ces 2016 02 - generalidades
TRANSCRIPT
Curso de Oncología para estudiantes de medicina – CES 2016.02Mauricio Lema Medina MD
@onconerd
Page 3
Sobre el cáncer, en general…
Curable en casi 2/3 de los pacientes
Evento catastrófico para el paciente y su entorno
Cambio en la imagen propia, familiar y social
Todo el cuerpo está enfermo – es una traición…
Nada nunca será igual
1
2
3
4
5
Algunas notas
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
10101212
101099
tiempotiempo
UmbralUmbralDiagnósticoDiagnóstico
(1cm)(1cm)
CáncerCáncerIndetectableIndetectable
CánerCánerDetectableDetectable
Límite deLímite deDetecciónDetección
ClínicaClínica
MuerteMuerte
Núm
ero
de C
élul
as C
ance
rosa
s
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Cinética de la historia natural del cáncer
Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000:50;22.
% de muertes totales, US
Enfermedades cardíacas
Cáncer
Cerebrovasculares
EPOC
Accidentes
Pneumonia & Influenza
Diabetes Mellitus
Suicidio
Homicidio
HIV
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Principales causas de mortalidad
Mortalidad por Cáncer y Cardiopatía en USA
Page 8
Cáncer en el mundo
7.6 millones
Hepatocelular (2x)
Cérvix uterino (2x)
Esófago (2-3x)
12.7 millones
Pulmón (2x)
Mama (3x)
Próstata (2.5x)
Colon y recto (3x)
Estadísticas en 2008: Prevalencia – 25 millones
Cáncer:7.6 millones de muertes / año
20.000/día… 14/minuto…Aproximadamente la población de: • Suiza• Israel • Bulgaria
Worlwide overall cáncer incidence
Harrison’s, 19th Ed, 2015
Cáncer es una enfermedad más común en adultos mayores y ancianos…
Harrison’s, 19th Ed, 2015
Lifetime risk: 44% Lifetime risk: 38%
1 de cada 3 cánceres causados por tabaquismo
1 de cada 5 cánceres
causados por obesidad
1 de cada 6 cánceres
causados por infecciones
1 de cada 6 cánceres
causados por infecciones
1 de cada 20 cánceres
causados por alcohol
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Epidemiología del cáncer
Pulmón Estómago Hígado Colon y recto Mama Esófago
Mundo
Pulmón Colon y recto Mama Páncreas Próstata Leucemia
Estados Unidos
Estómago Próstata Pulmón Mama Cérvix Colon y recto
Colombia
Mortalidad - Mundo, Estados Unidos, Colombia
Testículo Mama Hodgkin Próstata Vejiga Colon Ovario Pulmón PáncreasSupervivencia masculina
Supervivencia femenina
Muerte
No todos los cánceres son igualmente letales
Harrison’s, 19th Ed, 2015
Sospecha Clínica
Confirmación patológica
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
SIN DIAGNÓSTICOINCONTROVERTIBLE
(PATOLOGÍA)NO ES POSIBLE FORMULAR
UN PLAN DE MANEJOONCOLÓGICO
ADECUADO
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Page 24
Diagnóstico de cáncer
Tumor Método diagnóstico usual Comentario
Cáncer de mama Biopsia guiada por ecografía/mamografía Core-needleCáncer del pulmón Biopsia (broncoscopia/TAC) -Cáncer de próstata Biopsia guiada por ecografía TransrectalCáncer de estómago Biopsia guiada por endoscopia -
Cáncer de colon y rectal Biopsia guiada por endoscopia -Cérvix uterino Biopsia guida por colposcopia -Linfoma Biopsia escisional ArquitecturaCarcinoma de ovario Laparotomía -
Cáncer de páncreas Biopsia guiada por TAC -Carcinoma hepatocelular Clínico Biopsia
Leucemia Biopsia de médula ósea Mielograma
Estrategia diagnóstica usual (Colombia)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2016
Confirmación patológica
Estadificación Estado funcional
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Estadificación Estado funcional
Curabilidad
EstrategiaTerapéutica
CapacidadPara tolerarTratamiento
(tóxico)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Estadificación
Localizado
