World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 13, Number 2, April 2022, pages 69-83

Long-Term Cardiac Disease- and Cancer-Associated Mortalities in Patients With Non-Metastatic Stomach Adenocarcinoma Receiving Resection and Chemotherapy: A Large Competing-Risk Population-Based Cohort Study

Figure 1. Cumulative incidence function curves illustrating mortality from gastric cancer, other cancers, diseases of heart, and other non-cancer diseases in patients with gastric adenocarcinoma undergoing resection (and chemotherapy).

Figure 2. Cumulative incidence function curves illustrating mortality from gastric cancer, other cancers, diseases of heart, and other non-cancer diseases in patients with gastric adenocarcinoma undergoing resection, by age at diagnosis.

Figure 3. Cumulative incidence function curves illustrating mortality from gastric cancer, other cancers, diseases of heart, and other non-cancer diseases in patients with gastric adenocarcinoma undergoing resection and chemotherapy, by age at diagnosis.

**Table 1.** Demographic and Clinicopathologic Characteristics at Diagnosis of Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection (and Chemotherapy), 2004 - 2016^a
Variable	Category/comment	Resection	Resection and chemotherapy
^aCategorical data are shown as count (percentage (%)), and continuous data as mean ± standard deviation, median (interquartile range). Records are complete otherwise specified below. ^bLesser curvature, greater curvature, overlapping lesion of stomach, and stomach (NOS). ^cUnknown tumor local invasion: resection, 300 (1%); resection and chemotherapy, 210 (2%). ^dUnknown positive lymph node count: resection, 358 (2%); resection and chemotherapy, 257 (2%). ^eUnknown differentiation grade: 1,555 (7%); 621 (6%). ^fUnknown size: 2,948 (14%); 1,523 (14%). ^gThe other category for the non-surgical variables was “no/unknown”, considering the low sensitivity. ^hShown as median (interquartile range) and computed using the reverse Kaplan-Meier method. NOS: not otherwise specified.
N		21,257	10,718
Year of diagnosis	2010 - 2016	10,984 (52)	6,142 (57)
Sex	Male	13,485 (63)	7,237 (68)
Age (years)	As continuous	66 ± 13, 67 (57 - 76)	62 ± 12, 62 (54 - 70)
	< 50	2,399 (11)	1,730 (16)
	50 - 59	3,969 (19)	2,618 (24)
	60 - 69	5,800 (27)	3,451 (32)
	70 - 79	5,752 (27)	2,391 (22)
	≥ 80	3,337 (16)	528 (5)
Ethnicity	White	14,245 (67)	7,402 (69)
	Black	2,661 (13)	1,322 (12)
	American Indian/Alaska Native	181 (1)	107 (1)
	Asian/Pacific Islander	4,092 (19)	1,851 (17)
	Other unspecified/unknown	78 (< 1)	36 (< 1)
Tumor location	Gastric cardia	6,357 (30)	3,927 (37)
	Gastric fundus/body	2,537 (12)	1,152 (11)
	Gastric antrum/pylorus	6,106 (29)	2,614 (24)
	Other^b	6,257 (29)	3,025 (28)
Tumor local invasion^c	Lamina propria/submucosa	5,887 (28)	970 (9)
	Muscularis propria/subserosa	10,087 (48)	6,354 (60)
	Serosa	3,693 (18)	2,385 (23)
	Adjacent structures	1,290 (6)	799 (8)
Positive lymph node count^c	As continuous	3 ± 6, 1 (0 - 4)	5 ± 7, 2 (0 - 6)
	0	10,488 (50)	3,492 (33)
	1 - 2	3,420 (16)	2,255 (22)
	3 - 6	3,168 (15)	2,132 (20)
	7 - 15	2,720 (13)	1,855 (18)
	≥ 16	1,103 (5)	727 (7)
Tumor differentiation grade^e	Well	1,204 (6)	281 (3)
	Intermediate	5,618 (29)	2,438 (24)
	Poor/undifferentiated	12,880 (65)	7,378 (73)
Tumor size^f (cm)	As continuous	4.6 ± 4.1; 4.0 (2.2 - 6.0)	5.3 ± 4.2; 4.5 (3.0 - 6.5)
	< 2	3,298 (18)	795 (9)
	2 - 4	5,336 (29)	2,565 (28)
	4 - 6	4,707 (26)	2,799 (30)
	6 - 8	2,652 (14)	1,628 (18)
	≥ 8	2,316 (13)	1,408 (15)
Resection type	Partial/subtotal gastrectomy	14,182 (67)	6,764 (63)
	Total/near-total gastrectomy	4,365 (21)	2,741 (26)
	Gastrectomy (NOS)	2,710 (13)	1,213 (11)
Chemotherapy^g	Yes	10,718 (50)	10,718 (100)
Radiotherapy^g	Yes	7,410 (35)	6,981 (65)
Follow-up months^h	As continuous	73 (36 - 113)	66 (32 - 105)
Accumulated follow-up (person-years)	As continuous	73,711	34,265
Cause of death	Alive	9,953 (47)	4,943 (46)
	Gastric cancer	8,164 (38)	4,769 (45)
	Other cancers	676 (3)	285 (3)
	Diseases of heart	764 (4)	160 (1)
	Other non-cancer diseases	1,700 (8)	561 (5)

Table 1. Demographic and Clinicopathologic Characteristics at Diagnosis of Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection (and Chemotherapy), 2004 - 2016^a

Variable

Category/comment

Resection

Resection and chemotherapy

^aCategorical data are shown as count (percentage (%)), and continuous data as mean ± standard deviation, median (interquartile range). Records are complete otherwise specified below. ^bLesser curvature, greater curvature, overlapping lesion of stomach, and stomach (NOS). ^cUnknown tumor local invasion: resection, 300 (1%); resection and chemotherapy, 210 (2%). ^dUnknown positive lymph node count: resection, 358 (2%); resection and chemotherapy, 257 (2%). ^eUnknown differentiation grade: 1,555 (7%); 621 (6%). ^fUnknown size: 2,948 (14%); 1,523 (14%). ^gThe other category for the non-surgical variables was “no/unknown”, considering the low sensitivity. ^hShown as median (interquartile range) and computed using the reverse Kaplan-Meier method. NOS: not otherwise specified.

