New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer:An open-labeled,multicenter,randomized,prospective phase III trial(EXELOX)

Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.