Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial.

Importance: The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking. Objective: To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL). Design, Setting, and Participants: This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group. Interventions: Patients in each group were treated with the assigned regimen every 21 days for 6 cycles. Main Outcomes and Measures: The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared. Results: Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%). Conclusions and Relevance: In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01501149.

LINC00504 Promotes the Malignant Biological Behavior of Breast Cancer Cells by Upregulating HMGB3 via Decoying MicroRNA-876-3p.

PURPOSE: Long intergenic non-protein coding RNA 504 (LINC00504) is a long non-coding RNA that has an important regulatory role in a variety of human cancers. In this study, LINC00504 expression in breast cancer tissues and cell lines was detected. Studies were also conducted to determine the impact of LINC00504 on the tumor behavior of breast cancer cells. The potential mechanisms underlying the oncogenic role of LINC00504 in breast cancer cells were elucidated in detail. METHODS: Expression of LINC00504 in breast cancer was analyzed by quantitative real-time polymerase chain reaction. The effects of LINC00504 on proliferation, apoptosis, in vitro migration and invasion, and in vivo tumor growth were elucidated using Cell Counting Kit-8 assay, flow cytometry, Transwell assays, and tumor xenograft models, respectively. Bioinformatics analyses in conjunction with RNA immunoprecipitation, luciferase reporter assays, and rescue experiments were conducted to investigate the underlying molecular mechanisms. RESULTS: LINC00504 was upregulated in breast cancer tissues and cell lines. Knocking down LINC00504 suppressed breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro. In addition, tumor growth in vivo was significantly inhibited by LINC00504 depletion. Regarding the underlying mechanism, LIN00504 could function as a competing endogenous RNA in breast cancer by sponging microRNA-876-3p (miR-876-3p), resulting in the upregulation of high mobility group box 3 (HMGB3). Rescue experiments further revealed that miR-876-3p downregulation or HMGB3 upregulation effectively reversed the inhibitory effects of LIN00504 deficiency on breast cancer cells. CONCLUSION: The LIN00504-miR-876-3p-HMGB3 axis shows carcinogenic effects in modulating the biological behavior of breast cancer cells. This pathway may represent an effective target for CRC diagnosis and anticancer therapy.

Association of ABO Blood Groups and Risk of Gastric Cancer.

OBJECTIVE: This study sought to investigate the relationship between ABO blood groups and the risk of gastric cancer as well as clinical pathological parameters and prognosis. METHODS: Gastric cancer patient data were collected from January 1995 to January 2012 at Jilin Cancer Hospital, and the blood group information of the blood donors at Jilin City Blood Center was recorded. The relationships between ABO blood group and both clinicopathological parameters and the risk of gastric cancer were analyzed retrospectively. The impact of ABO blood type on the 5-year survival rate of patients with gastric cancer was evaluated through outpatient and telephone interviews. RESULTS: (1) Compared with the healthy population, the frequency distribution of gastric cancer patients with the A blood group was significantly increased (χ2 = 4.708, P = 0.000), whereas the frequency distribution of gastric cancer patients with the AB blood group was significantly decreased (χ2 = 9.630, P = 0.002). However, there was no significant difference in the distributions of the B blood group and O blood group (P > 0.05). (2) The risk of gastric cancer in people with the A blood group was higher, whereas the risk of gastric cancer in people with the AB blood group was lower. There was no significant difference in the risk of gastric cancer between type B and type O patients (P > 0.05). (3) The ABO blood group was not related to pathological factors, including the size of the gastric tumor or the T stage or N stage of the disease (P > 0.05). (4) Univariate analysis results showed that the degree of differentiation, tumor size, T stage, lymph node metastasis, and type O blood were factors affecting the 5-year survival rate of gastric cancer patients (P < 0.05). Multivariate analysis results showed that tumor size, T stage, lymph node metastasis, and O blood group were independent prognostic factors. The 5-year survival rate for gastric cancer was significantly better in patients with type O blood (hazard ratio = 0.97, 95% confidence interval = 1.67-3.92). CONCLUSION: (1) The risk of gastric cancer was higher in patients with the A blood group and lower in those with the AB blood group. (2) The ABO blood group showed no significant effect on the clinicopathological parameters of gastric cancer. (3) The O blood group may be a prognostic factor for gastric cancer patients.

Primary breast diffuse large B-cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB-DLBCL patients. We retrospectively reviewed data on 108 PB-DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow-up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5-year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5-year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10-year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB-DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB-DLBCL patients.

Effect of laparoscopic gastrectomy on compliance with adjuvant chemotherapy in patients with gastric cancer.