21,257

10,718

Year of diagnosis

2010 - 2016

10,984 (52)

6,142 (57)

Sex

Male

13,485 (63)

7,237 (68)

Age (years)

As continuous

66 ± 13, 67 (57 - 76)

62 ± 12, 62 (54 - 70)

< 50

2,399 (11)

1,730 (16)

50 - 59

3,969 (19)

2,618 (24)

60 - 69

5,800 (27)

3,451 (32)

70 - 79

5,752 (27)

2,391 (22)

≥ 80

3,337 (16)

528 (5)

Ethnicity

White

14,245 (67)

7,402 (69)

Black

2,661 (13)

1,322 (12)

American Indian/Alaska Native

181 (1)

107 (1)

Asian/Pacific Islander

4,092 (19)

1,851 (17)

Other unspecified/unknown

78 (< 1)

36 (< 1)

Tumor location

Gastric cardia

6,357 (30)

3,927 (37)

Gastric fundus/body

2,537 (12)

1,152 (11)

Gastric antrum/pylorus

6,106 (29)

2,614 (24)

Other^b

6,257 (29)

3,025 (28)

Tumor local invasion^c

Lamina propria/submucosa

5,887 (28)

970 (9)

Muscularis propria/subserosa

10,087 (48)

6,354 (60)

Serosa

3,693 (18)

2,385 (23)

Adjacent structures

1,290 (6)

799 (8)

Positive lymph node count^c

As continuous

3 ± 6, 1 (0 - 4)

5 ± 7, 2 (0 - 6)

10,488 (50)

3,492 (33)

1 - 2

3,420 (16)

2,255 (22)

3 - 6

3,168 (15)

2,132 (20)

7 - 15

2,720 (13)

1,855 (18)

≥ 16

1,103 (5)

727 (7)

Tumor differentiation grade^e

Well

1,204 (6)

281 (3)

Intermediate

5,618 (29)

2,438 (24)

Poor/undifferentiated

12,880 (65)

7,378 (73)

Tumor size^f (cm)

As continuous

4.6 ± 4.1; 4.0 (2.2 - 6.0)

5.3 ± 4.2; 4.5 (3.0 - 6.5)

< 2

3,298 (18)

795 (9)

2 - 4

5,336 (29)

2,565 (28)

4 - 6

4,707 (26)

2,799 (30)

6 - 8

2,652 (14)

1,628 (18)

≥ 8

2,316 (13)

1,408 (15)

Resection type

Partial/subtotal gastrectomy

14,182 (67)

6,764 (63)

Total/near-total gastrectomy

4,365 (21)

2,741 (26)

Gastrectomy (NOS)

2,710 (13)

1,213 (11)

Chemotherapy^g

Yes

10,718 (50)

10,718 (100)

Radiotherapy^g

Yes

7,410 (35)

6,981 (65)

Follow-up months^h

As continuous

73 (36 - 113)

66 (32 - 105)

Accumulated follow-up (person-years)

As continuous

73,711

34,265

Cause of death

Alive

9,953 (47)

4,943 (46)

Gastric cancer

8,164 (38)

4,769 (45)

Other cancers

676 (3)

285 (3)

Diseases of heart

764 (4)

160 (1)

Other non-cancer diseases

1,700 (8)

561 (5)

