Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases

Figures & data

Figure 1. Patient inclusion flowchart.

Table 1. Characteristics of the patients.

Characteristic	Total cohort (n = 160)	Training cohort (n = 128)	Validation cohort (n = 32)	p Value
Age at ablation, mean (SD), years	58.5 (8.4)	58.5 (8.2)	58.7 (9.3)	0.942
Sex				0.136
Male	110 (68.8)	92 (71.9)	18 (56.2)
Female	50 (31.2)	36 (28.1)	14 (43.8)
Primary tumour site				0.088
Left colon	79 (49.4)	67 (52.3)	12 (37.5)
Right colon	19 (11.9)	17 (13.3)	2 (6.3)
Rectum	62 (38.8)	44 (34.4)	18 (56.2)
Primary T stage				1.000
T1-3	126 (78.8)	101 (78.9)	25 (78.1)
T4	34 (21.2)	27 (21.1)	7 (21.9)
Nodal metastases				0.643
No	52 (32.5)	40 (31.2)	12 (37.5)
Yes	108 (67.5)	88 (68.8)	20 (62.5)
RAS mutation status				0.100
Wild type	93 (58.1)	79 (61.7)	14 (43.8)
Mutant	67 (41.9)	49 (38.3)	18 (56.2)
No. of previous hepatectomy				0.385
Single	151 (94.4)	122 (95.3)	29 (90.6)
Two	9 (5.6)	6 (4.7)	3 (9.4)
Initial CLM diagnosis				0.232
Synchronous	116 (72.5)	96 (75.0)	20 (62.5)
Metachronous	44 (27.5)	32 (25.0)	12 (37.5)
Factors associated with hepatectomy of CLM
Number of tumours, median (IQR)	4.0 (2.0–6.0)	3.5 (2.0–6.0)	4.0 (2.0–7.3)	0.507
Size of largest CLM, cm
Median (IQR)	2.2 (1.5–3.3)	2.2 (1.5–3.3)	2.1 (1.5–3.3)	0.667
≤3 cm	113 (70.6)	91 (71.1)	22 (68.8)
>3 cm	47 (29.4)	37 (28.9)	10 (31.2)
Type of procedure				0.452
Resection	116 (72.5)	95 (74.2)	21 (65.6)
Resection and RFA	44 (27.5)	33 (25.8)	11 (34.4)
Resection margin				0.965
R0	113 (70.6)	91 (71.1)	22 (68.8)
R1	47 (29.4)	37 (28.9)	10 (31.2)
Factors associated with RFA of recurrent CLM
Interval from hepatectomy to intrahepatic recurrence, median (IQR), months	6.0 (3.0–10.2)	6.0 (3.0–10.0)	7.0 (4.0–11.2)	0.426
Number of tumours, median (IQR)	1.0 (1.0–2.0)	1.0 (1.0–2.0)	1.0 (1.0–2.0)	0.375
Size of largest CLM, cm
Median (IQR)	1.8 (1.4–2.4)	1.8 (1.4–2.4)	1.7 (1.3–2.2)	0.265
≤3 cm	152 (95.0)	122 (95.3)	30 (93.7)
>3 cm	8 (5.0)	6 (4.7)	2 (6.3)
CEA level at ablation	5.4 (3.2–9.9)	5.3 (3.2–9.8)	5.5 (2.4–12.3)	0.969
Extrahepatic disease at ablation				0.373
No	123 (76.9)	96 (75.0)	27 (84.4)
Yes	37 (23.1)	32 (25.0)	5 (15.6)
Preablation chemotherapy				0.328
No	99 (61.9)	82 (64.1)	17 (53.1)
Cytotoxic chemo	13 (8.1)	11 (8.6)	2 (6.3)
Cytotoxic chemo + biological agent	48 (30.0)	35 (27.3)	13 (40.6)
Postablation chemotherapy				1.000
No	94 (58.8)	75 (58.6)	19 (59.4)
Yes	66 (41.2)	53 (41.4)	13 (40.6)
Ablation margin				0.400
<5mm	67 (41.9)	51 (39.8)	16 (50.0)
≥5mm	93 (58.1)	77 (60.2)	16 (50.0)

RFA, radiofrequency ablation; CLM, colorectal liver metastases; CEA, carcinoembryonic antigen.

Table 2. Univariate and multivariate analyses of risk factors for rIHR and OS after RFA.

