Gastric DLBCL Research Articles

Radiation Therapy for Patients With Primary Gastric DLBCL

Radiation Therapy for Patients With Primary Gastric DLBCL

The clinicopathological characteristics of gastric cancer and precancerous conditions in gastric DLBCL and MALT lymphoma patients: a multi-center retrospective study

Objective The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. Methods We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. Results A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. Conclusions Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer. Key messages 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer. 14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.

Abstract 1216: Virome characterization in different types of non-Hodgkin lymphoma

Abstract Non-Hodgkin's lymphoma (NHL) is a heterogeneous group of lymphoid tissue neoplasms, with different clinical, genetic and morphological aspects. It is the most common form of hematological malignancy worldwide. In addition to risk factors, some infectious agents cause or are related to the risk of developing NHL. These include Epstein Barr virus (EBV), human herpes virus 8, human T-cell lymphotropic virus type 1, human immunodeficiency virus, hepatitis C virus, and the H. pylori. Overall, cancer attributable to infections accounted for 15.4% of new cases in 2012, and this number may increase due to improvements in molecular methodologies. Recently, other infectious agents have been associated with NHL, such as human pegivirus and cutavirus. Although factors related to immune function and the infectious agents described play a relevant role in the etiology of NHL, these factors do not explain most cases, suggesting that others factors or infectious agents could be involved in NHL development. Identifying possible pathogens associated with NHL and understanding the cancer-infectious agents relationship is essential for the development of prevention and screening aproaches. The aim of this study is to characterize the viral composition of the tumor microbiome in different types of NHL. Tumor tissue samples from NHL stored at the Brazilian National Cancer Institute were processed for viral DNA and RNA extraction. The viral nucleic acids were prepared for 19 samples with the Nextera XT kit and sequenced on an Illumina MiSeq platform. Virus identification analyses were performed by comparing the sequences obtained with viral sequences in the GenBank database through the BLASTX tool. Most samples were from diffuse large B cell lymphoma (DLBCL; n = 11), followed by marginal zone and follicular lymphoma (three cases each), and small lymphocytic and non-B, non-T cell lymphoma (one case each). A median of 46% of the obtained reads mapped to the human genome. Among the remaining reads, four viral families were identified: Anelloviridae, Flaviviridae, Herpesviridae and Papillomaviridae. EBV, a herpervirus associated with different types of NHL, was found in one gastric DLBCL. Anelloviridae reads included only the genus Alphatorquevirus and were found in five DLBCL. This virus family has a ubiquitous presence, without any clinical manifestation so far described in humans. However, anellovirus viral load has been associated with the subject’s immune status. Different human papillomaviruses from the Alpha, Beta and Gamma genera were found in six samples, comprising follicular lymphoma and DLBCL. The flavivirus human pegivirus was found in one DLBCL. Some recent studies associated this later virus with risk of lymphoma. In summary, this study describes the viral diversity found in NHL, showing the presence of viruses not yet associated with this neoplasia. Additional studies are warranted to clarify the role of these viruses in the etiology of NHL. Citation Format: Juliana D. Siqueira, Esmeralda A. Soares, Marcelo A. Soares. Virome characterization in different types of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1216.

Evaluation of clinical and prognostic factors for primary gastric diffuse large B-cell lymphoma: Single-center experience.

Primary gastric lymphomas, which make up the vast majority of extranodal non-Hodgkin lymphoma, are rare and the most common subtype is primary gastric diffuse large B-cell lymphoma (PG-DLBCL). In our study, we investigated the clinical and prognostic factors of this lymphoma type as a single-center experience. Between January 2001 and February 2021, 91 patients aged ≥18 years, registered with the diagnosis of primary gastric DLBCL, diagnosed histopathologically, and whose evaluation parameters were reached, were retrospectively scanned. The median age of 91 patients with a diagnosis of PG-DLBCL was 58 (20-81, minimum-maximum) years. Of the patients, 64.8% were men and 35.2% were women. While the number of patients with an International Prognostic Index (IPI) score of 0-2 (low-low-intermediate risk) was 54 (59.4%), the number of patients with an IPI score of 3 (high intermediate) was 19 (20.9%), and the number of patients with an IPI score of 4-5 (high risk) was 18 (19.8%). While 52.7% of the patients had a complete response, 20.9% had a partial response, 3.3% had stable disease, and 23.1% had progressive disease. The 10-year event-free survival (EFS) and overall survival (OS) rates for all patients, respectively, were 52.1% and 53.2%. We found factors affecting survival in univariate analysis; age groups (≤60/>60), ECOG groups (0-1/≥2), Lugano stage (I-II/III-IV), LDH level (normal/high), IPI risk groups (low/low-intermediate/high-intermediate/high) and radiotherapy (yes/no). In multivariate analysis, only; age groups (≤60/>60) and IPI risk groups (low/low-intermediate/high-intermediate/high) were found to be independent factors affecting survival. In addition, in our study, we determined that the division of the IPI intermediate risk group into low intermediate and high intermediate is one of the factors predicting prognosis. Few studies of PG-DLBCL have investigated the long-term survival rates of patients and primarily examined small patient groups because of the low incidence of the disease. In our study, we think that detailed evaluation of age and especially IPI risk groups play a role in predicting survival.

Molecular and Genetic Study for Detection of Helicobacter pylori Virulence Genes among Patients with Diffuse Large B-Cell Lymphoma

Background: The bacteria Helicobacter pylori (Hp) has supposed to confirm an oncogenic consequence with the evolution of malignancy events in stomach, effectiveness of Hp consider a top risk factor of gastric-diffuse large B-cell lymphoma (DLBCL). Aims: the aim of this study was to observe the correlation between virulence factors, especially cytotoxin association gene A (CagA) and the progress of gastric DLBCL. Materials and Methods: Biopsy samples (50) involved in this study (28 were men, and 22 women, with a mean age up to 57.64 years), among gastric-DLBCL patients, with (25) control (were 14 men and 11 women) without DLBCL, tested at Medical City Teaching Hospital and Teaching Laboratories, study conducted from January 1st to September 30, 2022. Diagnosis was by molecular methods included DNA extraction for Hp by STR-Format kit (BIORON Diagnostics GmbHm In den Rauhweiden 20,67354 Germany), and “real-time polymerase chain reaction” methods using the (ABI PRISM 7700) Sequence Detection System, also applied the primers and probes, for Hp-CagA. Results: The mean of age was 55.7 ± 2 in DLBCL, while in control were 61.82 + 6, CagA +ve 66.66 + 2. In gastric DLBCL, the red blood cell count, white blood cell count, platelets count, and hemoglobin were all decline in DLBCL, not in the control group, lactate dehydrogenase levels in gastric DLBCL patients were rise (322 U/L), while less in control, while albumin (322g/dl) was less in gastric DLBCL patients. Hp 16S rRNA was detected relating to CagA variety, 66% (33/50) were CagA positive with highly significant in 23 patients with DLBCL (P = 0.004), and 10 in control patients. CagA gene expression was highly expression in gastric DLBCL patients with range up to (+), 8 (++), and 12 (+++), while in the control group was 5 (+), 2 (++), and 3 (+++), respectively. Conclusions: This present study fixed high frequency of CagA gene in gastric DLBCL patients. Moreover, confirmed this gene is significantly associated with gastric DLBCL in patients with Hp. Moreover, genotype EPIYA-ABC motif is related with the high risk of gastric DLBCL.

Systemic Inflammation Response Index (SIRI) Predicts Clinical Outcome and Improves NCCN-IPI Scoring in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Background: Systemic inflammation response index (SIRI) is a novel inflammatory hallmark that is proposed as an adverse prognosticator in a variety of malignancies. Nevertheless, the correlation between SIRI and primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) remains unknown. Our study aimed to evaluate the prognostic value of SIRI in PGI-DLBCL patients treated with CHOP-based therapies and establishing a highly discriminating risk prediction model compared with the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score.Methods: This retrospective analysis incorporated 102 PGI-DCBCL patients (57 patients with gastric DLBCL and 45 patients with intestinal DLBCL) newly diagnosed between January 2011 and June 2020. The SIRI was calculated by utilizing the peripheral blood neutrophil (N), monocyte (M), and lymphocyte (L) counts collected in the last ≤3 days before the initiation of the immunochemotherapy: SIRI= N × M/L. Pretreatment SIRI cutoff that may distinguish the study population into two gatherings with distinctive overall survival (OS) results which was calculated by the receiver operating characteristic (ROC) curve analysis. The prognostic factors associated with OS, the primary endpoint, were screened by multivariate Cox regression analyses and log-rank test as well as progression-free survival (PFS), the secondary endpoint. Performances of the novel model were compared using the area under the curve (AUC) and C-index in the cohort.Results: Among the 102 patients analyzed, there were 64 (62.7%) males and 38 (37.3%) females. The median follow-up time was 39.5 months (95% CI: 30.7-48.2), ranging from 2 to 102 months. A total of 33 patients (32.4%) presented B symptoms at the initial assessment, 74 (72.5%) of patients revealed stage III or IV disease, and 24 (23.5%) of patients had more than one extranodal involvement. Twenty-seven patients (26.5%) showed ECOG PS>2. The optimal SIRI cutoff was identified as 1.34 value by OS outcome, which divided patients into two groups. There were not significant differences in clinical characteristics between two groups (Table 1).Based on the cut-off value of SIRI, the outcomes of patients were distinct within two groups, which was shown in Figure 1. At a median follow-up of 39.5 (95% CI: 30.7-48.2) months, 86 (84.3%) patients were still alive (98.4% for SIRI <1.34 vs 62.5% for SIRI ≥1.34; p < 0.001). Cox regression analysis found three negative prognostic factors on OS: SIRI≥ 1.34 (P=0.001), B symptom (P=0.001), LDH>ULN (P=0.005). Accordingly, SIRI≥ 1.34 (P=0.002), age>60 (P=0.011) and LDH>ULN (P=0.002) emerged to be the indicators in relation to considerably inferior PFS times. Consequences of the multivariate analyses revealed that the prognostic significance of the SIRI on OS and PFS outcomes was independent of other confounders.SIRI could be used to combine with NCCN-IPI and develop a risk score to improve the NCCN-IPI score and identify PGI-DLBCL patients with poor prognosis. Patients with SIRI≥1.34 were allocated 2 points as a risk factor which was calculated in terms of the β coefficients compared with the effect of LDH level (>ULN) in the multivariate analysis of OS. This established an integrated scoring model with a maximum of 10 points when we combined NCCN-IPI with SIRI. Patients were divided into four risk groups and identified as low-risk group (0−3 points), low-intermediate-risk group (4−5 points), high-intermediate-risk group (6−7 points), and high-risk group (≥8 points). As a result, the prognostic and discriminatory capability of the NCCN-IPI plus SIRI was superior to NCCN-IPI alone (AUC: 0.858 vs. 0.814 and C-index: 0.826 vs. 0.801) based on OS in this patient population (Figure 2). Regarding the PFS, SIRI-PI also surpassed the NCCN-IPI with superior AUC (0.766 vs 0.709) and C-index (0.736 vs. 0.709) in discrimination.Conclusion: The results of this retrospective analysis suggested that the pretreatment SIRI was a potent and independent prognostic indicator that may be a potential candidate for identifying patients with poor prognosis in the future clinical practice of PGI-DLBCL.Keywords: Aggressive lymphoma, Clinically relevant, Systemic inflammation response index [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Development and validation of prognostic scoring in primary intestinal diffuse large B-cell lymphoma: a single-institution study of 184 patients.

BackgroundThe incidence of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is much lower than primary gastric DLBCL, and large-scale analyses on the clinical characteristics, molecular features, therapeutic strategies, and risk stratification have been seldomly performed in PI-DLBCL.MethodsTo assess prognostic model development, 107 PI-DLBCL patients diagnosed before 2014 were studied for prognosis factors including different primary involved sites and treatment strategies. For internal validation, a non-random split sample set with 77 PI-DLBCL patients after 2014 was included for validation of the prognosis factors.ResultsPatients with an ileocecal lesion presented with better survival time than those with non-ileocecal sites, with surgical resection significantly influencing the prognosis. Non-ileocecal patients who underwent surgery with lymphadenectomy had superior overall survival (OS) and progression-free survival (PFS) compared to those receiving surgery without lymphadenectomy or those not receiving (without) surgery. For ileocecal patients, surgery with or without lymphadenectomy resulted in better OS and PFS than those without surgery. For biomarker analysis, only BCL-2 >50% or Ki67 >80% on tumor cells indicated poor clinical outcome. In multivariate analysis, age, Eastern Cooperative Oncology Group (ECOG) score, and site of origin were independent prognostic factors for inferior OS in PI-DLBCL. A prognosis model was set up based on age, ECOG score, and site of origin, and validated well.ConclusionsThe prognosis in patients with PI-DLBCL with ileocecal involvement showed was better than those with non-ileocecal involvement. Surgical strategy can impact the clinical outcome of PI-DLBCL patients.

EZH2 overexpression in primary gastrointestinal diffuse large B-cell lymphoma and its association with the clinicopathological features

Gastrointestinal diffuse large B-cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma. Enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of several cancers. However, EZH2 has not been studied in GI DLBCL. Thus, we investigated EZH2 expression and EZH2 Y641 mutation in 100 GI DLBCL specimens by immunohistochemistry and sequencing. In addition, trimethylated H3K27 (H3K27me3), BCL2, c-MYC, and Ki-67 expression and Helicobacter pylori infection were detected, and BCL2 and c-MYC gene translocation was assessed. EZH2 was overexpressed in 50% of cases. EZH2 overexpression was significantly associated with higher stage (P = .014), higher International Prognostic Index score (P = .003), reduced overall survival rate (P = .030), and H3K27me3 (P = .001) and c-MYC expression (P = .008). We detected EZH2 mutations in 1 of 33 (3.0%) DLBCLs with a germinal center immunophenotype. The frequency of EZH2 Y641 mutation in GI DLBCL was significantly lower than that in patients with DLBCL without gastrointestinal features (P = .022). BCL2 and c-MYC translocation was detected in 6.5% and 5.1% of cases, respectively. BCL2 translocation was detected exclusively in the germinal center B-cell-like subtype. Chronic gastroenteritis was present in all cases, and 36.4% of gastric DLBCL cases had H pylori infection. The data indicate that primary GI DLBCL is closely related with chronic inflammation and has a low frequency of molecular abnormality, and EZH2 overexpression is significantly associated with inferior outcome in patients with primary GI DLBCL; evaluating EZH2 expression has therapeutic implications.

Risk for New Malignancies of Potential Infectious Etiology Among Adult Survivors of Specific Non-Hodgkin Lymphoma Subtypes

IntroductionSurvivors of non-Hodgkin lymphoma (NHL) have elevated risk for developing new malignancies. Although infections have been associated with the etiology of certain NHL subtypes, understanding of the patterns of potential infection-related new malignancies among NHL survivors is limited.MethodsWe conducted a registry-based cohort study among non-HIV infected adult (aged ≥20 years) one-year survivors of NHL diagnosed and treated in the modern era (2000-2013). The eligible cohort survived at least one year following diagnosis with one of the four most common NHL subtypes [diffuse large B-cell lymphoma (DLBCL, n=36,869), chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL, n=38,377), follicular lymphoma (FL, n=27,388), and marginal zone lymphoma (MZL, n=12,773)], as reported to 17 Surveillance, Epidemiology, and End Results registries. Standardized incidence ratios (SIRs) and 95% confidence intervals were used to quantify risks of infection-related second cancers, defined according to the International Agency for Research on Cancer to include cancers of the lung, stomach, liver, salivary gland, cervix, and anus.ResultsNon-small cell lung cancer was the most commonly occurring infection-related second cancer, with consistently elevated 1.2-1.5-fold risk among survivors of all four NHL subtypes. Similarly, risk of salivary gland cancer was elevated but with a greater magnitude of risk, with SIRs ranging from 2.4 among DLBCL survivors to 3.0 after FL. In contrast, stomach cancer risk was only elevated among survivors of DLBCL (SIR=1.5) and MZL (2.8). Stratifying the cohort of NHL survivors by the NHL site revealed the highest stomach cancer SIRs among survivors of gastric DLBCL (2.8) and MZL (6.8). Liver cancer also was only elevated among DLBCL (1.8) and MZL (2.0) survivors. Anal cancer risk was elevated after DLBCL (2.3) and borderline significantly elevated for MZL (2.4) and CLL/SLL survivors (1.7). Risk for cervical cancer was not elevated among survivors of any of the four most common NHL subtypes.DiscussionCertain infection-related cancers have elevated risks among all NHL survivors; in contrast, others are only elevated after DLBCL and MZL, which may reflect differences in infectious disease prevalence among primary NHL subtypes. For example, H. pylori and hepatitis C virus have been associated with the development of DLBCL and MZL and are also associated with second liver and stomach cancers, likely due to the increased prevalence of these infections among DLBCL and MZL survivors compared with the general population. In contrast, the persistently elevated risks for non-small cell lung cancer and cancer of the salivary gland among survivors of all four of the most common NHL subtypes warrants further investigation into potential infectious origins or immune dysfunction. Alternatively, the excess risk may be due to surveillance bias, as these patients receive regular CT scans and monitoring after their NHL diagnosis. To contradict this theory, when we investigated second lung and salivary gland cancer risks stratified by latency, we did not find a consistently elevated risk immediately following NHL diagnosis (<6 or 6-12 months) or a pattern in risk as survival time increased suggesting that this excess elevated risk is most likely not due to surveillance bias. Additionally, the lack of effect for second cervical cancers could be due to widespread screening for precancerous lesions among the general population.ConclusionSurvivors of the four most common NHL subtype have elevated risks of certain infection-related cancers. Differential patterns of risk provide clues to second cancer etiology as well as highlighting survivors at higher risk who might benefit the most from more intensive surveillance. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Immunohistochemistry and scoring of Ki-67 proliferative index and p53 expression in gastric B cell lymphoma from Northern African population: a pilot study.

This study aimed to clarify the Ki-67 distribution, p53 expression and their relationship with clinico-pathologic features of gastric B cell lymphoma from Northern African population. Twenty paraffin blocks of gastric lymphoma were retrieved from the archival materials of Department of Pathology, Central University Hospital of Sidi Bel Abbes (Western Algeria) from 2007 to 2013. Four µm section specimens were stained by immunohistochemical (IHC) technique with Ki-67 and p53 tumor markers. P values <0.05 were considered statistically significant. Expression of p53 proteins and the mean proliferative index (PI) were compared between high grade gastric B cell lymphomas (DLBCL) and low grade gastric B cell lymphomas (gastric MALTs). p53 overexpression (P=0.007) and a high proliferation index Ki-67 (P=0.001) were significantly associated with gastric DLBCL. We found also a statistically significant correlation between p53 and Ki-67 (P=0.007) but no obvious relationships were found between Ki-67 PI and p53 expression as well as clinico-pathological features (age, sex, location, macroscopic type). The IHC studies of Ki-67 and p53 expression in gastric B cell lymphoma can help in monitoring of patients at risk, and to give suitable treatment and management of patients.

