Osteoradionecrosis of the Jaw: Past, Present, Clinical and Economic Impact in Oncology ISOO Session 01: Bone Necrosis Jonn Wu Radiation Oncologist, Vancouver Canada Chair, Provincial H&N Tumour Group June 30, 2018

Presenter Disclosure

Disclosure:JonnWuRela1onshipswithCommercialInterests:Nil,relatedtothetopic.

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Outline

Introduc)on–WhatisOsteoradionecrosis(ORN)ClinicalImpact–EconomicImpact,QualityofLife(QOL)Past,Present-RiskFactorsandRadia1onDose

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What is Osteoradionecrosis (ORN)

•  Exposed,irradiatedboneintheabsenceofrecurrentorresidualtumor.

•  Marx,1983:§  Allcasesexposedtohighdosesofradia1on§  9/26casesnohistoryoftrauma§  Microorganisms:inconsistent,surfacecontaminants§  Histologicreview

•  ProposedPathophysiology§  Radia1on§  3H’sàHypoxicHypovascular&Hypocelluar1ssue§  Tissuebreakdown§  Chronicnon-healingwound

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Outline

Introduc1on–WhatisOsteoradionecrosis(ORN)ClinicalImpact–EconomicImpact,QualityofLife(QOL)Past,Present-RiskFactorsandRadia1onDose

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Clinical Impact

•  Incidence:3-7%•  Symptoms,Signs:

o  Pain,halitosis,dysgeusia,paresthesias,trismus,difficultychewing,swallowing,dysarthria

•  Severity:o  Asymptoma1cexposuretoprogressivefistula,fracture,

infec1on

•  Management:

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Clinical Impact – Quality of Life (QOL), Economic

Since2008,QOL:•  MostweresevereORN,postsurgical,equivocalresults•  3ar1cles:ORNvsnon-ORNinradiotherapypa1ents•  Limita1ons:Smallcohorts,retrospec1ve,non-standardgradingsystems

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Clinical Impact – QOL – Jacobson, 2013 •  42pa1ents,retrospec1vechartreview,BethIsraelHospital,NewYork•  SevereORN,allhadsegmentalmandibulectomy+freeflap

o  30:telephoneinterview(PerformanceStatusScale)o  18:QOLques1onnaires(SpeechHandicapIndex,EORTCH&N35,

Ea1ngAssessmentTool)o  Mean23.4monthspost-surgery

•  Pairwisematchversusnon-ORNHNCpa1ents

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Clinical Impact – QOL – Jacobson, 2013 •  Pairwisematchversusnon-ORNHNCpa1ents

o  Matching:Nospecifics,RTorSurgery?o  Verysmallnumbers–furthersubdividedbyyears

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18pa1entsEa1ngAssessmentToolSpeechHandicapIndex(lowerbeier)

30pa1entsTelephoneinterview+PerformanceStatusScale(higherbeier)

Clinical Impact – QOL – Rogers, 2015

•  71pa1ents,1993to2011,UniversityHospitalAintree(UK),UWQoL-4•  4Groups:Grade(Notani)versusTreatment

•  Treatments:o  NoSurgery:HBO,medical(tocopherolandpentoxyphylline)o  Surgery:Segmentalmandibulectomy+FreeFlap

•  EachGroupcomparedtonon-ORNpa1entso  Primaryradiotherapyo  Noradiotherapy

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GradeI/II GradeIII

NoSurgery 34 9

Surgery 10 18

Clinical Impact – QOL – Rogers, 2015 •  Pa1entswithORNreportedmoresevereproblemswith:

o  Pain,appearance,ac1vity,recrea1on,swallowing,andchewing.o  Sta1s1calsignificanceonlycomparedtonon-radiotherapypa1ents

•  WorstscoreswithgradeIIIORNandamermandibularresec1onandreconstruc1on

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Clinical Impact – QOL – Mucke, 2015

