2023
Novel use of alternate (Alt) response (Rp) criteria (Cr) for early prediction of outcomes in pancreatic (P) neuroendocrine tumors (NETs): Utilizing banked imaging data from the ECOG-ACRIN E2211 study.
Vijayvergia N, Handorf E, Kunz P, Alkim E, Burke L, Catalano P, Graham N, Levin L, Li W, Meeker C, Rubin D, Narasimhan Sridharan A, O'Dwyer P, Wong T, Anaokar J. Novel use of alternate (Alt) response (Rp) criteria (Cr) for early prediction of outcomes in pancreatic (P) neuroendocrine tumors (NETs): Utilizing banked imaging data from the ECOG-ACRIN E2211 study. Journal Of Clinical Oncology 2023, 41: 4133-4133. DOI: 10.1200/jco.2023.41.16_suppl.4133.Peer-Reviewed Original ResearchProgression-free survivalImproved progression-free survivalNeuroendocrine tumorsStable diseaseProgressive diseaseRadiomic featuresCT/MRI scansPancreatic neuroendocrine tumorsPortal venous phaseShort-term imagingSmaller threshold changesInter-reader agreementTumor sizeC-statisticFirst disease assessmentPotential adjunctTreatment decisionsVenous phasePD casesTime-varying outcomeMRI scansClinical practicePredictive valueTumor densityInter-reader variability
2022
A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161
Rajdev L, Lee JW, Libutti SK, Benson AB, Fisher GA, Kunz PL, Hendifar AE, Catalano P, O’Dwyer P. A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161. Investigational New Drugs 2022, 40: 1306-1314. PMID: 36264382, PMCID: PMC9795724, DOI: 10.1007/s10637-022-01311-w.Peer-Reviewed Original ResearchConceptsPancreatic neuroendocrine tumorsNeuroendocrine tumorsTreatment-related grade 3 adverse eventsGrade 3 adverse eventsAdvanced pancreatic neuroendocrine tumorsTwo-stage phase II trialObjective tumor responsePhase II studyPhase II trialContinuous dosing scheduleStage 1Lack of responseEligible patientsMedian OSMedian PFSII trialAdverse eventsII studyObjective responseDosing schedulesTumor responseClinical activityPatientsMTOR pathwayMTORC1/2 inhibitorsRandomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211)
Kunz PL, Graham NT, Catalano PJ, Nimeiri HS, Fisher GA, Longacre TA, Suarez CJ, Martin BA, Yao JC, Kulke MH, Hendifar AE, Shanks JC, Shah MH, Zalupski MM, Schmulbach EL, Reidy-Lagunes DL, Strosberg JR, O'Dwyer PJ, O'Dwyer P, Benson A. Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). Journal Of Clinical Oncology 2022, 41: 1359-1369. PMID: 36260828, PMCID: PMC9995105, DOI: 10.1200/jco.22.01013.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic neuroendocrine tumorsProgression-free survivalPancreatic neuroendocrine tumorsMedian progression-free survivalPrimary end pointNeuroendocrine tumorsResponse rateObjective responseOverall survivalRandomized studyIntermediate-grade pancreatic neuroendocrine tumorsLonger progression-free survivalEnd pointMGMT deficiencyMedian overall survivalPrimary analysis populationKey eligibility criteriaPhase II trialSmall prospective studiesHigh response rateMethylguanine methyltransferaseCapecitabine/Eligible patientsSecondary endpointsII trialA randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and evaluation of MGMT (ECOG-ACRIN E2211).
Kunz P, Graham N, Catalano P, Nimeiri H, Fisher G, Longacre T, Suarez C, Rubin D, Yao J, Kulke M, Hendifar A, Shanks J, Shah M, Zalupski M, Schmulbach E, Reidy D, Strosberg J, Wong T, O'Dwyer P, Benson A. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and evaluation of MGMT (ECOG-ACRIN E2211). Journal Of Clinical Oncology 2022, 40: 4004-4004. DOI: 10.1200/jco.2022.40.16_suppl.4004.Peer-Reviewed Original ResearchProgression-free survivalPancreatic neuroendocrine tumorsMedian progression-free survivalAdvanced pancreatic neuroendocrine tumorsCombination of capecitabineNeuroendocrine tumorsResponse rateEligible patientsPrimary endpointOverall survivalIntermediate-grade pancreatic neuroendocrine tumorsTwo-sided log-rank testLonger progression-free survivalEfficacy analysis populationObjective tumor responsePhase II trialLog-rank testHigh response rateSecondary endpointsII trialProspective studyAnalysis populationTreatment optionsTumor responseInterim analysisEverolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance).
