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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.

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.

AIM The prognosis and treatment options for follicular lymphoma (FL) remain heterogenous. This study aimed to analyze the prognostic impact of rituximab maintenance and evaluate the prognostic models in Chinese FL patients. METHODS We retrospectively evaluated patients with treatment-naive advanced stage FL who were treated in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between January 2008 and December 2018. We compared the baseline characteristics, long-term survival outcomes, prognostic factors and the performance of four common prognostic models (i.e., FLIPI, FLIPI2, PRIMA-PI and LDH+β2M) between them. RESULTS A total of 158 patients were included (rituximab maintenance group, 77 patients; observation group, 81 patients). The median follow-up time was 61.0 months. The rituximab maintenance group showed significantly higher 5-year progression-free survival (PFS; 83.3% vs 52.7%, P

Aim The aim of the study was to compare the therapeutic strategies and prognostic factors of patients with primary intestinal diffuse large B-cell lymphoma (PI-DLBCL). Methods A total of 50 PI-DLBCL patients who accepted standard first-line treatment at National Cancer Center in China were included in this retrospective study. Survival analysis was performed to evaluate the prognostic risk factors. Results The 3-year overall survival (OS) and 3-year progression-free survival (PFS) for the entire group were 76.0% and 65.9%, respectively. Univariate analysis showed that B symptom, advanced Lugano stage, elevated LDH status, poor ECOG PS and immunochemotherapy alone were significantly correlated with a poor PFS. Elevated LDH status, poor ECOG PS, advanced Lugano stage, high IPI score and immunochemotherapy alone were significantly correlated with a poor OS. Multivariate analysis revealed that ECOG PS (P= 0.035; HR = 0.233; 95% CI, 0.060-0.905), LDH level (P = 0.010; HR = 0.223; 95% CI, 0.072-0.693) and surgery (P = 0.002; HR = 5.584; 95% CI, 1.883-16.563) were independent prognostic factors for OS. LDH level (P = 0.035; HR = 0.210; 95% CI, 0.049-0.894) and surgery (P = 0.003; HR = 6.410; 95% CI, 1.903-21.593) were independent risk factors for PFS in PI-DLBCL. R-CHOP immunochemotherapy combined surgery treatment was also associated with a lower rate of refractory/relapsed (R/R) disease (P = 0.004). Furthermore, stratified analysis revealed that partial resection or radical resection combined with immunochemotherapy had no significantly difference which affect OS (P = 0.338) and PFS (P = 0.207). Conclusion R-CHOP immunochemotherapy plus surgery was associated with a superior prognosis compared with R-CHOP alone in Chinese PI-DLBCL population.

Purpose This is a first-in-human phase I study investigating the safety and efficacy of toripalimab, a humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor, in Chinese patients with advanced or recurrent malignant tumor refractory to standard treatment. Patients and methods During dose escalation, patients received a single-dose intravenous infusion of toripalimab for 56 days followed by multidose infusions every two weeks. The planned dosing groups were 1, 3 and 10 mg/kg. During dose expansion, patients received toripalimab every two weeks. Clinical response was evaluated by investigators every 6 weeks. Results Thirty-three patients were enrolled, including 12 patients with alveolar soft part sarcoma (ASPS), seven with non–small-cell lung cancer and 11 with lymphoma. Patients were heavily pretreated with a median of 3 prior lines of systemic treatments. Toripalimab was well tolerated without dose-limiting toxicity. All patients experienced treatment-related adverse events. Grade 3 and above treatment-related adverse events occurred in six (18.2%) patients. Among 22 solid tumors, the objective response rate (ORR) was 22.7% per RECIST v1.1. The ORR was 90.9% in 11 lymphoma patients per IWG 2007. The median duration of response was 21.5 months. The median progression-free survival was 5.7 months for solid tumors and 8.3 months for lymphomas. The median OS was not reached for all patients and the lymphoma subgroups. The median OS was 34.7 months for patients with ASPS. Conclusion Toripalimab was well tolerated up to 10 mg/kg Q2W without dose-limiting toxicity and showed promising and durable antitumour activities in patients with ASPS and lymphoma, who were heavily pretreated. Clinical trial information ClinicalTrials.gov Identifier: NCT02836834.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30–40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL. Here, we aimed to gather understanding of MYD88MUT in r/r DLBCL patients and to evaluate its influence on response to ibrutinib. In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin’s lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis. Seven MYD88MUT variants were identified, L265P (65.0%, n = 39), S219C (13.3%, n = 8), S243N (8.3%, n = 5), P258L (6.7%, n = 4), F283V (1.7%, n = 1), P141R (1.7%, n = 1), and V217F (1.7%, n = 1). One patient had MYD88 amplification. In addition, mutations in PIM1 (67%, n = 40), IGH fusion (48%, n = 29), CD79B (43%, n = 26), KMT2D (30%, n = 18), and TP53 (27%, n = 17) were identified. For patients with L265P, IRF4 (p = 0.011) was frequently mutated. Otherwise, TET2 (p = 0.016), NOTCH2 (p = 0.044), MET (p = 0.037), SOCS1 (p = 0.011), TNFRSF14 (p = 0.011), EZH2 (p = 0.037), and BCL6 (p

