Abordaje de la carcinomatosis de cáncer de colon vs cáncer de recto

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
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: 423-43.
Aoyagi T, et al. World J Gastroenterol 2014; 20(35): 12493-12500.
Resultados. Carcinomatosis Colon. Historia Natural.
Supervivencia Carcinomatosis Colorrectal.
Autor
Chu
Sadeghi
Jayne
Sadahiro
Pacientes
Mediana
Supervivencia
45
118
349
75
6 m
5,2 m
9 m
6,8 m
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.
Resultados. Carcinomatosis Colon. TRATAMIENTO SISTÉMICO.
Autor
Año
Revista
5FU
1957- 1989
Moertel
Quimioterapia iv
1990 NEJM
5FU LV
Mediana
Mediana Libre
Supervivencia
Enfermedad
10
4
14,7
6,2
Moertel C, et al. N Engl J Med 1990; 322: 352
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
Mediana
Libre
Supervivencia
Enfermeda
De Gramont
2000
JCO
5FU LV OXALIPLATINO FOLFOX 4
16,2
9
Saltz
2000
NEJM
5FU LV IRINOTECAN
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
IFL
Washington Cancer Institute
Y. YONEMURA
PH. SUGARBAKER
PH. SUGARBAKER
Dr. PH Sugarbaker
OBJETIVOS DE LA ESTRATEGIA DE TRATAMIENTO
Máxima
Máxima dosis
+
cirugía
quimioterapia
citorreductora
intraperitonea
l
QUIMIOTERAPIA INTRAPERITONEAL.
Weissberger y Cols 1955
La primera utilización de Quimioterapia Intraperitoneal.
Ascitis Neoplásica.
Weissberger AS , et al. JAMA, 159: 1704-1707. 1955.
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.
QUIMIOTERAPIA INTRAPERITONEAL
Los niveles de 5-FU intraperitoneales son 1000 veces
superiores a los plasmáticos.
Speyer JL, et al. Cancer Res 1981; 41: 1916-1922.
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: 414-421.
HIIC. TECNICA CERRADA
QUIMIOTERAPIA INTRAPERITONEAL
Figure 2. Blood-peritoneal barrier. Drug diffusion from
submesothelial artery and peritoneal surface.
Yonemura Y, et al. EJSO 2010;36:1131-1138
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
90´ a 42ºC
Taxol
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.
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: 576-587.
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.
Resultados. Carcinomatosis Colon. Citorreducción + HIPEC
Experiencia personal.
No Fase III.
Citostáticos obsoletos.
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: 97-106.
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: 3737-3743
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: 2426–2432
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: 3284-3292
Citostáticos actuales.
Hospital Gustave Roussy
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.
D. ELIAS
Citostáticos actuales.
QUIMIOTERAPIA INTRAPERITONEAL
PROTOCOLO SUGARBAKER
PROTOCOLO ELIAS
Citostáticos
Intraoperatorios
Tumor
Primario
Citostáticos
Postoperatorios
Citostáticos
Intraoperatorios
Tumor
Primario
Citostáticos
Postoperatorios
Mitomicina C
Pseudomixoma
Colorrectal
Gástrico
Pancreático
5 - FU
Oxaliplatino I.P.
Pseudomixoma
Colorrectal
Gástrico
Pancreático
No
Quimioterapia
Intraperitoneal
Postoperatoria.
Cisplatino
+
Adriamicina
90´ a 42ºC
Máxima dosis
+
quimioterapia
5-FU/ LV i.v.
Ovario intraperitoneal
Mesotelioma
Taxol
Sarcoma
30´ a 43ºC
Normotermia.
Dias 1º-5º
Postop
Si
Quimioterapia
Sistémica
Postoperatoria
Citostáticos actuales.
Supervivencia 1
2
3
años
83% 74% 65%
5
48%
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.
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: 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.
Experiencia Multiinstitucional.
Fig. 6. Survival rates according to the extent of the peritoneal carcinomatosis
(measured with the PCI), in the French registry (N 5 523 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.
Ampliación límites indicaciones.
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%
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.
Ampliación límites indicaciones.
43 pacientes.
37% Metas Hepáticas. (16).
Mediana
supervivencia 38,4 m.
CCR-0
2
4 años
72% 44%
Kinmmanesh R. ,et al. Ann Surg 2007; 245: 597-605.
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
Sugarbaker
Elias
Verwaal
Glehen
Masi
Tournigan
Hurwitz
Goldberg
Douillard
De
Masi
Saltz
Moertel
Bloemende
Jayne
Sadeghi
Chu
30
0
10
20
30
48
43
32
40
50
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
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
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
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: 2258–2263
Gomes Da Silva R, et. J Am Coll Surg 2006; 203: 878–886
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)
The 5-year overall survival rates
were not statistically different for
the colon (29.7%), rectum (37.9%)
Elias D Ann Surg 2010 251 896–901
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. 2013 April 20(4) 1088–1092
Gomes Da Silva R ET AL. Limited Survival in Rectal Carcinomatosis Dis Colon Rectum 2005 48 2258–2263