CÁNCER COLORECTAL POLIMETASTÁSICO: ABORDAJE MULTIDISCIPLINAR ABORDAJE DE LA CARCINOMATOSIS DE CÁNCER DE COLON VS CÁNCER DE RECTO

Transcripción

1 CÁNCER COLORECTAL POLIMETASTÁSICO: ABORDAJE MULTIDISCIPLINAR ABORDAJE DE LA CARCINOMATOSIS DE CÁNCER DE COLON VS CÁNCER DE RECTO VI Reunión GECOP. IV Reunión SEOQ. Madrid Jueves 19 Noviembre 12:00-13:30

2 Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, with an estimated 1.4 million cases and 693,900 deaths occurring in 2012 Torre LA, et al. CA Cancer J Clin 2015; 65:

3 Decreasing colorectal cancer mortality rates have been observed in a large number of countries worldwide and are most likely attributed to colorectal cancer screening, reduced prevalence of risk factors, and/or improved treatments. Siegel RL, et al. CA Cancer J Clin 2015; 65: 5 29

4 Figure 2. Colon and rectal cancer: Collaborative Stage derived AJCC 6th edition stage distributions for 2004 and 2010, SEER 18 areas. Data source: National Cancer Institute s Surveillance, Epidemiology, and End Results (SEER) Program; SEER 18 geographic areas: states of Connecticut, New Mexico, Utah, California (4 areas: San Francisco, San Jose Monterey, Los Angeles, greater California),Hawaii, Iowa, New Jersey, Louisiana, Kentucky, Georgia (3 areas: Atlanta, rural Georgia, and remainder of the state), Alaska Native Registry, and metropolitan areas of Detroit, Michigan, and Seattle (western Washington),Washington. Chen VW, et al. Cancer 2014; 120 (23 suppl):

5 M1b IVB

6

7 American Cancer Society, Inc., Surveillance Research, 2015

8 CARCINOMATOSIS PERITONEAL. Concepto La carcinomatosis peritoneal representa la diseminación loco-regional intraabdominal de los tumores con o sin evidencia de enfermedad sistémica. El mecanismo de diseminación es por Implantación. Sampson JA. Am J Pathol 1931; 7: Aoyagi T, et al. World J Gastroenterol 2014; 20(35):

9 Resultados. Carcinomatosis Colon. Historia Natural. Supervivencia Carcinomatosis Colorrectal. Autor Pacientes Mediana Supervivencia Chu 45 6 m Sadeghi 118 5,2 m Jayne m Sadahiro 75 6,8 m Chu DZJ, et al. Cancer 1989; 63: Sadeghi B, et al. Cancer 2000; 88: Jayne DG, et al. Br J Surg 2002; 89: Sadahiro S, et al. J Gastrointest Surg 2009; 13:

10 Resultados. Carcinomatosis Colon. TRATAMIENTO SISTÉMICO. Autor Año Revista Quimioterapia iv Mediana Mediana Libre Supervivencia Enfermedad FU 10 4 Moertel 1990 NEJM 5FU LV 14,7 6,2 Moertel C, et al. N Engl J Med 1990; 322: 352

11 Resultados. Carcinomatosis Colon. TRATAMIENTO SISTÉMICO. 5 nuevas drogas en la ULTIMA DECADA han cambiado el horizonte. IRINOTECAN. OXALIPLATINO. CAPECITABINA. BEVACIZUMAB. CETUXIMAB. Autor Año Revista Quimioterapia iv Mediana Supervivencia Mediana Libre Enfermeda De Gramont 2000 JCO 5FU LV OXALIPLATINO FOLFOX 4 16,2 9 Saltz 2000 NEJM 5FU LV IRINOTECAN IFL 14,8 7 Douillard 2000 Lancet 5FU LV IRINOTECAN 17,4 6,7 Tournigand 2003 JCO FOLFIRI + FOLFOX 20,6 14,2 Kabbinavar 2003 JCO 5FU LV BEVACIZUMAB 21,5 9 Hurwitz 2004 NEJM IFL BEVACIZUMAB 20,3 10,6 Goldberg 2004 JCO IFL // IROX // FOLFOX 19,5 9,7 Masi 2006 Ann Oncol 5FU LV OXALI IRI 15,2 8,1 Falcone 2006 PASCO FOLFOXFIRI 22,6 8,1 Masi 2010 Lancet Oncol FOLFOXFIRI + BEVACIZUMAB 30,9 13,6 Klaver 2013 AJCO BEVACIZUMAB, PANITUMUMAB, or CETUXIMAB 22,4 6

12 Washington Cancer Institute Y. YONEMURA PH. SUGARBAKER PH. SUGARBAKER

13 Dr. PH Sugarbaker

14 OBJETIVOS DE LA ESTRATEGIA DE TRATAMIENTO Máxima cirugía citorreductora + Máxima dosis quimioterapia intraperitonea l

15 QUIMIOTERAPIA INTRAPERITONEAL. Weissberger y Cols 1955 La primera utilización de Quimioterapia Intraperitoneal. Ascitis Neoplásica. Weissberger AS, et al. JAMA, 159:

16 BARRERA PERITONEO-PLASMATICA Peritoneal Cavity Drug Dedrick RL, et al. Cancer Treat Rep 1978; 62 (1): 1-11.

17 QUIMIOTERAPIA INTRAPERITONEAL HIPERTERMIA. John S. Spratt PRIMERA QUIMIOHIPERTERMIA.

18 QUIMIOTERAPIA INTRAPERITONEAL Los niveles de 5-FU intraperitoneales son 1000 veces superiores a los plasmáticos. Speyer JL, et al. Cancer Res 1981; 41:

19 QUIMIOTERAPIA INTRAPERITONEAL La administración de 5-FU intraperitoneal permitió un cambio en la historia natural de los pacientes tratados por cancer colorrectal, al disminuir la incidencia de la carcinomatosis peritoneal. Sugarbaker PH, et al. Surgery 1985; 98:

20 HIIC. TECNICA CERRADA

21 QUIMIOTERAPIA INTRAPERITONEAL

22 Figure 2. Blood-peritoneal barrier. Drug diffusion from submesothelial artery and peritoneal surface. Yonemura Y, et al. EJSO 2010;36:

23 HIIC. TECNICA ABIERTA

24 PRINCIPALES CITOSTATICOS INTRAPERITONEALES De Bree E, et al. J Surg Oncol, 79: PH. Sugarbaker. Tech Coloproctol 2005; 9: PH Sugarbaker. Cytoreductive Surgery & Perioperative Chemotherapy for Peritoneal Surface Malignancy: Text book and video atlas

25 QUIMIOTERAPIA INTRAPERITONEAL PROTOCOLO SUGARBAKER Citostáticos Intraoperatorios Tumor Primario Citostáticos Postoperatorios Mitomicina C Pseudomixoma 5 - FU Colorrectal Gástrico Pancreático Cisplatino + Adriamicina 90 a 42ºC Ovario Mesotelioma Sarcoma Taxol Normotermia. Dias 1º-5º Postop HIIC TECNICA ABIERTA MMC 10-12,5 mg/ m 2 90 a 42 ºC. EPIC Dia FU 650 mg/ m 2. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery. Manual for physicians and nurses. The Luddann Company. Grand Rapids, Michigan 1995.

26 100 pacientes 20% > 5 años. PCI < 10 50% > 5 años. Sugarbaker PH. Management of peritoneal-surface malignancy: the surgeon s role. Langebeck s Arch Surg 1999; 384:

27 170 pacientes 45% > 5 años. Sugarbaker PH. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005; 9:

28 Citorreduccion Completa 60% > 5 años. Sugarbaker PH. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005; 9:

29 Resultados. Carcinomatosis Colon. Citorreducción + HIPEC Experiencia personal. No Fase III. Citostáticos obsoletos.

30 Carcinomatosis Colon. Aportación Europea. 1. Estudios Fase III. 2. Experiencia Multiinstitucional. 3. Citostáticos actuales. 4. Ampliación límites indicaciones. Gómez Portilla A, et al. Rev Esp Enf Dig 2009; 101:

31 Estudios Fase III. The median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm Verwaal D, et al. Clin Oncol 2003; 21:

32 Estudios Fase III. It shows a median survival of 48 months and a 5-year survival of 45% for those patients for whom a complete cytoreduction could be achieved Verwaal D, et al. Ann Surg Oncol 2008; 15:

33 Experiencia Multiinstitucional. For CCR-0 patients, the 1-year, 3-year, and 5-year survival rates were 87%, 47%, and 31%, respectively, with a median survival time of 32.4 months Glehen O, et al. J ClinOncol 2004; 22:

34 Citostáticos actuales. Hospital Gustave Roussy D. ELIAS HIIC TECNICA ABIERTA I.P. Oxaliplatin (460 mg/m2) I.V. 5-FU (400 mg/m2) and leucovorin (20 mg/m2) During 30 min. At 43 C.

35 Citostáticos actuales. QUIMIOTERAPIA INTRAPERITONEAL PROTOCOLO SUGARBAKER Citostáticos Intraoperatorios Tumor Primario Citostáticos Postoperatorios Citostáticos Intraoperatorios PROTOCOLO ELIAS Tumor Primario Citostáticos Postoperatorios Mitomicina C Cisplatino + Adriamicina 90 a 42ºC Pseudomixoma Colorrectal Gástrico Pancreático Ovario Mesotelioma Sarcoma 5 - FU Máxima dosis quimioterapia intraperitoneal Taxol Normotermia. Dias 1º-5º Postop Oxaliplatino I.P. + 5-FU/ LV i.v. 30 a 43ºC Pseudomixoma Colorrectal Gástrico Pancreático No Quimioterapia Intraperitoneal Postoperatoria. Si Quimioterapia Sistémica Postoperatoria