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.

Purpose After the occurrence of natural disasters, the rapid and accurate delivery of geo-afforestation is the key to emergency rescue and is the fundamental solution to the “last mile” problem. It provides technical support for the territorial rapid and accurate delivery. The paper aims to discuss this issue. Design/methodology/approach Through literature and theoretical research, combined with the research experience of scholars, the qualitative research method is adopted. The paper establishes a three-dimensional analysis framework, including disaster predictability, resource availability and transport accessibility, and proposes the integrated delivery triangular technical framework, including integrated monitoring analysis, the territorial virtual public storage and transportation. Findings Based on the analysis of the factors affecting the effectiveness of emergency delivery, the paper establishes a three-dimensional analysis framework, including disaster predictability, resource availability and transport accessibility, and proposes the integrated delivery triangular technical framework, including integrated monitoring analysis, the territorial virtual public storage and transportation. The triangular technical characteristics and functions of emergency delivery are studied, providing theoretical basis and technical support for effective rescue and emergency planning. Originality/value The territorial emergency delivery refers to the process of rapid and accurate delivery without relying on external territorial supplies. The paper establishes a three-dimensional analysis framework, including disaster predictability, resource availability and transport accessibility, and proposes the integrated delivery triangular technical framework, including integrated monitoring analysis, the territorial virtual public storage and transportation.

The outbreak of COVID-19 has caused a huge shock for human society. As people experience the attack of the COVID-19 virus, they also are experiencing an information epidemic at the same time. Rumors about COVID-19 have caused severe panic and anxiety. Misinformation has even undermined epidemic prevention to some extent and exacerbated the epidemic. Social networks have allowed COVID-19 rumors to spread unchecked. Removing rumors could protect people’s health by reducing people’s anxiety and wrong behavior caused by the misinformation. Therefore, it is necessary to research COVID-19 rumor detection on social networks. Due to the development of deep learning, existing studies have proposed rumor detection methods from different perspectives. However, not all of these approaches could address COVID-19 rumor detection. COVID-19 rumors are more severe and profoundly influenced, and there are stricter time constraints on COVID-19 rumor detection. Therefore, this study proposed and verified the rumor detection method based on the content and user responses in limited time CR-LSTM-BE. The experimental results show that the performance of our approach is significantly improved compared with the existing baseline methods. User response information can effectively enhance COVID-19 rumor detection. © Copyright © 2021 Yang and Pan.

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.

