RESUMEN
A trombose representa um desafio no cenário do mieloma múltiplo. O avanço no arsenal terapêutico para o tratamento desse câncer trouxe aumento de sobrevida, mas paralelamente acarretou aumento na incidência dos eventos trombóticos, com impacto na morbidade e na mortalidade. Além disso, o perfil epidemiológico dessa população favorece a coexistência de doença cardiovascular, que compartilha com o câncer mecanismos fisiopatológicos trombogênicos. Assim, apesar do uso de anticoagulantes e antiagregantes plaquetários, a estratégia ideal para profilaxia permanece obscura e o desafio vai além da padronização do modelo de avaliação de risco e da terapia anticoagulante. Este trabalho buscou apresentar o estado da arte sobre o tema com o objetivo de discutir a tromboprofilaxia no mieloma múltiplo, enfatizando a abordagem da doença cardiovascular como parte integrante da estratégia.
Venous thromboembolism (VTE) is the second main cause of death of cancer patients and can be the first manifestation of neoplasms or occur at any time point of the course of the disease1-3. Subgroups have different risks with higher rates observed in specific cancers, including pancreas, stomach and multiple myeloma (MM)1.Associated with higher risk of death, thrombotic events do have an important adverse impact as they may lead to treatment interruption, increased morbidity and economic burden4. In this scenario, MM is challenging, it is the second most common hematologic cancer with a risk of VTE nine-fold higher than in the general population1,5. The high-risk results from patient, treatment and disease-related factors. The epidemiologic profile of the patient with MM favors the coexistence of additional thromboembolic risks, nevertheless, advances of oncologic treatment increased global survival and thrombotic risk4. It is known that 10% of the population with MM will develop VTE at some time point of the disease's course4,6, with high incidence in the first six months post-diagnosis5.Inconsistencies in applying the current thromboprophylaxis recommendations have been found. Due to the lack of robust data and standardized models of risk stratification, many physicians tend to rely on their clinical experience7.The ideal thromboprophylaxis of MM remains unknown
Asunto(s)
Mieloma Múltiple , Prevención Primaria , TromboemboliaRESUMEN
Introdução: O tromboembolismo venoso é uma condição potencialmente fatal e frequente no paciente oncológico. Muitas vezes, a anticoagulação é inviável, e a colocação do filtro de veia cava (FVC) torna-se uma opção. A indicação clínica, entretanto, é controversa e gera alto custo. Objetivo: Descrever as características demográficas, clínicas e epidemiológicas dos pacientes com colocação de FVC e seu impacto na sobrevida global. Método: Estudo de coorte retrospectiva com pacientes em tratamento oncológico no INCA, que tiveram FVC implantado de janeiro/2015 até abril/2017. Na análise de sobrevida global em cinco anos, foram considerados o tempo entre o diagnóstico de câncer e o óbito por qualquer causa. Realizaram-se análise descritiva, estimativas de sobrevida (Kaplan-Meier) e regressão de Cox. Resultados: Foram incluídos 74 pacientes com média de idade 54 (+-15) anos. Em sua maioria, apresentavam tumores ginecológicos (52,7%) e digestivos (20,3%). O tempo mediano entre o diagnóstico de câncer e a colocação do FVC foi de 3,48 meses (0-203). No seguimento, foram observados 40 óbitos (54,1%) com mediana de tempo de 25 meses (IC 95%; 1,76-47,32). Na análise ajustada, verificou-se risco 5,63 vezes maior de morrer nos pacientes com colocação do FVC em até seis meses após o diagnóstico de câncer (HR=4,99; IC 95%; 2,20-11,33; p<0,001), e risco 2,47 vezes maior entre aqueles que não fizeram no pré-operatório (HR=2,47; IC 95%; 1,08-5,66; p=0,032). Conclusão: A colocação do FVC foi realizada com maior frequência em pacientes com tumores ginecológicos e em até seis meses após o diagnóstico de câncer foi associada a maior risco de óbito.
Introduction: Venous thromboembolism is a potentially fatal condition and frequent in oncologic patients. Quite often full anticoagulation is unfeasible, and placement of an inferior vena cava (IVC) filter becomes an option. Clinical indication, however, is controversial and expensive. Objective: To describe the demographic, clinical and epidemiological characteristics of oncologic patients submitted to IVC filter placement and their impact on global survival. Method: Retrospective cohort study with patients undergoing cancer treatment at INCA submitted to IVC filter placement from January 2015 to April 2017. Time between cancer diagnoses and death from any cause was considered for the analysis of the global 5-years survival. Descriptive analysis, survival estimates (Kaplan-Meyer) and Cox regression were performed. Results: 74 patients with a mean age of 54 (+15) years were included. Most of them had gynecological (52.7%) and digestive (20.3%) tumors. The median time between cancer diagnosis and IVC filter placement was 3.48 months (0-203). In the follow-up, 40 deaths (54.1%) were observed with a median time of 25 months (95% CI; 1.76 to 47.32). In the adjusted analysis, 5.63 times greater risk of death was verified in patients with IVC filter placement within six months after cancer diagnosis (HR=4.99; 95% CI; 2.20-11.33; p<0.001), and 2.47 times greater risk among those who did not do it at pre-operation (HR=2.47; 95% CI; 1.08-5.66; p=0.032). Conclusion: IVC filter placement was performed more frequently in patients with gynecological tumors and in until six months after cancer diagnosis was associated with increased risk of death.
