2024
72 Impact of microbiome modulation on serum cytokine profile in a randomized, phase I trial of cabozantinib/nivolumab (cabo/nivo) with or without CBM588 in pts with metastatic renal cell carcinoma (mRCC)
Li Y, Ebrahimi H, Meza L, Malhotra J, Li X, Dizman N, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin Z, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Gillece J, Trent J, Lee P, Parks T, Takahashi M, Hayashi A, Caporaso J, Lee K, Tripathi A, Pal S. 72 Impact of microbiome modulation on serum cytokine profile in a randomized, phase I trial of cabozantinib/nivolumab (cabo/nivo) with or without CBM588 in pts with metastatic renal cell carcinoma (mRCC). The Oncologist 2024, 29: s36-s37. PMCID: PMC11301871, DOI: 10.1093/oncolo/oyae181.059.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaSerum cytokine profilesCytokine profileClinical outcomesCD8-positive subsetGranulocyte-macrophage colony stimulating factorLevels of IL-12Poor-risk diseasePhase I trialRenal cell carcinomaCirculating cytokine levelsWilcoxon matched-pairs testLevels of cytokinesColony stimulating factorFlow cytometric analysisMatched-pairs testSarcomatoid histologySarcomatoid featuresSystemic immunomodulationCell carcinomaI trialClear cellCytokine levelsInterferon-gIL-13Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin Z, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Jaime-Casas S, Govindarajan A, Gillece J, Trent J, Lee P, Parks T, Takahashi M, Hayashi A, Kortylewski M, Caporaso J, Lee K, Tripathi A, Pal S. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2024, 1-10. PMID: 38942995, DOI: 10.1038/s41591-024-03086-4.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaToxicity profileAbundance of Bifidobacterium sppControl armTreatment-naive participantsFirst-line treatmentPhase 1 studyPhase 1 trialSarcomatoid componentOpen-labelHistological confirmationPrimary endpointSecondary endpointsNo significant differenceClear cellNivolumabInvestigator-initiatedClinical outcomesCabozantinibClinical activityStool samplesStudy armsRenal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances.
Salgia N, Zengin Z, Pal S, Dizman N. Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances. American Society Of Clinical Oncology Educational Book 2024, 44: e438642. PMID: 38776514, PMCID: PMC11235416, DOI: 10.1200/edbk_438642.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaPapillary renal cell carcinomaBiology of renal cell carcinomaHistology renal cell carcinomaPatient populationRenal cell carcinoma histologyMetastatic renal cell carcinomaRenal cell carcinoma casesOptimization of treatment regimensNon-clear cellPrecision oncology approachesDiagnosed solid tumorsSarcomatoid dedifferentiationVariant histologyRare subtypeHistopathological subtypesCell carcinomaSolid tumorsClinical featuresTreatment regimensClinical findingsOncology approachesTherapeutic advancesTherapeutic approachesUnique pathogenesesPrevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy
Ebrahimi H, Battle D, Salgia N, Zengin Z, Dizman N, Meza L, Bergerot C, Barragan-Carrillo R, Hsu J, Castro D, Mercier B, Chawla N, Li X, Tripathi A, Liu S, Chehrazi-Raffle A, Vaishampayan U, Staehler M, Pal S. Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy. Nutrients 2024, 16: 1630. PMID: 38892563, PMCID: PMC11174627, DOI: 10.3390/nu16111630.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaRenal cell carcinomaCell carcinomaDietary modificationSupplement useDiagnosis of renal cell carcinomaFirst-line treatmentSupplement usageSystemic therapyCombination therapyAntineoplastic therapyKetogenic dietCarcinomaCancer therapyMediterranean dietPhysician-patient dialoguePatientsTherapyCancer treatmentGrowing body of evidenceBody of evidenceDietary changesCancerCancer diagnosisCannabidiolImpact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor–based Combinations
Gebrael G, Meza L, Li X, Zengin Z, Sayegh N, Ebrahimi H, Tripathi N, Castro D, Mercier B, Barragan-Carrillo R, Li H, Chehrazi-Raffle A, Swami U, Tripathi A, Agarwal N, Maughan B, Pal S. Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor–based Combinations. European Urology Focus 2024 PMID: 38580524, DOI: 10.1016/j.euf.2024.03.006.Peer-Reviewed Original ResearchTime to treatment failureDisease control rateRenal cell carcinomaSynchronous metastasesMetachronous metastasesOverall survivalMetachronous metastatic renal cell carcinomaMedian time to treatment failureICI-based combination therapyAssociated with worse OSMetastatic renal cell carcinomaFirst-line immunotherapyICI-based combinationsRenal cell carcinoma diagnosisDiagnosis of kidney cancerHypothesis-generating studyMedian OSMetachronous groupPoor OSTreatment failureCombination therapyMetastasis onsetCell carcinomaSurvival outcomesClinical outcomesClinical and molecular characterization of urothelial (UC) vs. small cell carcinoma (SCC) of the urinary tract.
