Gastrointestinal Diffuse Large B-cell Lymphoma Research Articles

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

PET Radiomics Score Generated By Cross-Combination Approach for Treatment Response and Prognosis Prediction in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma Patients

Background: Current risk stratification for primary gastrointestinal diffuse large B-cell lymphoma（PGI-DLBCL） relies on mainly on clinical factors. Radiomics score (RadScore) associated with survival outcomes have been developed for other cancer types, however few studies have thus far examined the role of radiomics in PGI-DLBCL. Objective: In this study, we investigated the value of PET RadScore constructed using a machine learning cross-combination approach in predicting the early treatment response and prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) treated with the R-CHOP-like regimen. Methods: A retrospective analysis was conducted on 108 PGI-DLBCL patients diagnosed through histopathological examination at two independent medical centers from March 2011 to March 2023, with 86 patients in the training cohort and 22 patients in the validation cohort. Seven different machine learning models were used to generate 49 feature selection-classification candidates, and the optimal candidate was selected based on the area under curve of ROC to establish RadScore. Risk factors were identified through logistic regression, and a radiomics nomogram was constructed by combining RadScore with the selected risk factors. The model was evaluated through calibration curves and decision curve analysis (DCA) using the training cohort and validation cohort. Results：A total of 111 radiomics features were extracted, and 19 features with strong predictive performance were selected to generate RadScore. The results suggest that RadScore can stratify patient prognosis.The logistic regression analysis results in the training cohort showed that elevated lactate dehydrogenase (LDH) level (OR=3.53, 95%CI: 1.21-10.31, p=0.021), intestinal involvement (OR=3.04, 95%CI: 1.04-8.88, p=0.042), and total lesion glycolysis (TLG) (OR=6.73, 95%CI: 2.23-20.29, p＜0.001) were independent risk factors for predicting early treatment response. A multi-parameter model incorporating clinical risk factors, metabolic factors, and RadScore was constructed (training cohort AUC: 0.834; validation cohort AUC: 0.902), and the performance of the model was evaluated. Conclusion：The RadScore, constructed based on a cross-combination approach using machine learning, can predict the survival of PGI-DLBCL patients. When RadScore is combined with clinical risk factors and metabolic factors, it forms a combinatorial model suitable for predicting early treatment response to R-CHOP-like chemotherapy regimens. Larger studies will be needed to validate these results. Keywords ： Primary gastrointestinal diffuse large B-cell lymphoma · [18F]FDG PET/CT · Early treatment response · Prognosis · Machine learning

Profiling risk factors for separation of infection complications in patients with gastrointestinal and nodal diffuse large B-cell lymphoma

ObjectiveTo identify risk factors for infection complications in patients with gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) and nodal DLBCL (N-DLBCL) during treatment, respectively.MethodsTotal 51 GI-DLBCL patients and 80 N-DLBCL patients were included after retrieving clinical data from a single medical center in the past ten years. Logistic regression analysis was utilized to analyze patients’ data, including baseline demographics, treatments and laboratory values, to determine independent risk factors of infection in these patients.ResultsTotal 28 of 51 patients (54.9%) in the GI-DLBCL group and 52 of 80 patients (65%) in the N-DLBCL group were observed infection events during treatment. A multivariate logistic regression model revealed that Ann-arbor stage IV (P = 0.034; odds ratio [OR]: 10.635; 95% confidence interval [CI]: 1.152-142.712), extra-nodal lesions ≥ 2 (P = 0.041; OR: 23.116; 95%CI: 1.144-466.949) and high serum lactate dehydrogenase (LDH) at the time of diagnosis (LDH > 252U/L; P = 0.033; OR: 6.058; 95%CI: 1.159–31.659) were independent risk factors for the development of infection in patients with GI-DLBCL after systemic treatment. In the N-DLBCL group, high serum C-reactive protein (CRP) (P = 0.027; OR: 1.104; 95%CI: 1.011–1.204) and a low platelet count (P = 0.041; OR: 0.991; 95%CI: 0.982-1.000) at routine blood tests just before infection occurred were identified as significant risk factors related to infection events during treatment.ConclusionsDiscordant independent risk factors induced infection may be present during the treatment in patients with GI-DLBCL and N-DLBCL. Close monitoring these risk factors is likely an effective strategy to prevent microbial infections in these patients.

Outcomes and Toxicities in Patients with Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract.

Diffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) tract is rare and long-term outcomes are not well defined. Combined modality therapy (CMT) with radiotherapy (RT) in addition to systemic therapy in this setting is not commonly pursued. We aim to characterize outcomes in patients with GI DLBCL treated with systemic therapy, with or without RT. Patients diagnosed with DLBCL of the GI tract (with or without mesenteric involvement) treated at a single institution from 1988-2022 were retrospectively reviewed on an IRB-approved protocol. Clinical and treatment data were collected including adverse events (AE; acute vs late defined as before or 4 weeks after therapy end). Kaplan-Meier and Cox regression models were used to estimate survival. Of 207 patients, 62% were male and median age at diagnosis was 63 (IQR 52-73). Gastric involvement was most common (n = 130, 63%), followed by small intestines (n = 48, 23%) and colon/rectum (n = 24, 12%). Most presented with early-stage disease (n = 124, 60%), with a median IPI score of 1. All patients received chemotherapy. Of 182 treated with CHOP/EPOCH, 36 (20%) were treated in the pre-rituximab era while 146 (80%) received rituximab. 66 patients (32%) were treated with RT, 89% as part of first line CMT. 50 cases (76%) received consolidative RT, while 10 (15%) targeted residual gross disease and 4 (6%) targeted distant sites. Median dose and fractionation were 36Gy (IQR 30.6-39.6) in 18 fractions (IQR 17-22). Over half (n = 132, 64%) developed grade 3+ acute chemotherapy AEs, and the most common were anemia (n = 64), febrile neutropenia (n = 40), and neutropenia (n = 20). Grade 3+ late chemotherapy AEs occurred in 14 patients (7%). Acute grade 3+ radiation AEs were uncommon (n = 2, 3%; colitis, emesis). No grade 3+ late radiation AEs were noted. Median follow-up was 46 months (IQR 16-97). 169 (81.6%) had a complete response (CR), with 154 (91%) after first line chemotherapy, 9 (5%) after second line, and 6 (4%) after RT. CR was defined by PET (62%), endoscopy (22%), CT (9%), or other methods (7%). The 5-year progression-free survival for those treated with one line of chemotherapy with or without RT was 95%. Median overall survival (OS) was not reached. Improved OS was associated with early-stage disease (p = 0.003), low IPI (p = 0.001), fewer chemotherapy lines (p<0.001), and CR (p<0.001). OS did not differ by gender, age, immunophenotype, GI site, SUVmax, or RT. Patients with early stage DLBCL treated with RT in the post-rituximab era received fewer chemotherapy cycles compared to those treated without RT (p = 0.02; median of 4 (IQR 3-6) vs 6 cycles (IQR 4-6)), with no OS difference. GI DLBCL patients have favorable outcomes after CMT with minimal late toxicity. CMT with RT to the GI tract is well tolerated with no OS difference compared to chemotherapy alone, and may mitigate risks from additional chemotherapy cycles for selected early-stage patients.

Prognosis and complications of patients with primary gastrointestinal diffuse large B-cell lymphoma: Development and validation of the systemic inflammation response index-covered score.

This study aimed to evaluate the predictive value of systemic inflammation response index (SIRI) in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) patients and establish a highly discriminating risk prediction model. This retrospective analysis included 153 PGI-DCBCL patients diagnosed between 2011 and 2021. These patients were divided into a training set (n=102) and a validation set (n=51). Univariate and multivariate Cox regression analyses were conducted to examine the significance of variables on overall survival (OS) and progression-free survival (PFS). An inflammation-covered score system was established according to the multivariate results. The presence of high pretreatment SIRI (≥1.34, p < 0.001) was significantly associated with poorer survival and identified as an independent prognostic factor. Compared with NCCN-IPI, the prognostic and discriminatory capability of the novel model SIRI-PI showed a more precise high-risk assessment with ahigher area under the curve (AUC) (0.916 vs 0.835) and C-index (0.912 vs 0.836) for OS in the training cohort, and similar results were obtained in the validation cohort. Moreover, SIRI-PI also showed good discriminative power for efficacy assessment. This new model identified patients at risk of developing severe gastrointestinal complications following chemotherapy. The results of this analysis suggested that the pretreatment SIRI may be a potential candidate for identifying patients with apoor prognosis. And we established and validated a better-performing clinical model, which facilitated the prognostic stratification of PGI-DLBCL patients and can serve as a reference for clinical decision-making.

Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed.MethodsWe performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed.ResultsA total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL.ConclusionsOur study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL.

S3393 Diffuse Large B Cell Lymphoma Presenting as Bleeding and Hypoalbuminemia: A Case Report

Introduction: Diffuse large B cell lymphoma (DLBCL) accounts for 38-57% of primary gastrointestinal (GI) lymphomas. Initial presentation can include nonspecific symptoms, such as weight loss, fatigue, and nausea. Imaging studies are typically nonspecific as well. Therefore, patients are commonly misdiagnosed or diagnosis is delayed. 20-30% of GI lymphomas are in the small intestine but are rarely in the jejunum. We present a rare case of jejunal DLBCL and illustrate the diagnostic difficulties. Case Description/Methods: A 49-year-old male presented with weeks of dizziness, dyspnea, hematochezia, and 30-pound unintentional weight loss over 4 months. Labs were notable for anemia and severe hypoalbuminemia (1.9 g/dL). Esophagogastroduodenoscopy and colonoscopy revealed diverticulosis and hemorrhoids, which were the presumed etiology of his symptoms. One month later, the patient presented similarly. Imaging demonstrated bilateral pulmonary emboli and intramural thickening of the jejunum. For worsening hypoalbuminemia (1.3 g/dL), the patient was scheduled for outpatient work-up. However, he presented again for acute GI bleed and severe anemia. Push enteroscopy revealed patchy mucosal changes in the jejunum and biopsies were consistent with DLBCL. The patient was started on chemotherapy and reported improvement in symptoms and resolution of his GI bleed. Discussion: Primary GI DLBCL is rarely found in the jejunum due to the lack of lymphoid tissue, making this case noteworthy. GI DLBCL is difficult to diagnose, since patients may be asymptomatic or present with nonspecific symptoms. Small intestinal DLBCL can present with GI bleeding, which can easily lead to a misdiagnosis of a diverticular or hemorrhoidal bleed. Imaging studies can be nonspecific and obtaining confirmation through biopsy can prove difficult due to its location, further complicating the diagnosis. One unique aspect of this case that led to the diagnosis was the severity of hypoalbuminemia. The patient was not malnourished, had no clinically apparent protein-losing enteropathy, and no proteinuria or liver failure, making underlying malignancy likely. Differential diagnoses of small bowel wall thickening on imaging is wide and includes infections, primary inflammatory processes such as IBD, and neoplastic lesions. DLBCL may have unusual clinical presentations, subtle laboratory findings and may not be easily diagnosed with initial imaging; thus, clinicians should remain vigilant of this possible diagnosis.

Serum miR-21 predicts the prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) lacks specific clinical manifestations and its malignancy renders prognostication and choice of treatment strategy difficult. The aim of this study was to evaluate microRNA (miR)-21 as potential non-invasive biomarkers for prognosis in PGI-DLBCL patients. Serum miR-21 expression in de novo PGI-DLBCL patients, consecutively enrolled for this study, was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression was calculated using the comparative Ct method. Statistical significance was determined using the Mann-Whitney rank sum and Fisher's exact test. Survival analysis was conducted using the Kaplan-Meier method. Compared with healthy controls, serum miR-21 levels were significantly elevated in the PGI-DLBCL patients (n=156). The high expression level of serum miR-21 at diagnosis was associated with worse progression-free survival (PFS) (30 (9-42) vs 42 (12-52) months in high and low miR-21 groups) and overall survival (OS) (35 (15-52) vs 48 (17-61) months in high and low miR-21 groups) and was an independent risk factor for PFS and OS (hazard ratios 4.345 and 3.311, respectively). Furthermore, Bcl-2, Bcl-6 and Ki-67 were independently and positively associated with miR-21 expression. Our results suggest that miR-21 is a potential prognostic marker to predict clinical outcomes in PGI-DLBCL patients and a high miR-21 level is associated with poor outcomes.