**Table 2.** Cumulative Incidences of Mortality (%) and 95% Confidence Intervals due to Diseases of Heart and Gastric Cancer in Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection (and Chemotherapy), Overall and Stratified by Patient Age
Group	Time	Resection	Resection and chemotherapy
Overall	6 months	0.7 (0.6 - 0.8)	7.8 (7.5 - 8.2)	0.2 (0.1 - 0.3)	4.4 (4.0 - 4.8)
	1 year	1.1 (1.0 - 1.2)	16.4 (15.9 - 16.9)	0.4 (0.3 - 0.6)	15.0 (14.3 - 15.7)
	2 years	1.7 (1.5 - 1.9)	29.0 (28.4 - 29.7)	0.8 (0.6 - 1.0)	32.8 (31.9 - 33.8)
	3 years	2.2 (2.0 - 2.5)	36.0 (35.3 - 36.6)	1.0 (0.9 - 1.3)	42.5 (41.5 - 43.5)
	5 years	3.0 (2.8 - 3.3)	42.0 (41.3 - 42.7)	1.4 (1.2 - 1.7)	50.7 (49.6 - 51.8)
	8 years	4.4 (4.1 - 4.7)	45.2 (44.5 - 46.0)	2.0 (1.6 - 2.3)	54.6 (53.5 - 55.8)
< 60 years	6 months	0.1 (0.1 - 0.3)	4.3 (3.8 - 4.8)	0.0 (0.0 - 0.2)	3.6 (3.1 - 4.2)
	1 year	0.3 (0.2 - 0.5)	13.2 (12.4 - 14.1)	0.2 (0.1 - 0.3)	13.9 (12.9 - 15.0)
	2 years	0.5 (0.3 - 0.7)	27.7 (26.6 - 28.9)	0.3 (0.2 - 0.6)	32.0 (30.5 - 33.4)
	3 years	0.6 (0.4 - 0.8)	36.1 (34.8 - 37.4)	0.4 (0.3 - 0.7)	42.6 (41.0 - 44.2)
	5 years	0.9 (0.7 - 1.2)	43.4 (42.0 - 44.8)	0.6 (0.4 - 0.9)	51.7 (50.0 - 53.4)
	8 years	1.4 (1.1 - 1.8)	47.4 (45.9 - 48.8)	0.8 (0.5 - 1.2)	56.1 (54.3 - 57.9)
60 - 69 years	6 months	0.3 (0.2 - 0.5)	6.2 (5.6 - 6.8)	0.1 (0.1 - 0.3)	4.1 (3.5 - 4.9)
	1 year	0.6 (0.4 - 0.8)	14.2 (13.3 - 15.1)	0.4 (0.2 - 0.7)	14.0 (12.9 - 15.3)
	2 years	1.0 (0.7 - 1.3)	27.2 (26.0 - 28.4)	0.7 (0.4 - 1.0)	31.6 (30.0 - 33.3)
	3 years	1.4 (1.1 - 1.8)	34.2 (32.9 - 35.5)	1.1 (0.7 - 1.5)	40.7 (38.9 - 42.5)
	5 years	1.9 (1.6 - 2.4)	40.4 (39.0 - 41.8)	1.4 (1.0 - 1.9)	48.7 (46.7 - 50.5)
	8 years	2.6 (2.1 - 3.1)	43.3 (41.9 - 44.8)	1.6 (1.1 - 2.2)	52.1 (50.0 - 54.0)
70 - 79 years	6 months	1.0 (0.8 - 1.3)	9.4 (8.7 - 10.2)	0.4 (0.2 - 0.8)	5.5 (4.6 - 6.5)
	1 year	1.5 (1.2 - 1.9)	17.8 (16.8 - 18.8)	0.8 (0.5 - 1.2)	17.3 (15.8 - 18.9)
	2 years	2.3 (2.0 - 2.8)	29.4 (28.2 - 30.7)	1.6 (1.1 - 2.2)	34.7 (32.7 - 36.7)
	3 years	2.9 (2.5 - 3.4)	35.7 (34.4 - 37.1)	2.1 (1.5 - 2.8)	44.0 (41.8 - 46.1)
	5 years	3.8 (3.2 - 4.3)	41.1 (39.8 - 42.5)	2.6 (1.9 - 3.3)	50.9 (48.6 - 53.2)
	8 years	5.3 (4.6 - 6.1)	44.3 (42.9 - 45.8)	3.7 (2.8 - 4.8)	55.4 (52.9 - 57.7)
≥ 80 years	6 months	1.7 (1.3 - 2.2)	14.7 (13.5 - 15.9)	0.6 (0.2 - 1.6)	8.2 (6.0 - 10.7)
	1 year	2.7 (2.2 - 3.3)	24.0 (22.5 - 25.5)	0.8 (0.3 - 1.9)	20.4 (17.0 - 24.0)
	2 years	4.2 (3.5 - 4.9)	34.0 (32.4 - 35.7)	1.2 (0.5 - 2.5)	40.0 (35.3 - 44.0)
	3 years	5.5 (4.7 - 6.4)	39.2 (37.5 - 40.9)	1.2 (0.5 - 2.5)	47.2 (42.5 - 51.6)
	5 years	7.4 (6.5 - 8.4)	43.8 (42.0 - 45.6)	3.0 (1.6 - 5.2)	54.2 (49.3 - 58.8)
	8 years	11.1 (9.8 - 12.4)	46.1 (44.3 - 48.0)	6.5 (3.9 - 9.9)	55.5 (50.5 - 60.1)

Table 2. Cumulative Incidences of Mortality (%) and 95% Confidence Intervals due to Diseases of Heart and Gastric Cancer in Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection (and Chemotherapy), Overall and Stratified by Patient Age

Group

Time

Resection

Resection and chemotherapy

Heart diseases

Gastric cancer

Heart diseases

Gastric cancer

Overall

6 months

0.7 (0.6 - 0.8)

7.8 (7.5 - 8.2)

0.2 (0.1 - 0.3)

4.4 (4.0 - 4.8)

1 year

1.1 (1.0 - 1.2)

16.4 (15.9 - 16.9)

0.4 (0.3 - 0.6)

15.0 (14.3 - 15.7)

2 years

1.7 (1.5 - 1.9)

29.0 (28.4 - 29.7)

0.8 (0.6 - 1.0)

32.8 (31.9 - 33.8)

3 years

2.2 (2.0 - 2.5)

36.0 (35.3 - 36.6)

1.0 (0.9 - 1.3)

42.5 (41.5 - 43.5)

5 years

3.0 (2.8 - 3.3)

42.0 (41.3 - 42.7)

1.4 (1.2 - 1.7)

50.7 (49.6 - 51.8)

8 years

4.4 (4.1 - 4.7)

45.2 (44.5 - 46.0)

2.0 (1.6 - 2.3)

54.6 (53.5 - 55.8)

< 60 years

6 months

0.1 (0.1 - 0.3)

4.3 (3.8 - 4.8)

0.0 (0.0 - 0.2)

3.6 (3.1 - 4.2)

1 year

0.3 (0.2 - 0.5)

13.2 (12.4 - 14.1)

0.2 (0.1 - 0.3)

13.9 (12.9 - 15.0)

2 years

0.5 (0.3 - 0.7)

27.7 (26.6 - 28.9)

0.3 (0.2 - 0.6)

32.0 (30.5 - 33.4)

3 years

0.6 (0.4 - 0.8)

36.1 (34.8 - 37.4)

0.4 (0.3 - 0.7)

42.6 (41.0 - 44.2)

5 years

0.9 (0.7 - 1.2)

43.4 (42.0 - 44.8)

0.6 (0.4 - 0.9)

51.7 (50.0 - 53.4)

8 years

1.4 (1.1 - 1.8)

47.4 (45.9 - 48.8)

0.8 (0.5 - 1.2)

56.1 (54.3 - 57.9)

60 - 69 years

6 months

0.3 (0.2 - 0.5)

6.2 (5.6 - 6.8)

0.1 (0.1 - 0.3)

4.1 (3.5 - 4.9)

1 year

0.6 (0.4 - 0.8)

14.2 (13.3 - 15.1)

0.4 (0.2 - 0.7)

14.0 (12.9 - 15.3)

