Abstract：
We aimed to determine the added value of baseline metabolic tumor volume (MTV) and interim PET (I-PET) to the age-adjusted international prognostic index (aaIPI) to predict 2-y progression-free survival (PFS) in diffuse large B-cell lymphoma. Secondary objectives were to investigate optimal I-PET response criteria (using Deauville score [DS] or quantitative change in SUVmax [ΔSUVmax] between baseline and I-PET4 [observational I-PET scans after 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone administered in 2-wk intervals with intensified rituximab in the first 4 cycles [R(R)-CHOP14]). Methods: I-PET4 scans in the HOVON-84 (Hemato-Oncologie voor Volwassenen Nederland [Haemato Oncology Foundation for Adults in the Netherlands]) randomized clinical trial (EudraCT 2006-005174-42) were centrally reviewed using DS (cutoff, 4-5). Additionally, ΔSUVmax (prespecified cutoff, 70%) and baseline MTV were measured. Multivariable hazard ratio (HR), positive predictive value (PPV), and negative predictive value (NPV) were obtained for 2-y PFS. Results: In total, 513 I-PET4 scans were reviewed according to DS, and ΔSUVmax and baseline MTV were available for 367 and 296 patients. The NPV of I-PET ranged between 82% and 86% for all PET response criteria. Univariate HR and PPV were better for ΔSUVmax (4.8% and 53%, respectively) than for DS (3.1% and 38%, respectively). aaIPI and ΔSUVmax independently predicted 2-y PFS (HR, 3.2 and 5.0, respectively); adding MTV brought about a slight improvement. Low or low-intermediate aaIPI combined with a ΔSUVmax of more than 70% (37% of patients) yielded an NPV of 93%, and the combination of high-intermediate or high aaIPI and a ΔSUVmax of 70% or less yielded a PPV of 65%. Conclusion: In this study on diffuse large B-cell lymphoma, I-PET after 4 cycles of R(R)-CHOP14 added predictive value to aaIPI for 2-y PFS, and both were independent response biomarkers in a multivariable Cox model. We externally validated that ΔSUVmax outperformed DS in 2-y PFS prediction.
摘要：
我们旨在确定基线代谢性肿瘤体积（MTV）和临时PET（I-PET）对年龄调整后的国际预后指数（aaIPI）的附加值，以预测弥漫性大B细胞淋巴瘤的2-y无进展生存期（PFS）。次要目标是研究最佳I-PET反应标准（使用Deauville评分[DS]或基线和I-PET4之间SUVmax[ΔSUVmax]的定量变化[利妥昔单抗4个周期后的观察性I-PET扫描，环磷酰胺,阿霉素,长春新碱,和泼尼松在前4个周期中间隔2周给予强化利妥昔单抗[R(R)-CHOP14])。方法：使用DS对HOVON-84（荷兰成人血液肿瘤基金会[荷兰成人血液肿瘤基金会]）的I-PET4扫描进行了集中审查（EudraCT2006-005174-42）的随机临床试验（截止，4-5).此外,ΔSUVmax(预先指定的截止值，70%)和基线MTV进行测量。多变量危险比(HR)，阳性预测值(PPV)，并获得2-yPFS的阴性预测值（NPV）。结果：总的来说，513I-PET4扫描根据DS进行审查，和ΔSUVmax和基线MTV可用于367和296例患者。对于所有PET反应标准,I-PET的NPV在82%和86%之间。单变量HR和PPV对ΔSUVmax更好(4.8%和53%，分别）比DS（3.1%和38%，分别)。aIPI和ΔSUVmax独立预测2-yPFS(HR，分别为3.2和5.0）；添加MTV带来了轻微的改善。低或低中间aaIPI与超过70％的ΔSUVmax（37％的患者）相结合，NPV为93％，并且高中间或高aaIPI与70%或更低的ΔSUVmax的组合产生65%的PPV。结论:在弥漫大B细胞淋巴瘤的研究中,在4个周期的R（R）-CHOP14后，I-PET对2-yPFS的aIPI增加了预测值，在多变量Cox模型中，两者都是独立的反应生物标志物。我们在外部验证了ΔSUVmax在2-yPFS预测中优于DS。
