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 4, August 2022, pages 159-171

Epidemiology and Determinants of Survival for Primary Intestinal Non-Hodgkin Lymphoma: A Population-Based Study

Figure 1. Description of patient selection and exclusion for the study. Patient listed in SEER 18 registries were included in the study. SEER: Surveillance, Epidemiology, and End Results; EN-NHL: extranodal non-Hodgkin lymphoma.

Figure 2. Kaplan-Meier plots for overall survival among all PI-NHL patients for effect: (a) year of diagnosis, (b) age, (c) sex, (d) stage of disease, (e) NHL subtypes, and (f) treatment. PI-NHL: primary intestinal non-Hodgkin lymphoma.

Figure 3. Kaplan-Meier plots for cause-specific survival among all PI-NHL patients for effect: (a) year of diagnosis, (b) age, (c) sex, (d) stage of disease, (e) NHL subtypes, and (f) treatment. PI-NHL: primary intestinal non-Hodgkin lymphoma.

Figure 4. Kaplan-Meier plots for overall survival probability for primary intestinal DLBCL for effects: (a) year of diagnosis, (b) age, (d) stage of disease, and (d) treatment. DLBCL: diffuse large B-cell lymphoma.

Figure 5. Kaplan-Meier plot showing cause-specific survival probability for PI-DLBCL for effects: (a) year of diagnosis, (b) age, (d) stage of disease, and (d) treatment. PI-DLBCL: primary intestinal diffuse large B-cell lymphoma

**Table 1.** Age-Adjusted Incidence for PI-NHL for Year 2000 - 2015 for Age ≥ 18
	Age-adjusted incidence (per 100,000 population)	Rate ratio	P value
^aArranged in descending order of age-adjusted incidence rate. PI-NHL: primary intestinal non-Hodgkin lymphoma.
Study population (age ≥ 18, year 2000 - 2015)	0.914 (0.896 - 0.934)	-	-
Sex^a
Male	1.24 (1.207 - 1.274)	Reference	-
Female	0.651 (0.629 - 0.673)	0.5246 (0.5026 - 0.5475)	0.00
Ethnicity^a
Non-Hispanic White	0.954	Reference	-
Non-Hispanic Asia-Pacific Islanders	0.923 (0.859 - 0.991)	0.9677 (0.8964 - 1.0433)	0.40
Hispanic	0.873 (0.818 - 0.932)	0.9156 (0.8533 - 0.9812)	0.01
Non-Hispanic American Indian	0.662 (0.47 - 0.904)	0.6946 (0.4921 - 0.9491)	0.02
Non-Hispanic Black	0.589 (0.540 - 0.641)	0.6175 (0.5644 - 0.6743)	0.00

Table 1. Age-Adjusted Incidence for PI-NHL for Year 2000 - 2015 for Age ≥ 18

Age-adjusted incidence (per 100,000 population)

Rate ratio

P value

^aArranged in descending order of age-adjusted incidence rate. PI-NHL: primary intestinal non-Hodgkin lymphoma.

Study population (age ≥ 18, year 2000 - 2015)

0.914 (0.896 - 0.934)

Sex^a

Male

1.24 (1.207 - 1.274)

Reference

Female

0.651 (0.629 - 0.673)

0.5246 (0.5026 - 0.5475)

0.00

Ethnicity^a

Non-Hispanic White

0.954

Reference

Non-Hispanic Asia-Pacific Islanders

0.923 (0.859 - 0.991)

0.9677 (0.8964 - 1.0433)

0.40

Hispanic

0.873 (0.818 - 0.932)

0.9156 (0.8533 - 0.9812)

0.01

Non-Hispanic American Indian

0.662 (0.47 - 0.904)

0.6946 (0.4921 - 0.9491)

0.02

Non-Hispanic Black

0.589 (0.540 - 0.641)

0.6175 (0.5644 - 0.6743)

