Purpose

Peptide receptor radionuclide therapy (PRRT) is effective for metastatic/inoperable neuroendocrine tumors (NETs). Imaging response assessment is usually efficient subsequent to treatment completion. Blood biomarkers such as PRRT Predictive Quotient (PPQ) and NETest are effective in real-time. PPQ predicts PRRT efficacy; NETest monitors disease. We prospectively evaluated: (1) NETest as a surrogate biomarker for RECIST; (2) the correlation of NETest levels with PPQ prediction.

Methods

Three independent ¹⁷⁷Lu-PRRT-treated GEP-NET and lung cohorts (Meldola, Italy: n = 72; Bad-Berka, Germany: n = 44; Rotterdam, Netherlands: n = 41). Treatment response: RECIST1.1 (responder (stable, partial, and complete response) vs non-responder). Blood sampling: pre-PRRT, before each cycle and follow-up (2–12 months). PPQ (positive/negative) and NETest (0–100 score) by PCR. Stable < 40; progressive > 40). CgA (ELISA) as comparator. Samples de-identified, measurement and analyses blinded. Kaplan–Meier survival and standard statistics.

Results

One hundred twenty-two of the 157 were evaluable. RECIST stabilization or response in 67%; 33% progressed. NETest significantly (p < 0.0001) decreased in RECIST “responders” (− 47 ± 3%); in “non-responders,” it remained increased (+ 79 ± 19%) (p < 0.0005). NETest monitoring accuracy was 98% (119/122). Follow-up levels > 40 (progressive) vs stable (< 40) significantly correlated with mPFS (not reached vs. 10 months; HR 0.04 (95%CI, 0.02–0.07).

PPQ response prediction was accurate in 118 (97%) with a 99% accurate positive and 93% accurate negative prediction. NETest significantly (p < 0.0001) decreased in PPQ-predicted responders (− 46 ± 3%) and remained elevated or increased in PPQ-predicted non-responders (+ 75 ± 19%). Follow-up NETest categories stable vs progressive significantly correlated with PPQ prediction and mPFS (not reached vs. 10 months; HR 0.06 (95%CI, 0.03–0.12).

CgA did not reflect PRRT treatment: in RECIST responders decrease in 38% and in non-responders 56% (p = NS).

Conclusions

PPQ predicts PRRT response in 97%. NETest accurately monitors PRRT response and is an effective surrogate marker of PRRT radiological response. NETest decrease identified responders and correlated (> 97%) with the pretreatment PPQ response predictor. CgA was non-informative.

目的

肽受体放射性核素疗法（PRRT）对于转移性/无法手术的神经内分泌肿瘤（NETs）有效。在完成治疗后，影像反应评估通常是有效的。诸如PRRT预测商（PPQ）和NETest的血液生物标记物是实时有效的。PPQ预测PRRT疗效；NETest监控疾病。我们进行了前瞻性评估：（1）NETest作为RECIST的替代生物标志物；（2）NETest水平与PPQ预测的相关性。

方法

三个独立的经过^177次Lu-PRRT治疗的GEP-NET和肺部队列研究（意大利梅多拉：n = 72；德国巴德-贝卡：n = 44；荷兰鹿特丹：n = 41）。治疗反应：RECIST1.1（反应者（稳定，部分和完全反应）对比无反应者）。血液采样：PRRT前，每个周期之前和随访（2-12个月）。通过PCR检测PPQ（阳性/阴性）和NETest（0-100分）。稳定< 40; 渐进> 40）。CgA（ELISA）作为对照。样品鉴定失败，测量和分析不知情。Kaplan–Meier生存率和标准统计量。

结果

157个中的122个是可评估的。RECIST稳定或响应率达到67％；33％取得了进展。RECIST“响应者”的NETest显着降低（p <0.0001）（-47±3％）；在“无反应者”中，其保持增加（+ 79±19％）（p <0.0005）。NETest监视准确性为98％（119/122）。随访水平> 40（进展）vs稳定（< 40）与mPFS显着相关（未达到vs. 10个月； HR 0.04（95％CI，0.02-0.07）。

PPQ反应预测在118个（97％）中是准确的，准确率为99％，阴性预测为93％。NETest在PPQ预测的应答者中显着降低（p <0.0001）（-46±3％），在PPQ预测的非应答者中保持升高或增加（+ 75±19％）。NETest类别稳定与进展的随访与PPQ预测和mPFS显着相关（未达到与10个月相比； HR为0.06（95％CI，0.03-0.12）。

CgA不能反映PRRT治疗：在RECIST中，有反应者下降38％，在无反应者中下降56％（p = NS）。

结论

PPQ预测PRRT响应率为97％。NETest可以准确地监测PRRT的反应，并且是PRRT放射学反应的有效替代指标。NETest减少可识别应答者，并与治疗前PPQ应答预测因子相关（> 97％）。CgA没有提供信息。