Cachexia
in NSCLC, 333
in SCLC, 346
Cadherins, 124
CA15-3, in malignant mesothelioma, 950,
950f
Cancer-associated retinopathy, in SCLC, 348
Cancer cell killing, 569
Cancer control. See Prevention,
population-based
Cancer stem cell (CSC) hypothesis,
163–168
caveats in CSC study and, 168
CSC biology in, 166–168
chemotherapeutic resistance in, 166–167
metastasis and, 167
molecular targets in, 167–168
transplantation and culture in
experiments on, 165–166
definition and overview of, 163
identifying CSCs in, 163–164, 164t
in NSCLC, 164–165
Canstatin, 119
Carbonic anhydrase IX, 115
Carboplatin
for malignant mesothelioma, 954
for NSCLC
advanced, 651–652, 651t, 652f
completely resected, 780–783, 780t,
783t
stage IIIB, in concurrent chemoradiotherapy,
828t, 829
Carboplatin-gemcitabine, for advanced
NSCLC, 646–647, 646t
Carboplatin-paclitaxel, for NSCLC
advanced, 646–647, 646t, 648t
completely resected, 780–783, 780t, 783t
stage III, plus radiotherapy, 580
Carboplatin-pemetrexed radiotherapy, 771
Carcinogenesis
from cigarette smoke carcinogens, 179
field, 275
lung field, 275–281
epigenetic airway abnormalities in, 276
history of, 275
lung cancer susceptibility and risk
stratification in, 276–277
prevention of, 277–281
basis of clinical strategies in, 277
clinical chemoprevention trials for, 277,
277t
future strategies in, 280–281
premalignancy reversal or secondary
prevention in, 278–279, 279t
primary chemoprevention studies in,
277–278, 278t
secondary primary tumor prevention
in, 279–280, 279t
principles of, 275–276
nontobacco-related, 33–41
arsenic in, 33–34
asbestos in, 34–35
beryllium in, 35–36
bis(chloromethyl) ether in, 36
chloromethyl ether in, 36
chromium in, 36–37
diesel exhaust in, 37
mineral oil in, 37–38
more information on, 40–41
nickel in, 38
radon in, 38–39
silica in, 39–40
vinyl chloride in, 40
tobacco-related, multistep pathway of, 215,
215t
Carcinogens. See specific carcinogens
Carcinoid syndrome, 976
Carcinoid tumors, 971–976
atypical
fine-needle aspiration cytology of, 246,
247f
molecular and cellular pathology of, 300,
300f
biologic behavior of, 974, 974t
classification of, 300, 971
clinical presentation of, 971–972
cytology of, 301
diagnosis of, 972, 972t
epidemiology of, 971
fine-needle aspiration cytology of,
246–248
in atypical carcinoids, 246, 247f
differential diagnosis of, 247–248
immunohistochemistry in, 246
in typical carcinoids, 246, 247f
INDEX 985
histology and molecular biology of,
972–974
atypical, 973, 973f
biologic behavior of, 973, 973f
as neuroendocrine tumors, 972
spindle cell peripheral, 973, 973f
typical, 973, 973f
typical vs. atypical, 973–974, 973t,
974t
immunohistochemistry of, 294t, 301
molecular and cellular pathology of
atypical, 300, 300f
typical, 300, 300f
precursor of, possible, 302
treatment of
adjuvant chemotherapy in, 975
with carcinoid syndrome, 976
histologic diagnosis and staging for, 974
with localized disease, 974–975, 975t
with locoregional unresectable disease,
975
with metastatic disease, 975–976
typical, molecular and cellular pathology
of, 300, 300f
Carcinoma-associated fibroblasts (CAFs), 172
Cardiovascular complications, postoperative,
541–544
cardiac arrhythmias, 542–543, 542t
cardiac herniation, 543–544
cardiac ischemia, 541–542
general considerations, 541
Carotene. See _-carotene
Carotenoids, 47, 216
Catheter, chronic indwelling pleural, for
malignant pleural effusion,
907, 907f
Cautery, electron, ablational, 896–897
CCI-779 (temsirolimus), 576, 741
plus radiotherapy on cell cycle, 194t, 197
for SCLC, 856–857, 856t
CD133, for identifying CSCs, 163–165,
165t
CDH13 hypermethylation, 105f, 106
Cdk inhibitors, 189, 190f, 192–193. See also
specific agents
CDK modulators, as radiotherapy targets,
