Background
Methods
Study design
Patient cohort
Pre-RFA assessment
RFA procedure
Post-RFA assessment of treatment efficacy
Post-RFA assessment of complications
Data analysis
Statistical analysis
Results
Patient characteristics and chemotherapy details
Characteristic | Value |
---|---|
Patients (n = 88) | |
Male, n (%) | 57 (65) |
Female, n (%) | 31 (35) |
Mean age ± SD, years | 67.8 ± 0.84 |
Primary tumor | |
Colon, n (%) | 69 (78) |
Rectum, n (%) | 19 (22) |
Node status | |
Positive, n (%) | 65 (74) |
Negative, n (%) | 23 (26) |
Colorectal liver metastases (CLM) | |
Synchronous, n (%) | 22 (25) |
Metachronous, n (%) | 66 (75) |
Mean number ± SD | 2.7 ± 0.13 |
Number of 1–3 CLM, n (%) | 67 (76) |
Number of 4–5 CLM, n (%) | 21 (24) |
Mean maximum size ± SD, cm | 3.1 ± 0.1 |
Maximum size ≤ 3 cm, n (%) | 51 (65) |
Maximum size 3–5 cm, n (%) | 27 (35) |
CEA levels before RFA, ng/mL | |
Mean CEA level ± SD | 132.2 ± 16.3 |
CEA ≤ 100, n (%) | 51 (58) |
CEA > 100, n (%) | 37 (42) |
Main cause of unresectability | |
Expected liver remnant ≤ 30%, n (%) | 19 (22) |
Proximity to critical structures, n (%) | 22 (25) |
Medical comorbidity, n (%) | 37 (42) |
Patient refusal, n (%) | 10 (11) |
Systemic therapies before RFA | |
Mean number of lines ± SD | 1.5 ± 0.07 |
5-Fluorouracile, n (%) | 36 (41) |
5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), n (%) | 59 (67) |
5-Fluorouracil, Leucovorin, Irinotecan (FOLFIRI), n (%) | 41 (47) |
+ Bevacizumab, n (%) | 13 (15) |
+ Cetuximab, n (%) | 5 (6) |
Systemic therapies before and after RFA | |
Mean number of lines ± SD | 3.1 ± 0.1 |
5-Fluorouracile, n (%) | 57 (65) |
5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), n (%) | 81 (92) |
5-Fluorouracil, Leucovorin, Irinotecan (FOLFIRI), n (%) | 82 (93) |
+ Bevacizumab, n (%) | 40 (45) |
+ Cetuximab, n (%) | 16 (18) |
Response to the immediate systemic therapy before RFA | |
Partial remission, n (%) | 49 (56) |
Stable disease, n (%) | 13 (15) |
Progressive disease, n (%) | 26 (29) |
Recurrence after RFA | |
Median time to recurrence, months (range) | 8 (1–24) |
Local tumor progression (RFA-site), n (%) | 8 (9) |
Intrahepatic recurrence, n (%) | 33 (37) |
Extrahepatic recurrence, n (%) | 14 (16) |
Intra-/and extrahepatic recurrence, n (%) | 27 (31) |
No recurrence, n (%) | 6 (7) |
Regimen | Line of therapy and regimen administered | Response to last line therapy regimen1
| |||||
---|---|---|---|---|---|---|---|
