disclaimer about preliminary versiondisclaimer about preliminary version the following article has...
TRANSCRIPT
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Disclaimer about preliminary version
The following article has been accepted after peer review for publication in JCO Oncology Practice. This preliminary version has been posted with author permission and will be replaced with the final published manuscript, after which this preliminary version will be removed. This version, including any author disclosures should be considered preliminary and may contain errors.
Suggested citation: Singh, A., Berman, A., Marmarelis, M., et al. Management of Lung Cancer during the COVID-19 Pandemic DOI: 10.1200/OP.20.00286 JCO Oncology Practice
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ManagementofLungCancerduringtheCOVID-19PandemicAditiP.Singh1,2,AbigailT.Berman2,3,MelinaE.Marmarelis1,2,AndrewR.Haas4,
StevenJ.Feigenberg2,3,JenniferBraun2,ChristineA.Ciunci1,2,JoshuaM.Bauml1,2,
RogerB.Cohen1,2,JohnC.Kucharczuk5,LawrenceN.Shulman1,2,CoreyJ.Langer1,2,
CharuAggarwal1,2
1DivisionofHematology-Oncology,DepartmentofMedicine,Universityof
Pennsylvania,Philadelphia,PA2AbramsonCancerCenter,Philadelphia,PA3DepartmentofRadiationOncology,UniversityofPennsylvania,Philadelphia,PA4DivisionofPulmonary,Allergy,andCriticalCare,DepartmentofMedicine,
UniversityofPennsylvania,Philadelphia,PA5DepartmentofSurgery,UniversityofPennsylvania,Philadelphia,PA
CorrespondingAuthor:CharuAggarwal,MD,MPH
LeslyeM.HeislerAssistantProfessorofMedicine
DivisionofHematology/Oncology
UniversityofPennsylvania
10-137,SouthPavilion
3400CivicCenterBoulevard
Philadelphia,PA19104
Tel:215-662-6318|Fax:215-349-5326
Acknowledgements:TheauthorsthankTomOliver,NofisatIsmalia,andmembersoftheASCOThoracic
GuidelinesAdvisoryGroupfortheirvaluablefeedbackandreviewoftheguidelines
outlinedinthismanuscript.
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Abstract
Coronavirusdisease–2019(COVID-19)hashadadevastatingimpactacross
theworld.Withhighratesoftransmissionandnocurativetherapiesorvaccineyet
available,thecurrentcornerstoneofmanagementfocusesonpreventionbysocial
distancing.Thisincludesdecreasedhealthcarecontactforpatients.Patientswith
lungcancerareaparticularlyvulnerablepopulation,wheretheriskofmortality
fromcancermustnowbebalancedbythepotentialriskofalife-threatening
infection.Intheseunprecedentedtimes,acollaborativeandmultidisciplinary
approachisrequiredtostreamline,butnotcompromisecare.Wehavedeveloped
guidelinesatouracademiccancercentertostandardizemanagementofpatients
withlungcanceracrossourhealthcaresystemandtoprovideguidancetothelarger
oncologycommunity.Werecommendthatgeneralprinciplesoflungcancer
treatmentcontinuetobefollowedformostcaseswheredelayscouldresultinrapid
cancerprogression.Werecognizethatourrecommendationsmaychangeovertime
basedonclinicalresourcesandtheevolvingnatureoftheCOVID-19pandemic.In
principle,however,treatmentparadigmsmustcontinuetobeindividualizedwith
carefulconsiderationofrisksandbenefitsofcontinuingoralteringlungcancer-
directedtherapy.
Introduction
Coronavirusdisease–2019(COVID-19),thediseasecausedbythesevere
acuterespiratorysyndromecoronavirus2(SARS-CoV-2),wasdeclaredapandemic
onMarch11,20201afteritwasfirstreportedinWuhan,China,inDecember2019.
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AsofApril15,2020,therehavebeennearly2millionconfirmedcasesofCOVID-19
andover123,000attributabledeathsworldwide1.Clinicalpresentationcanrange
fromminimalsymptoms,fever,fatigue,anosmiaandshortnessofbreathtomulti-
organandrespiratoryfailurerequiringmechanicalventilation.Althoughseveral
drugsareunderactiveinvestigation,noestablishedtreatmentexistsforthedisease
otherthansupportivecareandpreventivestrategies.SinceSARS-CoV-2spreads
primarilyviadroplets,themostimportantpreventativemeasuresarephysical
distancingandlimitingperson-to-personcontact.Giventherapidandhigh
transmissibility2,thispandemichasoverwhelmedthehealth-caresystemsofmany
countriesincludingtheUnitedStates3.
