2023
Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting
Singh S, Hope T, Bergsland E, Bodei L, Bushnell D, Chan J, Chasen B, Chauhan A, Das S, Dasari A, Del Rivero J, El-Haddad G, Goodman K, Halperin D, Lewis M, Lindwasser O, Myrehaug S, Raj N, Reidy-Lagunes D, Soares H, Strosberg J, Kohn E, Kunz P, Bergsland E, Beveridge T, Bodei L, Borek A, Brockman M, Bushnell D, Capala J, Chan J, Chasen B, Chauhan A, Das S, Dasari N, Davies-Venn C, Del Rivero J, Demaria S, Donoghue M, Eads J, El-Haddad G, Fielman N, Fishbein L, Gericke G, Goodman K, Halperin D, Hendifar A, Hicks R, Hobbs R, Hobday T, Hope T, Iyer R, Jaffe D, Kennedy A, Kohn E, Kulke M, Kunos C, Kunz P, Lewis M, Lin F, Lindwasser W, Mailman J, McDonald M, McEwan S, Myrehaug S, Nakasato A, Nothwehr S, Ou F, Padda S, Pavel M, Pilowa A, Raj N, Ramnaraign B, Reidy-Lagunes D, Rubinstein L, Saletan S, Shah M, Singh S, Soares H, Soulen M, Strosberg J, Untch B, Wahba M, Wong R, Yao J. Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting. Journal Of The National Cancer Institute 2023, 115: 1001-1010. PMID: 37255328, PMCID: PMC10483264, DOI: 10.1093/jnci/djad096.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapyClinical trialsNeuroendocrine tumorsNeuroendocrine neoplasmsClinical trial recommendationsLiver-dominant diseaseReceptor radionuclide therapyTumor clinical trialsUse of dosimetryImmunotherapy combinationsTherapeutic optionsTreatment optionsGastroenteropancreatic NETsTrial recommendationsConsensus reportNew agentsInhibitor combinationsRadionuclide therapyPatient advocatesMultidisciplinary expertsOptimal sequencingTrialsTreatmentTherapyDisease
2022
Exploratory genomic analysis of high-grade neuroendocrine neoplasms across diverse primary sites.
Sun TY, Zhao L, Van Hummelen P, Martin B, Hornbacker K, Lee H, Xia LC, Padda SK, Ji HP, Kunz P. Exploratory genomic analysis of high-grade neuroendocrine neoplasms across diverse primary sites. Endocrine Related Cancer 2022, 29: 665-679. PMID: 36165930, PMCID: PMC10043760, DOI: 10.1530/erc-22-0015.Peer-Reviewed Original ResearchMeSH KeywordsGenomicsHumansIntestinal NeoplasmsMutationNeuroendocrine TumorsPancreatic NeoplasmsPrognosisStomach NeoplasmsConceptsHigh-grade neuroendocrine neoplasmsDiverse primary sitesG3 NENNeuroendocrine neoplasmsPrimary siteHigh tumor mutation burdenExploratory genomic analysisTumor mutation burdenPoor survival outcomesMutations/MbDifferent primary sitesOrgan of originRare cancer typesSurvival outcomesWorse prognosisRare tumorCell cycling pathwaysMutation burdenTherapeutic implicationsClinical standpointSomatic copy number alterationsCopy number alterationsCancer typesNeoplasmsUpregulation of oncogenesA 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 trial
2020
Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.
