 269
sputum, for RNA-based markers, 269
blood-based markers, 267
bronchoscopic optical techniques, 266
candidate noninvasive risk assessment
tools, 265
complementary modalities, 265
conventional clinical disease detection
tools, 265–266
exfoliated upper airway cells, 271
lung tissue–based molecular assays, 266
staged approach, 265
mass spectrometry for
MALDI MS, 140–142, 141f
SELDI-TOF-MS, 140–141
for prevention, 211
proteomic biomarkers for, 140–142, 141f
survival with, 257
Early-stage NSCLC, survival rates for, 799,
800t
E-cadherin methylation, 154
Ectopic Cushing syndrome
in NSCLC, 335
in SCLC, 346–347
Edatrexate, for malignant mesothelioma, 953
EGF, 758
EGFR, 84–85
amplification of, 276
overexpression of, 758
in tumor cell repopulation after
radiotherapy, 575
EGFR inhibitors, 55. See also Erlotinib;
Gefitinib
in completely resected NSCLC, 785
on NSCLC, gender and, 363–364, 364t
patient selection for, 715–732
clinical factors in
clinical predictors in randomized
phase III trials, 716–717, 719
clinical trials for patients selected by
clinical factor, 719
early clinical trials, 715–716
histology, 717t–718t, 719
other clinical factors, 719
skin toxicity, 719
subsequent studies, 716, 717t–718t
EGFR gene copy number in, 720–723
EGFR FISH and outcome with
first-line EGFR TKIs, 721
EGFR FISH and outcome with
monoclonal antibodies, 721
EGFR FISH and outcome with
second-line EGFR TKIs,
720–721
EGFR protein expression in, 723, 723t
methodological considerations in, 722
on prognosis in NSCLC, 721–722
studies of EGFR FISH as predictive
marker for EGFR inhibitors,
722
interstitial lung disease from, 719–720
K- ras mutations and, 732
resistance mechanisms to EGFR -
targeted therapies in, 731–732
serum proteomics in, 732
plus radiotherapy, 767–769, 768f
for recurrent/refractory NSCLC,
676–678, 676t, 677f, 678f
research on, 715
EGFR mutations, 51, 60t, 62, 276
in invasive adenocarcinoma, 308
in molecular prognostication, 149
in NSCLC, 164, 724–731
biology of, 725–726, 726f
cigarette smoking and, 726–727
vs. clinical factors, 724–725, 725f
detection of, 728
EGFR-targeted agents and efficacy in
EGFR-mutant cancers in,
727–728, 727t
genotype/phenotype correlations in, 731
identification of, 724, 724f
phase III trials of, 729–731, 730f
phase II trials of EGFR inhibitors in
EGFR -mutant NSCLC on,
728–729, 729t
990 INDEX
prognosis and clinical efficacy of EGFRtargeted
therapies and, 728
EGFR pathway, 124, 359–360, 359f
EGFR pathway inhibition, with COX-2
pathway inhibition, 219–220
EGFR signaling, 62–64, 63f
EGFR-TKI, 769
for recurrent/refractory NSCLC
alone, 679–680
plus chemotherapy, 680–681
EGFR tyrosine kinase inhibitors. See also
specific agents
plus chemotherapy, for advanced NSCLC,
656–657, 656t
research on, 715
EGF vaccines, 755t, 756t, 758–759
Eicosanoid signaling pathway, as vascular
target for radiotherapy, 199–200
Elderly, chemotherapy in
adjuvant, for completely resected NSCLC,
784–785
for advanced NSCLC, 654
for SCLC, 858–860, 859t
Elective nodal irradiation (ENI), 551
Electromagnetic navigation, for early
detection, 261–262, 262t
Electron cautery, ablational, 896–897
Electronic portal imaging devices (EPIDs),
562–563, 562f
Electron transfer dissociation (ETD) mass
spectrometry, 136–137
Embolization, systemic, after radiofrequency
ablation, 518
EML4-ALK fusion gene, in invasive
adenocarcinoma, 307–308
EML4-ALK fusion proteins, 65, 87
Emphysema, on lung cancer incidence,
14–15
Empyema, postresection, 540
Endobronchial ultrasound (EUS, EBUS)
for early detection
of central lesions, 260, 260f
of peripheral lesions, 261, 261t
for evaluation and staging, 429–430,
430t, 475
for stage II NSCLC, 475
Endobronchial ultrasound-guided bronchoscope,
419, 419f
Endobronchial ultrasound-guided
transbronchial needle
aspiration (EBUS-TBNA), for
mediastinal/hilar lymph node
sampling, 419–421, 419f
Endocarditis, nonbacterial thrombotic, in
NSCLC, 337
Endocrinologic paraneoplastic syndromes
in NSCLC, 333–335, 334t
in SCLC, 346–347, 346t
Endoscopic ablational therapies, 893,
896–899
brachytherapy, 898
cryotherapy, 898
electron cautery and argon plasma
coagulation, 896–897
laser therapy, 897
photodynamic therapy, 897–898, 897f
rigid bronchoscopy, 896, 896f
role of, 896
Endostatin, 122, 127–128
Endothelial cells
migration of, 116
in radiotherapy-related lung damage, 607
Endothelial progenitor cells (EPCs), 117
Endothelial sprouting, 116, 116f
