Randomized Trial of Systemic Therapy After Involved-Field Radiotherapy in Patients With Early-Stage Follicular Lymphoma: TROG 99.03
Randomized Trial of Systemic Therapy After Involved-Field Radiotherapy in Patients With Early-Stage Follicular Lymphoma: TROG 99.03
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DOI：
10.1200/jco.2018.77.9892
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发表时间：
2018-10-10
影响因子：
45.3
通讯作者：
Seymour, John F.
中科院分区：
文献类型：
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作者：
MacManus, Michael;Fisher, Richard;Seymour, John F.
目的：滤泡性淋巴瘤（FL）在I ~ II期患者中，有50%以下的患者可通过受病灶放疗（IFRT）治愈。我们假设在IFRT中加入全身治疗可以改善长期无进展生存期（PFS）。患者和方法一项多中心随机对照试验纳入了分期计算机断层扫描和骨髓活检的I至II期低级别FL患者。f -18标记的氟脱氧葡萄糖正电子发射断层扫描（PET）不是强制性的。患者被随机分配到A组（单独30 Gy IFRT）或B组（IFRT加6个周期环磷酰胺、长春新碱和强的松龙[CVP]）。从2006年起，利妥昔单抗被添加到B组（R-CVP）。结果2000年至2012年间，150名患者入组，每组75名。在B组中，44名患者被分配接受CVP， 31名患者被分配接受R-CVP。随机分组时，75%为I期，中位年龄为57岁，52%为男性，48%为PET分期。中位随访9.6年（范围3.1至15.8年），B组的PFS优于对照组（风险比为0.57；95% CI为0.34至0.95;P = 0.033）。B组和A组的10年PFS分别为59% （95% CI, 46% - 74%）和41% （95% CI, 30% - 57%）。B组接受R-CVP治疗的患者的PFS明显优于A组同期患者（风险比，0.26;95% CI， 0.07至0.97;P = 0.045）。较少的受累区域（P = 0.047）和PET分期（P = 0.056）与较好的PFS相关。B组和A组分别有4例和10例患者发生组织学转变（P = 0.1）。A组有10例死亡，B组有5例死亡，但总生存率无显著差异（P = 0.40； 10年生存率分别为87%和95%）。结论放疗后全身应用R-CVP可减少放疗外复发，显著改善PFS。IFRT加免疫化疗治疗早期FL比IFRT更有效。
PurposeFollicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS).Patients and MethodsA multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. F-18-labeled fluorodeoxyglucose-positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP).ResultsBetween 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions (P = .047) and PET staging (P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively (P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different (P = .40; 87% and 95% at 10 years, respectively).ConclusionSystemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.