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Purpose This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. Methods DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. Results A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P P P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). Conclusion The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

Background: Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. Methods: In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. Results: Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 109/L (range 18–219) among patients who received rhTPO and 73 × 109/L (range 42–197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count

Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

PurposeUsing the logistics service supply chain (LSSC) as a research object, this study focuses on the relationship between integration quality (IQ), value co-creation (VCC), and LSSC resilience. Moreover, it discusses the moderating role of digital technology (DT).Design/methodology/approachBased on data about China, this study used the structural equation model to test the research hypothesis. To verify the validity of each construct, this study used various established scales in the literature to conduct exploratory and confirmatory analysis.FindingsThe results show that IQ is an essential antecedent variable that promotes VCC and LSSC resilience. Moreover, this study confirms that DT has a positive moderating effect on the relationship between IQ, VCC, and resilience.Originality/valueThis study constructs a research framework to examine LSSC resilience and expands the theoretical research on the VCC theory in the supply chain literature. Moreover, this paper studies supply chain integration from a new perspective, that is, IQ, which is more in line with the reality of LSSC.

Background/aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53 mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53 mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53 mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP-like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53 mut DLBCL patients compared to R-CHOP-only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

Background: To investigate the prognostic role of red blood cell distribution width (RDW) and platelet/lymphocyte ratio (PLR) in early-stage classical Hodgkin lymphoma (cHL). Materials & methods: Data from 402 patients with newly diagnosed early-stage cHL were retrospectively collected. The impact of factors on complete response (CR) rate and freedom from progression (FFP) was analyzed. Results: High PLR was associated with lower CR, but high RDW was not. The univariate analysis showed that RDW and PLR were predictive of FFP. On multivariate analysis, high PLR was an independent risk factor for inferior FFP. Subgroup analysis and a prognostic model for FFP based on PLR validated the prognostic role of PLR. Conclusion: PLR was a robust prognostic factor for newly diagnosed early-stage cHL.

Background: The clinical course of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is variable, with limited efficacy data of second-line treatment in a post-rituximab real-world context. Hence, we explored the predictors and constructed a nomogram for risk stratification in this population. Patients and methods: Among 296 r/r DLBCL patients pretreated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between 2006 and 2017, 231 were included for nomogram construction. After randomization, we constructed the prognostic nomogram in the primary cohort (n=161) based on a multivariate analysis and confirmed it in the validation cohort (n=70). Additionally, we explored predictive factors for second-line therapy using a ordinal regression analysis. Results: Four independent prognostic factors including rituximab in the second-line setting, initial Eastern Cooperative Oncology Group (ECOG) performance status (PS), response to front-line treatment, and invasion on progression/recurrence were used to construct the nomogram. The nomogram had a C index of 0.70 with AUC values of 0.73 and 0.71 for the primary and validation cohorts, respectively. Subsequently, three risk groups (low, intermediate, and high) were determined with median overall survival (OS) of 38.0, 25.0, and 7.0 months, respectively. Additionally, we conducted a multivariate ordinal regression analysis and identified prior response to front-line treatment (odds ratio=4.50, 95% CI: 1.84-11.27, p=0.001) and bulky disease at diagnosis (odds ratio=0.36, 95% CI: 0.182-0.702, p=0.003) were two independent factors for second-line treatment efficacy. Conclusions: The established predictors for treatment efficacy and the novel nomogram for survival in r/r DLBCL patients could potentially be applied for risk stratification and treatment guidance in the post-rituximab era.

Limited data about the prognostic significance ofProbe capture-based high-resolution sequencing was performed on 191 patients diagnosed withThe presence ofThis study showed that DLBCL patients treated with R-CHOP

Background: This study aimed to explore the interactions and relationships of genes and recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy.Method: RNA sequencing data of dataset GSE65135 (n=24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n=137) and patient cohort of Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n=32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA and Cytoscape analysis, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95%CI [0.25-0.86], p = 0.014). Higher Serum CCL19 concentration was associated with longer progression-free survival (PFS, p=0.014) and OS (p=0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line immunochemotherapy.

