Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Identifying SLC2A6 as the novel protective factor in breast cancer by TP53-related genes affecting M1 macrophage infiltration.

The high heterogeneity of breast cancer (BC) caused by pathogenic gene mutations poses a challenge to immunotherapy, but the underlying mechanism remains unknown. The difference in the infiltration of M1 macrophages induced by TP53 mutations has a significant impact on BC immunotherapy. The aim of this study was to develop a TP53-related M1 macrophage infiltration molecular typing risk signature in BC and evaluate the biological functions of the key gene to find new immunotherapy biomarkers. Weighted correlation network analysis (WGCNA) and negative matrix factorization (NMF) were used for distinguishing BC subtypes. The signature and the nomogram were both constructed and evaluated. Biological functions of the novel signature gene SLC2A6 were confirmed through in vitro and in vivo experiments. RNA-Sequencing and protein profiling were used for detecting the possible mechanism of SLC2A6. The results suggested that four BC subtypes were distinguished by TP53-related genes that affect M1 macrophage infiltration. The signature constructed by molecular typing characteristics could evaluate BC's clinical features and tumor microenvironment. The nomogram could accurately predict the prognosis. The signature gene SLC2A6 was found to have an abnormally low expression in tumor tissues. Overexpression of SLC2A6 could inhibit proliferation, promote mitochondrial damage, and result in apoptosis of tumor cells. The HSP70 family member protein HSPA6 could bind with SLC2A6 and increase with the increased expression of SLC2A6. In summary, the risk signature provides a reference for BC risk assessment, and the signature gene SLC2A6 could act as a tumor suppressor in BC.

Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3-4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies.

Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma.

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Discontinuation and nonpublication of nasopharyngeal carcinoma clinical trials.

OBJECTIVES: To determine the extent of research waste in the field of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this cross-sectional study, we explored the rates, causes and predictors of discontinuation and nonpublication of NPC clinical trials. The sample was derived using the ClinicalTrials.gov advanced search function. Adjusted logistic regression was used to ascertain the effect of trial characteristics on completion and publication status. If a trial discontinuation explanation or publication status could not be determined through the systematic search, the corresponding author was emailed. RESULTS: Ultimately, 311 NPC clinical trials were included (255 [82.0 %] completed and 56 [18.0 %] discontinued trials). The most common reason for trial discontinuation was poor accrual (50 %, 23/46). Industry funding (adjusted OR, 3.12; P = 0.003) and recurrent/metastatic setting (adjusted OR, 11.95; P = 0.003) were significantly associated with increased likelihood of trial discontinuation. Of the 207 completed trials included in the publication query, 141 (68.1 %) were published in peer-reviewed journals, 10 (4.8 %) had results only available on ClinicalTrials.gov, and 56 (27.1 %) remained unpublished 3 or more years after trial completion. Radiation with or without pharmacologic interventions significantly increased the potential of publication (adjusted OR, 3.20; P = 0.048). Among published trials, the median time to publication was 28.47 months (interquartile range, 15.27-44.98 months). CONCLUSION: We identified the difficulties inherent in NPC clinical trials from completion to publication. This represents considerable research waste in NPC, thus raising ethical concerns about the concealment of clinical data and futile patient participation and attendant risks.

Primary breast diffuse large B-cell lymphoma in the rituximab era: A retrospective study of the Chinese Southwest Oncology Group.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. METHODS: A total of 5089 newly diagnosed DLBCL patients treated with rituximab-containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group-affiliated institutes were identified, of whom 135 diagnosed with PB-DLBCL were eligible for this analysis. RESULTS: PB-DLBCL accounted for 2.7% of all DLBCLs. With a median follow-up of 4.2 years, the 5-year overall survival and progression-free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5-year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high-dose methotrexate (HD-MTX) than for patients who did not (5-year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB-DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD-MTX did not experience CNS relapse. CONCLUSION: Collectively, our results indicate combined modality therapy including rituximab-containing immunochemotherapy and consolidative breast RT is a promising approach for PB-DLBCL, while HD-MTX is useful for preventing CNS relapse.

Characteristics of immunotherapy trials for nasopharyngeal carcinoma over a 15-year period.