EarlyreportsfromChinaandItalyindicatethatpatientswithcancermight
bemoresusceptibletoCOVID-19andhaveinferioroutcomescomparedtopatients
withoutcancer.Inastudyof355deathsattributabletoCOVID-19inItaly,20%had
activecancer4.Of1590hospitalizedpatientcasesofCOVID-19inastudyfrom
China,18patients(1%)hadcancer,higherthanthe0.29%incidenceofcancerinthe
overallpopulation5.Patientswithcancerhadmuchhighermorbidityandmortality
asdefinedbyacompositeendpointofintensivecareunit(ICU)admissionsor
ventilatorrequirementanddeath(39%vs.8%,p=0.0003)5.Patientswithcancer
whoreceivedanti-tumortherapyincludingsurgery,radiation,chemotherapy,
immunotherapyortargetedtherapyinthe14dayspriortoSARS-CoV-2infection,
seemedtohaveworseoutcomes6.
Althoughthelong-termimpactofSARS-CoV-2infectiononcanceroutcomes
isunknown,therearecertainpopulationsthatmightbemoresusceptiblethan
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others.Patientswithlungcancerrepresentonesuchparticularlyvulnerablegroup
duearelativelyolderageatpresentation,presenceofbaselinecompromisein
pulmonaryfunctionandotherco-morbidities.Tomakemattersmorechallenging,
patientswithlungcanceroftenhavesymptomsthatoverlapwithCOVID-19(e.g.,
coughandshortnessofbreath),potentiallycausingadelayindiagnosis.Finally,
radiographicfindingsofCOVID-19maybeindistinguishablefrompneumonitis
causedbylungcancertherapeuticsincludingimmunotherapy,radiationandoral
tyrosinekinaseinhibitors7.
Thecurrentchallengeintreatingpatientswithlungcanceristheneedto
balancetheriskofapotentiallylife-threateninginfectionwithCOVID-19,againstthe
direconsequencesofdelayingornottreatingalife-threateningmalignancy.
Regionaldataoncommunityspread,testingcapabilities,resourceavailability
(includingpersonnel,personalprotectiveequipment,operatingroom/infusion
roomspaceandcriticalcareresources),andtheabilitytodelivertreatmentssafely
havetobefactoredintodecision-making.Whilewehaveextensivetreatment
guidelinesforthestandardmanagementoflungcancerfrommultiplesources,at
thiscriticaltimewemayneedtodeviatefromthisstandardofcareaswetryto
balancetheriskofCOVID-19andmortalityfromlungcancer.Amulti-disciplinary
collaborationisessentialtodevelopsafeandeffectiveguidelines.Workingwithour
colleagues,wehavedevelopedaworkflowtostandardizethedeliveryof
multidisciplinarycareforpatientswithNon-SmallCellLungCancer(NSCLC),Small
CellLungCancer(SCLC)andNeuroendocrineTumors(NETs)duringthispandemic.
Theseguidelinesarebasedonthefollowingprinciples:1)continuetotreatlung
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cancerwithmoderntechniquesandprinciplesalignedwiththemostup-to-date
research;2)maximizephysicaldistancing;and3)applyrecentadvancesin
radiationtechniquessuchasshorterfractionationschedules,andpersonalized
systemictherapeuticoptionswithoutsacrificingoncologicendpoints.This
consensushasbeenachievedthroughmultiplediscussionswithourteamofmedical
andradiationoncologists,thoracicsurgeons,interventionalpulmonologistsand
radiologistsandisalsobased,inpart,onpeer-reviewedliteraturethatappliesto
ourpopulationofpatients.Ourrecommendationsareintendedasaguide–wemust
continuetoindividualizediagnosticandtherapeuticapproachesforeachpatient
especiallywhenexceptionsaremadetotheestablishedstandardsofcare.
