放射性消化道(系统)副反应(损伤)临床研究

放射性消化道（系统）

副反应（损伤）临床研究

一、放射性损伤临床（应用）研究的现状。物理技术、生物学基础与临床特征二、消化道放射性毒副作用的临床研究研究放射治疗所致正常组织、器官

副反应所涉及的相关内容DoseLETFractionationTimeDose-ratePathogenesisVolumeCombinedTxReTxToleranceModifiersJoinerM,vanderKogelA.(eds).BasicClinicalRadiobiology(4th).2009,HodderArnold:LondonNatRevClinOncol,

2013,10:52-TimeofdiscoveryKilovoltageera1900-1940Megavoltageera1946-1996Computer-assisted1996-2012ThefutureCurative,conservative,andcost-effectivetreatment.物理技术LancetOncol,2012;13:e1691.newRT

techniquesandtechnologies.2.evidenceshowstheirdosimetricadvantages.undertheassumptionthat…

BUT…Fornewdrugs,randomisedtrials

1.substantialinvestmentshavetobemadeinnewequipment,QA,andtraining.evolveandbemodifiedovertime.2.extendedfollow-upisneededtomeasureoutcomes,especially,mercialsponsorshipismoredifficultthanfornewdrugs.4.ethicalissuesariseintestingatheoreticallysuperior.5.patient’smanagementcouldchangeinotherways.(1).TheWHOHandbookforReportingResultsofCancerTreatment(1979)(2).CommonTerminologyCriteriaforAdverseEvents(CTCAE)byNCI(1988)(3).Acute&LateRadiationMorbidityScoringSystembyEORTC/RTOG(1983-1992)(4).LENTSOMAScalesbyEORTC/RTOG(1995)

Lateeffectofnormaltissues:fourcategoriesofSubjective,Objective,ManagementandAnalyticparametersIntJRadiatOncolBiolPhys,1995;31(5)临床特征ASTRO,AAPM,RedJ.QuantitativeAnalysisofNormalTissueEffectsintheClinic

(QUANTEC).theRedJ,2010;76(3):S(1)通过现有资料的总结，对于正常组织特定观测终点，提供量化的剂量－效应与剂量－体积关系。(2)根据上述剂量－体积的数据与模型，给临床提供合理的毒性分类与工作指南。(3)提出有助于正确估测和减轻急性、晚期放射治疗副作用的研究方向。TheChallenges1.放疗前基础临床特征2.放射性毒副反应的准确分类、分期,endpointmeasurements,showalargedegreeofinterpatientvariabilityin

incidenceandseverity3.长期的随访与资料保存ASystemforContinualQualityImprovementofNormalTissueDelineationforRadiationTherapyTreatmentPlanningBreunigJ,theRedJ,2012;83:703-生物学基础及其临床应用BarnettGC,etal.

Normaltissuereactions

toradiotherapy:towardstailoringtreatmentdosebygenotype.

NatRevCancer,2009;9:134.

KernsSL,etal.

Radiogenomics:usinggeneticstoidentifycancerpatientsatriskfordevelopmentofadverseeffectsfollowingradiotherapy.

CancerDiscov,2014;4:155.候选基因病例对照关联研究筛选出易感基因Single-nucleotidepolymorphism(SNP,单核苷酸多态性)位点的。

Thegoalsoftheradiogenomics:(i)todevelopanassaycapableofpredictingwhichpatientsaremostlikelyto…(ii)toobtaininformationtoassist

withtheelucidationofthemolecularpathwaysresponsible

for…放射基因组学：全基因组关联分析(genome-wideassociationstudies,GWAS)

发现临床放射敏感性的预测基因vanOorschotR,etal.Reducedactivityofdouble-strandbreakrepairgenesinprostatecancerpatientswithlatenormaltissueradiationtoxicity.theRedJ,2014;88:664.

