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Pulmonary Complications of Cancer Treatment
Beth Zigmund, MD
1/12/2010
Objectives
PulmonaryComplicationsofCancer
Treatment
(Preliminary
PreliminaryVersion)
Version)
BethZigmund,MD
• Developawarenessofthemyriadpulmonarycomplications
ofcancertreatmentandofchallengeinmakingcorrect
diagnosis
• DescribeRadiationandChemotherapyͲInduced
Complications
• RadiationͲInducedComplications:RadiographicPatterns
– Conventionalwisdom
– Challengesofcurrentdeliverytechniques
– Patternsofinjury
– Challengesofnoveltherapies
PulmonaryComplicationsofCancer
Treatment
TUESDAY
• ChemotherapyͲInducedPulmonaryComplications
PulmonaryComplicationsofCancer
Treatment
• RadiationͲInducedPneumonopathy
• Radiation
RadiationͲͲInduced
InducedPneumonopathy
Pneumonopathy
• ChemotherapyͲInducedPneumonopathy
• Chemotherapy
ChemotherapyͲͲInduced
InducedPneumonopathy
Pneumonopathy
• Surgical
• Surgical
• Infectious:CommunityͲaquired,Atypical,
Aspiration
• Infectious:CommunityͲaquired,Atypical,Aspiration
• Pulmonaryemboli
• Pulmonaryemboli
PulmonaryComplicationsofCancer
Treatment
Lung
Cancer
Other
Cancers
PulmonaryComplicationsofCancer
Treatment
Lung
Cancer
Other
Cancers
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ElevatedRiskintheLungCancer
Patient
• Primaryneoplasmispulmonary:lungsurgeryprimarycurativemodality
• Underlyinglungdisease
CostofBetterTreatments
Aimtolengthensurvival,improvepalliation
Multimodality,multiregimen treatmentnow
standard
• Meanagemoreadvanced:~70%
~70%diagnosedat65yearsofageorgreater*
– Decreasingtissuemass
– Impaireddrugclearance
– GreaternumberofcoͲmorbidities
• Surgery
• Chemotherapy
• Radiationtherapy
MountingToxicity
TUESDAY
*Ries LAGetal.SEERCancerStatisticsReview1975Ͳ2000.
http://seer.cancer.gov/csr/1975_2000
New,escalatingrespiratorysymptoms
Recurrence
or
Progression
Drug
Toxicity
Diagnostc
Quandry
Recurrence
or
Progression
Radiation
Toxicity
Drug
Toxicity
Diagnostc
Quandry
Radiation
Toxicity
Infection
Infection
(CaseExample)
RadiationͲ
RadiationͲInducedToxicity
Radiotherapyindicatedinabout64%ofNSCLCpatientsoverall:
~46%initially,18%laterinillness
Radiotherapyindicatedinabout54%ofSCLCpatientsoverall:
45%initially,9%forrecurrenceorprogression
Tyldesley Setal.Estimatingtheneedforradiotherapyforlungcancer:anevidenceͲbased,
epidemiologicapproach.Int JRadiat Oncol Biol Phys2001;49:973Ͳ985
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RadiationTherapyRisks
•
IrradiationofnormallungmajordoseͲlimitingfactor
•
Typicaldose:60to70Gy totumorandlocalnodalmetastases
•
Invariablysomedamagetonormallung
•
Threshold for pneumonitis rangesfrom5to20Gy
Thresholdforpneumonitis
ranges from 5 to 20 Gy
•
50Ͳ90%ofpatientsundergoinglungirradiationdevelopradiographicorpulmonary
functionabnormalities*
•
Mechanismstillnotwellunderstood
*Tsoutsou etal.Int JRadiat Oncol Biol Phys.2006:66(5):1281Ͳ93.
FactorsInfluencingRisk
• Volumeofnormallungirradiated
• Cumulativedose
• Sizeoffractionsdelivered,scheduleofdelivery
Size of fractions delivered schedule of delivery
• Comcomitant chemotherapy:certainagentsin
particular
• PreviousIrradiation:lowersthreshold
• Geneticfactors?
TUESDAY
RadiationInducedLungToxicity
• Improvinggeometricaccuracyofdelivery
systems
– conformalRT
– intensitymodulatedRT
y
StagesofInjury
Acute,exudative
Acute,
exudative stage:Radiation
pneumonitis
0Ͳ2monthsaftertreatment
Steroidresponsive
• Complicationshavenotbeeneliminated.Ex:
Pneumonitis reportedin5Ͳ15%ofpatients
receivingexternalbeamradiationtherapyfor
lungcancer
Organizing,proliferativestage:Radiation
pneumonitis
2Ͳ9moaftertreatment
Steroidresponsive
Chronic,fibroticphase:Radiationfibrosis
>9moaftertreatment,stableafter24mo
Notsteroidresponsive;supportivetherapy
RadiologicManifestations:The
ConventionalW
onventionalWisdom
ConventionalRT
(ClinicalCaseImageslides)
(ClinicalExampleImageSlide)
Geographicmargins
Confinedtotheradiation
portal
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(CurrentRTTechniques:ImageSlides)
ChemotherapyͲͲInducedComplications
Chemotherapy
TUESDAY
Direct
Di t
Effects
ChemotherapyͲInducedComplications
Infection
DrugToxicity:ADifficultDiagnosis
• Directeffectsoftherapy:Incidencerangesfrom1to30%,
dependingonagent
• Overlap:Intercurrent infection,progressionoftumor,fluid
overload,pulmonaryedema,pulmonaryembolism
Di t
Direct
Effects
Infection
• Multidrugregimens:Difficulttoascribetoaparticularagent
• Nonspecificradiologicfindings,multiplepatterns
• Lessfrequentthanradiationtoxicity,butcanbefloridand
mayhavehighermortalityrate
• Consultwithreferringclinician!