Industry 4.0 aims to automate traditional manufacturing and industrial practices with the aids of recently developed information technologies such as cyber-physical systems, Internet of things, big data analytics, and cloud computing. Implementation of industry 4.0 in manufacturing leads to the digitization of all manufacturing businesses including computer aided design and manufacturing, enterprise resource planning, and supply chain management (SCM). This paper focuses on the challenges and solutions in digitizing supply chains in dynamic, distributed, and decentralized business environments. The complexity and dynamics of supply chains in industry 4.0 are discussed, the performance of a supply chain is evaluated from the perspectives of costs and quality of services, and supply chain management is formulated as an optimization problem for higher requirements of quality of services, efficiency, and timeliness. The challenges of developing digitization solutions to data acquisition, data fusion, and data-driven decision-making supports are discussed in detail. The potential solutions to these challenges are proposed and the impacts on supply chain management are assessed using the data from in a list of automotive manufacturers in China. It has been found the proposed solutions will make positive and significant impact on the digitation of supply chains.

Background Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population. Methods We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. Results The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR, This study provides real‐world evidence of survival and prognosis of untreated extensive stage small cell lung cancer (ES‐SCLC). We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from 2011 to 2018 in a Chinese top‐level cancer hospital. The median overall survival (OS) of all patients was 14.0 months, and the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. The median progression‐free survival (PFS) of 238 patients was 6.2 months, and the six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Moreover, several independent prognostic factors for OS and PFS of ES‐SCLC were identified.

Purpose This study aimed to develop a prognostic nomogram in diffuse large B-cell lymphoma (DLBCL) and compare it with traditional prognostic systems. Materials and methods We included 1,070 consecutive and nonselected patients with DLBCL in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, between 2006 and 2012. A nomogram based on the Cox proportional hazards model was developed. Results The entire group were divided into the primary (n = 748) and validation (n = 322) cohorts. The 5-year overall survival (OS) rate was 64.1% for the entire group. Based on a multivariate analysis of the primary cohort, seven independent prognostic factors including age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status score, lactate dehydrogenase, β2-microglobulin, CD5 expression, and Ki-67 index were identified and entered the nomogram. The calibration curve showed the optimal agreement between nomogram prediction and actual observation. In addition, the concordance index (C-index) of the nomogram for OS prediction was 0.77 (95% confidence interval [CI], 0.73–0.81) in the primary cohort and 0.76 (95% CI, 0.70–0.81) in the validation, superior to that of the international prognostic index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI (range, 0.69–0.74, p Conclusions The proposed nomogram provided an accurate estimate of survival of patients with DLBCL, especially for those receiving R-CHOP or R-CHOP-like regimens, allowing clinicians to optimized treatment plan based on individualized risk prediction. Implications for Practice A diffuse large B-cell lymphoma (DLBCL)-specific prognostic nomogram was developed based on Chinese patients with DLBCL. As a tertiary hospital, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences is the number 1 ranked cancer center in China, with more than 800,000 outpatients in 2018. Patients included in this study were nonselected and came from 29 different provinces, municipalities, and autonomous regions in China. Thus, the data is believed to be representative to an extent.

