2021
177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial
Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP, investigators N. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. The Lancet Oncology 2021, 22: 1752-1763. PMID: 34793718, DOI: 10.1016/s1470-2045(21)00572-6.Peer-Reviewed Original ResearchConceptsMedian overall survivalMidgut neuroendocrine tumorsTreatment-related serious adverse eventsLong-term safety resultsFinal overall survivalPrespecified final analysisPhase 3 trialProgression-free survivalSerious adverse eventsOverall survivalLu-DOTATATE treatmentAdverse eventsNeuroendocrine tumorsLu-DOTATATESecondary endpointsLast patientMyelodysplastic syndromeSafety resultsInteractive web-based response systemControl groupAdvanced midgut neuroendocrine tumorsFinal overall survival analysisWeb-based response systemFinal analysisNETTER-1 trialRapid Progression After 177Lu-DOTATATE in Patients With Neuroendocrine Tumors
Assi HA, Hornbacker K, Shaheen S, Wittenberg T, Silberman R, Kunz PL. Rapid Progression After 177Lu-DOTATATE in Patients With Neuroendocrine Tumors. Pancreas 2021, 50: 890-894. PMID: 34398071, DOI: 10.1097/mpa.0000000000001841.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapyProgressive diseaseNeuroendocrine tumorsBiopsy-proven neuroendocrine tumorHigher disease control rateMedian progression-free survivalShorter progression-free intervalStanford Cancer CenterDisease control rateMetastatic neuroendocrine tumorsMonths of therapyProgression-free survivalProgression-free intervalReceptor radionuclide therapyBetter patient selectionLarge patient cohortHigh-grade componentHigher disease gradeLow-grade componentRepeat biopsyMedian timePatient selectionInitial pathologyPredictive factorsCancer CenterAnalysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database
Cheng E, Blackburn HN, Ng K, Spiegelman D, Irwin ML, Ma X, Gross CP, Tabung FK, Giovannucci EL, Kunz PL, Llor X, Billingsley K, Meyerhardt JA, Ahuja N, Fuchs CS. Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database. JAMA Network Open 2021, 4: e2112539. PMID: 34132794, PMCID: PMC8209612, DOI: 10.1001/jamanetworkopen.2021.12539.Peer-Reviewed Original ResearchConceptsEarly-onset colorectal cancerOnset colorectal cancerNational Cancer DatabaseColorectal cancerAge 51Overall survivalCancer DatabaseIncidence of CRCCox proportional hazards regressionPrimary colorectal cancerKaplan-Meier analysisProportional hazards regressionAge 50 yearsAge 25 yearsAnalysis of survivalCohort studySurvival benefitHazards regressionUnadjusted analysesCancer incidenceMAIN OUTCOMEAge 35Survival advantageLower riskStage I
2020
PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker
Horton TM, Sundaram V, Lee CH, Hornbacker K, Van Vleck A, Benjamin KN, Zemek A, Longacre TA, Kunz PL, Annes JP. PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker. Scientific Reports 2020, 10: 10943. PMID: 32616904, PMCID: PMC7331689, DOI: 10.1038/s41598-020-68071-6.Peer-Reviewed Original ResearchConceptsPrimary neuroendocrine neoplasmsNeuroendocrine neoplasmsPAM immunoreactivityPAM stainingStage-independent predictorUnpredictable clinical behaviorRisk of deathIndividual patient prognosisRare epithelial tumorsHigh-grade tumorsPotential prognostic biomarkerMedian timeSmall bowelAvailable biomarkersTumor sizeDisease stageClinical associationsGrade tumorsClinical behaviorPatient prognosisPrognostic biomarkerEpithelial tumorsTherapy selectionSurvival implicationsPatients
2019
Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors
Toriihara A, Baratto L, Nobashi T, Park S, Hatami N, Davidzon G, Kunz PL, Iagaru A. Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2244-2251. PMID: 31350603, DOI: 10.1007/s00259-019-04455-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overDisease ProgressionDisease-Free SurvivalFemaleHumansImage Processing, Computer-AssistedKaplan-Meier EstimateLiver NeoplasmsMaleMiddle AgedMultivariate AnalysisNeoplasm MetastasisNeuroendocrine TumorsOrganometallic CompoundsPositron Emission Tomography Computed TomographyPrognosisProgression-Free SurvivalProportional Hazards ModelsProspective StudiesReceptors, SomatostatinRetrospective StudiesConceptsProgression-free survivalProportional hazards modelPET/CTPrognostic valueTumor volumeNeuroendocrine tumorsTumor gradeSomatostatin receptorsKaplan-Meier survival analysisCox proportional hazards modelPositron emission tomography/Volume of interestMaximum standardized uptake valueMethodsNinety-two patientsWHO tumor gradeLog-rank testSomatostatin receptor expressionEmission tomography/Standardized uptake valueSignificant differencesVolumetric parametersPrimary endpointIndependent predictorsResultsUnivariate analysisTomography/
2018
Surgical and molecular characterization of primary and metastatic disease in a neuroendocrine tumor arising in a tailgut cyst
Erdrich J, Schaberg KB, Khodadoust MS, Zhou L, Shelton AA, Visser BC, Ford JM, Alizadeh AA, Quake SR, Kunz PL, Beausang JF. Surgical and molecular characterization of primary and metastatic disease in a neuroendocrine tumor arising in a tailgut cyst. Molecular Case Studies 2018, 4: a003004. PMID: 30087100, PMCID: PMC6169824, DOI: 10.1101/mcs.a003004.Peer-Reviewed Original ResearchConceptsGene expression profilesTranscriptomic analysisExpression profilesGenomic characteristicsMolecular characterizationPutative cellSomatic mutationsL cellsGenomic profilingGastrointestinal cellsCellsUnknown significanceNeuroendocrine tumorsFrameshiftMutationsTailgut cystEnteroendocrine L cellsProfilingOriginGenomic testingPotential therapeutic optionRare neuroendocrine tumorsLong-Term Survivors of Pancreatic Cancer
Kardosh A, Lichtensztajn DY, Gubens MA, Kunz PL, Fisher GA, Clarke CA. Long-Term Survivors of Pancreatic Cancer. Pancreas 2018, 47: 958-966. PMID: 30074526, PMCID: PMC6095724, DOI: 10.1097/mpa.0000000000001133.Peer-Reviewed Original ResearchConceptsLong-term survivalPancreatic cancerPancreatic adenocarcinomaCalifornia Cancer RegistryLong-term survivorsPancreatic cancer mortalityAsian/Pacific IslandersNational Cancer InstituteNon-Hispanic whitesAdjuvant chemotherapyUnresectable patientsBaseline characteristicsSurgical resectionTerm survivorsCancer RegistryPoor prognosisSurgical interventionCancer CenterCancer mortalityDegree of differentiationCancer InstituteSurvival rateYounger ageLogistic regressionPatientsChanges in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
Weickert MO, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Öberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clinical Therapeutics 2018, 40: 952-962.e2. PMID: 29724499, DOI: 10.1016/j.clinthera.2018.04.006.Peer-Reviewed Original ResearchConceptsMetastatic neuroendocrine tumorsTelotristat ethylCarcinoid syndromePlacebo TIDWeek 12Neuroendocrine tumorsMetabolic parametersNutritional statusDouble-blind treatment periodWeight gainWeight lossUncontrolled carcinoid syndromeSomatostatin analogue therapyBowel movement frequencyStatistical analysis planOverall nutritional statusAnalogue therapyDiarrhea severityTreatment periodPatientsSyndromeWeight changeAnalysis planMovement frequencyTumorsTelotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial
Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Hörsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocrine Related Cancer 2018, 25: 309-322. PMID: 29330194, PMCID: PMC5811631, DOI: 10.1530/erc-17-0455.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsOpen-label extensionCarcinoid syndromeTelotristat ethylSomatostatin analoguesWeek 12Rates of TEAEsDouble-blind treatment periodPhase 3 trialTryptophan hydroxylase inhibitorMedian treatment differencesCS diarrheaBowel movementsEfficacy endpointAdverse eventsPrimary safetyTreatment periodHydroxylase inhibitorPatientsSerious eventsPercent changeTreatment differencesPlaceboEfficacySignificant reduction
2017
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. New England Journal Of Medicine 2017, 376: 125-135. PMID: 28076709, PMCID: PMC5895095, DOI: 10.1056/nejmoa1607427.Peer-Reviewed Original ResearchConceptsMidgut neuroendocrine tumorsProgression-free survivalAdvanced midgut neuroendocrine tumorsOverall survivalNeuroendocrine tumorsControl groupInterim analysisResponse rateLu-DOTATATEHigh-dose octreotide LARLonger progression-free survivalEnd pointMetastatic midgut neuroendocrine tumorsFinal analysisData cutoff dateObjective response rateOverall survival benefitPrimary end pointSecondary end pointsSomatostatin analogue therapyPhase 3 trialSide effect profileRenal toxic effectsHigh response rateOctreotide LAR
2016
Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome
Kulke MH, Hörsch D, Caplin ME, Anthony LB, Bergsland E, Öberg K, Welin S, Warner RR, Lombard-Bohas C, Kunz PL, Grande E, Valle JW, Fleming D, Lapuerta P, Banks P, Jackson S, Zambrowicz B, Sands AT, Pavel M. Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. Journal Of Clinical Oncology 2016, 35: 14-23. PMID: 27918724, DOI: 10.1200/jco.2016.69.2780.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, HormonalDefecationDiarrheaDouble-Blind MethodFemaleGamma-GlutamyltransferaseGastrointestinal AgentsHumansHydroxyindoleacetic AcidMaleMalignant Carcinoid SyndromeMiddle AgedNauseaOctreotidePeptides, CyclicPhenylalaninePyrimidinesSomatostatinTryptophan HydroxylaseConceptsDouble-blind treatment periodOpen-label extensionTelotristat ethylTryptophan hydroxylase inhibitorBM frequencyCarcinoid syndromeWeek 12Treatment periodHydroxylase inhibitorPlacebo-controlled phase III studyPrimary end pointSomatostatin analogue therapyBowel movement frequencyNew safety signalsPhase III studyGamma-glutamyl transferaseAsymptomatic increaseMild nauseaAnalogue therapyIII studyMethods PatientsSomatostatin analoguesSafety signalsPlaceboPatientsNeuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis
Cloyd JM, Kopecky KE, Norton JA, Kunz PL, Fisher GA, Visser BC, Dua MM, Park WG, Poultsides GA. Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery 2016, 160: 708-713. PMID: 27216830, DOI: 10.1016/j.surg.2016.04.005.Peer-Reviewed Original ResearchConceptsCystic pancreatic neuroendocrine tumorsPancreatic neuroendocrine tumorsRecurrence-free survivalNeuroendocrine tumorsCystic tumorCystic componentSolid tumorsTumor sizeSingle academic medical centerMost pancreatic neuroendocrine tumorsFavorable clinicopathologic featuresSynchronous liver metastasesLymph node positivityLymph node metastasisTotal tumor sizeHigh gradeCross-sectional imagingAcademic medical centerSynchronous liverImmediate resectionLiver metastasesMetastatic diseaseNode positivityOperative resectionClinicopathologic characteristicsA Multi-institutional Analysis of Duodenal Neuroendocrine Tumors: Tumor Biology Rather than Extent of Resection Dictates Prognosis