•  UniversityofMunchen,Germany•  3groupsofpa1ents:•  UWQoL-4

o  24monthsamertreatmento  Surgery+RTgroups

§  24monthsamerRT§  Twocopies,oneforsurgery,oneforRT

•  SurgeryvsSurgery+RTo  ReducedQOLamerradia1ontherapy,muchworsethansurgery

•  NosignificantdifferencebetweenSx/RTvsSx/RT/ORNo  Smallnumberso  Recallbias–ques1onnairesamerRTo  Pa1entsmightbefocusedonSxvsRTratherORNo  Surgeryasaconfounder(primarycompositeresec1onandfreeflapreconstruc1on)

•  Idealcohort=RTvsRT(ORN)

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Treatment Pa)ents

Surgery 32

Surgery+RT 32

Surgery+RTandORN 32

Clinical Impact – QOL - Summary •  Since2008,veryfewreports,andlimitedby:

o  Smallcohortso  Retrospec1veorprospec1vewithpoten1albiasesor

confoundingfactors§  Treatmentregimen§  ORNmanagement(+/-surgery)§  NonstandardORNgrading§  Mul1pleQOLtools§  SeverecasesofORN

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Author #Pa)ents Subgroups Surgery? Sta)s)calDifference?

Jacobson 30(phone) 18(survey) Yes Mixed

Rogers 71 9-34(byyear) Stra1fied Mixed

Mucke 96 3x32 Yes No

Outline

Introduc1on–WhatisOsteoradionecrosis(ORN)ClinicalImpact–EconomicImpact,QualityofLife(QOL)Past,Present-RiskFactorsandRadia)onDose

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ORN – Risk Factors – Caparrotti - 2017

•  Retrospec1veseries,1196pa1entsSCCoropharynx,2005–2014•  Cura1veintentIMRT+/-chemo•  Matchedcohort:ORNvsnon-ORN•  Incidence:•  Mul1variateAnalysissignificant:

o  Smokingo  Cardiovascularcomorbidi1eso  T-stageo  Bisphosphanateso  Pre-RTextrac1ons(poorhygiene?Lesspost-RTextrac1ons)

•  Volumeofmandiblereceiving50Gy,and60Gyo  Mustcompetewithtumourandsalivaryglands

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1Year 3Years 5years

3% 5% 7%

ORN – What about RT dose? •  Caparron,2017:Volumeofmandiblereceiving50Gyand60Gy•  Tsai,2013:Volumeofmandiblereceiving50Gyand60Gy•  Nabil,2011:Extrac1on+Doses>60Gy

•  Ifweknowaboutdose…•  Andradia1ontechniquehasevolved…

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ORN – What about RT dose? …whycan’twesparethemandible?

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ORN – But it might be possible…! •  ReviewofallH&NIMRTontrialsfrom1996-2005@AnnArbor•  176pa1ents,minimalFU6months

o  Extrac1ons:17%pre,7%postRTo  75%and50%>=65and70Gyto>=1%mandibleo  Averageparo1ddose:22Gy(contralateral),53Gy(ipsilateral)

•  MedianFU34months:noORN

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ORN – Brachytherapy – Extreme Past to Present •  NorwegianRadiumHospital,Oslo,Norway•  Ir-192brachytherapy–oralcavity•  1978to1994:calcula1onsystemunderes1mated(overdosed)by20-25%•  84pa1entss1llalive

o  Clinicalexamina1ono  EORTCQLQ-C30&HN35o  meanoverdosage:19.3%o  Noassocia1ondosevsQOL

•  **ORN=45%!!!o  Loca)on:lateraltongueo  Totalac)vity(dose)o  Doserate(intensity)

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Osteoradionecrosis - Summary •  Rarebutpoten1allycatastrophicforourpa1ents•  Mayoccuryearsamertherapy

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1Year 3Years 5years

3% 5% 7%

Author #Pa)ents Subgroups Surgery? Difference?

Jacobson 30(phone) 18EORTC Yes Yes

Rogers 71 9-34 Stra1fied Yes

Mucke 96 3x32 Yes No

•  Riskfactors:Smoking,OralHygiene,CardiovascularDisease

•  Minimizeradia1ondose–competewithtrea1ngtumourandsparingorgans

•  ?EconomicandQOLImpact