194–195, 194t
CDKN2A. See p16
CDKN2A/p16 hypermethylation, 104, 105f
CDKN2A/RB pathway, 65
CDKN2 gene, 82, 83f, 946
Cediranib (AZD2171), 704t, 707
for malignant mesothelioma, 955
plus radiotherapy, 198, 198t, 770
Celecoxib
on colorectal cancer risk, 175
plus radiotherapy, 198t, 199–200, 772
Cell–cell adhesion molecules, 123–124
Cell cycle
lung cancer alterations of, 192–193, 192t
phases of, 572
Cell cycle checkpoints, 189–191, 190f, 191f
Cell cycle genes
in small cell lung carcinoma, 299
in squamous carcinoma, 295, 295t
Cell cycle regulation, 189, 190f
Cell cycle regulators, for SCLC, 856–857
Cell cycle signaling, ionizing radiation on,
189–191, 190f, 191f
Cell cycle targets, for radiotherapy, 189–197
cell cycle alterations and, 192–193, 192t
cell cycle signaling response to radiation
in, 189–191, 190f, 191f
in combined treatment, 194–197
CDK modulators in, 194–195, 194t
potential targets in, 194, 194t
principles of, 194
Cell killing
bystander, 569
cancer, 569
from radiation, 569
radiotherapy models of, 591–592
Cell survival curves, after radiotherapy,
569–571, 571f
conventional fractionated, 591
stereotactic body, 592
Cellular vaccines, 754
Central airway lesions, 287
Central airway lesions, precursor, 287–288
Central bronchi tumors histopathology,
287–288, 288f
Central nervous system management in
NSCLC, after successful
therapy, 839–842
prophylactic cranial irradiation in, 839–842,
840t
routine CNS imaging in, 839
standard follow-up in, 839
Central nervous system metastases
brain ( See Brain metastases)
intramedullary spinal cord, 923–924
management of, 911–924
brain metastases, 911–920 ( See also Brain
metastases, management of)
intramedullary spinal cord metastasis,
923–924
radiosurgery boost trials on, 914t
spinal cord compression
corticosteroids in, 921
radiotherapy in, 921–922
surgery in, 922–923
surgical resection in, 913t
whole-brain radiotherapy in, 912t, 916t
spinal cord compression, 920–923
clinical presentation, diagnosis, and
prognosis with, 920–921
pathophysiology of, 920
Central nervous system metastases in NSCLC
age on, 837–838
clinical presentation, diagnosis, and
prognosis with, 911, 912t
histology of, 837
incidence of, 837, 838t
locoregional and systemic therapy timing
and, 839
overview of, 837
survival duration with, 838, 838t
time to CNS failure in, 838
Ceramide signaling pathway, as vascular
target for radiotherapy, 200
Cetuximab, 715
Cetuximab plus radiotherapy, 767–769,
768f, 771–772
c- fos, in malignant mesothelioma, 946
Chemically induced mouse models of lung
cancer, 179–181
Chemoattractants, 118
Chemokines, 123
Chemoprevention, 15, 214–217
clinical trials on, 277, 277t
conceptual basis for, 214–215
history and definition of, 215
primary studies on, 277–278, 278t
strategies for, 215–217
budesonide/fluticasone, 217
carotenoids, 216
COX inhibitors, 215–216
diet and nutrition, 215
other agents, 217
overview, 215
retinoids/vitamin A, 216–217
selenium, 217
statins, 216
tocopherols/vitamin E, 217
Chemopreventive nutrients, 13–14
Chemoradiotherapy, concurrent. See also
specific agents and cancers
for limited-stage SCLC, 867–878
early, 872t
evolution of, 868–874
addition of prophylactic cranial
irradiation, 873–874
combination chemotherapy with
adjuvant thoracic radiation,
869–870
integrated early concurrent chemotherapy
and radiotherapy,
870–873, 872t
surgery as standard treatment,
868–869
thoracic irradiation better than
surgery, 869
thoracic irradiation with adjuvant
chemotherapy, 869
future research on, 876–877, 877t
thoracic radiotherapy volume and dose
in, 874–876, 875f
for NSCLC, 559
for NSCLC stage IIIB
single-agent carboplatin in, 828t, 829
single-agent cisplatinum in, 827–828,
828t
for NSCLC stage IIIB treatment, 827–831
