Clinical implication of FDG uptake of bone marrow on PET/CT in gastric cancer patients with surgical resection

Table 1 Characteristics of the 309 enrolled patients with gastric cancer

Characteristics		n (%)	Median	Range
Age (yr)			60	29-82
Sex	Male	77 (24.9)
	Female	232 (75.1)
Tumor location	Upper	11 (3.6)
	Middle	134 (43.4)
	Lower	158 (51.1)
	Multiple	6 (1.9)
Operation type	Subtotal gastrectomy	139 (45.0)
	Total gastrectomy	170 (55.0)
Pathology	PAC/TAC	200 (64.7)
	PDAC	74 (23.9)
	SRC/MAC	35 (11.3)
Lauren classification	Intestinal	137 (44.3)
	Non-intestinal	172 (55.7)
T stage	T1	183 (59.2)
	T2	57 (18.4)
	T3	41 (13.3)
	T4	28 (9.1)
Lymph node metastasis	Absence	212 (68.6)
	Presence	97 (31.4)
Tumor size (cm)			3.0	0.5-17.0
Tumor involvement of resection margin	Negative	302 (97.7)
	Positive	7 (2.3)
Adjuvant chemotherapy	No	220 (71.2)
	Yes	89 (28.8)
White blood cell (× 1012 cells/L)			6.87	3.09-20.13
Hemoglobin (g/dL)			13.6	4.1-17.3
NLR			1.96	0.13-22.80
PLR			126.05	2.93-557.13
Albumin (g/dL)			4.3	2.5-5.4
CRP (mg/dL)			1.61	0.0-115.05
FDG uptake	Negative	153 (49.5)
	Positive	156 (50.5)
Tmax1			4.71	2.62-37.80
BM SUV			1.45	0.55-2.66
BLR			0.70	0.28-1.35

¹Measured only in 156 patients with positive FDG uptake. PAC: Papillary adenocarcinoma; TAC: Tubular adenocarcinoma; PDAC: Poorly-differentiated adenocarcinoma; SRC: Signet-ring cell carcinoma; MAC: Mucinous adenocarcinoma; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CRP: C-reactive protein; FDG: F-18 fluorodexoyglucose; PET/CT: Positron emission tomography/computed tomography; BM: Bone marrow; BLR: BM-to-liver uptake ratio.

Table 2 Correlation of F-18 fluorodexoyglucose uptake of bone marrow with clinical factors

	White blood cells	Hemoglobin	NLR	PLR	Albumin	CRP	Tmax1
BM SUV	r = 0.039	r = -0.117	r = 0.121	r = 0.158	r = -0.041	r = 0.100	r = 0.093
	P = 0.600	P = 0.039	P = 0.033	P = 0.005	P = 0.474	P = 0.079	P = 0.104
BLR	r = 0.033	r = -0.172	r = 0.224	r = 0.250	r = -0.168	r = 0.094	r = 0.212
	P = 0.563	P = 0.002	P = 0.001	P < 0.001	P = 0.003	P = 0.100	P = 0.002

¹Analyzed in 156 patients with positive FDG uptake. NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CRP: C-reactive protein; BM: Bone marrow; BLR: BM-to-liver uptake ratio.

Table 3 Comparison between bone marrow standardized uptake value and BM-to-liver uptake ratio according to tumor factors

		BM SUV	P value	BLR	P value
Pathology	PAC/TAC	1.49 ± 0.34	0.143	0.73 ± 0.17	0.081
	PDAC	1.54 ± 0.37		0.75 ± 0.16
	SRC/MAC	1.41 ± 0.32		0.68 ± 0.16
T stage	T1	1.46 ± 0.35	0.042	0.71 ± 0.16	0.003
	T2-T4	1.54 ± 0.33		0.78 ± 0.17
Lymph node metastasis	Absence	1.47 ± 0.34	0.123	0.72 ± 0.16	0.010
	Presence	1.54 ± 0.36		0.77 ± 0.17
FDG uptake	Negative	1.46 ± 0.30	0.007	0.71 ± 0.14	0.006
	Positive	1.52 ± 0.38		0.75 ± 0.18
Recurrence	No	1.47 ± 0.34	0.001	0.72 ± 0.16	<0.001
	Yes	1.68 ± 0.36		0.85 ± 0.16

BM: Bone marrow; BLR: BM-to-liver uptake ratio; PAC: Papillary adenocarcinoma; TAC: Tubular adenocarcinoma; PDAC: Poorly-differentiated adenocarcinoma; SRC: Signet-ring cell carcinoma; MAC: Mucinous adenocarcinoma; FDG: F-18 fluorodexoyglucose.

