Table Of ContentCancer Treatment and Research
Series Editor: Steven T. Rosen
Karen L. Reckamp Editor
Lung
Cancer
Treatment and Research
Cancer Treatment and Research
Volume 170
Series editor
Steven T. Rosen, Duarte, CA, USA
More information about this series at http://www.springer.com/series/5808
Karen L. Reckamp
Editor
Lung Cancer
Treatment and Research
123
Editor
Karen L. Reckamp
Department ofMedical Oncology
City of Hope
Duarte, CA
USA
ISSN 0927-3042
Cancer Treatment andResearch
ISBN978-3-319-40387-8 ISBN978-3-319-40389-2 (eBook)
DOI 10.1007/978-3-319-40389-2
LibraryofCongressControlNumber:2016942037
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Contents
Lung Cancer Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Geena X. Wu and Dan J. Raz
Diagnosis and Molecular Classification of Lung Cancer . . . . . . . . . . . 25
Jaime Rodriguez-Canales, Edwin Parra-Cuentas and Ignacio I. Wistuba
Lung Cancer Staging and Prognosis. . . . . . . . . . . . . . . . . . . . . . . . . . 47
Gavitt A. Woodard, Kirk D. Jones and David M. Jablons
Surgical Treatment of Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . 77
Osita I. Onugha and Jay M. Lee
Treatment: Radiation Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Sagus Sampath
Chemotherapy for Advanced Non-small Cell Lung Cancer . . . . . . . . . 119
Martin F. Dietrich and David E. Gerber
Multimodality Therapy for NSCLC . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Lingling Du, Saiama N. Waqar and Daniel Morgensztern
Targeted Therapies for Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . . 165
Thomas E. Stinchcombe
Resistance to Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Gabriel Rivera and Heather A. Wakelee
Immunotherapy in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Emily H. Castellanos and Leora Horn
Palliative Care in Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Arvind M. Shinde and Azadeh Dashti
Management of Lung Cancer in the Elderly. . . . . . . . . . . . . . . . . . . . 251
Archana Rao, Namita Sharma and Ajeet Gajra
v
vi Contents
Multidisciplinary Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Megan E. Daly and Jonathan W. Riess
Small Cell Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Erica B. Bernhardt and Shadia I. Jalal
Lung Cancer Screening
Geena X. Wu and Dan J. Raz
Abstract
Lung cancer is the leading cause of cancer mortality in the United States and
worldwide.Sincelungcanceroutcomesaredependentonstageatdiagnosiswith
earlydiseaseresultinginlongersurvival,thegoalofscreeningistocapturelung
cancerinitsearlystageswhenitcanbetreatedandcured.Multiplestudieshave
evaluated the use of chest X-ray (CXR) with or without sputum cytologic
examination for lung cancer screening, but none has demonstrated a mortality
benefit.Incontrast,themulticenterNationalLungScreeningTrial(NLST)from
the United States found a 20 % reduction in lung cancer mortality following
three consecutive screenings with low-dose computed tomography (LDCT) in
high-risk current and former smokers. Data from European trials are not yet
available. In addition to a mortality benefit, lung cancer screening with LDCT
also offers a unique opportunity to promote smoking cessation and abstinence
and may lead to thediagnosesof treatable chronic diseases, thus decreasingthe
overalldiseaseburden.Therisksoflungcancerscreeningincludeoverdiagnosis,
radiation exposure, and false-positive results leading to unnecessary testing and
possible patient anxiety and distress. However, the reduction in lung cancer
mortality is a benefit that outweighs the risks and major health organizations
currentlyrecommendlungcancerscreeningusingage,smokinghistory,andquit
time criteria derived from the NLST. Although more research is needed to
G.X.Wu(cid:1)D.J.Raz(&)
DivisionofThoracicSurgery,CityofHope,Duarte,CA,USA
e-mail:[email protected]
G.X.Wu
e-mail:[email protected]
©SpringerInternationalPublishingSwitzerland2016 1
K.L.Reckamp(ed.),LungCancer,CancerTreatmentandResearch170,
DOI10.1007/978-3-319-40389-2_1
2 G.X.WuandD.J.Raz
clearlydefineandunderstandtheapplicationandutilityoflungcancerscreening
in the general population, current data support that lung cancer screening is
effective and should be offered to eligible beneficiaries.
Keywords
(cid:1) (cid:1) (cid:1)
Lung cancer Screening Computed tomography Cancer prevention
Contents
1 WhyScreenforLungCancer?............................................................................................ 2
2 ScreeningwithChestX-RayandSputumCytologicStudies............................................ 3
3 ScreeningwithLow-DoseCToftheChest....................................................................... 8
4 BenefitsandRisksofLDCTScreening.............................................................................. 14
5 GuidelinesforLDCTScreening......................................................................................... 17
6 Conclusions.......................................................................................................................... 19
References.................................................................................................................................. 19
1 Why Screen for Lung Cancer?
As the most common cause of cancer-related deaths in the United States and
worldwide,lungcancerisapublichealthproblemofglobalmagnitude.In2015,an
estimated221,200newcasesoflungcancerwillbediagnosedintheUnitedStates
and158,040deathswilloccurasaresultoflungcancer[1].Worldwide,1.6million
lung cancer-associated deaths were estimated in 2012 [1].
Five-yearrelative survival rate forlung cancer isonly17.4 %duetomore than
half of patients being diagnosed with distant disease by the time-associated
symptoms manifest. Lung cancer outcomes are highly dependent on stage at
diagnosis.PatientswithstageInon-small-celllungcancer(NSCLC)havefive-year
overallsurvivalofatleast60 %,whereasthosewithstageIVdiseasehavesurvival
of less than 5 % [2]. Tumor size in early lung cancer (stage I) has also been
identified as a predictor of nodal status and thus stage [3]. Incidentally detected
NSCLCinasymptomaticpatientstendstobesmaller,earlierstage,andhavesimilar
stage-specific overall survival as symptomatic disease [4, 5]. Data on
screen-detected lung cancer report stage I disease in 85 % of participants and
estimate 10-year overall survival to be 88 % [6].
Inadditiontohavinghighmorbidityandmortality,alongpreclinicalphase,and
improved survival with early-stage diagnosis,lungcancer also hasidentifiable risk
factors such as age and smoking history, which can be used for screening criteria.
All these characteristics suggest that screening may be effective in improving lung
cancer outcomes as it has for other malignancies including colon, breast, and cer-
vical. For screening to be considered beneficial, it must lead to the reduction in
LungCancerScreening 3
disease-specific and overall mortality. Effective screening ideally involves an
inexpensive, low-risk, and easily accessible test that is sensitive and specific for
detecting cancer initsearly stagesbefore symptoms manifest asadvanced disease.
Chest X-ray (CXR) with or without sputum cytologic analysis and low-dose
computed tomography (LDCT) have been studied as lung cancer screening tools,
and the evidence is presented in this chapter.
2 Screening with Chest X-Ray and Sputum Cytologic
Studies
Six randomized controlledtrials (RCTs)from the 1960sand 1970s haveevaluated
the use of CXR in lung cancer screening (Table 1). None of these studies clearly
demonstrated a benefit in lung cancer mortality, although most studies had
limitations due to methodological flaws [7]. The Northwest London Mass Radio-
graphy Service Study began in 1960 and was a prospective trial of 55,023 male
factory workers of variable smoking status (19 % former smokers, 67 % current
smokers)whowere40 yearsorolder.Ofthese,29,723wererandomizedtoreceive
CXRevery6 monthsand25,300wererandomizedtoacontrolgroupthatreceived
screeningatbaselineandat3 years.After3 yearsofscreening,lungcancerpatients
inthescreeninggrouphadahigherproportionofresectablelungcancerthanthose
from the control group (44 % versus 29 %, p = 0.03). Five-year survival rate was
alsobetterinlungcancercasesidentifiedbytheinterventionthaninthoseidentified
in the control group (23 % versus 6 %, p < 0.01). However, the annual mortality
rates fromall lungcancerswerenotsignificantlydifferent between thegroups (0.7
versus 0.8 deaths per 1000 person-years). Only 65 % of lung cancers in the
intervention group were identified by 6-monthly CXR [8, 9].
In 1964, the Kaiser Permanente Study randomized 5156 Kaiser Foundation
HealthPlanmenandwomenaged35–54 yearstobeencouragedtoundergoannual
multiphasic health checkups (including CXR), while a comparable group of 5557
members were not encouraged to do so. Patients were followed for 16 years, and
those in the intervention group had 6.8 mean checkups and a mortality of 8.6 per
1000person-yearscomparedtomean2.8checkupsandamortalityof7.6per1000
person-yearsintheparticipantsfromthecontrolgroup.Thedifferencedidnotmeet
statistical significance [10, 11].
Inthe1970s,4RCTsstudiedlungcancerdetectioninmalesmokersusingCXR
and sputum cytology. The Mayo Lung Project was the first study to evaluate the
intense use of these dual-screening tools in lung cancer screening; 10,933 partici-
pants aged 45 years or older underwent baseline (prevalence screening) CXR and
sputum cytologic examination from 3-day pooled samples, and 91 (0.83 %) lung
cancer cases were detected [12]. Following the prevalence round, 4618 men were
randomized into the intervention group (CXR and sputum cytologic examination
every 4 months for 6 years) and 4593 were assigned to the control group (annual
CXR andsputumtesting advised asusual care). Over the6-year study period, 206
and160newlungcancercaseswerediagnosedinthescreeningandcontrolgroups,
