Impact of the Type and Modalities of Preoperative Chemotherapy on the Outcome of Liver Resection for
Colorectal Metastases
R. Adam, E. Barroso, C. Laurent, G. Nuzzo, C. Hubert, G. Mentha, J. Ijzermans, L. Capussotti, S. Lopezben, D. Mirza, G. Kaiser, E. Oussoultzoglou, T. Gruenberger, G. J. Poston, O. Skipenko, and The LiverMetSurvey Centers
Impact of the type and modalities of preoperative chemotherapy on the
outcome of liver resection for colorectal metastases
R. Adam, E. Barroso, C. Laurent, G. Nuzzo, C. Hubert, G. Mentha, J. Ijzermans, L. Capussotti, S. Lopez-Ben, D. Mirza, G. Kaiser, E. Housseau, T. Gruenberger,
G. J. Poston, O. Skipenko, The LiverMetSurvey Centers
LiverMetsurveyBackground
Prognostic factors of survival have been extensively reported after resection of colorectal liver metastases.
However, a specific analysis of patients submitted to preoperative chemotherapy (PCT), with the real impact of type and modalities of treatment on patient outcome is lacking.
LiverMetsurveyAim of the study
To evaluate impact of the type and modalities of PCT on the long-term outcome of resected patients for colorectal liver metastases in a large multicenter cohort, LiverMetsurvey.
LiverMetsurveyStudy design
LiverMetsurvey
Jan 1995 – June 2010
8912 Patients – 151 Centers in 39 Countries
No Preop Chemotherapy4468
Preop Chemotherapy4444
49.9%
Study population
LiverMetsurveyPatients and Methods
LiverMetSurvey is an international, internet-based prospective registry designed to assess the efficacy of multimodality treatment options for colorectal liver metastases (CLM) . 4444 patients (49.9%) received chemotherapy before liver resection. The distribution of potential prognostic factors including age, sex, primary tumor site, timing of metastasis diagnosis, tumor number, diameter of the largest metastasis, bilaterality, initial resectability, and type and duration of chemotherapy were compared to overall (OS) and disease-free (DFS) survivals using univariate and multivariate analyses.
LiverMetsurveyOverall Survival : Global Population
Without Preop. chemo
With Preop. chemo
No of exposed pts
Preop. chemo
65%
58% 47%
39%
LiverMetsurveyOverall Survival : Initially resectable patients
No of exposed pts
Preop. chemo
Without Preop. chemo
With Preop. chemo
65%
62%47%
44%
LiverMetsurveyOverall Survival : Initially non resectable patients
No of exposed pts
Preop. chemo
Without Preop. chemo
With Preop. chemo
54%
50%33%
33%
LiverMetsurveyPatients and Tumour Characteristics (1)
Characteristics
MaleAge (yrs,mean±sd)Tumor localization
Left including sigmoidRectumRightTransverseMultiple localizations
Metast. primary lymph nodesNo meta. at diagnosis
1-34-7>7
Meta. at diagnosis ≥ 30mm
No chemo preop
62.3%64 ± 11
42.3%32.1%18.7%3.5%3.4%
60.7%
88.9%8.9%2.2%
56.6%
Chemo preop
62.1%61 ± 11
46.3%30.7%16.9%3.2%3.0%
66.6%
67.5%23.8%8.7%
59.5%
P
NS< 0.0001
0.005
< 0.0001
< 0.0001
0.01
LiverMetsurveyPatients and Tumour Characteristics (2)
Characteristics
Synchronous
Initial resectability
Bilateral localization
Abnormal prehep CEA level (>5)
Concomitant extrahepatic disease
Major hepatectomy
R2 resection
Combined techniques
Post-op chemotherapy
Center volume (mean±sd)(Max done in a year)
No chemo preop
38.4%
95.0%
23.8%
67.0%
8.6%
46.2%
6.7%
14.1%
47.4%
45.1 ± 33.1
Chemo preop
68.7%
62.8%
49.0%
58.1%
12.8%
63.6%
12.9%
28.2%
57.9%
57.8 ± 38.4
P
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
LiverMetsurveyPatients with preoperative chemotherapy
No of exposed pts
Overall Survival Disease Free Survival(Non palliative pts)
90%
62%58%
30%
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
Multivariate Analysis
Risk factors
Metastatic primary lymph nodes
Abnormal CEA levels (>5)
Concomitant extrahepatic disease
Metastases >3
Tumoral progression
Type of chemotherapy
More than 1 line of Chemo.
