Prognostic Value of Metabolic Parameters in Patients with Synchronous Colorectal Cancer Liver Metastasis Following Curative-Intent Colorectal and Hepatic Surgery

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FIGURE 1.
Flow diagram outlining criteria used for patient inclusion and exclusion.
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FIGURE 2.
Kaplan–Meier curves for RFS dichotomized using median cutoff value of PS_RFS (A) and for OS dichotomized using 60th-percentile cutoff value of PS_OS (B).

TABLE 1

Demographics and Clinicopathologic Features of Primary Colorectal Cancers and Liver Metastases

Characteristic	n or mean ± SD
Age (y)	59.9 ± 10.1 (range, 35−80)
Sex
Male	82 (68%)
Female	38 (32%)
Preoperative carcinoembryonic antigen (ng/mL)	35.2 ± 99.8 (range, 0.32−812.8)
Pathologic stage
T
T2	1 (1%)
T3	107 (89%)
T4	12 (10%)
N
N0	29 (24%)
N1	47 (39%)
N2	44 (37%)
Location of primary tumor
Colon	74 (62%)
Rectum	46 (38%)
Bilobar hepatic metastasis
Yes	21 (17%)
No	99 (83%)
Hepatic resection margin
Positive	13 (11%)
Negative	107 (89%)
Differentiation grade
Well differentiated	4 (3%)
Moderately differentiated	110 (92%)
Poorly differentiated	6 (5%)
Number of hepatic metastasis
1	70 (59%)
2	29 (24%)
3	10 (8%)
>3	11 (9%)
Size of primary tumor (cm)	5.5 ± 1.8 (range, 1.7−11.2)
Size of hepatic metastasis (cm)	3.5 ± 2.4 (range, 0.4−14.0)
Adjuvant chemotherapy
No	4 (3%)
Yes	116 (97%)
Total	120 (100%)

TABLE 2

Metabolic Features of Primary Colorectal Cancers and Liver Metastases

Metabolic parameter	Mean ± SD
SUV_mean of normal liver	1.8 ± 0.3 (1.2−2.9)
SUV_peak of primary tumor	8.7 ± 4.0 (2.1−29.9)
nSUV_peak of primary tumor	5.0 ± 2.3 (1.4−16.9)
SUV_peak of hepatic metastasis	5.4 ± 2.8 (1.8−20.6)
nSUV_peak of hepatic metastasis	3.1 ± 1.6 (0.9−11.6)
MTV of primary tumor (cm³)	20.6 ± 15.3 (3.0−124.7)
MTV of hepatic metastasis (cm³)	32.2 ± 61.9 (0.0−450.4)
nTLG of primary tumor (cm³)	79.5 ± 75.4 (6.0−555.0)
nTLG of hepatic metastasis (cm³)	91.6 ± 182.7 (0.0−1215.6)

TABLE 3

Univariate Cox Regression Analysis for Clinicopathologic Risk Factors Associated with Survival

		RFS			OS
Variable	n	Hazard ratio	95% CI	P	Hazard ratio	95% CI	P
Age (y)	120	1.009	0.987−1.032	0.428	1.034	1.000−1.069	0.052
Sex
Female	38	—	—	—	—	—	—
Male	82	1.462	0.885−2.414	0.138	1.308	0.639−2.677	0.462
Size of primary tumor (cm)	120	1.034	0.908−1.176	0.617	0.982	0.826−1.168	0.838
Size of hepatic metastasis (cm)	120	1.088	0.998−1.187	0.055	1.131	1.016−1.259	0.025
Preoperative serum carcinoembryonic antigen (ng/mL)	120	1.001	0.999−1.003	0.298	1.002	0.999−1.004	0.179
T stage
T2, T3	108	—	—	—	—	—	—
T4	12	1.194	0.595−2.396	0.617	1.019	0.361−2.876	0.972
N stage
N0	29	—	—	0.822	—	—	0.776
N1	47	0.881	0.494−1.571	0.667	1.281	0.557−2.947	0.560
N2	44	1.031	0.578−1.839	0.919	1.035	0.434−2.471	0.937
Positive hepatic resection margin
No	107	—	—	—	—	—	—
Yes	13	1.315	0.656−2.639	0.440	1.518	0.637−3.620	0.346
No. of hepatic metastasis	120	1.200	1.009−1.427	0.039	1.058	0.858−1.304	0.596
Bilobar hepatic metastasis
No	99	—	—	—	—	—	—
Yes	21	0.886	0.488−1.609	0.691	0.735	0.288−1.880	0.521
Differentiation grade
Well or moderately differentiated	114	—	—	—	—	—	—
Poorly differentiated	6	1.934	0.703−5.324	0.202	5.234	1.803−15.196	0.002
Location of primary tumor
Colon	74	—	—	—	—	—	—
Rectum	46	1.265	0.803−1.992	0.310	0.986	0.524−1.857	0.966
Adjuvant chemotherapy
No	4	—	—	—	—	—	—
Yes	116	0.585	0.214−1.605	0.298	0.414	0.099−1.738	0.228
Fong’s clinical risk score	120	1.225	0.891−1.683	0.214	1.310	0.850−2.021	0.224