This study was designed to investigate the effect of laparoscopic gastrectomy on adjuvant chemotherapy in patients with gastric cancer.Patients with gastric cancer who underwent radical gastrectomy at our institution from January 2008 to January 2015 with R0 resection, as determined by a pathological examination, were included in this study. According to the surgical approach, patients were divided into the laparoscopic gastrectomy (LG) group and open gastrectomy (OG) group. Short-term and long-term outcomes were compared between the 2 groups.Of the 206 patients enrolled in the study, 114 patients were included in the LG group and 92 patients were included in the OG group. There was no significant difference in patients' general data, including age, sex, medical comorbidities, and pathological staging, between the 2 groups. However, patients in the LG group had less intraoperative blood loss, fewer postoperative complications, and a shorter hospital stay compared with patients in the OG group. There was no significant difference in the start time of adjuvant chemotherapy between the groups. However, compared with OG, LG had the following advantages: patients received more cycles of adjuvant chemotherapy, more patients received a full dose of on-schedule adjuvant chemotherapy, and more patients completed ≥75% of the planned dose. Long-term survival and disease-free survival rates were higher in the LG than in the OG.In summary, LG can improve compliance with adjuvant chemotherapy and long-term outcomes in patients with gastric cancer.

Circulating tumor cell counts/change for outcome prediction in patients with extensive-stage small-cell lung cancer.

AIMS: As data on the use of circulating tumor cells (CTCs) to predict patient outcomes in extensive-stage small-cell lung cancer (ES-SCLC) remain inconclusive, we investigated the clinical value of CTC determination in an open-label, multicenter study of 91 patients with newly diagnosed ES-SCLC. MATERIALS & METHODS: Blood CTC counts were determined using the CellSearch® system at baseline, after the second cycle of chemotherapy, and on disease progression. RESULTS & CONCLUSION: Following the second cycle of treatment, CTC numbers and the change in CTCs were strong, significant and independent indicators for both progression-free survival and overall survival in ES-SCLC. The CTC change was associated with both refractory disease (response to initial therapy ≤3 months) and sensitive disease (response to initial therapy >3 months).

Clinical Analysis of Five Cases of AIDS-related Non-Hodgkin Lymphoma.

OBJECTIVE: Secondary malignancy is a major life-threatening complication facing patients afflicted with acquired immunodeficiency syndrome (AIDS). This study aimed to retrospectively review clinical features and treatment course of five patients with AIDS-associated non-Hodgkin lymphoma (A-NHL) in Jilin Tumor Hospital. METHODS: Five A-NHL patients were retrospectively and consecutively hospitalized at our oncological unit between January 2012 and June 2014. All patients received pre-emptive highly active antiretroviral therapy (HAART) and chemotherapy, and were subsequently followed up at the outpatient clinic. All five patients were male, aged 27-53 years, and afflicted with A-NHL involving upper jaw, right inguinal region, right-side gingiva, mediastinum, or right-side neck. Histology showed diffuse large B-cell lymphoma (n = 3) or plasmablastic lymphoma (n = 2). RESULTS: Two patients achieved complete remission after HAART and chemotherapy, whereas other three patients required a second-line treatment, with two achieving stable disease and one dying within a follow-up period of 0.5-2 years. CONCLUSION: The findings of the present study showed that A-NHL is a disease often diagnosed in the middle-to-late stages, with diverse clinical manifestations and short overall survival. In the cases reviewed in this study, HAART in combination with standard dose or high-dose chemotherapy, HAART and molecular targeted chemotherapy was administered, and these treatments proved to be effective for improving the prognosis of these patients. Moreover, the CD4+ cell count was important for determining the prognosis of patients.

Ultrasensitive rapid detection of human serum antibody biomarkers by biomarker-capturing viral nanofibers.

Candida albicans (C. albicans) infection causes high mortality rates within cancer patients. Due to the low sensitivity of the current diagnosis systems, a new sensitive detection method is needed for its diagnosis. Toward this end, here we exploited the capability of genetically displaying two functional peptides, one responsible for recognizing the biomarker for the infection (antisecreted aspartyl proteinase 2 IgG antibody) in the sera of cancer patients and another for binding magnetic nanoparticles (MNPs), on a single filamentous fd phage, a human-safe bacteria-specific virus. The resultant phage is first decorated with MNPs and then captures the biomarker from the sera. The phage-bound biomarker is then magnetically enriched and biochemically detected. This method greatly increases the sensitivity and specificity of the biomarker detection. The average detection time for each serum sample is only about 6 h, much shorter than the clinically used gold standard method, which takes about 1 week. The detection limit of our nanobiotechnological method is approximately 1.1 pg/mL, about 2 orders of magnitude lower than that of the traditional antigen-based method, opening up a new avenue to virus-based disease diagnosis.

