2021
Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis
McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, Leung S, Bellone S, Wong A, Brucker SY, Lee CH, Clarke BA, Huntsman DG, Bernardini MQ, Ngeow J, Santin AD, Goodfellow P, Levine DA, Köbel M, Kommoss S, Bosse T, Gilks CB, Talhouk A. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis. Cancer 2021, 127: 2409-2422. PMID: 33793971, DOI: 10.1002/cncr.33516.Peer-Reviewed Original ResearchMeSH KeywordsDNA Polymerase IIEndometrial NeoplasmsFemaleHumansMutationPoly-ADP-Ribose Binding ProteinsPrognosisConceptsIndividual patient dataEndometrial cancerPOLE mutationsAdjuvant treatmentAdverse eventsSalvage rateClinical outcomesMeta-analyses (PRISMA) reporting guidelinesConcerns of overtreatmentPathogenic POLE mutationsPatient dataEvidence of diseaseRecurrence/progressionTraditional prognostic factorsProgression/recurrenceUnfavorable pathological featuresAssociation of treatmentMixed effects Cox modelPreferred Reporting ItemsAdditional therapyAdjuvant therapyLess therapyPrognostic factorsFirst diagnosisPathological features
2016
Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab
Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clinical Cancer Research 2016, 22: 5682-5687. PMID: 27486176, PMCID: PMC5135588, DOI: 10.1158/1078-0432.ccr-16-1031.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor nivolumabCheckpoint inhibitor nivolumabClinical responseInhibitor nivolumabAnti-PD-1 inhibitorsHyper-mutated tumorsPatient's clinical responseRemarkable clinical responsesAlternative therapeutic optionNovel treatment optionsRecurrent/metastaticHigh side effectsRecurrent diseaseEndometrial carcinomaTherapeutic optionsTreatment optionsModern chemotherapyGrade 3Side effectsPatientsHuman tumorsTumorsGene mutationsNivolumabChemotherapyPolymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors
2015
Polymerase 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