2024
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)
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 vaccinationImiquimod
2023
Timeliness of diagnostic evaluation for postmenopausal bleeding: A retrospective cohort study using claims data
Xu X, Chen L, Nunez-Smith M, Clark M, Wright J. Timeliness of diagnostic evaluation for postmenopausal bleeding: A retrospective cohort study using claims data. PLOS ONE 2023, 18: e0289692. PMID: 37682914, PMCID: PMC10490884, DOI: 10.1371/journal.pone.0289692.Peer-Reviewed Original ResearchConceptsPostmenopausal bleedingFirst diagnostic procedureDiagnostic evaluationDiagnostic proceduresGynecologic conditionsMedicaid patientsCox proportional hazards modelPrompt diagnostic evaluationRetrospective cohort studyMarketScan Research DatabasesAdditional risk factorsNon-clinical factorsCommon gynecologic conditionProportional hazards modelLower ratesCohort studyMost patientsPatient characteristicsBenign etiologyGynecologic cancerCancer patientsPreventive careUterine cancerInsurance typeRisk factorsIn 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 chemotherapyHyperthermic 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 dataUterine 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 vehicleLeiomyosarcomaChanges 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 systemRacial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries
Xu X, Chen L, Nunez-Smith M, Clark M, Wright J. Racial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries. Journal Of The National Cancer Institute 2023, 115: 636-643. PMID: 36788453, PMCID: PMC10248843, DOI: 10.1093/jnci/djad027.Peer-Reviewed Original ResearchConceptsAbnormal uterine bleedingWhite patientsUterine cancerFirst diagnostic procedureDiagnostic evaluationBlack patientsDiagnostic proceduresBlack-White disparitiesManagement visitsMarketScan Multi-State Medicaid DatabaseMulti-State Medicaid DatabaseUterine bleedingPatient characteristicsMedicaid databaseEarly diagnosisMedicaid beneficiariesMultivariable regressionPatientsCancerRacial disparitiesDiagnosisVisitsMore evaluationDisparitiesBleedingThe 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 activityCarbon Dioxide Emissions and Environmental Impact of Different Surgical Modalities of Hysterectomies.
Ramani S, Hartnett J, Karki S, Gallousis S, Clark M, Andikyan V. Carbon Dioxide Emissions and Environmental Impact of Different Surgical Modalities of Hysterectomies. JSLS Journal Of The Society Of Laparoscopic & Robotic Surgeons 2023, 27: e2023.00021. PMID: 37663433, PMCID: PMC10473183, DOI: 10.4293/jsls.2023.00021.Peer-Reviewed Original Research
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 vehicleValidation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer
Piedimonte S, Kim R, Bernardini M, Atenafu E, Clark M, Lheureux S, May T. Validation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer. Gynecologic Oncology 2022, 167: 417-422. PMID: 37191644, DOI: 10.1016/j.ygyno.2022.10.014.Peer-Reviewed Original ResearchConceptsKaplan-Meier survival analysisOutcomes of cytoreductionRetrospective cohort studyDays of chemotherapyCA 125 valuesMeier survival analysisLocal ethics boardCytoreductive outcomeMedian pfsCohort studyInhibitor useTreatment delayFunctional statusBRCA statusInclusion criteriaHigh riskPlatinum sensitivityStage IIIPatientsSurvival analysisEthics BoardHigh gradeSignificant differencesNACTPoly adenosine
2021
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIThe impact of a universal human papilloma virus (HPV) vaccination program on lower genital tract dysplasia and genital warts
Clark M, Jembere N, Kupets R. The impact of a universal human papilloma virus (HPV) vaccination program on lower genital tract dysplasia and genital warts. Preventive Medicine 2021, 150: 106641. PMID: 34048822, DOI: 10.1016/j.ypmed.2021.106641.Peer-Reviewed Original ResearchConceptsSchool-based human papillomavirus (HPV) vaccination programLower genital tract dysplasiaPre-invasive diseaseTreatment of HPVVaccination programGenital wartsCervical dysplasiaCytologic abnormalitiesRelative riskHuman papilloma virus vaccination programmesLow-grade cytologic abnormalitiesHuman papillomavirus vaccination programmeLower genital tractHigh-grade abnormalitiesRelative risk ratiosCervical conizationUnvaccinated womenVaccinated womenHPV vaccineColposcopy servicesUnvaccinated groupVaccinated groupRisk ratioCytology resultsAdministrative databasesEndometrial Carcinoma as the Presenting Malignancy in a Teenager With a Pathogenic TP53 Germline Mutation: A Case Report and Literature Review