Table 4 Univariate analysis of prognostic factors for recurrence-free survival and overall survival

Variables	RFS		OS
	P value	HR (95%CI)	P value	HR (95%CI)
Age (≤ 68 yr vs > 68 yr)	0.025	2.07 (1.10-3.91)	0.058	2.46 (0.97-6.23)
Sex (female vs male)	0.658	1.19 (0.56-2.53)	0.078	2.38 (0.91-6.22)
Tumor location
Body		1.00		1.00
Fundus	0.788	0.76 (0.10-5.72)	0.961	0.85 (0.18-6.62)
Antrum	0.869	0.94 (0.48-1.85)	0.591	1.30 (0.50-3.35)
Multiple	0.009	5.15 (1.50-17.72)	0.973	1.10 (0.15-7.54)
Pathology
PCA/TAC		1.00		1.00
PDAC	0.591	1.22 (0.59-2.53)	0.643	0.76 (0.24-2.41)
SRC/MAC	0.182	1.86 (0.75-4.64)	0.457	1.62 (0.45-5.83)
Lauren classification (intestinal vs non-intestinal)	0.368	1.35 (0.70-2.62)	> 0.999	1.00 (0.39-2.53)
T stage
T1		1.00		1.00
T2	0.005	4.97 (1.62-15.21)	0.300	2.83 (0.40-20.24)
T3	< 0.001	9.78 (3.34-28.64)	0.008	9.86 (1.80-53.93)
T4	< 0.001	34.10 (12.24-94.94)	< 0.001	52.24 (11.13-245.23)
Lymph node metastasis (absence vs presence)	< 0.001	11.14 (5.08-24.44)	< 0.001	13.62 (3.93-47.22)
Tumor size (≤ 3.0 cm vs > 3.0 cm)	< 0.001	5.50 (2.30-13.19)	0.006	17.13 (2.27-128.96)
Tumor involvement of resection margin (negative vs positive)	0.013	4.48 (1.38-14.60)	0.018	5.87 (1.35-25.56)
White blood cell (≤ 9.5 × 1012 cells/L vs > 9.5 × 1012 cells/L)	0.006	2.73 (1.32-5.62)	0.910	0.92 (0.21-3.99)
Hemoglobin (≤ 12.0 g/dL vs > 12.0 g/dL)	< 0.001	0.25 (0.13-0.48)	< 0.001	0.12 (0.05-0.31)
NLR (≤ 2.10 vs > 2.10)	0.002	4.04 (1.96-8.33)	0.117	2.13 (0.83-5.51)
PLR (≤ 210.0 vs > 210.0)	< 0.001	4.03 (2.03-7.99)	0.005	4.12 (1.55-10.98)
Albumin (≤ 3.9 g/dL vs > 3.9 g/dL)	0.001	0.27 (0.14-0.52)	0.003	0.23 (0.09-0.60)
CRP (≤ 20.0 mg/dL vs > 20.0 mg/dL)	0.013	2.49 (1.21-5.14)	0.306	1.79 (0.59-5.49)
FDG uptake (negative vs positive)	< 0.001	7.82 (3.05-20.07)	0.004	19.68 (2.61-148.27)
Tmax (≤ 6.0 vs > 6.0)1	< 0.001	5.72 (3.01-10.86)	0.002	5.35 (1.88-15.21)
BM SUV (≤ 1.50 vs > 1.50)	0.016	2.27 (1.16-4.45)	0.196	1.87 (0.72-4.84)
BLR (≤ 0.72 vs > 0.72)	< 0.001	8.25 (3.22-21.15)	0.003	20.69 (2.75-155.64)

¹Analyzed in 156 patients with positive FDG uptake. RFS: Recurrence-free survival; OS: Overall survival; PAC: Papillary adenocarcinoma; TAC: Tubular adenocarcinoma; PDAC: Poorly-differentiated adenocarcinoma; SRC: Signet-ring cell carcinoma; MAC: Mucinous adenocarcinoma; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CRP: C-reactive protein; FDG: F-18 fluorodexoyglucose; PET/CT: Positron emission tomography/computed tomography; BM: Bone marrow; BLR: BM-to-liver uptake ratio.

