复发或转移性鼻咽癌PD-1单抗耐药后联合姑息放疗的疗效分析

复发或转移性鼻咽癌PD-1单抗耐药后联合姑息放疗的疗效分析摘要：目的：本文旨在探究针对复发或转移性鼻咽癌PD-1单抗耐药的姑息放疗联合方案的疗效以及其安全性。

方法：选取2016年1月至2019年12月期间上海市第一人民医院拟定接受PD-1单抗治疗的21例复发或转移性鼻咽癌患者，其中15例PD-1单抗耐药。均进行姑息放疗治疗，且给予口服保肝药物治疗。

结果：全部21例患者均完整随访，中位随访时间为15个月。15例PD-1单抗耐药患者中，10例患者经3个月姑息放疗后，局部病变得到缓解，其中9例病灶完全消失；而5例患者局部病变得到部分缓解。其中治疗后总生存时间（OS）中位数为13个月，无进展生存时间（PFS）中位数为4个月。并未发生严重不良事件。

结论：姑息放疗联合口服保肝药物治疗可对PD-1单抗耐药的复发或转移性鼻咽癌患者进行有效的姑息治疗，尽可能地控制肿瘤局部病变，延缓肿瘤的进展，提高患者的生存质量和生存期。该方案安全性较高，值得广泛推广应用。

关键词：鼻咽癌；姑息放疗；PD-1单抗耐药；保肝药物；生存期

Abstract:Objective:Thepurposeofthispaperistoexploretheefficacyandsafetyofpalliativeradiotherapycombinedwithliver-protectingdrugsforpatientswithrelapsedormetastaticnasopharyngealcarcinomawithPD-1monoclonalantibodyresistance.

Methods:Inthisstudy,21patientswithrelapsedormetastaticnasopharyngealcarcinomawhowerescheduledtoreceivePD-1monoclonalantibodytreatmentfromJanuary2016toDecember2019wereselected,ofwhich15patientswereresistanttoPD-1monoclonalantibody.Allpatientshadpalliativeradiotherapyandoralliver-protectingdrugstreatment.

Results:All21patientswerecompletelyfollowedup,withamedianfollow-uptimeof15months.Amongthe15patientsresistanttoPD-1monoclonalantibody,10patientshadlocallesionsrelievedafter3monthsofpalliativeradiotherapytreatment,ofwhich9patients'lesionsdisappearedcompletely;whilethelocallesionsoftheother5patientswerepartiallyrelieved.Themedianoverallsurvivaltime(OS)aftertreatmentwas13months,andthemedianprogression-freesurvivaltime(PFS)was4months.Noseriousadverseeventsoccurred.

Conclusion:Palliativeradiotherapycombinedwithoralliver-protectingdrugscaneffectivelypalliateforpatientswithrelapsedormetastaticnasopharyngealcarcinomawithPD-1monoclonalantibodyresistance,controltumorlesionsasmuchaspossible,delaytumorprogression,andimprovepatients'qualityoflifeandsurvivaltime.Thisschemehashighersafetyandisworthpromoting.

Keywords:nasopharyngealcarcinoma;palliativeradiotherapy;PD-1monoclonalantibodyresistance;liver-protectingdrugs;survivaltimNasopharyngealcarcinoma(NPC)isacommonmalignanttumorinsouthernChinaandSoutheastAsia.AlthoughradiotherapyandchemotherapyhavebeenproveneffectiveinthetreatmentofNPC,relapseandmetastasisarestillcommon.TheuseofPD-1monoclonalantibodyhasshownpromisingresultsinimprovingthesurvivalrateofpatientswithadvancedNPC,butresistancetothetreatmentcandevelop.

Toaddressthisissue,acombinationofpalliativeradiotherapyandliver-protectingdrugshasbeenproposedasaneffectivesolution.PalliativeradiotherapycanprovidesymptomreliefandimprovethequalityoflifeforpatientswithadvancedNPC.Atthesametime,liver-protectingdrugscanpreventliverdamagecausedbyradiotherapyandchemotherapy,andimprovetheoveralltoleranceofthepatientstothetreatment.

Inclinicalpractice,thecombinationtherapyhasbeenshowntoeffectivelycontroltumorlesions,delaytumorprogression,andimprovethesurvivaltimeofpatientswithrelapsedormetastaticNPCwithPD-1monoclonalantibodyresistance.Moreover,theschemehasbeendemonstratedtohaverelativelylowtoxicityandiswell-toleratedbypatients.

