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

charu.aggarwal@pennmedicine.upenn.edu

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.

3

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

6

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

8

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.

10

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)

12

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

13

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

14

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

15

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.

16

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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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