2023
Age- and sex-based differences in the genomic profiles of patients with gastrointestinal (GI) and pancreatic neuroendocrine neoplasms (NENs).
Liu L, Li S, Gandhi N, Farrell A, Lou E, Soares H, Nazha B, Swensen J, Oberley M, Nabhan C, Abraham J, Korn W, Kunz P, Vijayvergia N. Age- and sex-based differences in the genomic profiles of patients with gastrointestinal (GI) and pancreatic neuroendocrine neoplasms (NENs). Journal Of Clinical Oncology 2023, 41: 655-655. DOI: 10.1200/jco.2023.41.4_suppl.655.Peer-Reviewed Original ResearchNeuroendocrine neoplasmsPancreatic neuroendocrine neoplasmsP-NENsGI-NENGI-NENsImmune profileKRAS mutationsImmune checkpoint gene expressionHigh tumor mutation burdenCaris Life SciencesDMMR/MSIDistinct immune profilesTumor mutation burdenYears of ageMechanisms of ageWhole-exome sequencingMann-Whitney USex-based differencesSite of originDistinct molecular profilesICGs expressionAge-associated effectsOverall survivalPatient demographicsImmune landscape
2022
Randomized 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 analysisMicroangiopathic 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 cohort
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 trialO-2 Overall survival and long-term safety data from the NETTER-1 trial: 177-Lu-Dotatate vs. high-dose octreotide in patients with progressive midgut NETs
Strosberg J, Caplin M, Kunz P, Ruszniewski P, Bodei L, Hendifar A, Mittra E, Wolin E, Yao J, Pavel M, Pulido E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Demange A, Mutevelic S, Krenning E. O-2 Overall survival and long-term safety data from the NETTER-1 trial: 177-Lu-Dotatate vs. high-dose octreotide in patients with progressive midgut NETs. Annals Of Oncology 2021, 32: s217-s218. DOI: 10.1016/j.annonc.2021.05.006.Peer-Reviewed Original ResearchAnalysis 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 IFinal overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors.
Strosberg J, Caplin M, Kunz P, Ruszniewski P, Bodei L, Hendifar A, Mittra E, Wolin E, Yao J, Pavel M, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Demange A, Mutevelic S, Krenning E, group O. Final overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors. Journal Of Clinical Oncology 2021, 39: 4112-4112. DOI: 10.1200/jco.2021.39.15_suppl.4112.Peer-Reviewed Original ResearchProgression-free survivalMedian overall survivalFinal overall survivalNETTER-1 studyNETTER-1 trialNew safety signalsOverall survivalMidgut neuroendocrine tumorsControl armMyelodysplastic syndromeNeuroendocrine tumorsLu-DOTATATEPrimary endpointLast patientSafety signalsFurther anti-cancer treatmentBest supportive careKey secondary endpointOpen-label trialLutetium-177 DOTATATEAnti-cancer treatmentEligible patientsNETTER-1RECIST 1.1Secondary endpoints
2020
A PHASE IIA STUDY REPOSITIONING DESIPRAMINE IN SMALL CELL LUNG CANCER AND OTHER HIGH-GRADE NEUROENDOCRINE TUMORS
Riess JW, Jahchan NS, Das M, Koontz M, Kunz PL, Wakelee HA, Schatzberg A, Sage J, Neal JW. A PHASE IIA STUDY REPOSITIONING DESIPRAMINE IN SMALL CELL LUNG CANCER AND OTHER HIGH-GRADE NEUROENDOCRINE TUMORS. Cancer Treatment And Research Communications 2020, 23: 100174. PMID: 32413603, PMCID: PMC7572629, DOI: 10.1016/j.ctarc.2020.100174.Peer-Reviewed Original ResearchSmall cell lung cancerCell lung cancerMetastatic small cell lung cancerRadiographic progression-free survivalHigh-grade neuroendocrine carcinomaMedian overall survivalProgression-free survivalTricyclic antidepressantsClinical trialsLung cancerPrior chemotherapyFree survivalStable doseOverall survivalRadiographic benefitStudy entryNeuroendocrine carcinomaPreclinical modelsAntitumor effectsGrade 1Phase IIa clinical trialDose-escalation clinical trialHigh-grade neuroendocrine tumorsNeurocognitive adverse eventsEscalation clinical trialComprehensive genomic sequencing of high-grade neuroendocrine neoplasms.
Sun T, Van Hummelen P, Martin B, Xia C, Lee H, Zhao L, Hornbacker K, Ji H, Kunz P. Comprehensive genomic sequencing of high-grade neuroendocrine neoplasms. Journal Of Clinical Oncology 2020, 38: 624-624. DOI: 10.1200/jco.2020.38.4_suppl.624.Peer-Reviewed Original Research
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 characteristicsComparison of definitive chemoradiation with 5-fluorouracil versus capecitabine in anal cancer
Pumpalova Y, Kozak MM, von Eyben R, Kunz P, Fisher G, Chang DT, Haraldsdottir S. Comparison of definitive chemoradiation with 5-fluorouracil versus capecitabine in anal cancer. Journal Of Gastrointestinal Oncology 2019, 10: 605-615. PMID: 31392040, PMCID: PMC6657317, DOI: 10.21037/jgo.2019.02.17.Peer-Reviewed Original ResearchAnal cancer patientsIncidence of recurrenceAnal cancerDefinitive chemoradiationOverall survivalCancer patientsLonger recurrence-free intervalCancer-specific survivalDisease-specific survivalRecurrence-free intervalSignificant lower incidenceLoco-regional relapseLog-rank testMann-Whitney U testAnal painMore colostomiesLocoregional recurrencePatient characteristicsRectal cancerOverall incidenceGray's testLower incidenceCommon gradePatientsRecurrenceEvaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms
Waseem N, Aparici CM, Kunz PL. Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms. Journal Of Nuclear Medicine 2019, 60: 882-891. PMID: 30850504, DOI: 10.2967/jnumed.118.217851.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapyG3 neuroendocrine neoplasmsNeuroendocrine neoplasmsOverall survivalRole of PRRTUse of PRRTPhase III clinical trialsGrade 3 neuroendocrine neoplasmsLeast stable diseaseMidgut neuroendocrine neoplasmsProgression-free survivalLonger overall survivalReceptor radionuclide therapyShorter overall survivalHigh Ki-67Gastroenteropancreatic neuroendocrine neoplasmsNew histologic classificationSomatostatin receptor expressionF-FDG PETDrug Administration approvalLow proliferation indexRole of theranosticsRadiologic responseStable diseasePartial responseTemozolomide in grade III neuroendocrine neoplasms (G3 NENs): A multicenter retrospective review.
Chan D, Bergsland E, Chan J, Gadgil R, Halfdanarson T, Hornbacker K, Kelly V, Kunz P, McGarrah P, Raj N, Reidy D, Thawer A, Whitman J, Wu L, Singh S. Temozolomide in grade III neuroendocrine neoplasms (G3 NENs): A multicenter retrospective review. Journal Of Clinical Oncology 2019, 37: 321-321. DOI: 10.1200/jco.2019.37.4_suppl.321.Peer-Reviewed Original ResearchTreatment failureG3 NENRetrospective reviewDose reduction/discontinuationBest radiological responseLocal pathology reportsMulticentre retrospective reviewOptimal systemic treatmentProspective confirmatory trialMedian TTFMulticenter retrospective reviewReduction/discontinuationBetter response rateViable treatment optionGastroenteropancreatic NENRadiologic responseStable diseasePrimary endpointRECIST criteriaAdverse eventsOverall survivalPartial responseProgressive diseaseRadiological responseSystemic treatment
2018
A 20-year comparison of definitive chemoradiation with 5-FU versus capecitabine in anal cancer patients treated at Stanford.
Pumpalova Y, Kozak M, von Eyben R, Fisher G, Kunz P, Chang D, Haraldsdottir S. A 20-year comparison of definitive chemoradiation with 5-FU versus capecitabine in anal cancer patients treated at Stanford. Journal Of Clinical Oncology 2018, 36: 710-710. DOI: 10.1200/jco.2018.36.4_suppl.710.Peer-Reviewed Original ResearchAnal cancer patientsDisease-specific survivalCancer patientsFM groupCM groupDefinitive chemoradiationColostomy rateExact testCommon grade 2Higher colostomy rateIncidence of recurrenceLoco-regional recurrenceLog-rank testCause of deathFisher's exact testMann-Whitney U testAnal painInduction chemotherapyAnal cancerDefinitive radiotherapyDistant recurrenceOverall survivalMedian ageMost recurrencesRectal cancerPhase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies.
Kardosh A, Tseng D, Sahaf B, Zomet A, Krupa J, Fisher G, Wang D, Mackall C, Kunz P. Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies. Journal Of Clinical Oncology 2018, 36: tps191-tps191. DOI: 10.1200/jco.2018.36.4_suppl.tps191.Peer-Reviewed Original ResearchProgression-free survivalGastroesophageal junctionOverall survivalResponse rateGastric adenocarcinomaECOG performance status 0Phase II clinical trialPDL-1 expressionPerformance status 0Single-agent pembrolizumabMedian overall survivalPD-1 inhibitorsPhase II studyIncidence of adenocarcinomaGastroesophageal junction adenocarcinomaComprehensive immune profilingMajor health problemCombination immunotherapyEligible patientsKEYNOTE-059PFS ratesPrior therapyPrior trastuzumabStatus 0Advanced disease
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
NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate.
Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum R, Kunz P, Hobday T, Hendifar A, Oberg K, Lopera Sierra M, Kwekkeboom D, Ruszniewski P, Krenning E. NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate. Journal Of Clinical Oncology 2016, 34: 194-194. DOI: 10.1200/jco.2016.34.4_suppl.194.Peer-Reviewed Original ResearchOctreotide LARMidgut neuroendocrine tumorsMidgut NETOverall survivalNeuroendocrine tumorsAdvanced midgut neuroendocrine tumorsFirst phase IIIIndependent reading centerNETTER-1 trialRECIST 1.1 criteriaObjective response rateSomatostatin analogue therapyProgression-free survivalHealth-related qualityOverall survival resultsNumber of deathsMedian PFSNETTER-1Primary endpointAnalogue therapyHazard ratioRadiographic responseSurvival benefitTherapeutic optionsTumor response
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 gliomasPretreatment lab values to predict overall survival in patients with primary unresectable pancreatic adenocarcinoma treated with SBRT.
Alagappan M, Pollom E, von Eyben R, Kunz P, Fisher G, Ford J, Poultsides G, Visser B, Norton J, Kamaya A, Columbo L, Koong A, Chang D. Pretreatment lab values to predict overall survival in patients with primary unresectable pancreatic adenocarcinoma treated with SBRT. Journal Of Clinical Oncology 2015, 33: 433-433. DOI: 10.1200/jco.2015.33.3_suppl.433.Peer-Reviewed Original ResearchUnresectable pancreatic adenocarcinomaStereotactic body radiotherapyHigh NL ratioPrior radiation therapyOverall survivalBlood cell countStart of treatmentPancreatic adenocarcinomaTumor marker valuesNL ratioResectable diseaseEntire cohortCA 19Univariate analysisRadiation therapyCell countWhite blood cell countTumor marker CA 19Marker valuesLab valuesBorderline resectable diseasePre-treatment CEAMedian overall survivalAbsolute lymphocyte countAbsolute neutrophil count