2024
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
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, 1-11. 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 cancerRandomized 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. 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 ratePatientsIntegrated 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 carcinomaRandomized 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 vaccinationImiquimodMutations in cancer-relevant genes are ubiquitous in histologically normal endometrial tissue
Pandya D, Tomita S, Rhenals M, Swierczek S, Reid K, Camacho-Vanegas O, Camacho C, Engelman K, Polukort S, RoseFigura J, Chuang L, Andikyan V, Cohen S, Fiedler P, Sieber S, Shih I, Billaud J, Sebra R, Reva B, Dottino P, Martignetti J. Mutations in cancer-relevant genes are ubiquitous in histologically normal endometrial tissue. Gynecologic Oncology 2024, 185: 194-201. PMID: 38452634, DOI: 10.1016/j.ygyno.2024.02.027.Peer-Reviewed Original ResearchMyometrial layerUterine tissueSomatic mutationsPrevalence of somatic mutationsIncreasing patient ageNormal endometrial tissuesComplex mutation patternsMutant allele frequencyCancer-relevant genesSomatic mutation landscapeMutation prevalencePatient ageEndometrial cancerNon-functional mutationsGene panelEndometrial tissueGynecologic cancerMutation profilesUterine samplesMutational landscapeScreening testMutation patternsFunction mutationsMortality rateUnique mutationsCorrection: 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 Research
2023
ICG Fluorescence Technique for Detection of Sentinel Lymph Nodes in Laparoscopic Endometrial Cancer Staging
AlAshqar A, Mutlu L, McNamara B, Harold J, Clark M, Huang G, Azodi M, Schwartz P, Santin A, Ratner E, Altwerger G, Andikyan V. ICG Fluorescence Technique for Detection of Sentinel Lymph Nodes in Laparoscopic Endometrial Cancer Staging. Journal Of Minimally Invasive Gynecology 2023, 30: s36. DOI: 10.1016/j.jmig.2023.08.110.Peer-Reviewed Original ResearchEndometrial cancer stagingSentinel lymph nodesLymph nodesCancer stagingSentinel lymph node identificationICG fluorescence techniqueTertiary care hospitalLymph node identificationICG techniqueSentinel lymphCare hospitalIntervention useStagingDye techniqueNode identificationLymphPatientsMalignancyHospitalIsolated torsion of the utero‐ovarian ligament
Hla A, Harold J, Andikyan V. Isolated torsion of the utero‐ovarian ligament. Clinical Case Reports 2023, 11: e8114. PMID: 37908789, PMCID: PMC10613714, DOI: 10.1002/ccr3.8114.Peer-Reviewed Original ResearchAdnexal torsionBlood supplyAcute pelvic painGynecologic surgical emergencyUtero-ovarian ligamentDual blood supplyAdditional diagnostic challengeLack of evidencePelvic painDiagnostic laparoscopyIsolated torsionSurgical emergencyOvarian ligamentHigh suspicionDiagnostic challengeDoppler ultrasoundLigamentPainLaparoscopyUltrasonographyCliniciansDiagnosisPathologySuspicionIn 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 ResearchDelayed presentation of placenta accreta following a first‐trimester medical abortion
Maurer J, Ramani S, Xu B, Gallousis S, Clark M, Andikyan V. Delayed presentation of placenta accreta following a first‐trimester medical abortion. Clinical Case Reports 2023, 11: e7849. PMID: 37636882, PMCID: PMC10457480, DOI: 10.1002/ccr3.7849.Peer-Reviewed Original ResearchHyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer
Gelissen J, Adjei N, McNamara B, Mutlu L, Harold J, Clark M, Altwerger G, Dottino P, Huang G, Santin A, Azodi M, Ratner E, Schwartz P, Andikyan V. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. Annals Of Surgical Oncology 2023, 30: 5597-5609. PMID: 37358686, DOI: 10.1245/s10434-023-13757-0.Peer-Reviewed Original ResearchConceptsHyperthermic intraperitoneal chemotherapyIntraperitoneal chemotherapyOvarian cancerStage III epithelial ovarian cancerUse of HIPECEpithelial ovarian cancerHigh-quality evidenceOvarian cancer treatmentHIPEC useInterval cytoreductionCytoreductive surgeryNeoadjuvant chemotherapyPerioperative careHIPEC protocolsHIPEC techniqueTreatment modalitiesPatient outcomesSingle administrationTumor disseminationChemotherapyCancerCancer treatmentOptimal candidatesMain siteLife dataEffectiveness of telehealth physical therapy for patients with pelvic floor disorders in a community hospital setting
Coad B, Ramani S, Michel L, Peled A, Morgan J, Hartnett J, Chudnoff S, Andikyan V. Effectiveness of telehealth physical therapy for patients with pelvic floor disorders in a community hospital setting. Archives Of Gynecology And Obstetrics 2023, 308: 661-665. PMID: 37268794, PMCID: PMC10238233, DOI: 10.1007/s00404-023-07078-6.Peer-Reviewed Original ResearchConceptsTraditional office visitsOffice visitsTelehealth visitsTelehealth physical therapyMethodsRetrospective chart reviewPrimary outcome measureCommunity hospital settingNumber of patientsPelvic floor disordersPhysical therapy patientsSignificant differencesRace/ethnicityChart reviewInsurance typeCommunity hospitalTherapy patientsOutcome measuresPhysical therapyTreatment goalsHospital settingShow visitsPatientsNumber/typeCohortDemographic dataPreliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.
