Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma:A systematic review and meta-analysis

Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

Clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma

Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background： The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma （DLBCL） remains to be defined. We aimed to compare CHOP plus rituximab （R-CHOP） with CHOP alone and determine the value of radiotherapy in these patients. Methods： Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. Results： Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response （CR） rate was 77% both in R-CHOP and CHOP groups （P=0.945）. After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival （PFS） （76% vs. 85%; log-rank P=0.215） and 5-year overall survival （OS） （90% vs. 96%; log-rank P=0.175） compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone （86% vs. 71%; log-rank P=0.005）. At multivariate analysis, patients who had CR （P=0.008） and received radiotherapy （P=0.003） were significantly associated with superior PFS. Conclusions： CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.

放疗在美罗华时代对局限期原发韦氏环弥漫大B细胞淋巴瘤的治疗价值

目的分析在美罗华联合化疗背景下,放疗对局限期韦氏环弥漫大B细胞淋巴瘤的治疗价值。方法收集2010年—2017年收治的93例Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤患者的临床资料,将仅接受美罗华联合CHOP或CHOP类似方案化疗的38例患者分为单纯化疗组,将接受化疗+巩固放疗的55例患者分为综合治疗组。采用Kaplan-Meier法计算无进展生存(PFS)、总生存(OS)、局部区域控制率(LRC),并行单因素分析;采用Logrank法检验两组患者生存差异,并行Cox多因素回归分析。结果本研究患者随访中位时间47个月,3年存活病例67例。单纯化疗组和综合治疗组患者的3年PFS分别为76.1%和94.2%(P=0.036),3年OS分别为78.6%和96.0%(P=0.032),3年LRC分别为83.1%和98.1%(P=0.015)。其中62例化疗后疗效评估为完全缓解(CR)的患者中,单纯化疗组和综合治疗组的3年PFS、OS和LRC分别为87.8%和97.6%(P=0.164)、93.8%和97.4%(P=0.522)、87.8%和100.0%(P=0.028)。进一步单因素分析结果显示,年龄>60岁和化疗疗效未达CR是PFS和OS的不良预后因素,B症状和化疗疗效未达CR是LRC的不良预后因素。多因素分析结果显示,年龄>60岁、B症状、化疗疗效未达CR是患者PFS的不良预后因素,年龄>60岁、化疗疗效未达CR是OS的不良预后因素,B症状、化疗疗效未达CR和未放疗是LRC的不良预后因素。结论Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤采用美罗华联合CHOP为主的化疗后的巩固性放疗可显著改善患者的PFS、OS和LRC,但仍需大样本和前瞻性研究进一步证实。

原发韦氏环弥漫性大B细胞与结外鼻型NK／T细胞淋巴瘤的临床特征和预后比较

目的比较原发韦氏环弥漫性大B细胞淋巴瘤（DLBCL）与结外鼻型NK／T细胞淋巴瘤（ENKTCL）的临床特征和预后差异。方法对2000--2008年间本院收治的122例DLBCL和44例ENKTCL进行回顾分析。DLBCL通常4—6周期CHOP方案化疗后加累及野放疗，早期NKTCL单纯扩大野放疗或加辅助化疗或放疗前加短周期（1—3周期）CHOP方案化疗。Kaplan—Meier法计算生存率并Logrank检验组间差异和单因素预后分析。结果随访率为82％，DLBCL和ENKTCL随访时间满5年者分别为32例和15例。DLBCL多见于扁桃体并伴有颈淋巴结累及，ENKTCL多见年轻男性、鼻咽Ⅰ期病变、B症状和侵犯周围结构。DLBCL和ENKTCL的5年总生存率、无进展生存率分别为74％、67％和68％、59％（X^2=0．53、1．06，P=0．468、0．303）；Ⅰ＋Ⅱ期的5年总生存率、无进展生存率分别为79％、76％和72％、62％（x^2=1．20、2．46，P=0．273、0．117）。单因素分析显示年龄〉60岁、乳酸脱氢酶升高、东部肿瘤协作组评分〉1、国际预后指数评分≥1、Ⅲ＋Ⅳ期病变和大肿块与DLBCL的预后相关（X^2=9．40、12．72、6．15、10．36、12．48、5．53，P=0．002、0．000、0．013、0．001、0．000、0．019），而国际预后指数评分≥1和年龄〉60岁与ENKTCL的预后相关（x^2=3．98、8．41，P=0．046、0．004）。结论原发韦氏环的DLBCL与ENKTCL临床特征不同，但不同治疗原则下两者预后相似。