Table 5 Multivariate analysis of prognostic factors for recurrence-free survival and overall survival in model with all 309 patients and 156 patients with positive F-18 fluorodexoyglucose uptake

Variables	Model with all patients		Model with patients with positive FDG uptake
	P value	HR (95%CI)	P value	HR (95%CI)
RFS
Age	0.461	1.38 (0.58-3.28)	0.228	1.69 (0.72-3.96)
Location
Body		1.00		1.00
Fundus	0.543	0.50 (0.05-4.78)	0.634	0.58 (0.06-5.32)
Antrum	0.276	0.64 (0.29-1.42)	0.695	0.86 (0.41-1.82)
Multiple	0.037	6.06 (1.36-26.92)	0.034	5.19 (1.13-23.76)
T stage
T1		1.00		1.00
T2	0.342	1.81 (0.53-6.19)	0.250	2.05 (0.60-6.99)
T3	0.200	2.31 (0.64-8.29)	0.096	3.01 (0.82-10.97)
T4	0.020	4.99 (1.29-19.38)	0.014	5.50 (1.42-21.31)
Lymph node metastasis	0.037	2.96 (1.07-8.21)	0.004	4.50 (1.61-12.54)
Tumor size	0.661	1.27 (0.43-3.75)	0.594	1.34 (0.46-3.95)
Tumor involvement of resection margin	0.035	4.32 (1.11-16.81)	0.023	4.94 (1.24-19.62)
White blood cell	0.150	1.96 (0.78-4.92)	0.053	2.37 (0.99-5.67)
Hemoglobin	0.652	1.24 (0.49-3.11)	0.955	0.97 (0.38-2.50)
NLR	0.611	1.25 (0.53-2.90)	0.607	1.24 (0.54-2.86)
PLR	0.563	1.30 (0.53-3.18)	0.197	1.78 (0.74-4.27)
Albumin	0.060	0.42 (0.17-1.04)	0.021	0.34 (0.14-0.85)
CRP	0.173	1.88 (0.76-4.68)	0.181	1.85 (0.75-4.55)
FDG uptake	0.058	2.72 (0.97-7.65)
Tmax			0.215	1.33 (0.70-2.39)
BM SUV	0.945	0.94 (0.38-2.33)	0.597	0.80 (0.34-1.86)
BLR	0.001	6.42 (2.07-19.84)	0.005	7.67 (2.44-24.12)
OS
T stage
T1		1.00		1.00
T2	0.994	1.01 (0.13-8.41)	0.965	1.93 (0.29-13.05)
T3	0.537	1.78 (0.28-11.15)	0.500	1.93 (0.29-13.05)
T4	0.002	5.33 (1.88-15.14)	< 0.001	6.15 (2.18-17.34)
Lymph node metastasis	0.016	5.08 (1.36-18.94)	0.092	3.40 (0.82-14.11)
Tumor size	0.243	3.62 (0.42-31.35)	0.242	3.77 (0.41-34.80)
Tumor involvement of resection margin	0.194	3.16 (0.56-17.93)	0.209	3.13 (0.53-18.54)
Hemoglobin	0.026	0.32 (0.11-0.87)	0.463	0.46 (0.14-1.57)
PLR	0.741	0.82 (0.25-2.66)	0.896	0.92 (0.29-2.99)
Albumin	0.759	0.84 (0.27-2.61)	0.675	0.78 (0.24-2.52)
FDG uptake	0.197	4.29 (0.47-39.12)
Tmax			0.059	2.89 (0.96-8.72)
BLR	0.025	10.39 (1.34-80.33)	0.022	10.87 (1.42-83.31)

FDG: F-18 fluorodexoyglucose; RFS: Recurrence-free survival; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CRP: C-reactive protein; PET/CT: Positron emission tomography/computed tomography; BM: Bone marrow; BLR: BM-to-liver uptake ratio.