We conducted a retrospective study in 274 previously untreated advanced Hodgkin lymphoma (HL) patients to investigate the prognostic value of baseline platelet (PLT) count, platelet distribution width (PDW), mean platelet volume (MPV), and platelet/lymphocyte ratio (PLR). The median follow-up time was 89 (range 0.3-240) months. By univariate analysis, PLT/PDW

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 Based on the context of the Internet of Things (IoT), the territorial public emergency supplies will be networked, platform-based management, unified emergency dispatch. The problem of supplies dispatching in the “last kilometer” of emergency is solved, and the supplies needed in the disaster area are promptly delivered to the hands of the victims so that they can quickly be rescued after the disaster and to save valuable time for rapid rescue, which can greatly decrease casualties and property losses. This paper aims to discuss these issues. Design/methodology/approach By analyzing the shortage of existing emergency supplies dispatching research and taking all factors such as disaster area demand, social reserve, road conditions, mode of transport, loading limit, disaster area satisfaction rate and road capacity into consideration under the background of IoT, a variety of the territorial emergency supplies dispatching model with more rescue points, more affected areas are constructed. The objective function of the model is to aim in finding the shortest rescue time, giving the solution algorithm, and finally simulating the simulation case. Findings Based on the context of the IoT, the territorial public emergency supplies will be networked, platform-based management, unified emergency dispatch. Considering factors such as road conditions, modes of transport and road capacity, the authors construct a number of emergency rescue plans, multiple disaster scenarios and various emergency supplies dispatching models. The authors simulate the situation through simulation cases with the shortest time being the ultimate goal. The problem of supplies dispatching in the “last kilometer” of emergency is solved, and the supplies needed in the disaster area are promptly delivered to the hands of the victims so that they can quickly be rescued after the disaster and to save valuable time for rapid rescue, which can greatly decrease casualties and property losses. Originality/value This paper provides little research on the dispatch of emergency supplies. The problems of direct dispatch from the rescue point to the affected area and dispatch of supplies without relying on the arrival of emergency supplies at the rear are addressed. Therefore, this study does not focus on the arrival of emergency supplies at the rear but on direct dispatching issues during territorial public emergency supplies from the rescue point to the disaster point.

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.

Aim Little is known about the outcome and prognostic factors of relapsed or refractory T-cell lymphoblastic lymphoma (T-LBL), especially in adult patients. The aim of this study was to analyze the characteristics, outcome and prognostic factors for this patient population. Methods Between January 2006 and December 2017, we retrospectively analyzed 84 adult patients with T-LBL, and 44 relapsed or primary refractory patients were included in this analysis. Clinical features, treatment and follow-up information were collected. Results For all 44 patients, the median time to disease progression or relapse was 9.5 months after diagnosis. At a median follow-up of 19.6 months, 40 (90.9%) patients died. The 3- and 5-year overall survival (OS) rates after disease progression or relapse were 7.8% and 5.2%, respectively. Among 30 patients who had detailed information of second-line treatment, only eight achieved a second complete remission (CR). Two of these eight patients subsequently underwent autologous or allogeneic stem cell transplantation (SCT), of whom one died from disease progression after autologous SCT, and one was free of event at 84 months after allogeneic SCT. Three of the rest six patients in second CR were still alive after chemotherapy alone. All the remaining patients who failed to gain second CR eventually died. In univariate analysis, only the achievement of second CR was positively predictive of OS (hazard ratio (HR) = 0.307; 95% confidence interval (CI), 0.104-0.905; P = 0.032). Conclusion The outcome of adult patients with relapsed or refractory T-LBL is extremely dismal. Patients with relapsed or refractory T-LBL should be encouraged to participate in clinical trials where novel therapeutic approaches are available.

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.

The paper propose an equilibrium decision-making method for the emergency relief medicine distribution during an earthquake response by considering demand uncertainty. The proposed method objects to minimize transport time, as well as distribution equity of each affected area. Besides, this model also consider the equilibrium between wrong decision risk and late decision risk. Then, simulation research is carried out in this paper. Results shows that the proposed model can generate proper distribution plan by inputting relative data.