DiagnosisandStaging
Werecommendpursuingimage-guidedtransthoracicbiopsiesforinitial
diagnosisoflungcancerovertransbronchialapproachestominimizegenerationof
aerosolsandlimitSARS-CoV-2transmission8.Non-invasivemediastinalstagingwith
imaging(CTorPET)ispreferredwherepossibleandifinvasivetestingisfelttobe
essential,mediastinoscopymay,incertaincircumstances,bepreferredover
bronchoscopy.Nodalstagingviaendobronchialultrasound(EBUS)forthe
radiographicallysilentmediastinum,withnoapparentinvolvementonCTorPET,
maybeomitted;andforstageIIIdisease,wherenodaldiseaseisradiographically
apparent,confirmationwithEBUSmaynotberequired9.Althoughtissuediagnosis
isstillthe‘goldstandard’fordiagnosisoflungcancer,ifresourcesareextremely
limited,considerationcouldbegiventouseplasma-basedgenotypingtodirect
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therapeuticcare,especiallyifadrivermutationisdetectedforcertainphenotypes
(e.g.,never-smoker,Asian,female)andtheradiographicfeaturesofalungcancer
arethoughttobeunequivocal(e.g.,spiculatedlungmass),10.
ManagementofEarlyStageNSCLC
Themainstayofmanagementofearlystage(stageIorII)NSCLCremains
surgicalresection.TheAmericanCollegeofSurgeons(ACS)hasdeveloped
guidelinesregardingthoracicsurgeryduringCOVID-1911.Recommendationsare
basedonthreephasesofthepandemic.PhaseIconsistsoffewhospitalizedCOVID-
19patientswithadequatehospitalresourcesandICUventilatorcapacity.PhaseIIis
manyhospitalizedCOVID-19patientscoupledwithlimitedICUandventilator
capacityorwhenthelocal/regionalcasetrajectoryisonasteepupwardtrend.In
PhaseIII,allhospitalresourcesarealreadyexhaustedorbeingdivertedtothecare
ofCOVID-19patients.Therearesignificantregionaldifferencesinthesephases,and
recommendationsformanagementwouldnaturallyhavesomegeographic
variations.
ForareasinphaseI,theACSrecommendscontinuingsurgeryasplannedfor
patientswithsolidorpredominantlysolidlungnodules>2cminmaximum
dimensionandinthosewithnodepositivedisease.Theyalsorecommend
continuingtoperformstagingmediastinoscopyanddiagnosticVATS.Surgical
managementofpredominantlygroundglassnodules,solidnodules<2cmand
indolenthistologylikecarcinoidsorslowlyenlargingnodulesshouldbedeferred.
EmergingevidencesuggeststhatsurgicalmortalityinpatientswithCOVID-19
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infectionmaybehigher12.Wherepossible,alternativetherapiescanbeusedsuchas
stereotacticbodyradiationtherapy(SBRT)forpatientswithstageINSCLC13.SBRT
hastypicallybeengivenin45-54Gray(Gy)/3fractionsor48-50Gy/4or5fractions.
Datafromtrialssupportthedelivery30-34Gy/1fractioninselectpatients,which
hascomparedfavorablyto3and4fractionregimensandisanoptiontodecrease
exposureriskstopatients,providersandsupportstaff14(Table1).
ForpatientswithNSCLC,whereadjuvantchemotherapyisindicated,we
recommenddelayingadjuvanttherapybyupto4monthsafterresectionbasedon
retrospectivedatademonstratingsimilarefficacyandsafetyastheusualstandardof
careof6-12weekspost-surgery15.Adjuvanttherapyshouldbereconsidered
altogetherinpatientswhoareolderthan75years(sincemanyadjuvant
chemotherapytrialsexplicitlyexcludedthissub-populationandthebenefitsof
cisplatin-basedtherapyinthisagegroupmaybeminimal)16,17andfrailpatientsor
thosewithnode-negativediseasewhererisksofchemotherapymightpotentially
outweighbenefits16.Induction/neoadjuvantchemotherapymaybeconsideredif
surgeryisnotpossibleintheshorttermduetolimitedhospitaloroperatingroom
(OR)capacity18(Table1).