Background: Palliative chemotherapy has been the mainstay treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, little is known about the efficacy and toxicity of nimotuzumab (NTZ) – a monoclonal antibody drug targeting epidermal growth factor receptor – plus chemotherapy (CT) versus CT alone for these patients. Methods: The database at Cancer Hospital of Chinese Academy of Medical Sciences was queried for patients diagnosed with NPC who received CT with or without NTZ between 2004 and 2018. Treatment compliance, survival outcomes, and adverse effects were compared among these groups. Results: Records of 70 patients with R/M-NPC were reviewed: 21 (30%) received NTZ plus CT (NTZ+CT) and 49 (70%) received CT. CT regimens included gemcitabine plus platinum, taxane plus platinum (TP), and fluorouracil plus platinum. Comparing the CT group with NTZ+CT group, the median follow up was 62 months (range = 3–133) versus 59 months (range = 9–117); median progression free survival was 7.5 [95% confidence interval (CI) 6.552–8.381] months versus 8.5 (95% CI 6.091–10.976) months, p = 0.424; median overall survival (OS) was 25.6 (95% CI 18.888–32.379) months versus 48.6 (95% CI 35.619–61.581) months, p = 0.017, respectively. Multivariable analysis established treatment group (CT versus NTZ+CT) as an independent prognostic factor for OS (hazard ratio, 0.5; 95% CI 0.255–0.979; p = 0.043). No significant difference with regard to toxicities was observed between the two groups. Among them, a subgroup analysis was performed in 53 (75.7%) patients who received TP with or without NTZ, which showed similar results. Conclusion: Our findings suggested that NTZ+CT provides a novel treatment option and prolongs survival significantly for R/M-NPC.

Background: Programmed cell death protein 1 (PD1) inhibitors have revolutionized cancer therapy, yet many patients fail to respond. Thus, the identification of accurate predictive biomarkers of therapy response will improve the clinical benefit of anti-PD1 therapy. Method: We assessed the baseline serological autoantibody (AAb) profile against ~2300 proteins in 10 samples and ~4600 proteins in 35 samples with alveolar soft part sarcoma (ASPS), non-small-cell lung cancer (NSCLC) and lymphoma using Nucleic Acid Programmable Protein Arrays (NAPPA). 23 selected potential AAb biomarkers were verified using simple, affordable and rapid enzyme linked immune sorbent assay (ELISA) technology with baseline plasma samples from 12 ASPS, 16 NSCLC and 46 lymphoma patients. SIX2 and EIF4E2 AAbs were further validated in independent cohorts of 17 NSCLC and 43 lymphoma patients, respectively, using ELISA. The IgG subtypes in response to therapy were also investigated. Results: Distinct AAb profiles between ASPS, NSCLC and lymphoma were observed. In ASPS, the production of P53 and PD1 AAbs were significantly increased in non-responders (p=0.037). In NSCLC, the SIX2 AAb was predictive of response with area under the curve (AUC) of 0.87, 0.85 and 0.90 at 3 months, 4.5 months, 6 months evaluation time points, respectively. In the validation cohort, the SIX2 AAb was consistently up-regulated in non-responders (p=0.024). For lymphoma, the EIF4E2 AAb correlated with a favorable response with AUCs of 0.68, 0.70, and 0.70 at 3 months, 4.5 months, and 6 months, respectively. In the validation cohort, the AUCs were 0.74, 0.75 and 0.66 at 3 months, 4.5 months, and 6 months, respectively. The PD1 and PD-L1 IgG2 AAbs were highly produced in ~20% of lymphoma responders. Furthermore, bioinformatics analysis revealed antigen functions of these AAb biomarkers. Conclusion: This study provides the first evidence that AAb biomarkers selected using high-throughput protein microarrays can predict anti-PD1 therapeutic response and guide anti-PD1 therapy.

