CES 2016 02 - Generalidades
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Curso de oncología para estudiantes de medicina, Universidad CES. Clase número 1, generalidades, factores de riesgo, prevención, y tamizaje.
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CES 2016 02 - Generalidades
- 1. Curso de Oncología para estudiantes de medicina – CES 2016.02 Mauricio Lema Medina MD
- 2. @onconerd
- 3. 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
- 4. Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 5. 10101212 101099 tiempotiempo UmbralUmbral DiagnósticoDiagnóstico (1cm)(1cm) CáncerCáncer IndetectableIndetectable CánerCáner DetectableDetectable Límite deLímite de DetecciónDetección ClínicaClínica MuerteMuerte NúmerodeCélulasCancerosas Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004 Cinética de la historia natural del cáncer
- 6. 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
- 7. Mortalidad por Cáncer y Cardiopatía en USA
- 8. 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
- 9. Cáncer: 7.6 millones de muertes / año 20.000/día… 14/minuto… Aproximadamente la población de: • Suiza • Israel • Bulgaria
- 10. Worlwide overall cáncer incidence Harrison’s, 19th Ed, 2015
- 11. Cáncer es una enfermedad más común en adultos mayores y ancianos…
- 12. Harrison’s, 19th Ed, 2015 Lifetime risk: 44% Lifetime risk: 38%
- 14. 1 de cada 3 cánceres causados por tabaquismo
- 15. 1 de cada 5 cánceres causados por obesidad
- 16. 1 de cada 6 cánceres causados por infecciones
- 17. 1 de cada 6 cánceres causados por infecciones
- 18. 1 de cada 20 cánceres causados por alcohol
- 19. Page 19 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
- 20. Testículo Mama Hodgkin Próstata Vejiga Colon Ovario Pulmón Páncreas Supervivencia masculina Supervivencia femenina Muerte No todos los cánceres son igualmente letales
- 21. Harrison’s, 19th Ed, 2015
- 22. Sospecha Clínica Confirmación patológica Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 23. SIN DIAGNÓSTICO INCONTROVERTIBLE (PATOLOGÍA) NO ES POSIBLE FORMULAR UN PLAN DE MANEJO ONCOLÓGICO ADECUADO Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 24. Page 24 Diagnóstico de cáncer Tumor Método diagnóstico usual Comentario Cáncer de mama Biopsia guiada por ecografía/mamografía Core-needle Cáncer del pulmón Biopsia (broncoscopia/TAC) - Cáncer de próstata Biopsia guiada por ecografía Transrectal Cáncer de estómago Biopsia guiada por endoscopia - Cáncer de colon y rectal Biopsia guiada por endoscopia - Cérvix uterino Biopsia guida por colposcopia - Linfoma Biopsia escisional Arquitectura Carcinoma 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
- 25. Confirmación patológica Estadificación Estado funcional Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 26. Estadificación Estado funcional Curabilidad Estrategia Terapéutica Capacidad Para tolerar Tratamiento (tóxico) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 27. Estadificación Localizado Metastásico Búsqueda sistemática De enfermedad Metastásica en los Sitios donde es más común Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 28. 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
- 29. TNM – 1: T (Cáncer de colon y recto) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011 AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
- 30. TNM – 2: N (Cáncer de colon y recto) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011 AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
- 31. TNM – 2: Estadificación (Cáncer de colon) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011 AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
- 32. TNM – 1: T (Cáncer de mama) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011 AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
- 33. TNM – 2: N (Cáncer de mama) Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011 AJCC – TNM 7th Ed, 2010 http://www.cancerstaging.org/ 06.02.2011
- 34. Page 34 Estadificación del cáncer Tumor Estadificación Otros Mama TAC de tórax, abdomen y pelvisl, Gammagrafía ósea Receptores hormonales, HER2 Pulmón TAC de tórax, RM cráneo, Gamma ósea / PET CT Mutación EGFR Próstata Gammagrafía ósea, Rayos X tórax / WBMRI PSA Estómago 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
- 35. 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
- 36. 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
- 37. 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
- 38. Estadío Desempeño E: Temprano D: Bueno E: Avanzado D: Bueno E: Temprano D: Malo E: Avanzado D: Malo Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 39. • 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: Avanzado D: Malo Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
