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Summary Background Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. Methods In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology–Oncology Programs Evaluation System in China. Young patients (16–60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61–80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1–5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT01852435 . Findings From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6–77·6) and in the R-CEOP70 group was 72·4% ([66·5–77·5]; HR 1·00 [0·73–1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1–93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7–82·3]; 0·44 [0·25–0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4–83·7%]; 0·49 [0·27–0·86]; p=0·017). Grade 3–4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. Interpretation R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. Funding National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.

Background This study aimed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin's lymphoma. Methods A total of 228 patients with diffuse large B-cell lymphoma (DLBCL) received R-CHOP-based regimens from a prospective randomized study (NCT01852435) were included as a training cohort. Other cohorts of 886 lymphoma patients were served as validation cohorts. Lymphocyte-monocyte ratio (LMR), serum levels of soluble interleukin s(IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α), were assessed before treatment. Least absolute shrinkage and selection operator (LASSO) regression were used to select variables for nomogram of overall survival (OS). The predictive accuracy of the nomogram was determined by concordance index (C-index). Findings The nomogram included lactate dehydrogenase (LDH), sIL-2R, TNF-α and decreased LMR. The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL, PTCL, NKTCL and ASCT, which were superior to the predictive power of International Prognostic Index (IPI, 0.67 to 0.84) or NCCN-IPI (0.59 to 0.78), but not in those of indolent lymphoma like FL and MALT. Interpretations The nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin's lymphomas. Fund National Natural Science Foundation of China, the Shanghai Commission of Science and Technology, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of SHDC, and Chang Jiang Scholars Program.

Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5 mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients.A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial.Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group.The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M). The sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12.The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3.A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were +9.20 letters in the conbercept group and +2.02 letters in the sham group, respectively (P .001). At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group (P = .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure.A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.

Background The prognosis of Chinese patients with eyelid sebaceous carcinoma (SC) has not been updated for >3 decades. The prognostic predictors are multifactorial, and there is no validated prognostic model for eyelid SC. Methods This study included 238 consecutive patients with eyelid SC. All eligible patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between the nomogram and the Tumor, Node, Metastasis (TNM) staging system. Findings After a median follow-up period of 55.5 months, 27 (11.3%) patients died of metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rates were 88.1% and 77.9%, respectively. Orbital involvement (HR: 3.11, p = .022), the greatest tumor basal diameter (HR: 1.06, p = .003), the presence of pagetoid spread (HR: 2.90, p = .017), and having lymph node metastasis at initial diagnosis (HR: 13.66, p

Background: The prognosis of Chinese patients with eyelid sebaceous gland carcinoma (SC) has not been updated for more than 3 decades. The predictors for the prognoses are multifactorial, there is no validated prognostic model for eyelid SC. Methods: The study included 238 consecutive patients with eyelid SC. All patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between nomogram and Tumor, Node, Metastasis (TNM) staging system. Findings: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of the metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rate was 88.1% and 77.9%, respectively. Prior radiation therapy (HR:5.63, p=0.003), tumor with orbital involvement (HR:4.64, p=0.001), greatest tumor basal diameter (HR:1.07, p