2 years

1.0 (0.7 - 1.3)

27.2 (26.0 - 28.4)

0.7 (0.4 - 1.0)

31.6 (30.0 - 33.3)

3 years

1.4 (1.1 - 1.8)

34.2 (32.9 - 35.5)

1.1 (0.7 - 1.5)

40.7 (38.9 - 42.5)

5 years

1.9 (1.6 - 2.4)

40.4 (39.0 - 41.8)

1.4 (1.0 - 1.9)

48.7 (46.7 - 50.5)

8 years

2.6 (2.1 - 3.1)

43.3 (41.9 - 44.8)

1.6 (1.1 - 2.2)

52.1 (50.0 - 54.0)

70 - 79 years

6 months

1.0 (0.8 - 1.3)

9.4 (8.7 - 10.2)

0.4 (0.2 - 0.8)

5.5 (4.6 - 6.5)

1 year

1.5 (1.2 - 1.9)

17.8 (16.8 - 18.8)

0.8 (0.5 - 1.2)

17.3 (15.8 - 18.9)

2 years

2.3 (2.0 - 2.8)

29.4 (28.2 - 30.7)

1.6 (1.1 - 2.2)

34.7 (32.7 - 36.7)

3 years

2.9 (2.5 - 3.4)

35.7 (34.4 - 37.1)

2.1 (1.5 - 2.8)

44.0 (41.8 - 46.1)

5 years

3.8 (3.2 - 4.3)

41.1 (39.8 - 42.5)

2.6 (1.9 - 3.3)

50.9 (48.6 - 53.2)

8 years

5.3 (4.6 - 6.1)

44.3 (42.9 - 45.8)

3.7 (2.8 - 4.8)

55.4 (52.9 - 57.7)

≥ 80 years

6 months

1.7 (1.3 - 2.2)

14.7 (13.5 - 15.9)

0.6 (0.2 - 1.6)

8.2 (6.0 - 10.7)

1 year

2.7 (2.2 - 3.3)

24.0 (22.5 - 25.5)

0.8 (0.3 - 1.9)

20.4 (17.0 - 24.0)

2 years

4.2 (3.5 - 4.9)

34.0 (32.4 - 35.7)

1.2 (0.5 - 2.5)

40.0 (35.3 - 44.0)

3 years

5.5 (4.7 - 6.4)

39.2 (37.5 - 40.9)

1.2 (0.5 - 2.5)

47.2 (42.5 - 51.6)

5 years

7.4 (6.5 - 8.4)

43.8 (42.0 - 45.6)

3.0 (1.6 - 5.2)

54.2 (49.3 - 58.8)

8 years

11.1 (9.8 - 12.4)

46.1 (44.3 - 48.0)

6.5 (3.9 - 9.9)

55.5 (50.5 - 60.1)

**Table 3.** Fine-Gray Subdistribution and Cause-Specific Hazard Ratios and 95% Confidence Intervals for Heart- and Gastric Cancer-Associated Mortalities Among Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection^a
Variable	Subdistribution hazard ratios	Cause-specific hazard ratios
*Statistically significant P values. ^aAdjusted for: period of diagnosis, sex, age group, ethnicity, tumor location, local invasion, positive lymph node number, differentiation grade, and resection type. ^bLesser curvature, greater curvature, overlapping lesion of stomach, and stomach (NOS). NOS: not otherwise specified.
Period of diagnosis	Reference: 2010 - 2016
2004 - 2009	1.66 (1.40 - 1.96)	< 0.001*		1.13 (1.08 - 1.18)	< 0.001*		1.24 (1.04 - 1.49)	0.019*		1.10 (1.05 - 1.15)	< 0.001*
Sex	Reference: male
Female	0.88 (0.76 - 1.03)	0.117		1.00 (0.95 - 1.05)	0.871		0.83 (0.70 - 0.97)	0.019*		0.97 (0.93 - 1.02)	0.295
Age group	Reference: 60 - 69 years
< 50 years	0.36 (0.21 - 0.60)	< 0.001*	< 0.001*	0.90 (0.83 - 0.97)	0.006*	< 0.001*	0.31 (0.19 - 0.53)	< 0.001*	< 0.001*	0.85 (0.79 - 0.92)	< 0.001*	< 0.001*
50 - 59 years	0.58 (0.41 - 0.82)	0.002*		0.94 (0.88 - 1.01)	0.080		0.54 (0.38 - 0.77)	0.001*		0.92 (0.86 - 0.99)	0.017*
70 - 79 years	1.99 (1.59 - 2.49)	< 0.001*		1.22 (1.14 - 1.29)	< 0.001*		2.39 (1.91 - 3.00)	< 0.001*		1.33 (1.25 - 1.42)	< 0.001*
≥ 80 years	3.88 (3.11 - 4.84)	< 0.001*		1.49 (1.38 - 1.61)	< 0.001*		6.06 (4.83 - 7.61)	< 0.001*		1.79 (1.67 - 1.93)	< 0.001*
Ethnicity	Reference: White
Black	1.31 (1.05 - 1.63)	0.017*	< 0.001*	0.99 (0.92 - 1.06)	0.735	< 0.001*	1.41 (1.13 - 1.75)	0.003*	< 0.001*	1.04 (0.97 - 1.11)	0.298	< 0.001*
American Indian/Alaska Native	1.54 (0.72 - 3.31)	0.269		1.18 (0.91 - 1.52)	0.225		1.95 (0.92 - 4.12)	0.082		1.31 (1.04 - 1.65)	0.021*
Asian/Pacific Islander	0.81 (0.66 - 0.99)	0.043*		0.78 (0.74 - 0.83)	< 0.001*		0.73 (0.59 - 0.89)	0.002*		0.75 (0.70 - 0.80)	< 0.001*
Tumor location	Reference: gastric cardia
Gastric fundus/body	1.23 (0.93 - 1.63)	0.155	0.043*	0.70 (0.65 - 0.76)	< 0.001*	< 0.001*	1.13 (0.85 - 1.49)	0.413	0.436	0.70 (0.64 - 0.76)	< 0.001*	< 0.001*
Gastric antrum/pylorus	1.39 (1.11 - 1.75)	0.004*		0.74 (0.69 - 0.79)	< 0.001*		1.21 (0.96 - 1.53)	0.102		0.73 (0.68 - 0.78)	< 0.001*
Other^b	1.24 (0.99 - 1.56)	0.064		0.74 (0.70 - 0.79)	< 0.001*		1.11 (0.88 - 1.40)	0.362		0.74 (0.69 - 0.78)	< 0.001*
Tumor local invasion	Reference: muscularis propria/subserosa
Lamina propria/submucosa	1.14 (0.95 - 1.37)	0.150	0.025*	0.44 (0.41 - 0.48)	< 0.001*	< 0.001*	0.95 (0.79 - 1.14)	0.553	0.569	0.43 (0.40 - 0.47)	< 0.001*	< 0.001*
Serosa	0.76 (0.59 - 0.98)	0.034*		1.44 (1.37 - 1.53)	< 0.001*		0.99 (0.78 - 1.28)	0.960		1.49 (1.41 - 1.58)	< 0.001*
Adjacent structures	0.77 (0.52 - 1.14)	0.197		1.94 (1.78 - 2.11)	< 0.001*		1.27 (0.86 - 1.88)	0.232		2.07 (1.92 - 2.24)	< 0.001*
Positive lymph node count	Reference: 0
1 - 2	0.82 (0.66 - 1.03)	0.084	0.003*	1.66 (1.55 - 1.78)	< 0.001*	< 0.001*	0.96 (0.77 - 1.20)	0.736	0.374	1.68 (1.57 - 1.81)	< 0.001*	< 0.001*
3 - 6	0.66 (0.51 - 0.86)	0.002*		2.10 (1.96 - 2.25)	< 0.001*		0.88 (0.68 - 1.14)	0.324		2.18 (2.04 - 2.34)	< 0.001*
7 - 15	0.71 (0.53 - 0.96)	0.023*		2.81 (2.61 - 3.02)	< 0.001*		1.23 (0.92 - 1.65)	0.156		3.05 (2.85 - 3.28)	< 0.001*
≥ 16	0.52 (0.31 - 0.86)	0.012*		3.69 (3.36 - 4.05)	< 0.001*		1.12 (0.68 - 1.86)	0.657		4.15 (3.79 - 4.54)	< 0.001*
Differentiation	Reference: poor/undifferentiated
Well	1.11 (0.84 - 1.47)	0.449	0.734	0.67 (0.58 - 0.77)	< 0.001*	< 0.001*	0.99 (0.74 - 1.31)	0.920	0.681	0.65 (0.57 - 0.75)	< 0.001*	< 0.001*
Intermediate	1.04 (0.88 - 1.22)	0.674		0.75 (0.71 - 0.79)	< 0.001*		0.93 (0.79 - 1.10)	0.388		0.73 (0.69 - 0.78)	< 0.001*
Resection type	Reference: partial/subtotal gastrectomy
Total/near-total gastrectomy	1.04 (0.84 - 1.30)	0.712	0.020*	1.16 (1.09 - 1.22)	< 0.001*	< 0.001*	1.12 (0.90 - 1.40)	0.306	0.001*	1.17 (1.11 - 1.24)	< 0.001*	< 0.001*
Gastrectomy (NOS)	1.40 (1.11 - 1.78)	0.005*		1.18 (1.09 - 1.28)	< 0.001*		1.63 (1.27 - 2.08)	< 0.001*		1.22 (1.13 - 1.32)	< 0.001*

Table 3. Fine-Gray Subdistribution and Cause-Specific Hazard Ratios and 95% Confidence Intervals for Heart- and Gastric Cancer-Associated Mortalities Among Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection^a

Variable

Subdistribution hazard ratios

Cause-specific hazard ratios

Heart diseases

P_trend

Gastric cancer

P_trend

Heart diseases

P_trend

Gastric cancer

P_trend

*Statistically significant P values. ^aAdjusted for: period of diagnosis, sex, age group, ethnicity, tumor location, local invasion, positive lymph node number, differentiation grade, and resection type. ^bLesser curvature, greater curvature, overlapping lesion of stomach, and stomach (NOS). NOS: not otherwise specified.

Period of diagnosis

Reference: 2010 - 2016

2004 - 2009

1.66 (1.40 - 1.96)

< 0.001*

1.13 (1.08 - 1.18)

< 0.001*

1.24 (1.04 - 1.49)

0.019*

1.10 (1.05 - 1.15)

< 0.001*

Sex

Reference: male

Female

0.88 (0.76 - 1.03)

0.117

1.00 (0.95 - 1.05)

0.871

0.83 (0.70 - 0.97)

0.019*

0.97 (0.93 - 1.02)

0.295

Age group

Reference: 60 - 69 years

< 50 years

0.36 (0.21 - 0.60)

< 0.001*

0.90 (0.83 - 0.97)

0.006*

< 0.001*

0.31 (0.19 - 0.53)

< 0.001*

0.85 (0.79 - 0.92)

< 0.001*

50 - 59 years

0.58 (0.41 - 0.82)

0.002*

0.94 (0.88 - 1.01)

0.080

0.54 (0.38 - 0.77)

0.001*

0.92 (0.86 - 0.99)

0.017*

70 - 79 years

1.99 (1.59 - 2.49)

< 0.001*

1.22 (1.14 - 1.29)

< 0.001*

2.39 (1.91 - 3.00)

< 0.001*

1.33 (1.25 - 1.42)

< 0.001*

≥ 80 years

3.88 (3.11 - 4.84)

< 0.001*

1.49 (1.38 - 1.61)

< 0.001*

6.06 (4.83 - 7.61)

< 0.001*

1.79 (1.67 - 1.93)