	Repeat intrahepatic recurrence				Overall survival
	Univariate		Multivariate		Univariate		Multivariate
Variable	SHR (95% CI)	p Value	SHR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
Age (≤60 as ref.)
>60	1.00 (0.68–1.46)	0.993			1.29 (0.80–2.08)	0.302
Gender (female as ref.)
Male	0.95 (0.60–1.51)	0.828			0.79 (0.48–1.32)	0.374
Primary tumour site (left colon as ref.)
Right colon	1.79 (1.03–3.11)	0.038	1.26 (0.70–2.27)	0.430	1.60 (0.80–3.19)	0.185
Rectum	1.39 (0.91–2.11)	0.120	1.16 (0.77–1.75)	0.480	1.10 (0.65–1.88)	0.720
Primary T stage (T1-3 as ref.)
T4	1.29 (0.82–2.03)	0.279			1.30 (0.75–2.24)	0.349
Nodal metastases (no as ref.)
Yes	0.95 (0.65–1.37)	0.772			1.46 (0.85–2.51)	0.171
RAS mutational status (wild type as ref.)
Mutant	2.28 (1.52–3.42)	<0.001	1.92 (1.29–2.84)	0.001	2.79 (1.71–4.53)	<0.001	2.15 (1.29–3.60)	0.003
Initial CLM diagnosis (metachronous as ref.)
Synchronous	1.37 (0.86–2.18)	0.186			1.58 (0.87–2.86)	0.131
No. of previous hepatectomy (one as ref.)
Two	1.19 (0.54–2.64)	0.668			1.45 (0.53–3.99)	0.473
Factors associated with hepatectomy of CLM
No. of CLM (solitary as ref.)
Multiple	1.49 (0.82–2.68)	0.189			0.98 (0.50–1.93)	0.961
Size of largest CLM (≤3 cm as ref.)
>3 cm	1.05 (0.65–1.69)	0.839			1.82 (1.11–3.00)	0.018	2.10 (1.26–3.50)	0.004
Type of procedure (resection as ref.)
Resection and RFA	1.39 (0.95–2.02)	0.087			0.83 (0.47–1.46)	0.512
Surgical margin (R0 as ref.)
R1	1.43 (0.94–2.17)	0.098			1.46 (0.87–2.44)	0.148
Factors associated with RFA of recurrent CLM
Interval from hepatectomy to recurrence (>12 months as ref.)
≤12 months	2.13 (1.22–3.72)	0.008	2.00 (1.07–3.73)	0.029	1.17 (0.61–2.23)	0.642
No. of CLM (unique as ref.)
Multiple	1.15 (0.78–1.70)	0.487			1.21 (0.74–1.98)	0.444
Size of largest CLM (≤3 cm as ref.)
>3 cm	1.16 (0.54–2.47)	0.704			1.30 (0.47–3.58)	0.616
CEA level at ablation (≤5 ng/ml as ref.)
>5 ng/ml	1.87 (1.25–2.79)	0.002	1.57 (1.04–2.36)	0.032	2.48  (1.47–4.16)	<0.001	2.05 (1.16–3.62)	0.013
Extrahepatic disease (no as ref.)
Yes	1.17 (0.75–1.81)	0.496			3.27 (1.98–5.41)	<0.001	1.88 (1.07–3.32)	0.028
Preablation chemotherapy (none as ref.)
Done	1.08 (0.72–1.62)	0.697			0.89 (0.54–1.48)	0.662
Postablation chemotherapy (none as ref.)
Done	0.86 (0.59–1.26)	0.441			1.30 (0.79–2.13)	0.298
Ablation margin (≥5 mm as ref.)
<5 mm	1.92 (1.31–2.81)	<0.001	1.69 (1.14–2.50)	0.009	2.05 (1.27–3.33)	0.003	1.44 (0.84–2.49)	0.188

RFA, radiofrequency ablation; CLM, colorectal liver metastases; CEA, carcinoembryonic antigen; rIHR, repeat intrahepatic recurrence; OS, overall survival; SHR, subdistribution hazard ratio; HR, hazard ratio.

Figure 2. Nomograms for predicting 1- and 2-year rIHR rates after RFA for patients with recurrent CLMs. RFA, radiofrequency ablation; CLM, colorectal liver metastases; CEA, carcinoembryonic antigen; rIHR, repeat intrahepatic recurrence.

Figure 3. Nomograms for predicting 3- and 5-year OS rates after RFA for patients with recurrent CLMs. RFA, radiofrequency ablation; CLM, colorectal liver metastases; CEA, carcinoembryonic antigen; OS, overall survival.

Figure 4. Calibration curves for rIHR after RFA based on nomogram prediction and actual observation. (A–B) 1- and 2-year rIHR rates in the training cohorts. (C–D) 1- and 2-year rIHR rates in the validation cohorts. RFA, radiofrequency ablation; rIHR, repeat intrahepatic recurrence; OS, overall survival.

Figure 5. Calibration curves for OS after RFA based on nomogram prediction and actual observation. (A–B). 3- and 5-year OS rates in the training cohorts. (C–D) 3- and 5-year OS rates in the validation cohorts. RFA, radiofrequency ablation; OS, overall survival.

Figure 6. The risk score was closely related to the prognosis of recurrent CLM patients treated with RFA. (A) Kaplan–Meier curves of OS. (B) CIF curves of rIHR. RFA, radiofrequency ablation; CLM, colorectal liver metastases; rIHR, repeat intrahepatic recurrence; OS, overall survival; CIF, cumulative incidence function.

Data availability statement

The data presented in this study are available on request from the corresponding authors.