Metastásico
Búsqueda sistemáticaDe enfermedad
Metastásica en losSitios donde es más
común
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Estadificación con el TNM
• T: • Tumor
• N: • Compromiso de los ganglios linfáticos regionales
(lymph Nodes)• M:
• Compromiso a distancia (Metastasis)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
TNM – 1: T (Cáncer de colon y recto)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
TNM – 2: N (Cáncer de colon y recto)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
TNM – 2: Estadificación (Cáncer de colon)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
TNM – 1: T (Cáncer de mama)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
TNM – 2: N (Cáncer de mama)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
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Estadificación del cáncer
Tumor Estadificación Otros
Mama TAC de tórax, abdomen y pelvisl, Gammagrafía óseaReceptores hormonales,
HER2Pulmón TAC de tórax, RM cráneo, Gamma ósea / PET CT Mutación EGFRPróstata Gammagrafía ósea, Rayos X tórax / WBMRI PSAEstómago TAC de abdomen total, Rayos X de tórax, Laparoscopia -
Colon y recto TAC (o RM) de tórax y abdomen total CEA, mutación KRAS (metastásico)
Cérvix uterino RM de abdomen y pelvis, Rayos X de tórax -
Linfoma TAC de cuello, tórax, abdomen y pelvis, biopsia médula ósea / PET CT
CD20, CD5, Ciclina, bcl-2, LDH, etc
Ovario TAC de abdomen total, rayos X de tórax Ca 125, resección óptima vs subóptima
Páncreas TAC de abdomen total / PET-CT Ca 19.9
Hepatocelular TAC de abdomen, Childs-Pugh Alfa feto proteina
Leucemia Citogenética, translocaciones, mutaciones -
Estrategia diagnóstica usual (Colombia)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2016
Tumor markers (1)Tumor marker Cancer Nonneoplastic condition
Hormones
hCG GTN, gonadal GCT Pregnancy
Calcitonin MTC
Catecholamines Pheochromocytoma
Oncofetal antigens
AFP HCC, gonadal GFT Cirrhosis, hepatitis
CEA Adenocarcinomas of the colon, pancreas, lung, breast, ovary
Pancreatitis, hepatitis, IBD, smoking
Enzymes
Prostatis Acid Phosphatase Prostatic cancer Porstatis, BPH
Neuron-specific enolase SCLC, Neuroblastoma
LDH Lymphomas, Ewing’s sarcoma, melanoma
Hepatitis, hemolytici anemia, many others
Harrison’s, 19th Ed, 2015
Tumor markers (2)Tumor marker Cancer Nonneoplastic condition
Tumor-associated antigens
PSA Prostate cancer Prostatis, BPH
Monoclonal IG Multiple myeloma Infection, MGUS
Ca 125 Ovarian cancer, some lymphomas
Mensturation, peritonitis, pregnancy
Ca 19.9 Colon, pancreatic, breast cancer
Pancreatitis, ulcerative colitis
CD30 Hodgkin’s lymphoma, anaplastic large-cell lymphoma
CD25 Heiry cell leukemia, Adult T cell leukemia / Lymphoma
CD20 B-cell malignancies
Harrison’s, 19th Ed, 2015
Page 37
Desempaño (Performance status)
ECOG Grado
Actividad normal 0
Sintomático, ambulatorio 1
Confinado ≤ 50% tiempo vigilia 2
Confinado > 50% tiempo vigilia 3
Confinado 100% tiempo 4
Muerto 5
Estado funcional
ECOG: Eastern Cooperative Oncology Group
Karnofsky (KPS) Grado
Actividad normal 100%
No labora, cuida de si mismo 70%
Incapaz de cuidar de si mismo 60%
Hospitalizado/Institucionalizado 40%
Moribundo 20%
Muerto 0%
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
EstadíoD
esem
peño
E: TempranoD: Bueno
E: AvanzadoD: Bueno
E: TempranoD: Malo
E: AvanzadoD: Malo
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
• Usualmente incurable• Expectativa de vida corta (< 3 meses)• Terapia para controlar los síntomas
• Dolor• Disnea• Ansiedad• Constipación, etc
• Alto riesgo de muerte por TOXICIDAD del tratamiento antineoplásico específico