Enhanced green fluorescent protein (eGFP)
mesenchymal stem cells, for
radiotherapy risk reduction,
631
Enterogenous cysts, mediastinal, 968, 968f
Environmental tobacco smoke (ETS), 7–8,
8t, 47, 212
Enzastaurin, 743
Epidemic, tobacco. See Tobacco epidemic
Epidemiology, 3–19, 47, 275, 777
descriptive, 3–6
age and gender, 3–4, 4f, 4t
international patterns, 5–6
race and ethnicity, 4–5, 4t, 5t
socioeconomic status, 5, 5t
gender in, 353–355
Asian data, 355
European data, 354–355, 355f
U.S. data, 353–354, 354f
gene–environment interactions in, 15,
18–19
genetic susceptibility in, 47–54 ( See also
Genetic susceptibility)
incidence in, 3
lifestyle and environmental factors in,
6–15
air pollution, 8–9
asbestos, 10, 11t, 13
environmental tobacco smoke, 7–8, 8t
indoor radon, 9
nonneoplastic lung diseases, 14–15,
16t–18t
nutrition and antioxidants, 13–14
occupational respiratory carcinogens,
9–10, 11t–12t
tobacco, 6–7
molecular biology in, 62
mortality in, 3
mortality trends in, 25, 26f
nontobacco-related carcinogenesis in,
33–41 ( See also Carcinogenesis,
nontobacco-related)
overview of, 211
patterns, mortality and incidence in, 3
prevention on ( See Prevention, populationbased)
quitting smoking in, 7, 25, 26f
of SCLC, 847
tobacco epidemic in, 23–31 ( See also
Tobacco epidemic)
U.S. cancer
female, 3, 4f, 4t
male, 3, 4f
Epidermal growth factor (EGF), 758
Epidermal growth factor receptor (EGFR).
See EGFR
Epidermal growth factor receptor (EGFR)
gene. See EGFR
Epidermal growth factor (EGF) vaccines,
755t, 756t, 758–759
Epigenetic changes, 95–107
airway abnormalities in, in lung field
carcinogenesis, 276
definition of, 95
DNA methylation in, 96–98 ( See also
DNA methylation)
genetic and epigenetic interactions in,
95–96, 96f
reversibility of, 95
therapy and, 107
Epigenetic lung cancer therapy, 107
Epigenetic regulation, 65–66
Epigenetics, 95
Epigenetic silencing, in molecular prognostication,
154–155
Epithelial to mesenchymal transition
(EMT), fibroblasts in, 172
Epothilones, plus radiotherapy on cell cycle,
194t, 196
EP2101 vaccine, 758
Equivalent pathophysiology of length (EPL)
method, 558
ERBB2, 84, 85
ERBB3, 84, 85
ERBB4, 84, 85
ErbB2/HER2/neu, in molecular
prognostication, 149
ERCC1, 787
mRNA expression and, 787
as predictor for platinum resistance,
684–685, 684f–686f
Erlotinib. See also EGFR inhibitors, patient
selection for
biomarkers for benefits from, 144, 144f
interstitial lung disease from, 719–720
on invasive adenocarcinoma, 307
for NSCLC, 164
completely resected, 785–786
gender and, 363–364, 364t
recurrent/refractory, 676–678, 676t,
677f, 678f
plus bevacizumab, 700–701
plus bevacizumab, with carboplatin, paclitaxel,
and radiotherapy, 772
plus carboplatin and paclitaxel, and
radiotherapy, 772
plus cisplatin and etoposide, and
radiotherapy, 772
EGFR mutations (continued )
INDEX 991
plus everolimus, 742
plus radiotherapy, 769, 772
Errors, in radiotherapy treatment
preparation
random, 552
systematic, 552
Erythema gyratum repens, in SCLC, 348
Erythema, in NSCLC, 336, 336t
Esophageal ultrasound (EUS), for evaluation
and staging, 429–430, 430t,
475
Estrogen and estrogen receptors, 357–360,
357f
aromatase in, 358–359
hormone replacement therapy in, 358
in lung cancer, 357–360, 357f
mechanisms of, 357, 357f
nongenomic estrogen signaling and
EGFR signaling pathway in,
359–360, 359f
on risk, 358
studies of, 357–358
on survival, 358
targeting of, 358
therapeutic implications of, 360
Ethnicity, on lung cancer incidence, 4–5,
4t, 5t
Etoposide
for advanced NSCLC, 646–647, 647t
cisplatin with, for limited-stage SCLC,
876
Evaluation, primary tumor. See also specific
cancers
CT for, in NSCLC, 378–383
chest wall invasion, 370f, 378–381,
379f–380f
mediastinal invasion, 370f, 381–383,
381f–382f
pleural invasion, 378, 379f
in predicting lobectomy vs. pneumonectomy
need, 383, 383f
MRI for, in NSCLC, 393–396
chest wall invasion, 393–394, 393f,
394f
vs. CT, 393
mediastinal invasion, 394–396
superior sulcus tumors, 394, 395f
Everolimus (RAD001), 741
plus erlotinib, 742
plus geftinib, 741
plus radiotherapy on cell cycle, 194t, 197
Excise taxes, 213
Exfoliated upper airway cells, for early
detection, 271
Exisulind, for SCLC, 856, 856t
Expression microarrays, for squamous
carcinoma, 296
Extensive-stage SCLC (ESCLC), 867
Extracapsular extension (ECE), 551–552
Extracellular matrix metalloproteinase
inducer (EEMMPRIN), 150
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