< 0.001*

Ethnicity

Reference: White

Black

1.31 (1.05 - 1.63)

0.017*

< 0.001*

0.99 (0.92 - 1.06)

0.735

< 0.001*

1.41 (1.13 - 1.75)

0.003*

< 0.001*

1.04 (0.97 - 1.11)

0.298

< 0.001*

American Indian/Alaska Native

1.54 (0.72 - 3.31)

0.269

1.18 (0.91 - 1.52)

0.225

1.95 (0.92 - 4.12)

0.082

1.31 (1.04 - 1.65)

0.021*

Asian/Pacific Islander

0.81 (0.66 - 0.99)

0.043*

0.78 (0.74 - 0.83)

< 0.001*

0.73 (0.59 - 0.89)

0.002*

0.75 (0.70 - 0.80)

< 0.001*

Tumor location

Reference: gastric cardia

Gastric fundus/body

1.23 (0.93 - 1.63)

0.155

0.043*

0.70 (0.65 - 0.76)

< 0.001*

1.13 (0.85 - 1.49)

0.413

0.436

0.70 (0.64 - 0.76)

< 0.001*

Gastric antrum/pylorus

1.39 (1.11 - 1.75)

0.004*

0.74 (0.69 - 0.79)

< 0.001*

1.21 (0.96 - 1.53)

0.102

0.73 (0.68 - 0.78)

< 0.001*

Other^b

1.24 (0.99 - 1.56)

0.064

0.74 (0.70 - 0.79)

< 0.001*

1.11 (0.88 - 1.40)

0.362

0.74 (0.69 - 0.78)

< 0.001*

Tumor local invasion

Reference: muscularis propria/subserosa

Lamina propria/submucosa

1.14 (0.95 - 1.37)

0.150

0.025*

0.44 (0.41 - 0.48)

< 0.001*

0.95 (0.79 - 1.14)

0.553

0.569

0.43 (0.40 - 0.47)

< 0.001*

Serosa

0.76 (0.59 - 0.98)

0.034*

1.44 (1.37 - 1.53)

< 0.001*

0.99 (0.78 - 1.28)

0.960

1.49 (1.41 - 1.58)

< 0.001*

Adjacent structures

0.77 (0.52 - 1.14)

0.197

1.94 (1.78 - 2.11)

< 0.001*

1.27 (0.86 - 1.88)

0.232

2.07 (1.92 - 2.24)

< 0.001*

Positive lymph node count

Reference: 0

1 - 2

0.82 (0.66 - 1.03)

0.084

0.003*

1.66 (1.55 - 1.78)

< 0.001*

0.96 (0.77 - 1.20)

0.736

0.374

1.68 (1.57 - 1.81)

< 0.001*

3 - 6

0.66 (0.51 - 0.86)

0.002*

2.10 (1.96 - 2.25)

< 0.001*

0.88 (0.68 - 1.14)

0.324

2.18 (2.04 - 2.34)

< 0.001*

7 - 15

0.71 (0.53 - 0.96)

0.023*

2.81 (2.61 - 3.02)

< 0.001*

1.23 (0.92 - 1.65)

0.156

3.05 (2.85 - 3.28)

< 0.001*

≥ 16

0.52 (0.31 - 0.86)

0.012*

3.69 (3.36 - 4.05)

< 0.001*

1.12 (0.68 - 1.86)

0.657

4.15 (3.79 - 4.54)

< 0.001*

Differentiation

Reference: poor/undifferentiated

Well

1.11 (0.84 - 1.47)

0.449

0.734

0.67 (0.58 - 0.77)

< 0.001*

0.99 (0.74 - 1.31)

0.920

0.681

0.65 (0.57 - 0.75)

< 0.001*

Intermediate

1.04 (0.88 - 1.22)

0.674

0.75 (0.71 - 0.79)

< 0.001*

0.93 (0.79 - 1.10)

0.388

0.73 (0.69 - 0.78)

< 0.001*

Resection type

Reference: partial/subtotal gastrectomy

Total/near-total gastrectomy

1.04 (0.84 - 1.30)

0.712

0.020*

1.16 (1.09 - 1.22)

< 0.001*

1.12 (0.90 - 1.40)

0.306

0.001*

1.17 (1.11 - 1.24)

< 0.001*

Gastrectomy (NOS)

1.40 (1.11 - 1.78)

0.005*

1.18 (1.09 - 1.28)

< 0.001*

1.63 (1.27 - 2.08)

< 0.001*

1.22 (1.13 - 1.32)

