abordaje de la carcinomatosis de cáncer de colon vs cáncer de recto

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

VI Reunión GECOP. IV Reunión SEOQ. Madrid. 2015. Jueves 19 Noviembre 12:00-13:30

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: 87–108

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

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): 3793-806

M1b

IVB

American Cancer Society, Inc., Surveillance Research, 2015

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.

CARCINOMATOSIS PERITONEAL. Concepto

Sampson JA. Am J Pathol 1931; 7: 423-43. Aoyagi T, et al. World J Gastroenterol 2014; 20(35): 12493-12500.

Chu DZJ , et al. Cancer 1989; 63: 364-367. Sadeghi B , et al. Cancer 2000; 88: 358-363. Jayne DG , et al. Br J Surg 2002; 89: 1545-1550. Sadahiro S , et al. J Gastrointest Surg 2009; 13: 1593- 1598.

Supervivencia Carcinomatosis Colorrectal. Autor Pacientes Mediana Supervivencia Chu 45 6 m Sadeghi 118 5,2 m Jayne 349 9 m Sadahiro 75 6,8 m

Resultados. Carcinomatosis Colon. Historia Natural.

Autor Año Revista Quimioterapia iv Mediana Mediana Libre Supervivencia Enfermedad

1957- 1989 5FU 10 4

Moertel 1990 NEJM 5FU LV 14,7 6,2

Resultados. Carcinomatosis Colon. TRATAMIENTO SISTÉMICO.

Moertel C, et al. N Engl J Med 1990; 322: 352

Resultados. Carcinomatosis Colon. TRATAMIENTO SISTÉMICO.

Autor Año Revista Quimioterapia iv Mediana Mediana

Libre

Supervivencia 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

5 nuevas drogas en la ULTIMA DECADA han cambiado el horizonte. IRINOTECAN. OXALIPLATINO. CAPECITABINA. BEVACIZUMAB. CETUXIMAB.

Y. YONEMURA PH. SUGARBAKER

Washington Cancer Institute PH. SUGARBAKER

Dr. PH Sugarbaker

OBJETIVOS DE LA ESTRATEGIA DE TRATAMIENTO Máxima cirugía citorreductora

Máxima dosis quimioterapia intraperitoneal

+

Weissberger y Cols 1955 La primera utilización de Quimioterapia Intraperitoneal. Ascitis Neoplásica.

Weissberger AS , et al. JAMA, 159: 1704-1707. 1955.

QUIMIOTERAPIA INTRAPERITONEAL.

BARRERA PERITONEO-PLASMATICA

Peritoneal Cavity

Drug

Dedrick RL, et al. Cancer Treat Rep 1978; 62 (1): 1-11.

QUIMIOTERAPIA INTRAPERITONEAL HIPERTERMIA.

John S. Spratt 1929-2005

1980 PRIMERA QUIMIOHIPERTERMIA.

Speyer JL, et al. Cancer Res 1981; 41: 1916-1922.

Los niveles de 5-FU intraperitoneales son 1000 veces superiores a los plasmáticos.

QUIMIOTERAPIA INTRAPERITONEAL

Sugarbaker PH, et al. Surgery 1985; 98: 414-421.

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.

QUIMIOTERAPIA INTRAPERITONEAL

HIIC. TECNICA CERRADA

QUIMIOTERAPIA INTRAPERITONEAL

Yonemura Y, et al. EJSO 2010;36:1131-1138

Figure 2. Blood-peritoneal barrier. Drug diffusion from submesothelial artery and peritoneal surface.

HIIC. TECNICA ABIERTA

PRINCIPALES CITOSTATICOS INTRAPERITONEALES

De Bree E, et al. J Surg Oncol, 79: 46-61. 2002. PH. Sugarbaker. Tech Coloproctol 2005; 9: 95-103. PH Sugarbaker. Cytoreductive Surgery & Perioperative Chemotherapy for Peritoneal Surface Malignancy: Text book and video atlas. 2013.

QUIMIOTERAPIA INTRAPERITONEAL

PROTOCOLO SUGARBAKER Citostáticos

Intraoperatorios Tumor

Primario Citostáticos

Postoperatorios

Mitomicina C Pseudomixoma Colorrectal

Gástrico Pancreático

5 - FU

Cisplatino +

Adriamicina

Ovario Mesotelioma

Sarcoma

Taxol

90´ a 42ºC

Normotermia. Dias 1º-5º

Postop

HIIC TECNICA ABIERTA MMC 10 -12,5 mg/ m2

90´ a 42 ºC. EPIC Dia1-5. 5-FU 650 mg/ m2.

Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery. Manual for physicians and nurses. The Luddann Company. Grand Rapids, Michigan 1995.

PCI < 10 50% > 5 años.

Sugarbaker PH. Management of peritoneal-surface malignancy: the surgeon´s role. Langebeck´s Arch Surg 1999; 384: 576-587.

100 pacientes 20% > 5 años.

170 pacientes 45% > 5 años.

Sugarbaker PH. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005; 9: 95-103.