Barnes JI, Lin JK, Gupta D, Owens DK, Goldhaber-Fiebert JD, Kunz PL. Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors. Journal Of The National Comprehensive Cancer Network 2020, 18: 1200-1209. PMID: 32886901, DOI: 10.6004/jnccn.2020.7563.Peer-Reviewed Original ResearchConceptsIncremental cost-effectiveness ratioMetastatic enteropancreatic neuroendocrine tumorsEnteropancreatic neuroendocrine tumorsNeuroendocrine tumorsInitial therapyActive surveillanceNCCN Clinical Practice GuidelinesProlonged progression-free survivalProgression-free survivalClinical practice guidelinesActive surveillance strategyLifetime time horizonCost-effectiveness ratioHealthcare sector perspectiveProbabilistic sensitivity analysesCLARINET trialPostprogression treatmentPlacebo armAdrenal tumorsTumor trialsTreatment optionsPractice guidelinesLanreotideSurveillance strategiesQALY
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 ResearchMeSH KeywordsDatabases, FactualHumansNeuroendocrine TumorsPancreatic NeoplasmsProportional Hazards ModelsProspective StudiesConceptsNational 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
Long-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 regressionPatients
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 ResearchMeSH KeywordsCarcinoid Heart DiseaseDiagnosis, DifferentialHumansMaleMiddle AgedNeuroendocrine TumorsPancreatic NeoplasmsSyndromeConceptsPancreatic 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 entityDyspneaEmesisPainUnderstanding Neuroendocrine Tumors—A NET Gain
Kunz PL. Understanding Neuroendocrine Tumors—A NET Gain. JAMA Oncology 2017, 3: 1343-1344. PMID: 28448658, DOI: 10.1001/jamaoncol.2017.0575.Peer-Reviewed Original Research
2016
Neuroendocrine 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
DNA-repair defects in pancreatic neuroendocrine tumors and potential clinical applications
Liu IH, Ford JM, Kunz PL. DNA-repair defects in pancreatic neuroendocrine tumors and potential clinical applications. Cancer Treatment Reviews 2015, 44: 1-9. PMID: 26924193, DOI: 10.1016/j.ctrv.2015.11.006.Peer-Reviewed Original ResearchConceptsDNA repair pathwaysDNA repair defectsRepair pathwaysRepair genesRelevant DNA repair pathwaysPromoter hypermethylationDNA repair gene MGMTDNA repair processesDNA repair genesMMR genesTumor samplesDNA repairGene MGMTSpecific genesLoss of expressionUnderexpressed genesRepair defectsGenetic landscapeGenesMLH1 MMR geneDNA mismatch repair genesRepair mechanismsMGMT geneMismatch repair genesPTENNew and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.
Phan AT, Kunz PL, Reidy-Lagunes DL. New and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors. Clinical Advances In Hematology And Oncology 2015, 13: 1-18; quiz 1 p following 18. PMID: 26430956.Peer-Reviewed Original ResearchConceptsGastroenteropancreatic neuroendocrine tumorsGEP-NETsSomatostatin analoguesTreatment optionsNeuroendocrine tumorsPancreatic NETsLanreotide depot/autogelClassical carcinoid syndromeExtent of metastasisFirst-line treatmentHepatic arterial embolizationMetastatic carcinoid tumorsValvular heart diseasePrimary tumor siteComplex of symptomsAgents everolimusUnresectable diseaseCarcinoid syndromeCytoreductive surgeryArterial embolizationLiver metastasesPalliative treatmentCarcinoid tumorsClinical symptomsAblative therapy
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
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
Pancreatic 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
2011
Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma
Abelson JA, Murphy JD, Minn AY, Chung M, Fisher GA, Ford JM, Kunz P, Norton JA, Visser BC, Poultsides GA, Koong AC, Chang DT. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma. International Journal Of Radiation Oncology • Biology • Physics 2011, 82: e595-e601. PMID: 22197234, DOI: 10.1016/j.ijrobp.2011.09.035.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overAntimetabolites, AntineoplasticChemotherapy, AdjuvantDeoxycytidineDisease-Free SurvivalFemaleFluorouracilGemcitabineHumansMaleMiddle AgedNeoplasm Recurrence, LocalPancreatic NeoplasmsRadiotherapy DosageRadiotherapy, Intensity-ModulatedRetrospective StudiesSurvival RateConceptsIntensity-modulated radiotherapyLocal-regional control ratesPancreatic adenocarcinomaAdjuvant patientsDefinitive patientsControl rateSurvival rateGrade 3 late toxicityRecurrence-free survival ratesThree-dimensional conformal radiotherapyOverall survival rateProspective clinical trialsRecurrence-free survivalDurable disease controlPlanning target volumeGreater acute toxicityAcute toxicityLate toxicityOverall survivalSystemic therapyMedian agePancreatic cancerClinical trialsPrescription doseGrade 3Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer
Schellenberg D, Kim J, Christman-Skieller C, Chun CL, Columbo LA, Ford JM, Fisher GA, Kunz PL, Van Dam J, Quon A, Desser TS, Norton J, Hsu A, Maxim PG, Xing L, Goodman KA, Chang DT, Koong AC. Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer. International Journal Of Radiation Oncology • Biology • Physics 2011, 81: 181-188. PMID: 21549517, DOI: 10.1016/j.ijrobp.2010.05.006.Peer-Reviewed Original ResearchConceptsSingle-fraction stereotactic body radiotherapyAdvanced pancreatic cancerSequential gemcitabinePancreatic cancerGrade 3Local controlIntensity-modulated radiotherapy techniqueStereotactic body radiation therapyGreater nonhematologic toxicityLate grade 3Nonmetastatic pancreatic adenocarcinomaAcute grade 3Cycles of chemotherapyFraction Stereotactic Body Radiation TherapyExcellent local controlPhase II trialStereotactic body radiotherapyBody radiation therapyInternal target volumeInstitutional review boardNonhematologic toxicityAlive patientsII trialLocal progressionDuodenal perforation