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A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing live…

2010

Abstract Background The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibito…

OncologyCancer ResearchTime Factorsmedicine.medical_treatmentMedizinIntracellular Signaling Peptides and Proteins - antagonists & inhibitors metabolismKaplan-Meier Estimate312 Clinical medicineProtein-Serine-Threonine KinaseLiver transplantationTHERAPYStudy ProtocolImmunosuppressive Agentendothelial growth-factor renal-cell carcinoma tumor progression rapamycin cancer cyclosporine efficacy therapy target model0302 clinical medicineRENAL-CELL CARCINOMARisk FactorsRecurrenceSurgical oncologyMedicine and Health SciencesLiver Neoplasms - drug therapy enzymology mortality surgerySirolimuProspective StudiesTUMOR PROGRESSIONTransplantation Homologoueducation.field_of_studyliver transplantationTOR Serine-Threonine KinasesLiver NeoplasmsIntracellular Signaling Peptides and ProteinsImmunosuppressionhepatocellular carcinomalcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensCANCER3. Good healthEuropeMulticenter StudyTreatment OutcomeTARGETsirolimusOncologyLiver Neoplasm030220 oncology & carcinogenesisHepatocellular carcinomaRandomized Controlled TrialmTORCarcinoma Hepatocellular - drug therapy enzymology mortality surgery030211 gastroenterology & hepatologyImmunosuppressive AgentsRCTHumanmedicine.drugCanadamedicine.medical_specialtyCarcinoma HepatocellularTime FactoreducationPopulationLiver Transplantation - adverse effects mortalityProtein Serine-Threonine Kinaseslcsh:RC254-282Disease-Free Survival03 medical and health sciencesInternal medicineGeneticsmedicineTransplantation HomologousHumansComparative StudyRapamycinddc:610educationProtein-Serine-Threonine Kinases - antagonists & inhibitors metabolismKaplan-Meiers Estimatebusiness.industryRisk FactorAustraliaImmunosuppressive Agents - therapeutic useSirolimus - therapeutic useEFFICACYHumans; Liver Transplantation; Hepatocellular Carcinoma; Randomized Controlled Trial; RCT; Multicenter Study; Comparative Study; Rapamycin; mTOR; Sirolimusmedicine.diseaseSurgeryMODELTransplantationClinical trialProspective StudieIntracellular Signaling Peptides and ProteinSirolimusENDOTHELIAL GROWTH-FACTORCYCLOSPORINERAPAMYCINbusiness
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Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis.

2013

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval […

OncologyCancer Researchmedicine.medical_specialtyBioinformaticsBrief CommunicationDisease-Free Survivallaw.inventionRandomized controlled triallawPredictive Value of TestsStomach NeoplasmsInternal medicinemedicineOdds RatioHumansProgression-free survivalRandomized Controlled Trials as Topicddc:616Surrogate endpointbusiness.industryOdds ratioChemotherapy regimenConfidence intervalTreatment OutcomeOncologyPredictive value of testsMeta-analysisNeoplasm Recurrence LocalbusinessBiomarkersJournal of the National Cancer Institute
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The mTOR Inhibitor Temsirolimus Added to Rituximab Combined With Dexamethasone, Cytarabine, and Cisplatinum (R-DHAP) for the Treatment of Patients Wi…

2021

There is a high need for novel treatment options in relapsed and refractory diffuse large B-cell lymphoma. Single agent mammalian target of rapamycin (mTOR) inhibitor treatment has shown promising efficacy in this entity. Here, we report on the results of the mTOR-inhibitor temsirolimus combined to standard rituximab-DHAP salvage regimen in a prospective, multicenter, phase II, open-label study. The STORM regimen consisted of rituximab 375 mg/m(2) (day 2) and DHAP (dexamethasone 40 mg day 3-6, cisplatinum 100 mg/m(2) day 3, cytarabine 2 × 2  g/m(2) day 4) with temsirolimus added on day 1 and 8 of a 21-day cycle, with 2 to 4 cycles planned. In part I, dose levels of 25, 50, 75, and 100 mg fo…

