Effect of prior malignancy on the prognosis of gastric cancer and somatic mutation

Table 1 Baseline characteristics of patients diagnosed with gastric cancer (n = 35, 492) by prior cancer status

Characteristics	No previous cancer, n = 31491 (88.73%)		With prior cancer, n = 4001 (11.27%)		P value
Age (yr)					< 0.001
< 65	13160	(41.79%)	714	(17.85%)
≥ 65	18331	(58.21%)	3287	(82.15%)
Sex					< 0.001
Male	19479	(61.86%)	2777	(69.41%)
Female	12012	(38.14%)	1224	(30.59%)
Race					< 0.001
White	22087	(70.14%)	2926	(73.13%)
Black	4090	(12.99%)	555	(13.87%)
AI/AN	285	(0.91%)	16	(0.4%)
AP	4898	(15.55%)	504	(12.6%)
Unknown	131	(0.42%)	0	(0%)
Marital status					< 0.001
Married	17571	(55.80%)	2366	(59.14%)
Unmarried	12473	(39.61%)	1416	(35.39%)
Unknown	1447	(4.59%)	219	(5.47%)
Site
Cardia and Fundus	10537	(33.46%)	1486	(37.14%)
Body of stomach	6340	(20.13%)	844	(21.09%)
Antrum and Pylorus	7370	(23.40%)	862	(21.54%)
Stomach, NOS	7244	(23.00%)	809	(20.22%)
Lymph nodes examined					< 0.001
No examined	16884	(53.62%)	2287	(57.16%)
1-15	7020	(22.29%)	909	(22.72%)
≥ 16	6338	(20.13%)	686	(17.15%)
Unknown	1249	(3.97%)	119	(2.97%)
Positive lymph nodes					< 0.001
0	4914	(36.79%)	693	(43.45%)
1-2	2599	(19.46%)	327	(20.50%)
3-6	2399	(17.96%)	276	(17.30%)
7-15	2355	(17.63%)	207	(12.98%)
≥ 16	1066	(7.98%)	89	(5.58%)
Unknown	25	(0.19%)	3	(0.19%)
SEER stage					< 0.001
Localized	7209	(22.89%)	1190	(29.74%)
Regional	8978	(28.51%)	1051	(26.27%)
Distant	12615	(40.06%)	1242	(31.04%)
Unstaged	2689	(8.54%)	518	(12.95%)
Grade					< 0.001
G1	1087	(3.45%)	181	(4.52%)
G2	7012	(22.27%)	1027	(25.67%)
G3	18112	(57.51%)	2108	(52.69%)
G4	567	(1.80%)	68	(1.70%)
Unknown	4713	(14.97%)	617	(15.42%)
Surgery					0.088
No	16692	(53.01%)	2194	(54.84%)
Yes	14630	(46.46%)	1785	(44.61%)
Unknown	169	(0.54%)	22	(0.55%)
Radiation					< 0.001
None	23413	(74.35 %)	3098	(77.43%)
Radiation	7789	(24.73%)	866	(21.64%)
Unknown	289	(0.92%)	37	(0.92%)
Chemotherapy					< 0.001
No/Known	17189	(54.58%)	2569	(64.21%)
Chemotherapy	14302	(45.42%)	1432	(35.79%)

AI/AN: American Indian/Alaska Native; AP: Asian or Pacific Islander; G1: Well-differentiated; G2: Moderately differentiated; G3: Poorly differentiated; G4: Undifferentiated.

Table 2 Overall 3-year survival rate of gastric patients stratified by age

Prior initial cancer site	All-cause survival (95%CI)
	Overall	Age < 65 yr (%)	Age ≥ 65 yr (%)
No prior cancer	26.42 (25.90, 26.94)	28.95 (28.14, 29.77)	24.49 (23.82, 25.16)
With prior cancer	25.20 (23.80, 26.63)	30.12 (26.68, 33.62)	24.08 (22.55, 25.65)
Prostate	24.79 (21.39, 28.32)	23.33 (16.23, 31.21)	25.16 (21.35, 29.14)
Gastrointestinal	26.47 (23.96, 29.04)	31.13 (22.60, 40.03)	26.00 (23.38, 28.68)
Hematologic	28.06 (22.75, 33.58)	42.17 (31.11, 52.80)	22.16 (16.49, 28.38)
Breast	26.80 (22.96, 30.78)	33.27 (25.47, 41.25)	24.36 (20.04, 28.92)
Genitourinary	23.64 (20.14, 27.30)	34.29 (25.39, 43.35)	21.06 (17.36, 25.02)
Lung	19.32 (13.87, 25.45)	12.50 (3.95, 26.23)	20.83 (14.64, 27.79)
Other	22.90 (18.79, 27.26)	24.61 (16.44, 33.66)	22.33 (17.66, 27.35)