< 0.001*

**Table 4.** Fine-Gray Subdistribution and Cause-Specific Hazard Ratios and 95% Confidence Intervals for Heart- and Gastric Cancer-Associated Mortalities Among Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection and Chemotherapy^a
Variable	Subdistribution hazard ratios	Cause-specific hazard ratios
*Statistically significant P values. ^aAdjusted for: period of diagnosis, sex, age group, ethnicity, tumor location, local invasion, positive lymph node number, differentiation grade, and resection type. ^bLesser curvature, greater curvature, overlapping lesion of stomach, and stomach (NOS). NOS: not otherwise specified.
Period of diagnosis	Reference: 2010 - 2016
2004 - 2009	1.40 (1.00 - 1.95)	0.048*		1.11 (1.05 - 1.19)	0.001*		1.00 (0.69 - 1.45)	0.998		1.08 (1.02 - 1.15)	0.013*
Sex	Reference: male
Female	0.84 (0.58 - 1.22)	0.360		0.98 (0.92 - 1.05)	0.643		0.80 (0.55 - 1.15)	0.233		0.98 (0.92 - 1.05)	0.547
Age group	Reference: 60 - 69 years
< 50 years	0.25 (0.11 - 0.61)	0.002*	< 0.001*	0.95 (0.87 - 1.04)	0.247	< 0.001*	0.23 (0.10 - 0.55)	0.001*	< 0.001*	0.92 (0.84 - 1.00)	0.060	< 0.001*
50 - 59 years	0.50 (0.29 - 0.86)	0.012*		1.01 (0.93 - 1.09)	0.841		0.48 (0.28 - 0.83)	0.009*		0.99 (0.92 - 1.08)	0.869
70 - 79 years	1.88 (1.27 - 2.77)	0.002*		1.16 (1.07 - 1.26)	0.001*		2.23 (1.51 - 3.29)	< 0.001*		1.24 (1.14 - 1.35)	< 0.001*
≥ 80 years	2.72 (1.58 - 4.68)	< 0.001*		1.17 (1.01 - 1.37)	0.040*		3.76 (2.18 - 6.48)	< 0.001*		1.30 (1.13 - 1.50)	< 0.001*
Ethnicity	Reference: White
Black	1.63 (1.04 - 2.57)	0.035*	< 0.001*	0.97 (0.88 - 1.07)	0.544	< 0.001*	1.74 (1.11 - 2.71)	0.015*	0.010*	0.99 (0.90 - 1.09)	0.851	< 0.001*
American Indian/Alaska Native	1.69 (0.40 - 7.10)	0.477		1.19 (0.87 - 1.64)	0.283		2.28 (0.55 - 9.35)	0.255		1.31 (0.99 - 1.74)	0.061
Asian/Pacific Islander	0.70 (0.41 - 1.17)	0.173		0.79 (0.73 - 0.86)	< 0.001*		0.61 (0.36 - 1.01)	0.057		0.76 (0.70 - 0.83)	< 0.001*
Tumor location	Reference: gastric cardia
Gastric fundus/body	0.97 (0.52 - 1.81)	0.912	0.723	0.69 (0.62 - 0.77)	< 0.001*	< 0.001*	0.78 (0.42 - 1.44)	0.423	0.655	0.66 (0.59 - 0.74)	< 0.001*	< 0.001*
Gastric antrum/pylorus	1.18 (0.76 - 1.83)	0.454		0.75 (0.68 - 0.81)	< 0.001*		0.94 (0.59 - 1.49)	0.794		0.72 (0.66 - 0.79)	< 0.001*
Other^b	0.92 (0.58 - 1.47)	0.741		0.75 (0.69 - 0.82)	< 0.001*		0.77 (0.49 - 1.22)	0.270		0.73 (0.67 - 0.79)	< 0.001*
Tumor local invasion	Reference: muscularis propria/subserosa
Lamina propria/submucosa	1.20 (0.72 - 2.00)	0.481	0.331	0.59 (0.51 - 0.68)	< 0.001*	< 0.001*	1.04 (0.63 - 1.71)	0.887	0.702	0.59 (0.51 - 0.67)	< 0.001*	< 0.001*
Serosa	0.69 (0.44 - 1.09)	0.113		1.38 (1.29 - 1.48)	< 0.001*		0.85 (0.54 - 1.32)	0.461		1.42 (1.33 - 1.53)	< 0.001*
Adjacent structures	0.90 (0.47 - 1.74)	0.763		1.80 (1.62 - 2.00)	< 0.001*		1.30 (0.67 - 2.52)	0.436		1.87 (1.69 - 2.07)	< 0.001*
Positive lymph node count	Reference: 0
1 - 2	0.86 (0.56 - 1.31)	0.474	0.656	1.42 (1.29 - 1.55)	< 0.001*	< 0.001*	0.95 (0.62 - 1.45)	0.798	0.268	1.42 (1.30 - 1.56)	< 0.001*	< 0.001*
3 - 6	0.70 (0.44 - 1.14)	0.151		1.82 (1.66 - 1.99)	< 0.001*		0.83 (0.52 - 1.34)	0.452		1.86 (1.70 - 2.03)	< 0.001*
7 - 15	0.92 (0.57 - 1.50)	0.748		2.46 (2.24 - 2.69)	< 0.001*		1.45 (0.89 - 2.36)	0.137		2.61 (2.38 - 2.86)	< 0.001*
≥ 16	0.73 (0.35 - 1.56)	0.423		3.26 (2.89 - 3.67)	< 0.001*		1.47 (0.68 - 3.19)	0.324		3.59 (3.19 - 4.04)	< 0.001*
Differentiation	Reference: poor/undifferentiated
Well	1.18 (0.51 - 2.70)	0.704	0.898	0.80 (0.65 - 0.99)	0.038*	< 0.001*	1.16 (0.50 - 2.67)	0.732	0.647	0.80 (0.65 - 0.99)	0.038*	< 0.001*
Intermediate	0.96 (0.67 - 1.38)	0.829		0.73 (0.67 - 0.79)	< 0.001*		0.86 (0.59 - 1.25)	0.418		0.72 (0.66 - 0.78)	< 0.001*
Resection type	Reference: partial/subtotal gastrectomy
Total/near-total gastrectomy	0.99 (0.65 - 1.49)	0.942	0.185	1.22 (1.14 - 1.31)	< 0.001*	< 0.001*	1.06 (0.70 - 1.61)	0.791	0.121	1.23 (1.15 - 1.32)	< 0.001*	< 0.001*
Gastrectomy (NOS)	1.52 (0.96 - 2.43)	0.075		1.28 (1.16 - 1.42)	< 0.001*		1.68 (1.02 - 2.76)	0.041*		1.29 (1.17 - 1.43)	< 0.001*

Table 4. Fine-Gray Subdistribution and Cause-Specific Hazard Ratios and 95% Confidence Intervals for Heart- and Gastric Cancer-Associated Mortalities Among Patients With Non-Metastatic Gastric Adenocarcinoma Undergoing Resection and Chemotherapy^a

Variable

Subdistribution hazard ratios

Cause-specific hazard ratios

Heart diseases

P_trend

Gastric cancer

P_trend

Heart diseases

P_trend

Gastric cancer

P_trend

Period of diagnosis

Reference: 2010 - 2016

2004 - 2009

1.40 (1.00 - 1.95)