E: AvanzadoD: Malo
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Intención y agresividad terapéutica en oncología
Estadío: TempranoDesempeño: Bueno (PS0-1)
Estadío: TempranoDesempeño: Limítrofe (PS2)
Estadío: TempranoDesempeño: Malo (PS3-4)
Estadío: AvanzadoDesempeño: Bueno (PS0-1)
Estadío: AvanzadoDesempeño: Limítrofe (PS2)
Estadío: AvanzadoDesempeño: Malo (PS3-4)
Intención: CurativaAgresividad: Total
Estadío: CurativaAgresividad: Variable
Intención: Curativo/paliativoAgresividad: Limitada
Estadío: PaliativoAgresividad: Total
Estadío: PaliativoAgresividad: Limitada
Intención: Control síntomasAgresividad: Ninguna
ON
CO
LOG
ÍAC
. PA
LIA
TIVO
Cirugía
Radioterapia
Oncología clínica
Supportive care
“To cure sometimes, to extend life often, and to confort always”
Pain
Setting Prevalence
Diagnosis 25-30%
Treatment associated 20%
Progressive disease 75%
Mechanism
By the tumor 70%
Caused by treatment 20%
Unrelated to cancer 10%
Treatment options
Pharmacologic intervention Will help in 85%
Antitumor therapy
Neurostimulation
Regional analgesia
Neuroablative
Refractory to all measures About 3%
Harrison’s, 19th Ed, 2015
Depression
Dysphoria
Sleep disturbances
Appetite change
Fatigue
Lack of concentrati
on
Worthlessness
Guilt
Guilt
Psychomotor
retardation or
agitation
25%
3 or more
Anhedonia
Depression
25%
FluoxetineSertralineParoxetineAmitriptylineDesipramine
Allow 4-6 weeksContinue for 6 months
83% in 1982 – 13% in 2016
CINV
Taste Chan
ge
Taste Chan
ge
Sun C et al. Support Care Cancer. 2005Sun C et al. Support Care Cancer. 2005
Thrombocytopenia
Thrombocytopenia
Med
ian
VAS
Scor
es
Remission
Remission
CINV 1CINV 1
Current H
ealth
Current H
ealth
Alopecia
Alopecia
Depression
Depression
Ototoxicity
Ototoxicity
Weight G
ain
Weight G
ain
Sexu
al Dysf
unction
Sexu
al Dysf
unction
Memory loss
Memory loss
Constipation
Constipation
Leg pain
Leg pain
Fatigu
e
Fatigu
e FluFlu
Peripheral
Neuropathy
Peripheral
Neuropathy
Diarrhea
Diarrhea
Dysuria
Dysuria
CINV 4CINV 4
CINV 6CINV 6
CINV 5CINV 5
DeathDeath
Perfect
Health
CINV 2CINV 2
Mucositi
s
Mucositi
s
CINV 3CINV 3
Febrile
Neutropenia
Febrile
Neutropenia
Complete Complete ControlControl
Mucositis
Death
Moderate Delayed NauseaModerate Delayed NauseaPoorly Controlled Poorly Controlled Acute & Delayed CINVAcute & Delayed CINV
Chemotherapy Experienced Patients Chemotherapy Experienced Patients Rank Severe CINV Near DeathRank Severe CINV Near Death
49
Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia
Quimioterapia
Central
Periférica
50
Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia
C. Enterocromafín
Liberación de serotonina
Quimioterapia
Periférica
51
Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia
C. Enterocromafín
Liberación de Serotonina
Aferentes vagales receptores de 5-HT3
Quimioterapia
Periférica
52
Quimioterapia
Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia
Complejo Dorsal Vagal – área
postrema
Periférica
Central
C. Enterocromafín
Liberación de Serotonina
Aferentes vagales receptores de 5-HT3
53
Quimioterapia
Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia
ReceptoresNK1 de Sustancia P
Periférica
Central Complejo Dorsal Vagal – área
postrema
C. Enterocromafín
Liberación de Serotonina
Aferentes vagales receptores de 5-HT3
MASC
ASCO
NCCN
5-HT3-RA (ie, Ondansetron)Dexamethasone
NK1-RA (ie, fosaprepitant)
Guideline recommendations for acute CINV in Highly Emetogenic Chemotherapy (including AC)
Olanzapine – Palonosetron – Dexamethasone
(alternative)
Navari RM, Aapro M, NEJM, 2016
Nutrition
Weight loss Decreased appetite, citokynes, altered metabolism
When to intervene?
