Historia Natural de la Enfermedad y Pronóstico Describir la severidad para establecer prioridades de manejo Los pacientes quieren y deben de saber Es importante establecer las características basales de la historia natural para evaluar efectividad de nuevos tratamientos. Importancia: Describir la severidad para establecer prioridades de manejo Los pacientes quieren y deben de saber Es importante establecer la situacion basal de la hist nat para evaluar efectividad de nuevos tratamientos. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Figure 6-2 The natural history of disease in a patient. Historia Natural de la Enfermedad Para inciciar la discusion, vamos a revisar una grafica de la hist nat de la enfermedad. Donde empezamos a medir sobrevida despues de la enfermedad? Puede haber muertes antes del diagnostico. Figure 6-2 The natural history of disease in a patient. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Estrategias para medir pronóstico Tasa de fatalidad o letalidad Numero de “eventos” por persona-tiempo observadas Sobrevida a 5 años Tablas de vida (sobrevida observada) Sobrevida en periodos regulares (1 año) Sobrevida en periodos irregulares (K-M) Tiempo medio de sobrevida Tasa de relativa de sobrevida

Útil en enfermedades agudas Util para enfermedades con cursos cortos. Útil en enfermedades agudas

Año Persona Observación Son equivalentes. Si la probabilida de muerte es mayor en los primeros 20 meses, entonces? Figure 6-3 Two examples of 10 person-years: five people, each observed for 2 years, and two people, each observed for 5 years. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Algunos problemas Figure 6-4 Timing of period of greatest risk is from shortly after diagnosis until about 20 months after diagnosis. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

10 persona-año Figure 6-5 Two people, each observed for 5 years, and the relation to the period of greatest risk. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

10 persona-año Figure 6-6 Five people, each observed for 2 years, and the relation to the period of greatest risk. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Figure 6-7 Two examples of 10 person-years in which the period of greatest risk is from shortly after diagnosis until about 20 months after diagnosis. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Tasa de sobrevida a 5 años Utilizado para evaluar efectividad de tratamientos en enfermedades oncológicas Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Antes y después de un programa agresivo para diagnóstico de cáncer de mama El caso de una mujer en un sitio con programas agresivos de diagnostico comunitario de cancer de mama. Dx en el 2005 y murio en el 2010 . Es mejor proinostico. Another problem with 5-year survival is that if we want to look at the survival experience of a group of patients who were diagnosed less than 5 years ago, we clearly cannot use this criterion, because 5 years of observation are necessary in these patients to calculate 5-year survival. Therefore, if we want to assess a therapy that was introduced less than 5 years ago, 5-year survival is not an appropriate measure. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Figure 6-10 Five-year survival curves in two hypothetical populations. ¿Son diferentes? ¿Que grupo prefieren? A final issue relating to 5-year survival is shown in Figure 6-10. Here we see survival curves for two populations, A and B. Five-year survival is about 10%. However, the curves leading to the same 5-year survival are quite different. For although survival at 5 years is the same in both groups, most of the deaths in group A did not occur until the fifth year, whereas most of the deaths in group B occurred in the first year. Thus, despite the identical 5-year survivals, survival during the 5 years is clearly better for those in group A. Figure 6-10 Five-year survival curves in two hypothetical populations. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Sobrevida utilizando tablas de vida Intervalos regulares (1 año) Figure 6-11 Survival curve for a hypothetical example of patients treated from 2000 to 2004 and followed until 2005. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Tablas de vida

Censuras son pérdidas a seguimiento Ejemplo mas realista

Cálculos:

Ejemplo hipotético de seis pacientes analizados con K-M. Método de Kaplan Meier Ejemplo hipotético de seis pacientes analizados con K-M. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Column (1): The times for each death from the time of enrollment (time that treatment was initiated). Column (2): The number of patients who were alive and followed at the time of that death, including those who died at that time. Column (3): The number who died at that time. Column (4): The proportion of those who were alive and followed (column 2) who died at that time (column 3) [column 3/column 2]. Column (5): The proportion of those who were alive and survived (1 - column 4). Column (6): Cumulative survival (the proportion of those who were initially enrolled and survived to that point).

K-M: Sobrevida a diferentes intervalos (de acuerdo a ocurrencia del evento de interés) Figure 6-13 Kaplan-Meier plot of the survival study shown in Figure 6-12. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

“remplazo de válvula temprano” Kaplan Meier 1. Sobrevida de pacientes con estenosis aortica no es diferente estadísticamente significativa a 5 años comparado con controles pareados de acuerdo a edad y sexo. 2. Sobrevida sin “eventos” de acuerdo a severidad de la enfermedad (estenosis aortica) Pacientes con estenosis moderada a severa, peor pronóstico aun después de la cirugía. “remplazo de válvula temprano” Figure 6-14A shows their Kaplan-Meier analysis of survival among 126 patients with aortic stenosis compared with age- and sex-matched people in the general population. Although survival was slightly worse in patients with aortic stenosis, the difference was not significant. When they examined several risk factors, they found that moderate and severe calcification of the aortic valve was a significant predictor of subsequent cardiac events and very poor prognosis (see Fig. 6-14B). Event-free survival was much worse in patients with moderate or severe valve calcification than in patients with no or mild calcification. The authors concluded that such patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Tablas de Vida: Supuestos No existe un cambio secular Pocas censuras No siempre se mide ocurrencia de muerte, pueden ser otros eventos (desarrollo de complicaciones, hospitalizaciones, etc.) Métodos estadísticos para comparar curvas de diferentes grupos./

