Primary Gastric Diffuse Large B-cell Lymphoma Research Articles

Primary gastric diffuse large B-cell lymphoma: A multicentre retrospective study.

Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) accounts for the majority of extra-nodal DLBCL. Even so, literature is lacking on early, localised presentations. We studied a cohort of patients with stage I disease, diagnosed between 2006 and 2018, from six centres between Australia, Canada and Denmark. Our goal was to characterise outcomes, review treatmentand investigate the role of interim positron emission tomography (iPET). Thirty-seven eligible patients were identified. The median duration of follow-up was 42.2 months. All received chemoimmunotherapy with 91.9% (n = 34) given rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). 35.1% (n = 13) underwent consolidative radiotherapy. Eighteen patients were H. pylori positive and 11 had the documentation of H. pylori eradication therapy. The 4-year progression-free survival and overall survival of R-CHOP was 88% (95% CI: 71-95) and 91% (95% CI: 75-97) respectively. All patients who achieved a partial metabolic response or complete metabolic response on iPET went on to achieve complete response at the end of treatment. R-CHOP-based therapy with iPET assessment appears to offer favourable outcomes, with radiotherapy and H. pylori eradication therapy implemented on a case-by-case basis.

Helicobacter pylori eradication treatment for primary gastric diffuse large B-cell lymphoma: A single-center analysis.

Unlike the already established effect of Helicobacter pylori (H. pylori) eradication on gastric mucosa-associated lymphoid tissue (MALT) lymphoma, its therapeutic effect on primary gastric diffuse large B-cell lymphoma (DLBCL) is still unclear. To clarify the efficacy of H. pylori eradication treatment for primary gastric DLBCL. We reported on 3 new cases, and added them to 3 previously reported cases. We analyzed the usefulness of H. pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center. Of the 6 patients (27-90 years old, 3 males and 3 females), all 3 patients with single lesions (one transformed from MALT lymphoma) achieved complete remission (CR) after H. pylori eradication. Regarding the 2 newly reported cases, CR was maintained for more than 6 years with eradication treatment alone. In contrast, none of the 3 patients with 2 lesions achieved CR. In 1 newly reported case, endoscopic CR was achieved in one lesion, while stable disease was obtained in the other lesion. Two patients with progressive disease responded to standard chemotherapy ± radiation and remained in CR for more than 6 years. We believe it is worthwhile to attempt H. pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden.

Outcome and patterns of relapse in primary gastric diffuse large B cell lymphoma treated with RCHOP

ABSTRACTObjectivesPatterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP).MethodsFrom 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS).Results64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6–185) months. The median time to progression or relapse was 9 months (range: 5–54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35–8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09–71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS.ConclusionTreatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.

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.

A study on the prevention of hemorrhage and perforation in patients with primary gastric diffuse large-B cell lymphoma during treatment with immunochemotherapy.

Stomach hemorrhage and perforation are very severe and common complications in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL) during treatment with immunochemotherapy. However, no relevant clinical studies have been performed on the prevention of these serious complications. Patients diagnosed with PG-DLBCL were enrolled in this retrospective study. The prevention group received standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment without prednisone combined with antacids and anti-Helicobacter pylori (Hp) therapy. These patients received R-CHOP-based treatment until the complete recovery of gastric ulcers, as proven by gastroscopy. The control group received a standard R-CHOP regimen. Toxicity and survival were the main endpoints. A total of 52 patients received preventative treatment, while 146 patients did not. Among patients with stage I, II-1, and II-2 disease, the prevention group had a lower rate of hemorrhage and perforation (0/40) than the control group (10/78, p=0.044). At a median follow-up time of 25 months, the 5-year event-free survival (EFS) rates were 97.1% in the prevention group and 66.1% in the control group (p=0.025), and the 5-year overall survival (OS) rates were 100% and 72.0%, respectively (p=0.021). However, the differences in the 5-year EFS and OS of patients with disseminated disease were not statistically significant. Preventative treatment can decrease the risk of hemorrhage and perforation in patients with localized PG-DLBCL during immunochemotherapy, leading to better EFS and OS in these patients. However, preventative treatment failed to reduce the risk of gastric hemorrhage and perforation and did not improve survival (EFS and OS) in advanced-stage patients.