986 INDEX
biological rationale of, 827
vs. sequential chemoradiotherapy,
829–830, 829t
as systemic control, 830–831, 831t
toxicity profiles of, 830
Chemotherapy. See also specific agents and
cancers
adjuvant ( See Adjuvant chemotherapy)
combination, with adjuvant thoracic
radiation for limited-stage
SCLC, 869–870
individualized, 683–684, 684f
neoadjuvant ( See Neoadjuvant
chemotherapy)
pulmonary effects of, 252f, 253
second-line ( See also Chemotherapy, for
NSCLC, recurrent/refractory)
for recurrent/refractory NSCLC, vs.
EGFR-TKI, 679–680
on survival and quality of life, 669–671,
670t, 671f
sequencing of, 574–575, 575f
single nucleotide polymorphisms on, 689
tumor cell repopulation after, 575
Chemotherapy, for NSCLC, advanced,
645–662
combined, plus targeted therapies, 656–661
EGFR tyrosine kinase inhibitors, 656–657,
656t
HER-1/2 antibodies, 657–658, 658t
insulin-like growth factor receptor
inhibitors, 658t, 659
matrix metalloproteinases, 658–659, 658t
toll-like receptor 9 antagonists, 658t,
659
vascular endothelial growth factor
inhibitors, 659–661, 659t, 660f
in elderly patients, 654
evolution of, 646–654
cisplatin vs. carboplatin, 651–652, 651t,
652f
duration of therapy, 648–650, 649t,
650f
maintenance therapy, 650–651, 651t
new agents and trials, 646–647, 646t,
647t
platinum vs. non–platinum-containing
chemotherapy, 653, 653f
triplet vs. doublet platinum-based drug
combinations, 648, 649t
tumor-related symptom palliation,
653–654
historical background on, 645–646
personalizing, 661–662, 662t
in poor performance status patients,
654–656, 655t
Chemotherapy, for NSCLC, recurrent/
refractory, 669–680
combination, 674–676, 675t
docetaxel ( See also Docetaxel)
dose and schedule of administration of,
671–672, 672t
evidence for, 669–671, 670t, 671f
dose and schedule of administration of,
671–672, 672t
EGFR inhibitors, 676–678, 676t, 677f,
678f
historical background on, 669, 670t
pemetrexed, 672–674, 673f
second-line vs. EGFR-TKI, 679–680
on survival and quality of life, 669–671,
670t, 671f
targeted agents plus, 680
topotecan, 674
vinflunine plus docetaxel, 674
Chemotherapy, for SCLC, 847–861
biological therapy, 854–858
angiogenesis inhibitors, 857–858, 857t
apoptotic modulators, 856, 856t
cell cycle regulators, 856–857
immunotherapy, 855–856, 855t
matrix metalloproteinase inhibitors, 855,
855t
tyrosine kinase inhibitors, 854–855,
855f
combination, 847–853
alternating non–cross-resistant
chemotherapy in, 852
dose intensification in, 850–852, 850t
history and overview of, 847–849
novel, 849–850, 849t
treatment duration and maintenance
therapy in, 852–853
in elderly, 858–860, 859t
in poor performance status patients,
860–861
second-line, 853–854, 853t
single-agent, 847, 848t
survival with, 847
Chemotherapy, for SCLC, limited-stage
multiagent, 876
multiagent with radiotherapy, 876
Chemotherapy, neoadjuvant
for malignant mesothelioma, 953
rationale for, 791
for thymomas, locally advanced, 937
Chemotherapy, preoperative, for early-stage
NSCLC, 791–797
background on, 791
early studies on, 791–792
rationale for, 791
recent evidence on, 793–795, 794t, 795f
surgical morbidity and mortality after,
792–793
systematic reviews and metaanalysis of,
795–796, 796f, 796t
Chemotherapy/radiation, preoperative, for
early-stage and locally advanced
NSCLC, 799–816
arguments against, 799
background on, 799
for locally advanced stage IIIA/IIIB
cancer, 800–807 ( See also
Induction therapy, for stage
IIIA/IIIB NSCLC)
phase III trials of
chemoradiotherapy with/without
surgery, 810–812, 811t
third-generation chemoradiotherapy
agents, 812–813, 812t
phase II trials of, ongoing and planned,
816
radiotherapy in induction regimen in,
809–810
randomized trials of, surgery alone vs.