TABLE 4

Univariate Cox Regression Analysis for Metabolic Risk Factors Associated with Survival

		RFS			OS
Variable	n	Hazard ratio	95% CI	P	Hazard ratio	95% CI	P
nSUV_peak of primary tumor	120	0.932	0.837−1.038	0.202	0.984	0.860−1.127	0.820
nSUV_peak of hepatic metastasis	120	1.106	0.982−1.245	0.097	1.209	1.055−1.386	0.006
M/P ratio of nSUV_peak	120	2.351	1.308−4.226	0.004	1.849	0.891−3.837	0.099
MTV of primary tumor (cm³)	120	1.012	0.996−1.028	0.139	1.005	0.988−1.021	0.589
MTV of hepatic metastasis (cm³)	120	1.003	1.000−1.006	0.068	1.003	1.000−1.006	0.058
M/P ratio of MTV	120	1.036	0.983−1.092	0.184	1.051	0.989−1.117	0.108
nTLG of primary tumor (cm³)	120	1.001	0.997−1.005	0.702	1.000	0.996−1.004	0.949
nTLG of hepatic metastasis (cm³)	120	1.001	1.000−1.002	0.065	1.001	1.000−1.002	0.023
M/P ratio of nTLG	120	1.040	0.989−1.093	0.129	1.049	0.989−1.112	0.108

TABLE 5

Multivariate Cox Regression Models for RFS

Model	Variable	β	Hazard ratio	95% CI	P
1	Sex (male)	0.491	1.634	0.979−2.726	0.060
	nSUV_peak of primary tumor	−0.136	0.872	0.763−0.998	0.047
	nSUV_peak of hepatic metastasis	0.218	1.244	1.002−1.543	0.048
	Size of hepatic metastasis (cm)	0.050	1.051	0.937−1.180	0.393
	No. of hepatic metastasis	0.169	1.184	0.994−1.410	0.058
2	Sex (male)	0.508	1.663	0.997−2.774	0.051
	M/P ratio of SUV_peak	0.735	2.086	1.041−4.180	0.038
	Size of hepatic metastasis (cm)	0.070	1.073	0.967−1.190	0.183
	No. of hepatic metastasis	0.185	1.204	1.011−1.433	0.037
3	Sex (male)	0.492	1.635	0.979−2.730	0.060
	MTV of hepatic metastasis (cm³)	0.000	1.000	0.994−1.005	0.887
	Size of hepatic metastasis (cm)	0.127	1.136	0.964−1.338	0.129
	No. of hepatic metastasis	0.213	1.237	1.040−1.472	0.016
4	Sex (male)	0.490	1.633	0.978−2.726	0.061
	nTLG of hepatic metastasis (cm³)	0.000	1.000	0.998−1.002	0.937
	Size of hepatic metastasis (cm)	0.123	1.131	0.955−1.338	0.153
	No. of hepatic metastasis	0.212	1.237	1.039−1.472	0.017

TABLE 6

Multivariate Cox Regression Models for OS

Model	Variable	β	Hazard ratio	95% CI	P
5	Age (y)	0.035	1.036	1.001−1.073	0.047
	nSUV_peak of primary tumor	−0.152	0.859	0.717−1.030	0.101
	nSUV_peak of hepatic metastasis	0.363	1.438	1.080−1.916	0.013
	Size of hepatic metastasis (cm)	0.032	1.033	0.895−1.191	0.660
	Differentiation grade (poor)	1.344	3.836	1.255−11.724	0.018
6	Age (y)	0.032	1.032	0.997−1.069	0.070
	M/P ratio of SUV_peak	0.233	1.263	0.497−3.207	0.624
	Size of hepatic metastasis (cm)	0.112	1.118	0.986−1.269	0.082
	Differentiation grade (poor)	1.546	4.694	1.515−14.515	0.007
7	Age (y)	0.031	1.031	0.997−1.067	0.077
	MTV of hepatic metastasis (cm³)	0.000	1.000	0.993−1.007	0.914
	Size of hepatic metastasis (cm)	0.138	1.148	0.915−1.440	0.234
	Differentiation grade (poor)	1.635	5.127	1.756−14.975	0.003
8	Age (y)	0.031	1.031	0.997−1.067	0.077
	nTLG of hepatic metastasis (cm³)	0.001	1.001	0.998−1.003	0.643
	Size of hepatic metastasis (cm)	0.078	1.081	0.854−1.368	0.516
	Differentiation grade (poor)	1.651	5.214	1.783−15.248	0.003