Background: Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) who are ineligible for or progressed from autologous stem-cell transplantation have poor outcomes and few treatment options. Programmed cell death-1 (PD-1) inhibitor monotherapy has limited efficacy in pretreated DLBCL. Previous study has demonstrated that pembrolizumab plus R-CHOP was effective and safe as first-line treatment in patients with DLBCL and in vitro data suggests that rituximab acts partly via antibody-dependent cellular cytotoxicity, which may be enhanced by programmed cell death-1 (PD-1) blockade. Here, we report the preliminary results of a real-world, single-arm study investigating efficacy and safety of PD-1 inhibitor plus rituximab for r/r DLBCL. Methods: This is a real-world, single-center, single-arm study enrolling patients who received at least one dose of PD-1 inhibitor combined with rituximab as salvage therapeutic regimen after R-CHOP treatment in Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College. Eligible patients received PD-inhibitors in combination with rituximab (375 mg/m2, q3w) for 6 cycles followed by maintenance therapy of PD-1 inhibitors plus rituximab (q8w) for 6 cycles until unacceptable toxicity, disease progression, death, or completion of 2-year treatment. The outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Responses were assessed by Lugano 2014 criteria, and PD-L1 staining (22C3) was performed at a validated central laboratory. Genomic analysis was performed including next generation sequencing (NGS) based sequence variant detection, copy number analysis and structural variant detection. Results: Between Oct 16, 2018, and May 10, 2021, 34 patients were enrolled and received at least one dose of both PD-1 inhibitor including toripalimab (n=24), pembrolizumab (n=3), nivolumab (n=3) and sintilimab (n=4), combined with rituximab. Key baseline characteristics included median age 56.5 (range 20-78) years; stage III/IV disease 58.8%; elevated LDH 41.2%; IPI ≥3 47.1%; median number of prior treatment regimen 2 (range 1-4); primary chemotherapy-refractory disease after R-CHOP 73.5%; median interval from last rituximab administration 5 (range 0.7-26) months. Histology included 30 DLBCL NOS (88.2%; 11 GCB, 19 non-GCB by Han's algorithm), 4 primary mediastinal B-cell lymphoma (PMBCL; 11.8%). Patients received a median of four (range 1-24) doses of PD-1 inhibitor and rituximab. Eight patients (6 DLBCL-NOS, 2 PMBCL) remained on treatment at the time of data cutoff on Jul 5, 2021. With a median follow-up of 21.3 months (95% CI: 9.6-24.2), 16 (53.3%; 95% CI: 34.3%-71.7%) of 30 patients with DLBCL-NOS had an objective response, with 2 (6.7%) having a complete response and 14 (46.7%) achieving a partial response. The median DOR was 16.8 (95%CI: 2.8-NR) months. The median PFS was 2.9 (95%CI: 1.5-18.5) months, and median OS was 25.3 (95%CI: 9.9-NR) months. The 1-year PFS and OS rates were 34.1% (95%CI: 17.3%-51.8%) and 73.6% (95%CI: 49.8%-87.4%), respectively. All of 4 PMBCL cases achieved CR, and their PFS were 21.2, 21.6, 22.9 and 29.2 months, respectively. Overall, 19 of 34 patients had available baseline biopsy samples for NGS analysis. Patients with TET2 mutations had higher ORR (100% versus 31.3%, p=0.058) and longer PFS (NR versus 1.6 months, p=0.019) while patients with β2-MG mutations had lower ORR (0% versus 53.3%, p=0.1) and shorter PFS (1.0 versus 2.8 months, p=0.0025). In addition, patients with BCL2 alteration/amplification/rearrangement had inferior OS than those BCL2 wild-type patients (5.0 versus 17.4 months, p=0.024). PD-L1 expression at baseline had no impact on response and survival. Most treatment-related adverse events were grade 1-2 including rash and neutropenia. Treatment was discontinued in 3 patients (2 interstitial pneumonia and 1 hypophysitis). Conclusion: PD-1 inhibitor combined with rituximab was effective and well tolerated in r/r DLBCL, achieving promising ORR and long-term remission. Further investigation is warranted. Disclosures No relevant conflicts of interest to declare.