Sobrevida de pacientes pediátricos con LLA de acuerdo a raza Figure 6-15 Survival of children aged 0 to 19 years with acute lymphocytic leukemia by race, metropolitan Baltimore, 1960-1975. (From Szklo M, Gordis L, Tonascia J, Kaplan E: The changing survivorship of white and black children with leukemia. Cancer 42:59-66, 1978. Copyright © 1978 American Cancer Society. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.) Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Cambios temporales de sobrevida en niños blancos Figure 6-16 Temporal changes in survival of white children aged 0 to 19 years with acute lymphocytic leukemia, metropolitan Baltimore, 1960-1975. (From Szklo M, Gordis L, Tonascia J, Kaplan E: The changing survivorship of white and black children with leukemia. Cancer 42:59-66, 1978. Copyright © 1978 American Cancer Society. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.) Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Cambios temporales de sobrevida en niños de raza negra What accounts for this racial difference? First, we must take account of the small numbers involved and the possibility that the differences could have been due to chance. Let us assume, however, that the differences are real. During the past several decades, tremendous strides have occurred in the treatment of leukemia through combined therapy, including central nervous system radiation added to chemotherapy. Why, then, does a racial difference exist in survivorship? Why is it that the improvement in therapy that has been so effective in white children has not had a comparable benefit in black children? Further analyses of the interval from the time the mother noticed symptoms to the time of diagnosis and treatment indicated that the differences in survival did not appear to be due to a delay in black parents seeking or obtaining medical care. Because acute leukemia is more severe in blacks and more advanced at the time of diagnosis, the racial difference could reflect biologic differences in the disease, such as a more aggressive and rapidly progressive form of the illness. The definitive explanation is not yet clear Figure 6-17 Temporal changes in survival of black children aged 0 to 19 years with acute lymphocytic leukemia, metropolitan Baltimore, 1960-1975. (From Szklo M, Gordis L, Tonascia J, Kaplan E: The changing survivorship of white and black children with leukemia. Cancer 42:59-66, 1978. Copyright © 1978 American Cancer Society. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.) Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Efecto aparente de pronóstico al mejorar estrategias diagnósticas Figure 6-18 Stage migration. A, Classification of cases by presence or absence of detectable metastases in 1980. B, Presence of undetectable micro-metastases in 1980. C, Impact of improved diagnosis of micro-metastases in 2000, on the stage-specific case-fatality rate. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Efecto aparente de pronóstico al mejorar estrategias diagnósticas Figure 6-19 Hypothetical example of stage migration. A, Assumed case-fatality by stage. B, Impact of improved diagnosis of micro-metastases on stage-specific case-fatality (CFR). C, Apparent improvements in stage-specific survival as a result of stage migration even without any improvement in effectiveness of treatment. Fenómeno de Will Rogers Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Solo se requiere esperar hasta que mueran la mitad Another approach to expressing prognosis is the median survival time, which is defined as the length of time that half of the study population survives. Why should we use median survival time rather than mean survival time, which is an average of the survival times? Median survival offers two advantages over mean survival. First, it is less affected by extremes, whereas the mean is significantly affected by even a single outlier. One or two persons with a very long survival time could significantly affect the mean, even if all of the other survival times were much shorter. Second, if we used mean survival, we would have to observe all of the deaths in the study population before the mean could be calculated. However, to calculate median survival, we would only have to observe the deaths of half of the group.

Proporción de sobrevivientes a 5 años y tasa relativa de acuerdo a edad.

¿Por que?

Sobrevida perfecta a 10 años Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Figure 6-21 Relative suvival rate II: Observed survival. Sobrevida observada en pacientes > 75 años Figure 6-21 Relative suvival rate II: Observed survival. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Sobrevida esperada (> muertes no atribuidas a cáncer de colon) Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Sobrevida relativa, se aleja de la sobrevida observada Figure 6-23 Relative survival rate IV: Observed, expected, and relative survival. Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Generalización: Selección de pacientes de centros comunitarios vs.de clínicas especializadas Selección de pacientes de centros comunitarios vs.de hospitales Niños con un episodio de convulsiones por fiebre que experiemtaron convulsiones no-febriles posteriormente JAMA 243:1337-1340, 1980.) Downloaded from: StudentConsult (on 20 August 2009 09:52 PM) © 2005 Elsevier

Estadísticas de Sobrevida Paramétricas: Distribución Exponencial Distribución de Weibull Distribución Lognormal No paramétricas: Kaplan Meier Logrank Regresión de Cox