0.00

**Table 2.** Demography, and Clinical Characteristics of PI-NHL Patients in the Study
Characteristics	N (% or range)
IQR: interquartile range; DLBCL: diffuse large B-cell lymphoma; NOS: not otherwise specified; PI-NHL: primary intestinal non-Hodgkin lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma.
Total	8,568
Median age in years (IQR)	66.5 (55 - 77)
< 60 years	2,933 (34.23)
≥ 60 years	5,635 (65.77)
Sex
Female	3,352 (39.12)
Male	5,216 (60.88)
Ethnicity
Non-Hispanic White	6,240 (72.83)
Non-Hispanic Black	533 (6.22)
Hispanic	967 (11.29)
Others	828 (9.66)
Staging
Stage 1	4,013 (46.84)
Stage 2	2,329 (27.18)
Stage 3	456 (5.32)
Stage 4	1,770 (20.66)
Site
Small intestine	4,696 (54.81)
Large intestine	3,872 (45.19)
Histology
Follicular lymphoma	1,563 (18.24)
MALToma	1,160 (13.54)
DLBCL	3,835 (44.76)
Mantle cell lymphoma	447 (5.22)
Burkitt lymphoma	344 (4.01)
Other B-cell lymphoma	232 (2.71)
T-Cell non-Hodgkin lymphoma	392 (4.58)
Non-Hodgkin lymphoma, NOS	595 (6.94)
Treatment
Chemotherapy only	2,018 (23.55)
Surgery only	2,446 (28.55)
Surgery and chemotherapy	2,506 (29.25)
None	1,598 (18.65)
Year of diagnosis
2000 - 2005	2,911 (33.98)
2006 - 2010	2,815 (32.85)
2011 - 2015	2,842 (33.17)

Table 2. Demography, and Clinical Characteristics of PI-NHL Patients in the Study

Characteristics

N (% or range)

IQR: interquartile range; DLBCL: diffuse large B-cell lymphoma; NOS: not otherwise specified; PI-NHL: primary intestinal non-Hodgkin lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma.

Total

8,568

Median age in years (IQR)

66.5 (55 - 77)

< 60 years

2,933 (34.23)

≥ 60 years

5,635 (65.77)

Sex

Female

3,352 (39.12)

Male

5,216 (60.88)

Ethnicity

Non-Hispanic White

6,240 (72.83)

Non-Hispanic Black

533 (6.22)

Hispanic

967 (11.29)

Others

828 (9.66)

Staging

Stage 1

4,013 (46.84)

Stage 2

2,329 (27.18)

Stage 3

456 (5.32)

Stage 4

1,770 (20.66)

Site

Small intestine

4,696 (54.81)

Large intestine

3,872 (45.19)

Histology

Follicular lymphoma

1,563 (18.24)

MALToma

1,160 (13.54)

DLBCL

3,835 (44.76)

Mantle cell lymphoma

447 (5.22)

Burkitt lymphoma

344 (4.01)

Other B-cell lymphoma

232 (2.71)

T-Cell non-Hodgkin lymphoma

392 (4.58)

Non-Hodgkin lymphoma, NOS

595 (6.94)

Treatment

Chemotherapy only

2,018 (23.55)

Surgery only

2,446 (28.55)

Surgery and chemotherapy

2,506 (29.25)

None

1,598 (18.65)

Year of diagnosis

2000 - 2005

2,911 (33.98)

2006 - 2010

2,815 (32.85)

2011 - 2015

2,842 (33.17)

**Table 3.** Distribution of Histological Subtypes of Non-Hodgkin Lymphoma Across the Intestinal Tract
Histological subtype of NHL	Total	Small intestine	Large intestine
NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B-cell lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma; NOS: not otherwise specified.
Follicular lymphoma	1,563 (18.24)	1,185 (25.23)	378 (9.76)
MALToma	1,160 (13.54)	443 (9.43)	717 (18.52)
DLBCL	3,835 (44.76)	2,138 (45.53)	1,697 (43.83)
Mantle cell lymphoma	447 (5.22)	82 (1.75)	365 (9.43)
Burkitt lymphoma	344 (4.01)	166 (3.53)	178 (4.60)
Other B-cell lymphoma	232 (2.71)	80 (1.70)	152 (3.93)
T-cell non-Hodgkin lymphoma	392 (4.58)	305 (6.49)	87 (2.25)
Non-Hodgkin lymphoma, NOS	595 (6.94)	297 (6.32)	298 (7.70)

Table 3. Distribution of Histological Subtypes of Non-Hodgkin Lymphoma Across the Intestinal Tract

Histological subtype of NHL

Total

Small intestine

Large intestine

NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B-cell lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma; NOS: not otherwise specified.