Table 3 Multivariable Cox regression analysis of survival in patients with gastric cancer¹

Characteristics	All-cause adjusted HR	P value	Cancer-specific adjusted HR	P value
Age (yr; vs < 65)
≥ 65	1.32 (1.28, 1.35)	< 0.001	1.25 (1.22, 1.29)	< 0.001
Sex (vs male)
Female	0.93 (0.91, 0.96)	< 0.001	0.95 (0.92, 0.98)	< 0.001
Race (vs white)
Black	1.09 (1.05, 1.13)	< 0.001	1.07 (1.03, 1.12)	< 0.001
AI/AN	1.14 (1.01, 1.29)	0.033	1.16 (1.02, 1.32)	0.023
AP	0.79 (0.76, 0.82)	< 0.001	0.79 (0.76, 0.82)	< 0.001
Marital status (vs married)
Unmarried	1.14 (1.12, 1.17)	< 0.001	1.11 (1.08, 1.14)	< 0.001
Gastric cancer site (vs cardia and fundus)
Body of stomach	0.96 (0.92, 0.99)	0.013	0.93 (0.90, 0.97)	< 0.001
Antrum and Pylorus	0.99 (0.96, 1.03)	0.727	0.97 (0.93, 1.01)	0.114
Lymph nodes examined (vs no examined)
1-15	0.73 (0.69, 0.77)	< 0.001	0.72 (0.68, 0.77)	< 0.001
≥ 16	0.65 (0.61, 0.68)	< 0.001	0.66 (0.62, 0.71)	< 0.001
Prior history of cancer (vs none)
Yes	1.01 (0.97, 1.05)	0.644	0.82 (0.78, 0.85)	< 0.001
SEER stage (vs localized)
Regional	2.34 (2.26, 2.44)	< 0.001	2.83 (2.70, 2.96)	< 0.001
Distant	3.43 (3.31, 3.57)	< 0.001	4.35 (4.16, 4.54)	< 0.001
Grade (vs G1)
G2	1.19 (1.10, 1.28)	< 0.001	1.27 (1.16, 1.38)	< 0.001
G3	1.56 (1.45, 1.67)	< 0.001	1.75 (1.61, 1.91)	< 0.001
G4	1.60 (1.43, 1.79)	< 0.001	1.85 (1.63, 2.09)	< 0.001
Surgery (vs none)
Yes	0.45 (0.43, 0.48)	< 0.001	0.44 (0.42, 0.47)	< 0.001
Radiation (vs none)
Radiation	0.92 (0.89, 0.95)	0.007	0.92 (0.89, 0.96)	< 0.001
Chemotherapy (vs none)
Chemotherapy	0.52 (0.51, 0.54)	< 0.001	0.53 (0.51, 0.55)	< 0.001

¹Adjusted for age, race, sex, marital status, grade, stage, size, radiation, surgery, chemotherapy. AI/AN: American Indian/Alaska Native; AP: Asian or Pacific Islander; CI: Confidence interval; G1: Well-differentiated; G2: Moderately differentiated; G3: Poorly differentiated; G4: Undifferentiated; HR: Hazard ratio.

Table 4 Multivariable Cox regression analysis of survival in gastric cancer patients stratified by age, stage, and timing of prior cancer (prior cancer vs < none)

Characteristics	All-cause survival (CI)	P value	Gastric cancer-specific survival (CI)	P value
Age (yr)
< 65	1.08 (1.00, 1.18)	0.064	0.77 (0.69, 0.85)	< 0.001
≥ 65	1.00 (0.96, 1.04)	0.843	0.83 (0.79, 0.87)	< 0.001
Stage
Localized	1.10 (1.02, 1.19)	0.012	0.82 (0.74, 0.91)	< 0.001
Regional	0.99 (0.92, 1.06)	0.777	0.84 (0.78, 0.92)	< 0.001
Distant	0.92 (0.87, 0.98)	0.014	0.79 (0.73, 0.85)	< 0.001
Timing of prior cancer
< 5	1.03 (0.98, 1.09)	0.275	0.77 (0.72, 0.82)	< 0.001
5-10	0.98 (0.92, 1.04)	0.525	0.84 (0.78, 0.90)	< 0.001
≥ 10	1.01 (0.94, 1.08)	0.811	0.88 (0.81, 0.95)	0.001

Adjusted for age, race, sex, marital status, grade, stage, size, radiation, surgery, chemotherapy. AHR: Adjusted hazard ratio; CI: Confidence interval.