Clinical Characteristics and Outcome of 104 Patients with Gastric Diffuse B-Cell Non-Hodgkin Lymphoma (DLBCL) a Multicenter Study

Background: Gastric lymphoma is the most common extra nodal B cell Non Hodgkin Lymphoma and DLBCL accounts for 70% of cases in the stomach. The clinical course is heterogeneous and clinical symptoms, laboratorial abnormalities and Helicobacter pylori and hepatitis B and C infections, in addition to classical IPI factors, have been related to prognosis. Different clinical behaviors may reflect distinct pathogenic mechanisms. In order to improve outcomes, a better characterization of prognostic factors is required.Aim: We aimed to identify factors with a potential prognosis impact in a consecutive series of gastric DLBCL patients diagnosed and treated in three referee Centers in Brazil, Portugual and Italy, by analyzing demographic and clinical characteristics, response to treatment and outcome (overall survival). The clinical picture of European and Brazilian populations was also compared.Patients and Methods: Between January 2010 and May 2015, 104 DLBCL were enrolled in this study. In order to establishing correlations between the clinical features and response to treatment the following parameters were analyzed: clinical symptoms, serum albumin, serum lactate dehydrogenize (LDH),b 2microglobulin, tumor bulky stage of disease, age-adjusted international prognostic index (aaIPI), and response to treatment. Statistical analysis using SPSS software included descriptive analyses, Kaplan-Meyer estimates for overall survival and Cox regression;p values <0.05 were considered significant. The final analyses were adjusted to Brazilian and European patients due to different clinical data at diagnosis.Results: 104 patients, median age 69 (28-88) years, were enrolled in this study, with a female: male ratio of 1.2:1. Their ECOG performance status was 0 in 48.5%; 1 and 2 in 42.6% and ≥3 in 8.9% cases, whereas aaIPI risk distribution was 12 (12.6%) high risk, 20 (21.1.%) high-intermediate risk and 63 (66.3%) low/low-intermediate high in 57/80 patients (71.2%). The test for identification of Helicobacter Pillory (HP) was performed in 45 patients and was positive in 13 (28.9%); also Hepatitis B serology, available in 97 cases, 46.4% positive. The most common symptoms included abdominal pain (63/74) and weight loss (57/73), dysphalgia (37/72) and nausea, vomiting (37/72). Bulky wasfound in 24%, plus anemia (33/76) and bleeding (22/72). Endoscopic examination was realized in 95%, however, only 10% was submitted to surgery. Brazilian patients were younger and more frequently symptomatic at diagnosis, although aaIPI was similar among the two populations. Almost all patients received chemotherapy (96% RCHOP-like).The median follow-up time was 14 (1-77) months, with 1- and 5-year survival rates of 79 and 76%, respectively. 5-year survival rates were significantly influenced by anemia (p= 0.007), LDH at the diagnosis (p< 0.0001), B symptoms (p<0.0001), clinical stage (p= 0.003), aaIPI 2 and 3 (p<0.0001), nausea (p=0.04) and bulky disease (p=0.02). Other variables, including gender (p= 0.17), presence of dysphagia (p= 0.08), weigh loss (p= 0.11), pain (p= 0.14) and bleeding (p= 0.06) and elevated β2microglobulin at diagnosis (p= 0.09) didn't influence the outcome.Furthermore, multivariate analysis applying Cox Regression and adjusted by Brazilian and European patients confirmed that overall survival was only influenced by aaIPI 2 and 3 (HR 9.16, CI95%: 2.16-16.8; p< 0.0001) and female gender (HR 2.71, CI95%: 1.03-7.13; p= 0.004).In conclusionIn this series of European and Brazilian gastric DLBCL patients were confirmed the impact of aaIPI on survival and identified female gender as poor prognosis factor. Differences in clinical presentation among countries may relate to heterogeneous disease biology and deserve further investigations. DisclosuresLuminari:Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees.

Effect of rituximab on outcomes in gastric B-cell lymphomas and on early mortality in gastric DLBCL.

e19501 Background: Rituximab has improved outcomes in B-cell NHL though early complications, such as gastric perforation have been reported (median time to event 6 days). Methods: Using case listin...

A Clinicopathological Analysis Of Primary Gastric Lymphoma

Introduction:Primary gastrointestinal lymphoma represents the most common location of extranodal lymphoma (1).The stomach represents 50-75% of the gastrointestinal tract localizations (2). Primary gastric lymphomas are divided into indolent (low grade) and aggressive (high grade) types. They are mainly the disease of middle age, with a male predominance reported by most of the studies (3). Controversy remains regarding the best treatment for early stages of the disease. Chemotherapy, Surgery and combination have been studied and shared almost comparable results with survival rate of 70-90%. However, chemotherapy possesses the advantage of preserving gastric anatomy (4). Recent years have seen a dramatic paradigm shift in the treatment approach to the most common gastrointestinal lymphomas, i.e. DLBCL and MALT lymphoma of the stomach. While surgery had been the main stay of treatment for decades, it has now virtually been abolished due to the absence of a beneficial effect as compared to conservative therapy (5). The discovery of an association between Helicobacter pylori (HP) and gastric MALT lymphoma and the subsequent reports of lymphoma regression following HP-eradication have revolutionized treatment options for such patients. HP-eradication is currently considered standard first-line therapy in patients with gastric MALT lymphoma and evidence of HP-infection, with complete responses being obtained in roughly 75% of selected patients [My paper] (6). Also combined modality treatment by chemo-radiation for localized gastric lymphoma is associated with a low risk of treatment related complications, with avoidance of long term sequelae after gastric resection (7). In DLBCL of the stomach, the association with HP-infection is less pronounced than in MALT lymphoma at roughly 50% of patients. While gastric DLBCL had also been subjected to surgery in order to prevent bleeding and perforation during subsequent chemotherapy and radiation, it has been demonstrated that such prophylactic surgery is not necessary with the consequent application of a high dose proton pump inhibitors for the whole duration of therapy. In addition, the relapse rate and survival are not beneficially influenced by additional surgery, while quality of life may be severely impaired. Most large studies have been performed combining anthracycline - based chemotherapy and radiation therapy (5). The response rate after Chemotherapy was 90%, while after radiotherapy it was 100%, only 10% of patients had relapse after ending treatment. Only one case died during the follow up Table 2.Grade I nausea and vomiting was the most frequent complication of chemotherapy among studied patients* Oncology Department of Ain Shams University.** Oncology Department of Ahmed Maher Teaching Hospitalfollowed by Grade I myelosuppression where only 25% of patients complained from it Fig 2Grade I anorexia was the most common complication of radiotherapy among studied patients followed by Grade I nausea and vomiting where 40% of patients complained from it Fig 3.The mean overall survival time was 21 months, from the survival curve; the survival rate was estimated at 24 months to be 94.7%. The mean disease free survival time was 19.97 months, from the survival curve; the disease free survival rate was estimated at 12 and 24 months to be 98.7% and 94.2% respectively. There was no significant difference between male and females, high and low grade type, different tumor stage, H.Pylori infection, increased LDH level, fungating or ulcerating mass as regarding the mean survival time and mean disease free survival time. Significant association between B2 microglobulin increase and relapse of patients, as 50% of relapsed patients had an increase in B2 microglobulin. Highly significant association between LDH increase during follow up and occurrence of relapse as 100% of relapsed patients showed increases LDH levels during follow up, on the other hand none of the non-relapsed patients had elevated LDH.

R-CHOP with dose-attenuated radiation therapy could induce good prognosis in gastric diffuse large B cell lymphoma

BackgroundThe treatment strategy for gastric diffuse large cell lymphoma (DLBCL) has not been standardized in such as to the cycles of chemotherapy, dose of radiation, or necessity for the surgery. Although the results of CHOP or R-CHOP treatments have demonstrated the good prognosis, the treatments have been controversial in many cases.MethodsWe retrospectively analyzed 40 gastric DLBCL patients receiving chemotherapy with or without radiation in our institute. Those in stages II-IV were treated with six cycles of R-CHOP without radiation; for those in stage I, we administered three cycles of R-CHOP with radiation.ResultsThe three-year overall survival (OS) and progression-free survival (PFS) rates were 95.2 and 91.8%, respectively. Those in stage I obtained 100% of OS. The radiation dose prescribed was 30.6 Gy for CR cases and 39.6 to 40 Gy for PR after chemotherapy. Although survival rates tended to correlate with staging groups or age-adjusted IPI classifications, multivariate statistical analysis did not show clear differences. All 14 patients with initial bleeding were successfully managed without surgery during treatment.ConclusionR-CHOP therapy was very effective for gastric DLBCL. It may be not necessary to use more than 30.6 Gy of radiotherapy in the highly chemo-sensitive cases. Less toxic treatments should be made available to gastric DLBCL patients.

Abstract 1747: Helicobacter pylori-positive diffuse large b-cell lymphoma: a distinct clinicopathologic entity

Abstract Background We previously reported that H. pylori-positive gastric DLBCL, with or without evidence of MALT origin, may respond to H. pylori eradication therapy. In this study, we further investigated the clinicopathologic features of H. pylori-positive DLBCL without histologic evidence of MALT origin. Methods We reviewed consecutive cases of gastric DLBCL without histologic evidence of MALT origin. H. pylori infection was documented by histologic examination, a urease test or bacterial culture. H. pylori-positive cases were further examined for CagA protein expression. Results A group of 45 patients positive for H. pylori were not histomorphologically different from a group of 48 patients negative for H. pylori. However, patients with H. pylori infection had a better International Prognostic Index score (0-1, 70% vs 30%, P = ·001), a lower clinical stage (I-IIE1, 73% vs 33%, P &amp;lt; [[Unable to Display Character: &amp;#8729;]]001), a better tumor response to chemotherapy (complete response, 80% vs 50%, P = .01), and significantly better 5-year event-free survival (EFS) (71% vs 24%, P &amp;lt; [[Unable to Display Character: &amp;#8729;]]001) and overall survival (OS) (73% vs 30%, P &amp;lt; [[Unable to Display Character: &amp;#8729;]]001). CagA expression, as defined by more than 5% of tumor cells with CagA staining, was identified in 23 (68%) of 34 H. pylori-positive tumors. Compared with the 11 H. pylori-positive but CagA-negative cases, the 23 H. pylori-positive, CagA-positive cases were associated with significantly better 5-year EFS (73% vs 15%, P = [[Unable to Display Character: &amp;#8729;]]002) and OS (91% vs 27%, P = [[Unable to Display Character: &amp;#8729;]]001). Conclusion H. pylori-positive gastric DLBCL, particularly with CagA expression in tumor cells, appears to be a distinct tumor entity, sharing some key clinicopathologic features with H. pylori-associated gastric MALT lymphoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1747.

Role of chemotherapy in gastric MALT lymphoma, diffuse large B-cell lymphoma and other lymphomas

Primary gastrointestinal lymphomas are relatively common, with the large majority occurring in the stomach. In the commonest histological subtype, i.e. diffuse large B-cell lymphoma (DLCBL), chemotherapy has widely been applied in the past, either following surgery or - in more recent years - as part of conservative management in combination with radiotherapy. Relatively little data, however, exist for chemotherapy as sole treatment modality in localised gastric DLBCL, which nevertheless are highly promising and suggest that combination therapy might overtreat a substantial proportion of patients. In gastric MALT-lymphoma, the use of chemotherapy has been restricted either to patients with a priori disseminated disease or individuals judged to be at high risk or failing local treatment approaches. Only a few prospective phase II studies have been performed, and one controlled trial has shown that chemotherapy was superior in terms of event free survival at ten years when compared to radiation and surgery. These suggest that systemic treatment approaches might be highly effective both in gastric DLBCL as well as MALT-lymphoma, and the scope of this article is to briefly summarize current data on chemotherapy in gastric and GI-lymphomas according to histologic subtypes.

Gastric Diffuse Large B-Cell Lymphoma: Analyses of Prognostic Factors and Value of Pretreatment FDG-PET Scan.

Abstract 3703Poster Board III-639 BackgroundUp to 40% of patients with DLBCL present with extranodal involvement of lymphoma, among which stomach is a common site. Patients with gastric DLBCL are generally treated with chemotherapy with or without radiotherapy similar to other DLBCL, but the disease may carry specific biological features. We herein present our experience with gastric DLBCL, and attempted to identify potential prognostic factors. Furthermore, the value of pretreatment PET scan was analyzed in this population, since CT scan is generally not sensitive in detecting gastrointestinal lesions. MethodsWe reviewed patients with gastric DLBCL treated with CHOP or R-CHOP based therapy in Aichi Cancer Center Hospital from 1995 to 2008. Multiple characteristics were evaluated for their prognostic values for complete response rate (CRR), overall survival (OS) and progression free survival (PFS). We also calculated the sensitivity of PET scan in detection of gastric involvement of lymphoma. ResultsSeventy-five patients with gastric DLBCL were identified and analyzed. The median age of patients was 66 (range 21-87). Thirty-five patients (47%) had Lugano stage I or II1, defined here as limited disease. International prognostic index (IPI) was low in 39 patients (52%), low-intermediate in 17 (23%), high-intermediate in 7 (9%) and high in 12 (16%). The CRR after initial treatment was 83%, and 5-year overall survival (OS) rate was 72% (median follow up duration was 32months). In 35 patients with limited disease, 25 patients (71%) underwent three courses of CHOP or R-CHOP followed by involved field radiation. Eight patients (23%) underwent gastrectomy (curative intent [n=6], control of bleeding [n=1] or obstruction [n=1],) followed by CHOP or R-CHOP. Two of those with limited disease (avoided radiation due to large primary lesion [n=2]) and all with advanced stage (Lugano II2 or IV; n=40) were treated with 6 to 8 cycles of CHOP with or without rituximab. Multivariate analysis with logistic regression model for CRR revealed that rituximab (odds ratio [OR] 0.1, p=0.007), Hb>12.0g/dl (OR 0.11, p=0.004) were independently associated with higher CRR. Multivariate analysis with Cox proportional hazard model for OS revealed that treatment without rituximab (hazard ratio [HR] 3.27, p=0.027), Hb<12.0g/dl (HR 4.06, p=0.006), and serum albumin level < lower limit of normal range (HR 3.43, p=0.023) were independently associated with shorter OS. An analysis for PFS revealed that treatment without rituximab (HR 2.73, p=0.03), advanced stage (HR 3.36, p=0.006), Hb<12.0g/dl (HR 3.61, p=0.004), and serum albumin level < lower limit of normal range (HR 2.96, p=0.021) were independently associated with shorter PFS.In the initial work up of patients with newly diagnosed DLBCL in general, upper gastrointestinal endoscopy has been a part of staging studies in our institution. PET scan was introduced as a part of pretreatment staging studies in 2003. Gastric lymphoma was diagnosed by gastroscopy performed for screening purposes or digestive symptoms (i.e. DLBCL was diagnosed by biopsy of gastric tumor, group A) in 52 patients (69%), by gastroscopy performed as a part of staging evaluations for proven lymphoma by biopsies of other site in 17 patients (23%, group B) and the diagnostic process was not well documented in 6 (8%). Twenty-two patients in group A underwent pretreatment PET scans, among which five did not show any abnormalities (sensitivity 77%). All these 5 had small stage I disease originally detected by screening gastroscopy. Eleven patients in group B underwent pretreatment PET scan, which all showed gastric lesions (sensitivity: 100%). ConclusionsWe showed the survival benefit of rituximab in gastric DLBCL. Furthermore, hemoglobin and albumin levels were determined to be potential prognostic factors in these patients. While PET scan seems reasonably sensitive to detect gastric involvement of lymphoma as a part of staging evaluation, small stage I gastric DLBCL can be missed by PET scan. Larger scale studies are needed to validate the prognostic factors identified here, and more data is needed to determine the value of pretreatment PET scan in this patient group. Disclosures:No relevant conflicts of interest to declare.