Follicular lymphoma

1,563 (18.24)

1,185 (25.23)

378 (9.76)

MALToma

1,160 (13.54)

443 (9.43)

717 (18.52)

DLBCL

3,835 (44.76)

2,138 (45.53)

1,697 (43.83)

Mantle cell lymphoma

447 (5.22)

82 (1.75)

365 (9.43)

Burkitt lymphoma

344 (4.01)

166 (3.53)

178 (4.60)

Other B-cell lymphoma

232 (2.71)

80 (1.70)

152 (3.93)

T-cell non-Hodgkin lymphoma

392 (4.58)

305 (6.49)

87 (2.25)

Non-Hodgkin lymphoma, NOS

595 (6.94)

297 (6.32)

298 (7.70)

**Table 4.** Overall Survival and Cause-Specific Survival at 1-Year, 5-Year and 10-Year for All PI-NHL Patients
	Cause-specific survival (95% CI)	Overall survival (95% CI)
PI-NHL: primary intestinal non-Hodgkin lymphoma; CI: confidence interval.
1-year survival	0.80 (0.796 - 0.813)	0.76 (0.749 - 0.767)
5-year survival	0.71 (0.706 - 0.725)	0.61 (0.600 - 0.621)
10-year survival	0.66 (0.654 - 0.677)	0.48 (0.469 - 0.493)

Table 4. Overall Survival and Cause-Specific Survival at 1-Year, 5-Year and 10-Year for All PI-NHL Patients

Cause-specific survival (95% CI)

Overall survival (95% CI)

PI-NHL: primary intestinal non-Hodgkin lymphoma; CI: confidence interval.

1-year survival

0.80 (0.796 - 0.813)

0.76 (0.749 - 0.767)

5-year survival

0.71 (0.706 - 0.725)

0.61 (0.600 - 0.621)

10-year survival

0.66 (0.654 - 0.677)

0.48 (0.469 - 0.493)

**Table 5.** Multivariate Cox Proportional Hazard Analysis of the Survival Factors for Cause-Specific and Overall Survival for All PI-NHL Patients
Variable	Cause-specific survival HR (95% CI)	P value	Overall survival HR (95% CI)	P value
HR: hazard ratio; NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B-cell lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma; NOS: not otherwise specified; PI-NHL: primary intestinal non-Hodgkin lymphoma; CI: confidence interval.
Year of diagnosis
2000 - 2005	Reference		Reference
2006 - 2010	0.87 (0.80 - 0.96)	0.004	0.88 (0.82 - 0.95)	< 0.001
2011 - 2015	0.72 (0.65 - 0.80)	< 0.001	0.78 (0.72 - 0.84)	< 0.001
Age
< 60 years	Reference		Reference
≥ 60 years	2.13 (1.94 - 2.34)	< 0.001	2.87 (2.65 - 3.10)	< 0.001
Sex
Female	Reference		Reference
Male	1.14 (1.05 - 1.23)	0.006	1.17 (1.10 - 1.24)	< 0.001
Stage
Stage 1	Reference		Reference
Stage 2	1.54 (1.40 - 1.71)	< 0.001	1.26 (1.17 - 1.36)	< 0.001
Stage 3	1.88 (1.59 - 2.22)	< 0.001	1.45 (1.27 - 1.66)	< 0.001
Stage 4	2.56 (2.31 - 2.83)	< 0.001	1.93 (1.79 - 2.09)	< 0.001
Histology
DLBCL	Reference		Reference
Follicular lymphoma	0.19 (0.16 - 0.23)	< 0.001	0.29 (0.26 - 0.32)	< 0.001
MALToma	0.21 (0.17 - 0.25)	< 0.001	0.37 (0.33 - 0.41)	< 0.001
Mantle cell lymphoma	0.60 (0.51 - 0.70)	< 0.001	0.59 (0.52 - 0.67)	< 0.001
Other B-cell lymphoma	0.61 (0.49 - 0.77)	< 0.001	0.68 (0.58 - 0.81)	< 0.001
NHL, NOS	0.76 (0.66 - 0.89)	< 0.001	0.83 (0.74 - 0.93)	0.001
Burkitt lymphoma	1.36 (1.13 - 1.64)	0.001	1.17 (1.00 - 1.38)	0.052
T-Cell non-Hodgkin lymphoma	3.04 (2.67 - 3.46)	< 0.001	2.56 (2.28 - 2.88)	< 0.001
Treatment
None	Reference		Reference
Surgery	0.82 (0.73 - 0.93)	0.008	0.96 (0.88 - 1.05)	0.395
Chemotherapy	0.52 (0.46 - 0.60)	< 0.001	0.59 (0.53 - 0.65)	< 0.001
Chemotherapy and surgery	0.39 (0.34 - 0.44)	< 0.001	0.45 (0.40 - 0.49)	< 0.001