T cell lymphoblastic lymphoma (T-LBL) has an aggressive clinical behavior. To date, powerful and consistent prognostic factors have not been established for T-LBL. In this study, we first evaluated the association of event-free survival (EFS) at 24 months (EFS24) with overall survival (OS) in T-LBL patients. Besides, we sought to identify clinical factors of prognostic importance in this rare entity. Between January 2006 and December 2017, ninety-one patients with newly diagnosed T-LBL were retrospectively analyzed. EFS was defined as the time from diagnosis to relapse or progression, unplanned retreatment, death from any cause, or to the last follow-up. In total, 91 patients with a median age of 24 years were enrolled. At a median follow-up of 40.4 months (range, 1.4 to 163.3 months), the 5-year OS and EFS was 47.9% and 43.2%, respectively. Of all patients, 45 (49.5%) achieved EFS24 and 46 (50.5%) did not. Patients who achieved EFS24 showed a markedly superior outcome, compared with those who failed to achieve EFS24 (5-year OS, 90.5% vs 3%, P

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.

After large-scale disasters, the earthquake refuge site-allocation is the key content of emergency management to quickly resettle the victims and launch emergency rescue. From the perspective of the needs of victims’ evacuation, considering various factors such as traffic convenience, environmental safety, facility completeness and service efficiency, this paper constructs the site-distribution optimization model based on the maximization of earthquake refuge weights. The case verifies the validity of the model. Finally, the sensitivity analysis provides inspiration to management decision makers: when the refuge carries more than a certain range, the overall optimality of the refuge becomes worse.

Coagulative dysfunction is frequently observed among patients with extranodal nasal-type natural killer/T cell lymphoma (NKTCL) in our clinical practice. However, the true prognostic value of coagulation factors in patients with NKTCL has not been evaluated systemically. Data for patients with stage I/II NKTCL who were treated in the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2008 to January 2019 were collected retrospectively. The patients enrolled in this study were initially diagnosed as having early-stage disease. The patients’ baseline characteristics and pretreatment laboratory tests for coagulation function, including fibrinogen (FIB) and d-dimer (d-D), were reviewed and analyzed. The influence of coagulative factors on the responses and prognosis of patients with early-stage NKTCL was evaluated. Among 394 patients assessed, 154 were included in this study. Abnormal coagulation function was found in nearly half of the patients (48.1%). Univariate analysis showed that reduced complete remission (CR) was associated with elevated d-D (P = 0.001) and elevated FIB levels (P = 0.006). The d-D level was demonstrated as associated with unfavorable progression-free survival (PFS) (P = 0.003) and overall survival (OS) (P = 0.002). Multivariate analysis indicated that an elevated d-D level was an independent factor for poor clinical response (P = 0.019), PFS (P = 0.046), and OS (P = 0.024). Elevated pretreatment levels of coagulation factors, especially d-D and plasma FIB, are unfavorable predictors for clinical response, OS, and PFS in early-stage NKTCL.

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naive patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.

Background The prognostic value of platelet count in diffuse large B-cell lymphoma (DLBCL) has not been extensively investigated. We aimed to examine the association of pretreatment platelet count with disease features, and further examine the prognostic significance of platelet count in DLBCL treated with the R−CHOP regimen. Methods Patients with DLBCL diagnosed between Jan 1 st, 2005 and Dec 31 st, 2018 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Propensity score matching (PSM) was used to balance confounding factors. Results A total of 1007 eligible patients who received frontline R−CHOP or R−CHOP-like regimens were included in this study. The optimal cutoff value of platelet count was 157 × 109/L, as determined by the Maximally Selected Rank Statistics method. Patients with the platelet count ≤157 × 109/L had significantly inferior overall survival (OS) (5-year OS, 44.4 % vs. 74.9 %, P 157×109/L. Multivariate analyses showed that pretreatment platelet count ≤ 157 × 109/L was an adversely independent prognostic factor for OS (hazard ratio [HR] 1.960, 95 % confidence interval [CI] 1.418−2.709, P Conclusion The pretreatment platelet count may be a simple, cost-effective and useful prognostic factor in DLBCL patients treated with frontline R−CHOP regimens. Further investigation is warranted to elucidate the biologic mechanism underlying the prognostic significance of platelet count in DLBCL.

e19549 Background: Unlike BCL2 translocation ( BCL2TR), limited data about the prognostic significance of BCL2 mutations ( BCL2MUT) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2GA/AMP) and BCL2MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2TR. As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P< 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2GA/AMP. By contrast, neither BCL2MUT nor BCL2TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P< 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P< 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P< 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P< 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2GA/AMP, and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

// 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.