Santin A, McNamara B, Siegel E, Harold J, Mutlu L, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Dottino P, Schwartz P, Bellone S. Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2. Journal Of Clinical Oncology 2023, 41: 5599-5599. DOI: 10.1200/jco.2023.41.16_suppl.5599.Peer-Reviewed Original ResearchRecurrent endometrial carcinomaSacituzumab govitecan-hziyTrop-2 overexpressionPhase 2 trialEndometrial carcinomaUterine serous carcinomaTrop-2Endometrioid adenocarcinomaSerous carcinomaClinical activityMetastatic triple-negative breast cancerAnti-Trop-2 antibodyGrade 3 endometrioid adenocarcinomaTriple-negative breast cancerAdequate bone marrowUnexpected safety signalsMetastatic urothelial cancerClear cell histologyPhase II trialSystemic corticosteroid usePlatinum-based chemotherapyFavorable safety profileDurable disease controlRemarkable clinical activityStage 1Incisional infiltration versus transversus abdominis plane block of liposomal bupivacaine after midline vertical laparotomy for suspected gynecologic malignancy: a pilot study
Moon A, Andikyan V, Agarwal R, Stroever S, Misita D, Laibangyang A, Doo D, Chuang L. Incisional infiltration versus transversus abdominis plane block of liposomal bupivacaine after midline vertical laparotomy for suspected gynecologic malignancy: a pilot study. Gynecologic Oncology Reports 2023, 47: 101203. PMID: 37251783, PMCID: PMC10220396, DOI: 10.1016/j.gore.2023.101203.Peer-Reviewed Original ResearchLiposomal bupivacaineTransversus abdominis planeIncisional infiltrationOpioid requirementsPain scoresVertical laparotomyTAP blockGynecologic malignanciesBupivacaine hydrochlorideTransversus abdominis plane blockPilot studyOpen gynecologic surgeryTAP block groupTotal opioid useOpioid usePlane blockPostoperative periodSecondary outcomesPrimary outcomeGynecologic cancerInfiltration groupGynecologic surgeryClinical differencesGynecologic laparotomyBupivacaineUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcomaCorrigendum 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 ResearchChanges to same day discharge after minimally invasive hysterectomy throughout COVID‐19 pandemic
Sullivan M, Michel L, Wasser T, Clark M, Chudnoff S, Andikyan V. Changes to same day discharge after minimally invasive hysterectomy throughout COVID‐19 pandemic. Journal Of Obstetrics And Gynaecology Research 2023, 49: 1418-1423. PMID: 36808793, DOI: 10.1111/jog.15617.Peer-Reviewed Original ResearchConceptsRate of SDDSame-day dischargeInvasive hysterectomyDay dischargeCOVID-19 pandemicRetrospective chart reviewEmergency department visitsNumber of readmissionsMultivariable logistic regressionSame dayCommon gynecologic proceduresChi-square testChart reviewED visitsDepartment visitsHospital admissionElective surgerySurgical complexityGynecologic proceduresInclusion criteriaNosocomial infectionsHysterectomyPatientsLogistic regressionHealthcare systemThe Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expressionTrastuzumab 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