ManagementofLocallyAdvancedNon-SmallCellLungCancer
PatientswithlocallyadvancedNSCLCrequireamulti-disciplinaryapproach
andshouldbetreatedwithcurativeintent.Forpatientswheretri-modalitytherapy
isanoption(youngerpatientswhomaybealobectomycandidatewithno
significantcomorbiditiesandsinglestationnon-bulkymediastinalinvolvement],we
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recommendinductionchemotherapyalonefollowedbysurgeryandpost-operative
radiationtherapyoverconcurrentchemo-radiationfollowedbysurgery.Hospital
resources,includingaccesstoOR,andventilatorsmustbetakenintoaccountduring
decision-making.Forpatientswithmoreadvancedunresectabledisease,we
recommendthattheyreceiveconcurrentchemo-radiationfollowedby
immunotherapywithdurvalumabforuptoone1year19.Forconcurrentchemo-
radiation,tominimizepatientexposurewerecommendtheuseofaneverythree-
weekplatinum-basedregimenoveraweeklyschedule20.Infrailpatientsorthose
withmajorco-morbidities,weprefersequentialchemotherapywithgrowthfactor
supportfollowedbyradiationinsteadofconcurrentchemo-radiation.Typical
radiationdosesare60-66Gy/30-33fractionswhengivenconcurrentlywith
chemotherapy.Severalstudiesoverthepast5yearshaveinvestigated
hypofractionationschemes,suchas60Gy/24fractionsor55Gy/20fractionswith
concurrentchemotherapyorupto60Gyin15fractionswhendelivered
sequentiallywithchemotherapy;theseschemeshaveshownbothsafetyand
comparable2-yearsurvivalratesversusmorestandardradiotherapeutic
approachesandshouldbeincorporatedwherefeasible.21-23Consolidation
chemotherapyshouldnotbegivenafterconcurrentchemo-radiation,particularly
sincethereisnodocumentedsurvivalbenefitintheeraofimmunotherapy24.
Wealsorecommenddelayingconsolidationimmunotherapyforupto6
weeksaftercompletionofchemo-radiationwheredeemedappropriateinrelationto
timingoftheCOVID-19surge19,25.Iffeasible,immunotherapyshouldbeinitiatedas
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earlyaspossibleforoptimaloutcomesalthoughemergingdatasuggeststhat
delayingconsolidationupto8weeksmaybeasefficacious2627(Table1).
ManagementofMetastaticNon-SmallCellLungCancer
Duringthisunprecedentedcrisis,itisimportanttoemphasizethat
managementofmetastaticnon-smallcelllungcancer(mNSCLC)shouldstillfollow
theprinciplesofprovidingthebestpossiblecareandpalliativemanagementofour
patientswithanefforttoimproveoverallsurvivalandmaintainqualityoflife.
EspeciallyforpatientswithmNSCLC,thereisafinelinebetweenproviding
incrementalbenefitinoverallsurvivalversusexposingpatientstorisksofinfection
andworseoutcomesiftheyweretobecomeinfectedwithSARS-CoV-2.
Allpatientswithmetastaticnon-squamousNSCLCregardlessofsmoking
historyandallnever-smokers,lightsmokers(<10packyears)orremoteformer
smokersregardlessofhistologyshouldbetestedformolecularalterationsupon
initialdiagnosis.Ifbiopsysamplesarelimited,useofplasmabasednext-generation
genesequencingshouldbeincorporatedtoincreasethelikelihoodofdetecting
actionablemutations28.Ifanactionablemutationisdetected,patientsshouldbe
treatedwiththeappropriatetargetedtherapy29.Atthistime,intheabsenceof
targetablemutations,westillrecommendobtainingPD-L1testing,andmaking
treatmentdecisionsinthefirst-linesettingbasedonPD-L1testing.Patientsshould
receiveinductionchemo-immunotherapyorimmunotherapyatthecurrently
recommendedtreatmentintervalsastheanticipatedbenefitoutweighsthepotential
risk30-32.
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Whileimmunotherapyinfusionsaregenerallydosedevery3-4weeks,there
arecompellingdatafrompharmacokineticmodelingthatshowsthatlessfrequent
intervalsofimmunotherapymaybeassociatedwithsimilarefficacy,safety,and
benefit-riskprofile33,34.Keepingthesedatainmind,considerationshouldbemade
tospaceoutimmunotherapyintervalsasappropriate.Thismaybeespecially
relevantforpatientswithmNSCLCwhohavebeenontherapyfor>6–12months,
andhaveongoingsustainedclinicalbenefitfromtherapy.Forpatientswhohave
beenonimmunotherapyforgreaterthan2years,furthertherapyshouldbestopped
inlinewithcurrentlyavailabledata31,35.Homeinfusionoptions,includingdelivery
ofimmunotherapywithhomenursingservicescoupledwithtelemedicinevisits,
warrantfurtherexploration.
