marcadores tumorales en el diagnostico precoz y ......harm than good because lung cancer screening...
TRANSCRIPT
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1
Marcadores Tumorales en el diagnostico precoz y diagnostico del cáncer
de pulmón
Rafael Molina Porto. Servicio Bioquímica y Genética Molecular, Hospital Clínic
de Barcelona, Barcelona
Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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INTRODUCCIÓN
España: Ambos sexos, todas las edades
Colorectal
Próstata
Pulmón
Mama
Incidencia
MortalidadCongreso Nacio
nal Laboratorio Clínico 2018
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Ser un problema de salud (frecuente)
Historia Natural conocida
Método de diagnostico adecuado
Tratamiento eficaz (demuestre
incremento de supervivencia)
Población de riesgo (Coste/Eficiencia)
Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Lung cancer
Diagnóstico Precoz
Nuevas Terapias
PrevenciónCongreso Nacio
nal Laboratorio Clínico 2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Tenemos la población riesgo
¿Método de Despistaje?Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Fumadores/
Exfumadores
50-75 años
En Asia?
¿Periodicidad?Congreso Nacional Laboratorio Clínico
2018
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Please if your are a patient with a high risk of lung cancer,
come and we will explain you options and vantages and
disadvantages for cancer screening..
IMPOSIBLE COSTE/EFICIENCIA
Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
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Screening everyone may cause more harm than good because lung cancer screening has certain risks.
For example, doctors find a lung nodule suspicious for lung cancer in about 25% of patients who get a screening CT scan. All of these abnormalities require further testing to determine if they are cancer, but only a few (less than 4%) are actually lung cancerCongreso Nacio
nal Laboratorio Clínico 2018
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SABEMOS DONDE, A QUIEN HACER EL SCREENING
PERO……..
NO TENEMOS PRUEBAS CON UN COSTE/EFICIENCIA ADECUADO.
Congreso Nacional Laboratorio Clínico
2018
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Aplicaciones Clínicas de los Biomarcadores
Beneficio Teorico
Alta sensibiidad y especificidad
Facil, economico, y con control calidad
Beneficio Teorico
Alta sensibiidad y especificidad
Facil, economico, y con control calidad
Congreso Nacional Laboratorio Clínico
2018
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Diagnóstico….Grupos de Riesgo
- Tos
- Disnea
- Hemoptisis
- Imagen RX
Riesgo
Molina R. Tumor Biol 2009, 30:121-129.
Molina R. Tumor Biol 2008, 29:371-80.
Molina R, et al. Am J Respir Crit Care Med.
2016;193: 427-437
CEA, CYFRA; CA 15.3
SCC, NSE, ProGRP
Congreso Nacional Laboratorio Clínico
2018
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Criterios:1) Valores anormales de Marcadores tumorales (Especificidad 83%)2) Evolución≥25% Incremento en relación al valor previo, separados al
menos 3 semanas y al menos con uno de los dos superior al intervalo normal
Alto riesgo
Bajo riesgo
Bajo Riesgo
Niveles sericos de ProGRP
Molina R, et al. Am J Respir Crit Care Med. 2016;193: 427-37.
Congreso Nacional Laboratorio Clínico
2018
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CEA <5 ng/mL
CYFRA <3.3 ng/mL
SCC <2.5 ng/mL
CA 125 <35 U/mL
CA 15.3 <35 U/mL
NSE <25 ng/mL
ProGRP <65 pg/mL
CEA <5 ng/mL
CYFRA <3.3 ng/mL
SCC <2.5 ng/mL
CA 125 <35 U/mL
CA 15.3 <35 U/mL
NSE <25 ng/mL
ProGRP <65 pg/mL
Congreso Nacional Laboratorio Clínico
2018
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Tomografia confirma benignidad
Especificidad 99%
Mujer de 76 con un nódulo pulmonar (11mm) en el lóbulo superior derecho. Recomendamos descartar cáncer de pulmón
Congreso Nacional Laboratorio Clínico
2018
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NCICP 1509 pacientes Sensibilidad
Al menos uno
CEA > 5 ng/ml
CYFRA > 3.3 ng/ml
CA 15.3 > 35 U/ml
NSE: > 25 ng/ml
ProGRP >65 pg/ml
SCC > 2.5 ng/ml
CA 19.9 > 37 U/ml
327 CICP pacientes
Congreso Nacional Laboratorio Clínico
2018
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Marcadores tumorales en NCICP: 1807 pacientes
Total sensibility (one or another tumor marker)
Pacientes 103 161 17 137 197 220 856
¿?
Valor Predictivo positivo 77.8%
Congreso Nacional Laboratorio Clínico
2018
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Model AUC und 95% CI
Predictor for age 0.54 (0.5; 0.58)
Predictor for smoker status 0.6 (0.56; 0.64)
Predictor for image 0.84 (0.82; 0.87)
Predictor for image + age + smoker status 0.85 (0.83; 0.88)
Predictor for biomarkers 0.89 (0.88; 0.91)
Predictor for biomarkers + Image 0.92 (0.91; 0.94)
Predictor for full model 0.93 (0.91; 0.94)
Molina R, et al. Am J Respir Crit Care Med. 2016;193: 427-437.