Background: Immunotherapy has been a hotspot in nasopharyngeal carcinoma (NPC) in recent years. This study aimed to provide a comprehensive landscape of the characteristics of immunotherapy clinical trials in NPC and to determine whether contemporary studies are of sufficient quality to demonstrate therapeutic value. Methods: This is a cross-sectional analysis of NPC trials registered on ClinicalTrials.gov in the last 15 years (Jan 1, 2008-Nov 20, 2022). Only interventional trials with a primary purpose of treatment were included in the final analysis. Characteristics of immunotherapy trials were compared with those of other NPC trials. Chronological shifts in NPC immunotherapy trials were also analyzed. Results: Of the 440 NPC studies selected, 161 (36.6%) were immunotherapy trials and 279 (63.4%) were other NPC trials. NPC immunotherapy trials were more likely than other NPC trials to be phase 1-2 (82.6% vs. 66.7%, P < 0.001), single-arm (51.3% vs. 39.6%, P = 0.020), non-randomized (64.8% vs. 44.4%, P < 0.001), and enroll fewer than 50 participants (46.3% vs. 34.4%, P = 0.015). Blinding was used in 8.8% of NPC immunotherapy trials. Also, 90.7% of NPC immunotherapy trials were recruited nationally and 82.6% were Asia-centric. Although academic institutions and governments (72.7%) were the major sponsors of NPC trials, immunotherapy trials were more likely to be industry-funded than other NPC trials (34.2% vs. 11.5%, P < 0.001). The number of NPC immunotherapy trials increased exponentially after 2017, attributed to the exploration of immune checkpoint inhibitors. Immunotherapy combined with chemotherapy was the most commonly investigated regimen. Conclusion: NPC immunotherapy trials over a 15-year period were predominantly exploratory. To generate high-quality evidence and advance the clinical application of immunotherapy in NPC, more attention and concerted efforts are needed.

Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review).

Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein­Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early­stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC. After comprehensive radiochemotherapy, 20­30% of patients with advanced NPC still fail treatment, mainly due to recurrence and/or metastasis (R/M). Conventional salvage treatments, such as radiotherapy, chemotherapy and surgery, are suboptimal and frequently accompanied by severe adverse effects and limited efficacy. In recent years, immunotherapy has emerged as a promising treatment modality for R/M NPC. An increasing number of clinical studies have investigated the safety and efficacy of immunotherapy for advanced NPC and have shown considerable progress. In the present review, the rationale for the use of immunotherapy to treat NPC was summarized and the current status, progress and challenges of NPC clinical research on different immunotherapeutic approaches were highlighted, including immune checkpoint inhibitors, vaccines, immunomodulators, adoptive cell transfer and EBV­specific monoclonal antibodies. The comprehensive overview of immunotherapy in NPC may provide insight for clinical practice and future investigation.

A prognostic 15-gene model based on differentially expressed genes among metabolic subtypes in diffuse large B-cell lymphoma.

The outcomes of patients with diffuse large B-cell lymphoma (DLBCL) vary widely, and about 40% of them could not be cured by the standard first-line treatment, R-CHOP, which could be due to the high heterogeneity of DLBCL. Here, we aim to construct a prognostic model based on the genetic signature of metabolic heterogeneity of DLBCL to explore therapeutic strategies for DLBCL patients. Clinical and transcriptomic data of one training and four validation cohorts of DLBCL were obtained from the GEO database. Metabolic subtypes were identified by PAM clustering of 1,916 metabolic genes in the 7 major metabolic pathways in the training cohort. DEGs among the metabolic clusters were then analyzed. In total, 108 prognosis-related DEGs were identified. Through univariable Cox and LASSO regression analyses, 15 DEGs were used to construct a risk score model. The overall survival (OS) and progression-free survival (PFS) of patients with high risk were significantly worse than those with low risk (OS: HR 2.86, 95%CI 2.04-4.01, p < 0.001; PFS: HR 2.42, 95% CI 1.77-3.31, p < 0.001). This model was also associated with OS in the four independent validation datasets (GSE10846: HR 1.65, p = 0.002; GSE53786: HR 2.05, p = 0.02; GSE87371: HR 1.85, p = 0.027; GSE23051: HR 6.16, p = 0.007) and PFS in the two validation datasets (GSE87371: HR 1.67, p = 0.033; GSE23051: HR 2.74, p = 0.049). Multivariable Cox analysis showed that in all datasets, the risk model could predict OS independent of clinical prognosis factors (p < 0.05). Compared with the high-risk group, patients in the low-risk group predictively respond to R-CHOP (p = 0.0042), PI3K inhibitor (p < 0.05), and proteasome inhibitor (p < 0.05). Therefore, in this study, we developed a signature model of 15 DEGs among 3 metabolic subtypes, which could predict survival and drug sensitivity in DLBCL patients.