Ⅰ/Ⅱ期韦氏环弥漫大B细胞淋巴瘤免疫化疗后放疗疗效观察

目的评价免疫化疗后早期韦氏环弥漫大B细胞淋巴瘤(DLBCL)的预后因素及放疗价值。方法回顾性分析2009-03-21-2017-05-16本院收治的60例Ⅰ/Ⅱ期韦氏环DLBCL患者临床资料。将患者分为放疗组(33例)和未放疗组(27例),均接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)方案的免疫化疗,放疗组在免疫化疗后接受累及野放疗(中位剂量:46 Gy)。生存分析采用Kaplan-Meier曲线描述并行log-rank检验,Cox比例风险模型分析影响预后的因素。结果全组随访达5年者有46例,5年总生存(OS)率、无进展生存(PFS)率和局部区域控制(LRC)率分别为80.00%、67.95%和84.47%。单因素分析结果显示,Ann Arbor分期为Ⅱ期、美国东部肿瘤协作组(ECOG)评分≥2分、分期改良国际预后指数(smIPI)评分≥2分和未放疗是OS的预后不良因素,Ann Arbor分期为Ⅱ期、ECOG评分≥2分是PFS的预后不良因素,而放疗则是LRC的有利因素。多因素分析结果显示,与OS有关联的因素包括年龄(HR=3.660,95%CI:1.026~13.053)、Ann Arbor分期(HR=10.249,95%CI:1.633~64.322)和放疗(HR=0.386,95%CI:0.160~0.933);与PFS有关联的因素为Ann Arbor分期(HR=7.343,95%CI:1.702~31.683);与LRC有关联的因素为放疗(HR=0.143,95%CI:0.031~0.667)。免疫治疗后获得部分缓解的患者接受放疗可改善5年LRC率(100.00%vs 57.14%),χ^(2)=5.691,P=0.017。结论早期韦氏环DLBCL免疫化疗后预后良好,放疗可改善免疫化疗后达到部分缓解者的局部控制。

IMRT早期韦氏环DLBCL的长期观察

目的 研究IMRT对原发于韦氏环早期DLBCL的疗效、预后、放射剂量及不良反应。 方法 收集2008—2015年Ⅰ、Ⅱ期韦氏环DLBCL病例 80例,放化疗为主,3例单纯放疗。化疗后CR 24例,PR 53例。原发灶及颈部淋巴结引流区IMRT。采用Kaplan-Meier法计算生存率,Cox模型预后因素分析,不良反应分级使用RTOG标准。 结果 中位随访时间为64个月,5年LRC、OS、PFS率分别为94%、88%、84%。DVH显示PGTV最高、平均和最低剂量分别为54.47、52.27、38.83 Gy。因素分析显示年龄〉60岁、LDH升高为OS影响因素（P=0.009、0.002）,年龄〉60岁、IPI≥2分及LDH升高为PFS影响因素（P=0.001、0.035、0.007）。全组急性口腔黏膜反应1级 12例、2级 53例、3级 8例,晚期不良反应口干1级 16例、2级 13例。 结论 应用IMRT技术治疗原发韦氏环的早期DLBCL,获得了较理想的LRC、PFS、OS率,同时不良反应可耐受。

利妥昔单抗时代放疗对早期韦氏环弥漫大B细胞淋巴瘤的作用价值

目的：分析早期韦氏环弥漫大B细胞淋巴瘤接受利妥昔单抗加CHOP为主方案化疗后放疗的作用价值。方法2000—2013年收治83例确诊为原发韦氏环弥漫大B细胞淋巴瘤患者，其中Ⅰ期25例、Ⅱ期58例。全组接受了利妥昔单抗加CHOP为主方案化疗，62例接受了受累野放疗（韦氏环＋颈部淋巴结区域），21例未接受放疗。 Kaplan-Meier法计算OS、PFS、LRC并Logrank法检验和单因素分析，Cox模型多因素分析。结果全组5年样本数18例，5年OS、PFS和LRC率分别为89％、84％和90％。单因素分析显示年龄＞60岁、LDH升高、ECOG≥2分和IPI≥2分是OS的预后不良因素。年龄＞60岁、肿瘤≥5 cm、ECOG≥2分和IPI≥2分是PFS和LRC的影响因素。在利妥昔单抗治疗基础上加入巩固性放疗比未放疗者提高了5年PFS、LRC，分别为94％比58％（ P＝0.003）、100％比61％（ P＝0.000），OS有增加趋势（94％比71％，P＝0.063）。结论早期韦氏环弥漫大B细胞淋巴瘤利妥昔单抗加CHOP为主方化疗后巩固性放疗显著改善了PFS、LRC率，并可能改善OS率，需大样本和前瞻性研究证实。

早期韦氏环弥漫大B细胞淋巴瘤预后分析

目的分析早期韦氏环弥漫大B细胞淋巴瘤(WR-DLBCL)接受CHOP为主治疗的疗效及预后因素.方法2006-2018年间收治137例确诊为WR-DLBCL患者,其中Ⅰ期22例,Ⅱ期115例.全组接受了CHOP类为主方案化疗,其中62例使用了利妥昔单抗,87例接受了累及野放疗.Kaplan-meier法计算总生存(OS)、无进展生存(PFS)、无局部区域复发生存(LRRFS),并Logrank法检验和单因素分析,Cox模型多因素分析.结果全组5年OS、PFS、LRRFS分别为78.6%、69.5%、83.2%,综合治疗组分别为87.5%、80.2%、90.9%,单纯化疗组分别为64.2%、53.6%、72.9%.单因素分析显示乳酸脱氢酶、国际预后指数评分、大肿块、利妥昔单抗、化疗周期及综合治疗是影响OS、PFS因素;乳酸脱氢酶、大肿块、综合治疗是影响LRRFS因素.多因素分析显示乳酸脱氢酶、综合治疗模式、利妥昔单抗是影响OS因素,LDH、综合治疗模式是影响PFS因素,LDH是影响LRRFS因素.结论早期WR-BLBCL预后良好,在利妥昔单抗治疗的时代,化疗联合放疗的综合治疗方式仍然是早期WR-BLBCL的有效手段.