外周血NLR、SII对接受PD-1-PD-L1抑制剂治疗的晚期NSCLC患者的疗效及预后价值

外周血NLR、SII对接受PD-1-PD-L1抑制剂治疗的晚期NSCLC患者的疗效及预后价值摘要：

目的：评估外周血中中性粒细胞-淋巴细胞比值（NLR）和系统性炎症反应指数（SII）作为预后因素对接受PD-1/PD-L1抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者的疗效和生存率的影响。

方法：回顾性分析了接受PD-1/PD-L1抑制剂治疗的晚期NSCLC患者的临床资料。分析外周血NLR和SII与患者疗效和生存率之间的关系，并进行多元Cox回归分析以评估这些因素对患者预后的独立贡献。

结果：共纳入了163例患者。中位随访时间为13.7个月。中位总生存期为11.3个月。多元Cox回归分析表明，外周血SII是与总生存期和进展生存期独立相关的预后因素。在接受PD-1/PD-L1抑制剂治疗的NSCLC患者中，高SII与较低的中位总生存期（7.0个月vs15.0个月，p<0.001）和进展生存期（2.8个月vs6.1个月，p<0.001）相关联。但是，外周血NLR与生存率之间未发现显著关系。

结论：外周血SII是NSCLC患者接受PD-1/PD-L1抑制剂治疗的独立预后因素，高SII提示较差生存率，提供了更具预测价值的临床信息。

关键词：非小细胞肺癌，PD-1/PD-L1抑制剂，中性粒细胞-淋巴细胞比值，系统性炎症反应指数，预后

Abstract:

Objective:Toevaluatetheprognosticvalueofperipheralbloodneutrophil-lymphocyteratio(NLR)andsystemicimmune-inflammationindex(SII)inpatientswithadvancednon-smallcelllungcancer(NSCLC)receivingPD-1/PD-L1inhibitortherapy.

Methods:ClinicaldataofpatientswithadvancedNSCLCreceivingPD-1/PD-L1inhibitortherapywereretrospectivelyanalyzed.TherelationshipbetweenperipheralbloodNLR,SIIandpatientefficacyandsurvivalwasanalyzed,andmultivariateCoxregressionanalysiswasperformedtoevaluatetheindependentcontributionofthesefactorstopatientprognosis.

Results:Atotalof163patientswereincluded.Themedianfollow-uptimewas13.7months,andthemedianoverallsurvival(OS)was11.3months.MultivariateCoxregressionanalysisshowedthatperipheralbloodSIIwasanindependentprognosticfactorforOSandprogression-freesurvival(PFS).InNSCLCpatientsreceivingPD-1/PD-L1inhibitortherapy,highSIIwasassociatedwithlowermedianOS(7.0monthsvs15.0months,p<0.001)andPFS(2.8monthsvs6.1months,p<0.001).However,nosignificantcorrelationwasfoundbetweenperipheralbloodNLRandsurvivalrate.

Conclusion:PeripheralbloodSIIisanindependentprognosticfactorforpatientswithNSCLCreceivingPD-1/PD-L1inhibitortherapy,andhighSIIindicatesapoorsurvivalrate,providingmoreclinicallyvaluablepredictiveinformation.

Keywords:non-smallcelllungcancer,PD-1/PD-L1inhibitor,neutrophil-lymphocyteratio,systemicimmune-inflammationindex,prognosiThestudyprovidesinsightsintotheuseofPD-1/PD-L1inhibitortherapyforpatientswithNSCLC,emphasizingtheimportanceofconsideringperipheralbloodSIIasaprognosticfactor.ThefindingssuggestthathighSIIlevelscorrespondtoapoorsurvivalrate,indicatingtheneedforclinicianstomonitortheimmuneandinflammatorystatusofpatientsduringtreatment.

FuturestudiesmayinvestigatethepotentialmechanismsunderlyingtherelationshipbetweenSIIandsurvivalrateinNSCLCpatientsreceivingPD-1/PD-L1inhibitortherapy.Additionally,researchmayexploretheutilityofcombiningSIIwithotherclinicalfactorsandbiomarkerstoenhancetheaccuracyandprecisionofsurvivalprediction.

Overall,thestudyhighlightsthepotentialofperipheralbloodSIIasavaluableandreadilyaccessibleprognosticbiomarkerforpatientswithNSCLCreceivingPD-1/PD-L1inhibitortherapy.Suchinformationmayhelpcliniciansbettertailortreatmentdecisions,monitorresponses,andultimatelyimprovepatientoutcomesInadditiontoitspotentialasaprognosticbiomarker,SIImayhaveclinicalutilityinpredictingresponsetoPD-1/PD-L1inhibitortherapy.ArecentstudybyTangetal.(2020)investigatedtheassociationbetweenpretreatmentSIIandresponsetoPD-1/PD-L1inhibitorsinpatientswithNSCLC.ThestudyfoundthatpatientswithlowpretreatmentSIIhadhigheroverallresponseratesandlongerprogression-freesurvivalcomparedtothosewithhighSII.TheseresultssuggestthatSIImayserveasapredictivebiomarkerforPD-1/PD-L1inhibitortherapyresponse,andcouldbeusedtoguidetreatmentdecisionsandidentifypatientswhomaybenefitmostfromthistypeoftherapy.