OncologyCancer Researchmedicine.medical_specialtybusiness.industryHematology002ArticleTemsirolimusddc:TransplantationRegimenRefractoryInternal medicineDHAPmedicineCytarabineDiseases of the blood and blood-forming organsRituximabRC633-647.5businessDexamethasonemedicine.drug
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Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT…

2021

Abstract Background Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry. Patients and methods Age-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy (“CARBO/ETO + HDCT”), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry …

OncologyCancer Researchmedicine.medical_specialtymedicine.medical_treatmentMedizinClinical InvestigationsImproved survival610 Medicine & healthBrain Neoplasms/drug therapyCentral Nervous System NeoplasmsHigh dose chemotherapychemistry.chemical_compoundCarboplatin/therapeutic useInternal medicinemedicineHigh-dose chemotherapyHumansNeuroectodermal Tumors Primitive1306 Cancer ResearchProspective StudiesChildOutcomeEtoposideRetrospective StudiesChemotherapyddc:618business.industryBrain NeoplasmsIncidence (epidemiology)IncidenceInfantInduction ChemotherapyNeoplasms Germ Cell and EmbryonalCarboplatinETMRRadiation therapyClinical trialClinical trial2728 Neurology (clinical)Oncologychemistry10036 Medical ClinicChild Preschool2730 OncologyNeurology (clinical)Antineoplastic Combined Chemotherapy Protocols/therapeutic usebusinessCarboplatin/etoposideNeoplasms Germ Cell and Embryonal/drug therapy
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Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO stud…

2014

Background: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study. Patients and methods: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0–2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks + 1-week rest followed by once 3-weeks + 1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were p…

OncologyMaleCancer ResearchAdvanced biliary tract cancerPDGFRβPhases of clinical researchHif1αKaplan-Meier Estimateurologic and male genital diseasesGastroenterologyDeoxycytidineMetastasisAntineoplastic Combined Chemotherapy Protocolsheterocyclic compoundsProspective StudiesLymph nodeAged 80 and overVascular Endothelial Growth FactorsMiddle AgedSorafenibBTCfemale genital diseases and pregnancy complicationsmedicine.anatomical_structureBiliary Tract NeoplasmsTreatment OutcomeOncologyAdenocarcinomaFemaleGallbladder NeoplasmsHand-Foot Syndromemedicine.drugSorafenibAdultNiacinamidemedicine.medical_specialtyPlaceboDisease-Free SurvivalDrug Administration ScheduleDouble-Blind MethodInternal medicinemedicineBiomarkers TumorHumansddc:610neoplasmsAgedbusiness.industryGallbladderPhenylurea Compoundsmedicine.diseaseVascular Endothelial Growth Factor Receptor-2Gemcitabinedigestive system diseasesGemcitabineChemokine CXCL12VEGFR-3VEGFR-2Bile Ducts IntrahepaticBile Duct Neoplasmsc-kitQuality of LifebusinessEuropean journal of cancer (Oxford, England : 1990)
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Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

2020

PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided i…

OncologyMaleCancer ResearchMedizinradiotherapy [Medulloblastoma]Neuropsychological Testsadverse effects [Cranial Irradiation]Craniospinal Irradiation0302 clinical medicinemortality [Cerebellar Neoplasms]drug therapy [Medulloblastoma]Early childhoodProspective Studiesddc:618Systemic chemotherapyCerebellar Neoplasms / mortality3. Good healthOncology030220 oncology & carcinogenesisChild PreschoolMedulloblastoma / radiotherapyFemalemortality [Medulloblastoma]medicine.medical_specialtyCerebellar Neoplasms / drug therapyCerebellar Neoplasms / radiotherapyMEDLINEMedulloblastoma / drug therapyadministration & dosage [Methotrexate]03 medical and health sciencesInternal medicinedrug therapy [Cerebellar Neoplasms]medicineHumansddc:610Cerebellar NeoplasmsMedulloblastomaCranial Irradiation / adverse effectsbusiness.industryEditorialsInfantMethotrexate / administration & dosageDNA Methylationmedicine.diseaseClinical trialMethotrexateMedulloblastoma / mortalityradiotherapy [Cerebellar Neoplasms]Cranial IrradiationbusinessValidation cohort030217 neurology & neurosurgeryMedulloblastoma
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Efficacy and safety of irinotecan-based chemotherapy for advanced colorectal cancer outside clinical trials: an observational study.

2010

Background: This prospective observational study in typical community-based outpatient clinics evaluated the efficacy and toxicity of weekly and biweekly irinotecan-based chemotherapies and their compatibility depending on age. Methods: 601 patients with advanced or metastatic colorectal cancer receiving first-, second-, or third-line irinotecanbased therapy were regularly analyzed for response and toxicity until the end of therapy. Results: The median age was 65 (28–87) years, approximately one-third of the patients were ≥70 years old. Of all patients, 405 were treated weekly and 68 biweekly. Median overall survival (OS) for first-line therapy was 26.5 months for the <70-year-old patients …

OncologyMaleCancer ResearchOrganoplatinum CompoundsColorectal cancermedicine.medical_treatmentLeucovorinAntineoplastic Combined Chemotherapy ProtocolsOutpatient clinicProspective StudiesAged 80 and overClinical Trials as TopicAge FactorsHematologyGeneral MedicineMiddle AgedCombined Modality TherapyTumor BurdenSurvival RateTreatment OutcomeOncologyChemotherapy AdjuvantDisease ProgressionFemaleFluorouracilColorectal Neoplasmsmedicine.drugAdultmedicine.medical_specialtyCombination therapyDrug-Related Side Effects and Adverse ReactionsMedizinische Fakultät -ohne weitere Spezifikation--AdenocarcinomaIrinotecanDrug Administration ScheduleAdvanced colorectal cancerInternal medicinemedicineHumansddc:610AgedNeoplasm StagingChemotherapybusiness.industrymedicine.diseaseClinical trialIrinotecanObservational studyCamptothecinbusinessOnkologie
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Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective …

2017

Abstract Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Out…

OncologyMaleTransplantation ConditioningCancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]Chronic lymphocytic leukemiaMedizinQUALITY MANAGEMENT-SYSTEMKaplan-Meier Estimaterisk factor analysisGUIDELINESBiochemistryallogeneic stem cell transplantation; centre effects; chronic lymphocytic leukaemia; frailties; risk factor analysiscentre effectsTransplantation Conditioning / methods0302 clinical medicineRecurrenceRisk Factorsallogeneic stem cell transplantationLeukemia Lymphocytic Chronic B-Cell / mortalityRegistriesDelivery of Health Care / statistics & numerical dataIBRUTINIBddc:6160303 health sciencesALEMTUZUMABHazard ratioHematopoietic Stem Cell TransplantationProfessional PracticeHematologyMiddle Aged3. Good healthEurope030220 oncology & carcinogenesisABT-199CohortSURVIVALAlemtuzumabFemaleEurope / epidemiologymedicine.drugAdultmedicine.medical_specialtyAllogeneic transplantationImmunologyLower riskDIAGNOSISSettore MED/01 - Statistica Medica03 medical and health sciencesLeukemia Lymphocytic Chronic B-Cell / therapyHematopoietic Stem Cell Transplantation / methodsInternal medicinemedicineHumansKarnofsky Performance Status030304 developmental biologyAgedRetrospective Studiesbusiness.industryProportional hazards modelCHRONIC LYMPHOCYTIC-LEUKEMIARetrospective cohort studySTEM-CELL TRANSPLANTATIONCell Biologymedicine.diseaseLeukemia Lymphocytic Chronic B-CellConfidence intervalSurgeryProfessional Practice / statistics & numerical dataTransplantationbusinessDelivery of Health Carefrailtieschronic lymphocytic leukaemia030215 immunologyRESPONSES
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Incidence, survival and prevalence of myeloid malignancies in Europe.