28
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2018
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43,8%
71,1%
87,7%
8,6%
39,2%
7,6%
<1cm 1-3 cm >3cm
TM+
TM-
Tamaño del tumor
Valor Predictivo Positivo
29
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2018
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CEA <5 ng/mL
CYFRA <3.3 ng/mL
SCC <2.5 ng/mL
CA 125 <35 U/mL
CA 15.3 <35 U/mL
NSE <25 ng/mL
ProGRP <65 pg/mL
CEA <5 ng/mL
CYFRA <3.3 ng/mL
SCC <2.5 ng/mL
CA 125 <35 U/mL
CA 15.3 <35 U/mL
NSE <25 ng/mL
ProGRP <65 pg/mL
Congreso Nacional Laboratorio Clínico
2018
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Caso clínico – Paciente 3
31
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Después de 10 días de antibioticos
Enf. Infecciosa
Los biomarcadores mejoran la imagen
Caso clínico – Paciente 3
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2018
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Paciente de 79, fumador, que acude para mediastinoscopia por
múltiples nódulos mediastínicos, sugestivos de linfoma.
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mL
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mL
Congreso Nacional Laboratorio Clínico
2018
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CICP intratorácico
Los Biomarcadores mejoran la imagen
Caso clínico – Paciente 5
Congreso Nacional Laboratorio Clínico
2018
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CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mL
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mLCongreso Nacional Laboratorio Clínico
2018
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Raquel R. C. Paciente 35 años, no fumadora que acude con
nódulo pulmonar sospechoso
36
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2018
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37
Raquel R. C. Paciente 35 años, no fumadora que acude con
nódulo pulmonar sospechoso
Congreso Nacional Laboratorio Clínico
2018
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Descenso del tamaño de los nódulos que sugiere con elevada
probabilidad origen no neoplásico. Se decide esperar y no
realizar biopsia
38
Agosto 2017
Los biomarcadores mejoran la imagen
Pero
¿Informan sobre la histología?
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2018
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Marcadores Tumorales en la clasificación
histológica
Probabilidad 99,1%
NSCLC SCLC
Probabilidad 97,9%
NSCLC SCLC
ProGRP <100 pg/ml, NSE < 35 ng/ml y CEA> 5 ng/ml o CYFRA >3.3 ng/l o SCC > 1.5 ng/ml
ProGRP >150 pg/ml, o NSE > 50 ng/ml o ProGRp >100 pg/ml y NSE >30 ng/ml
2204 pacientes 471 pacientes
Congreso Nacional Laboratorio Clínico
2018
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CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mL
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP< 65 pg/mLCongreso Nacional Laboratorio Clínico
2018
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H-1
Escamoso, Estadio IIIA
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Hallazgo casual de incremento de CEA en paciente no fumadora
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP < 65 pg/mL
CEA < 5 ng/mL
CYFRA <3.3 ng/mL
SCC < 2,5 ng/mL
CA 125 < 35 U/mL
CA 15.3 < 35 U/mL
NSE < 25 ng/mL
ProGRP < 65 pg/mL
Congreso Nacional Laboratorio Clínico
2018
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[i]
• Incrementan eficacia de la imagen
• Faciles de hacer, escasa morbilidad
• Baratos
• Relación con la histologia
Beneficios Teóricos de los Biomarcadores
Tumor Sensibilidad Especificidad Prevalencia
Colon 35-50% 45% Alta
Próstata 40% 35% Alta
Ovario 80% 75% Baja
Pulmón 80% 80-99% Alta
Once we accept our limits, we go beyond them.
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2018
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2018
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Prevalencia 0.5 x 4000…….20 pacientes Cáncer
1000 falsos + (5.000 Tac)
Marcadores tumorales……..10 pacientes (50%). ¿Seriada? ¿12?
10% falsos +.. Solo 400 TAC
Coste/paciente……10%.....
10 veces más pacientes
MT…40.000 personas
100 cánceres
4000 TACCongreso Nacional Laboratorio Clínico
2018
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0
5
10
15
20
25
30
35
Basal 1 mes 1 año 2 años
SospechaMarcadores tumorales
Incremento >50%
Dentro normalidad
…riesgo
AUMENTO DE LA SUPERIVENCIA
Incrementar sensibilidad
1) Control evolutivo dentro de la normalidad…..10-15%
Congreso Nacional Laboratorio Clínico
2018
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Congreso Nacional Laboratorio Clínico
2018
![Page 50: Marcadores Tumorales en el diagnostico precoz y ......harm than good because lung cancer screening has certain risks. For example, doctors find a lung nodule suspicious for lung cancer](https://reader031.vdocument.in/reader031/viewer/2022011812/5e325764847cea35f956aa9b/html5/thumbnails/50.jpg)
Nuevos Biomarcadores proteicos
Marcadores Moleculares (EFGR..)
Patrones proteicos…. Ser un problema de salud (frecuente)
Método de diagnostico adecuado
Fácil de realizar
Tratamiento eficaz (demuestre
incremento de supervivencia
Población de riesgo (Coste/Eficiencia)
Congreso Nacional Laboratorio Clínico
2018
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GRACIAS POR SU ATENCION
Congreso Nacional Laboratorio Clínico
2018