2024
Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer
Greenman M, Bellone S, Demirkiran C, Hartwich T, Santin A. Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer. Gynecologic Oncology Reports 2024, 54: 101459. PMID: 39108617, PMCID: PMC11300917, DOI: 10.1016/j.gore.2024.101459.Peer-Reviewed Original ResearchHigh grade serous ovarian cancerAntibody-drug conjugatesSerous ovarian cancerSacituzumab govitecanOvarian cancerTreatment optionsPlatinum-resistant ovarian cancer patientsDose-limiting toxicityOvarian cancer patientsNovel treatment optionsPartial responseRecurrent diseaseDose reductionCancer patientsClinical trialsBackground treatmentTargeted treatmentChemotherapyTreatmentCancerDoseDiseaseOptionsTrop2PatientsIncreased von Willebrand and Factor VIII plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID
Bellone S, Siegel E, Scheim D, Santin A. Increased von Willebrand and Factor VIII plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID. Gynecologic Oncology Reports 2024, 51: 101324. PMID: 38273933, PMCID: PMC10809113, DOI: 10.1016/j.gore.2024.101324.Peer-Reviewed Original ResearchElevated von Willebrand factorFactor VIII levelsVon Willebrand factorLong COVIDGynecologic patientsVIII levelsControl patientsD-dimerPlasma levelsFactor VIIID-dimer levelsPost-acute sequelaeLong COVID symptomsFactor VIII plasma levelsMicrovascular damageMicrovascular inflammationRed blood cellsThrombotic complicationsAcute infectionLC patientsPersistent inflammationPathophysiological mechanismsCancer patientsCOVID symptomsPatients
2023
Increased serum 1,25-dihydroxyvitamin D levels in gynecologic cancer patients with Post-Acute-Covid-Sequela (PASC)/Long COVID
Bellone S, Siegel E, Santin A. Increased serum 1,25-dihydroxyvitamin D levels in gynecologic cancer patients with Post-Acute-Covid-Sequela (PASC)/Long COVID. Gynecologic Oncology Reports 2023, 50: 101301. PMID: 38029227, PMCID: PMC10654147, DOI: 10.1016/j.gore.2023.101301.Peer-Reviewed Original ResearchGynecologic cancer patientsLong COVIDCancer patientsVitamin DPotent anti-inflammatory activityDihydroxyvitamin D levelsPost-acute sequelaeLong COVID symptomsAnti-inflammatory activityMental health impairmentControl cancer patientsExtrarenal conversionPost-AcuteControl patientsAcute infectionBone healthLC patientsPersistent inflammationD levelsCOVID symptomsImmune cellsPlasmatic levelsNovel biomarkersPatientsAbnormal levelsThe 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 expression
2022
Advances in antibody-drug conjugates for gynecologic malignancies
Tymon-Rosario J, Gorman M, Richardson D, Washington C, Santin A. Advances in antibody-drug conjugates for gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2022, 35: 6-14. PMID: 36484278, DOI: 10.1097/gco.0000000000000838.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancer patientsGynecologic malignanciesCancer patientsPlatinum-resistant ovarian cancer patientsUse of ADCsOngoing phase 3 trialsRecurrent ovarian cancer patientsNovel antibody-drug conjugateReceptor-targeting antibodiesPhase 3 trialProgression-free survivalFirst U.S. FoodOngoing clinical trialsHER2/neuPersonalized cancer careTisotumab vedotinPrimary endpointCervical cancerGynecologic cancerCancer careClinical trialsMultiple tumorsCurrent evidenceDrug Administration
2021
Financial toxicity in patients with gynecologic malignancies: a cross sectional study