Chawla N, Mercier B, Govindarajan A, Li X, Castro D, Ebrahimi H, Barragan-Carrillo R, Zang P, LeVee A, Dizman N, Hsu J, Meza L, Zengin Z, Salgia N, Chehrazi-Raffle A, Dorff T, Pal S, Tripathi A. Clinical and molecular characterization of urothelial (UC) vs. small cell carcinoma (SCC) of the urinary tract. Journal Of Clinical Oncology 2024, 42: 682-682. DOI: 10.1200/jco.2024.42.4_suppl.682.Peer-Reviewed Original ResearchSmall cell carcinomaFeatures of small cell carcinomaGenome sequencePrevalence of genomic alterationsSmall cell carcinoma patientsSmall cell carcinoma groupFrequency of CDKN2APrevalence of TP53Fisher's exact testTumor gradeCell carcinomaPathological variablesUse of bloodUrinary tractBladder cancerExact testGenomic alterationsProportion Z testGenomic profilingGenomic featuresPathological featuresTherapeutic strategiesGenomic datasetsGenomic characteristicsBonferroni correctionAssociation between thymectomy and incidence of renal cell carcinoma (RCC).
Barragan-Carrillo R, Ebrahimi H, Chawla N, Salgia N, Castro D, Chehrazi-Raffle A, Dizman N, Hsu J, Meza L, Zengin Z, LeVee A, Tripathi A, Dorff T, Bergerot C, Bergerot P, Eilber K, Dallas K, Pal S. Association between thymectomy and incidence of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2024, 42: 371-371. DOI: 10.1200/jco.2024.42.4_suppl.371.Peer-Reviewed Original ResearchRenal cell carcinomaIncidence of nephrectomyIncidence of renal cell carcinomaMedian age of patientsFrequency of nephrectomyAge of patientsT cell productionProportion of patientsRate of nephrectomyFisher's exact testGeneral populationAge-matched populationICD-9/10 codesPopulation-based cohortPopulation-based studyImmunogenic cancerPrior thymectomyChi-square testCell carcinomaMedian ageSurgical interventionNephrectomyThymectomyExact testOSHPD database
2023
Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab
Tripathi N, Meza L, Sayegh N, Govindarajan A, Byron S, Zhang J, Chigarira B, Jo Y, Zengin Z, Li H, Gebrael G, Desai A, Agarwal N, Swami U, Maughan B, Pal S. Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab. Kidney Cancer 2023, 7: 137-145. DOI: 10.3233/kca-230011.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClear cell metastatic renal cell carcinomaClinical benefit groupRenal cell carcinomaClinical benefitNivolumab therapyCell carcinomaPoor-risk metastatic renal cell carcinomaMetastatic clear cell renal cell carcinomaBenefit groupClear cell renal cell carcinomaFirst-line ipilimumabIMDC risk scoresFirst-line treatmentCell renal cell carcinomaAlteration frequencyChi-square testMRCC patientsStable diseaseComplete responsePartial responseSystemic therapyLine treatmentInflammatory pathwaysTumor-specific gene expressionAssociation Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma
Dizman N, Govindarajan A, Zengin Z, Meza L, Tripathi N, Sayegh N, Castro D, Chan E, Lee K, Prajapati S, Feng M, Loo V, Pace M, O'Brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Hsu J, Li X, Agarwal N, Pal S. Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 530-536. PMID: 37495481, DOI: 10.1016/j.clgc.2023.06.004.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaObjective response rateTreatment failureRenal cell carcinomaHazard ratioOverall survivalCell carcinomaMultivariate analysisHigh Cut-OffNivolumab/ipilimumabProspective Randomized StudyBaseline characteristicsRandomized studyClinical outcomesMedian timePreclinical evidenceUnivariate analysisPatientsResponse rateImmune systemInfusion timeStatistical significanceOutcomesCarcinomaInfusionAssessment of short-chain fatty acid (SCFA) and circulating cytokine trends in a clinical trial of nivolumab/ipilimumab and CBM588 in metastatic renal cell carcinoma (mRCC).