Irshaid L, Clark M, Fadare O, Finberg KE, Parkash V. Endometrial Carcinoma as the Presenting Malignancy in a Teenager With a Pathogenic TP53 Germline Mutation: A Case Report and Literature Review. International Journal Of Gynecological Pathology 2021, 41: 258-267. PMID: 33990091, DOI: 10.1097/pgp.0000000000000792.Peer-Reviewed Original ResearchConceptsGermline TP53 mutationsEndometrial carcinomaTP53 mutationsGermline mutationsMissense substitution p.Predominant tumor typePremenopausal breast carcinomaAdrenal cortical tumorsTP53 geneTP53 germline mutationsSoft tissue sarcomasEndometrioid endometrial carcinomaEarly-onset malignanciesLi-Fraumeni syndromeAutosomal dominant disorderCortical tumorsPresenting tumourGynecologic malignanciesTissue sarcomasUterine carcinomaCase reportSpinal cordBreast carcinomaGrade 3Characteristic syndromeIntegrated mutational landscape analysis of uterine leiomyosarcomas
Choi J, Manzano A, Dong W, Bellone S, Bonazzoli E, Zammataro L, Yao X, Deshpande A, Zaidi S, Guglielmi A, Gnutti B, Nagarkatti N, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Jeong K, Zhao S, Buza N, Hui P, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Ardighieri L, Bilguvar K, Quick CM, Silasi DA, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Imielinski M, Schwartz PE, Alexandrov LB, Lifton RP, Schlessinger J, Santin AD. Integrated mutational landscape analysis of uterine leiomyosarcomas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025182118. PMID: 33876771, PMCID: PMC8053980, DOI: 10.1073/pnas.2025182118.Peer-Reviewed Original ResearchConceptsHomologous recombination DNA repair deficiencySequencing dataWhole-genome sequencing dataRNA sequencing dataTCGA samplesCopy number variation analysisATRX/DAXXCopy number lossNumber variation analysisDNA repair deficiencyWhole-exome sequencing dataRecurrent somatic mutationsCopy number gainsCancer Genome AtlasPatient-derived xenograftsTumor suppressorAkt geneGenetic landscapeHRD signaturesPTEN geneGenesMost fusionsC-MycMutational signaturesC-myc/Survival of Older Women With Cervical Cancer Based on Screening History.
Clark M, Jembere N, Wang L, Kupets R. Survival of Older Women With Cervical Cancer Based on Screening History. Journal Of Lower Genital Tract Disease 2021, 25: 9-14. PMID: 33347044, DOI: 10.1097/lgt.0000000000000582.Peer-Reviewed Original ResearchConceptsInvasive cervical cancerWomen 50 yearsPrimary care physiciansCervical cancerOverall survivalScreening historyCare physiciansPopulation-level retrospective cohort studyMultivariate analysisHealth care administrative databasesFour-year OSRetrospective cohort studyCervical screening historyUnscreened womenAdvanced diseaseCohort studyScreened groupSurvival benefitImproved survivalCervical screeningKaplan-MeierUnivariate analysisAdministrative databasesOlder womenAge groups
2019
Limitations in Correspondence Programs for Cervical Cancer Screening: Who Are the Women We Are Missing?
Clark M, Lee A, Kupets R. Limitations in Correspondence Programs for Cervical Cancer Screening: Who Are the Women We Are Missing? Journal Of Obstetrics And Gynaecology Canada 2019, 41: 1410-1415. PMID: 30803876, DOI: 10.1016/j.jogc.2018.11.034.Peer-Reviewed Original ResearchConceptsPrimary care physiciansCare physiciansHealth care encountersCervical cancerCare encountersMore health care encountersRetrospective observational studyCervical cancer screeningHealth care servicesBasis of ageEligible womenCancer screeningAdministrative databasesObservational studyScreening programCare servicesHealth servicesPhysiciansCorrespondence programWomenFurther riskOutreach methodsCancerMailingInfrequent usersPseudovascular Invasion: Minimally Invasive Surgery for Endometrial Cancer
Seifi F, Parkash V, Clark M, Menderes G, Tierney C, Silasi DA, Azodi M. Pseudovascular Invasion: Minimally Invasive Surgery for Endometrial Cancer. JSLS Journal Of The Society Of Laparoscopic & Robotic Surgeons 2019, 23: e2019.00021. PMID: 31285650, PMCID: PMC6596444, DOI: 10.4293/jsls.2019.00021.Peer-Reviewed Original ResearchConceptsLymphovascular space invasionEndometrial cancerSpace invasionEarly-stage endometrial cancerPatients meeting eligibility criteriaInvasive surgical stagingStage endometrial cancerRetrospective cohort studyBody mass indexMeeting eligibility criteriaPeritoneal cytologyAdjuvant radiotherapyAdjuvant therapyAdjuvant treatmentSurgical stagingCohort studyLymphovascular invasionSerous histologyPathologic evaluationMass indexGynecologic pathologistsSubgroup analysisTumor gradeUterine manipulatorIntrauterine manipulator