Table 5. Multivariate Cox Proportional Hazard Analysis of the Survival Factors for Cause-Specific and Overall Survival for All PI-NHL Patients

Variable

Cause-specific survival HR (95% CI)

P value

Overall survival HR (95% CI)

P value

HR: hazard ratio; NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B-cell lymphoma; MALToma: mucosa-associated lymphoid tissue lymphoma; NOS: not otherwise specified; PI-NHL: primary intestinal non-Hodgkin lymphoma; CI: confidence interval.

Year of diagnosis

2000 - 2005

Reference

2006 - 2010

0.87 (0.80 - 0.96)

0.004

0.88 (0.82 - 0.95)

< 0.001

2011 - 2015

0.72 (0.65 - 0.80)

< 0.001

0.78 (0.72 - 0.84)

< 0.001

Age

< 60 years

Reference

≥ 60 years

2.13 (1.94 - 2.34)

< 0.001

2.87 (2.65 - 3.10)

< 0.001

Sex

Female

Reference

Male

1.14 (1.05 - 1.23)

0.006

1.17 (1.10 - 1.24)

< 0.001

Stage

Stage 1

Reference

Stage 2

1.54 (1.40 - 1.71)

< 0.001

1.26 (1.17 - 1.36)

< 0.001

Stage 3

1.88 (1.59 - 2.22)

< 0.001

1.45 (1.27 - 1.66)

< 0.001

Stage 4

2.56 (2.31 - 2.83)

< 0.001

1.93 (1.79 - 2.09)

< 0.001

Histology

DLBCL

Reference

Follicular lymphoma

0.19 (0.16 - 0.23)

< 0.001

0.29 (0.26 - 0.32)

< 0.001

MALToma

0.21 (0.17 - 0.25)

< 0.001

0.37 (0.33 - 0.41)

< 0.001

Mantle cell lymphoma

0.60 (0.51 - 0.70)

< 0.001

0.59 (0.52 - 0.67)

< 0.001

Other B-cell lymphoma

0.61 (0.49 - 0.77)

< 0.001

0.68 (0.58 - 0.81)

< 0.001

NHL, NOS

0.76 (0.66 - 0.89)

< 0.001

0.83 (0.74 - 0.93)

0.001

Burkitt lymphoma

1.36 (1.13 - 1.64)

0.001

1.17 (1.00 - 1.38)

0.052

T-Cell non-Hodgkin lymphoma

3.04 (2.67 - 3.46)

< 0.001

2.56 (2.28 - 2.88)

< 0.001

Treatment

None

Reference

Surgery

0.82 (0.73 - 0.93)

0.008

0.96 (0.88 - 1.05)

0.395

Chemotherapy

0.52 (0.46 - 0.60)

< 0.001

0.59 (0.53 - 0.65)

< 0.001

Chemotherapy and surgery

0.39 (0.34 - 0.44)

< 0.001

0.45 (0.40 - 0.49)

< 0.001

**Table 6.** Overall and Cause-Specific Survival Probability at 1-Year and 3-Year for Each Year of Diagnosis Group
Year of diagnosis	2000 - 2005	2006 - 2010	2011 - 2015
OS: overall survival; CSS: cause-specific survival.
1-year OS probability	0.72 (0.71 - 0.74)	0.77 (0.75 - 0.78)	0.78 (0.77 - 0.80)
3-year OS probability	0.63 (0.61 - 0.68)	0.68 (0.67 - 0.70)	0.71 (0.69 - 0.72)
1-year CSS probability	0.77 (0.76 - 0.79)	0.81 (0.79 - 0.82)	0.83 (0.82 - 0.85)
3-year CSS probability	0.71 (0.69 - 0.72)	0.75 (0.74 - 0.77)	0.79 (0.77 - 0.80)

Table 6. Overall and Cause-Specific Survival Probability at 1-Year and 3-Year for Each Year of Diagnosis Group

Year of diagnosis

2000 - 2005

2006 - 2010

2011 - 2015

OS: overall survival; CSS: cause-specific survival.