Background: Lung adenocarcinoma (LUAD) possesses a poor prognosis with a low 5-year survival rate even for stages I-III resected patients, it is thus critical to understand the determinants that affect the survival and discover new potentially prognostic biomarkers. Somatic copy number alterations (CNAs) are major source of genomic variations driving tumor evolution, CNAs screening may identify prognostic biomarkers. Methods: Oncoscan MIP array was used to analyze the patterns of CNAs on formalin fixed paraffin embedded(FFPE) tumor specimens from 163 consecutive stage I-III resected LUAD patients, 145 out of which received platinum-based adjuvant chemotherapy. Results: Of the 163 patients, 91(55.8%) were recurred within 3 years after surgery. The most common aberrations in our cohort were 1q, 5p, 5q, 7p, 8q, 14p, 16p, 17q, 20q for copy number gains and 8p, 9p, 13p, 16q, 18q for losses. The GISTIC2 analysis produced 45 amplification peaks and 40 deletion peaks, involving some reported genes TERT, EGFR, MYC, CCND1, CDK4, MDM2, ERBB2, NKX2-1, CCNE1, and CDKN2A, most of which were consistent with TCGA database. The amplifications of 12p12.1 (CMAS, GOLT1B, YS2, LDHB, RECQL, ETNK1, IAPP, PYROXD1, KRAS) and KDM5A were correlated with worse prognosis in our cohort, this result was further validated in 506 LUAD patients from TCGA. In addition, 163 patients could be well-classified into five groups, and the clinical outcomes were significantly different based on threshold copy number at reoccurring alteration peaks. Among the 145 patients who received adjuvant chemotherapy, focal amplification of ERBB2 and deletion of 4q34.3 were found to be specific in relapsed patients, this result was validated in an independent group of Imielinski et al., demonstrating these two CNAs may contribute to resected LUAD recurrence after adjuvant chemotherapy. Conclusion: This study suggests that CNAs profiling may be a potential prognostic classifier in resected LAUD patients. Amplifications of 12p12.1 and KDM5A might be prognostic biomarkers for LUAD, and amplification of ERBB2 and deletion of 4q34.3 predicted early relapse after adjuvant chemotherapy. These novel findings may provide implication for better implementation of precision therapy for lung cancer patients.

Early/upfront radiation was associated with improved survivals compared with late radiation for early-stage NK/T-cell lymphoma (NKTCL) in the old era when anthracycline-base chemotherapy (CT) prevailed. However, in the modern era of effective l-asparaginase/gemcitabine-based CT, the optimal timing of radiation is unclear. In this study, 75 patients with newly diagnosed NKTCL, who were treated with combined involved-field intensity-modulated radiotherapy and GDP (gemcitabine, dexamethasone, and cisplatin) were retrospectively reviewed, including 45 from the RT + CT group and 30 from the CT + RT ± CT group. Compared with CT + RT ± CT, RT + CT sequence achieved superior progression-free survival (5-year PFS: 81.6% vs. 56.0%

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.