1st line | 2nd line | 3rd line | Last line2
| PR | SD | PD | |
5-FU, n | 30 | 5 | 0 | 17 | 10 | 3 | 4 |
5-FU + Bevacizumab, n | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
FOLFOX, n (%) | 31 | 19 | 2 | 35 (40) | 20 | 5 | 10 |
FOLFOX + Bevacicumab, n | 1 | 0 | 1 | 2 | 1 | 1 | 0 |
FOLFOX + Cetuximab, n | 3 | 2 | 0 | 5 | 3 | 1 | 1 |
FOLFIRI, n (%) | 18 | 12 | 1 | 20 (23) | 10 | 1 | 9 |
FOLFIRI + Bevacizumab, n | 3 | 4 | 3 | 8 | 3 | 3 | 2 |
FOLFIRI + Cetuximab, n | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Total number (%) | 88 (100) | 40 (45) | 8 (9) | 88 (100) | 49 | 13 | 26 |
Outcome and complications after RFA treatment
Patient | Systemic therapy | Clinical features | ||||
---|---|---|---|---|---|---|
Response1
| No. of lines | Regimen(s) administered | Number of CLM | Size2of CLM | CEA level (ng/ml) | |
1 | Partial remission | 1 | FOLFIRI | 1 | 2.5 cm | 12 |
2 | Partial remission | 2 | FOLFOX, FOLFIRI | 1 | 2.1 cm | 23 |
3 | Partial remission | 1 | FOLFOX | 2 | 2.2 cm | 13 |
4 | Partial remission | 2 | FOLFIRI + Bevacizumab, FOLFOX + Cetuximab | 3 | 3.0 cm | 114 |
5 | Partial remission | 1 | FOLFIRI + Bevacizumab | 2 | 3.1 cm | 57 |
6 | Partial remission | 1 | FOLFOX | 1 | 2.7 cm | 4 |
Univariate and multivariate analysis
Overall survival | Recurrence-free survival | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | ||||||||||
Variable | No. of patients | Median months (95% CI) | 5-years, % (95% CI) | p-value | p-value | HR | HR 95% CI | Median months (95% CI) | 5-years % (95% CI) | p-value | p-palue | HR | HR 95% CI |
Age | 0.8381 | 0.4263 | |||||||||||
≤ 60 years | 16 | 19 (14–37) | 8.3 (0.6-30.2) | 8 (5–13) | 13.3 (2.2-34.6) | ||||||||
> 60 years | 72 | 25 (18–31) | 12.4 (5.8-21.5) | 8 (6–10) | 5.6 (1.8-12.5) | ||||||||
Gender | 0.6264 | 0.8117 | |||||||||||
Male | 57 | 23 (17–30) | 10.5 (3.9-28.4) | 7 (5–11) | 7.1 (2.3-15.8) | ||||||||
Female | 31 | 24 (15–37) | 14.3 (4.6-29.3) | 9 (6–11) | 6.5 (1.1-18.6) | ||||||||
Primary tumor | 0.1872 | 0.7773 | |||||||||||
Colon | 69 | 19 (16–27) | 8.6 (3.3-17.2) | 8 (6–10) | 5.9 (1.9-13.2) | ||||||||
Rectum | 19 | 33 (23–58) | 23.7 (7.2-45.5) | 7 (4–13) | 10.5 (1.8-28.4) | ||||||||
Node status | 0.8512 | 0.4566 | |||||||||||
Positive | 65 | 25 (19–32) | 11.4 (5.0-2.8) | 8 (6–10) | 6.2 (2.0-13.8) | ||||||||
Negative | 23 | 18 (14–33) | 13.0 (2.6-32.3) | 10 (5–13) | 9.1 (1.6-25.1) | ||||||||
CLM | 0.9861 | 0.2889 | |||||||||||