Dizman N, Pathak K, Alcantara M, Meza L, Bergerot P, Willey M, Dorff T, Hsu J, Zengin Z, Castro D, Ebrahimi H, Chehrazi-Raffle A, Tripathi A, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Pirrotte P, Pal S. Assessment of short-chain fatty acid (SCFA) and circulating cytokine trends in a clinical trial of nivolumab/ipilimumab and CBM588 in metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 4556-4556. DOI: 10.1200/jco.2023.41.16_suppl.4556.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaNivolumab/ipilimumabObjective response rateShort-chain fatty acidsPlasma short-chain fatty acidsImmune checkpoint blockadeCheckpoint blockadeCytokine levelsSCFA levelsClinical trialsRandomized phase I clinical trialSarcomatoid Metastatic Renal Cell CarcinomaPhase I clinical trialStool SCFA levelsAcid levelsTreatment-naïve patientsAltered amino acid metabolismRenal cell carcinomaIpilimumab armNaïve patientsButyric acid levelsSerum cytokinesClinical outcomesCell carcinomaBiologic rationaleAssociation between intra-tumoral microbiome and clinical benefit (CB) from immunotherapy (IO) in patients with metastatic renal cell carcinoma (mRCC).
Meza L, Choi Y, Zhang J, Dizman N, Zengin Z, Ebrahimi H, Barragan-Carrillo R, Hsu J, Chawla N, Chehrazi-Raffle A, Tripathi A, Castro D, Mercier B, Govindarajan A, Chan A, Schork N, Byron S, Pal S. Association between intra-tumoral microbiome and clinical benefit (CB) from immunotherapy (IO) in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 4561-4561. DOI: 10.1200/jco.2023.41.16_suppl.4561.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClinical benefitLine immunotherapyMicrobial diversityNivolumab/ipilimumabStart of immunotherapyBacterial diversityClear cell histologyPD-L1 expressionRenal cell carcinomaRelative abundanceAvailable RNA sequencing dataRelative microbial abundanceParaffin-embedded samplesRNA sequencing dataRNA-seq readsCell histologyCommon regimenMedian ageLine treatmentCell carcinomaPoor riskShannon diversity indexRCC tumorsImmunotherapyUltrasensitive Circulating Tumor DNA Pilot Study Distinguishes Complete Response and Partial Response With Immunotherapy in Patients With Metastatic Renal Cell Carcinoma
Chehrazi-Raffle A, Muddasani R, Dizman N, Hsu J, Meza L, Zengin Z, Malhotra J, Chawla N, Dorff T, Contente-Cuomo T, Dinwiddie D, McDonald B, McDaniel T, Trent J, Baehner F, Murtaza M, Pal S. Ultrasensitive Circulating Tumor DNA Pilot Study Distinguishes Complete Response and Partial Response With Immunotherapy in Patients With Metastatic Renal Cell Carcinoma. JCO Precision Oncology 2023, 7: e2200543. PMID: 37027813, PMCID: PMC10309555, DOI: 10.1200/po.22.00543.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaPartial responseComplete responseVariant allele fractionRenal cell carcinomaCell carcinomaCtDNA analysisImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyDiscontinuation of immunotherapyDepth of responseICI therapyNivolumab monotherapyEligible patientsRadiographic progressionInhibitor therapyPeripheral bloodDisease progressionCtDNA assessmentSubsequent progressionPatientsMultiple indicationsSingle time pointPatient-specific mutationsSecondary objectiveTwelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis
Meza L, Zengin Z, Salgia S, Malhotra J, Karczewska E, Dorff T, Tripathi A, Ely J, Kelley E, Mead H, Hsu J, Dizman N, Salgia N, Chawla N, Chehrazi-Raffle A, Muddasani R, Govindarajan A, Rock A, Liu S, Salgia R, Trent J, Altin J, Pal S. Twelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis. The Oncologist 2023, 28: e748-e755. PMID: 36971500, PMCID: PMC10485287, DOI: 10.1093/oncolo/oyad067.Peer-Reviewed Original ResearchConceptsCOVID-19 vaccinationGenitourinary cancersRenal cell carcinomaBooster doseCell carcinomaImmune responseBlood samplesSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2T-cell receptor sequencingRespiratory syndrome coronavirus 2Baseline blood samplesMajority of patientsMinority of patientsProspective cohort analysisSyndrome coronavirus 2Twelve-month followAntibody titer analysisCOVID-19 vaccineSeroconversion ratesMedian ageUrothelial cancerCoronavirus 2Prostate cancerCohort analysisEvaluation of eligibility criteria in contemporary renal cell carcinoma based on ASCO-FCR recommendations.
Prajapati S, Feng M, Castro D, Lee K, Chan E, Sehgal I, Patel J, O'Dell A, Zengin Z, Li X, Chehrazi-Raffle A, Dizman N, Tripathi A, Rock A, Liu S, Mercier B, Meza L, Philip E, Dorff T, Pal S. Evaluation of eligibility criteria in contemporary renal cell carcinoma based on ASCO-FCR recommendations. Journal Of Clinical Oncology 2023, 41: 612-612. DOI: 10.1200/jco.2023.41.6_suppl.612.Peer-Reviewed Original ResearchRestrictive eligibility criteriaEligibility criteriaHCV positivityHIV positivityInclusion criteriaExclusion criteriaExact testClass of therapyReal-world populationRenal cell carcinomaFisher's exact testChi-square testConcurrent malignancyBrain metastasesAdult patientsCell carcinomaCombination therapyPatient populationCancer trialsRCC trialsConsensus statementRadiation therapyClinical OncologyPrognostic toolReal-world settingPrevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma (mRCC).
Ebrahimi H, Battle D, Zengin Z, Dizman N, Meza L, Castro D, Govindarajan A, Mercier B, Chawla N, Chehrazi-Raffle A, Tripathi A, Liu S, Vaishampayan U, Staehler M, Pal S. Prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 662-662. DOI: 10.1200/jco.2023.41.6_suppl.662.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaRenal cell carcinomaDietary modificationSupplement useCell carcinomaSupplement intakeKetogenic dietSupplement usageActive systemic therapyNivolumab/ipilimumabFirst-line treatmentMajority of patientsT-testPatient advocacy groupsChi-square testStudent's t-testClinical trial candidatesOnly patientsSystemic therapyMedian ageAntineoplastic treatmentProspective studyPotential confoundersInclusion criteriaMediterranean dietAssociation between time-of-day of the immune checkpoint inhibitor (ICI) infusion and disease outcomes among patients with metastatic renal cell carcinoma (mRCC).
