BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS: Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. CONCLUSIONS: Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).

• MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doutnající mnohočetný myelom * diagnóza   mortalita   terapie   MeSH
• injekce subkutánní MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   epidemiologie   prevence a kontrola   MeSH
• monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• pozorné vyčkávání * statistika a číselné údaje   MeSH
• progrese nemoci MeSH
• protinádorové látky * aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• C-reaktivní protein * analýza   MeSH
• cévní mozková příhoda prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu * prevence a kontrola   mortalita   MeSH
• Kaplanův-Meierův odhad MeSH
• kolchicin * terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• recidiva MeSH
• sekundární prevence MeSH
• senioři MeSH
• spironolakton terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   škodlivé účinky   MeSH
• cévní mozková příhoda mortalita   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu * mortalita   farmakoterapie   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• spironolakton * terapeutické užití   škodlivé účinky   MeSH
• srdeční selhání * farmakoterapie   mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

• MeSH
• adalimumab terapeutické užití   MeSH
• ankylózující spondylitida * farmakoterapie   mortalita   MeSH
• antirevmatika * terapeutické užití   MeSH
• dospělí MeSH
• etanercept * terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• psoriatická artritida * farmakoterapie   mortalita   MeSH
• registrace * MeSH
• revmatoidní artritida * farmakoterapie   mortalita   MeSH
• senioři MeSH
• tendenční skóre * MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: There is a paucity of data on treatment outcomes following stereotactic radiosurgery (SRS) for brain metastases from sarcoma primaries. METHODS: The International Radiosurgery Research Foundation member-sites were queried for patients with brain metastases from sarcoma primaries treated with SRS. Overall survival (OS) and local control (LC) were calculated via Kaplan-Meier analysis. Univariate analyses examined prognostic factors associated with LC and OS via log-rank t-tests and multivariate analyses (MVA) via Cox proportional hazards model. RESULTS: A total of 146 patients with 309 brain metastases were identified. Two-hundred and thirty lesions were treated with single-fraction SRS with a median dose of 20 Gy (15-24 Gy). Ninety-five patients had extracranial metastases, including 75 oligometastatic patients. One- and 2-year OS and LC rates were 47.7% and 37.3%, and 78.3% and 62.2%, respectively. On univariate analyses, superior 1-year OS was noted among leiomyosarcomas (69.7% vs. 42.6%; p = .02) with poorer outcomes among pleomorphic histologies (10.5% vs. 50.7%; p = .002). Pleomorphic histologies were associated with poorer OS on MVA (hazard ratio [HR], 3.13; p = .006). On MVA, LC was inferior among patients of age ≥45 years (HR, 3.78; p < .001) and superior among leiomyosarcomas (HR, 0.31; p = .03). OS was prognosticated based on adverse factors (ie, nonleiomyosarcoma histology and progressive extracranial metastases). Two-year OS for patients with and without adverse features were 78.6% and 31.5%, respectively. CONCLUSIONS: LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age <45 years. OS was driven by nonleiomyosarcoma histology and the presence of progressive extracranial disease.

• MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory mozku * sekundární   radioterapie   mortalita   chirurgie   MeSH
• prognóza MeSH
• radiochirurgie * metody   MeSH
• retrospektivní studie MeSH
• sarkom * patologie   mortalita   radioterapie   sekundární   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The poor prognosis of colorectal cancer (CRC) contributes to a yearly increase in CRC mortality, while microRNAs (miRNAs) were found to play a regulatory function in diversiform cancers, including CRC. The objective of this research was to evaluate the clinical value and possible regulatory mechanisms of miR-767-5p in CRC. The expression level of miR-767-5p in CRC tissues and cells was examined. The Kaplan-Meier curve was utilized to analyse the function of miR-767-5p in CRC prognosis. The independent prognostic factors in CRC were assessed by a multivariate COX regression analysis. Additionally, the regulatory mechanism of miR-767-5p in CRC was determined through an in vitro cell experiment. The miR-767-5p expression was down-regulated in CRC tumour tissues and CRC cells. Indicators such as tumour differentiation, TNM, LNM and miR-767-5p were identified as independent prognostic factors for a poor CRC prognosis. The regulatory relationship between miR-767-5p and nuclear factor I A (NFIA) was verified by the dual-luciferase reporter assay, and the NFIA expression level was significantly suppressed by over-expressed miR-767-5p. The proliferation, migration and invasion of CRC cells were inhibited by over-expressing miR-767-5p, while the inhibition effect could be reversed by over-expressing NFIA. The over-expressed miR-767-5p could serve as a tumour suppressor to inhibit the progression of CRC by suppressing the expression level of NFIA.