Aim The clinical course of diffuse large B-cell lymphoma (DLBCL) is variable and there is a lack of prognostic markers and models for relapsed or refractory (r/r) DLBCL. Hence, we conducted this study to identify independent factors that can predict the survival rate of r/r DLBCL patients. Methods A total of 416 r/r DLBCL patients who were pretreated with first-line anthracycline-based chemotherapy at the National Cancer Center in China between 2006 and 2016 were divided into the primary (n = 291) and validation (n = 125) cohorts. The effect of preclinical and clinical indicators on DLBCL survival rates of the two cohorts were evaluated by univariate and multivariate analyses. Factors showing good correlation with patient survival rates were used to construct a prognostic nomogram. Results Multivariate analysis of the primary cohort revealed five independent prognostic factors: lactate dehydrogenase level at diagnosis, response to front line treatment, progression/recurrence pattern, location, and invasion on progression/recurrence, which were then used to construct a nomogram. The nomogram was shown to have a C-index of 0.76 and AUC values of 0.81 and 0.80 for the primary and validation cohorts, respectively, suggesting good prognostic power. We further stratified the r/r DLBCL patients into four risk groups according to the newly developed nomogram. Conclusion The prognostic nomogram constructed using the five identified clinical indicators can potentially be applied in the clinical setting to guide treatment decision.

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.

Purpose: TP53 mutation was recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Exploratory therapy for this group of patients is in great need for potential clinical benefit. Here, we investigated the effect of adding surgical procedure to standard immunochemotherapy on survival of TP53 MUT DLBCL patients. Methods: Capture-based targeted sequencing was performed on 214 DLBCL patients, of which 47 was detected TP53MUT and included for further analysis. Refractory patients were defined as individuals did not achieve complete remission (CR) or develop relapse after 6 months in response to initial treatment. Findings: For 47 patients confirmed with TP53 mutation, 44 (93·6%) received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regime were included for survival analysis with a median follow-up of 13 months. The median progression-free survival (PFS) and overall survival (OS) were 10.0 months (95%CI, 6·7-13·3) and 46.0 months (95%CI, 11·8-80·2). Among them, 26 patients developed refractory and received second-line chemotherapy. Seven limited-stage patients after early complete resection and one patient with residue resection remained event free with a median follow-up of 37 months. A multivariate analysis showed adding surgery to R-CHOP regime significantly improved PFS of TP53 MUT DLBCL patients compared to R-CHOP only treatment (p=0·039, HR=0·109, 95%CI=0·013-0·894). Conclusions: TP53 mutation is associated with unfavorable prognosis in DLBCL patients. Our study showed surgical resection may provide additional clinical benefit, which offered new treatment consideration for this group of patients. Funding Statement: This study was supported by National Key Technology Support Program (2014BAI09B12), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), and National New Drug Innovation Program (2017ZX09304015). Declaration of Interests: JL is an employee of Burning Rock Biotech. All other authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the local ethic committee and was conducted in accordance with the Declaration of Helsinki.

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.

Purpose To investigate the efficacy and toxicity profile of sequential intensity modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, and cisplatin (GDP) on previously untreated high-risk, early stage upper aerodigestive tract natural killer/T-cell lymphoma (UADT-NKTCL). Methods and Materials A phase 2 study was designed, and 40 high-risk patients with stage I(E)/II(E) UADT-NKTCL were enrolled between June 2010 and June 2014. High-risk patients were defined as those with at least 1 predefined risk factor: age >60 years, elevated serum lactate dehydrogenase, regional lymph node involvement, B symptoms, and primary tumor invasion. Patients received extended involved-site IMRT and GDP chemotherapy. The primary endpoint was the 2-year progression-free survival rate. Secondary endpoints were the 2-year overall survival rate, overall response rate, and toxicity. Results Median follow-up time was 60.1 months. The overall response rate and complete remission rate were 97.5% and 95.0%, respectively. The 2- and 5-year progression-free survival rates were 84.7% and 79.4%, and the corresponding overall survival rates were 89.9% and 82.1%, respectively. The most frequent radiation-induced toxicities were mild mucositis and skin reaction. Grade 3/4 neutropenia (12 of 40 patients), thrombocytopenia (7 of 40), and anemia (2 of 40) were observed during chemotherapy. Conclusions First-line IMRT followed by GDP represents an effective and well-tolerated protocol for high-risk, early stage UADT-NKTCL.