10% unexplained weight loss
Serum transferrin 150 mg/dL or less
Ablumin 3.4 gr/dL, o less
How to intervene?
Enteral preferred over parenteral
Harrison’s, 19th Ed, 2015
RECIST: Response Evaluation Criteria In Solid Tumors
Change in the sum of the longest diameters↑20% (or new lesion): Progressive disease↓30%: partial response (PR)↓100%: unconfirmed complete response (uCR)↓100% + Negative biopsy: complete response (CR)
Education and healthful habits
Tobacco Comments
Risk factor Cardiovascular disease, pulmonary diseasse and cancer
Tobacco-related death 1/3 of smokers
Cancers Lung, laryng, oropharynx, esophagus, kidney, bladder, pancreas, and stomach
Risk after quitting 30-50% lower 10-yr lung cancer mortality
Second-hand smoke also harmful
Early adoption 80% smokers begin befor age 18
Cigars also increase cancer risk Oral and esophageal cancer
Smokeless tobacco also increases cancer risk
Oral cancer
Benefits of e-cigarettes unclear
Harrison’s, 19th Ed, 2015
Physical inactivity Comments
Risk factor Colon and breast cancer
Some biases may obscure this relationship
Harrison’s, 19th Ed, 2015
Diet modification Comments
High fat diet increases risk of Breast, colon, prostate, endometrium
High dietary fiber decreases the risk Colonic polyps and colon cancer
High fruit and vegetable intake NOT proven of benefit
RCT
Low-fat, High fiber diet faild to decrease risk of colonic polyp
RCTx 2
No dietary intervention has proven effective in preventing cancer
WHI
Harrison’s, 19th Ed, 2015
Energy balance Comments
Obesity increases risk of Colon, breast (postmenopausal), endometrial, kidney, esophagus (GEJ)
Magnitud of the effect
Colon cancer RR 1.5-2 in males, 1.2-15 in females
Breast cancer Risk increases by 30-50%
Adipose tissue harbors aromatase that can create estrogen from androgens
Harrison’s, 19th Ed, 2015
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Asociación Obesidad y Cáncer
Gordura corporal Unión gastroesofágica Páncreas Colon y recto Mama Endometrio Riñón Gordura abdominal Colon y recto
Convincente
Gordura corporal Vesícula Gordura abdominal Páncreas Mama Endometrio Ganancia de peso
adulto Mama
Probable
Gordura corporal Hígado Peso bajo Pulmón
Sugestivo
Se atribuye a la obesidad aprox. 20% y 14% de los cánceres en mujeres y hombres, respectivamente, en USA
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sun avoidance Comments
Cumulative exposure to UV radiation Non-melanoma skin cancers
Intermittent acute sun exposure Melanoma (maybe)
Protective clothing, reduction of sun exposure
Reduce risk of skin caner
Sunscreen Decreases risk of actinic keratoses
No evidence of decrease risk of melanoma
Freckling High risk of skin malignancies
Risk factors for melanoma Sunburns, large number of melanocytic nevi, and atypical nevi
Harrison’s, 19th Ed, 2015
Cancer chemoprevention
Chemoprevention Comments
Upper aerodigestive tract and lung Smoking cessation
HPV vaccination
B-carotene increases lung cancer risk
Colon cancer Aspirin (75 mg QD) dicreases colon cancer risk by 24%
Cox-2 inhibitors increase CV risk, so studies on cancer chemoprevention were abandoned
High calcium diets decrease CRC risk (not supperted by the WHI)
Estrogen + progestin decreases CRC risk by 44% (WHI)
Statins may decrease CRC risk
Breast cancer Tamoxifen dicreases BC risk by 49%
Raloxifen and Exemestane ara also effective chemopreventive strategies for women with high risk (1.55% 5-yr risk) of BC