A New Staging System Based on the Dynamic Prognostic Nomogram for Elderly Patients With Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

ObjectiveThe purpose of this study is to establish an accurate prognostic model based on important clinical parameters to predict the overall survival (OS) of elderly patients with primary gastrointestinal diffuse large B-cell lymphoma (EGI DLBCL).MethodsThe Cox regression analysis is based on data from the Surveillance, Epidemiology, and End Results (SEER) database.ResultsA total of 1,783 EGI DLBCL cases were eligible for the study [median (interquartile range, IQR) age, 75 (68–82) years; 974 (54.63%) males], of which 1,248 were randomly assigned to the development cohort, while 535 were into the validation cohort. A more accurate and convenient dynamic prognostic nomogram based on age, stage, radiation, and chemotherapy was developed and validated, of which the predictive performance was superior to that of the Ann Arbor staging system [C-index:0.69 (95% CI:0.67–0.71) vs. 56 (95%CI:0.54–0.58); P < 0.001]. The 3- and 5-year AUC values of ROC curves for 3-year OS and 5-year OS in the development cohort and the validation cohort were were alll above 0.7.ConclusionWe establish and validate a more accurate and convenient dynamic prognostic nomogram for patients with EGI DLBCL, which can provide evidence for individual treatment and follow-up.

Diffuse Large B-Cell Lymphoma, Epstein–Barr Virus -Positive Kappa Monotypic Plasma Cell Proliferation and Invasive Carcinoma, Developing in a Child With Defective Mismatch Repair

Constitutional mismatch repair deficiency (CMMRD) syndrome is characterized by biallelic mutations in a mismatch repair gene and is associated with development of childhood cancers and symptoms resembling neurofibromatosis type 1, like café-au-lait spots. We describe the extremely rare case of a 12-year-old male presenting with several light brown macular lesions on the skin, gastrointestinal diffuse large B-cell lymphoma, adenomatous polyposis throughout the gastrointestinal tract and an intra-abdominal invasive carcinoma derived from upper gastrointestinal system. All neoplasia, as well as normal tissues, showed loss of Msh6 expression with immunohistochemistry. Molecular studies showed pathogenic homozygous p.F1088Sfs*2 mutation in MSH6. Furthermore, signs consistent with immunodeficiency, namely decreased levels of IgG and IgA in the serum, nodular lymphoid hyperplasia and EBV-associated plasma cell proliferation with monotypic kappa light chain expression in the ileum, were also noted. Our case depicts the phenotypic diversity of CMMRD syndrome and emphasizes its association with immunodeficiency, raising awareness to a feature not widely recognized.

Abstract PO-123: Palliative care use among people living with HIV and cancer: An analysis of the National Cancer Database (2004-2018)

Abstract Background: Prior studies demonstrate that people living with HIV (PLWH) are less likely to receive any curative cancer treatment compared to their HIV-negative counterparts. Data regarding trends of palliative treatment use among PLWH with cancer are lacking. Timely intervention with palliative care can increase survival and improve patient-reported quality of life among all cancer patients, particularly those with metastatic disease. Our objective was to compare the use of palliative care by HIV status among patients with cancer in the United States. Methods: We used data from more than 19 million patients 18-90 years of age in the National Cancer Database diagnosed between 2004 and 2018. The eleven most common cancers diagnosed among PLWH were selected, including Kaposi Sarcoma, cancers of the head and neck, upper gastrointestinal tract, colorectum, anus, lung, female breast, cervix, and prostate, Hodgkin lymphoma, and diffuse large B-cell lymphoma (DLBCL). HIV status was determined from reported comorbidities using the ICD-9-CM diagnosis codes 04200-044.90, 07593, V0800 and ICD-10-CM codes B20-B22, B24, Z21. Palliative care was defined as any surgery, radiation, systemic therapy, or pain management treatment with non-curative intent. Multivariate logistic regression was used to examine associations between HIV-status and palliative care use by cancer site and stage-at diagnosis and adjusted for age at diagnosis, race/ethnicity, gender, insurance, geographic region, comorbidity index, and cancer diagnosis year. Results: The study population included 52,306 HIV-positive (Avg. age: 56.5 years) and 19,115, 520 HIV-negative (Avg. age: 63.7 years) cancer cases. PLWH with cancer were more likely to be Non-Hispanic (NH)-Black (35.1% vs. 10.8%, p&amp;lt;0.001) and Hispanic (11.2% vs. 5.6%, p&amp;lt;0.001) compared to HIV-negative cancer patients. PLWH with stage 1-3 cancer at diagnosis were more likely to receive palliative care compared to their HIV negative counterparts (aOR:1.96, 95% CI:1.80-2.14). Conversely, PLWH with stage-4 cancer at diagnosis were less likely to receive palliative care (aOR:0.70, 95% CI:0.66-0.74). When evaluated by cancer site, stage-4 lung (aOR:0.80, 95% CI: 0.73-0.87) and colorectal (aOR: 0.72, 95% CI: 0.54-0.95) HIV-positive cancer patients were less likely to receive palliative care than HIV-negative cancer patients. PLWH diagnosed with stage I-III cancer who received palliative care were less likely to receive curative cancer treatment (aOR:0.48, 95% CI:0.40-0.59). Conclusion: Overall, utilization of palliative care is low among PLWH with cancer. PLWH diagnosed with stage-four cancer, particularly lung and colorectal cancer patients, are less likely to receive palliative care compared to their HIV-negative counterparts. PLWH with non-metastatic disease are more likely to receive palliative care, reinforcing prior data that curative treatment is not offered. Efforts to address the overall low utilization and better understand disparate utilization by cancer stage among PLWH should be prioritized. Citation Format: Jessica Y. Islam, Leticia Nogueria, Gita Suneja, Anna Coghill, Tomi Akinyemiju. Palliative care use among people living with HIV and cancer: An analysis of the National Cancer Database (2004-2018) [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-123.