R2 resection
P
0.005
< 0.0001
< 0.0001
0.006
0.04
NS
0.0002
< 0.0001
RR
1.29
1.46
1.66
1.29
1.31
-
1.45
1.65
CI 95%
[1.1-1.5]
[1.2-1.7]
[1.4-2.0]
[1.1-1.5]
[1.0-1.7]
-
[1.2-1.8]
[1.3-2.1]
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
No of exposed ptsMetastatic primary lymph nodes
No metastatic primary lymph nodes
Metastatic primary lymph nodes
67%
54%47%
35%
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
No of exposed ptsConcomitant extrahep. metastases
No concomitant extrahep. metastases
Concomitant extrahep. metastases
60%
42% 42%
18%
No of exposed pts
Prehep. CEA ≥ 5
Prehep. CEA < 5 ng/ml
Prehep. CEA ≥ 5 ng/ml
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
67%
52%49%
31%
No of exposed pts
Pre-op last line result
No preop. Progression
Preop. Progression
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
59%
42%
41%
23%
No of exposed pts
No Metastases at diagnosis
> 3 Metastases
1-3 Metastases
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
63%
51%46%
31%
No of exposed pts
Liver curative
Palliative resection
Curative resection
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
62%
36%
43%
20%
No of exposed pts
No lines preop
> 1 line chemotherapy
Only 1 line chemotherapy
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
59%
51% 42%
27%
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
No of exposed ptsPreop. Chemo. type
Irino-based
Oxali-based
Oxali-Irino-based
61%
57%41%
34%
No of exposed pts
Preop. Targeted therapy
No preop. Targeted therapy
Preop. Targeted therapy
LiverMetsurvey - Overall survivalPatients with Oxaliplatin-based preop. chemo.
62%
58% 48%
41%
No of exposed pts
Preop. Targeted therapy
No preop. Targeted therapy
Preop. Targeted therapy
LiverMetsurvey - Overall survivalPatients with Irinotecan-based preop. chemo.
58%
56%54%
40%
No of exposed pts
Preop. Targeted therapy
No preop. Targeted therapy
Preop. Targeted therapy
LiverMetsurvey - Overall survivalPatients with Oxali-Irino-based preop. chemo.
70%
56%42%
34%
No of exposed pts
Preop. Targeted therapy
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
No preop. Targeted therapy
Preop. Targeted therapy
59%
58% 48%
39%
No of exposed ptsPreop. Targeted therapy
Bevacizumab
Cetuximab/Panitumumab
Without Preop. Targeted therapy
LiverMetsurvey - Overall survivalPatients with preoperative chemotherapy
59%
57% 50%
39%
Risk factors
Metastatic primary lymph nodes
Abnormal CEA levels (>5)
Metastases >3
Tumoral progression
Type of chemotherapy
Major hepatectomy
More than 6 cycles
P
0.0008
0.005
0.0001
0.05
NS
0.04
0.004
RR
1.32
1.25
1.4
1.3
-
1.2
1.25
CI 95%
[1.1-1.6]
[1.1-1.5]
[1.2-1.7]
[1.0-1.7]
-
[1.0-1.4]
[1.1-1.5]
LiverMetsurvey – Disease free survivalPatients with preoperative chemotherapy
Multivariate Analysis
LiverMetsurvey – Disease free survivalPatients with preoperative chemotherapy
No of exposed pts
No cycles preop
> 6 cycles
1-6 cycles
33%
25%
26%
17%
LiverMetsurveyConclusion
Preoperative Chemotherapy is used in half patients overall, 63% of whom with initially resectable CLM.
The type of Chemotherapy does not influence the outcome provided that resection is achieved.
However, the shorter is the Chemotherapy and the more limited is the number of lines, the best is the survival after surgery.