RESUMO
Daratumumab is the first anti-CD38 targeting monoclonal antibody approved as monotherapy in multiply relapsed myeloma patients who progressed following prior treatment with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). We present real world data on the efficacy of single agent daratumumab in a cohort of 55 multiply relapsed patients treated in the UK.The median age was 72 years, the majority (96%) received ≥ 3 previous lines of treatment; 54.5% were PI-refractory, 76.4% were IMiD-refractory and 47.2% were double refractory; 20% of patients had high-risk (HR) disease.The overall response rate was 49%. After a median follow up of 9.2 months, the median progression-free survival (PFS) for the total cohort was 5.1 months. Patients who achieved a partial response or better (≥PR) demonstrated a significantly longer PFS compared to those with Assuntos
Mieloma Múltiplo
, Humanos
, Idoso
, Mieloma Múltiplo/tratamento farmacológico
, Agentes de Imunomodulação
, Resultado do Tratamento
, Anticorpos Monoclonais/efeitos adversos
, Reino Unido
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
RESUMO
OBJECTIVE: Strategies to improve outcomes for patients with ruptured abdominal aortic aneurysm (rAAA) are becoming more evident. The aging population, however, continues to make the decision to intervene often difficult, especially given that traditional risk models do not reflect issues of aging and frailty. This study aimed to integrate measures of function alongside comorbidity- and frailty-specific factors to determine outcome. METHODS: Patients treated for a rAAA between January 2006 and April 2014 were assessed. Demographics, mortality, and requirement for care after discharge as well as a variety of measures of function (physical, social, and psychological) and comorbidity were recorded. The primary outcome was 1-year mortality. Outcome models were generated using multivariate logistic regression and were compared with models of vascular frailty and AAA-related outcome. RESULTS: Of 184 patients treated, 108 (59%) underwent an open surgical repair. The overall 30-day and 1-year mortality were 21.5% and 31.4%, respectively, with an overall median hospital length of stay of 13 days (interquartile range, 6-27 days). An optimal logistic regression model for 12-month mortality used Katz score, Charlson score, number of admission medicines, visual impairment, hearing impairment, hemoglobin level, and statin use as predictors, achieving an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS: This novel rAAA model incorporating function and comorbidity offers good predictive power for mortality. It is quick to calculate and may ultimately become helpful for both counseling and selection of patients and comparative audit at a time when outcome in patients with rAAA increasingly comes under the spotlight.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Idoso Fragilizado , Nível de Saúde , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/mortalidade , Área Sob a Curva , Comorbidade , Registros Eletrônicos de Saúde , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Modelos Logísticos , Masculino , Alta do Paciente , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
OBJECTIVE: To investigate the clinical and pathological trends, over a 10-year period, in robot-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. PATIENTS AND METHODS: In all, 1 500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data were collected on clinicopathological details at presentation as well as surgical outcomes and compared over time. RESULTS: The median (range) age of patients throughout the period was 62 (35-78) years. The proportion of preoperative high-grade cases (Gleason score 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (P < 0.001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (P < 0.001). The median prostate-specific antigen (PSA) level at diagnosis did not alter significantly. Overall, 11.6% of men in 2005-2008 were classified preoperatively as high-risk by National Institute for Health and Care Excellence criteria, compared with 33.6% in 2013-2015 (P < 0.001). The corresponding proportions for low-risk cases were 48.6% and 17.3%, respectively. Final surgical pathology showed an increase in tumour stage, Gleason grade, and nodal status over time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-2015 (P < 0.001), Gleason score 9-10 tumours increased from 1.8% to 9.1% (P < 0.001) and positive nodal status increased from 1.6% to 12.9% (P < 0.001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (P = 0.72). CONCLUSION: This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher stage and more advanced disease being referred and operated on. However, surgical margin outcomes have remained good.
