放射性消化道(系統(tǒng))副反應(yīng)(損傷)臨床研究

放射性消化道（系統(tǒng)）

副反應(yīng)（損傷）臨床研究

一、放射性損傷臨床（應(yīng)用）研究的現(xiàn)狀。物理技術(shù)、生物學(xué)基礎(chǔ)與臨床特征二、消化道放射性毒副作用的臨床研究研究放射治療所致正常組織、器官

副反應(yīng)所涉及的相關(guān)內(nèi)容DoseLETFractionationTimeDose-ratePathogenesisVolumeCombinedTxReTxToleranceModifiersJoinerM,vanderKogelA.(eds).BasicClinicalRadiobiology(4th).2009,HodderArnold:LondonNatRevClinOncol,

2013,10:52-TimeofdiscoveryKilovoltageera1900-1940Megavoltageera1946-1996Computer-assisted1996-2012ThefutureCurative,conservative,andcost-effectivetreatment.物理技術(shù)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)臨床特征ASTRO,AAPM,RedJ.QuantitativeAnalysisofNormalTissueEffectsintheClinic

(QUANTEC).theRedJ,2010;76(3):S(1)通過現(xiàn)有資料的總結(jié)，對于正常組織特定觀測終點(diǎn)，提供量化的劑量－效應(yīng)與劑量－體積關(guān)系。(2)根據(jù)上述劑量－體積的數(shù)據(jù)與模型，給臨床提供合理的毒性分類與工作指南。(3)提出有助于正確估測和減輕急性、晚期放射治療副作用的研究方向。TheChallenges1.放療前基礎(chǔ)臨床特征2.放射性毒副反應(yīng)的準(zhǔn)確分類、分期,endpointmeasurements,showalargedegreeofinterpatientvariabilityin

incidenceandseverity3.長期的隨訪與資料保存ASystemforContinualQualityImprovementofNormalTissueDelineationforRadiationTherapyTreatmentPlanningBreunigJ,theRedJ,2012;83:703-生物學(xué)基礎(chǔ)及其臨床應(yīng)用BarnettGC,etal.

Normaltissuereactions

toradiotherapy:towardstailoringtreatmentdosebygenotype.

NatRevCancer,2009;9:134.

KernsSL,etal.

Radiogenomics:usinggeneticstoidentifycancerpatientsatriskfordevelopmentofadverseeffectsfollowingradiotherapy.

CancerDiscov,2014;4:155.候選基因病例對照關(guān)聯(lián)研究篩選出易感基因Single-nucleotidepolymorphism(SNP,單核苷酸多態(tài)性)位點(diǎn)的。

Thegoalsoftheradiogenomics:(i)todevelopanassaycapableofpredictingwhichpatientsaremostlikelyto…(ii)toobtaininformationtoassist

withtheelucidationofthemolecularpathwaysresponsible

for…放射基因組學(xué)：全基因組關(guān)聯(lián)分析(genome-wideassociationstudies,GWAS)

發(fā)現(xiàn)臨床放射敏感性的預(yù)測基因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＼晚反應(yīng)組織、早＼晚期毒副反應(yīng)臨床觀測終點(diǎn)（指標(biāo)）的選擇嚴(yán)重程度的分級＼發(fā)生率的高低時(shí)間：發(fā)生的早晚、持續(xù)的長短其他治療的影響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定義食管體積面臨的問題整個(gè)食管的長度上至環(huán)狀軟骨，下至胃食管連接部；在計(jì)劃CT掃描時(shí)需包括一部分頸部和上腹部；一些研究沒有包括頸部食管，導(dǎo)致食管絕對體積小了20%；食管周長由于受吞咽活動的影響在CT圖像上有明顯差異，因此，傳統(tǒng)的DVHs可能并不能準(zhǔn)確反映部分的劑量體積；三維劑量學(xué)參數(shù)的使用（例如：劑量-表面積、劑量-周長直方圖，解剖校正DVHs）作為預(yù)測值的作用并不是很清楚。推薦使用CTCAE

胃與小腸1.急、慢性毒性包括惡心、腹瀉、梗阻、出血／潰瘍、體重下降、穿孔等。2.受照射劑量與體積，單組腸袢V15=120cc，所有腸袢V45=195cc。目前沒有關(guān)于胃的數(shù)據(jù)。慢性毒性與急性有關(guān)，而且要注意最大劑量。3.手術(shù)、化療有明顯的關(guān)系。4.推薦使用CTCAE十二指腸VermaJ,etal.RedJ,2014;88:357LimitingV55tobelow15cm3mayreducetheriskofduodenalcomplications.Duodenaltoxicitywasassessedonthebasisofendoscopicfindings(endoscopywasperformedinpatientswithsymptomsofgastrointestinaltoxiceffectssuchaspainorbleeding)它不適合于胰腺癌放療？腸道

Smallbowel&largebowelloopswerecontoured2cmabovethetargetvolume.CTCAE3.0withmedianfollow-upof18months.V15GySBandLBareindependentpredictorsoflategrade3orhighertoxicity.RestrictingV15SB&LBto<275cc&<250cccanreducegrade3orhighertoxicitytolessthan5%.ChopraS,etal.PredictorsofGrade3orHigherLateBowelToxicityinPatientsUndergoingPelvicRadiationforCervicalCancer:ResultsFromaProspectiveStudy.theRedJ,2014;88:630直腸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。前列腺癌放療提供了相關(guān)的資料。asignificantreductionofboweldysfunctionalsymptomswasconfirmedinmenselectedforIGRT,eventhoughtheyhadlargervolumesofrectumtreatedtohigherdoses.

RedJ,2013;85:1018-OptimisingRadiotherapyBowelInjuryTherapy(ORBIT)inUKBowelDiseaseQuestionnaire-Bowelsubsetscore(IBDQ-B)&Changesinquality-of-lifesecondaryendpointsin6&12monthsLENT-SOMAAndreyevHJN,etal.Lancet2013;382:2084-給病人有計(jì)劃的處置方案就可以明顯改善病人胃腸道狀態(tài)。FerreiraMR,etal.LancetOncol2014;15:e139-1.Similaritiesbetweenradiation-inducedgast