- 40. Intención y agresividad terapéutica en oncología Estadío: Temprano Desempeño: Bueno (PS0-1) Estadío: Temprano Desempeño: Limítrofe (PS2) Estadío: Temprano Desempeño: Malo (PS3-4) Estadío: Avanzado Desempeño: Bueno (PS0-1) Estadío: Avanzado Desempeño: Limítrofe (PS2) Estadío: Avanzado Desempeño: Malo (PS3-4) Intención: Curativa Agresividad: Total Estadío: Curativa Agresividad: Variable Intención: Curativo/paliativo Agresividad: Limitada Estadío: Paliativo Agresividad: Total Estadío: Paliativo Agresividad: Limitada Intención: Control síntomas Agresividad: Ninguna ONCOLOGÍAC.PALIATIVO
- 42. Supportive care “To cure sometimes, to extend life often, and to confort always”
- 43. 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
- 44. Depression Dysphoria Sleep disturbances Appetite change Fatigue Lack of concentrati on Worthlessn ess Guilt Guilt Psychomot or retardatio n or agitation 25% 3 or more Anhedonia
- 45. Depression 25% Fluoxetine Sertraline Paroxetine Amitriptyline Desipramine Allow 4-6 weeks Continue for 6 months
- 47. 83% in 1982 – 13% in 2016 CINV
- 48. Taste Change Taste Change C et al. Support Care Cancer. 2005C et al. Support Care Cancer. 2005 Throm bocytopenia Throm bocytopenia MedianVASScores Rem ission Rem issionCINV 1 CINV 1 CurrentHealth CurrentHealthAlopecia Alopecia Depression Depression Ototoxicity Ototoxicity W eightGain W eightGain SexualDysfunction SexualDysfunction M em oryloss M em oryloss Constipation ConstipationLeg pain Leg painFatigue Fatigue Flu Flu PeripheralNeuropathy PeripheralNeuropathy Diarrhea Diarrhea Dysuria Dysuria CINV 4 CINV 4CINV 6 CINV 6CINV 5 CINV 5Death Death PerfectHealth CINV 2 CINV 2 M ucositis M ucositis CINV 3 CINV 3 Febrile Neutropenia Febrile Neutropenia CompleteComplete ControlControl Mucositis Death Moderate Delayed NauseaModerate Delayed Nausea Poorly ControlledPoorly Controlled Acute & Delayed CINVAcute & Delayed CINV Chemotherapy Experienced PatientsChemotherapy Experienced Patients Rank Severe CINV Near DeathRank Severe CINV Near Death
- 49. 49 Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia Quimioterapia Central Periférica
- 50. 50 Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia C. Enterocromafín Liberación de serotonina Quimioterapia Periférica
- 51. 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. 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. 53 Quimioterapia Mecanismos de las Náuseas y Vómito inducidos por la quimioterapia Receptores NK1 de Sustancia P Periférica Central Complejo Dorsal Vagal – área postrema C. Enterocromafín Liberación de Serotonina Aferentes vagales receptores de 5-HT3
- 54. 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
- 55. 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
- 56. 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)
- 57. Education and healthful habits
- 58. 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
- 59. Physical inactivity Comments Risk factor Colon and breast cancer Some biases may obscure this relationship Harrison’s, 19th Ed, 2015
- 60. 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
- 61. 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
- 62. Page 62 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
- 63. 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
- 65. 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
- 66. 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
- 67. Cancer screening
- 68. 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
- 69. 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
- 70. 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
- 71. 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
- 72. 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
Notas del editor
- Preliminary preference (utility) data from nausea and vomiting health states from 3 studies involving ovarian cancer patients, clinicians, and healthy female controls were evaluated. Preferences were assessed using the visual analog scale (VAS), with scores ranging from 0.0 (worst) to 1.0 (best). Definitions of CINV were: CINV 1 - Days 1-5 = little to no nausea or vomiting. CINV 2 - Day 1 = complete control; Days 2-5 = moderate nausea, no vomiting. CINV 3 - Day 1 = complete control; Days 2-5 = moderate nausea, severe vomiting. CINV 4 - Day 1 = nausea and vomiting; Days 2-5 = moderate nausea. CINV 5 - Day 1 = nausea and vomiting; Days 2-5 = moderate nausea, severe vomiting. CINV 6 - Day 1 = complete control; Days 2-5 = severe nausea. Patients rated significant CINV (CINV 3-6) comparable to the score for death. 1. Sun C, Bodurka D, Donato M et al. Nausea and vomiting side-effects of cancer therapies: preference assessments from patients, health care providers and healthy women. Support Care Cancer. 2002:10:378. Abstract #93.