Positron Emission Tomography-Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group
Positron Emission Tomography-Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group
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DOI：
10.1200/jco.19.00964
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发表时间：
2019-11-01
影响因子：
45.3
通讯作者：
Engert, Andreas
中科院分区：
文献类型：
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作者：
Fuchs, Michael;Goergen, Helen;Engert, Andreas
联合治疗（CMT）2倍ABVD（多柔比星、博莱霉素、长春碱和达卡巴嗪）和小野放疗是早期有利霍奇金淋巴瘤（HL）患者的标准治疗。然而，放射治疗的作用受到了挑战。2x ABVD（PET-2）后的正电子发射断层扫描（PET）可能有助于预测个体结局并指导治疗。方法2009年11月至2015年12月，我们招募了年龄18至75岁的新诊断的早期有利HL患者，用于这项国际随机III期试验。患者被分配接受标准CMT 2 x ABVD和20-戈伊受累野放疗或PET引导治疗，PET-2阴性后省略受累野放疗（Deauville评分<3）。主要目的是在PET-2阴性患者的符合方案分析中排除单独ABVD与CMT相比5年无进展生存期（PFS）的10%或以上的劣效性（风险比的非劣效性界值为3.01），并确认PET-2阳性（Deauville评分≥ 3）是CMT治疗患者PFS的风险因素。中位随访时间为45个月。在628例PET-2阴性、符合方案治疗的患者中，5年PFS为93.4%（95% CI，90.4%至96.5%），CMT和86.1%（95% CI，81.4%至90.9%）与ABVD（差异7.3%[95% CI，1.6%至13.0%];风险比，1.78 [95% CI，1.02至3.12]）。CMT组的5年总生存率为98.1%（95% CI，96.5%-99.8%），ABVD组为98.4%（95% CI，96.5%-100.0%）。在693例分配至CMT的患者中，PET-2阴性患者的5年PFS为93. 2%（95% CI，90. 2%至96. 2%），PET-2阳性患者的5年PFS为88. 4%（95% CI，84. 2%至92. 6%）（P = 0. 047）。当使用更常见的肝脏截止值时（Deauville评分，4）对于PET-2阳性，差异更明显（5年PFS，93.1%[95% CI，90.7%至95.5%] vs 80.9%[95% CI，72.2%至89.7%];结论在早期有利的HL中，两个周期ABVD后阳性PET表明治疗失败的高风险，特别是当Deauville评分4用作阳性截止值时。在PET-2阴性患者中，在没有临床相关的肿瘤控制丧失的情况下，不能从CMT中省略放疗。
PURPOSE Combined-modality treatment (CMT) with 2x ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and small-field radiotherapy is standard of care for patients with early-stage favorable Hodgkin lymphoma (HL). However, the role of radiotherapy has been challenged. Positron emission tomography (PET) after 2x ABVD (PET-2) might help to predict individual outcomes and guide treatment.METHODS Between November 2009 and December 2015, we recruited patients age 18 to 75 years with newly diagnosed, early-stage favorable HL for this international randomized phase III trial. Patients were assigned to standard CMT of 2x ABVD and 20-Gy involved-field radiotherapy or PET-guided treatment, omitting involved-field radiotherapy after negative PET-2 (Deauville score < 3). Primary objectives were to exclude inferiority of 10% or more in 5-year progression-free survival (PFS) of ABVD alone compared with CMT in a per-protocol analysis among PET-2-negative patients (noninferiority margin for hazard ratio, 3.01) and to confirm PET-2 positivity (Deauville score >= 3) as a risk factor for PFS among CMT-treated patients.RESULTS We enrolled 1,150 patients. Median follow-up was 45 months. Among 628 PET-2-negative, per-protocol-treated patients, 5-year PFS was 93.4% (95% CI, 90.4% to 96.5%) with CMT and 86.1% (95% CI, 81.4% to 90.9%) with ABVD (difference 7.3% [95% CI, 1.6% to 13.0%]; hazard ratio, 1.78 [95% CI, 1.02 to 3.12]). Five-year overall survival was 98.1% (95% CI, 96.5% to 99.8%) with CMT and 98.4% (95% CI, 96.5% to 100.0%) with ABVD. Among 693 patients who were assigned to CMT, 5-year PFS was 93.2% (95% CI, 90.2% to 96.2%) among PET-2-negative patients and 88.4% (95% CI, 84.2% to 92.6%) in PET-2-positive patients (P = .047). When using the more common liver cutoff (Deauville score, 4) for PET-2 positivity, the difference was more pronounced (5-year PFS, 93.1% [95% CI, 90.7% to 95.5%] v 80.9% [95% CI, 72.2% to 89.7%]; P = .0011).CONCLUSION In early-stage favorable HL, a positive PET after two cycles ABVD indicates a high risk for treatment failure, particularly when a Deauville score of 4 is used as a cutoff for positivity. In PET-2-negative patients, radiotherapy cannot be omitted from CMT without clinically relevant loss of tumor control.