Proposed prognostic subgroups and facilitated clinical decision-making for additional locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a retrospective study based on recursive partitioning analysis.

BACKGROUND: The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups. METHODS: The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables. RESULTS: After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein-Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort. CONCLUSIONS: The novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical features and treatment outcome of lymphoepithelioma-like carcinoma from multiple primary sites: a population-based, multicentre, real-world study.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear. MATERIALS AND METHODS: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis. RESULTS: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001). CONCLUSION: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).

A genomic-augmented multivariate prognostic model for the survival of natural-killer/T-cell lymphoma patients from an international cohort.

With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E). Cox-proportional hazard multivariate regression also showed that the new GPM is independent and significant for both progression-free survival (PFS, HR: 3.73, 95% CI 2.07-6.73; p < .001) and overall survival (OS, HR: 5.23, 95% CI 2.57-10.65; p = .001) with known risk-features of these indices. When we assign an additional risk-score to samples, which are mutant for the GPM, the Harrell's C-indices of GPM-augmented IPI, PINK, and PINK-E improved significantly (p < .001, χ2 test) for both PFS and OS. Thus, we report on how genomic mutational information could steer toward better prognostication of NKTCL patients.

A novel prognostic nomogram for patients with extragastric mucosa-associated lymphoid tissue lymphoma: A multicenter study.

BACKGROUND: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression-free survival (PFS)-related nomogram. We also performed external validation of the nomogram in an independent cohort. RESULTS: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C-index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5-year PFS was 98.9% for the low-risk group and 69.3% for the high-risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low-risk group and 94.6% for the high-risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5-year PFS rates were 94.8% and 66.7% for the low-risk and high-risk groups, respectively (p < 0.001). The 5-year OS rates were 97.9% and 88.4%, respectively (p = 0.016). CONCLUSION: The nomogram could well distinguish the prognosis of low- and high-risk patients with extragastric MALT lymphoma and is thus recommended for clinical use.

Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study.

PURPOSE: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. MATERIALS AND METHODS: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. RESULTS: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor-positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. CONCLUSION: This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor-positive patients.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Surgery and Chemotherapy versus Chemotherapy Only in Older Persons with Primary Intestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND: The management of primary intestinal diffuse large B cell lymphoma (PI-DLBCL) in elderly patients (aged >60 years) remains controversial. We conducted a retrospective study to assess the efficacy of different treatment strategies and prognostic factors for elderly Chinese patients with PI-DLBCL. PATIENTS AND METHODS: Forty-six untreated elderly patients with PI-DLBCL were included in this retrospective study. Twenty-four patients were treated with surgery (prior to chemotherapy) plus chemotherapy (SCT). The other 22 patients did not undergo surgery before chemotherapy (CT). RESULTS: Patients treated with SCT had a higher overall response rate of 91.7% than patients receiving CT, but the difference between groups was not significant (P=0.581). Regarding survival, SCT resulted in a greater 3-year overall survival (OS) rate (87.3% vs 56.9%, P=0.130) and significantly higher 3-year event-free survival (EFS) rate (74.1% vs 27.3%, P=0.002) than CT. The univariate analysis showed that male sex, advanced Lugano stage, poor performance status and chemotherapy alone were associated with a shorter EFS. Only the male sex was correlated with a shorter OS. The multivariate analysis showed that sex (P=0.040) and treatment strategy (P=0.022) were independent prognostic factors for EFS. CONCLUSION: Surgery plus chemotherapy produced a better outcome for EFS, but not OS, than chemotherapy alone in elderly Chinese patients with PI-DLBCL.