Margonis GA, Samaha M, Kim Y, Postlewait LM, Kunz P, Maithel S, Tran T, Berger N, Gamblin TC, Mullen MG, Bauer TW, Pawlik TM. A Multi-institutional Analysis of Duodenal Neuroendocrine Tumors: Tumor Biology Rather than Extent of Resection Dictates Prognosis. Journal Of Gastrointestinal Surgery 2016, 20: 1098-1105. PMID: 27008594, DOI: 10.1007/s11605-016-3135-x.Peer-Reviewed Original ResearchConceptsDuodenal neuroendocrine tumorsLocal surgical resectionNeuroendocrine tumorsAdvanced tumor gradeEndoscopic resectionLymph nodesTumor gradeProcedure typeTumor biologyLonger hospital stayOutcomes of patientsSevere postoperative complicationsMetastatic lymph nodesLymph node metastasisMulti-institutional analysisMulti-institutional databaseWorse RFSHospital stayPerioperative complicationsPostoperative complicationsSurgical resectionClinicopathologic characteristicsNode metastasisMedian lengthPD patients
2015
Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma
Nagpal S, Recht CK, Bertrand S, Thomas RP, Ajlan A, Pena J, Gershon M, Coffey G, Kunz PL, Li G, Recht LD. Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma. Journal Of Neuro-Oncology 2015, 123: 277-282. PMID: 25935109, PMCID: PMC4452613, DOI: 10.1007/s11060-015-1795-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic AgentsBevacizumabBrain NeoplasmsDrug Resistance, NeoplasmFemaleFollow-Up StudiesGliomaHeterocyclic Compounds, 4 or More RingsHumansMaleMiddle AgedNeoplasm GradingNeoplasm Recurrence, LocalPilot ProjectsPolyethylene GlycolsPrognosisProspective StudiesSurvival RateYoung AdultConceptsHigh-grade gliomasEtirinotecan pegolOverall survivalRANO criteriaPhase II pilot studyGrade 3 toxicityMedian overall survivalOpen-label trialFurther clinical investigationMedian KPSChemotherapy cyclesHematologic toxicityPrimary endpointSecondary endpointsPartial responseMedian agePatient agePoor prognosisHGG patientsTumor exposureClinical dataAnaplastic astrocytomaBevacizumabClinical investigationGrade gliomas
2014
Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors
Cives M, Kunz P, Morse B, Coppola D, Schell M, Campos T, Nguyen P, Nandoskar P, Khandelwal V, Strosberg J. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors. Endocrine Related Cancer 2014, 22: 1-9. PMID: 25376618, PMCID: PMC4643672, DOI: 10.1530/erc-14-0360.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall radiographic response rateOverall survivalPasireotide LARSomatostatin analoguesFirst-line systemic agentMedian progression-free survivalPhase II clinical trialGrade 3 hyperglycemiaMetastatic grade 1Neuroendocrine tumor growthPrevious systemic therapyRadiographic response rateRates of hyperglycemiaGrade 3/4 toxicitiesMedian overall survivalMetastatic neuroendocrine tumorsPhase II studySolid Tumors criteriaTreatment-naïve patientsHepatic tumor burdenResponse Evaluation CriteriaNovel somatostatin analogReceptor subtype 1LAR treatmentSingle- versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity
Pollom EL, Alagappan M, von Eyben R, Kunz PL, Fisher GA, Ford JA, Poultsides GA, Visser BC, Norton JA, Kamaya A, Cox VL, Columbo LA, Koong AC, Chang DT. Single- versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity. International Journal Of Radiation Oncology • Biology • Physics 2014, 90: 918-925. PMID: 25585785, DOI: 10.1016/j.ijrobp.2014.06.066.Peer-Reviewed Original ResearchConceptsStereotactic body radiation therapyCumulative incidence rateSingle-fraction groupUnresectable pancreatic adenocarcinomaBody radiation therapyPancreatic adenocarcinomaToxicity gradeSurvival rateLocal recurrenceIncidence rateRadiation therapySingle-fraction stereotactic body radiation therapyGastrointestinal toxicity gradeMajority of patientsGastrointestinal toxicityMedian survivalWorse survivalIndependent predictorsPancreatic cancerLocal controlPatientsAdenocarcinomaRecurrenceTherapyMonthsPostradiotherapy CA19-9 Kinetics Correlate With Outcomes in Patients With Pancreatic Adenocarcinoma