Dizman N, Govindarajan A, Zengin Z, Meza L, Tripathi N, Sayegh N, Castro D, Chan E, Lee K, Prajapati S, Feng M, Loo V, Pace M, O'brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Li X, Agarwal N, Pal S. Association between time-of-day of the immune checkpoint inhibitor (ICI) infusion and disease outcomes among patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 678-678. DOI: 10.1200/jco.2023.41.6_suppl.678.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaMedian overall survivalOverall survivalHazard ratioPotential confoundersMedian TTFDisease outcomeMultivariate analysisCox proportional hazards modelEfficacy of ICIsObjective response ratePoor-risk diseaseProgression-free survivalSecond-line treatmentClear cell histologyRenal cell carcinomaProportional hazards modelBaseline characteristicsFree survivalCell histologyMedian ageRisk diseaseTreatment failureEntire cohortCell carcinomaGenomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma
Zengin Z, Govindarajan A, Salgia N, Sayegh N, Tripathi N, Muddasani R, Chehrazi-Raffle A, Feng M, Mercier B, Ladbury C, Hao C, Salgia S, Chawla N, Meza L, Malhotra J, Dizman N, Hsu J, Castro D, Barragan-Carrillo R, Ebrahimi H, Philip E, Chang M, Zhang J, Byron S, Lyou Y, Dorff T, Pal S, Dandapani S. Genomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma. European Urology Oncology 2023, 6: 447-450. PMID: 36609061, DOI: 10.1016/j.euo.2022.11.006.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaStereotactic body radiation therapyRenal cell carcinomaBody radiation therapyCell carcinomaRadiation therapyClear cell renal cell carcinomaFirst-line treatmentCell renal cell carcinomaStereotactic body radiotherapyKidney cancer patientsOligoprogressive diseaseSystemic treatmentReactive oxygen species pathwayBody radiotherapyCancer patientsTreatment selectionPatientsTreatment changesOxygen species pathwayRadiation treatmentCarcinomaCell proliferationPotential roleRadiotherapy
2022
880 Activation of STAT3 signaling is associated with resistance to immune checkpoint inhibitors in patients (pts) with metastatic renal cell carcinoma (mRCC)
Chehrazi-Raffle A, Alcantara M, Dizman N, Tang W, Meza L, Zengin Z, Wang D, Moreira D, Castro D, Govindarajan A, Horsager A, Hsu J, Pal S, Kortylewski M. 880 Activation of STAT3 signaling is associated with resistance to immune checkpoint inhibitors in patients (pts) with metastatic renal cell carcinoma (mRCC). 2022, a917-a917. DOI: 10.1136/jitc-2022-sitc2022.0880.Peer-Reviewed Original Research1479P Ultra-sensitive circulating tumor DNA (ctDNA) assay distinguishes partial response (PR) and complete response (CR) with immunotherapy in metastatic renal cell carcinoma (mRCC)
Chehrazi-Raffle A, Muddasani R, Dizman N, Hsu J, Meza L, Zengin Z, Malhotra J, Chawla N, Lyou Y, Dorff T, Contente-Cuomo T, Dinwiddie D, McDonald B, Trent J, Murtaza M, Pal S. 1479P Ultra-sensitive circulating tumor DNA (ctDNA) assay distinguishes partial response (PR) and complete response (CR) with immunotherapy in metastatic renal cell carcinoma (mRCC). Annals Of Oncology 2022, 33: s1223. DOI: 10.1016/j.annonc.2022.07.1582.Peer-Reviewed Original ResearchTemporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer
Zengin Z, Pal S, McDermott D, Escudier B, Hutson T, Porta C, Verzoni E, Atkins M, Kasturi V, Rini B. Temporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer. Clinical Genitourinary Cancer 2022, 20: 553-557. PMID: 36096984, DOI: 10.1016/j.clgc.2022.08.005.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaRenal cell carcinomaDose modificationSorafenib armAdverse eventsCell carcinomaVascular endothelial growth factor receptor inhibitorEndothelial growth factor receptor inhibitorImproved progression-free survivalGrowth factor receptor inhibitorsProgression-free survivalDuration of toxicityMeasurable diseaseOpen labelFree survivalPrimary endpointTreatment discontinuationTreatment armsReceptor inhibitorsDose reductionKidney cancerTRAEsPatientsTivozanibSorafenib