36 Citostáticos actuales. Supervivencia años 83% 74% 65% 48% Elias D, et al. Ann Surg Oncol 2002; 13: Elias D, et al. Oncology 2002; 63: Elias D. Surg Oncol Clin N Am 2003; 12: Elias D et,al. Br J Surg 2004; 91: Elias D., et al. EJSO 2006; 32: Elias D,et al.cancer Treat & Research 2007; 134:

37 Citostáticos actuales. HIIC TECNICA ABIERTA I.P. Oxaliplatin (300 mg/m2) + irinotecan (200 mg/m2) I.V. 5-FU (400 mg/m2) and leucovorin (20 mg/m2) During 30 min. At 43 C. Irinotecan. 58% Toxicidad Hematológica. Elias D,et al. Ann Oncol 2004; 15: Elias D, et al. EJSO 2006; 32: Elias D, et al. J Clin Oncol 2010; 28: Quenet F,et al. Ann Surg 2011;254:

38 Experiencia Multiinstitucional. Fig. 6. Survival rates according to the extent of the peritoneal carcinomatosis (measured with the PCI), in the French registry (N patients). a PCI greater than 20 is currently a contraindication for surgery and HIPEC Elias D,et al J Clin Oncol 2010; 28:63-68.

39 Ampliación límites indicaciones. 12 pacientes pacientes Nº Metas Hepáticas. 3,4 (1-15). PCI. 12,4 (2-25). Hepatectomias Mayores 11 Menores 13 Supervivencia 3 5 Años 41,5% 26,5% Elias D, et al. Hepato-Gastroenetrol 1999; 46: Elias D, et al. J Surg Invest 2001; 3: Elias D, et al. Ann Surg Oncol 2004; 11: Elias D, et al. EJSO 2006; 32:

40 Ampliación límites indicaciones. 43 pacientes. 37% Metas Hepáticas. (16). Mediana supervivencia 38,4 m. 2 4 años CCR-0 72% 44% Kinmmanesh R.,et al. Ann Surg 2007; 245:

41 Thomassen I, et al. Dis Colon Rectum 2013 ; 56:

42 Thomassen I, et al. Dis Colon Rectum 2013 ; 56:

43 Resultados. Carcinomatosis Colon. CC0-CC1. Sugarbaker Elias Verwaal Glehen Masi Tournigan Hurwitz Goldberg Douillard De Masi Saltz Moertel Bloemende Jayne Sadeghi Chu

44 Por todo ello, desde luego ya no es éticamente aceptable privar de esta opción a pacientes potencialmente curables, y puede que en el futuro implique responsabilidades legales. Gomez Portilla A. Cir Esp 2006; 79:

45 Rectal and colon cancer represent two distinct entities with completely different biologic behaviors and prognoses. In rectal carcinomas visceral metastases often occurr independtly

46 SYSTEMIC SYSTC Total mesorectal excision and neoadjuvant chemoradiation therapy have been widely adopted to reduce local recurrence and improve the surgical outcome of rectal cancer. Unfortunately, most studies have not been able to show any significant improvement in survival because the frequency of distant metastases remained high Chiang JM et al. World Journal of Surgical Oncology 2014, 12 19

47 The risk of lung metastases was more than three times higher for the distal rectum than for the upper rectum The rectal cancer level significantly affected surgical outcomes including rates and patterns of distant metastases. For lower rectal cancer, systemic venous circulation plays a more important role in the metastatic process. Chiang JM et al. World Journal of Surgical Oncology 2014, 12 19

48 The median survival was 20 months. There have been no five-year survivals in this group of patients When primary rectal cancer has progressed in its natural history to cause carcinomatosis, the disease is far advanced. Gomes Da Silva R, et. Dis Colon Rectum 2005; 48: Gomes Da Silva R, et. J Am Coll Surg 2006; 203:

49 The median survival of the six rectal cancer patients with complete cytoreduction was 17 (range, 12 29) months and 35 (range, 3 241) months for 64 colon cancer patients with complete cytoreduction (P = 0.126). The five-year survival for patients with rectal cancer with complete cytoreduction was 0 % and for patients with colon cancer was 33 % Patients with peritoneal carcinomatosis secondary to rectal cancer treated by cytoreductive surgery combined with intraperitoneal chemotherapy have a poor prognosis. Gomes Da Silva R ET AL. Limited Survival in Rectal Carcinomatosis Dis Colon Rectum

50 615 patients treated for PC originating from these 4 types of primaries in 23 French centers Primary sites were: colon (n= 341), rectum (n= 27) The 5-year overall survival rates were not statistically different for the colon (29.7%), rectum (37.9%) Elias D Ann Surg

51 A total of 13 and 204 patients with PC from rectal and colon cancer Median survival for the rectal and colon groups was 14.6 versus 17.3 months, while the 3-year survival was 28.2 versus 25.1 %. Selected rectal cancer PC should not be excluded from attempted cytoreduction and HIPEC Votanopoulos KI, et al. Ann Surg Oncol April 20(4)

52 Gomes Da Silva R ET AL. Limited Survival in Rectal Carcinomatosis Dis Colon Rectum