// Wumin Dai 1 , Bo Jia 1 , Jianliang Yang 1 , Shengyu Zhou 1 , Peng Liu 1 , Xiaohui He 1 , Yan Qin 1 , Lin Gui 1 , Changgong Zhang 1 , Xiaohong Han 1 , Yan Sun 1 , Yuankai Shi 1 1 Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China Correspondence to: Yuankai Shi, email: syuankai@cicams.ac.cn , syuankaipumc@126.com Keywords: beta2-microglobin to lymphocytes ratio index, lactate dehydrogenase to lymphocytes ratio index, systemic immune-inflammation, prognosis, extranodal natural killer/T cell lymphoma Received: January 13, 2017 Accepted: March 15, 2017 Published: March 30, 2017 ABSTRACT To identify simple non-invasive prognostic factors for extranodal natural killer/T cell lymphoma (ENKTL), we have investigated the prognostic value of pretreatment β2-microglobin to lymphocytes ratio index (βLRI) or lactate dehydrogenase to lymphocytes ratio index (LLRI), by analyzing the retrospective data from 211 ENKTL patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of pretreatment βLRI and LLRI. The univariate analysis indicated that Ann Arbor Stage ( p = 0.008), Eastern Cooperative Oncology Group score (ECOG) ( p = 0.009), International Prognostic Index (IPI) ( p = 0.023), βLRI ( p = 0.003), LLRI ( p = 0.04), neutrophil-lymphocyte ratio index ( p = 0.025) and monocyte/granulocyte to lymphocyte ratio ( p = 0.030) were significantly associated with overall survival (OS) in ENKTL patients. However, multivariate analysis demonstrated that only Ann Arbor Stage ( p = 0.028), βLRI ( p < 0.001) and LLRI ( p = 0.006) were only correlated independently with OS. Furthermore, βLRI and LLRI based new prognostic model showed improved discrimination for stage IE/IIE upper aerodigestive tract in ENKTL patients than IPI and Korean Prognostic Index. Overall, our study concluded that new βLRI-based prognosis model is useful to stratify ENKTL patients and higher βLRI and LLRI can act as independent prognostic predictor candidates in early stage ENKTL.

The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (p = 0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (p = 0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0368-9) contains supplementary material, which is available to authorized users.

Clinical named entity recognition is an essential task for humans to analyze large-scale electronic medical records efficiently. Traditional rule-based solutions need considerable human effort to build rules and dictionaries, machine learning-based solutions need laborious feature engineering. For the moment, deep learning solutions like Long Short-term Memory with Conditional Random Field (LSTM&ndash, CRF) achieved considerable performance in many datasets. In this paper, we developed a multitask attention-based bidirectional LSTM&ndash, CRF (Att-biLSTM&ndash, CRF) model with pretrained Embeddings from Language Models (ELMo) in order to achieve better performance. In the multitask system, an additional task named entity discovery was designed to enhance the model&rsquo, s perception of unknown entities. Experiments were conducted on the 2010 Informatics for Integrating Biology &amp, the Bedside/Veterans Affairs (I2B2/VA) dataset. Experimental results show that our model outperforms the state-of-the-art solution both on the single model and ensemble model. Our work proposes an approach to improve the recall in the clinical named entity recognition task based on the multitask mechanism.

Introduction Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. Materials and Methods We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. Results We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Conclusions Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.

ObjectivesPatients’ stress and satisfaction concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate stress and satisfaction in CCT and the influencing factors.DesignCross-sectional analysis done by a questionnaire after informed consent.SettingCancer Hospital, Chinese Academy of Medical Sciences.Participants199 CCT participants. Primary and secondary outcome measures self-assessed stress and satisfaction in CCT.ResultsAmong 199 participants, 83.9% would join CCT again; 72.9% had enough time to decide on trial participation; 73.9% claimed complete awareness of CCT; 3.5% doubted CCT’s significance and scientific quality; 33.2% deemed CCT time-consuming; 73.9% scored satisfaction ≥9/10; and 25.6% claimed moderate to severe stress. Positive factors for satisfaction were enough decision time (OR=0.36, p=0.0003), better impressions of doctors (OR=0.41, p=0.047) and less time-consuming trials (OR=0.43, pConclusionsOur study addressed factors influencing CCT participants’ stress and satisfaction. We suggested measures to improve patients’ experiences in CCT.Trial registration numberNCT03412344; Pre-results.

