2024
Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Xu F, Hui P, Altwerger G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses. Gynecologic Oncology 2024, 190: s299-s301. DOI: 10.1016/j.ygyno.2024.07.449.Peer-Reviewed Original ResearchUtility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas
Greenman M, Bellone S, Hartwich T, Buza N, Santin A. Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas. Gynecologic Oncology Reports 2024, 56: 101524. PMID: 39435258, PMCID: PMC11492078, DOI: 10.1016/j.gore.2024.101524.Peer-Reviewed Original ResearchOvarian carcinomaNext generation sequencingPrimary uterine tumorsDiagnostically challenging casesOvarian tumorsPrimary tumorUterine tumorsEndometrial malignancyMetastatic tumorsAdjuvant treatmentClonal relationshipTargeted therapyUtilization of next generation sequencingTumor clonalityGeneration sequencingProtein expression profilesTumorChallenging casesImprove outcomesCarcinomaGold standardGenetic landscapeMalignancyClonalityExpression profilesTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerDiandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?
Nagy A, Niu N, Sun T, Buza N, Hui P. Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction? Histopathology 2024 PMID: 39031756, DOI: 10.1111/his.15247.Peer-Reviewed Original ResearchPositive predictive valueTriploid gestationsPartial moleTrophoblastic hyperplasiaVillous sizeCistern formationHistological parametersPostmolar gestational trophoblastic neoplasiaTriploid partial molesGenotype-phenotype correlation studiesGestational trophoblastic neoplasiaPartial hydatidiform moleModerate interobserver agreementVillous populationsTrophoblastic neoplasiaGestational weeksHydatidiform moleClinical presentationPatient ageDigynic triploidyAbnormal histologyInterobserver agreementGestationSyncytiotrophoblastHistological assessmentRandomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Reports 2024, 2: 43. PMCID: PMC11523995, DOI: 10.1038/s44276-024-00067-5.Peer-Reviewed Original ResearchPre-treated ovarian cancerOverall survivalBev armsDose reductionOvarian cancerTaxane responseRandomized phase 2 trialRandomized phase II trialPaclitaxel-resistant diseaseResultsThirty-seven patientsTreated with paclitaxelPhase 2 trialBiweekly bevacizumabDays 1,8,15Taxane-sensitiveUpdate survivalProgression-freePeritoneal cancerDose modificationTaxane sensitivityPlatinum resistanceSubset analysisSubgroup analysisResponse ratePatientsTargetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.
Manrai P, McHenry A, Sun T, Santin A, Ratner E, Lin D, Elvin J, Hui P, Buza N. Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations. International Journal Of Gynecological Pathology 2024 PMID: 38914011, DOI: 10.1097/pgp.0000000000001050.Peer-Reviewed Original ResearchEndometrial carcinomaGynecologic malignanciesTyrosine kinase domainHER2-mutated non-small cell lung cancerTargeted anti-HER2 therapyNon-small cell lung cancerHigh-grade endometrioid adenocarcinomasFam-trastuzumab deruxtecanOvarian mucinous adenocarcinomaAnti-HER2 therapyAnti-HER2 drugsHER2 3+US Food and Drug AdministrationCell lung cancerEndometrial serous carcinomaSolid tumor typesStandard treatment recommendationsFood and Drug AdministrationFluorescence in situ hybridizationGynecological cancer typesEndometrial primaryMullerian originSerous carcinomaHER2 IHCEndometrioid adenocarcinomaRandomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimodCorrection: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque D, Siegel E, Buza N, Bellone S, Silasi D, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Reader J, Hui P, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin A. Correction: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2024, 130: 1073-1073. PMID: 38438590, PMCID: PMC10951353, DOI: 10.1038/s41416-024-02628-4.Peer-Reviewed Original ResearchNovel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications
Nagy A, Niu N, Ratner E, Hui P, Buza N. Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications. International Journal Of Gynecological Pathology 2024, 43: 631-636. PMID: 38426544, DOI: 10.1097/pgp.0000000000001024.Peer-Reviewed Original ResearchAdult granulosa cell tumorGranulosa cell tumorsOvarian sex cord-stromal tumorsSex cord-stromal tumorsCord-stromal tumorsCell tumorsFOXL2 mutationMutation c.Fibromatous stromaMalignant ovarian sex cord-stromal tumorAdjuvant vaginal cuff brachytherapyOvarian adult granulosa cell tumorsBilateral salpingo-oophorectomyRight ovarian massVaginal cuff brachytherapyAtypical endometrial hyperplasiaSuperficial myometrial invasionRoutine molecular testingUniform tumor cellsEndometrioid endometrial adenocarcinomaNested growth patternPoint mutation c.Months follow-upSalpingo-oophorectomyTotal hysterectomy
2023
Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient
Roth L, Smith A, Buza N, Coons B, Stitelman D, Vash-Margita A. Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient. Journal Of Pediatric And Adolescent Gynecology 2023, 37: 217-219. PMID: 38110028, DOI: 10.1016/j.jpag.2023.11.014.Peer-Reviewed Original ResearchPolycystic ovarian syndromeOvarian tumorsCell tumorsRecurrent ovarian torsionAbnormal uterine bleedingPost-menopausal womenLeydig cell tumorUterine bleedingOvarian syndromeOvarian torsionYounger patientsOvarian functionOvarian hilumAdolescent patientsNodular proliferationSecrete androgensTumor AssociatedRecurrent torsionPrimary amenorrheaCurrent recommendationsReinke crystalsTumorsLeydig cellsIncidence increasesVirilizationExtrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges
Niu N, Ordulu Z, Burak Z, Buza N, Hui P. Extrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges. Histopathology 2023, 84: 325-335. PMID: 37743102, DOI: 10.1111/his.15054.Peer-Reviewed Original ResearchConceptsEpithelioid trophoblastic tumorGestational trophoblastic tumorsTrophoblastic tumorExtrauterine sitesSomatic carcinomasDifferential diagnosisDiagnosis of ETTExtrauterine epithelioid trophoblastic tumorsTriple-negative breast carcinomaTrophoblastic differentiationMetastatic triple-negative breast carcinomaPrimary lung carcinomaMain differential diagnosisMajor differential diagnosisEctopic gestationImmunohistochemical featuresDiagnostic challengeMetastatic tumorsLung carcinomaBreast carcinomaPatient managementEpithelioid malignanciesImmunohistochemical levelCarcinomaTumor tissueIn Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyUterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315)
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Schlessinger J, Santin A. Uterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315). Gynecologic Oncology 2023, 176: s193. DOI: 10.1016/j.ygyno.2023.06.218.Peer-Reviewed Original ResearchKRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence
McHenry A, Rottmann D, Buza N, Hui P. KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence. Virchows Archiv 2023, 483: 71-79. PMID: 37219599, DOI: 10.1007/s00428-023-03564-z.Peer-Reviewed Original ResearchConceptsOvarian serous borderline tumorsSerous borderline tumorsNon-invasive implantsDisease-free survivalKRAS mutationsTumor recurrenceExtraovarian implantsAdverse disease-free survivalWorse disease-free survivalHigher stage diseaseKRAS mutation testingHigher tumor stageWild-type KRASBRAF V600E mutationBRAF mutational analysisBorderline tumorsClinical outcomesHistological subtypesTumor stageBRAF mutationsUseful biomarkerInvasive implantsTumors correlatesV600E mutationMutational status86. Leydig Cell Tumor in an Adolescent
Roth L, Smith A, Buza N, Coons B, Stitleman D, Vash-Margita A. 86. Leydig Cell Tumor in an Adolescent. Journal Of Pediatric And Adolescent Gynecology 2023, 36: 210. DOI: 10.1016/j.jpag.2023.01.229.Peer-Reviewed Original ResearchLeydig cell tumorOvarian stromal tumorsCell tumorsOvarian tumorsRight ovaryPrimary amenorrheaOvarian torsionStromal tumorsLeydig cell ovarian tumorsOvarian Leydig cell tumorAreas of hypodensityEnlarged right ovaryQuadrant abdominal painMainstay of treatmentIntraoperative frozen sectionTanner stage 4Breast stage 3Years of ageAbsent menarcheLaparoscopic detorsionAbdominal painFinal pathologyPostmenopausal womenRight oophorectomyPostoperative courseCorrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”
Harold J, Bellone S, Manavell D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Corrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”. Gynecologic Oncology 2023, 170: 334. PMID: 36906375, PMCID: PMC10266020, DOI: 10.1016/j.ygyno.2023.01.029.Peer-Reviewed Original ResearchTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleThe role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma
Talia K, Banet N, Buza N. The role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma. Pathology 2022, 55: 8-18. PMID: 36503635, DOI: 10.1016/j.pathol.2022.11.004.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Uterine serous carcinomaRole of HER2Serous carcinomaClinical trialsHER2 overexpressionPrognostic biomarkerTherapeutic targetHigh-grade endometrioid carcinomaEpidermal growth factor receptor 2Vulvar Paget's diseaseGrowth factor receptor 2Time of diagnosisFuture clinical trialsGynaecological cancer careClinical trial dataHER2 protein overexpressionFactor receptor 2P53 mutant tumorsRecurrent diseaseSurvival benefitGynaecological malignanciesPaget's diseaseClinical benefitEndometrial carcinoma