Patients and Methods
Patients
Preoperative Management
Hepatic Resection
Postoperative Follow-Up
Statistical Considerations
Results
Patient Characteristics
Characteristics | Total study population (N = 119) |
---|---|
Patients | |
Mean age at HR, years ± SD | 61 ± 10 |
Male/female | 79 (66%)/40 (34%) |
Primary tumor | |
Colon/rectum | 95 (80%)/24 (20%) |
T classification | |
1 | 2 (2%) |
2 | 7 (8%) |
3 | 41 (49%) |
4 | 33 (40%) |
N classification | |
0 | 33 (39%) |
1 | 28 (33%) |
2 | 24 (28%) |
Liver metastases at initial diagnosis | |
Synchronous/metachronousa
| 41 (34%)/78 (66%) |
Number of CLM | |
1 | 34 (30%) |
2–3 | 44 (38%) |
>3 | 37 (32%) |
Mean maximum size, mm ± SD | 46 ± 32 |
Unilateral/bilateral | 61 (52%)/57 (48%) |
Initial unresectability | 55 (46%) |
Preoperative Chemotherapy
Feature | Total study population (N = 119) |
---|---|
Preoperative chemotherapy | 119 (100%) |
Total no. of lines | |
1 | 87 (73%) |
>1 | 32 (27%) |
Total no. of cycles | |
<6 | 27 (24%) |
≥6 | 85 (76%) |
Regimen last preoperative line | |
5-FU LV | 32 (27%) |
5-FU LV oxaliplatin | 61 (51%) |
5-FU LV irinotecan | 18 (15%) |
Other | 8 (7%) |
Chronomodulated delivery | 59 (50%) |
Clinical response at CT scana
| |
Response | 72 (60%) |
Stabilization | 28 (24%) |
Progression | 19 (16%) |
Change in CEA level after chemotherapy (N = 113)b
| |
Response | 75 (66%) |
Stabilization | 14 (12%) |
Progression | 24 (21%) |
Change in CA19.9 level after chemotherapy (N = 68)b
| |
Response | 48 (71%) |
Stabilization | 8 (12%) |
Progression | 12 (18%) |
Hepatectomy | |
PVE | 14 (12%) |
Major hepatectomy (≥3 segments) | 62 (52%) |
Mean no. of CLM at histopathology ± SD | 3 ± 3 |
Mean maximum size of CLM at histopathology, mm ± SD | 44 ± 36 |
Surgical margin statusc
| |
R0 | 71 (60%) |
R1 | 43 (36%) |
R2 | 4 (3%) |
Postoperative mortality (≤2 months) | 1 (1%) |
Postoperative complications | 43 patients (36%) |
Hepaticd
| 31 (26%) |
Generale
| 20 (17%) |
Postoperative chemotherapy | 105 (88%) |
Tumor Marker Evolution
Clinical response at CTb
| ||||
---|---|---|---|---|
Response | Stabilization | Progression | Total | |
Change from preoperative CEA levela
| ||||
Response | 61 | 13 | 1 | 75 (66%) |
Stabilization | 3 | 11 | 0 | 14 (12%) |
Progression | 4 | 2 | 18 | 24 (21%) |
Total | 68 (60%) | 26 (23%) | 19 (17%) | 113 (100%) |
Change from preoperative CA19.9 levela
| ||||
Response | 38 | 9 | 1 | 48 (70%) |
Stabilization | 1 | 4 | 3 | 8 (12%) |
Progression | 0 | 5 | 7 | 12 (18%) |
Total | 39 (57%) | 18 (26%) | 11 (16%) | 68 (100%) |
Hepatic Resection
Long-Term Outcome
Overall Survival (OS)
Progression-Free Survival (PFS)
Prognostic Factors of Overall Survival
Variable |
N
| 5-Year OS (%) | UV P
| MVa
P
| HR (95% CI) |
---|---|---|---|---|---|
All patients | 119 | 26 | |||
Patient factors | |||||
Gender | |||||
Male | 79 | 23 | 0.12 | – | – |
Female | 40 | 30 | |||
Age at hepatectomy | |||||
<60 years | 46 | 21 | 0.49 | – | – |
≥60 years | 73 | 29 | |||
Primary malignancy | |||||
Location | |||||
Colon | 95 | 25 | 0.73 | – | – |
Rectum | 24 | 29 | |||
T classification | |||||
1–2 | 9 | 22 | 0.24 | – | – |
3–4 | 74 | 24 | |||
N classification | |||||
0 | 33 | 25 | 0.77 | – | – |
1–2 | 52 | 18 | |||
CLM at diagnosis | |||||
Timing of diagnosisb
| |||||
Synchronous | 41 | 14 |
0.009
| NS | – |
Metachronous | 78 | 33 | |||
No. of CLM | |||||
<4 | 78 | 32 |
0.002
|
<0.001
| 2.6 (1.6–4.3) |
≥4 | 37 | 17 | |||
Max. size of CLM | |||||
<35 mm | 50 | 34 |
0.005
|
0.002
| 2.2 (1.3–3.7) |
≥35 mm | 58 | 16 | |||
Distribution | |||||
Unilateral | 61 | 35 |
0.004
| NS | – |
Bilateral | 57 | 16 | |||
Initial resectability | |||||
Yes | 64 | 40 |
0.01
| NS | – |
No | 55 | 15 | |||
Hepatic resection | |||||
Preoperative chemotherapy | |||||
Total no. of lines | |||||