Prostate cancer Finasteride and Dutasteride dcrease low-grade, but increase high-grade prostatic cancer. No survival benefit
Vitamin E supplementation increases prostate cancer risk
Harrison’s, 19th Ed, 2015
Vaccine and cancer prevention Comments
Hepatitis B and C are related to liver cancer
Hepatitis B vaccination has proven effective for B-hepatitis and hepatomas
HPV are linked to cervical, anal and head and neck cancers
HPV vaccination may decrease cervical cancer risk by 70%, but studies are ongoing. Vaccination of females and males is recommendd in the US at ages 9-26
H. Pylori is related to gastric adenocarcinomas and gastric lymphoma
No vaccination stretegy exists
Surgical prevention of cancer
Cervical dysplasia Conization
FAP or UC Colectomy
BRCA1/BRCA2 Prophylactic bilateral mastectomy
Prophylactic oophorectomy
Breast cancer Prophylacti oophorectomy (in premenopausal women)
Harrison’s, 19th Ed, 2015
Cancer screening
Breast cancer screening Comments
Mammography Q1-2 years, 50 and older: decreases BC by 15-30%
Benefits in less than 50 less clear
High false positive rates
High risk of overdiagnosis
Considerable amount of overdiagnosis has ensued in the US
BSE No evidence of benefit in BC detection or mortality
Breast MRI May be effective in BRCA1/2 carriers (not proven in prospective trials)
Harrison’s, 19th Ed, 2015
Cervical cancer screening Comments
Pap-smear Begin at age 21, every 3 years, up to age 30.
At 30, Pap-smear + HPV testing may be offered. If both negativa, screening can be decreased to q5 years
Stop at 65 in women with 10 years history of normal screening tests
Screening may be discontinued after histerectomy for non-oncologic reasons
Harrison’s, 19th Ed, 2015
CRC screening Comments
FOBT 15% risk reduction
False positive in 1-5%
Only 2-10% of positive tests have cancer
Fecal immunochemical tests have higher sensitiviity
Fecal DNA tests may be superior to FOBT, but studies are ongoning
Sigmoidoscopy Decreases CRC risk by 18%, and mortality by 28%
Should be performed between ages 50-74
Optimal interval unknown, 5 year interval recommended
Colonoscopy Detects 25% more advanced lesions than FOBT + sigmoidoscopy
Perforation risk 3/1000
Expensive
Start at 50, q10years, up to 70
CT colonography Comparable to colonoscopy
High incidence of incidental findings of unknown significance (15-30%)
High radiation risk
Harrison’s, 19th Ed, 2015
Prostate cancer screening Comments
DRE + PSA Dramatic increase in prostate cancer diagnosis
Unclear overall benefit due to lead-time bias, length-bias, and overdiagnosis
False positive results induce invasive testing
Even true positive results may not always detect cancers that will impact survival
Two major trials with conflicting results
American PLCO: negativa (but close to half the control group underwent opportunistic PSA evaluation)
European ERSPC: positive. But, to avert 1 death, more than 1000 patients needed to be screened, and 37 prostate cancers needed to be detected
Screen detected low-grade prostate cancer therapy may cause more harm than good.
UPSTF recommends against routing prostate cancer screening
ACS recommends PSA and DRE starting at age 50, in highly motivated men, fully informed of the poetnatial consequences
Harrison’s, 19th Ed, 2015
Lung cancer screening Comments
LD CT 15-20% reduction of lung cancer mortality (about 3/1000 screened)
Yearly, 55-74, in heavy smokers (30ç ppy)
High incidence of incidental findings
Radiation exposure
CXR Ineffective
Harrison’s, 19th Ed, 2015