Theuseoforaltyrosinekinaseinhibitors(TKIs)asthepreferredagents
managingmNSCLCbearingoncogenicdrivermutationsshouldcontinue,astherisks
ofadverseeventsduetothesedrugsinthesettingoftheCOVID19pandemicare
eitheryetunknownorminimal(Table1).
Forpatientswithrespiratorysymptomsandimagingconcerningfor
immunotherapy/TKIorradiationpneumonitis,COVID-19shouldbestrongly
consideredinthedifferentialdiagnosis.Thiscouldposeadiagnosticchallenge;
althoughtypicalCTfindingsinCOVID-19arebilateral,multifocalroundedand
peripheralgroundglassopacities(GGOs),atypicalfindingsofpatchyGGOsinanon-
specificpatternmaybedifficulttodistinguishfromTKIorimmunotherapyrelated
drugtoxicity36,37.Thissituationcanalsoposeatherapeuticdilemma;whereasthe
mainstayoftreatmentforimmunotherapy/radiation/TKIpneumonitisishighdose
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corticosteroids,steroidsarenotrecommendedinCOVID-19infectionsdueto
concernregardingdelayedviralclearance38.Inadditiontoacarefulhistoryof
symptomssuchasfeverandpossiblesickcontacts,rapidCOVID-19testinginthis
situationisessentialandmayproveinvaluable.
Patientswithanestablishedclinicalresponsetocancertherapythatarenot
exhibitinganysignsorsymptomsoftumorprogressionmaydeferroutinerestaging
scans.Whenthelikelybenefitofadditionalpalliativesystemictherapyisverysmall,
particularlyinthethirdlinesetting,patientsandprovidersmayconcludethatthe
risksoftreatmentoutweighthepossiblegainsinoutcome.Agoalsofcare
discussionandshareddecision-makingatthatpointisimperative.
ManagementofSmallCellLungCancer
Small-celllungcancer(SCLC)isanaggressivemalignancy,whichneedstobe
treatedexpeditiouslyforthebestoutcomes.TreatmentofSCLCcanbeextremely
challengingduetotheoften-significantmyelosuppressionassociatedwith
chemotherapyandtheneedforconcurrentradiationtherapyinlimitedstage
patients.
ForlimitedstageSCLC,werecommendpromptinitiationofconcurrent
chemo-radiationasstandardofcare,wheneverfeasible.Startingradiationwith
cycle2isstandardofcareandcoulddelayfrequenthospitalvisitsand
myelosuppressionbyafewweeks.Eventhoughtwiceadayradiotherapyis
infrequentlyusedincurrentpractice39,itshouldbeusedwhereverfeasibleto
minimizethedurationofradiationtherapy.ProphylacticCranialIrradiation(PCI)
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shouldstillbethestandardinpatientswithlimitedstageSCLCundertheageof75
yearswhohavecompletedchemo-radiationwithoutdiseaseprogression.
ForextensivestageSCLC,chemo-immunotherapyshouldbeadministeredas
thecurrentstandardofcare35,40ineligiblepatients.Oraletoposidecanbeusedon
days2andday3ofthechemotherapycyclestominimizeexposure,aswellas
contactwithhealthcareworkersandfacilities.Afterthecompletionofthefirstfour
cyclesofinductionchemo-immunotherapy,aq4-weekregimenofimmunotherapy
shouldbeused,withdurvalumabat1500mgIV,whichhasrecentlybeenapproved
bytheFDA35,oratezolizumab,atthe1680mgIVdoseevery4weeks33.
SincetherearelimiteddatasupportingefficacyofPCIinpatientswith
extensivestageSCLC41,42,PCIshouldbedeferredandsurveillanceimagingused
instead.Discussionsregardingconsolidativeradiationtherapytothemediastinum
43shouldcontinueonacase-by-casebasisinthemultidisciplinarysettingbasedon
responsivenesstochemo-immunotherapyandbothinitialandcurrentextentof
disease(Table2).
