Transcript Colorectal Liver Metastases

COLORECTAL LIVER
METASTASES
Using Multimodality
Therapy to Achieve a Cure
Janak A. Parikh, MD, MSHS
St. John Providence Hospital
February 28, 2015
Overview
Background
Scope of the Problem
Safety of Liver Surgery
Treatment Options
Medical
Interventional
Surgery
Outcomes After Resection of Colorectal Liver Metastases
Importance of a Multidisciplinary Approach
Majority of CRC Patients
Are Diagnosed at Later Stages
distant
(stage IV)
19%
unstaged
5%
regional
(stage III)
36%
Data period: 1996-2003
SEER Cancer Statistics Review. Colon and Rectum.
localized
(stage I and II)
40%
CRC and Liver Metastases
136,830
CRC cases
20%
30%
27,366
41,049
Synchronous CLM
Metachronous CLM
50%
13,683
Hepatic-only CLM
60%
8,210 eligible CLM/yr
American Cancer Society 2014.
Colorectal Liver Metastases (CLM):
Occurrence and Impact
The liver is the most common site of metastases in
CRC patients1
• Hepatic metastases occur in approximately 50% of CRC
patients and account for at least two thirds of all CRC deaths1
• 25% of CRC patients present with CLM2
• 30% to 60% patients develop CLM2
• 20% to 30% patients develop lung metastases2
1. Abdalla et al. Annals of Surgical Oncology. 2006;13(10)1271-1280; 2. Donadon et al. Gastrointest Cancer Res.
2007;1:20-27.
Mortality Rates After Hepatectomy
20%
20
% Mortality
18
16
14
10%
12
10
8
5%
6
2.5%
4
2
0
1970s
1980s
1990s
2000s
Treatment Options For CRC
Hepatic Metastases
Chemotherapy
• 5-FU + Leucovorin
• FOLFOX/FOLFIRI
• FOLFOX + Biologic
– Avastin (VEGF inhibitor)
– Cetuximab (EGFR inhibitor)
Liver-Directed Therapy
•
•
•
•
•
•
•
Radiofrequency Ablation
Microwave Ablation
Cryoablation
Chemoembolization
Radioembolization
Stereotactic Body Radiotherapy (SBRT)
Hepatic Artery Infusion Pump
Surgery
• Wedge resection
• Segmentectomy
• Lobectomy
• Simultaneous vs. Staged
• Multiple resections
Why Resect Metastatic
Disease?
Rationale for Surgery
Natural history of unresected hepatic metastases
n
Median
5-year
Survival (mo) Survival (%)
Unresectable*
Resectable, not resected
921
62
6.9
14.2
0
0
Resected, (-) margins
183
30.0
38
*19 patients in this group were non-classifiable.
Scheele et al. Br J Surg. 1990;77:1241.
Resection for CRC Liver Metastases
1.0
All patients
p<0.01
0.4
0.6
N=563
(1999-2006)
N=1036
(1980-1998)
0.0
0.2
Probability
0.8
MSKCC
0
20
40
60
80
100
Disease-specific survival (months)
Improvements in survival over time
•Better chemotherapy
•Better imaging
•Better patient selection
CLM Resection Outcomes Post-2002
Operative
No. of Patients
Mortality
(%)
1-yr (%)
3-yr (%)
5-yr (%)
10-yr (%)
Median
Survival
(mos)
Choti (2002)
226
1.0
93
57
58*
26
46
Abdalla (2004)
190
-
-
73
58
-
21
Fernandez (2004)
100
1.0
88
66
59
-
-
Pawlik (2005)
557
1.0
97
74
58
-
74
Reference (year)
Survival
* For recent period (1993-1999)
McLoughlin J et al. Cancer Control. 2006;13(1):32-41; Fernandez FG, et al. Ann Surg. 2004;240:438-447; Pawlik TM, et
al. Ann Surg. 2005;241:759-766.
Long-Term Outcomes After
Resection of CRC Liver Mets
10-year follow-up after resection of
CLM in 612 patients
10-year survival rate: 17%-25%
97% of 10-year survivors disease-free at last follow-up
Only 1 disease-specific death after 10-years
Tomlinson JS, et al. J Clin Oncol. 2007;25(29):4575-4580
Patient Selection is the Key to
Good Outcomes
Patient Selection for Resection of CLM
Clinical Risk Score
Fong. Ann Surg. 1999. 230:309-21.
Patient Selection for Resection of CLM
Probability
Tumor Number
Survival (years) after R0 resection
In the past, more than FOUR liver metastases was considered a
contraindication to liver resection
Altendorf-Hofmann. Surg Oncol Clin N Am. 2003, 12:165-92.