Introducción: El tromboembolismo venoso es una afección potencialmente mortal y frecuente en pacientes con cáncer. La anticoagulación a menudo no es factible, y la colocación de un filtro de vena cava (FVC) se convierte en una opción. Sin embargo, las indicaciones clínicas son controvertidas y generan un alto costo. Objetivo: Describir las características demográficas, clínicas y epidemiológicas de los pacientes con colocación de CVF y su impacto en la supervivencia general. Método: Estudio de cohorte retrospectivo de pacientes sometidos a tratamiento contra el cáncer en INCA a quienes se les implantó FVC entre enero de 2015 y abril de 2017. En el análisis de la supervivencia general a cinco años, el tiempo transcurrido entre el diagnóstico de cáncer y la muerte cualquier causa Se realizó un análisis descriptivo, estimaciones de supervivencia (Kaplan-Meier) y regresión de Cox. Resultados: Se incluyeron 74 pacientes con una edad media de 54 (+-15) años. La mayoría de ellos tenían tumores ginecológicos (52,7%) y digestivos (20,3%). La mediana del tiempo entre el diagnóstico de cáncer y la colocación de FVC fue de 3,48 meses (0-203). En el período de seguimiento, se observaron 40 muertes (54,1%) con una mediana de tiempo de 25 meses (IC 95%: 1,76 a 47,32). En el análisis ajustado, se observó un riesgo de muerte 5,63 veces mayor en pacientes con colocación de FVC dentro de los seis meses posteriores al diagnóstico de cáncer (HR=4,99; IC 95%: 2,20-11,33; p<0,001) y 2,47 veces mayor riesgo entre aquellos que no lo hicieron antes de la operación (HR=2,47; IC 95%; 1,08-5,66; p=0,032). Conclusión: La colocación de FVC se realizó con mayor frecuencia en pacientes con tumores ginecológicos. La colocación de FVC dentro de los seis meses posteriores al diagnóstico de cáncer se asoció con un mayor riesgo de muerte.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Filtros de Vena Cava/efectos adversos , Tromboembolia Venosa/mortalidad , Neoplasias/mortalidad , Pronóstico , Factores de Tiempo , Análisis de Supervivencia , Estudios Retrospectivos , Tromboembolia Venosa/cirugía , Tromboembolia Venosa/complicaciones , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias/complicacionesRESUMEN
INTRODUCTION: Venous thromboembolism (VTE) is a frequent clinical event in patients with gynecologic cancer. However, studies that exclusively address the incidence of VTE according the type of gynecologic cancer are poorly reported. OBJECTIVE: To analyze the incidence of VTE and the associated factors in women with different types of gynecologic cancer. RESULTS: A total of 1.885 women with gynecologic cancer was included. Among them, 40.8% (769) experienced venous thromboembolic events, most of them in the first two years after cancer diagnosis. There was no statistically significant difference in the incidence of VTE according to the type of gynecologic cancer. However, we observed statistically significant difference in the incidence of pulmonary embolism when stratified by type of thromboembolic events. Multiple regression analysis identified the absence of cancer treatment as a factor associated with VTE in patients with gynecologic cancer (ORâ¯=â¯3.14, CI 95% 2.50-3.96), particularly in patients with cervical (ORâ¯=â¯2.48, CI 95% 1.81-3.42), endometrial (ORâ¯=â¯4.18, CI 95% 2.46-7.10), and ovarian (ORâ¯=â¯3.55, CI 95% 2.22-5.68) cancer. For the total study population, especially patients with cervical and endometrial cancer an advanced stage of cancer was found to be associated with the incidence of VTE. CONCLUSION: We observed that 40.8% experienced venous thromboembolic events. These events were associated with the treatment modality and the stage of cancer.