• MeSH
• invazivní růst nádoru MeSH
• Kaplanův-Meierův odhad MeSH
• kolorektální nádory * genetika   patologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk genetika   MeSH
• prognóza MeSH
• proliferace buněk genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• transkripční faktory NFI metabolismus   genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Revision total hip arthroplasty (rTHA) is an increasingly common procedure due to the growing number of primary total hip arthroplasties (THAs) performed worldwide. This study evaluates the long-term implant survival, functional outcomes, and radiographic performance of cemented femoral stem (Beznoska s.r.o., Kladno, Czechia) in rTHA. METHODS: A retrospective analysis was conducted on 183 patients who underwent rTHA with cemented stem between March 2012 and December 2023. The mean follow-up duration was 71.26(± 39.31) months. Implant survival was analyzed using Kaplan-Meier survival estimates, and failure modes were assessed. Radiographic changes were classified using the Gruen Zones system. Functional outcomes were evaluated using the Harris Hip Score (HHS). Cox proportional hazard models were applied to identify prognostic factors influencing implant survival. RESULTS: The five-year implant survival rate was 98.1%, declining to 83.9% at twelve years. The overall failure rate was 3.83%, with periprosthetic infection (4 cases) being the most common cause, followed by aseptic loosening (2 cases). Radiographic changes were observed in 24.03% of cases, predominantly in Gruen Zones 2, 6, and 1. Functional outcomes were favorable, with a mean HHS of 81.28(± 5.74), comparable to outcomes reported for uncemented revision stems. Age, stem diameter, and stem length did not significantly impact implant survival. CONCLUSION: The cemented stem demonstrated favourable long-term survival, with high implant retention rates. Functional outcomes indicated overall satisfactory performance. Radiographic evaluation revealed localized changes around the implant, predominantly in Gruen Zones 2, 6, and 1. Implant failure was relatively rare, with periprosthetic infection being the most common cause.

• MeSH
• cementování MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• kostní cementy MeSH
• kyčelní kloub diagnostické zobrazování   chirurgie   MeSH
• kyčelní protézy * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu * metody   přístrojové vybavení   škodlivé účinky   MeSH
• protézy - design MeSH
• radiografie MeSH
• reoperace * MeSH
• retrospektivní studie MeSH
• selhání protézy * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Valvuloplastika aortálnej chlopne s extenziou cípov sa rutinne používa v liečbe chýb aortálnej chlopne u detí a dospievajúcich. Materiál použitý na valvuloplastiku môže ovplyvniť funkciu aortálnej chlopne a jej trvácnosť. Ciele: Zhodnotiť dlhodobé výsledky valvuloplastiky aortálnej chlopne technikou extenzie cípov pomocou autológneho perikardu alebo polytetraflóretylénu (Ptfe) a odhaliť rizikové faktory vedúce k reoperácii aortálnej chlopne na našom pracovisku. Metódy: retrospektívna analýza 89 pacientov, ktorí sa podrobili valvuloplastike aortálnej chlopne technikou extenzie cípov pomocou autológneho perikardu alebo Ptfe na našom pracovisku v období 2005 – 2023. Výsledky: 89 pacientov (75 % mužského pohlavia) sa podrobilo valvuloplastike aortálnej chlopne technikou extenzie cípov pomocou autológneho perikardu (n = 42) alebo Ptfe (n = 47). Medián veku pacientov bol 14 rokov (iQr: 7 mesiacov – 26 rokov). Počas strednej dĺžky sledovania 13,3 roka (iQr: 1 mesiac – 18 rokov) sme zaznamenali 4 úmrtia a u 41 (46 %) pacientov bola potrebná reoperácia priemerne 7,8 ± 4,2 roka od primárnej operácie. V skupine s autológnym perikardom to nastalo u 24 (57 %) pacientov a v skupine s Ptfe u 17 (36 %) pacientov. celkové prežívanie pacientov v čase 18 rokov od operácie bolo 95 %. reoperovanosť v celom súbore v 5 rokoch od operácie bola 12,4 %, v 10 rokoch 43 % a v 15 rokoch 64,6 %. Pri multivariabilnej coxovej analýze boli identifikované nasledujúce rizikové faktory pre reoperáciu na aortálnej chlopni: aortálna insuficiencia ako primárna diagnóza, diameter aortálnej chlopne, infekčná endokarditída, dĺžka klemu na aorte a mimotelového obehu a predchádzajúca valvuloplastika v minulosti. Záver: Dlhodobé výsledky aortálnej valvuloplastiky technikou extenzie cípov pomocou autológneho perikardu alebo Ptfe u pacientov s vrodenou chybou aortálnej chlopne odrážajú vynikajúce prežívanie bez významného rozdielu z hľadiska výskytu reoperácií kvôli dysfunkcii aortálnej chlopne medzi obomi skupinami pacientov.

Background: Aortic valve repair with leaflet extension is routinely utilized in the management of aortic valve disease in children and adolescents. The material chosen may have an effect on the valve function and durability. Aims: To evaluate long-term outcomes of aortic valve repair using autologous pericardium and polytetrafluoroethylene (PTFE) leaflet extensions and to investigate risk factors for aortic valve reoperation at single centre. Methods: A retrospective single-centre review of 89 patients undergoing aortic valvuloplasty by leaflet extensions with either autologous pericardium or PTFE from 2005 to 2023. Results: Eighty-nine patients (75% male) underwent aortic leaflet extension valvuloplasty, using either autologous pericardium (n = 42) or PTFE (n = 47). Median age was 14 years (IQR: 7 months-26 years). During median follow-up duration of 13.3 years (IQR: 1 month-18 years), there were 4 deaths and 41 (46%) patients required reoperation at a mean of 7.8 ± 4.2 years, 24 (57%) within autologous pericardium group, and 17 (36%) within PTFE group. Overall survival at 18 years was 95%. Overall reoperation-free survival at 5, 10 and 15 years was 87.6%, 57%, and 35.4%, respectively. Multivariable Cox analysis identified primary diagnosis of aortic regurgitation, aortic annulus diameter, infective endocarditis, aortic cross-clamp and cardiopulmonary bypass time, and preoperative aortic surgical valvuloplasty as risk factors for aortic valve reoperation. Conclusions: Long-term results of aortic leaflet extension valvuloplasty, utilizing either autologous pericardium or PTFE, in patients with congenital aortic valve disease suggest excellent survival with no significant difference in the reoperation rate for aortic valve dysfunction between the groups.

• MeSH
• analýza přežití MeSH
• aortální chlopeň chirurgie   MeSH
• chirurgická náhrada chlopně metody   mortalita   MeSH
• dítě MeSH
• Kaplanův-Meierův odhad MeSH
• katetrizace * metody   mortalita   MeSH
• lidé MeSH
• mladiství MeSH
• onemocnění aortální chlopně * chirurgie   mortalita   vrozené   MeSH
• polytetrafluoroethylen terapeutické užití   MeSH
• reoperace statistika a číselné údaje   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• statistika jako téma MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.

• MeSH
• deep learning MeSH
• dítě MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kostí * mortalita   patologie   MeSH
• nekróza * MeSH
• neoadjuvantní terapie * metody   MeSH
• neuronové sítě * MeSH
• osteosarkom * mortalita   patologie   terapie   MeSH
• prognóza MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. METHODS: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. RESULTS: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. CONCLUSIONS: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).

• MeSH
• adjuvantní chemoterapie škodlivé účinky   metody   MeSH
• analýza přežití MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• cystektomie * MeSH
• deoxycytidin * aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• gemcitabin MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• nádory močového měchýře * mortalita   patologie   terapie   MeSH
• neoadjuvantní terapie škodlivé účinky   metody   MeSH
• protinádorové látky imunologicky aktivní * aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie * aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH