Approximately 40% of all non-Hodgkin lymphomas (NHLs) occur in extranodal locations. The gastrointestinal tract is the predominant site of extranodal NHL [
Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT) type accounted for 40–48% of PGL cases [
In this study, we aimed to determine the clinical characteristics of patients with PGL who were referred to our clinic over the last 12 years. We also aimed to evaluate patient survival and prognostic factors affecting survival and the effect of combined surgical and conservative treatment.
We retrospectively reviewed and analyzed the data of patients treated for PGL in our clinic (Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Medical Oncology) from 1998 through 2010. All patients with MALT lymphoma who did not respond to antibiotic therapy for
The following characteristics or results were recorded for each patient: medical history, physical examination, biochemistry, computed tomography (CT) of the thorax and abdomen, multiple gastroscopic biopsies of the upper and lower gastrointestinal tract, examination of Waldeyer’s ring, and bone marrow biopsy. Disease staging was performed using the Lugano Staging System [
Overall and disease-free survival (OS and DFS) were the primary endpoints. OS and DFS were calculated from the date of diagnosis. DFS was defined as the time until disease recurrence, progression, or death from disease or chemotherapy related toxicity, whichever occurred first. OS was defined as the time of death from any cause. The effects of age, sex, LDH level, tumor stage and pathological subtype, performance status, presenting symptoms, and tumor treatment modality on OS and DFS were evaluated.
Categorical and continuous variables were summarized using descriptive statistics (e.g., median, range, frequency, and percentage) and compared with chi-square and Mann-Whitney
Data from 79 patients with PGL were retrospectively analyzed. The corpus and antrum of the stomach were the predominant sites of PGL. Abdominal pain and dyspepsia were the main symptoms of presentation in 70% of patients, followed by weight loss, fever, or night sweats (B symptoms) in 53% and nausea and vomiting in 10% of patients (Table
Predominant site of primary gastric lymphoma and symptoms at diagnosis (
|
% | |
---|---|---|
Predominant site of gastric lymphoma | ||
Corpus | 28 | 35 |
Antrum | 26 | 33 |
Cardia | 7 | 9 |
Fundus | 2 | 3 |
Multiple site | 5 | 6 |
Unknown | 11 | 14 |
Symptoms | ||
Abdominal pain and dyspepsia | 55 | 70 |
Weight loss, fever, night sweat | 42 | 53 |
Nausea and vomiting | 13 | 17 |
Weakness | 11 | 14 |
Gastrointestinal bleeding | 8 | 10 |
The median age at presentation was 57 years (range, 18−85 years) and 37 patients (47%) were male. Of the 79 patients, 63 (79%) were classified as having non-MALT and 16 (21%) as having MALT lymphoma. Eleven patients had a poor performance status, according to the Karnofsky scale (<80). Of the 79 total patients, 57 (81%) had stage I/II or IIE disease and 22 (19%) had stage IV disease. The clinical characteristics of the patients with respect to MALT status are shown in Table
Clinical characteristics of study patients (
Non-MALT |
MALT |
||
---|---|---|---|
Age |
53 (43–63) | 56 (32–80) | |
Gender ( |
Male | 28 (45%) | 9 (56%) |
Female | 34 (55%) | 7 (44%) | |
Stage ( |
I/II, IIE | 44 (71%) | 13 (81%) |
IV | 19 (29%) | 3 (19%) | |
Karnofsky performance status |
≥80 | 56 (89%) | 12 (75%) |
<80 | 7 (11%) | 4 (25%) | |
LDH level ( |
>240 mg | 26 (42%) | 9 (56%) |
Normal range | 28 (45%) | 5 (31%) | |
Unknown | 9 (13%) | 2 (13%) |
MALT: mucosa associated lymphoid tissue, LDH: lactate dehydrogenase.
The treatment modalities applied to patients with respect to MALT status and stage of disease are shown in Table
Treatment modality applied for study patients (
Non-MALT ( |
MALT ( |
|||
---|---|---|---|---|
Stage |
Stage IV | Stage |
Stage IV | |
Conservative | 27 (63%) | 12 (67%) | 7 (54%) | 3 (100%) |
CT | 22 | 10 | 3 | 3 |
CT + RT | 5 | 2 | 1 | |
RT | 3 | |||
| ||||
Nonconservative | 17 (37%) | 7 (33%) | 6 (46%) | 0 |
Surgery + CT | 16 | 6 | 4 | |
Surgery + CT + RT | 1 | 1 | 2 |
MALT: mucosa associated lymphoid tissue, CT: chemotherapy, and RT: radiotherapy.