Asunto(s)
Neoplasias de los Genitales Femeninos , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/epidemiología , Humanos , Incidencia , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
Introdução: A trombose venosa profunda é uma complicação comum e intimamente relacionada às neoplasias. Novos anticoagulantes orais foram lançados nos últimos anos, entre eles, a rivaroxabana. Objetivo: O estudo analisou o custo-efetividade e o impacto orçamentário da rivaroxabana versus enoxaparina. Método: Trata-se de uma coorte retrospectiva, realizada com população oncológica sob a perspectiva do Sistema Único de Saúde. Por meio do modelo de árvore de decisão, foram comparados desfechos de sangramento e retrombose, e custos do tratamento da trombose venosa profunda com rivaroxabana ou enoxaparina, em um horizonte temporal de sete meses. Custos diretos foram extraídos do Sistema de Gerenciamento da Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos, Órteses, Próteses e Materiais e Medicamentos Especiais do SUS (SIGTAP-SUS), e empregou-se a Planilha Brasileira de Impacto Orçamentário de tecnologias da saúde para avaliação do impacto orçamentário com base na população brasileira de 2017, em cinco anos. A análise de sensibilidade simulou cenários tanto na avaliação de custo-efetividade quanto na de impacto orçamentário. Resultados: Cento e cinquenta e três pacientes foram incluídos na análise de custo-efetividade com diversas neoplasias. A rivaroxabana demonstrou não inferioridade terapêutica comparada à enoxaparina. A razão de custo-efetividade incremental foi de R$ 5.521,71 por unidade de benefício ganho com a nova alternativa, rivaroxabana. Na análise de sensibilidade, a rivaroxabana manteve-se dominante. Foi demonstrada uma economia no impacto orçamentário incremental de R$ 85.950.791.129,21 com a utilização de rivaroxabana ao longo de cinco anos em comparação ao cenário de referência, e esta se manteve como opção mais econômica perante as análises de sensibilidade. Conclusão: A rivaroxabana, nesse contexto, apresentou-se como uma importante alternativa terapêutica.
Introduction: Deep vein thrombosis is a common complication and closely related to neoplasms. New oral anticoagulants have been launched in recent years, among them rivaroxaban. Objective: The study analyzed the cost-effectiveness and budget impact of rivaroxaban versus enoxaparin. Method: This is a retrospective cohort, performed with oncological population from the perspective of Sistema Único de Saúde (National Health System). The decision tree model compared outcomes of bleeding and rethrombosis, and costs of treatment of deep venous thrombosis with rivaroxaban or enoxaparin in a time horizon of seven months. Direct costs were extracted from the SIGTAP-SUS, and the Brazilian Spreadsheet for Budgetary Impact of Health Technologies was used to evaluate the budgetary impact based in the Brazilian population of 2017 over a five-year period. The sensitivity analysis simulated scenarios for both cost-effectiveness and budget impact assessments. Results: One hundred and fifty-three patients were included in the cost-effectiveness analysis with several neoplasms. Rivaroxaban demonstrated no therapeutic inferiority compared to enoxaparin. The incremental cost-effectiveness ratio was R$ 5,521.71 per benefit unit spared with the new alternative, rivaroxaban. In the sensitivity analysis, rivaroxaban remained dominant. An economy in incremental budget impact of R$ 85,950,791,129.21 was demonstrated with the use of rivaroxaban over five years in comparison to the reference scenario, and this continued as the most economic option in relation to sensitivity analyzes. Conclusion: In this context rivaroxaban was an important therapeutic alternative.
Introducción: La trombosis venosa profunda es una complicación común e íntimamente relacionada a las neoplasias. Los nuevos anticoagulantes orales. Objetivo: El estudio analizó el Costo-Efectividad y el Impacto Presupuestario de la rivaroxabana versus enoxaparina. Método: En el modelo de árbol de decisión se compararon los resultados de la hemorragia y la retrombosis, y los costos del tratamiento de la trombosis venosa profunda con rivaroxabana o enoxaparina, con una cohorte retrospectiva, realizada con población oncológica bajo la perspectiva del Sistema Único de Salud en un horizonte temporal de siete meses. Los costos directos fueron extraídos del SIGTAP-SUS, y se empleó la Planilla Brasileña de Impacto Presupuestario de Tecnologías de la Salud para evaluación del Impacto Presupuestario con base en la población brasileña de 2017 en un horizonte temporal de cinco años. El análisis de sensibilidad simuló escenarios tanto en la evaluación de Costo-Efectividad y en la de Impacto Presupuestario. Resultados: Ciento cincuenta y tres pacientes fueron incluidos en el análisis de Costo-Efectividad con diversas neoplasias. La rivaroxabana demostró no inferioridad terapéutica comparada a la enoxaparina. La razón de costo-efectividad incremental fue de R $ 5.521,71 por unidad de beneficio ganada con la nueva alternativa, rivaroxabana. En el análisis de sensibilidad, la rivaroxabana se mantuvo dominante. Se demostró una economía em el Impacto Presupuestario incremental de R$ 85.950.791.129,21 con la utilización de rivaroxabana a lo largo de 5 años en comparación al escenario de referencia, y ésta se mantuvo como opción más económica ante los análisis de sensibilidad. Conclusión: La rivaroxabana, en este contexto, se presentó como una importante alternativa terapéutica.