Kulke MH, Ou FS, Niedzwiecki D, Huebner L, Kunz P, Kennecke HF, Wolin EM, Chan JA, O'Reilly EM, Meyerhardt JA, Venook A. Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance). Endocrine Related Cancer 2022, 29: 335-344. PMID: 35324465, PMCID: PMC9257687, DOI: 10.1530/erc-21-0239.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic neuroendocrine tumorsProgression-free survivalPancreatic neuroendocrine tumorsVEGF pathway inhibitorsCombination armPrimary endpointMedian overall survival durationTreatment-related adverse eventsImproved progression-free survivalRandomized phase II studySuperior progression-free survivalPathway inhibitorOverall survival durationPhase II studyTreatment-related toxicityCombination of everolimusMTOR inhibitor everolimusHigh response rateAdverse eventsII studyInvestigator reviewCombination therapyStandard doseInhibitor everolimusNeuroendocrine tumors
2019
Surgery Versus Surveillance for Well‐Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11‐Year Analysis of the National Cancer Database
Assi HA, Mukherjee S, Kunz PL, Machiorlatti M, Vesely S, Pareek V, Hatoum H. Surgery Versus Surveillance for Well‐Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11‐Year Analysis of the National Cancer Database. The Oncologist 2019, 25: e276-e283. PMID: 32043766, PMCID: PMC7011621, DOI: 10.1634/theoncologist.2019-0466.Peer-Reviewed Original ResearchConceptsNational Cancer DatabaseIndependent prognostic factorPancreatic neuroendocrine tumorsCharlson-Deyo comorbidity scoreNonfunctional pancreatic neuroendocrine tumorsImproved overall survivalSurgical resectionNF-PanNETOverall survivalPrognostic factorsTumor sizeNeuroendocrine tumorsActive surveillanceCancer DatabaseComorbidity scoreClinicopathologic characteristicsLarge tumorsTumor locationProspective randomized clinical trialsSafe approachActive interventionLarge asymptomatic tumorTumor size 1Underwent surgical resectionPatients' clinicopathologic characteristics
2018
A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211).
Kunz P, Catalano P, Nimeiri H, Fisher G, Longacre T, Suarez C, Yao J, Kulke M, Hendifar A, Shanks J, Shah M, Zalupski M, Schmulbach E, Reidy D, Strosberg J, O'Dwyer P, Benson A. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211). Journal Of Clinical Oncology 2018, 36: 4004-4004. DOI: 10.1200/jco.2018.36.15_suppl.4004.Peer-Reviewed Original Research
2017
Carcinoid Syndrome Complicating a Pancreatic Neuroendocrine Tumor
Gerson JN, Witteles RM, Chang DT, Beygui RE, Iagaru AH, Kunz PL. Carcinoid Syndrome Complicating a Pancreatic Neuroendocrine Tumor. Pancreas 2017, 46: 1381-1385. PMID: 29040196, DOI: 10.1097/mpa.0000000000000932.Peer-Reviewed Original ResearchConceptsPancreatic neuroendocrine tumorsNeuroendocrine tumorsCarcinoid syndromeRight upper quadrant abdominal painUpper quadrant abdominal painMetastatic pancreatic neuroendocrine tumorsRight-sided heart diseaseQuadrant abdominal painPulmonic valve replacementAbdominal painSystemic chemotherapyTreatable complicationHormone excessSerum serotoninValve replacementHeart diseaseHeterogeneous groupSyndromeElevated levelsTumorsDiseaseImportant entityDyspneaEmesisPain
2016
Oxaliplatin–Fluoropyrimidine Chemotherapy Plus Bevacizumab in Advanced Neuroendocrine Tumors
Kunz PL, Balise RR, Fehrenbacher L, Pan M, Venook AP, Fisher GA, Tempero MA, Ko AH, Korn WM, Hwang J, Bergsland EK. Oxaliplatin–Fluoropyrimidine Chemotherapy Plus Bevacizumab in Advanced Neuroendocrine Tumors. Pancreas 2016, 45: 1394-1400. PMID: 27171514, DOI: 10.1097/mpa.0000000000000659.Peer-Reviewed Original ResearchConceptsRadiographic response rateAdvanced neuroendocrine tumorsPrimary end pointProgression-free survivalNeuroendocrine tumorsPancreatic neuroendocrine tumorsNeuroendocrine carcinomaProspective phase II studyB studyEnd pointProlonged disease stabilityPhase II studyEffectiveness of bevacizumabDifferentiated neuroendocrine carcinomaPredictable toxicityRR-18Maintenance therapyDisease stabilityII studyRadiographic responsePatientsResponse rateNET subtypesBevacizumabMonthsNeuroendocrine 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 characteristics
2015
Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance).