2012

Abstract Background The Surveillance of Rare Cancers in Europe (RARECARE) project aims at increasing knowledge of rare cancers in Europe. This manuscript describes the epidemiology of myeloid malignancies (MMs), taking into account the morphological characterisation of these tumours. Methods We used data gathered by RARECARE on cancer patients diagnosed from 1995 to 2002 and archived in 64 European population-based cancer registries, followed up to 31st December 2003 or later. Results The overall annual crude incidence of MMs was 8.6 per 100,000. Acute myeloid leukaemia (AML) and myeloproliferative neoplasms (MPN) were most common, with incidence rates of 3.7 and 3.1 per 100,000 year respec…

OncologyMyeloidMaleCancer ResearchMyeloidSurvivalChronic myelomonocytic leukaemiaCancer registry Incidence Prevalence Survival Myeloid malignancies Acute myeloid leukaemia Myelodysplastic syndrome Chronic myeloid leukaemia Chronic myelomonocytic leukaemiaImmunophenotypingEpidemiologyPrevalenceChildLeukemiaIncidence (epidemiology)IncidenceMyeloid malignanciesCancer registryMiddle AgedEuropeLeukemia Myeloid AcuteLeukemiamedicine.anatomical_structureOncologyChild PreschoolMyelodysplastic-Myeloproliferative Diseases/epidemiology/mortalityMyelodysplastic Syndromes/epidemiology/mortalityFemaleAdultmedicine.medical_specialtyAdolescentAcute myeloid leukaemiaNOEurope/epidemiologyInternal medicinemedicinecancer Incidence; survival and prevalence; myeloid malignanciesHumansPreschoolChronic myeloid leukaemiaddc:613AgedMyeloproliferative Disorders/epidemiology/mortalityMyeloproliferative Disordersbusiness.industryMyelodysplastic syndromesInfant NewbornCancerInfantcancer Incidencemedicine.diseaseNewbornMyelodysplastic-Myeloproliferative DiseasesCancer registrysurvival and prevalenceMyelodysplastic SyndromesImmunologyAcute/epidemiology/mortalitybusinessMyelodysplastic syndrome
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Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

2012

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian …

Oncologyendocrine system diseases[SDV]Life Sciences [q-bio]Càncer d'ovariDCN PAC - Perception action and controlCohort StudiesBreast cancer0302 clinical medicinebrca1brca2Odds RatioGenetics (clinical)ComputingMilieux_MISCELLANEOUSOvarian NeoplasmsGenetics0303 health scienceseducation.field_of_studyBRCA1 ProteinHazard ratioMiddle Aged3. Good healthovarian cancer030220 oncology & carcinogenesisFemaleAdultHeterozygotemedicine.medical_specialtyHereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1]PopulationSingle-nucleotide polymorphismBiologyOvarian Neoplasms - geneticsPolymorphism Single NucleotideArticleCàncer de mama03 medical and health sciencesBreast cancerGermline mutationSDG 3 - Good Health and Well-beingTranslational research [ONCOL 3]Ovarian cancerInternal medicineGeneticsmedicineHumansGenetic Predisposition to Diseaseddc:610Genetics and epigenetic pathways of disease Translational research [NCMLS 6]educationRetrospective Studies030304 developmental biologyBRCA2 ProteinHereditary cancer and cancer-related syndromes [ONCOL 1]associationRetrospective cohort studysnpOdds ratioBRCA1 Protein - geneticsmedicine.diseaseBRCA2 Protein - geneticsMutationOvarian cancerbrca2; snp; brca1; association; ovarian cancer
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