CES201701-Clase 1

Curso de Oncología para estudiantes de medicina – CES 2017.01Mauricio Lema Medina MD

@onconerd

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

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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


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


Principales causas de mortalidad

Mortalidad por Cáncer y Cardiopatía en USA

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…


Lifetime risk: 44% Lifetime risk: 38%

1 de cada 3 cánceres causados por tabaquismo

1 de cada 5 cánceres

causados por obesidad


causados por infecciones


causados por alcohol

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

Sospecha Clínica

Confirmación patológica


SIN DIAGNÓSTICOINCONTROVERTIBLE

(PATOLOGÍA)NO ES POSIBLE FORMULAR

UN PLAN DE MANEJOONCOLÓGICO

ADECUADO


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)


Confirmación patológica

Estadificación Estado funcional


Estadificación Estado funcional

Curabilidad

EstrategiaTerapéutica

CapacidadPara tolerarTratamiento

(tóxico)


Estadificación

Localizado

Metastásico

Búsqueda sistemáticaDe enfermedad

Metastásica en losSitios donde es más

común


Estadificación con el TNM

• T: • Tumor

• N: • Compromiso de los ganglios linfáticos regionales

(lymph Nodes)• M:

• Compromiso a distancia (Metastasis)


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)


TNM – 2: Estadificación (Cáncer de colon)


TNM – 1: T (Cáncer de mama)


TNM – 2: N (Cáncer de mama)


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)


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


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


Desempeño (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%


EstadíoD

esem

peño

E: TempranoD: Bueno

E: AvanzadoD: Bueno

E: TempranoD: Malo

E: AvanzadoD: Malo


• 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


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

Intención: CurativaAgresividad: Variable

Intención: Curativo/paliativoAgresividad: Limitada

Intención: PaliativoAgresividad: Total

Intención: 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%


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


C. Enterocromafín

Liberación de serotonina

Quimioterapia

Periférica

51


C. Enterocromafín

Liberación de Serotonina

Aferentes vagales receptores de 5-HT3

Quimioterapia

Periférica

52

Quimioterapia


Complejo Dorsal Vagal – área

postrema

Periférica

Central

C. Enterocromafín



53

Quimioterapia


ReceptoresNK1 de Sustancia P

Periférica

Central Complejo Dorsal Vagal – área

postrema

C. Enterocromafín



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


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


Physical inactivity Comments

Risk factor Colon and breast cancer

Some biases may obscure this relationship


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


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


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


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


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


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)


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)


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


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


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


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


CES201701-Clase 1

Health & Medicine

Transcript of CES201701-Clase 1