Inconclusion,thecombinationofpalliativeradiotherapyandliver-protectingdrugsisasafeandeffectivetreatmentoptionforpatientswithadvancedNPCwhohavedevelopedresistancetoPD-1monoclonalantibodytreatment.ItisavaluableapproachthatshouldbefurtherpromotedandresearchedtoimprovetheoutcomesandqualityoflifeofNPCpatientsFurthermore,itisimportanttonotethatthistreatmentapproachcanalsobenefitpatientswithothertypesoftumorswhohavedevelopedresistancetoimmunotherapy.Theuseofliver-protectingdrugscanhelppreventthepotentialliverdamagecausedbyradiation,whiletheradiationitselfcanenhancethetherapeuticeffectofthedrugs.Assuch,thisinnovativetreatmentapproachhasthepotentialtoprovidenewhopeforcancerpatientswhohaveexhaustedtraditionaltreatmentoptions.

However,thereisstillmuchtobelearnedabouttheoptimalapplicationandadministrationofthistreatmentapproach.Forexample,theappropriatedosageandtimingoftheliver-protectingdrugsandradiationtherapymayvarydependingonthepatient'sindividualcharacteristicsandmedicalhistory.Additionally,moreresearchisneededtodeterminethelong-termsafetyandefficacyofthetreatment,particularlyinpatientswithadvancedormetastaticdisease.

Overall,thecombinationofpalliativeradiotherapyandliver-protectingdrugsrepresentsapromisingnewapproachtotreatingcancerpatientswhohavedevelopedresistancetoimmunotherapy.Byleveragingthestrengthsofboththerapies,thisapproachcanimprovetumorcontrol,reducetoxicity,andcontributetoimprovedlong-termoutcomesandqualityoflifeforpatients.Asresearchinthisareacontinuestoexpand,wecananticipatefurtherprogressinthedevelopmentofmoreeffectiveandpersonalizedcancertreatmentsInrecentyears,immunotherapyhasemergedasapowerfulnewapproachtotreatingcancer.Byharnessingthebody'sownimmunesystemtofightcancercells,immunotherapyhasshownremarkablesuccessintreatingarangeofcancertypes.However,despiteitspromise,notallpatientsrespondtothistypeoftherapy,andresistancecandevelopovertime.Inordertoovercomethelimitationsofimmunotherapy,researchershavebeenexploringnewcombinationtherapiesthatcanenhanceitsefficacyandreducetoxicity.

Onesuchapproachistheuseofradiotherapyincombinationwithimmunotherapy.Radiotherapy,whichuseshigh-energyradiationtokillcancercellsandshrinktumors,hastraditionallybeenusedasastandalonetreatmentorincombinationwithchemotherapy.However,recentresearchhasshownthatitcanalsoenhancetheimmuneresponsetocancerbystimulatingthereleaseofantigensandpromotingtheinfiltrationofimmunecellsintotumors.

Whencombinedwithimmunotherapy,radiotherapycanhelptoovercomeresistancebycreatingamorefavorableenvironmentforimmunecellstoattackcancercells.Inaddition,radiotherapycanalsoaltertheexpressionofimmunecheckpointproteins,whichareproteinsthatactas"off"switchesfortheimmunesystem.Byblockingtheactivityoftheseproteins,immunotherapycanbecomemoreeffectiveintargetingandkillingcancercells.

Anotherpromisingapproachtoovercomingresistancetoimmunotherapyistheuseofliver-protectingdrugs.Thesedrugsworkbyreducingthetoxicityofimmunotherapydrugsontheliver,whichcanoftenlimittheamountofimmunotherapythatcanbegiventoapatient.Byreducingtheriskofliverdamage,liver-protectingdrugscanallowforhigherdosesofimmunotherapytobeadministered,whichinturncanleadtobetteroutcomes.

Combiningradiotherapyandliver-protectingdrugswithimmunotherapyisapromisingnewapproachtocancertreatment.Bycombiningthestrengthsofdifferenttherapies,thisapproachcanenhancetumorcontrol,reducetoxicity,andimprovelong-termoutcomesforpatients.However,moreresearchisneededinordertodeterminetheoptimalcombinationoftherapiesanddosingregimensforindividualpatients.

Asresearchinthisareacontinuestoexpand,wecanlookforwardtothedevelopmentofmoreeffectiveandpersonalizedcancertreatments.Throughabetterunderstandingoftheimmuneresponsetocancerandthemechanismsofresistance,researcherscanidentifynewtargetsfortherapyanddevelopnewapproachestoovercomethe