Kulke M, Niedzwiecki D, Foster N, Fruth B, Kunz P, Kennecke H, Wolin E, Venook A. Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance). Journal Of Clinical Oncology 2015, 33: 4005-4005. DOI: 10.1200/jco.2015.33.15_suppl.4005.Peer-Reviewed Original ResearchA randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211).
Kunz P, Catalano P, Nimeiri H, Fisher G, Longacre T, Schrijver I, Reidy D, Strosberg J, O'Dwyer P, Benson A. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211). Journal Of Clinical Oncology 2015, 33: tps4145-tps4145. DOI: 10.1200/jco.2015.33.15_suppl.tps4145.Peer-Reviewed Original Research
2013
Reassessment 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
2012
Neuroendocrine tumors.
Kulke MH, Benson AB, Bergsland E, Berlin JD, Blaszkowsky LS, Choti MA, Clark OH, Doherty GM, Eason J, Emerson L, Engstrom PF, Goldner WS, Heslin MJ, Kandeel F, Kunz PL, Kuvshinoff BW, Moley JF, Pillarisetty VG, Saltz L, Schteingart DE, Shah MH, Shibata S, Strosberg JR, Vauthey JN, White R, Yao JC, Freedman-Cass DA, Dwyer MA. Neuroendocrine tumors. Journal Of The National Comprehensive Cancer Network 2012, 10: 724-64. PMID: 22679117, DOI: 10.6004/jnccn.2012.0075.Peer-Reviewed Original ResearchConceptsNeuroendocrine tumorsIntermediate-grade tumorsPancreatic neuroendocrine tumorsNCCN guidelinesSurgical managementTumorsDiagnosisRecommendations pertainGuidelinesPancreasPathologyA renaissance in therapeutic options for pancreatic neuroendocrine tumors.
Kunz PL. A renaissance in therapeutic options for pancreatic neuroendocrine tumors. American Society Of Clinical Oncology Educational Book 2012, 271-4. PMID: 24451747, DOI: 10.14694/edbook_am.2012.32.136.Peer-Reviewed Original ResearchProgression-free survivalPancreatic neuroendocrine tumorsNeuroendocrine tumorsTherapeutic optionsRandomized placebo-controlled studyPlacebo-controlled studyNovel therapeutic optionsChemotherapy backboneLocoregional diseaseAdvanced diseaseBiologic therapySurgical resectionSomatostatin analoguesClinical trialsDrug AdministrationU.S. FoodAntiproliferative agentsTumorsDiseaseFuture studiesResectionEverolimusSunitinibPatientsOptionsPancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis
Poultsides GA, Huang LC, Chen Y, Visser BC, Pai RK, Brooke Jeffrey R, Park WG, Chen AM, Kunz PL, Fisher GA, Norton JA. Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis. Annals Of Surgical Oncology 2012, 19: 2295-2303. PMID: 22396008, DOI: 10.1245/s10434-012-2305-7.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenoma, Islet CellAdultAgedCalcinosisFemaleFollow-Up StudiesGastrinomaHumansInsulinomaLiver NeoplasmsLymphatic MetastasisMaleMiddle AgedNeoplasm StagingNeoplasms, Multiple PrimaryNeuroendocrine TumorsPancreatectomyPancreatic NeoplasmsPrognosisRetrospective StudiesStomach NeoplasmsTomography, X-Ray ComputedConceptsPancreatic neuroendocrine tumorsSynchronous liver metastasesLymph node metastasisLiver metastasesNode metastasisOverall survivalRadiographic calcificationsHigh-grade pancreatic neuroendocrine tumorsComputed tomography correlateIntermediate tumor gradeRegional lymph nodesPreoperative computed tomographyPresence of calcificationCurative intentFormal pancreatectomyMethodsFrom 1998Surgical resectionIndependent predictorsLymph nodesPrognostic significanceCalcified tumorClinicopathologic variablesNeuroendocrine tumorsPrimary tumorTumor grade