(Imageslide– caseexample)
Agents(NSCLCandSCLC)
• Toxicitywelldescribedincertainestablishedagents:mitomycin,
bleomycin
• Novelchemotherapeuticagents
–
–
–
–
–
–
Antimetabolites:gemcitabine
Taxanes:paclitaxel,docetaxel
Topoisomerase IInhibitors:topotecan,irinotecan
I Inhibitors: topotecan irinotecan
Topoisomerase IIInhibitors:etoposide
TyrosineKinase EGFRInhibitors:erlotinib,gefitinib
VascularEndothelialGrowthFactorInhibitor:bevacizumab
• CombinationregimensnowthestandardforbothSCLCandNSCLC
• Clinicaltrialscontinuetorevealtoxicityprofilesofvarious
combinationregimens
• Higherresponseratesmaybeoffsetbygreatertoxicity
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Class
Agents
Observed Toxicities
Class
Agents
Observed PulmonaryToxicities
PlatinumAgents
Cisplatin
Carboplatin
Minor exceptwhenusedincombination
PlatinumAgents
Cisplatin
Carboplatin
Minor exceptwhenusedincombination;
variouspatternsincombination
regimens
Taxanes
Paclitaxel
Docetaxel
NSIP, InterstitialFibrosis,HP,DAD,
CapillaryLeakEdema,Eosinophilic
Pneumonia
Taxanes
Paclitaxel
Docetaxel
NSIP, InterstitialFibrosis,HP,DAD,
CapillaryLeakEdema,Eosinophilic
Pneumonia
Antimetabolites
Gemcitabine
NSIP, InterstitialFibrosis,DAD, DAH,
VenoͲocclusiveDisease
Antimetabolites
Gemcitabine
NSIP, InterstitialFibrosis,DAD, DAH,
VenoͲocclusiveDisease
Tyrosinekinase EGFR
Inhibitors
Gefitinib
Erlotinib
DAD,DAH
Tyrosinekinase EGFR
Inhibitors
Gefitinib
Erlotinib
DAD,DAH
Topoisomerase Inhibitors
Etoposide
Topotecan
Irinotecan
NSIP, BronchiolitisObliterans,DAD
Topoisomerase Inhibitors
Etoposide
Topotecan
Irinotecan
NSIP, BronchiolitisObliterans,DAD
MonoclonalAntibodies
Bevacizumab
DAH
MonoclonalAntibodies
Bevacizumab
DAH
www.pneumotox.com
www.pneumotox.com
Dimopoulou I,Bamias A,Lyberopoulos P,etal.Pulmonarytoxicityfromnovelantineoplastic agents.AnnOncol
2006;17:372Ͳ379.
Dimopoulou I,Bamias A,Lyberopoulos P,etal.Pulmonarytoxicityfromnovelantineoplastic agents.AnnOncol
2006;17:372Ͳ379.
TUESDAY
(ImageslidesͲvariouspatterns,various
agents)
PulmonaryDrugToxicity:Treatment
• Removeoffendingagent
• Steroids
• Supportivetreatment
Summary (CaseExampleImageSlide)
Summary
• Longdifferentialdiagnosisincancerpatientwith
respiratorycomplaints,lungcancerpatientin
particular
• Radiation
RadiationTherapy:continuedchallengedespite
Therapy: continued challenge despite
improvementsindeliverytechniques,confusing
radiologicpatterns
• Chemotherapy:widespectrumofabnormalities,
challengeposedbynewagentsandcombination
regimens
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KeyReferences
SpiroSG,DouseJ,ReadC,etal.ComplicationsofLungCancer
Treatment.Semin Respir Crit CareMed2008;29:302Ͳ318.
ParkKJ,ChungJY,ChunMS,Suh JH.RadiationͲinducedlungdisease
andtheimpactofradiationmethodsonimagingfeatures.
Radiographics 2000;20:83Ͳ98.
Dimopoulou I,Bamias A,Lyberopoulos P,etal.Pulmonarytoxicityfrom
novelantineoplastic agents.AnnOncol 2006;17:372Ͳ379.
Abeloff Metal.Abeloff’s ClinicalOncology,4th Edition.Philadelphia:
ChurchillLivingstone,2008.
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www.pneumotox.com
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