Synchronous | 22 | 20 (18–35) | 9.1 (1.6-25.1) | 10 (7–13) | 4.5 (0.3-18.9) | ||||||||
Metachronous | 66 | 26 (16–32) | 12.4 (5.4-22.4) | 7 (5–10) | 7.7 (2.8-15.8) | ||||||||
CEA level before RFA | 0.0189 | 0.0325 | 0.0062 | 0.0442 | |||||||||
≤ 100 ng/ml | 51 | 29 (19–37) | 15.3 (6.7-27.0) | 10 (8–12) | 9.8 (3.6-19.7) | ||||||||
> 100 ng/ml | 37 | 15 (11–25) | 6.9 (1.4-19.1) | 1.672 | 1.044-2.678 | 6 (4–7) | 2.8 (0.2-12.4) | 1.637 | 1.013-2.647 | ||||
Maximum size of CLM | 0.0001 | 0.0939 | <0.0001 | 0.0771 | |||||||||
≤ 3 cm | 61 | 30 (23–36) | 15.3 (7.2-26.1) | 10 (8–11) | 9.8 (4.0-18.8) | ||||||||
3-5 cm | 27 | 12 (10–19) | 3.8 (0.3-16.4) | 1.548 | 0.928-2.581 | 5 (4–6) | 0 | 1.600 | 0.950-2.694 | ||||
Number of CLM | <0.0001 | <0.0001 | 0.0093 | 0.0389 | |||||||||
1-3 | 67 | 27 (21–36) | 15.6 (7.8; 25.9) | 8 (7–11) | 9.0 (3.6-17.2) | ||||||||
4-5 | 21 | 12 (10–18) | 0 | 3.128 | 1.771-5.526 | 5 (4–10) | 0 | 1.771 | 1.029-3.048 | ||||
Response to systemic therapy before RFA | <0.0001 | 0.0005 | <0.0001 | <0.0001 | |||||||||
Partial remission | 49 | 37 (32–48) | 21.6 (10.9-34.7) | 11 (10–13) | 12.5 (5.1-23.4) | ||||||||
Stable disease | 13 | 19 (15–25) | 0 | 8 (6–10) | 0 | ||||||||
Progressive disease | 26 | 10 (9–11) | 0 | 5.456 | 2.289-13.005 | 4 () | 0 | 6.458 | 2.644-15.78 |
Scoring system for predicting outcome
Variable | Reference category | Points |
---|---|---|
Systemic therapy | Objective response1
| 1 |
Number of CLM | ≤ 3 CLM | 1 |
Maximum size of CLM | ≤ 3 cm2
| 1 |
CEA level | ≤ 100 ng/mL | 1 |
Clinical criteria | Overall survival | Recurrence-free survival | |||||||
---|---|---|---|---|---|---|---|---|---|
Score2
| Subgroup3
| Response4PR | No. of CLM ≤ 3 | Size of CLM5 ≤ 3 cm | CEA value ≤ 100 ng/mL | median (months) | 5-Years (%) | median (months) | 5-years (%) |
0
|
-
|
-
|
-
|
-
| 16 | 0 | 4 | 0 | |
1
|
1A
|
-
|
-
|
-
|
+
| 17 | 0 | 3 | 0 |
1B
|
-
|
-
|
+
|
-
| 19 | 0 | 6 | 0 | |
1C
|
-
|
+
|
-
|
-
| 19 | 0 | 4 | 0 | |
1D
|
+
|
-
|
-
|
-
| 31 | 0 | 11 | 0 | |
2
|
2A
|
-
|
-
|
+
|
+
| 18 | 0 | 4 | 0 |
2B
|
-
|
+
|
-
|
+
| 24 | 0 | 5 | 0 | |
2C
|
+
|
-
|
-
|
+
| no | no | no | no | |
2D
|
-
|
+
|
+
|
-
| 19 | 0 | 4 | 0 | |
2E
|
+
|
-
|
+
|
-
| 33 | 0 | 9 | 0 | |
2 F
|
+
|
+
|
-
|
-
| 36 | 11 | 10 | 0 | |
3
|
3A
|
-
|
+
|
+
|
+
| 27 | 7 | 5 | 0 |
3B
|
+
|
+
|
-
|
+
| 44 | 15 | 9 | 0 | |
3C
|
+
|
-
|
+
|
+
| 40 | 0 | 11 | 0 | |
3D
|
+
|
+
|
+
|
-
| 44 | 27 | 11 | 9 | |
4
|
+
|
+
|
+
|
+
| 46 | 39 | 13 | 22 |