A Novel Prognostic Model for Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common phenotype of extranodal non-Hodgkin's lymphoma (NHL). This research aims to identify a model for predicting overall survival (OS) and cancer-specific survival (CSS) in PG-DLBCL. A total of 1716 patients diagnosed with PG-DLBCL between 1975 and 2017 were obtained from the SEER database and further randomly divided into the training and validating cohorts at a ratio of 7 : 3. Univariate and multivariate cox analyses were conducted to determine significant variables for the construction of nomogram. The performance of the model was then assessed by the concordance index (C-index), the calibration plot, and the area under the receiver operating characteristic (ROC) curve (AUC). Multivariate analysis revealed that age, race, insurance status, Ann Arbor stage, marital status, chemotherapy, and radiation therapy all showed a significant association with OS and CSS. These characteristics were applied to build a nomogram. In the training cohort, the discrimination of nomogram for OS and CSS prediction was excellent (C-index = 0.764, 95% CI, 0.744-0.784 and C-index = 0.756, 95% CI, 0.732-0.780). The AUC of the nomogram for predicting 3- and 5-year OS was 0.779 and 0.784 and CSS was 0.765 and 0.772. Similar results were also observed in the internal validation set. We have successfully established a novel nomogram for predicting OS and CSS in PG-DLBCL patients with good accuracy, which can help physicians to quickly and accurately complete the evaluation of survival probability, risk stratification, and therapeutic strategy at diagnosis.

5-Hydroxymethylation alterations in cell-free DNA reflect molecular distinctions of diffuse large B cell lymphoma at different primary sites

Background5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almost any organ, but the prognosis of patients with DLBCL at different primary sites varies greatly. Previous studies have shown that 5hmC displays a tissue-specific atlas, but its role in DLBCLs at different primary sites remains unknown.ResultsWe found that primary gastric DLBCL (PG-DLBCL) and lymph node-involved DLBCL (LN-DLBCL) patients had a favorable prognosis, while primary central nervous system DLBCL (PCNS-DLBCL) patients faced the worst prognosis, followed by primary testicular DLBCL (PT-DLBCL) and primary intestinal DLBCL (PI-DLBCL) patients. Thus, we used hmC-CATCH, a bisulfite-free and cost-effective 5hmC detection technology, to first generate the 5hmC profiles from plasma cell-free DNA (cfDNA) of DLBCL patients at these five different primary sites. Specifically, we found robust cancer-associated features that could be used to distinguish healthy individuals from DLBCL patients and distinguish among different primary sites. Through functional enrichment analysis of the differentially 5hmC-enriched genes, almost all DLBCL patients were enriched in tumor-related pathways, and DLBCL patients at different primary sites had unique characteristics. Moreover, 5hmC-based biomarkers can also highly reflect clinical features.ConclusionsCollectively, we revealed the primary site differential 5hmC regions of DLBCL at different primary sites. This new strategy may help develop minimally invasive and effective methods to diagnose and determine the primary sites of DLBCL.

Rituximab-Based Regimens for Treatment of Primary Gastric Diffuse Large B-Cell Lymphoma

To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL). From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively. The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%（42/53）. The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P5-year OS=0.035). Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.

A Novel Prognostic Model for Primary Gastric Diffuse Large B-Cell Lymphoma in the Rituximab Era, Integrating EBV Harboring on Tumor Cells