Assuntos
Laparoscopia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Prostatectomia/métodos , Encaminhamento e Consulta , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
OBJECTIVES: Dental caries is the most common reason for hospital admissions for children aged 6-10 years in England. The prevalence in the experience of hospital admission is not uniform across all populations. This paper reports on the analysis of secondary data on dental hospital episodes for children residing in London, and its association with oral health inequalities. DESIGN, SETTING AND PARTICIPANTS: Retrospective, non-identifiable patient data sourced from the Hospital Episode Statistics dataset was analysed. Finished consultant episodes (FCEs) were extracted for children aged 1-19 years, residing in London and admitted with a primary diagnosis of caries between 2015/2016 and 2020/2021. OUTCOME MEASURES: The number and rates of FCEs with a primary diagnosis of dental caries for children aged 1-19 years old was analysed for six consecutive financial years (2015/2016 to 2020/2021). To assess oral health inequalities in children experiencing hospital admission due to dental caries, several demographic variables were analysed: deprivation, age, and sex. RESULTS: Between the financial years of 2015-2016 and 2020-2021, there were a total of 57 055 hospital admissions for dental caries for children aged 1-19 years (average rate of admission was 465.1 per 100 000 of children). A year-on-year decline was noted between 2015-2016 and 2020-2021. Regression analysis demonstrated clear social gradients with significant oral health inequalities; those from the most deprived areas experienced over two times the number of hospital admissions (58%). Children aged 4-9 years accounted for 68.9% (39 325) for the total dental hospital episodes from 2015-2016 to 2020-2021. CONCLUSION: London's year-on-year reduction in hospital admission for dental caries is due to various factors including effective prevention interventions and an effective paediatric clinical care pathway. Sociodemographic factors remain to act as key predictors for hospital admission for child with dental caries. While health service level changes may reduce the number of hospital admissions, persistent child oral health inequalities continue to exist.
Assuntos
Cárie Dentária , Saúde Bucal , Criança , Humanos , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Londres/epidemiologia , Estudos Retrospectivos , Cárie Dentária/epidemiologia , Cárie Dentária/terapia , HospitaisRESUMO
Bortezomib, a first generation proteasome inhibitor, is used in both newly diagnosed and relapsed myeloma settings. Considerable differences exist in the usage of bortezomib therapy in the clinical practice setting in comparison to clinical trial setting as well manufacturer's recommendations. These differences include route of administration (intravenous (iv) vs. subcutaneous (sc)), frequency from twice to once weekly, choice of alkylating agent used in combination with bortezomib (melphalan or cyclophosphamide), and choice of glucocorticoids (dexamethasone or prednisolone). We reviewed data from 272 consecutive bortezomib-treated myeloma patients, who received therapy within the regional Thames Valley Cancer Network for both newly diagnosed myeloma (NDMM, n = 120) and relapsed MM (RMM, n = 152). We investigated the influence of age, sex, transplant, bortezomib combinations (doublet vs. triplet), cumulative bortezomib dose per treatment line (<50mg vs. ≥50mg), and route of administration (iv vs. sc) on time to next treatment (TTNT) and on overall survival (OS). Route of bortezomib administration (iv vs. sc) influenced neither OS (41 vs 35 months, p = 0.5), nor TTNT (14 vs. 19 months, p = 0.052). Our study showed a statistically significant improvement in median OS in patients receiving a cumulative dose ≥50mg compared to <50mg (42 vs. 33months, p = 0.003), although presence of confounders need to be taken into account, such as disease stage, performance status, genetic changes and prior therapies. Median OS was longer using triplet therapies compared to a doublet in the RMM cohort (37 vs. 29 months, p = 0.06), although this did not reach statistical significance. Multivariate Cox Regression analysis showed that cumulative bortezomib dose ≥50mg (p = 0.002, HR = 1.83, 95% CI 1.25-2.67) and autologous transplant (p = 0.002, HR = 2.6, 95% CI 1.41-3.98) were both significant factors associated with improved OS. Our data argues in favour of continuing bortezomib for the recommended duration as per Summary of Product Characteristics (SPC), subject to good tolerability, in order to deepen response or extend the duration of best response.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Esquema de Medicação , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Caracteres Sexuais , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC. METHODS: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan-Meier method. RESULTS: 91 mChRCC patients from 26 centres were included. Median follow-up from the date of first metastasis was 6.1 years (range: 0-13.9). Median OS was 37.9 months (95% confidence interval [CI]: 21.4-46.8) from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months (95% CI: 5.2-10.9) and 22.9 months (95% CI: 17.8-49.2) versus 1.9 months (95% CI: 1.0-6.0) and 3.2 months (95% CI: 2.3-not evaluable) with mTOR inhibitors, respectively. A stratified log-rank test was used to compare AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (p = 0.26) or for OS (p = 0.55). CONCLUSION: We report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS.