Radiofrequency ablation with or without capecitabine maintenance therapy for lung oligometastases from colorectal cancer

Table 1 Clinical characteristics of patients enrolled, n (%)

Variables	Total (n = 247)	Only RFA (n = 99)	Combined (n = 148)	P value
Sex				0.509
Female	96 (38.9)	36 (36.4)	60 (40.5)
Male	151 (61.1)	63 (63.6)	88 (59.5)
Age, median (IQR) (years)	58.0 (48.0, 66.0)	58.0 (53.0, 66.5)	58.5 (48.0, 66.0)	0.633
KRAS				0.846
Wild-type	154 (62.3)	61 (61.6)	93 (62.8)
Mutated	93 (37.7)	38 (38.4)	55 (37.2)
CA19-9				0.029
< 27 U/mL	216 (87.4)	81 (81.8)	135 (91.2)
≥ 27 U/mL	31 (12.6)	18 (18.2)	13 (8.8)
CEA				0.267
< 5 ng/mL	188 (76.1)	79 (79.8)	109 (73.6)
≥ 5 ng/mL	59 (23.9)	20 (20.2)	39 (26.4)
Location				0.658
Left	129 (52.2)	50 (50.5)	79 (53.4)
Right	118 (47.8)	49 (49.5)	69 (46.6)
Number of lesions				0.006
1	171 (69.2)	78 (78.8)	93 (62.8)
2	67 (27.1)	21 (21.2)	46 (31.1)
3	9 (3.6)	0 (0)	9 (6.1)
Lesion diameter, median (IQR)	1.0 (0.8, 1.5)	1.0 (0.8, 1.5)	1.0 (0.8, 1.4)	0.521
Distance between the lesion and the mediastinum or great vessels				0.392
≤ 1 cm	124 (50.2)	53 (53.5)	71 (48)
> 1 cm	123 (49.8)	46 (46.5)	77 (52)
Distance between the lesion and the pleural surface				0.495
≤ 1 cm	81 (32.8)	30 (30.3)	51 (34.5)
> 1 cm	166 (67.2)	69 (69.7)	97 (65.5)
Primary lesion pathology				0.807
Rectum	159 (64.4)	66 (66.7)	93 (62.8)
Left half colon	52 (21.2)	19 (19.2)	33 (22.3)
Right half colon	36 (14.6)	14 (14.1)	22 (14.9)
Primary tumor (T) staging				0.8
1	4 (1.6)	2 (2)	2 (1.4)
2	25 (10.1)	10 (10.1)	15 (10.1)
3	128 (51.8)	48 (48.5)	80 (54.1)
4	90 (36.4)	39 (39.4)	51 (34.5)
Neural invasion				0.308
None	168 (68.0)	71 (71.7)	97 (65.5)
Exist	79 (32.0)	28 (28.3)	51 (34.5)
Lymphovascular invasion				0.974
None	150 (60.7)	60 (60.6)	90 (60.8)
Exist	97 (39.3)	39 (39.4)	58 (39.2)
Synchronous or metachronous				0.217
Metachronous	139 (56.3)	51 (51.5)	88 (59.5)
Synchronous	108 (43.7)	48 (48.5)	60 (40.5)
Pneumothorax				0.694
None	194 (78.5)	79 (79.8)	115 (77.7)
Grade 1	42 (17.0)	18 (18.2)	24 (16.2)
Grade 2	11 (4.5)	5 (5.1)	6 (4.1)
Grade 3	3 (1.2)	1 (1.0)	2 (1.4)
Alveolar hemorrhage				0.643
None	203 (82.2)	80 (80.8)	123 (83.1)
Grade 1	39 (15.8)	17 (17.2)	22 (14.9)
Grade 2	5 (2.0)	2 (2.0)	3 (2.0)

IQR: Interquartile range; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; RFA: Radiofrequency ablation; Combined: Radiofrequency ablation plus capecitabine; Only RFA: Radiofrequency ablation alone.

