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 sequencingTrialsTreatmentTherapyDiseaseA 46-Year-Old Woman With Chronic Dyspnea and Diarrhea
Kshattry S, White M, Tchack J, Laskin W, Kunz P. A 46-Year-Old Woman With Chronic Dyspnea and Diarrhea. CHEST Journal 2023, 163: e23-e29. PMID: 36628681, DOI: 10.1016/j.chest.2022.08.2214.Peer-Reviewed Original ResearchConceptsPack-year historyCurrent tobacco usePertinent medical historyReview of systemsNew edemaAbdominal painChest painChronic dyspneaHealthy womenHot flashesRecent travelMedical historyDegree relativesFamily historyTobacco useOlder womenColon cancerHeart palpitationsMedical careWeight lossDyspneaPainDiarrheaWomenEpisodes
2022
PRESTO 2: An International Survey to Evaluate Patients’ Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly
O’Toole D, Kunz P, Webb S, Goldstein G, Khawaja S, McDonnell M, Boiziau S, Gueguen D, Houchard A, Ribeiro-Oliveira A, Prebtani A. PRESTO 2: An International Survey to Evaluate Patients’ Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly. Advances In Therapy 2022, 40: 671-690. PMID: 36502449, PMCID: PMC9741754, DOI: 10.1007/s12325-022-02360-6.Peer-Reviewed Original ResearchConceptsInjection site painNeuroendocrine tumorsInjection experienceRecent injectionLanreotide autogel/depotMultivariate logistic regression modelOdds of painSomatostatin analogue therapyProportion of patientsInjection site reactionsLogistic regression modelsSSA useAnalogue therapySecondary endpointsDisease subgroupsPainPatientsAcromegalyInjection modalitiesMonthsInjectionTumorsWhere Are All the Women in Industry Advisory Boards?
Shroff R, Goodman K, Mehnert J, Vose J, Moran S, Yessaian J, Baldo L, Alexander B, Highsmith Q, Mills J, Kunz P. Where Are All the Women in Industry Advisory Boards? Journal Of Clinical Oncology 2022, 41: 1659-1663. PMID: 36331246, DOI: 10.1200/jco.21.02219.Peer-Reviewed Original ResearchExploratory 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 ResearchConceptsHigh-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 trialMicroangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study
Lam R, Tarangelo N, Wang R, Horibe M, Grimshaw AA, Jain D, Haffar S, Bazerbachi F, Kunz PL, Li DK. Microangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study. The Oncologist 2022, 27: 751-759. PMID: 35589098, PMCID: PMC9438916, DOI: 10.1093/oncolo/oyac093.Peer-Reviewed Original ResearchConceptsGastric signet ring cell carcinomaSignet ring cell carcinomaMicroangiopathic hemolytic anemiaHemolytic anemiaCell carcinomaMultivariable Cox proportional hazards regression modelingCox proportional hazards regression modelingSystematic reviewRare paraneoplastic syndromeStage-matched casesEnd Results (SEER) databaseLate-stage complicationsRisk of mortalityCase-control studyBone painParaneoplastic syndromeFatal complicationMedian survivalMetastatic diseaseOverall survivalLymph nodesIndex presentationPrognostic featuresResults databasePooled cohortEverolimus 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
2021
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: clinical characteristics and progression to carcinoid tumour
Sun TY, Hwang G, Pancirer D, Hornbacker K, Codima A, Lui NS, Raj R, Kunz P, Padda SK. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: clinical characteristics and progression to carcinoid tumour. European Respiratory Journal 2021, 59: 2101058. PMID: 34795035, PMCID: PMC8792466, DOI: 10.1183/13993003.01058-2021.Peer-Reviewed Original ResearchConceptsDiffuse idiopathic pulmonary neuroendocrine cell hyperplasiaIdiopathic pulmonary neuroendocrine cell hyperplasiaPulmonary neuroendocrine cell hyperplasiaElderly white womenNeuroendocrine cell hyperplasiaBasement membraneSuch hyperplasiaClinical characteristicsCarcinoid tumorsCell hyperplasiaIdentifiable causeLung diseasePreinvasive lesionsRare diseaseTumorsWhite womenNeuroendocrine cellsLung nodulesHyperplasiaTumourletsDiseaseNodulesNeoplasmsLesionsYears177Lu-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 trialMaking Sense of a Complex Disease: A Practical Approach to Managing Neuroendocrine Tumors
Zhang JY, Kunz PL. Making Sense of a Complex Disease: A Practical Approach to Managing Neuroendocrine Tumors. JCO Oncology Practice 2021, 18: 258-264. PMID: 34652954, DOI: 10.1200/op.21.00240.Peer-Reviewed Original ResearchConceptsNeuroendocrine tumorsFunctional statusPrimary sitePrevalence of NETsMetastatic neuroendocrine tumorsExtent of diseaseOngoing clinical trialsSomatostatin receptor statusIndividualized treatment planHeterogeneous clinical entityPace of diseaseConsideration of patientsPerformance statusSystemic therapyReceptor statusTumor characteristicsClinical entityTherapeutic optionsPathologic classificationClinical trialsTherapeutic decisionsDiagnostic modalitiesTreatment planDiseasePatientsComparison of Design, Eligibility, and Outcomes of Neuroendocrine Neoplasm Trials Initiated From 2000 to 2009 vs 2010 to 2020
Das S, Du L, Lee CL, Arhin ND, Chan JA, Kohn EC, Halperin DM, Berlin J, LaFerriere H, Singh S, Kunz PL, Dasari A. Comparison of Design, Eligibility, and Outcomes of Neuroendocrine Neoplasm Trials Initiated From 2000 to 2009 vs 2010 to 2020. JAMA Network Open 2021, 4: e2131744. PMID: 34705010, PMCID: PMC8552059, DOI: 10.1001/jamanetworkopen.2021.31744.Peer-Reviewed Original ResearchConceptsNeuroendocrine neoplasmsClinical trialsNational Cancer Institute Clinical TrialsEU Clinical Trials RegisterCoprimary end pointsObjective response rateProgression-free survivalClinical Trials RegisterKi-67 indexAllied Health LiteratureQuality improvement studyPhase IISpecific disease populationsWeb of ScienceDrug licensureTrials RegisterCochrane DatabaseTumor differentiationNovel agentsDisease populationInclusion criteriaMAIN OUTCOMECumulative IndexEnrollment periodResponse rateTemozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review
Chan DL, Bergsland EK, Chan JA, Gadgil R, Halfdanarson TR, Hornbacker K, Kelly V, Kunz PL, McGarrah PW, Raj NP, Reidy DL, Thawer A, Whitman J, Wu L, Becker C, Singh S. Temozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review. The Oncologist 2021, 26: 950-955. PMID: 34342086, PMCID: PMC8571741, DOI: 10.1002/onco.13923.Peer-Reviewed Original ResearchConceptsG3 neuroendocrine neoplasmsFirst-line settingPercent of patientsMulticenter retrospective reviewTreatment failureGastroenteropancreatic neuroendocrine neoplasmsNeuroendocrine neoplasmsRetrospective reviewOptimal treatmentResponse rateGastrointestinal neuroendocrine neoplasmsLocal pathology reportsDiscontinuation of therapyMedian TTFFirst-line treatmentOverall response rateConfirmatory prospective studiesViable treatment optionPancreatic neuroendocrine neoplasmsRadiologic responseTemozolomide regimenPrimary endpointAdverse eventsMedian durationRadiographic responseRapid 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 IThe North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.
Fishbein L, Del Rivero J, Else T, Howe JR, Asa SL, Cohen DL, Dahia PLM, Fraker DL, Goodman KA, Hope TA, Kunz PL, Perez K, Perrier ND, Pryma DA, Ryder M, Sasson AR, Soulen MC, Jimenez C. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma. Pancreas 2021, 50: 469-493. PMID: 33939658, DOI: 10.1097/mpa.0000000000001792.Peer-Reviewed Original ResearchConceptsUnresectable pheochromocytomaMedical managementNorth American Neuroendocrine Tumor Society Consensus GuidelinesRadiologists/nuclear medicine physiciansNuclear medicine physiciansMedical oncologistsConsensus guidelinesMedicine physiciansConsensus conferenceRadiation oncologistsPheochromocytomaParagangliomaOncologistsSurveillancePanel membersFinal recommendationsLiterature reviewFinal approvalControversial topicExamination of factors associated with lymph node metastases in lung carcinoids: Results from a single institution retrospective cohort study
Pathipati MP, Yohannan TK, Tian L, Hornbacker K, Benson JA, Berry GJ, Lui NS, Kunz PL, Padda SK. Examination of factors associated with lymph node metastases in lung carcinoids: Results from a single institution retrospective cohort study. Lung Cancer 2021, 154: 186-194. PMID: 33551175, PMCID: PMC8026717, DOI: 10.1016/j.lungcan.2021.01.017.Peer-Reviewed Original ResearchConceptsLung neuroendocrine tumorsLymph nodesNeuroendocrine tumorsLung carcinoidsSSTR imagingLN metastasisAtypical carcinoidExact testSingle-institution retrospective cohort studyLymph node-positive diseaseAssociation of lymphPositive lymph nodesRetrospective cohort studyLymph node diseaseLymph node involvementNode-positive diseaseLymph node metastasisMultivariable logistic regressionFisher's exact testPre-operative workupN2 diseaseAdjuvant therapyLN involvementN1 diseaseNode involvement
2020
Angiogenesis inhibitors in neuroendocrine tumours: finally coming of age
Kunz PL. Angiogenesis inhibitors in neuroendocrine tumours: finally coming of age. The Lancet Oncology 2020, 21: 1395-1397. PMID: 33152282, DOI: 10.1016/s1470-2045(20)30560-x.Peer-Reviewed Original ResearchCost-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