Shultz DB, Chan C, Shaffer JL, Kunz PL, Koong AC, Chang DT. Postradiotherapy CA19-9 Kinetics Correlate With Outcomes in Patients With Pancreatic Adenocarcinoma. Pancreas 2014, 43: 777-783. PMID: 24632549, DOI: 10.1097/mpa.0000000000000098.Peer-Reviewed Original ResearchConceptsPostoperative chemoradiotherapyPancreatic ductal adenocarcinomaDuctal adenocarcinomaNonmetastatic pancreatic ductal adenocarcinomaCA19-9 kineticsPretreatment CA19-9Carbohydrate antigen 19Definitive chemoradiotherapyRadiotherapy correlatesOverall survivalMultivariable analysisAntigen 19CA19-9Disease progressionPancreatic adenocarcinomaTreatment decisionsChemoradiotherapyPrognostic toolPatientsKinetics correlateAdenocarcinomaRT correlateFFPTTNProgression
2013
False positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography liver lesion mimicking metastasis in 2 patients with gastroesophageal cancer
Paudel N, Kunz PL, Poultsides GA, Koong AC, Chang DT. False positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography liver lesion mimicking metastasis in 2 patients with gastroesophageal cancer. Practical Radiation Oncology 2013, 4: 368-371. PMID: 25407856, DOI: 10.1016/j.prro.2013.11.005.Peer-Reviewed Original ResearchReassessment of the Current American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Tumors
Qadan M, Ma Y, Visser BC, Kunz PL, Fisher GA, Norton JA, Poultsides GA. Reassessment of the Current American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Tumors. Journal Of The American College Of Surgeons 2013, 218: 188-195. PMID: 24321190, DOI: 10.1016/j.jamcollsurg.2013.11.001.Peer-Reviewed Original ResearchConceptsPancreatic neuroendocrine tumorsAmerican Joint CommitteeStaging systemTNM systemOverall survivalSurgical resectionAJCC systemNeuroendocrine tumorsStage IIIJoint CommitteeCurative-intent surgical resectionEnd Results program dataStage IICurrent American Joint CommitteeCurrent AJCC staging systemCurrent AJCC systemDistant metastatic diseaseUnified staging systemDiscriminatory abilityCancer (AJCC) staging systemAJCC staging systemLymph node metastasisImproved discriminatory abilityNew TNM systemTNM subgroupsPancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness
Worhunsky DJ, Krampitz GW, Poullos PD, Visser BC, Kunz PL, Fisher GA, Norton JA, Poultsides GA. Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. Hepato Pancreato Biliary 2013, 16: 304-311. PMID: 23991643, PMCID: PMC3967881, DOI: 10.1111/hpb.12139.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCell DifferentiationChi-Square DistributionFemaleHumansKaplan-Meier EstimateMaleMiddle AgedMultivariate AnalysisNeuroendocrine TumorsPancreatectomyPancreatic NeoplasmsPredictive Value of TestsProportional Hazards ModelsRetrospective StudiesRisk FactorsTime FactorsTomography, X-Ray ComputedTreatment OutcomeConceptsPancreatic neuroendocrine tumorsOverall survivalArterial phasePre-operative decisionsSynchronous liver metastasesWorse overall survivalMultidisciplinary treatmentSurgical resectionIndependent predictorsLiver metastasesLymph nodesPoor outcomePrognostic significanceClinicopathological variablesNeuroendocrine tumorsCT appearancePancreatic adenocarcinomaBiological aggressivenessTumor enhancementMultivariate analysisTumorsHypoenhancementIntermediate gradeResectionPatients