Introduction: EBV‐positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) often shows an aggressive clinical course with frequent extranodal disease including gastrointestinal involvement. However, the clinicopathological and prognostic significance of the EBV+ disease among primary gastric DLBCL (gDLBCL) has not been confirmed. Recently targeted therapies using antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) have shown great promise in the treatment of relapsed or refractory DLBCL, but there remains a need for reliable methods to identify the candidates for novel immune-therapies.We analyzed the clinicopathological characteristics of gDLBCL and shed the light on the EBV harboring on tumor cells and PD-L1 expression as prognostic indicators for the future clinical trials of PD-1 blockade.Patients and methods: A total of 157 patients previously diagnosed as primary gDLBCL and treated with rituximab-containing chemotherapies were retrospectively examined. All cases were tested for EBV-encoded small RNA (EBER) by in situ hybridization (ISH). The expression of PD-L1 was immunohistochemically evaluated (clone SP142, Spring Bioscience, Pleasanton, CA).Results: Our series consisted of 157 patients: 92 males and 65 females (male: female ratio = 1.4), with a median onset age of 67 years (range, 32-89 years). 66 patients (42%) showed Lugano stage Ⅱ2/ⅡE/Ⅳ, 59 (40%) with high levels of soluble interleukin -2 receptors (sIL-2R >1000U/ml), 45 (29%) with IPI HI/H, and 34 (22%) with B symptoms. 39 patients (38%) had multiple gastric lesions, 19 (12%) with the presence of Bulky mass, and 29 (60%) with Helicobacter pylori infection. 92 patients (61%) had a non-germinal center B-cell immunophenotype (non-GCB). All of 157 patients received multiagent chemotherapy combined with rituximab, with an additional irradiation in 55 (35%). EBV harboring was found on the tumor cells in 12 (7.6%). There was no significant difference in the clinicopathological findings between EBV+ and EBV‐negative (EBV−) subgroups. But, notably, the EBV+ patients had a significantly worse overall survival (OS) than EBV− ones (P=0.004). Multivariate analysis of survival revealed that EBER positivity (P=0.012), the presence of multiple gastric lesions (P=0.014), and IPI HI/H (P=0.017) were adverse independent prognostic factors in gDLBCL. We constructed a prognostic model by combining these prognostic variables as follows: patients with a score of 0 (n=43), no adverse factors; patients with a score of 1 (n=36), one factor; and patients with a score of 2/3 (n=24), two or three factors. The 5-year OS rates for these 3 groups were 100%, 91%, and 43%, respectively. Furthermore, this model significantly stratified gDLBCL patients separately by survival (P <0.001, Figure). Although none of gDLBCL cases expressed PD-L1 on tumor cells, 7 (78%) of 9 cases with EBV+ gDLBCL were positive for PD-L1 in ≥20% of nonmalignant stromal cells in microenvironment (miPD-L1+), which showed a higher frequency than in EBV− ones (78% vs 42%, P=0.13).Conclusions: EBV+ gDLBCL showed a significantly worse prognosis. Our prognostic model appeared to well define the clinical outcome of gDLBCL patients. PD-L1 expression in nonmalignant stromal cells was a common feature of EBV+ gDLBCL. They could be good candidates to benefit from anti-PD-1/PD-L1 therapy. A novel prognostic model by integrating EBV harboring on tumor cells may serve as a risk‐stratification for future clinical trials in which high‐risk patients can be treated with newly developing immune-therapies to improve their outcomes. [Display omitted] DisclosuresShimada:Kyowa Hakko Kirin Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria.

Prognostic Impact of Pretreatment 2-[18F]-FDG PET/CT Parameters in Primary Gastric DLBCL.

Background and Objectives: Primary gastric diffuse large-B cell lymphoma (DLBCL) is an aggressive lymphoma subtype with high 18F-FDG avidity but unclear criteria for 2-[18F]-FDG PET/CT in the evaluation of treatment response and prognostication. Our aim was to investigate whether the pretreatment 2-[18F]-FDG PET/CT variables may predict treatment response (at end of first-line therapy) and prognosis in primary gastric DLBCL. Materials and Methods: we included 57 patients with a diagnosis of primary gastric DLBCL and a baseline 2-[18F]-FDG PET/CT and an end of treatment PET/CT after 6 cycles of R-CHOP chemotherapy. We analyzed PET images qualitatively and semi-quantitatively by deriving the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume and total lesion glycolysis of gastric lesion (gMTV and gTLG), and total MTV (tMTV) and TLG. Survival curves were plotted according to the Kaplan–Meier analysis. Results: at a median follow up of 80 months, the median PFS and OS were 69 and 80 months. Baseline gMTV, gTLG, tMTV, and TLG were significantly higher in patients with incomplete response (partial response and progression) compared to complete response group. tMTV and TLG were confirmed to be independent prognostic factors both for PFS (p = 0.023 and p = 0.038) and OS (p = 0.038 and p = 0.026); instead, the other metabolic parameters were not related to outcome survival. Conclusions: high tMTV and TLG were significantly correlated with shorter survival (PFS and OS) and may predict incomplete response after therapy.

Absolute Monocyte and Platelet Counts May Provide Additional Prognostic Information in Primary Gastric Diffuse Large B-cell Lymphoma Patients Treated with Rituximab and CHOP.

Primary gastric diffuse large B cell lymphoma (PG-DLBCL) is the most common histological subtype of primary gastric lymphoma. The standard of care of PG-DLBCL patients is the combination rituximab-based immunochemotherapy (R-CHOP). Re-cently, different host-related factors have been shown to have significant prognostic significance in non-Hodgkin lymphoma. However, data regarding their prognostic contribution to PG-DLBCL are limited. To assess the prognostic impact of a panel of simple, cost-effective laboratory variables which are easy to apply in routine labora-tory use for R-CHOP-treated PG-DLBCL patients in an attempt to identify those among them that are high-risk category. We retrospectively assessed the possible prognostic impact of different laboratory markers in 42 R-CHOP treated PG-DLBCL patients treated between 2004 and 2014 and followed at a single institution. The estimated 5-year overall (OS) and progression-free survival (PFS) of the whole group were 80.9% and 78%, respectively. The absolute monocyte and platelet counts in univariate analysis predicted PFS and OS when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the stage-modified International Prognostic Index (m-IPI), the absolute monocyte and platelet counts remained independent predictors of PFS and OS. Therefore, the absolute monocyte and platelet counts were combined to generate a prognostic index that identified patients with an especially poor overall survival. This prognostic index was independent of the m-IPI and could provide additional prognostic information for better stratification of these patients.

Will Baseline Total Lesion Glycolysis Play a Role in Improving the Prognostic Value of the NCCN-IPI in Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated With the R-CHOP Regimen?

The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P < 0.001) and OS (P < 0.001): high-risk group (TLG > 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.

Pattern of failure and optimal treatment strategy for primary gastric diffuse large B-cell lymphoma treated with R-CHOP chemotherapy.

PurposeThe optimal treatment for primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is still unknown. We evaluated unfavorable prognostic factors and pattern of failure in PG-DLBCL to determine the optimal treatment strategy.MethodsBetween April 2001 and November 2018, 120 patients with complete remission following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were retrospectively reviewed. According to the Lugano staging system, 80 patients (66.7%) had localized disease and 40 patients (33.3%) had advanced disease. A total of 93 (77.5%) patients had single gastric lesion and 27 (22.5%) patients had multiple gastric lesions. Ninety patients (75%) were treated with R-CHOP chemotherapy alone and 30 patients (25%) received R-CHOP chemotherapy with additional local treatment for gastric lesions.ResultsThe 5-year locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) rates in patients treated with R-CHOP chemotherapy with local treatment were 100%, 100%, and 100%, respectively, whereas the LRFS, PFS, and OS rates in patients treated with R-CHOP chemotherapy alone were 86.3%, 78.2%, and 87.4%, respectively (p = 0.031, p = 0.095, and p = 0.025, respectively). During the follow-up period, 17 patients (14.2%) had disease recurrence. Only 3 of the 17 patients had relapse in a completely new site without relapse in the initial involved site. All, except 2, cases of local recurrence included gastric failure. In the multivariate analysis, performance status and number of gastric lesions were independent prognostic factors for treatment outcome.ConclusionsPatients with complete remission following R-CHOP chemotherapy showed a good prognosis. The main pattern of failure in patients with PG-DLBCL was local recurrence, especially in the stomach. Patients who received local treatment for gastric lesions showed improved gastric control. Therefore, in patients with unfavorable prognostic factors, we recommend R-CHOP chemotherapy with additional local treatment for gastric lesions.

Switching Fractioned R-CHOP Cycles to Standard R-CHOP Cycles Guided by Endoscopic Ultrasonography in Treating Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

BackgroundPrimary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common subtype of extranodal non-Hodgkin lymphoma (NHL), with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as the commonly used treatment regimen. However, full cycles of standard R-CHOP present the risk of severe bleeding or perforation, even leading to emergency surgery, especially for those with deep lesions in their first 1–2 cycles of treatment. This study aims to explore the safety and efficacy of fractioned R-CHOP (rituximab d0, 50% dose of CHOP d1 and d5) followed by standard R-CHOP cycles in PG-DLBCL patients guided by endoscopic ultrasonography (EUS).Patients and MethodsThirty-one PG-DLBCL patients were analyzed in this retrospective study. All patients had lesions infiltrated to at least the 3rd layer of the stomach under EUS at baseline. Patients switched to standard R-CHOP if they showed the reduced infiltrated layers and restricted lesions after fractioned R-CHOP cycles.ResultsThe overall response rate, 5-year progression-free survival (PFS) and overall survival (OS) of patients in our study were 93.5%, 75% and 84%, respectively. No treatment delay or dosage reduction from gastric adverse event was observed. None of the patients in our study suffered from severe bleeding or perforation during the treatment. Kaplan–Meier analyses showed that PG-DLBCL patients characterized by multiple localization, lesions ≥3cm, having B symptoms, lower serum albumin level, and elevated LDH level were associated with worse PFS and OS.ConclusionOur data indicate that it might be an effective approach in treating deeply infiltrated PG-DLBCL patients by switching fractioned R-CHOP to standard R-CHOP cycles guided by EUS.

Primary Gastric Diffuse Large B-Cell Lymphoma: Prognostic Factors in the Immuno-Oncology Therapeutics Era

Objective:This study aimed to explore the prognostic factors for primary gastric diffuse large B-cell lymphoma (PG-DLBCL).Materials and Methods:This retrospective study analyzed 72 PG-DLBCL patients between January 2012 and December 2017 in the Shanxi Cancer Hospital of Shanxi Medical University to identify the different prognostic factors in PG-DLBCL. The clinical features, treatment, and follow-up information were analyzed.Results:The low CD4:CD8 ratio group (median subsequent overall survival [OS]: 36.06 months; 95% confidence interval [CI]: 25.73-46.40) showed a significant decrease in subsequent OS compared to the normal group among PG-DLBCL patients who were newly diagnosed and did not receive rituximab (median OS: 52.58 months; 95% CI: 44.18-60.97; p=0.029). Event-free survival status 24 months after the date of diagnosis (EFS24) also decreased significantly in the low CD4:CD8 group (median EFS24: 16.27 months; 95% CI: 13.09-19.45) compared to the normal group (median EFS24: 20.34 months; 95% CI: 17.05-23.63; p=0.014). Multivariate analysis showed that low CD4:CD8 at diagnosis was an independent poor prognostic factor for subsequent OS and EFS24.Conclusion:Our data suggest that identifying prognostic factors, especially host immunity, may provide useful information for assessing prognosis or clinical management.

Prediction of Overall Survival and Progression-Free Survival by the 18F-FDG PET/CT Radiomic Features in Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

Purpose. To determine whether the radiomic features of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) contribute to prognosis prediction in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients. Methods. This retrospective study included 35 PG-DLBCL patients who underwent PET/CT scans at West China Hospital before curative treatment. The volume of interest (VOI) was drawn around the tumor, and radiomic analysis of the PET and CT images, within the same VOI, was conducted. The metabolic and textural features of PET and CT images were evaluated. Correlations of the extracted features with the overall survival (OS) and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were conducted to assess the prognostic value of the radiomic parameters. Results. In the univariate model, many of the textural features, including kurtosis and volume, extracted from the PET and CT datasets were significantly associated with survival (5 for OS and 7 for PFS (PET); 7 for OS and 14 for PFS (CT)). Multivariate analysis identified kurtosis (hazard ratio (HR): 28.685, 95% confidence interval (CI): 2.067–398.152, p=0.012), metabolic tumor volume (MTV) (HR: 26.152, 95% CI: 2.089–327.392, p=0.011), and gray-level nonuniformity (GLNU) (HR: 14.642, 95% CI: 2.661–80.549, p=0.002) in PET and sphericity (HR: 11.390, 95% CI: 1.360–95.371, p=0.025) and kurtosis (HR: 11.791, 95% CI: 1.583–87.808, p=0.016), gray-level nonuniformity (GLNU) (HR: 6.934, 95% CI: 1.069–44.981, p=0.042), and high gray-level zone emphasis (HGZE) (HR: 9.805, 95% CI: 1.359–70.747, p=0.024) in CT as independent prognostic factors. Conclusion. 18F-FDG PET/CT radiomic features are potentially useful for survival prediction in PG-DLBCL patients. However, studies with larger cohorts are needed to confirm the clinical prognostication of these parameters.

1070PD - Treatment outcomes and pattern of failure in primary gastric diffuse large B cell lymphoma with complete remission following R-CHOP chemotherapy

BackgroundThe optimal treatment for primary gastric diffuse large B cell lymphoma (DLBCL) is unclear. The treatment for primary gastric DLBCL is in accordance with the principle of treatment for general DLBCL. We aimed to evaluate the treatment outcomes and pattern of failure in primary gastric DLBCL. MethodsBetween April 2001 and November 2018, 120 patients with stage I–IV primary gastric DLBCL were retrospectively reviewed in this study. All patients had been in complete remission after receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Ninety patients (75%) were treated with R-CHOP alone, and the other 30 patients (25%) underwent R-CHOP with local treatment for gastric lesions. Twelve patients (10%) underwent gastrectomy, and 18 patients (15%) received consolidation radiotherapy (RT). ResultsThe median follow-up time was 49 (range, 5 to 197) months. The 5-year locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 85.6%, 86.5%, 83.4%, and 90.3%, respectively. During the follow-up, 17 patients (14.2%) experienced disease recurrence. Only 3 patients developed distant metastasis without locoregional failure (LRF). All except two cases of LRF included gastric failure. There was no LRF in patients who received R-CHOP with local treatment. On multivariate analysis, poor performance status was an independent prognostic factor for LRFS, and multiple gastric lesions influenced LRFS, DMFS, DFS, and OS. ConclusionsThe main pattern of initial failure is LRF, especially in the stomach in patients with primary gastric DLBCL. Gastric local treatment such as consolidation RT can effectively prevent gastric failure. Therefore, gastric local treatment should be considered for patients at high risk of LRF, such as multiple gastric lesions. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