Table 2 Survival and local control outcomes in colorectal cancer patients with lung metastases stratified by treatment modalities

	All patients (n = 247)	Only RFA (n = 99)	Combined (n = 148)
OS (%)
1-year	99.1	97.9	99.2
3-year	95.4	94.7	95.9
5-year	80.0	69.1	88.7
PFS (%)
1-year	81.8	79.8	83.1
3-year	43.4	38.4	46.8
5-year	26.2	23.7	27.8
LTP (%)
1-year	3.2	5.1	2.0
3-year	18.2	28.8	10.9
5-year	33.8	49.0	22.7

OS: Overall survival; PFS: Progression-free survival; LTP: Local tumor progression; RFA: Radiofrequency ablation; Combined: Radiofrequency ablation plus capecitabine; Only RFA: Radiofrequency ablation alone.

Table 3 Univariate analysis of factors associated with overall survival in colorectal cancer patients with lung metastases

Variables	HR (95%CI)	P value (Wald’s test)
Sex
Female	1 (Reference)
Male	0.74 (0.34-1.64)	0.464
Age	0.96 (0.93-1)	0.065
KRAS
Wild-type	1 (Reference)
Mutated	1.43 (0.64-3.18)	0.388
CA19-9
< 27 U/mL	1 (Reference)
≥ 27 U/mL	1.23 (0.42-3.61)	0.703
CEA
< 5 ng/mL	1 (Reference)
≥ 5 ng/mL	1.82 (0.8-4.15)	0.155
Location
Left	1 (Reference)
Right	0.91 (0.41-2.01)	0.821
Diameter	3.2 (1.57-6.55)	0.001
Distance between the lesion and the mediastinum or great vessels
≤ 1 cm	1 (Reference)
> 1 cm	0.77 (0.34-1.74)	0.529
Distance between the lesion and the pleural surface
≤ 1 cm	1 (Reference)
> 1 cm	0.38 (0.17-0.86)	0.02
Primary lesion pathology
Rectum	1 (Reference)
Left half colon	2.38 (0.93-6.09)	0.07
Right half colon	2.2 (0.83-5.87)	0.115
Neural invasion
None	1 (Reference)
Exist	1.27 (0.57-2.83)	0.562
Lymphovascular invasion
None	1 (Reference)
Exist	0.84 (0.35-2.02)	0.699
Synchronous or metachronous
Metachronous	1 (Reference)
Synchronous	0.68 (0.31-1.52)	0.348
Pneumothorax
None	1 (Reference)
Exist	0.19 (0.03-1.42)	0.105
Alveolar hemorrhage
None	1 (Reference)
Exist	7.5 (3.34-16.84)	< 0.001

CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; HR: Hazard ratio; CI: Confidence interval.

Table 4 Multivariate Cox proportional hazards analysis of the association between whether chemotherapy was combined after radiofrequency ablation and overall survival in colorectal cancer patients with lung metastases

Group	n (total)	n (%)	Crude	Model 1	Model 2	Model 3	Model 4
Only RFA	99	17 (17.2)	1 (Reference)
Combined	148	8 (5.4)	0.35 (0.15-0.81)	0.33 (0.14-0.77)	0.31 (0.13-0.73)	0.29 (0.11-0.77)	0.31 (0.12-0.79)
P value			0.011	0.014	0.008	0.012	0.014

RFA: Radiofrequency ablation; Combined: Radiofrequency ablation plus capecitabine; Only RFA: Radiofrequency ablation alone; Model 1: Adjusted for sex, age; Model 2: Adjusted for model 1 + KRAS + carcinoembryonic antigen; Model 3: Adjusted for model 2 + lesion diameter + distance between the lesion and the mediastinum or great vessels + distance between the lesion and the pleural surface + primary lesion pathology + neural invasion + lymphovascular invasion; Model 4: Adjusted for model 3 + synchronous or metachronous + pneumothorax.