0.048*

1.11 (1.05 - 1.19)

0.001*

1.00 (0.69 - 1.45)

0.998

1.08 (1.02 - 1.15)

0.013*

Sex

Reference: male

Female

0.84 (0.58 - 1.22)

0.360

0.98 (0.92 - 1.05)

0.643

0.80 (0.55 - 1.15)

0.233

0.98 (0.92 - 1.05)

0.547

Age group

Reference: 60 - 69 years

< 50 years

0.25 (0.11 - 0.61)

0.002*

< 0.001*

0.95 (0.87 - 1.04)

0.247

< 0.001*

0.23 (0.10 - 0.55)

0.001*

< 0.001*

0.92 (0.84 - 1.00)

0.060

< 0.001*

50 - 59 years

0.50 (0.29 - 0.86)

0.012*

1.01 (0.93 - 1.09)

0.841

0.48 (0.28 - 0.83)

0.009*

0.99 (0.92 - 1.08)

0.869

70 - 79 years

1.88 (1.27 - 2.77)

0.002*

1.16 (1.07 - 1.26)

0.001*

2.23 (1.51 - 3.29)

< 0.001*

1.24 (1.14 - 1.35)

< 0.001*

≥ 80 years

2.72 (1.58 - 4.68)

< 0.001*

1.17 (1.01 - 1.37)

0.040*

3.76 (2.18 - 6.48)

< 0.001*

1.30 (1.13 - 1.50)

< 0.001*

Ethnicity

Reference: White

Black

1.63 (1.04 - 2.57)

0.035*

< 0.001*

0.97 (0.88 - 1.07)

0.544

< 0.001*

1.74 (1.11 - 2.71)

0.015*

0.010*

0.99 (0.90 - 1.09)

0.851

< 0.001*

American Indian/Alaska Native

1.69 (0.40 - 7.10)

0.477

1.19 (0.87 - 1.64)

0.283

2.28 (0.55 - 9.35)

0.255

1.31 (0.99 - 1.74)

0.061

Asian/Pacific Islander

0.70 (0.41 - 1.17)

0.173

0.79 (0.73 - 0.86)

< 0.001*

0.61 (0.36 - 1.01)

0.057

0.76 (0.70 - 0.83)

< 0.001*

Tumor location

Reference: gastric cardia

Gastric fundus/body

0.97 (0.52 - 1.81)

0.912

0.723

0.69 (0.62 - 0.77)

< 0.001*

0.78 (0.42 - 1.44)

0.423

0.655

0.66 (0.59 - 0.74)

< 0.001*

Gastric antrum/pylorus

1.18 (0.76 - 1.83)

0.454

0.75 (0.68 - 0.81)

< 0.001*

0.94 (0.59 - 1.49)

0.794

0.72 (0.66 - 0.79)

< 0.001*

Other^b

0.92 (0.58 - 1.47)

0.741

0.75 (0.69 - 0.82)

< 0.001*

0.77 (0.49 - 1.22)

0.270

0.73 (0.67 - 0.79)

< 0.001*

Tumor local invasion

Reference: muscularis propria/subserosa

Lamina propria/submucosa

1.20 (0.72 - 2.00)

0.481

0.331

0.59 (0.51 - 0.68)

< 0.001*

1.04 (0.63 - 1.71)

0.887

0.702

0.59 (0.51 - 0.67)

< 0.001*

Serosa

0.69 (0.44 - 1.09)

0.113

1.38 (1.29 - 1.48)

< 0.001*

0.85 (0.54 - 1.32)

0.461

1.42 (1.33 - 1.53)

< 0.001*

Adjacent structures

0.90 (0.47 - 1.74)

0.763

1.80 (1.62 - 2.00)

< 0.001*

1.30 (0.67 - 2.52)

0.436

1.87 (1.69 - 2.07)

< 0.001*

Positive lymph node count

Reference: 0

1 - 2

0.86 (0.56 - 1.31)

0.474

0.656

1.42 (1.29 - 1.55)

< 0.001*

0.95 (0.62 - 1.45)

0.798

0.268

1.42 (1.30 - 1.56)

< 0.001*

3 - 6

0.70 (0.44 - 1.14)

0.151

1.82 (1.66 - 1.99)

< 0.001*

0.83 (0.52 - 1.34)

0.452

1.86 (1.70 - 2.03)

< 0.001*

7 - 15

0.92 (0.57 - 1.50)

0.748

2.46 (2.24 - 2.69)

< 0.001*

1.45 (0.89 - 2.36)

0.137

2.61 (2.38 - 2.86)

< 0.001*

≥ 16

0.73 (0.35 - 1.56)

0.423

3.26 (2.89 - 3.67)

< 0.001*

1.47 (0.68 - 3.19)

0.324

3.59 (3.19 - 4.04)

< 0.001*

Differentiation

Reference: poor/undifferentiated

Well

1.18 (0.51 - 2.70)

0.704

0.898

0.80 (0.65 - 0.99)

0.038*

< 0.001*

1.16 (0.50 - 2.67)

0.732

0.647

0.80 (0.65 - 0.99)

0.038*

< 0.001*

Intermediate

0.96 (0.67 - 1.38)

0.829

0.73 (0.67 - 0.79)

< 0.001*

0.86 (0.59 - 1.25)

0.418

0.72 (0.66 - 0.78)

< 0.001*

Resection type

Reference: partial/subtotal gastrectomy

Total/near-total gastrectomy

0.99 (0.65 - 1.49)

0.942

0.185

1.22 (1.14 - 1.31)

< 0.001*

1.06 (0.70 - 1.61)

0.791

0.121

1.23 (1.15 - 1.32)

< 0.001*

Gastrectomy (NOS)

1.52 (0.96 - 2.43)

0.075

1.28 (1.16 - 1.42)

< 0.001*

1.68 (1.02 - 2.76)

0.041*

1.29 (1.17 - 1.43)

< 0.001*