Citorreduccion Completa 60% > 5 años.

Sugarbaker PH. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005; 9: 95-103.

Experiencia personal. No Fase III. Citostáticos obsoletos.

Resultados. Carcinomatosis Colon. Citorreducción + HIPEC

1. Estudios Fase III.

2. Experiencia Multiinstitucional.

3. Citostáticos actuales.

4. Ampliación límites indicaciones.

Carcinomatosis Colon. Aportación Europea.

Gómez Portilla A, et al. Rev Esp Enf Dig 2009; 101: 97-106.

Verwaal D, et al. Clin Oncol 2003; 21: 3737-3743

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. Ann Surg Oncol 2008; 15: 2426–2432

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

Glehen O, et al. J ClinOncol 2004; 22: 3284-3292

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

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.

Citostáticos actuales.

Máxima dosis quimioterapia intraperitoneal

QUIMIOTERAPIA INTRAPERITONEAL

Citostáticos Intraoperatorios

Tumor Primario

Citostáticos Postoperatorios

Mitomicina C Pseudomixoma Colorrectal

Gástrico Pancreático

5 - FU

Cisplatino +

Adriamicina

Ovario Mesotelioma

Sarcoma

Taxol

90´ a 42ºC

Normotermia. Dias 1º-5º

Postop

Citostáticos Intraoperatorios

Tumor Primario

Citostáticos Postoperatorios

Oxaliplatino I.P.

+

5-FU/ LV i.v.

Pseudomixoma Colorrectal

Gástrico Pancreático

No Quimioterapia Intraperitoneal Postoperatoria.

Si Quimioterapia

Sistémica Postoperatoria

30´ a 43ºC

PROTOCOLO SUGARBAKER PROTOCOLO ELIAS

Citostáticos actuales.

Citostáticos actuales.

Elias D, et al. Ann Surg Oncol 2002; 13: 267-272. Elias D, et al. Oncology 2002; 63: 346-352. Elias D. Surg Oncol Clin N Am 2003; 12: 755-769. Elias D et ,al. Br J Surg 2004; 91: 455-456. Elias D., et al. EJSO 2006; 32: 607-613. Elias D,et al.Cancer Treat & Research 2007; 134: 303-18.

Supervivencia 1 2 3 5 años

83% 74% 65% 48%

Elias D,et al. Ann Oncol 2004; 15: 1558-1565. Elias D, et al. EJSO 2006; 32: 607-613. Elias D, et al. J Clin Oncol 2010; 28:63-68. Quenet F,et al. Ann Surg 2011;254:294–301.

Irinotecan. 58% Toxicidad Hematológica.

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.

a PCI greater than 20 is currently a contraindication for surgery and HIPEC

Fig. 6. Survival rates according to the extent of the peritoneal carcinomatosis (measured with the PCI), in the French registry (N 5 523 patients).

Elias D,et al J Clin Oncol 2010; 28:63-68.

Experiencia Multiinstitucional.

Elias D, et al. Hepato-Gastroenetrol 1999; 46:360-363. Elias D, et al. J Surg Invest 2001; 3: 31- 36. Elias D, et al. Ann Surg Oncol 2004; 11: 274-280. Elias D, et al. EJSO 2006; 32: 632-636.

12 pacientes. 1999. 24 pacientes. 2006. 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%

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: 597-605.

Ampliación límites indicaciones.

Thomassen I, et al. Dis Colon Rectum 2013 ; 56: 1373-1380

Thomassen I, et al. Dis Colon Rectum 2013 ; 56: 1373-1380

Resultados. Carcinomatosis Colon. CC0-CC1.

60

43 32

30

48

0 10 20 30 40 50

Chu Sadeghi

Jayne Bloemende

Moertel Saltz Masi

De Douillard Goldberg

Hurwitz Tournigan

Masi Glehen

Verwaal Elias

Sugarbaker

60

“ 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: 386-387.

Rectal and colon cancer represent two distinct entities with completely different biologic behaviors and prognoses.

In rectal carcinomas visceral metastases often occurr independtly

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

SYSTC SYSTEMIC

Chiang JM et al. World Journal of Surgical Oncology 2014, 12 19

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.

The risk of lung metastases was more than three times higher for the distal rectum than for the upper rectum

Gomes Da Silva R, et. Dis Colon Rectum 2005; 48: 2258–2263 Gomes Da Silva R, et. J Am Coll Surg 2006; 203: 878–886

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.

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 2005 48 2258–2263

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)

Elias D Ann Surg 2010 251 896–901

The 5-year overall survival rates were not statistically different for the colon (29.7%), rectum (37.9%)

Votanopoulos KI, et al. Ann Surg Oncol. 2013 April 20(4) 1088–1092

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 %.

A total of 13 and 204 patients with PC from rectal and colon cancer

Selected rectal cancer PC should not be excluded from attempted cytoreduction and HIPEC

Gomes Da Silva R ET AL. Limited Survival in Rectal Carcinomatosis Dis Colon Rectum 2005 48 2258–2263