2782 Disguised as IBD: A Rare Presentation of Diffuse Large B Cell Lymphoma in a Young Male

INTRODUCTION: About 1-4% of all gastrointestinal malignancies are primary non-Hodgkin Lymphoma (NHL) and the most common pathologic subtype is diffuse large B-cell lymphoma (DLBCL). Risk factors include environmental exposure, Epstein Barr Virus (EBV), immunosuppression, Helicobacter Pylori (H.Pylori), and human T-cell leukemia virus type 1. The majority of patients are males over the age of 40. Patients can present with vague abdominal pain, dyspepsia, vomiting, weight loss, and bleeding. Endoscopic findings vary and include ulcers, erosions, nodules, mass, erythema, and gastric fold thickening. With appropriate therapy, the 5 year survival can be up to 90%. This case illustrates a rare presentation of gastric DLBCL, emphasizes the importance of both a broad differential diagnosis in the immunocompromised and prompt endoscopy in those with alarm symptoms. CASE DESCRIPTION/METHODS: An 18 year old male with selective IgA deficiency and a family history of Crohn’s in his father presented with 3 months of cramping abdominal pain, diarrhea with small amounts of blood and tenesmus. He also reported night sweats and a 10 pound weight loss. History was negative for fevers, localizing infectious symptoms, arthralgias, skin or visual manifestations of IBD. Laboratory evaluation revealed normal WBCs at 7.2 × 109/L with relative lymphocytosis [lymphocytes: 68% (Norm 18-52%), Neutrophils: 22% (Norm 18-52%)]. The rest of labs including Hbg, liver enzymes, albumin and CRP were normal. Given concern for Crohn’s, EGD and colonoscopy were performed. Colonoscopy to the terminal ileum with ileal and colonic biopsies was normal. EGD revealed a 1 cm non-bleeding cratered gastric ulcer with elevated edges and mild erythema in the gastric body. Biopsy of the ulcer demonstrated atypical dense lymphoid cell infiltrate with morphology and immunohistochemical features consistent with EBV + DLBCL. Duodenal biopsies were negative for Celiac disease. Gastric biopsies were negative for H. Pylori. He completed chemotherapy with R-CHOP and is in remission. DISCUSSION: This case illustrates a rare presentation of primary gastric DLBCL, given his young age and presentation with bleeding (occurring in ∼10% of cases). Even though this patient had a seemingly classic presentation for Crohn’s Disease, it is critical to maintain a broad differential diagnosis in immunocompromised patients and prioritize endoscopy in those with type B symptoms (weight loss, night sweats) in order to lead to prompt diagnosis and treatment.

Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression. This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018. Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL. The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.

A case of primary gastric diffuse large B-cell lymphoma occurring in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) and Non-Hodgkin Lymphoma (NHL) are two different origins of hematological malignancies, which rarely occur at the same time. Moreover, NHL secondary to CML is common in T cell lymphoma, while NHL of B cell origin is rare. Since 1999, only 22 cases with B cell lymphoma have been reported, of which 4 cases have diffuse large B-cell lymphoma (DLBCL). The lesions of DLBCL were in lymph node, liver, jejunum, and soft palate. To our knowledge, it has no report for the primary gastric DLBCL (PG-DLBCL) occurring in CML. Here we reported a 63-year-old man of chronic phase (CP) CML associated with PG-DLBCL. The patient was diagnosed with CML nearly eight years ago and was treated with imatinib and nilotinib successively. However, gastroscopy found malignant lesions in the patient’s stomach in March 2018, and the masses were diagnosed as PG-DLBCL. Subsequently, with the treatment of the RCOP + lenalidomide regimen chemotherapy for 3 cycles, the patient achieved nearly complete remission (CR).