All 79 patients were enrolled into our survival analysis study. The median followup was 41 months (range, 9−52 months). The five-year OS and DFS, which were estimated by using the Kaplan-Meier method, were 83.1% and 78.6%, respectively (Figures
The clinical variables and their prognostic impact on five-year DFS and OS.
DFS (%) |
|
OS (%) |
|
||
---|---|---|---|---|---|
Gender | Female | 76.4 | 0.7 | 84.1 | 0.6 |
Male | 81.2 | 81.9 | |||
Age | >60 | 77.9 | 0.4 | 75.5 | 0.04 |
≤60 | 79.9 | 89.8 | |||
LDH | >240 mg | 72.5 | 0.007 | 79.9 | 0.09 |
Normal range | 86.8 | 90.9 | |||
Symptoms | B symptoms present | 82.3 | 0.4 | 79.2 | 0.2 |
B symptoms absent | 74 | 88.6 | |||
Lymphoma subtype | MALT | 81.3 | 0.57 | 91.2 | 0.38 |
Non-MALT | 76.9 | 81.2 | |||
Karnofsky index | ≥80 | 89.5 | 0.002 | 89.5 | 0.002 |
<80 | 54.5 | 63.6 | |||
Stage | I/II, IIE | 83.9 | 0.02 | 91.2 | 0.002 |
IV | 65.5 | 70.6 | |||
Treatment (for stage I/II, IIE) | Surgery | 85.7 | 0.18 | 86.5 | 0.8 |
Conservative | 82.1 | 94 |
aLong-rank test.
DFS: disease-free survival, OS: overall survival, LDH: lactate dehydrogenase, and MALT: mucosa associated lymphoid tissue.
Kaplan-Meier curve for overall survival of 79 patients with PGL.
Kaplan-Meier curve for disease-free survival of 79 patients with PGL.
Based on the results from the univariate analyses, we performed multivariate analyses using a Cox proportional hazard model (Table
Multivariate analyses for DFS and OS.
DFS | OS | ||||||
---|---|---|---|---|---|---|---|
RR | 95% CI |
|
RR | 95% CI |
|
||
Karnofsky index | ≥80 | 1 | 1.5–10.9 | 0.005 | 1 | 1.6–11.2 | 0.001 |
<80 | 4.1 | 4.1 | |||||
Stage | I/II, IIE | 1 | 1.2–1.9 | 0.01 | 1 | 1.5–9.7 | 0.004 |
IV | 1.4 | 3.8 | |||||
LDH | Normal range | 1 | 1.05–1.63 | 0.02 | |||
>240 mg | 1.18 | ||||||
Age | ≤60 years | 1 | 1.15–1.9 | 0.04 | |||
>60 years | 1.4 |
RR: relative risk; CI: confidence interval, DFS: disease-free survival, OS: overall survival, and LDH: lactate dehydrogenase.
PGLs represent more than half of all primary gastrointestinal lymphomas, accounting for 5% of all malignant tumors of the stomach [
Epigastric pain, epigastric discomfort, anorexia, weight loss, nausea, vomiting, and gastrointestinal bleeding were the most common symptoms in the present study, as reported in other series [
In PGL, there are multiple factors that affect survival. In previous studies, advanced stage, poor performance status, age >60 years, and elevated LDH at presentation of the disease were associated with poor outcome; female sex, low-grade histology, good performance status, and surgical resection for local disease have been reported to be associated with high OS and DFS rates [
There are no standard therapeutic guidelines for patients in whom antibiotic therapy has failed. In two retrospective studies of patients with MALT lymphoma, no significant differences in survival were found between different treatment modalities [
In the present study, there was no difference between conservative and surgical treatment approaches with regard to DFS and OS. The main limitations of this study were its retrospective design and the lack of data on patient quality of life and toxicities in patients treated with a conservative approach or surgery.
In conclusion, poor performance status, advanced stage of disease, high LDH level, and advanced age were bad prognostic factors for patients with PGL. Surgery provides no advantage for survival over conservative treatment; thus, conservative treatment modalities should be preferred initially at early stages of PGL. Further prospective, large-scale, controlled studies are needed to determine the impact of different treatment modalities on the outcome of patients with PGL.