osteoradionecrosis of the jaw: past, present, clinical and ... · osteoradionecrosis of the jaw:...
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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