1 | 87 | 30 | 0.6 | – | – |
≥2 | 32 | 13 | |||
Total no. of cycles | |||||
<10 | 72 | 34 | 0.13 | – | – |
≥10 | 40 | 7 | |||
Regimen last preoperative line | |||||
5-FU LV | 32 | 25 | 0.17 | – | – |
5-FU LV oxaliplatin | 61 | 32 | |||
5-FU LV irinotecan | 18 | 16 | |||
Other | 8 | 0 | |||
Chronomodulated therapy | |||||
Yes | 59 | 28 | 0.57 | – | – |
No | 60 | 23 | |||
Radiological response at CT scanc
| |||||
Response or stabilization | 100 | 29 | 0.09 | 0.004 | 2.6 (1.3–4.9) |
Progression | 19 | 7 | |||
Biological response, CEAd
| |||||
Response or stabilization | 89 | 28 | 0.36 | – | – |
Progression | 24 | 14 | |||
Biological response, CA19.9d
| |||||
Response or stabilization | 56 | 33 |
0.002
| NS | – |
Progression | 12 | 0 | |||
Extent of hepatic resection | |||||
Minor (<3 segments) | 57 | 32 | 0.06 | NS | – |
Major (≥3 segments) | 62 | 20 | |||
Resection type | |||||
Anatomical | 58 | 31 | 0.49 | – | – |
Nonanatomical | 26 | 29 | |||
Both | 35 | 12 | |||
Vascular occlusion | |||||
Yes | 97 | 25 | 0.95 | – | – |
No | 17 | 30 | |||
Intraoperative RBC transfusion | |||||
Yes | 32 | 25 | 0.85 | – | – |
No | 60 | 30 | |||
Postoperative chemotherapy | |||||
Yes | 105 | 27 | 0.37 | – | – |
No | 11 | 12 | |||
Surgical margin statuse
| |||||
R0 | 71 | 28 | 0.16 | – | – |
R1 | 43 | 21 | |||
R2 | 4 | 25 |
Prognostic Factors of Progression-Free Survival
Variable |
N
| 5-Year PFS (%) | UV P
| MVa
P
| HR (95% CI) |
---|---|---|---|---|---|
All patients | 116 | 9 | |||
Patient factors | |||||
Gender | |||||
Male | 76 | 20 |
0.05
|
0.04
| 1.9 (1.0–3.5) |
Female | 40 | 3 | |||
Age at hepatectomy | |||||
<70 years | 92 | 9 | 0.85 | – | – |
≥70 years | 24 | 10 | |||
Primary malignancy | |||||
Location | |||||
Colon | 93 | 9 | 0.44 | – | – |
Rectum | 23 | 10 | |||
T classification | |||||
1–2 | 9 | 0 | 0.64 | – | – |
3–4 | 72 | 9 | |||
N classification | |||||
0 | 32 | 8 | 0.91 | – | – |
1–2 | 51 | 5 | |||
CLM at diagnosis | |||||
Timing of diagnosisb
| |||||
Synchronous | 39 | 3 |
0.05
| NS | – |
Metachronous | 77 | 13 | |||
No. of CLM | |||||
<3 | 62 | 18 |
<0.001
|
0.02
| 1.9 (1.1–3.4) |
≥3 | 50 | 0 | |||
Max. size of CLM | |||||
<35 mm | 48 | 15 | 0.28 | – | – |
≥35 mm | 57 | 6 | |||
Distribution | |||||
Unilateral | 58 | 18 |
0.006
| NS | – |
Bilateral | 57 | 0 | |||
Initial resectability | |||||
Yes | 63 | 18 | 0.28 | – | – |
No | 53 | 3 | |||
Hepatic resection | |||||
Preoperative chemotherapy | |||||
Total no. of lines | |||||
1 | 86 | 9 | 0.97 | – | – |
≥2 | 30 | 10 | |||
Total no. of cycles | |||||
<10 | 69 | 11 | 0.08 | NS | – |
≥10 | 40 | 4 | |||
Regimen last preoperative line | |||||
5-FU LV | 31 | 10 |
0.03
| NS | – |
5-FU LV oxaliplatin | 61 | 12 | |||
5-FU LV irinotecan | 16 | 6 | |||
Other | 8 | 0 | |||
Chronomodulated therapy | |||||
Yes | 59 | 9 | 0.89 | – | – |
No | 57 | 10 | |||
Radiological response at CT scanc
| |||||
Response or stabilization | 97 | 11 |
0.02
| NS | – |
Progression | 19 | 0 | |||
Biological response, CEAd
| |||||
Response or stabilization | 87 | 10 | 0.07 | NS | – |
Progression | 24 | 0 | |||
Biological response, CA19.9d
| |||||
Response or stabilization | 54 | 13 |
0.01
|
0.002
| 3.2 (1.6–6.6) |
Progression | 12 | 0 | |||
Extent of hepatic resection | |||||
Minor (<3 segments) | 54 | 13 | 0.31 | – | – |
Major (≥ 3 segments) | 62 | 6 | |||
Resection type | |||||
Anatomical | 57 | 14 | 0.12 | – | – |
Nonanatomical | 24 | 9 | |||
Both | 35 | 0 | |||
Vascular occlusion | |||||
Yes | 95 | 8 | 0.49 | – | – |
No | 17 | 18 | |||
Intraoperative RBC transfusion | |||||
Yes | 32 | 6 | 0.90 | – | – |
No | 58 | 13 | |||
Postoperative chemotherapy | |||||
Yes | 105 | 10 |
0.009
| NS | – |
No | 10 | 0 | |||
Surgical margin statuse
| |||||
R0 | 69 | 13 |
0.04
| NS | – |
R1 | 42 | 3 | |||
R2 | 4 | 0 |