induction therapy plus surgery,
mixed-stage, 807–809, 808t
treatment-related morbidity/mortality in,
814–816
after 30-day postoperative period, 815
in 30-day postoperative period, 814–815
during induction therapy, 814
reducing radiotherapy morbidity in,
815–816
Chest pain, in NSCLC, 328–329
Chest radiography, single-exposure,
dual-energy digital, 370
Chest radiotherapy (CRT)
beam arrangements/aids in, 555–557,
556f
3D, planning target volume in, 556
Chest radiotherapy timing, 574–575, 575f
Chest tube
drainage via, for malignant pleural
effusion, 904, 905f
placement of, after radiofrequency
ablation, 517–518
Chest wall
invasion of
CT evaluation of, 370f, 378–381,
379f–380f
MRI evaluation of, 393–394, 393f,
394f
reconstruction of, for Pancoast tumors,
487
resection of, for NSCLC stage II,
477–478
Chk1 inhibitors, plus radiotherapy on cell
cycle, 194t, 195
Chloromethyl methyl ether (CMME), lung
cancer from, 11t, 36
Cholesterol consumption, on lung cancer
incidence, 15
Chromatin, salt and pepper, 298
Chromium, lung cancer from, 11t, 36–37
Chromosomal aberrations, 61t
Chromosomal-based CGH (cCGH), 76
Chromosomal structural alterations,
detection of, 75–76, 76f
Chromosome 3p deletion, 82, 84f
Chromosome 3p tumor suppressor genes,
65, 82, 84f
Chemoradiotherapy, concurrent (continued )
INDEX 987
Chromosomes, preneoplastic heterogeneity
and instability of, 290–291,
290f, 291f
Chronic indwelling pleural catheter, for
malignant pleural effusion,
907, 907f
Chronic inflammation, on lung cancer
incidence, 14–15
Chronic obstructive pulmonary disease
(COPD)
gender on lung cancer from, 356
on lung cancer incidence, 14–15, 16t–18t
from tobacco, 23
Chylothorax, postoperative, 540–541
CI-1040, 744
Cigarette smoking. See also Epidemiology;
Tobacco
chronic obstructive pulmonary disease
from, 14–15
EGFR mutations in NSCLC and, 726–727
emphysema from, 14–15
lung cancer from, 47–48, 179, 211
( See also Tobacco)
on lung cancer mortality, 25, 25f–27f
per capita trends of, 25, 25f
quitting ( See Smoking cessation)
squamous cell carcinoma from, 241
tobacco consumption via, 24–25, 25f
Cigar smoking
lung cancer from, 7
smoke content in, 6
Circulating endothelial cells (CECs), 115
Circulating endothelial progenitor cells
(CEPs), 115, 117, 125
Cisplatin, 684, 684f
biomarkers for resistance to, 684–688,
684f–686f, 687t
for malignant mesothelioma, 953
for NSCLC
advanced, 646–647, 646t–648t,
651–652, 651t, 652f
completely resected, 780–783, 780t,
783t
for NSCLC stage III
plus radiotherapy, 580
plus resection, 580
for SCLC, limited-stage, 876
Cisplatin-docetaxel, for advanced NSCLC,
646–647, 646t–648t
Cisplatin-etoposide
for advanced NSCLC, 646–647, 647t
for limited-stage SCLC, 876
Cisplatin-gemcitabine, for advanced