Predictive value of serum anti-p53 antibodies, carcino-embryonic antigen, carbohydrate antigen 15-3, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in taxane-based and anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer patients.

Breast carcinoma is the most common malignancy in Chinese women. The purpose of this study is to evaluate the predictive value of serum anti-p53 antibodies (p53 Abs), carcino-embryonic antigen (CEA), carbohydrate antigen (CA) 15-3, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2 in taxane-based and anthracycline-based neoadjuvant chemotherapy (NAC). Sixty-eight patients with locally advanced breast carcinoma were included. Thirty-two were treated with taxane (the taxane group) and 36 with anthracycline (the anthracycline group). The standard dosage of docetaxel was 100 mg/m2 (day 1) and those of cyclophosphamide, adriamycin and 5-flurouracil were 500 mg/m2 (day 1-8), 40 mg/m2 (day 1) and 500 mg/m2 (day 1-8), respectively. The p53 Abs were detected by enzyme-linked immunosorbent assay; CEA and CA15-3 were detected by Elecsys 2010 Disc System; ER, PR and HER-2 were detected by immunohistochemistry staining. The biomarkers p53 Abs, CEA and CA15-3 were detected in serum samples, and the immunohistochemistry staining for ER, PR and HER-2 was performed in tumor samples before and after NAC. The expression of p53 Abs was significantly reduced by taxane (P = 0.006). The serum CEA and CA15-3 levels were significantly affected by both taxane (P = 0.004 and P = 0.008) and anthracycline (P = 0.002 and P = 0.000) drugs. HER-2-negative status (pre-neoadjuvant) was correlated with a high objective response rate (OR) in both taxane-based and anthracycline-based chemotherapy (P = 0.022 and P = 0.025), whereas p53 Ab-negative status (pre-neoadjuvant) was correlated with high OR rate in anthracycline-based chemotherapy (P = 0.039). This study shows that the serum p53 Ab level is easily changed by taxane. CEA and CA15-3 levels are easily changed by taxane and anthracycline. The p53 Ab-negative patients may predict a high clinical OR rate in anthracycline-based NAC. HER-2-negative may predict a high OR in both taxane-based and anthracycline-based NAC.

Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasis.

The secreted aspartyl proteinases (Saps) of Candida albicans have been implicated as immunodominant antigens and virulence factors associated with adherence and tissue invasion. A hybrid phage displaying the Sap epitope VKYTS was constructed by cloning the corresponding DNA fragments into the pfd88 vector. Similar to native Sap, the phage-displayed epitope showed reactivity to sera from mice and patients with systemic C. albicans infection but not from those with oropharyngeal candidiasis and healthy individuals on Western blot. Furthermore, a new enzyme-linked immunosorbent assay was developed to detect the anti-Sap antibody with hybrid phage displaying Sap epitope VKYTS that can be recognised by anti-Sap antibodies. Sequential sera were tested from patients and mice with systemic candidiasis and oropharyngeal candidiasis, and serum samples from healthy individuals were also included. The sensitivity and specificity were 77% and 88.3% for experimental mice, respectively. These values reached 60% and 85%, respectively, for human patients. These data indicate this phage-displayed epitope as an effective and less expensive reagent would be a valuable probe for the detection of specific Sap antibody in the sera of patients and mice with systemic C. albicans infection.

The detection of serum anti-p53 antibodies from patients with gastric carcinoma in China.

BACKGROUND: Gastric carcinoma is one of the most frequently occurring cancers. The aim of this research was to increase the detection efficiency of anti-p53 antibodies in the sera of patients with gastric carcinoma and to improve the diagnosis for patients with gastric carcinoma. METHODS: We prepared phage-displayed peptide DO7 and established an enzyme-linked immunosorbent assay method to detect the anti-p53 antibodies. We detected the anti-p53 antibodies of 61 patients with gastric carcinoma using the method and our previous ELISA method assisted by the recombinant wild-type human p53 protein to detect the anti-p53 antibodies. We studied the correlation between the anti-p53 antibodies and the clinicopathological data including sex, age, carcinoembryonic antigen, tumor size, tumor TNM staging, and lymph-node status. RESULTS: The anti-p53 antibodies positive rate for patients with gastric carcinoma was increased (31.1%, 19/61) through the combination of p53-ELISA and phage-ELISA. We found that the positive anti-p53 antibodies correlated significantly with tumor size (P=0.047). The combination of the anti-p53 antibodies and carcinoembryonic antigen could improve the diagnosis for patients with gastric carcinoma. CONCLUSIONS: This approach indicated an increased anti-p53 antibodies positive rate for patients with gastric carcinoma and provided a useful marker for clinical diagnosis for patients with gastric carcinoma.

The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters.

Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.