i sessione “terapia come e quando” - progetto...

09,40 – 15,30

I Sessione“Terapia come e quando”

Moderatore:

Roberto Labianca

10,40 – 11,10

Trattamenti radioterapici

Isacco Desideri

RuolodellaradioterapianelpazienteanzianoDott.IsaccoDesideri

UniversitàdegliStudidiFirenzeSODc Radioterapia– Careggi

Firenze

Background:radiotherapy inelderly patients

Radiotherapyisakeycomponentofthemanagementofoldercancerpatients

Technologicalimprovementsinradiationoncologyfieldmaysignificantlycontributetoasubstantialimprovementinthemanagementofelderlypopulation.

Dataregardingcomprehensivegeriatricassessmentandtoxicityinthissubsetofpatientsarestillscarceandcontroversial.

Priorities for futureradiotherapy research

Kunkler IHetal.Ann Oncol 2014

Appropriateness

Doseandvolumereduction

Newtechnology implementation (SBRT,VMATetc.)

Updateinradiotherapy:Primary CNSTUMORS

Short-course radiotherapy apossible solutionfor frail/elderly patients affected by GBM?

• 98patients• Frail:age≥50yearsandKPSof50%to70%;• Elderlyandfrail:age≥65yearsandKPSof50%to70%;• Elderly :age≥65yearsandKPSof80%to100%)

• Short-courseRT(5x5Gy)vsstandardhypofractionated-RT(15x2.6Gy)

Roa Wet al.JCO2015

Anew paradigm of treatmentinHGG?

NOdifference interms of OSandPFSbetween shortcourseandstandardhypofractionated treatment

Roa Wet al.JCO2015

Updateinradiotherapy:Lung Cancer

Is SBRTsuitable for elderly patients?

• 70years orolder patients affected by early stageNSCLC(cT1-T3cN0)• 3147patients extracted from NationalUSDatabase• SBRTdelivered in289patients (8.2%)vsno-treatmentin2889(91.2%)• Nodifference interms of comorbidity between two groups

NandaRHetal.Cancer 2015

NandaRHetal.Cancer 2015

Updateinradiotherapy:Lung cancer

• Improvement of survival acrossall ages group dueto SBRT• Median OS:29.1vs10.1months(p<0.001)• Benefitof SBRTonOSnotinfluenced by thenumber ofcomorbidities,

How to identify predictors of lung toxicity inSBRT?

• Specific predictors of lungtoxicity inSBRTstill controversial• Age-only paramateris not asufficient predictor of lungtoxicity.• Functional parameters (SPECT)may provide informations onradiation pneumonitis risk.

Farr KPet al.Radiother Oncol 2015

Updateinradiotherapy:ProstateCancer

Managementof prostatecancer intheelderly

Bekelman JEet al.JCO2015

• Non-randomizedeffectivenessstudiesofADTplusRTversusADTinthreegroupsofpatientsdiagnosedbetween1995and2007andobservedthrough2009intheSEER-Medicaredataset:

• (1)therandomizedclinicaltrial(RCT)cohort:(age65-75yearswithlocallyadvancedprostatecancer)• (2)theelderlycohort :(age≥75yearswithlocallyadvancedprostatecancer)• (3)thescreen-detectedcohort:(age≥65yearswithhig-riskprostatecancer)

Should we always try to de-intensificatetreatments inelderly population ?

Adrogen-deprivation therapy alonehas adetrimental effect onOSeven inmen older than 75years with high-risk prostatecancer

Bekelman JEet al.JCO2015

Headandneck Cancer

Background

25%of all H&N patients arediagnosed >70years of age

Elderly population steadily increasing inwesternsocieties

Noprospective randomized dataexist regarding thepotentialbenefitofconcurrent chemoradiotherapy inelderly patientsaffected bylocally advanced disease

Theelderly population:aneasydefinition?