NSCLC, 646–647, 647t, 648t
Cisplatin-irinotecan
for advanced NSCLC, 646–647, 647t, 648t
for recurrent/refractory NSCLC, 674, 675t
Cisplatin-paclitaxel, for advanced NSCLC,
646–647, 647t, 648t
Cisplatin-teniposide, for advanced NSCLC,
646–647, 647t
Cisplatinum, in concurrent chemoradiotherapy
for stage IIIB NSCLC,
827–828, 828t
Cisplatin-vinblastine-mitomycin, in
completely resected NSCLC,
780–783, 780t, 783t
Cisplatin-vindesine, for advanced NSCLC,
646–647, 647t
Cisplatin-vinorelbine, for advanced NSCLC,
646–647, 647t, 648t
c- jun, in malignant mesothelioma, 946
CK7, in invasive squamous carcinoma,
294t, 295
CK20, in invasive squamous carcinoma,
294t, 295
c-Kit, 739, 744
CK19 tumor marker, 142
Classification, of lung cancer, 164. See also
specific cancers and diagnostic
techniques
radiographic, 426, 427f
WHO, 314t–315t
Clinical presentation. See specific cancers
Clinical target volume (CTV), 551
determination of, 551–552
in stage III NSCLC
around nodal disease, margins in, 582
around primary tumor, 582
in stereotactic body radiotherapy, 593
Clonogenic cancer cells, 163. See also
Cancer stem cell (CSC)
hypothesis
Clubbing
in NSCLC, 336
in SCLC, 346t, 348
c-Met, 64, 86, 739, 743–744
Coal-burning heating devices, lung cancer
from, 9
Collagen formation from radiation,
prevention of, 632–633
Combination chemotherapy. See
Chemotherapy; specific agents
and cancers
Combined small cell carcinoma, fine-needle
aspiration cytology in, 249
Combustion-source air pollution, on lungs,
8–9
Comparative genomic hybridization
(CGH), 76–78, 76f
Complications. See Surgical complications;
specific disorders and treatments
Comprehensive tobacco control programs.
See also Smoking cessation
outcomes of, 214
Compton effect, 569, 570f
Compton scattering, 569, 570f
Computed tomography (CT)
4D
with intensity-modulated radiotherapy
(IMRT), for radiotherapy risk
reduction, 629–630, 630f
navigational techniques in, for diagnosis
and evaluation, 418
for NSCLC
hilar nodal involvement in, 474
stage II evaluation and staging, 474
with PET ( See PET/CT)
Computed tomography (CT), of NSCLC,
378–392
for hilar and mediastinal lymph node
evaluation, 383–390
clinical T1N0M0 patients, 391
criteria for lymph node metastasis
detection, 383–385, 385f
distant metastases, 390–391, 391f
hilar metastases (N1 disease), 380f,
385–386, 385f, 386f
mediastinal metastases (N2/N3 disease),
380f, 386–390, 386f–388f, 389t
predicting resectability, 392
pretreatment CT usefulness, 392
significance, 383
therapeutic response evaluation, 392
for primary tumor evaluation, 378–383
chest wall invasion, 370f, 378–381,
379f–380f
mediastinal invasion, 370f, 381–383,
381f–382f
pleural invasion, 378, 379f
for predicting lobectomy vs.