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.

828MO Exonic mutation profile of primary gastrointestinal diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed.

Increased MALAT1 expression predicts poor prognosis in primary gastrointestinal diffuse large B-cell lymphoma.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.

Analysis of the Predictive Value of EZH2 Expression Level on the Clinical Efficacy and Long-term Prognosis of Patients with Primary Gastrointestinal Diffuse Large B-cell Lymphoma

To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.

A Prognostic Model of Gastrointestinal Diffuse Large B Cell Lymphoma.

BackgroundThe digestive tract is the most common site of extranodal involvement in diffuse large B cell lymphoma (DLBCL) and its prognostic evaluation is different from that of ordinary DLBCL. Currently, for gastrointestinal lymphoma, in addition to the Ann Arbor staging system, the Lugano and the TNM staging systems are commonly used. However, there is no effective prognostic model to identify poor prognosis in patients with localized gastrointestinal diffuse large B cell lymphoma (GI-DLBCL).Material/MethodsThis study included 82 patients with GI-DLBCL that had a median follow-up of 75 months, and developed a model (HLAMA) with 5 variables: hemoglobin, age, lactate dehydrogenase (LDH), serum albumin, and the maximum intra-abdominal lesion diameter (MIALD). The specific indicators are: HGB <105 g/L (2 points); LDH ≥300 U/L; age ≥75 years, ALB <38 g/L, MIALD ≥4 cm (each scoring 1 point). We also developed a simplified model, which includes only 3 variables (HGB, LDH, and age).ResultsHLAMA model and the simplified model both demonstrated good ability to predict prognosis of patients with GI-DLBCL (P<0.001), performing better than the IPI score as it could distinguish low-risk groups in relatively elderly patients (60–75 years old).ConclusionsThis study established a prognostic model for diffuse large B cell lymphoma of the gastrointestinal tract. Both the HLAMA model and its simplified version are similar to the IPI score, but could be considered better as they can provide a simpler and more accurate prognostic assessment in patients with GI-DLBCL. For patients with localized GI-DLBCL, our model could distinguish high-risk patients.

Role of MUM-1 immunohistochemistry in prognosis of primary gastrointestinal diffuse large cell lymphoma

: Diffuse large B-cell lymphoma (DLBCL) is the most common type of primary gastrointestinal lymphomas. It is a clinically heterogenous disease as most patients respond well to therapy, however a significant proportion of these patients become refractory or eventually relapse. Different prognostic factors for response and survival have been described for DLBCL. Immunophenotypic algorithms with small panels of biomarkers have been developed to translate the robust information from molecular studies into a routine clinical.platform. One of these biomarkers is MUM-1 which is used as a marker for classification of diffuse large B cell lymphoma into ABC type and its expression is associated with poorer overall survival as stated by various studies. We aim to study the expression pattern of MUM-1 IHC in primary gastrointestinal diffuse large B cell lymphomas and its role in prognosis and survival outcome. It was a five-year retrospective study where 40 cases of primary gastrointestinal DLBCL were identified, and MUM-1 IHC was done in 29 cases. Follow up and subsequent survival analysis was done.MUM-1 was positive in 7 (24%) and negative in 22 (76%) cases of primary gastrointestinal DLBCL. The overall survival of patients with DLBCL with MUM-1 expression (42.9%) was shorter than those without MUM-1 expression (72.7%). This suggested that MUM-1 expression in cases with DLBCL is associated with poorer prognosis.Multicentre large studies are warranted to study the role of MUM-1 IHC in prognosis of primary gastrointestinal DLBCL.

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.

Texture Analysis Improves the Value of Pretreatment 18F-FDG PET/CT in Predicting Interim Response of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Objectives To explore the application of pretreatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) texture analysis (TA) in predicting the interim response of primary gastrointestinal diffuse large B-cell lymphoma (PGIL-DLBCL). Methods Pretreatment 18F-FDG PET/CT images of 30 PGIL-DLBCL patients were studied retrospectively. The interim response was evaluated after 3-4 cycles of chemotherapy. The complete response (CR) rates in patients with different clinicopathological characteristics were compared by Fisher's exact test. The differences in the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and texture features between the CR and non-CR groups were compared by the Mann–Whitney U test. Feature selection was performed according to the results of the Mann–Whitney U test and feature categories. The predictive efficacies of the SUVmax, MTV, and the selected texture features were assessed by receiver operating characteristic (ROC) analysis. A prediction probability was generated by binary logistic regression analysis. Results The SUVmax, MTV, some first-order texture features, volume, and entropy were significantly higher in the non-CR group. The energy was significantly lower in the non-CR group. The SUVmax, volume, and entropy were excellent predictors of the interim response, and the areas under the curves (AUCs) were 0.850, 0.805, and 0.800, respectively. The CR rate was significantly lower in patients with intestinal involvement. The prediction probability generated from the combination of the SUVmax, entropy, volume, and intestinal involvement had a higher AUC (0.915) than all single parameters. Conclusions TA has potential in improving the value of pretreatment PET/CT in predicting the interim response of PGIL-DLBCL. However, prospective studies with large sample sizes and validation analyses are needed to confirm the current results.

2642 Diffuse Large B-Cell Lymphoma Presenting as Partial Small Bowel Obstruction and a Fistula

INTRODUCTION: Non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States, accounting for 4% of all cancers. Diffuse Large B-Cell Lymphoma (DLBCL) the most common type of NHL. Gastrointestinal (GI) tract is a significant site of extranodal NHL and accounts for 30%–40% of all extranodal NHL. Out of this, 44 % are due to DLBCL. Ileocecal DLBCL accounts for 9.7% to 15% of total GI DLBCL. They lack specific symptoms and diagnosed when complications occur. We report a case of elderly male hospitalized for partial small bowel obstruction and a possible fistula due to DLBCL involving the ileocecal valve extending to the ileum. CASE DESCRIPTION/METHODS: A 75-year-old male presented with complaints of abdominal pain, nausea, and nonbilious vomiting for a day. He denied any fever, chills, sick contact, night sweat, or weight loss. On physical exam, he had moderate lower abdomen tenderness without palpable masses. CT scan of the abdomen and pelvis showed partial small bowel obstruction with a transition point at an ileocecal junction with amorphous soft tissue at the level of the terminal ileum and possible stricture or neoplastic involvement (Figure 1). Three days later, he had a colonoscopy which showed a large mass behind the ileocecal valve with a fistula (Figures 2 and 3). We were unable to intubate the ileocecal valve. Multiple biopsied taken from the mass that confirmed the diagnosis of DLBCL. PET scan showed cecal mass without any distal involvement. As recommended by surgery and oncology consultations, he had right hemicolectomy. DISCUSSION: Ileocecal region is a rare place for DLBCL occurrence. Majority of the cases are diagnosed incidentally or when complication like obstruction, perforation, or bleeding occurs like our patient who had bowel obstruction on presentation. We also found a fistula in cecum during colonoscopy. Clinically we suspect fistula as the patient was able to tolerate diet and complete bowel preparation easily in spite of having complete closure of ileocecal valve on colonoscopy. Due to the lack of oral contrast, it was not identified on the initial CT scan. Endoscopic features of DLBCL are nondiagnostic. The only way to confirm a diagnosis is, immunohistopathology staining specific for DLBCL. Majority of ileocecal DLBCL are at stage I or II diseases at the time of diagnosis. Surgical resection followed by chemotherapy had shown prolongation of survival. In conclusion, ileocecal DLBCL should be considered as a differential diagnosis for bowel obstruction or fistula.