Herrmann Ken, Buck Andreas K, Schuster Tibor, Abbrederis Kathrin, Blümel Christina, Santi Ivan, Rudelius Martina, Wester Hans-Jürgen, Peschel Christian, Schwaiger Markus, Dechow Tobias, Keller Ulrich
Department of Nuclear Medicine, Technische Universität München, Munich, Germany. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany. These Authors contributed equally to this work.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.
Oncotarget. 2014 Jun 30;5(12):4050-9. doi: 10.18632/oncotarget.1990.
Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.
尽管在利妥昔单抗（R）时代患者生存率有所提高，但仍有相当数量的弥漫性大B细胞淋巴瘤（DLBCL）患者最终死于该疾病。建议使用[18F]氟脱氧葡萄糖-PET进行功能成像，以便在治疗早期评估残留的存活肿瘤，但炎症病变中示踪剂的非特异性滞留会影响其效果。PET示踪剂[18F]氟脱氧胸苷（FLT）作为肿瘤增殖的替代标志物可能会克服这一局限性。我们展示了一项前瞻性临床研究的结果，该研究测试了FLT-PET作为DLBCL化疗反应和预后的优越且早期预测指标。54例患者在R-CHOP化疗开始前和开始后一周接受了FLT-PET检查。重复性FLT-PET成像很容易应用于诊断检查。我们的数据表明，化疗一周后，达到完全缓解（CR，n = 48；非CR，n = 6；p < 0.006）的患者中，FLT标准摄取值均值（SUVmean）和SUV最大值的降低更为显著。鞅残差分析和Cox比例风险分析表明，随着SUV变化的增加，死亡风险显著单调降低。与这些结果一致，早期FLT-PET反应在预测CR方面具有显著的鉴别能力。总之，在R-CHOP化疗过程中进行早期FLT-PET检查是可行的，并且能够识别有治疗失败风险的患者。