Managementofwell-differentiatedlungneuroendocrinetumors(NETs)
Forearlystagewell-differentiatedlungNETs,surgerymaybedeferredby
severalweeks11.Forpatientsthathaveundergoneresection,adjuvanttherapy
shouldbeavoided,particularlyinpatientswithoutadversehistologicalfeatures
(e.g.,positivemargins,grossresidualdisease,extensivenecrosisorhighKi67)given
lackofdatasupportingitsutilityinthisdisease44,45.Forpatientswithadvancedor
metastaticdiseaseonmaintenancesomatostatinanalogs(SSAs),withnohistoryof
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carcinoidsyndrome,thistreatmentcanbedelayedbyafewweeksifminimally
symptomatic.ForpatientsonSSAs,homeinjectionsareideal,ifavailable.
Othergeneralprinciples
Growthfactorsupportforregimenswithconcernforneutropeniashould
continue.TheNationalComprehensiveCancerNetwork(NCCN)guidelineswere
expandedrecentlytoincludesupportforregimenswithintermediateriskof
myelosuppression.Theseguidelinescautionregardinguseincasesofsuspectedor
confirmedCOVID-19diseaseduetothepotentialofanincreasedriskofpulmonary
inflammationorhypotheticalriskofincreasinginflammatorycytokinesassociated
withadverseoutcome46.Telemedicineshouldbeutilized(withphoneandorvideo
capability)toreducetheriskoftransmissionofSARS-CoV-2topatientsand
providers47,48.Routinefollow-upsurveillanceimagingcanbedeferred/delayedby
3-6months;patientreportedoutcomescoupledwithsymptomassessmentcanbe
usedtodictatescanfrequency49.Interventionsthatalleviateseveresymptoms
shouldremainahighpriority.Whenusingpalliativeradiationtherapy,hypo-
fractionationshouldbetheconsideredwithsinglefractionregimensforbone
metastases(8-24Gy/1fraction),andspinalcordcompressionor2fraction
regimensforairwayobstruction(17Gy/2fractions)50.Bonemodifyingtreatments
(intravenousbisphosphonatesordenosumab)canbedeferredinpatientswithout
hypercalcemiaoractive,symptomaticboneinvasion.
Ensuringthatpatientsreceivecarethatisconsistentwiththeirgoalsand
valuesmustremainacriticalcomponentofourpractice.Priorityshouldbegivento
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patients’wishesaboutresuscitation,ventilatorsupportandoverallgoalsofcare.
Thisissueisallthemoreacuteinthecurrentsetting,wherepatientsareatriskfor
pulmonarycompromisenotonlyfromtheircancerbutalsofrompotentialof
COVID-19andtheinteractionbetweenthesefactorslikelyplacespatientswithlung
canceratexceptionalriskforpooroutcomesevenwithmaximalsupportive
measuressuchasintensivecareandmechanicalventilation.Guidessuchasthose
developedbytheAriadneLabscanbeusedtoaidthesecrucialconversations51.
Itisalsoimportanttonotethatclinicaltrialenrollmenthasbeenadversely
affectedduringthispandemic;manyclinicaltrialshavebeenhaltedorsuspended
foraccrualatseveralinstitutions.Enrollmentonclinicaltrialsshouldstillcontinue,
iffeasible,especiallyintheabsenceofstandardofcaretherapeuticoptions.
Institutionaleffortsmustbedirectedtocreatedatabasesforlungcancerpatients
withandwithoutCOVID-19,sothattheiroutcomescanbeanalyzedinalongitudinal
manner.
NowthatwearefullyinthemidstoftheCOVID-19pandemic,thequestion
oftenariseshowtoproceedwithpatientsthatmaypresentwithsymptoms,ormay
havebeenincontactwithapersonwhohastestedpositiveforCOVID-19.Atour
center,allpatientswithlungcancerarescreenedwithasimplequestionnaire
(SupplementaryTable1),whichincludestravelhistoryandaninventoryof
currentrelevantsymptoms(Figure1).Forpatientswhoscreenpositive,orthose
withconcerningsymptoms,werecommendtestingforCOVID-19eitheratadrive-
throughfacility(ifstable)ormanagementintheemergencyroomforpatientswith
moresevereclinicalsymptoms.Managementdecisionsregardingsystemictherapy
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fortheirlungcancerarethenbasedonCOVID-19testresults.Individualpatientsdo
notnecessarilyneedtestingpriortoinitiationofsystemictherapyalthoughthe
availabilityofrapidpointofcaretestingmaychangeourapproach.Whetherto
deferoraltargetedagentsinpatientswitheithersuspectedCOVID19symptomsor
areunderCOVID19investigationisanareaofmedicaluncertainty,andclinical
judgmentmustbeexercisedtomakethosenuancedtherapeuticdecisions.