pneumonectomy need, 383,
383f
for tumor vs. adjacent atelectasis/
pneumonia differentiation, 383
Computed tomography (CT) screening,
217–218, 226–227. See also
Screening, lung cancer
diagnostic and prognostic performance of,
229, 230t
guidelines for, 228–229
low-dose
incidence screen protocol, 238–239,
238t, 239t
NELSON Management System
(NMS), 236–238, 237t, 238t
baseline screen protocol, 237–238,
237t
image reading, 236–237
screens, 236
NELSON trial, 233–239
NELSON trial design, 233–235
overview, 233
participant selection, 233–235
power and required sample size, 235
recruitment, 233, 234f, 235t, 236t
NODCAT 4 and GROWCAT C
nodule management, 239, 239t
Computer-aided diagnosis (CAD) for
NSCLC, 369–371
Conditionally replicating oncolytic
adenoviruses (CRAds), in mice,
182, 182f
988 INDEX
Continuous hyperfractionated accelerated
RT (CHART), 559
Copy number, aberrant, DNA-based
genome-wide search for, 266
Corticosteroids
for CNS metastases, 911–912
for cough in NSCLC, 328
for spinal cord compression, metastatic,
921
Cough, in NSCLC, 327–328
COX-2 inhibitors
as chemoprevention, 215–216
on lung cancer risk, 216
COX-2 pathway inhibition, with EGFR
pathway inhibition, 219–220
CP-751,871, 740
CpG dinucleotides, 96–97
CpG island hypermethylation, 97, 100,
154
Cranial irradiation, prophylactic, 561, 575
neurotoxicity and quality of life with,
886–887, 886t, 887f, 888t
for NSCLC, 837–842
brain/CNS metastases and
locoregional and systemic therapy
timing on incidence of, 839
overview of, 837
risk of, 837–839, 838t
survival with, 838, 838t
CNS management after successful
therapy and
routine CNS imaging in, 839
standard follow-up in, 839
toxicity of, 841–842
trials on, 839–842, 840t
overview of, 839–840, 840t
prospective, 840–841, 840t
retrospective reviews of, 840t, 841
for SCLC, 883–888
limited-stage, 873–874
metaanalysis of, 885–886
neurotoxicity and quality of life with,
886–887, 886t, 887f, 888t
studies on, 883–885, 884t
timing of, 575
value of, 883
Cryoablation, 898
for NSCLC
clinical results of, 514
mechanism of, 510–511
technique for, 512
Cryotherapy, 898
CSCs. See Cancer stem cell (CSC)
hypothesis
CT. See Computed tomography (CT)
CT density, assessing regional lung function
with, 618, 618f
C-terminal fragments, as antiangiogenic
agents, 122
cTNM, 437
Curability, screening on, 227–228
Cushing syndrome
ectopic, in NSCLC, 335
paraneoplastic, in SCLC, 346–347
C-X-C chemokine family, 123
CXCL12, 117, 123
CXCR4, in metastasis, 167–168
Cyclin B1, in molecular prognostication,
148
Cyclin D1
Cdk inhibitors on, 192–193
in lung cancer, 192
in molecular prognostication, 148
Cyclin-dependent kinases (Cdks), 189, 190f
Cyclin E, in molecular prognostication, 148
Cyclophilin B (CypB), 760
Cyclophilin B (CypB) vaccine, 755t, 756t,
760–761
CypB peptides, 760
Cytokeratin 19 fragment (CYFRA 21-1),
for radiation sensitivity risk
prediction, 629
Cytokeratin (CK), in invasive squamous
carcinoma, 294–295, 294t
Cytokines. See also specific cytokines
inflammatory
for radiation sensitivity risk prediction,
628–629
in radiotherapy-related lung damage,
610–611
in radiation-induced lung damage, 609
for radiotherapy risk reduction, 631
Cytology, pulmonary. See also specific cancers
pitfalls in, 250–254
acute lung injury, 252
asthma, 253
chemotherapy and radiation effects,
252f, 253
diffuse alveolar damage, 252–253
false-negative diagnosis, 250
false-positive diagnosis, 251, 251f
infections
cytomegalovirus, 252
fungal, 251, 251f
mycobacterial, 251–252
parasitic (dirofilariasis), 252
Pneumocystic pneumoniae, 252
lipoid pneumonia, 253
megakaryocytes, 253–254
mesothelial cell proliferations, 253
pulmonary embolism/infarction, 253
pulmonary hamartomas, 253
type II pneumocytes vs. malignancy, 253
vegetable contaminant, 253
Wegener’s granulomatosis, 252
sensitivity and specificity of, 250
Cytomegalovirus infection, pulmonary, 252
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