Asunto(s)
Humanos , Enoxaparina/economía , Trombosis de la Vena/tratamiento farmacológico , Rivaroxabán/economía , Neoplasias/complicaciones , Sistema Único de Salud , Análisis Costo-Beneficio , Economía Farmacéutica , Anticoagulantes/economíaRESUMEN
Existe uma estreita relação entre o tromboembolismo venoso e o câncer. Pacientes com neoplasias apresentam maior incidência de eventos tromboembólicos em sua evolução clínica. A ocorrência desses eventos é considerada um marcador preditivo negativo nesse grupo de pacientes. Revisamos, então, a ativação dos mecanismos de coagulação neste grupo de pacientes. Trata-se de um processo complexo e multifatorial, relacionado tanto a características tumorais, estadiamento clínico, agressividade da doença e sítios tumorais, dentre outros. Novos biomarcadores vêm sendo pesquisados ao longo dos anos na tentativa de correlacioná-los ao risco trombótico, visando uma intervenção que melhore a evolução clínica desses pacientes oncológicos
There is a strong relationship between venous thromboembolism and cancer. Patients with tumors have a higher incidence of thromboembolic events in their clinical evolution. The occurrence of such events is considered a negative predictive marker in this group of patients. Thus, we aim to review activation of coagulation mechanisms in this group of patients. Activation of coagulation mechanisms in cancer patients is a complex and multifactorial process, related to tumor characteristics, clinical staging, the disease's aggressiveness, tumor sites, and additional factors caused by disease progression. New biomarkers have been under investigation over the years in the attempt to correlate them to the risk of thrombosis, aiming to develop interventions that improve the clinical evolution of these cancer patients
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias , Tromboembolia Venosa/complicaciones , Factores de Edad , Biomarcadores , Coagulación Sanguínea , Arteria Pulmonar , Embolia Pulmonar , Factores de Riesgo , Factores Sexuales , Trombosis de la VenaRESUMEN
INTRODUCTION: Venous thromboembolism (VTE) is a major complication of malignant diseases and is a frequent cause of death in patients with cancer. Managing anticoagulation in these patients is challenging because of the high risk of recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that provides rapid onset of anticoagulation. OBJECTIVE: The aim of this study was to describe the complications of rivaroxaban and potentially associated factors in patients with gynecologic cancer and VTE. METHODS: This was an observational study in women with gynecological cancer who developed VTE and were treated with 15 and 20 mg rivaroxaban at Instituto Nacional de Câncer from July 2014 to July 2015. RESULTS: Forty-one patients were treated with rivaroxaban. Most patients were younger than 60 years and presented cervical cancer; 58.5% of women did not have complications, thus remaining at a dose of 20 mg/d. Because of complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug suspended, 7.3% had progressive worsening of the disease with suspension of anticoagulation, and 9.8% progressed to death because of progression of the disease. CONCLUSIONS: Rivaroxaban has been documented as a low-cost, easily controlled option compared with standard therapy. Most participants in this study had no complications. However, it was not possible to assess associations with statistical significance. Further analytical studies with larger samples are required to evaluate the safety and efficacy of this treatment in patients with gynecologic cancer.
Asunto(s)
Neoplasias de los Genitales Femeninos/sangre , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Persona de Mediana Edad , Tromboembolia Venosa/sangre , Tromboembolia Venosa/patologíaRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the effect of thromboembolic event (TEE) on the prognosis and survival of women diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer undergoing treatment at the National Cancer Institute (Instituto Nacional de Câncer [INCA], Ministério da Saúde), Brazil. METHODS: A total of 1020 women with FIGO stage IIIB cervical cancer (International Classification of Diseases, C53.9), who had received treatment at this institute between 2000 and 2004, were identified. Data were obtained from the hospital cancer registry at INCA. Patients were followed up from the date of their diagnosis of cervical cancer at INCA until their death or last follow-up visit. The date of TEE diagnosis was defined as the date of one of the following tests diagnosing this condition: Doppler ultrasound scan, computed tomography scan, or in 1 single case echocardiography. The Kaplan-Meyer method was used to perform long-term survival analysis. CONCLUSIONS: The presence of TEE in patients with FIGO stage IIIB cervical cancer seems to be indicative of the severity of the disease and poorer prognosis. The most important finding is that in the patients who developed TEE, this complication occurred around the time of diagnosis of progression of the disease. Disease progression may have been the triggering factor for the development of TEE.