2025
Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: Results from an ongoing phase I trial.
Capdevila J, Gambardella V, Kuboki Y, Alese O, Morgensztern D, Sayehli C, Sanmamed M, Arriola E, Studeny M, Bouzaggou M, Chen Z, Lifke V, Wolf J, Wermke M. Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: Results from an ongoing phase I trial. Journal Of Clinical Oncology 2025, 43: 3004-3004. DOI: 10.1200/jco.2025.43.16_suppl.3004.Peer-Reviewed Original ResearchDelta-like ligand 3Disease control rateExtrapulmonary neuroendocrine carcinomasNeuroendocrine carcinomaMedian DORDose escalationImmune effector cell-associated neurotoxicity syndromeDose-escalation regimensDose-escalation trialDuration of responseT-cell engagersCytokine release syndromePhase I trialRECIST v1.1Systemic therapyI trialBaseline characteristicsNeurotoxicity syndromeSafety profileStandard treatmentControl rateTumor cellsEfficacy dataDisease progressionResponse rate681 Gastrointestinal Neuroendocrine Carcinoma Associated with Adenoma: A Tumor More Aggressive than Neuroendocrine Carcinoma Mixed with Adenocarcinoma
Sekhri R, Liu X, Kang L, Zhang D, González I, Gonzalez R, Zhang X, Wang X, Liao X, Yang Z, Wang L, Westerhoff M, Cheng J, Wang H, Yu W, Choi W, Xue Y, Anzar A, Alpert L, Toro P, Karaaslan S, Sweeney J, Zhang X, Allende D, Hu S. 681 Gastrointestinal Neuroendocrine Carcinoma Associated with Adenoma: A Tumor More Aggressive than Neuroendocrine Carcinoma Mixed with Adenocarcinoma. Laboratory Investigation 2025, 105: 102912. DOI: 10.1016/j.labinv.2024.102912.Peer-Reviewed Original ResearchNeuroendocrine carcinoma
2024
Big Decisions on Small Cell Lung Cancer: A Focus on Clinical Care Updates and Patient Perspectives.
Wang X, Chiang A. Big Decisions on Small Cell Lung Cancer: A Focus on Clinical Care Updates and Patient Perspectives. American Society Of Clinical Oncology Educational Book 2024, 44: e432520. PMID: 38830134, DOI: 10.1200/edbk_432520.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerCell lung cancerLung cancerSystemic therapyHigh-grade neuroendocrine carcinomaAssociated with tobacco useIntracranial radiotherapySCLC treatmentChemosensitive diseaseNeuroendocrine carcinomaTargeted therapyPatientsCancerTherapyTobacco usePsychosocial burdenDiseasePatient perspectiveRadiotherapyImmunotherapyCarcinomaRelapseThoracicLungClinicExploring systemic treatment approaches for advanced pure large cell neuroendocrine carcinoma (LCNEC): A multicenter retrospective analysis.
Nassar A, Matteson K, Ardeshir F, Gray J, Baena Espinar J, Kwiatkowski D, Aboubakar Nana F, Grohe C, Citarella F, Pancirer D, Cheung J, Watson A, Sridhar A, Crowley F, Kaldas D, Kim C, Sankar K, Awosika N, Naqash A, Chiang A. Exploring systemic treatment approaches for advanced pure large cell neuroendocrine carcinoma (LCNEC): A multicenter retrospective analysis. Journal Of Clinical Oncology 2024, 42: 8106-8106. DOI: 10.1200/jco.2024.42.16_suppl.8106.Peer-Reviewed Original ResearchLarge cell neuroendocrine carcinomaProgression-free survivalTreatment-related adverse eventsPD-L1 statusOverall survivalPD-L1Systemic therapyRetrospective analysisGrades treatment-related adverse eventsTreatment approachesCell neuroendocrine carcinomaMedian Follow-UpMulticenter retrospective analysisTreated with chemotherapySystemic treatment approachesChemo-regimenPlatinum-etoposideNeuroendocrine carcinomaOS outcomesLine treatmentToxicity profileClinical outcomesAdverse eventsImmunotherapyIO groupComparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: A multi-institutional international retrospective study.
Matteson K, Nassar A, Ellis-Caleo T, Mingo E, Aggarwal V, Sridhar A, Alam S, Crowley F, Aboubakar Nana F, Ahmed M, Grohe C, Zurera Berjaga M, Pinato D, Watson A, Chiang A, Naqash A. Comparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: A multi-institutional international retrospective study. Journal Of Clinical Oncology 2024, 42: 8602-8602. DOI: 10.1200/jco.2024.42.16_suppl.8602.Peer-Reviewed Original ResearchProgression-free survivalTreatment-related adverse eventsFirst-line treatmentMedian progression-free survivalOverall survivalChemo-ImmunotherapyMedian OSLung cancerAll-grade treatment-related adverse eventsRare subtype of lung cancerMulti-institutional retrospective analysisSmall cell lung cancerCell neuroendocrine carcinomaInternational retrospective studyCell lung cancerSubtype of lung cancerLog-rank testFeatures of adenocarcinomaOptimal treatment approachClinical trial dataChemo-regimensNeuroendocrine carcinomaChemo groupSystemic therapyRare subtypeIntegrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix
Bellone S, Jeong K, Halle M, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich T, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Quick C, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov L, Siegel E, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321898121. PMID: 38625939, PMCID: PMC11046577, DOI: 10.1073/pnas.2321898121.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingPatient-derived-xenograftsBase excision repairCopy number lossMultiregion whole-exome sequencingCopy number gainHigh-grade neuroendocrine carcinomaCNV analysisPhylogenetic analysisEvolutionary historyNeuroendocrine cervical cancerHuman papillomavirus DNAMutator phenotypeSensitivity to afatinibGenetic landscapeRecurrent mutationsRNA sequencingGene fusionsMutational landscape analysisExcision repairGenesMutationsPan-HERConsistent with deficiencyNeuroendocrine carcinoma
2023
Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study
Hou T, Yang Z, Zhang Q, Zhang X, Liao X, Lin J. Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study. International Journal Of Surgical Pathology 2023, 32: 920-925. PMID: 37899731, DOI: 10.1177/10668969231208029.Peer-Reviewed Original ResearchNeoadjuvant therapyEsophageal adenocarcinomaNeuroendocrine neoplasmsNeuroendocrine carcinomaSurvival rateOverall median survival timeEsophageal neuroendocrine carcinomaPreoperative neoadjuvant therapyAdvanced esophageal adenocarcinomaMedian survival timeObserved survival ratesMainstay treatmentResidual adenocarcinomaConventional adenocarcinomaEsophageal cancerNeuroendocrine morphologyFocal positivitySurvival timeNeuroendocrine componentAdenocarcinomaBiopsyResectionSmall seriesPatientsNeoplasmsSurgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States
Kerekes D, Frey A, Bakkila B, Kunstman J, Khan S. Surgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States. Journal Of Surgical Oncology 2023, 128: 790-802. PMID: 37435780, DOI: 10.1002/jso.27392.Peer-Reviewed Original ResearchConceptsGastroenteropancreatic neuroendocrine carcinomasGEP-NECSingle-site surgeryOverall survivalSurgical treatmentNeuroendocrine carcinomaMortality reductionSite surgeryPrimary siteNational Cancer DatabaseRetrospective cohort studyPrimary tumor typeSurgical resectionCohort studyAggressive diseaseSurgical interventionSurvival outcomesTreatment optionsCancer DatabaseSurgeryPatientsTumor typesNECStrongest predictorCarcinomaPhase Ia/Ib Study of BAY1895344 Plus Topoisomerase I Inhibitors with a Focus on Poorly Differentiated Neuroendocrine Carcinomas and Pancreatic Adenocarcinoma
Stockton S, Dan A, Cecchini M, Ajumaily R, Whisenant J, Gore S, Ivy P, LoRusso P, Berlin J, Das S. Phase Ia/Ib Study of BAY1895344 Plus Topoisomerase I Inhibitors with a Focus on Poorly Differentiated Neuroendocrine Carcinomas and Pancreatic Adenocarcinoma. Endocrine Abstracts 2023 DOI: 10.1530/endoabs.89.t1.Peer-Reviewed Original ResearchIntegrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap
Umetsu S, Kakar S, Basturk O, Kim G, Chatterjee D, Wen K, Hale G, Shafizadeh N, Cho S, Whitman J, Gill R, Jones K, Navale P, Bergsland E, Klimstra D, Joseph N. Integrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap. Modern Pathology 2023, 36: 100065. PMID: 36788102, DOI: 10.1016/j.modpat.2022.100065.Peer-Reviewed Original ResearchConceptsPancreatic neuroendocrine neoplasmsNeuroendocrine carcinomaNeuroendocrine neoplasmsHigh-grade pancreatic neuroendocrine neoplasmsGrade 3 neuroendocrine tumorsPancreatic neuroendocrine tumorsHigh-grade neoplasmsCDKN2A alterationsP16 stainingTP53 alterationsNeuroendocrine tumorsRecurrent alterationsClinical behaviorDiagnostic challengeRare casePanNECClinicopathological approachPanNETsDiagnostic accuracyMolecular profilingTP53CDKN2ANeoplasmsCapture-based sequencingImmunohistochemistry
2022
Atypical Carcinoid Tumor Versus Large-Cell Neuroendocrine Carcinoma
Yoon E, Cai G. Atypical Carcinoid Tumor Versus Large-Cell Neuroendocrine Carcinoma. Practical Anatomic Pathology 2022, 75-81. DOI: 10.1007/978-3-031-14402-8_14.ChaptersLarge cell neuroendocrine carcinomaSmall cell carcinomaAtypical carcinoidNeuroendocrine carcinomaTypical carcinoidHigh-grade malignant neoplasmIntermediate-grade malignancyAtypical carcinoid tumorPulmonary neuroendocrine tumorsSmall biopsy specimensClinical characteristicsCarcinoid tumorsClinicopathologic differencesMalignant neoplasmsNeuroendocrine tumorsBiopsy specimensDifferential diagnosisPOU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC
Baine MK, Febres-Aldana CA, Chang JC, Jungbluth AA, Sethi S, Antonescu CR, Travis WD, Hsieh MS, Roh MS, Homer RJ, Ladanyi M, Egger JV, Lai WV, Rudin CM, Rekhtman N. POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC. Journal Of Thoracic Oncology 2022, 17: 1109-1121. PMID: 35760287, PMCID: PMC9427708, DOI: 10.1016/j.jtho.2022.06.004.Peer-Reviewed Original ResearchConceptsNeuroendocrine markersDiagnostic utilityLarge cell neuroendocrine carcinomaDiagnosis of SCLCSquamous cell carcinomaCell neuroendocrine carcinomaLung cancer typesMajor lung cancer typesNeuroendocrine marker expressionLung carcinoma subtypesWarrants further studyDistinct genomic alterationsClinical characteristicsCell carcinomaNeuroendocrine carcinomaLung tumorsCarcinoma subtypesLarge cohortDiagnostic mimicsTP53 alterationsMYC amplificationRecent markersTherapeutic targetingTuft cellsChallenging subset
2021
Genomic characterization of small cell carcinomas of the uterine cervix
Schultheis A, de Bruijn I, Selenica P, Macedo G, da Silva E, Piscuoglio S, Jungbluth A, Park K, Klimstra D, Wardelmann E, Hartmann W, Gerharz C, von Petersdorff M, Buettner R, Reis‐Filho J, Weigelt B. Genomic characterization of small cell carcinomas of the uterine cervix. Molecular Oncology 2021, 16: 833-845. PMID: 33830625, PMCID: PMC8847983, DOI: 10.1002/1878-0261.12962.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerSmall cell carcinomaSquamous cell carcinomaUterine cervixCell carcinomaHuman papillomavirus (HPV)-positive headHead and neck squamous cell carcinomaHPV-positive cervical carcinomasNeck squamous cell carcinomaHPV-driven cancersLow mutational burdenTargeted massively parallel sequencingHPV-positive headCell lung cancerCopy number alterationsCombination of whole-exomePoor survival rateAPOBEC mutational signaturesCancer-related genesMassively parallel sequencingNeuroendocrine carcinomaRB1 alterationsHPV16-positiveMutational burdenRB1 mutationsUterine Epithelial Neoplasia
Hui P, Flynn C, Quddus M. Uterine Epithelial Neoplasia. Practical Anatomic Pathology 2021, 113-130. DOI: 10.1007/978-3-030-68608-6_5.Peer-Reviewed Original ResearchCommon endometrioid adenocarcinomaClear cell carcinomaHigh-grade carcinomaGestational alterationsEndometrial malignancyCurettage specimenEndometrial hyperplasiaEndometrial polypsEndometrial cancerEndometrioid adenocarcinomaHistological typeAtypical hyperplasiaCell carcinomaDedifferentiated carcinomaMixed carcinomasNeuroendocrine carcinomaNonneoplastic lesionsPreneoplastic conditionsInflammatory processPrognostic informationUndifferentiated carcinomaEpithelial neoplasiaSmall biopsiesCarcinomaMolecular classification
2020
Alterations in Ki67 Labeling Following Treatment of Poorly Differentiated Neuroendocrine Carcinomas
Vyas M, Tang L, Rekhtman N, Klimstra D. Alterations in Ki67 Labeling Following Treatment of Poorly Differentiated Neuroendocrine Carcinomas. The American Journal Of Surgical Pathology 2020, 45: 25-34. PMID: 33177340, PMCID: PMC8549487, DOI: 10.1097/pas.0000000000001602.Peer-Reviewed Original ResearchConceptsHigh-grade neuroendocrine neoplasmsWD-NETsKi67 indexPD-NECsPoor-differentiated neuroendocrine carcinomasWell-differentiated neuroendocrine tumorsTreatment-associated alterationsSemi-quantitative scoreLow Ki67WHO G1Neuroendocrine carcinomaAdenoneuroendocrine carcinomaNeuroendocrine tumorsNeuroendocrine neoplasmsPrognostic significanceG2 gradeKi67 labelingDiagnostic pitfallsWHO gradePosttreatment groupStudy cohortAnatomical sitesKi67Pretreatment groupPosttreatment samplesA 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 trial
2019
A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma
Baine MK, Sinard JH, Cai G, Homer RJ. A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma. American Journal Of Clinical Pathology 2019, 153: 165-174. PMID: 31593583, PMCID: PMC7571487, DOI: 10.1093/ajcp/aqz149.Peer-Reviewed Original ResearchCervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Buza N, Lopez S, Perrone E, Manara P, Bellone S, Zammataro L, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Journal Of Clinical Oncology 2019, 37: e17028-e17028. DOI: 10.1200/jco.2019.37.15_suppl.e17028.Peer-Reviewed Original ResearchSquamous cell carcinomaPrimary cervical cancer cell linesControl antibody drug conjugatesAntibody-drug conjugatesIMMU-132Clear cell carcinomaTrop-2 expressionCervical cancer cell linesCell carcinomaCancer cell linesCervical cancerSacituzumab govitecanNeuroendocrine carcinomaCervical tumorsCell linesTrop-2Cervical cancer cell viabilityNaked antibodiesWeekly intravenous administrationSignificant tumor growth inhibitionStrong diffuse stainingUnmet medical needPrimary tumor cell linesReal-time polymerase chain reactionTumor growth inhibitionStage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices
Rekhtman N, Desmeules P, Litvak A, Pietanza M, Santos-Zabala M, Ni A, Montecalvo J, Chang J, Beras A, Preeshagul I, Sabari J, Rudin C, Ladanyi M, Klimstra D, Travis W, Lai W. Stage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices. Modern Pathology 2019, 32: 1106-1122. PMID: 30923345, PMCID: PMC6746332, DOI: 10.1038/s41379-019-0248-2.Peer-Reviewed Original ResearchConceptsNeuroendocrine carcinomaLung carcinoidsKi-67Metastatic carcinoidMetastatic sitesPrimary tumorProliferation rateProliferation indexTherapeutic response of patientsElevated proliferation indexMedian overall survivalKi-67 rateCharacteristics of tumorsResponse of patientsLow proliferation rateElevated proliferation rateMetastatic settingTypical carcinoidOverall survivalNeuroendocrine neoplasmsClonal relationshipMitotic countTherapeutic responseMetastatic samplesProliferative progressionNETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease
Malczewska A, Oberg K, Bodei L, Aslanian H, Lewczuk A, Filosso PL, Wójcik-Giertuga M, Rydel M, Zielińska-Leś I, Walter A, Suarez A, Kolasińska-Ćwikła A, Roffinella M, Jamidar P, Ziora D, Czyżewski D, Kos-Kudła B, Ćwikła J. NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease. Neuroendocrinology 2019, 108: 219-231. PMID: 30654372, PMCID: PMC7472425, DOI: 10.1159/000497037.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerLarge cell neuroendocrine carcinomaSquamous cell carcinomaIdiopathic pulmonary fibrosisBronchopulmonary carcinoidsNETest levelsLung cancerAtypical carcinoidLiquid biopsyLung neuroendocrine tumorsRECIST 1.1Stable diseaseMetastatic diseaseProgressive diseaseStudy cohortClinical progressionPulmonary fibrosisCell carcinomaNeuroendocrine carcinomaNeuroendocrine tumorsLung neoplasiaHealthy controlsNeuroendocrine neoplasiaBlinded studyBlood samples
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