Objective To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma (DLBCL) patients in China according to the primary site. Methods A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site. Results In the 1,085 patients, 679 (62.6%) cases were nodal DLBCL (N-DLBCL) and 406 cases (37.4%) were extranodal DLBCL (EN-DLBCL). The most common sites of N-DLBCL were lymphonodus (64.8%), Waldeyer's ring (19.7%), mediastinum (12.8%) and spleen (2.7%), while in EN-DLBCL, stomach (22.4%), intestine (16.0%), nose and sinuses (8.9%), testis (8.4%), skin (7.9%), thyroid (6.9%), central nervous system (CNS) (6.4%), breast (5.7%), bone (3.4%), and salivary gland (2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9% (P=0.008), and the 5-year PFS were 57.0% and 49.0% (P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate (83.6%) and PFS rate (76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach, breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%, respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%. Conclusions In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

Additional file 5: Figure S2. Total SNVs detected in plasma. (A) The total SNVs of each sample during chemotherapy was shown. The y-axis represented the mutation number. Each bar represented each sample. Each color represented one of the subsets: all detected mutations, coding region or Non-silent mutations. (B) The distribution of non-silent SNVs between individuals with chemotherapy sensitivity (PR/SDa) and other (PD/SD). Ligth blue represents these individuals with chemotherapy sensitivity (PR/SDa). (C) The distribution of C>G substitutions between individuals with chemotherapy sensitivity (PR/SDa) and other (PD/SD). (D) Boxplot showed the C>A substitution subtype comparison of pre-chemotherapy and post-chemotherapy. The y-axis represented the total SNVs. Each box represented each group and each red dot was on behalf of one sample. (E) Boxplot showed the comparison of pre-chemotherapy and post-chemotherapy. Box with lightcoral represented nonsmoker and box with medium turquoise represented smoker. Horizontal axis represented the chemotherapy cycles.

This paper intends to study the layout of emergency centers in the chemical park in two stages. First, a multi-agent collaborative location model is established to find out the sites of emergency centers. Second, DEA method is adopted to evaluate the efficiency of the existing reserve structure of each center, along with the optimization suggestions for the inefficient center. Finally, the safety system of the chemical park is improved by the combination of the location model and the DEA.

Reasonable siting layout of reserve emergency supplies plays a critical role in rapid response and accurate rescue after disaster. People&rsquo, s life safety and health, as well as the psychological satisfaction brought by the government&rsquo, s excellent emergency rescue level, is an important guarantee for maintaining social stability and sustainable development. Based on the coverage model, considering demand graduation, this paper develops a bi-objective optimization model to determine the optimal location plan of graduated supplies by maximizing the rescue satisfaction and minimizing the number of warehouses. A heuristic multi-center clustering location algorithm is designed to solve the model. This model is applied to the prepositioning of emergency supplies in an earthquake affected area in Sichuan province, China to verify the effectiveness of the model and algorithm. Finally, the paper discusses the influence of demand graduation on the location of emergency supplies. The results show that reasonable location planning of different levels of supplies can effectively improve the rescue satisfaction.