500prostatecancerpatients,34over-respondingVS27non-respondingofgrade3toxicitytothebladderand/orrectumatmorethan1timepointbeyond2yearsoffollow-up.DNAdamagerepairkinetics(γ-H2AXassay)andexpressionprofilesofDNArepairgenesweredeterminedinexvivoirradiatedlymphocytes.InductionlevelsofDSBrepairgenes(eg,RAD51)maypotentiallybeusedtoassesstheriskforlateradiationtoxicity.ForoP,etal.Relationshipbetweenradiation-inducedapoptosisofTlymphocytesandchronictoxicityinpatientswithprostatecancertreatedbyradiationtherapy:AProspectiveStudy.theRedJ,2014;88:1057.214patientswereprospectivelyincluded.Peripheralbloodbeforetreatmentandirradiatedwith8Gy.ThepercentageofCD4andCD8Tlymphocytesthatunderwentradiation-inducedapoptosiswasassessedbyflowcytometry.198caseswithLateGIandGUtoxicityandmortalitywerecorrelated.invitroradiation-inducedapoptosisofCD4TlymphocytesassessedbeforeradiationtherapywasassociatedwiththeprobabilityofdevelopingchronicGUtoxicity.早＼晚反应组织、早＼晚期毒副反应临床观测终点（指标）的选择严重程度的分级＼发生率的高低时间：发生的早晚、持续的长短其他治疗的影响LENTSOMA、CTCAENO!口腔、咽部（上消化呼吸道）黏膜RTOGacuteradiationmorbidityscoringcriteria01234NochangeoverbaselineInjection/mayexperiencemildpainnot

requiring

analgesicPatchymucositisthatmayproduceaninflammatoryserosanguinousdischarge/mayexperiencemoderatepainrequiring

analgesia

Confluentfibrinousmucositis/mayincludeseverepainrequiring

narcotic

Ulceration,hemorrhageornecrosisCoxJD,etal.theRedJ,1995;31(5):1341-46定义食管体积面临的问题整个食管的长度上至环状软骨，下至胃食管连接部；在计划CT扫描时需包括一部分颈部和上腹部；一些研究没有包括颈部食管，导致食管绝对体积小了20%；食管周长由于受吞咽活动的影响在CT图像上有明显差异，因此，传统的DVHs可能并不能准确反映部分的剂量体积；三维剂量学参数的使用（例如：剂量-表面积、剂量-周长直方图，解剖校正DVHs）作为预测值的作用并不是很清楚。推荐使用CTCAE

胃与小肠1.急、慢性毒性包括恶心、腹泻、梗阻、出血／溃疡、体重下降、穿孔等。2.受照射剂量与体积，单组肠袢V15=120cc，所有肠袢V45=195cc。目前没有关于胃的数据。慢性毒性与急性有关，而且要注意最大剂量。3.手术、化疗有明显的关系。4.推荐使用CTCAE十二指肠VermaJ,etal.RedJ,2014;88:357LimitingV55tobelow15cm3mayreducetheriskofduodenalcomplications.Duodenaltoxicitywasassessedonthebasisofendoscopicfindings(endoscopywasperformedinpatientswithsymptomsofgastrointestinaltoxiceffectssuchaspainorbleeding)它不适合于胰腺癌放疗？肠道

Smallbowel&largebowelloopswerecontoured2cmabovethetargetvolume.CTCAE3.0withmedianfollow-upof18months.V15GySBandLBareindependentpredictorsoflategrade3orhighertoxicity.RestrictingV15SB&LBto<275cc&<250cccanreducegrade3orhighertoxicitytolessthan5%.ChopraS,etal.PredictorsofGrade3orHigherLateBowelToxicityinPatientsUndergoingPelvicRadiationforCervicalCancer:ResultsFromaProspectiveStudy.theRedJ,2014;88:630直肠Lyman-Kutcher-Burman模型：n=0.09(0.04–0.14);m=0.13(0.10–0.17)；而TD50=76.9(73.7–80.1)Gy。前列腺癌放疗提供了相关的资料。asignificantreductionofboweldysfunctionalsymptomswasconfirmedinmenselectedforIGRT,eventhoughtheyhadlargervolumesofrectumtreatedtohigherdoses.

RedJ,2013;85:1018-OptimisingRadiotherapyBowelInjuryTherapy(ORBIT)inUKBowelDiseaseQuestionnaire-Bowelsubsetscore(IBDQ-B)&Changesinquality-of-lifesecondaryendpointsin6&12monthsLENT-SOMAAndreyevHJN,etal.Lancet2013;382:2084-给病人有计划的处置方案就可以明显改善病人胃肠道状态。FerreiraMR,etal.LancetOncol2014;15:e139-1.Similaritiesbetweenradiation-inducedgast