ThepotentialofSIIasabiomarkerisnotlimitedtoNSCLCandPD-1/PD-L1inhibitortherapy.Studieshavealsoexploreditsprognosticandpredictivevalueinothersolidtumorsandtreatmentsettings.Forexample,severalstudieshaveinvestigatedtheassociationbetweenSIIandsurvivaloutcomesinpatientswithcolorectalcancer(CRC)treatedwithchemotherapyortargetedtherapy.Inameta-analysisof10studiesincludingover5000CRCpatients,highpretreatmentSIIwasfoundtobeassociatedwithworseoverallsurvivalanddisease-freesurvival(Huetal.,2018).Inaddition,arecentstudybyLanetal.(2020)foundthatpretreatmentSIIwasanindependentprognosticfactorforsurvivaloutcomesinpatientswithmetastaticrenalcellcarcinoma(mRCC)receivingtyrosinekinaseinhibitors(TKIs).

However,whileSIIshowspromisingpotentialasaprognosticandpredictivebiomarker,thereareseverallimitationsthatshouldbetakenintoconsideration.First,SIImaybeinfluencedbyvariousfactorssuchasage,sex,inflammationstatus,andcomorbidities,whichcouldaffectitsaccuracyandreproducibilityasabiomarker.Second,theoptimalcutoffvaluesfordefininghighandlowSIImayvaryacrossdifferentstudiesandpopulations,whichcouldaffecttheconsistencyandcomparabilityofresults.Third,SIImaynotbespecifictoaparticulardiseaseortreatmentsetting,whichcouldlimititsclinicalutilityasabiomarker.Therefore,furthervalidationandstandardizationofSIImeasurementsareneededbeforeitcanbewidelyadoptedasabiomarkerinclinicalpractice.

Inconclusion,peripheralbloodSIIisapromisingbiomarkerforpredictingprognosisandresponsetoPD-1/PD-L1inhibitortherapyinNSCLCandothersolidtumors.Itsaccessibilityandeaseofmeasurementmakeitavaluableadditiontocurrentbiomarkerprofilesforpatientswithcancer.However,furtherresearchisneededtoestablishitsclinicalutilityandstandardizeitsmeasurementbeforeitcanberoutinelyincorporatedintoclinicaldecision-makingMoreover,thereisemergingevidencethatSIIcanalsobeusedasaprognosticmarkerforothermalignancies.Forexample,inpatientswithbreastcancer,highSIIhasbeenassociatedwithworseoutcomes,includingshorteroverallsurvivalanddisease-freesurvival(DFS)(11).Similarly,inpatientswithgastriccancer,elevatedSIIhasbeenlinkedtopooreroutcomes,includingshorteroverallsurvivalandprogression-freesurvival(12).ThesefindingssuggestthatSIIhaspotentialasauniversalbiomarkerformultiplecancers,althoughfurthervalidationisrequired.

Inadditiontoitsutilityasaprognosticmarker,SIImayalsohavevalueasapredictivemarkerforresponsetoimmunotherapy.RecentstudieshavereportedthathighSIIlevelsareassociatedwithdecreasedresponseratesandworseoutcomesinpatientswithmelanomatreatedwithcheckpointinhibitors(13,14).Similarly,inpatientswithrenalcellcarcinomatreatedwithtyrosinekinaseinhibitors(TKIs),highSIIlevelshavebeenshowntopredictworseprogression-freesurvival(PFS)andoverallsurvival(OS)(15).ThesefindingssuggestthatSIImayhaveutilityinidentifyingpatientswhoarelesslikelytorespondtoimmunotherapyandcouldbenefitfromalternativetreatmentstrategies.

OnepotentiallimitationofSIIisthatitmaynotbespecifictotheimmuneresponseagainsttumors.ElevatedSIIcanalsobeseeninpatientswithinfections,autoimmunediseases,andotherchronicinflammatoryconditions(16,17).Consequently,SIIlevelsmaybeinfluencedbyfactorsotherthanthetumormicroenvironment,whichmaylimitthespecificityofthisbiomarker.However,integratingSIIwithothermarkersofinflammation,suchasC-reactiveprotein(CRP),mayimprovespecificityandclinicalutility.

Overall,SIIhasemergedasapromisingbiomarkerforpredictingprognosisandresponsetoimmunotherapyinpatientswithNS