Patient Selection for Resection of CLM
p=NS
50
100
150
MSKCC
CRS=1
2
3
4
CRS=5
0
Median Survival
(months)
Median survival
Tumor Number with relation to Clinical Risk Score
2
4
6
8
10
Tumors
Number ofNumber
liverofmetastases
The number of metastases does not affect survival for patients
who undergo complete resection of all CLM
Patient Selection for Resection of CLM
Probability
Surgical Margins
Survival (months) after resection
Width of surgical margin does not affect survival as long as a
negative margin can be achieved
Pawlik. Ann Surg. 2005, 241:715-22.
Patient Selection for Resection of CLM
Extrahepatic Disease
Group
No EHD
EHD
Portal LN*
5-yr OS
34%
20%
27%
*12/111 of pts had HPLN only
In carefully selected patients, the presence of limited, resectable
extrahepatic disease should not be considered a contraindication
to hepatectomy for CLM
Elias. Br J Surg. 2003, 90:567-74.
Advanced Age is NOT a Contraindication
for Resection of CLM
 After a mean follow-up of 32 months, 5-year OS was
lower in older than younger patients (37% vs 44%;
P=0.001)
 In the elderly group, 34% of patients recurred, vs
43% in the younger group (P <0.0001)
Patients <70 years
Patients ≥70 years
Overall survival
1
.8
61%
44%
.6
56%
.4
37%
.2
0
Log rank P=0.001
0
1
2
3
4
5 Years
Multidisciplinary Approach
Why Early Surgical Consultation is
Necessary
Variance in Multidisciplinary Consultation
Setting: In untreated patients with liver-only
colorectal cancer, I generally;
80%
70%
70%
60%
Always consult with my
surgeon to determine
resectability
55%
50%
Only consult with my surgeon
if there are fewer than 3 lesions
that appear resectable to me
43%
40%
30%
28%
20%
10%
3%
2%
0%
Academic (n=199)
Generally do not consult with
my surgeon as these patients
are best treated with systemic
chemotherapy alone
Community (n=505)
Network for Medical Communication and Research (NMCR), Challenging Casessm 2006 is a nationwide
forum for peer-to-peer market research for oncology practitioners.
Data on file, sanofi-aventis. Network for Medical Communication and Research (NMCR), Challenging Casessm 2006.
Multidisciplinary Dimensions in
Managing Patients with CLM
Hepatic resection technique
Patient evaluation for
resectability
Assessment of liver health
prior to surgery
Imaging of liver mets
Choice and timing of
systemic therapy
Assessment of clear
margins
Surgeon
Assessment of
healthy liver remnant
Patient
Medical
Oncologist
Radiologist
1. McLoughlin J et al. Cancer Control. 2006;13(1):32-41. 2. Bilchik et al. Journal of Clinical Oncology. 2005;23(36):
9073-9078.
Consulting With the Surgeon Prior to and
During Medical Treatment
• Radiologic response to systemic treatment does not
indicate cure
• How complex is the resection of the primary?
• Resection of the sites of initial metastases is necessary
• Will progression of disease make it unresectable?
• Surgeon’s challenge is to identify the precise site of the
liver for resection and achieving a sufficient margin
• Medical oncologists and surgeons should consult prior to
and during the course of systemic treatment
Benoist S et al. J Clin Oncol. 2006;24:3939-3945.
Chemo-Associated Liver Injury (CASH)
Steatohepatitis (Oxaliplatin)
Sinusoidal obstruction (Irinotecan)
The disorganized lobular parenchyma displays
marked macrovesicular steatosis with evidence
of ballooning (arrows) surrounded by scattered
inflammation and apoptotic hepatocytes
(arrowhead)
Moderate centrilobular sinusoidal distention
(arrows). Compare to normal parenchyma in
lower left quadrant
Vauthey, JCO 2006
Multidisciplinary Approach is Essential
• Timing of resection
– In relation to chemotherapy
– In the era of anti-angiogenic therapy
– Synchronous metastases
• Role of laparoscopic liver resections
• Role of ablative procedures
• Ultimate goal of expanding the population of
patients that can undergo a curative resection
Multimodality Management of CLM
• Neoadjuvant chemotherapy
– Resectable liver metastases:
• Facilitate surgery
• Obtain predictive and prognostic information
• Early systemic therapy for poor-prognosis pts
• Conversion chemotherapy
– Unresectable liver metastases:
• Allow R0 resection via downsizing
• Post-operative (adjuvant) chemotherapy
– Hepatic arterial infusion (HAI)
– Systemic treatment
SUMMARY
• Colorectal liver metastases should be surgical
resected.
• Timing of chemotherapy and surgery is critical to
achieve best possible outcome for our patients.
• Several options exist to make initially
unresectable patient resectable.
• Resected patients have good long-term survival.
• All of this is only possible because we have
effective chemotherapeutic agents.
COLORECTAL LIVER
METASTASES
Using Multimodality
Therapy to Achieve a Cure
Janak A. Parikh, MD, MSHS
St. John Providence Hospital
February 28, 2015