1-year OS probability

0.72 (0.71 - 0.74)

0.77 (0.75 - 0.78)

0.78 (0.77 - 0.80)

3-year OS probability

0.63 (0.61 - 0.68)

0.68 (0.67 - 0.70)

0.71 (0.69 - 0.72)

1-year CSS probability

0.77 (0.76 - 0.79)

0.81 (0.79 - 0.82)

0.83 (0.82 - 0.85)

3-year CSS probability

0.71 (0.69 - 0.72)

0.75 (0.74 - 0.77)

0.79 (0.77 - 0.80)

**Table 7.** Multivariate Cox Proportional Hazard Analysis of the Survival Factors for Cause-Specific and Overall Survival for PI-DLBCL Patients
Variable	Number of patients	Cause-specific survival (95% CI)	P value	Overall survival (95% CI)	P value
PI-DLBCL: primary intestinal diffuse large B-cell lymphoma; CI: confidence interval.
Year of diagnosis
2000 - 2005	1,387 (36.17)	Reference		Reference
2006 - 2010	1,243 (32.41)	0.96 (0.85 - 1.08)	0.505	0.95 (0.86 - 1.05)	0.318
2011 - 2015	1,205 (31.42)	0.72(0.63 - 0.82)	< 0.001	0.79 (0.71 - 0.88)	< 0.001
Age
< 60 years	1,232 (32.13)	Reference		Reference
≥ 60 years	2,603 (67.87)	1.92 (1.69 - 2.18)	< 0.001	2.51 (2.26 - 2.78)	< 0.001
Stage
Stage 1	1,519 (39.61)	Reference		Reference
Stage 2	1,245 (32.46)	1.48 (1.30 - 1.69)	< 0.001	1.20 (1.08 - 1.32)	< 0.001
Stage 3	248 (6.47)	1.66 (1.33 - 2.07)	< 0.001	1.27 (1.06 - 1.52)	< 0.001
Stage 4	823 (21.46)	2.69 (2.35 - 3.08)	< 0.001	2.01 (1.81 - 2.24)	< 0.001
Treatment
None	355 (9.26)	Reference		Reference
Surgery	970 (25.29)	0.52 (0.44 - 0.62)	< 0.001	0.60 (0.53 - 0.69)	< 0.001
Chemotherapy	1,008 (26.28)	0.33 (0.28 - 0.39)	< 0.001	0.36 (0.31 - 0.42)	< 0.001
Chemotherapy and surgery	1,502 (39.17)	0.22 (0.19 - 0.26)	< 0.001	0.26 (0.23 - 0.30)	< 0.001

Table 7. Multivariate Cox Proportional Hazard Analysis of the Survival Factors for Cause-Specific and Overall Survival for PI-DLBCL Patients

Variable

Number of patients

Cause-specific survival (95% CI)

P value

Overall survival (95% CI)

P value

PI-DLBCL: primary intestinal diffuse large B-cell lymphoma; CI: confidence interval.

Year of diagnosis

2000 - 2005

1,387 (36.17)

Reference

2006 - 2010

1,243 (32.41)

0.96 (0.85 - 1.08)

0.505

0.95 (0.86 - 1.05)

0.318

2011 - 2015

1,205 (31.42)

0.72(0.63 - 0.82)

< 0.001

0.79 (0.71 - 0.88)

< 0.001

Age

< 60 years

1,232 (32.13)

Reference

≥ 60 years

2,603 (67.87)

1.92 (1.69 - 2.18)

< 0.001

2.51 (2.26 - 2.78)

< 0.001

Stage

Stage 1

1,519 (39.61)

Reference

Stage 2

1,245 (32.46)

1.48 (1.30 - 1.69)

< 0.001

1.20 (1.08 - 1.32)

< 0.001

Stage 3

248 (6.47)

1.66 (1.33 - 2.07)

< 0.001

1.27 (1.06 - 1.52)

< 0.001

Stage 4

823 (21.46)

2.69 (2.35 - 3.08)

< 0.001

2.01 (1.81 - 2.24)

< 0.001

Treatment

None

355 (9.26)

Reference

Surgery

970 (25.29)

0.52 (0.44 - 0.62)

< 0.001

0.60 (0.53 - 0.69)

< 0.001

Chemotherapy

1,008 (26.28)

0.33 (0.28 - 0.39)

< 0.001

0.36 (0.31 - 0.42)

< 0.001

Chemotherapy and surgery

1,502 (39.17)

0.22 (0.19 - 0.26)

< 0.001

0.26 (0.23 - 0.30)

< 0.001