•Cut-offpoint ofelderly is still controversial:•Re-definition ofelderly ≥65years (NIH/NIA):• «young old»:65-74years• «older old»:74-85years• «oldest old»:above 85years

•Upto10comorbidity scores aredefined(+++Charlson Comorbidity index,ACE-27)

Characteristics ofelderly patients H&Ncancers patients

HPV-related tumors less commoninelderly

Incidence will increase inthefollowing years (34%@10years;64%@20years

Sexratio:Females >males

Oropharynx andlarynx most frequently involved

Gucic etalRepPract Oncol Radiother 2013

Where it all began

• CRTImprovessurvivalinlocallyadvancedheadandneckcancer• Decreasedsurvivalbenefitwithage,specifically≥71,seenonseminalmeta-analysis• Only6%ofpatientsonmeta-analysiswere>70yearsofage• Under-representedelderlypatientpopulationonclinicaltrials

Pignon etal.Radiother Oncol 2009

Does Agereally matter?NewdatafromH&Nsymposium2016

• TheNationalCancerDatabase(NCDB)• 1998-2011• 23%>70

• Patients:≥71years,receivingRT+/-CT• Oropharynx,larynx,hypopharynx• StageIIIandIV(T1-2,N(+)orT3-4,N0-3)• CRT:CTstarts14daysbeforeor14daysafterRT

KARAMSD,Multidiscipinary HeadandNeck Symposium2016

Summary

individualizedclinicaljudgmentand

personalizedmedicalcarearefundamental

Norandomizedtrialandchronic

underrepresentationofthesepatientsin

largetrials

Needtodefineoptimalsubpopulationof

elderlypatientswhowillbenefitthemost

fromCRT

Possible algorithm

Verma Vetal.JGeriatric Oncol 2016

functionalstatus

nutritionalstatus

comorbiditiesPatients

preference

Quality oflife

Updateinradiotherapy:BREASTCANCER

Currentquestionsaboutradiotherapyafterbreast-conservingsurgery:

IsabsolutebenefitfromRTgreaterforsomegroupsofwomenthanforothers?

DoallwomenneedRT?

RelationshipbetweeneffectsofRTonrecurrenceandonbreastcancerdeath

AdjuvantRTomissionintheelderly(1)

• 2003- 2009,1326 womenaged65yearsorolderearlyBC

• Hormonereceptor-positive,axillarynode-negative,T1–T2upto3cm,grade3orLVI,butnotboth,werepermitted

• 76centersinfourcountries

• whole-breastRT(40–50Gy in15–25fr)orNORT

• Primaryendpointwasipsilateralbreasttumorrecurrence(IBTR)Kunkler IH,etal.LancetOncol,2015

AdjuvantRTomissionintheelderly(2)

• Postoperativewhole-breastRTafterBCSandadjuvantendocrinetreatmentresultedinasignificantbutmodestreductioninlocalrecurrenceforwomenaged65yearsorolder

• 5-yearrateofIBTRisprobablylowenoughforomissionofRTtobeconsideredforsomepatients

Kunkler IH,etal.LancetOncol,2015

Evidences gained fromRTCs

SignificantimpactofradiotherapyomissiononIBTRrate

NOimpactofradiotherapyomissiononOS

NOidentificationofafavorablesubgroupofpatients

NODefinitionofaverylowriskgroupofpatientsinwhomRTcouldbesafelyavoided

Kunkler IH,etal.LancetOncol,2015FisherB,etal.JCO,2002HughesKS,etal.JCO,2013

● 5yearsOS:96.6%forWBRTgroupand99.4forIMRTgroup

● IBTR was 1.5%intheIMRTgroupvs 0.1-3%intheWBRTgroup(p=0.86)

● NostatisticaldifferenceintermsofIBTRat5yearsofFup

● ThefirststudyusingexclusivelyIMRTtechniquesforAPBIdelivery

Is APBIsuitable for elderly women?

Very lowrateof local recurrence across two treatmentarms

Nodifference interms of OSbetween APBIandWBI

Significant less toxicity inAPBIarm (possible gain inQoL?Datacoming soon…)

Meattini Iet al.Breast Cancer Res Treat 2015

Futureperspectives..toward atailored treatment

Primary EndpointQuality of Life

Exclusive surgery vs exclusive aPBI versus exclusive ET

Primary endpoint assessmentGlobal Health Status (GHS)

EORTC QLQ-C30/BR-23

Secondary endpointsIBTR, LRR, DM, OS, overall grade 3-4 AEs, contralateral BC, treatment compliance

EORTC1625

CONCLUSIONS

Tailoredandpersonalisedradiotherapytreatmentsforelderlypopulationareemerginginalmosteverycancertype

Technologicaladvancesinradiationoncologyrepresentanusefultoolfortreatingelderlypatientswhenappropriatelyadopted

Chroniclackofrandomizeddataregardingthispatientpopulation…

But trialsaddressing this issue areontheir way,at least inthemorefrequentcancer types (e.g.breast)