Zeybek B, Webster E, Pogosian N, Tymon-Rosario J, Balch A, Altwerger G, Clark M, Menderes G, Huang G, Azodi M, Ratner ES, Schwartz PE, Santin AD, Andikyan V. Financial toxicity in patients with gynecologic malignancies: a cross sectional study. Journal Of Gynecologic Oncology 2021, 32: e87. PMID: 34431257, PMCID: PMC8550931, DOI: 10.3802/jgo.2021.32.e87.Peer-Reviewed Original ResearchConceptsCross-sectional studyGynecologic malignanciesFinancial toxicityPatient demographicsSectional studyMalignancy typeGynecologic oncology patientsOvarian cancer patientsPatient/diseaseCost of careFinancial burdenHigh financial burdenTreatment regimenHigh financial toxicityOncology patientsDisease characteristicsGynecologic cancerCancer careCancer patientsRisk factorsClinical trialsCOST scoreMedian COST scorePatientsSignificant burdenTrastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu
Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecologic Oncology 2021, 163: 93-99. PMID: 34372971, PMCID: PMC8721852, DOI: 10.1016/j.ygyno.2021.07.033.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaRecurrent uterine serous carcinomaAdverse eventsTreatment armsSerous carcinomaExperimental armToxicity profileTreatment-related adverse eventsTrastuzumab maintenance therapyCarboplatin/paclitaxelCardiac adverse eventsEndometrial cancer patientsGastrointestinal adverse eventsManageable toxicity profilePhase II trialEfficacy of trastuzumabSystem organ classII trialMaintenance therapyPrimary endpointSecondary endpointsMaintenance treatmentSafety profileCancer patientsCumulative toxicityA phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).
Roque D, Bellone S, Siegel E, Buza N, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Schwartz P, Ratner E, Alexandrov L, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin A. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Journal Of Clinical Oncology 2021, 39: 5523-5523. DOI: 10.1200/jco.2021.39.15_suppl.5523.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint inhibitorsEndometrial cancer patientsTumor mutational burdenCancer patientsGrade 3/4 treatment-related adverse eventsSolid Tumors version 1.1Treatment-related adverse eventsSporadic tumorsPhase II pilot studyOverall survival proportionPrimary end pointResponse Evaluation CriteriaPhase II evaluationAntigen processing/presentationProcessing/presentationAdverse eventsICI resistancePrognostic significanceMechanisms of resistancePolymerase chain reactionII evaluationClinical studiesMutational burdenPatientsA phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793)
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 J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin AD. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Annals Of Oncology 2021, 32: 1045-1046. PMID: 33932502, PMCID: PMC9465821, DOI: 10.1016/j.annonc.2021.04.013.Commentaries, Editorials and LettersImmunotherapy in Cervical Cancer
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Current Oncology Reports 2021, 23: 61. PMID: 33852056, DOI: 10.1007/s11912-021-01052-8.Peer-Reviewed Original ResearchConceptsCervical cancerDifferent immune checkpoint inhibitorsPlatinum-based chemotherapy regimenTumor-infiltrating T lymphocytesPoly adenosine diphosphate ribose polymerase inhibitorsImmune checkpoint inhibitorsCombination therapy trialsCervical cancer patientsPositive cervical cancerNovel therapeutic modalitiesRibose polymerase inhibitorsAntibody-drug conjugatesCheckpoint inhibitorsChemotherapy regimenImmunotherapy studiesTherapeutic vaccinesInvestigative treatmentCancer patientsChemotherapy treatmentT lymphocytesTherapeutic modalitiesRecent FindingsThereTumor angiogenesis inhibitorTherapy trialsAngiogenesis inhibitors
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsGOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study
Brooks RA, Tritchler DS, Darcy KM, Lankes HA, Salani R, Sperduto P, Guntupalli S, DiSilvestro P, Kesterson J, Olawaiye AB, Moxley K, Waggoner S, Santin A, Rader JS, Kizer NT, Thaker PH, Powell MA, Mutch DG, Birrer MJ, Goodfellow PJ. GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study. Gynecologic Oncology 2019, 153: 335-342. PMID: 30827726, PMCID: PMC6486855, DOI: 10.1016/j.ygyno.2019.02.028.Peer-Reviewed Original ResearchConceptsProgression-free survivalLymph node metastasisHazard ratioOverall survivalNode metastasisSingle nucleotide polymorphismsOdds ratioNRG Oncology/Gynecologic Oncology Group studyG alleleGynecologic Oncology Group studyEndometrioid endometrial cancer patientsGynecologic Oncology GroupEndometrial cancer patientsPrognostic clinical variablesWorse OSOncology GroupEEC patientsEndometrial cancerNodal metastasisPrimary outcomeClinical outcomesRisk stratificationWashington University SchoolClinical variablesCancer patients
2018
Identification of ovarian cancer patients for immunotherapy by concurrent assessment of tumor mutation burden (TMB), microsatellite instability (MSI) status, and targetable genomic alterations (GA)
Feinberg J, Elvin J, Bellone S, Santin A. Identification of ovarian cancer patients for immunotherapy by concurrent assessment of tumor mutation burden (TMB), microsatellite instability (MSI) status, and targetable genomic alterations (GA). Gynecologic Oncology 2018, 149: 36. DOI: 10.1016/j.ygyno.2018.04.081.Peer-Reviewed Original Research
2016
Chemotherapy for Elderly Ovarian Cancer Patients
Muralikrishnan S, Hatzis C, Katz A, Santin A, Schwartz PE, Abu-Khalaf MM. Chemotherapy for Elderly Ovarian Cancer Patients. Gynecology & Obstetrics 2016, 69: 1-5. PMID: 27695647, PMCID: PMC5042145, DOI: 10.4172/2161-0932.1000397.Peer-Reviewed Original ResearchPrimary ovarian cancerOvarian cancerYears of ageDose reductionDose reduction/discontinuationElderly ovarian cancer patientsPaclitaxel 175mg/Standard intravenous chemotherapyYale Cancer CenterAdditional prospective studiesReduction/discontinuationOvarian cancer patientsDifferent treatment modalitiesSignificant adverse effectsAUC 5Chemotherapy discontinuationIntravenous chemotherapyTreatment discontinuationHazard ratioStandard chemotherapyPrescribed regimenProspective studyRetrospective studyCancer CenterCancer patientsImmune checkpoint inhibitors in gynecologic cancers with lessons learned from non-gynecologic cancers
Menderes G, Hicks C, Black JD, Schwab CL, Santin AD. Immune checkpoint inhibitors in gynecologic cancers with lessons learned from non-gynecologic cancers. Expert Opinion On Biological Therapy 2016, 16: 989-1004. PMID: 27070175, DOI: 10.1080/14712598.2016.1177018.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCytotoxic T-lymphocyte antigen-4Checkpoint inhibitorsGynecologic cancer patientsGynecologic cancerCancer patientsImmune responseT-lymphocyte antigen-4Non-gynecologic cancersEffective cancer immunotherapyLong-term remissionCheckpoint inhibitor immunotherapySurvival of patientsCancer cellsImmunotherapeutic researchAnticancer immunityPD-1Advanced cancerImmunotherapeutic agentsTreatment regimensAntigen-4Cancer immunotherapyClinical activityClinical experienceImmunotherapy
2015
Immunotherapy and targeted therapy for cervical cancer: an update
Menderes G, Black J, Schwab CL, Santin AD. Immunotherapy and targeted therapy for cervical cancer: an update. Expert Review Of Anticancer Therapy 2015, 16: 83-98. PMID: 26568261, DOI: 10.1586/14737140.2016.1121108.Peer-Reviewed Original ResearchConceptsCervical cancer patientsCervical cancerCancer patientsImmune check pointsUse of immunotherapyMetastatic cervical cancerPrognosis of patientsActionable driver mutationsTyrosine kinase inhibitorsImmune system interactionsImmunotherapy studiesMedian survivalAngiogenesis inhibitorsChemotherapeutic drugsPatientsDriver mutationsKinase inhibitorsNew therapeuticsCancerNext-generation sequencingImmunotherapyTherapyGeneration sequencingInhibitorsPrognosisEvaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery
Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, Bandiera E, Tassi R, Zanotti L, Pecorelli S, Sartori E, Odicino FE, de Marco A, Santin AD, Ravaggi A, Mitola S. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget 2015, 6: 34617-34628. PMID: 26416446, PMCID: PMC4741477, DOI: 10.18632/oncotarget.5315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeoplasmAntibody AffinityAntineoplastic AgentsBlotting, WesternCell Line, TumorClaudin-3Drug CarriersDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunoglobulin GMiceMice, SCIDMicroscopy, ConfocalMicroscopy, FluorescenceOvarian NeoplasmsReal-Time Polymerase Chain ReactionRNA, Small InterferingSurface Plasmon ResonanceTransfectionXenograft Model Antitumor AssaysConceptsClostridium perfringens enterotoxinTumor cellsActive anti-cancer compoundsHuman IgG1 Fc domainHuman ovarian cancer cell linesOvarian cancer cell linesOvarian cancer patientsOvarian carcinoma xenograftsOvarian cancer cellsIgG1 Fc domainCancer cell linesAggressive tumorsCancer patientsCarcinoma xenograftsOncological settingIgG1 antibodiesClaudin3Anti-cancer compoundsChimeric antibodyAntitumor efficacySelective drug deliveryPerfringens enterotoxinCancer cellsAntibodiesFc domainClostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer
Cocco E, Shapiro EM, Gasparrini S, Lopez S, Schwab CL, Bellone S, Bortolomai I, Sumi NJ, Bonazzoli E, Nicoletti R, Deng Y, Saltzman WM, Zeiss CJ, Centritto F, Black JD, Silasi DA, Ratner E, Azodi M, Rutherford TJ, Schwartz PE, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer. International Journal Of Cancer 2015, 137: 2618-2629. PMID: 26060989, PMCID: PMC4573336, DOI: 10.1002/ijc.29632.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsTumor fluorescenceChemotherapy-resistant ovarian cancerClaudin-3Human ovarian cancer xenograftsTime of surgeryOvarian cancer patientsNeoadjuvant chemotherapy treatmentOvarian cancer xenograftsHealthy organsVivo visualizationTime of intervalBackground fluorescence ratioClostridium perfringens enterotoxinChemotherapy-naïveMicrometastatic diseaseMalignant ascitesOvarian diseaseResidual diseaseOvarian tumorsCancer patientsCancer xenograftsChemotherapy treatmentIP injectionOvarian cancerPolymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients
Bellone S, Centritto F, Black J, Schwab C, English D, Cocco E, Lopez S, Bonazzoli E, Predolini F, Ferrari F, Silasi DA, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients. Gynecologic Oncology 2015, 138: 11-17. PMID: 25931171, PMCID: PMC4469551, DOI: 10.1016/j.ygyno.2015.04.027.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesCancer patientsPole tumorsT cellsHigher IFN-γ expressionLevels of CD8Endometrial cancer patientsTumor-specific CD4T cell responsesEndometrial cancer cellsIFN-γ expressionHelper armCTL responsesEndometrial cancerFavorable prognosisBetter prognosisEndometrial carcinomaLymphoid subsetsNaïve CD4T lymphocytesTumor extractsCD4CD8Immune systemCell responses
2014
FIGO 2008 staging for endometrial cancer
English D, Santin A. FIGO 2008 staging for endometrial cancer. 2014, 82-96. DOI: 10.2217/fmeb2013.13.115.Peer-Reviewed Original ResearchFIGO staging systemEndometrial cancer patientsStaging systemEndometrial cancerCancer patientsCervical glandular involvementFIGO stage 1AObstetrics (FIGO) staging systemPositive peritoneal cytologySurgical staging systemClinical staging systemPeritoneal cytologySurgical stagingClinicopathologic studyOverall survivalGlandular involvementPathologic findingsEndometrial carcinomaDisease stageSignificant changesStage 1ACurrent evidenceInvolved nodesAssignment of stageCancer