Immunohistochemical Expression of Germinal Center and Non-Germinal Center Markers in Primary Gastric Diffuse Large B-Cell Lymphoma

BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma.AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis.PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method.RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%.CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

Differences in germinal centre and non-germinal center phenotype in gastric and intestinal diffuse large B-cell lymphomas

The gastrointestinal tract is the most common extranodal site of lymphoma, and the most common gastrointestinal lymphoma is diffuse large B-cell type (DLBCL). DLBCL can be separated into germinal centre (GCP) and non-germinal centre phenotypes (non-GCP) using CD10, BCL-6 and MUM1 immunohistochemistry, but primary gastrointestinal DLBCL has not been extensively studied. We investigated 48 cases of primary gastrointestinal DLBCL (33% involving the small intestine, 50% the stomach, 13% the large intestine and 4% the ileocecal junction) and found that most (88%) DLBCL in the intestines were of GCP, while only 58% of gastric DLBCL were of GCP. This difference in GCP and non-GCP in gastric vs. intestinal DLBCL may be due to variations in lymphomagenesis reflecting acquired vs. native mucosa-associated lymphoid tissue. There was no significant difference in either overall survival or disease-free survival between the germinal centre and non-germinal centre groups. The distribution of Helicobacter pylori in different gastric DLBCL phenotypes raises interesting questions about the pathogenesis of H. pylori-associated lymphomas.

Clinical Profile of Patients with Primary Gastric Lymphoma: A Single Centre Experience.

BACKGROUND/AIMS: There are many controversies regarding the treatment for primary gastric non-Hodgkin's lymphoma (PGL). We hypothesized that chemotherapy and local radiotherapy would improve patient survival in the treatment of with PGL.METHODOLOGY: Between January 2003 and July 2007, retrospectively evaluated 15 patients with stage IE and IIE PGL. All patients clinical, biochemical, radiological and endoscopic features were evaluated. The histological diagnosis was established by endoscopic biopsies in all cases. All patients were treated with CHOP,RCHOP with or without radiotherapy. Patients with MALT as histopathology received H.pylori treatment. Upon the completion of chemotherapy, IFRT was given in the doses of 40.0 Gy. None of the patients underwent surgery. The response rates of chemotherapy and radiotherapy were analyzed.RESULTS: We have treated 300 patients of non hodgkins lymphomas, extranodal NHLs were 80, GI lymphomas were 50,15 patients had PGL. The age rage was 39–71 years. Nine patients were males and 6 were females. The most common symptom was abdominal pain in 46.66% followed by abdominal mass in 33.33%,dyspepsia in 13.33% and weakess in 6.66% of patients. Duration of symptoms varied from 15 days to 6 months. Histological subtypes were diffuse large B-cell in 80% and marginal zone B-cell NHL of the mucosa-associated lymphoid tissue (MALT)-type in 20% of patients. Helicobacter pylori infection (HPI) was seen in all MALT type NHLs. Six patients(40%) received RCHOP with RT followed by RCHOP in 4(26.66%), CHOP in 3(20%) and R-CHOP with RT in 2 (13.33%) patients. Response was evaluated by repeat endoscopy after completion of 3 and 6 cycles. Fourteen (93.33%) patients showed complete response only after 3 cycles of chemotherapy. Only one (6.66%) relapsed who received CHOP alone. All patients are alive with a median follow-up of 30 months (range 2 to 54 months).CONCLUSIONS: Primary chemotherapy with or without radiotherapy may produce complete remission in Stage IE-IIE PGL. The gastric function was well preserved with negligible stomach-related symptoms in all the patients. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.