The prognostic value of pretreatment serum beta-2 microglobulin (B2MG) level in advanced Hodgkin lymphoma (HL) patients treated in the modern era has not been well established. We conducted a retrospective study involving 202 advanced classical HL (cHL) patients treated from 1998.5 to 2015.7 to evaluate the impact of serum B2MG level on prognosis. Multivariate analysis showed that serum B2MG level ≥ 2.5 mg/L was an independent predictor for freedom from progression (FFP) (P = 0.001), lymphoma-specific survival (P = 0.030) and overall survival (P = 0.034). The 5-year FFP of patients with serum B2MG level ≥ 2.5 mg/L was 66.8%, compared with 89.7% in patients with B2MG level < 2.5 mg/L (P < 0.001). The traditionally used International Prognostic Score (IPS) remained prognostic for FFP (P = 0.013) but the predictive range narrowed, with 5-year FFP ranging from 90.9% to 62.3%. The 5-year FFP of the 44 patients with both IPS ≥ 3 and serum B2MG ≥ 2.5 mg/L was 50.7%, which was significantly worse than that of the 87 patients with only one of the two factors (81.9%, P < 0.001) or the 71 patients with both B2MG < 2.5 mg/L and IPS < 3 (91.1%, P < 0.001). The difference of FFP between the latter two groups was smaller but also significant (P = 0.038). In summary, our data suggest pretreatment serum B2MG level ≥ 2.5 mg/L was an independent unfavorable prognostic factor in advanced cHL patients treated in the modern era. It improves IPS in predicting the outcomes as the combination of IPS and B2MG indentified a wider prognostic range than IPS alone with a sizable number of patients in different risk groups.

Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20+ B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods: Fifteen patients with CD20+ B-cell NHL received dose-escalating SCT400 infusions (250 mg/m2: n=3; 375 mg/m2: n=9; 500 mg/m2: n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P

The effective distribution of public storage materials is the key to realizing rapid and accurate rescue of territories, which could truly solve the &ldquo, last kilometer&rdquo, problem of emergency rescue. At present, it is relatively rare to study the rapid and accurate distribution of emergency supplies by taking demand forecasts, emergency reserves, and distribution models as an organic whole. In view of the bottleneck of rapid and accurate rescue in the complex disaster environment, this paper selects various means such as field research, literature retrieval, and previous case analysis and uses the system analysis method. Next, this paper explains that the three main factors that affect the distribution of public storage materials are the demand of &ldquo, black box&rdquo, the scarcity of materials, and the blindness of distribution and constructs an effective analysis framework of demand predictability, material availability, and distribution accuracy. Finally, this paper puts forward the triangle structure framework of demand forecasting, virtual public storage, and comprehensive distribution and further explains the triangle structure relationship, operation mechanism, and operation strategy of effective distribution of public storage materials.

The development of economic globalization makes the cooperation relationship between enterprises and suppliers closer. How to optimize suppliers becomes a research hotspot. This paper studies the selection process and selection method of quotient evaluation indicators based on the analysis of supplier data by using information visualization tools. The multi-dimensional data and analytic hierarchy process are used to evaluate the supplier’s commercial value and product information. The example of z agricultural machinery company is used to verify the effectiveness and feasibility of the new scheme.

The essence of agricultural products logistics is the entity flow and information transfer from producer to consumer, which not only meets the needs of customers, but also realizes the value of agricultural products. Huairen city has a huge demand for the modernization of agricultural products logistics because of its natural location advantage and the active guidance of national policies. Although the city has made progress in the construction of transportation facilities and logistics industry, there are still problems such as backward level of cold chain logistics, low level of standardization and informatization, and shortage of talents. Therefore, based on the theory and practice, this paper analyzes the current situation, explores the future development direction of Huairen city’s agricultural products logistics, so as to accelerate the establishment of a modern agricultural products circulation system, promote the rationalization and adjustment of the agricultural structure.

The evaluation of logistics performance of harbor-front station is conducive to the realization of efficient and coordinated logistics operations at harbor-front station, thereby achieving seamless connection between railways and ports, accelerating the turnover of sea-rail combined transport containers, thereby improving the logistics efficiency of sea-rail combined transport. This paper points out the role and responsibility of harbor-front station in sea-rail combined transportation. It uses C2R model of data envelopment (DEA) analysis method, in consideration of input and output indexes determined on the basis of the logistics evaluation index, then establishes horizontal logistics performance evaluation system to carry out the logistics performance evaluation. According to the results, this paper puts forward specific and constructive measures for the logistics operation and management of the harbor-front station.