Conclusion
TheCOVID-19pandemichascreatedagenerationalcrisis,andan
unprecedentedstrainonhealthcareresourcesandourabilitytodeliverhighquality
seamlesscareforpatientswithlungcancer.Managementofpatientswithlung
cancerhasalwaysrequiredahighlyintegratedandmultidisciplinaryapproach.In
thisarticle,wepresentguidanceandofferinsightonsuggestedbestpracticesfor
lungcancermanagementfromalargetertiaryacademicmedicalcenter.Itiscritical
forphysicianstounderstandtherapidlychanginglocalconditionsandavailable
resourcesaswellasrisks/benefitsofvarioustreatmentsandtheirimplicationsfor
patients,staffandhospitalsystems.Thebasictenetsofcancercaredeliveryand
coordinationshouldbefollowedasmuchaspossibleduringtheCOVID-19
pandemic.
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Table 1. Management recommendations and additional considerations for patients with NSCLC by stage of disease
STAGE RECOMMENDATIONS ADDITIONAL CONSIDERATIONS STAGE I Defer surgery for lung nodules < 2cm, GGO, carcinoid
tumors Follow ACS guidelines, and decisions must be based on institutional resources
Consider SBRT/ Ablation
STAGE II/III Delay adjuvant chemotherapy to 3-4 months post-operatively
Consider withholding adjuvant chemotherapy for patients > 75 years of age or with significant comorbidity Consider Neo-adjuvant/ Induction if surgery not immediately feasible
STAGE III Delay start of consolidation durvalumab up to 6 weeks from completion of concurrent Chemo Radiation Hypo-fractionated RT schedules should be used with concurrent chemotherapy, when feasible No consolidation chemotherapy should be administered after completion of concurrent Chemo Radiation
Consider delaying start of concurrent Chemo Radiation on case-by-case basis, discuss with Radiation Oncology about sequential chemotherapy followed by Concurrent Chemo Radiation Consider using Q3W chemotherapy regimens, instead of QW chemotherapy to minimize exposure
STAGE IV After initial induction chemo-immunotherapy, consideration should be made to space out interval between maintenance infusions, especially for those who have been on therapy for > 6 months and those with an excellent clinical/ radiographic response Stop immunotherapy for patients who have completed 2 years of treatment
For patients on TKI: Do not routinely hold TKI for Covid-19 positive patients unless symptomatic If symptomatic and concern for pneumonitis, advise testing for Covid-19 before making a decision about stopping therapy
Abbreviations: GGO: ground glass nodules, ACS: American College of Surgeons, SBRT: Stereotactic Body Radiation Therapy, TKI: Tyrosine Kinase Inhibitor
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Table 2. Management recommendations and additional considerations for patients with SCLC by stage of disease
STAGE RECOMMENDATIONS ADDITIONAL CONSIDERATIONS LS-SCLC Continue with therapy as planned
Consider BID Radiation Therapy to minimize duration and exposure Start Radiation Therapy with cycle 2 of chemotherapy PCI should be recommended for patients < 75 years of age
ES-SCLC Use oral instead of intravenous etoposide on days 1-3 of chemotherapy After induction chemo-immunotherapy, maintenance immunotherapy should be dosed Q4W (atezolizumab 1680 mg or durvalumab 1500 mg IV)
Consider oral therapies such as PO temozolomide or PO topotecan for second line platinum resistant, refractory SCLC Refrain from PCI in consultation with radiation oncology
Abbreviations: BID: Twice Daily, PO: Oral, IV: Intravenous, PCI: Prophylactic Cranial Irradiation
Supplementary Table 1. Screening Questionnaire used at UPHS
TRAVEL HISTORY OR CONTACT Travel Outside the US or to the NYC Metro Area in the past 2 weeks
Contact with a Person Under Investigation COVID-19 Testing Pending
INFECTIOUS DISEASE SCREENING Fever Headache Arthralgia Myalgia Cough Difficulty Breathing Shortness of Breath Abdominal Pain Vomiting Hemorrhage
Abbreviations: UPHS: University of Pennsylvania Health System
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