目的:在之前,回顾性研究,接受177Lu-DOTATOC分子放疗(MRT)的晚期神经内分泌肿瘤患者中有76%在第一个MRT周期的8个月内表现出最佳反应。在24%的患者中,在第一个周期后的22个月内,潜伏期要大得多,在上一个周期177Lu几乎完全衰变后很久。MRT诱导的免疫反应似乎是一个可能的解释。作为免疫能力的粗略测量,作者研究了血细胞计数(BCCs)对177Lu-DOTATOC的MRT结局是否具有预测价值.方法:56例神经内分泌肿瘤(NET)患者以3个月的间隔给药177Lu-DOTATOC(平均2.1个周期;范围1-4个周期),中位放射性为7.0GBq/周期。对患者的BCC进行了四个响应者类别的评估:CR,PR,SD,和PD(RECIST1.1)。此外,基线BCC与无进展生存期(PFS)相关。最后,比较了有(PMT)和没有先前药物治疗(PMT-)的患者的BCC。结果:基线血红蛋白(Hb)在响应者类别之间存在显着差异,红细胞,中性粒细胞,淋巴细胞,中性粒细胞/淋巴细胞比率(NLR),血小板/淋巴细胞比率(PLR),和LEHN-score,整合淋巴细胞,红细胞,和中性粒细胞计数,和Hb水平,但不是白细胞和血小板。LEHN评分在CR和PD组之间几乎完全分离。以此类推,PFS时间与基线Hb显著相关,红细胞,中性粒细胞,淋巴细胞,NLR,PLR,和LEHN-score,LEHN得分显示出最强的相关性,但没有白细胞和血小板.对于PMT患者,中位PFS为34.5个月,与PMT+患者的20.8个月相比,与相应的基线淋巴细胞(32.1±9.6%vs.24.5±11.6%,p=0.028)和中性粒细胞(54.9±11.6%vs.63.5±13.7%,p=0.039)计数。结论:这些发现强调了对MRT的免疫反应对于获得最佳治疗效果的重要性,并支持在MRT之前增强免疫功能较弱的患者的免疫反应的概念。似乎建议避免事先或同时进行免疫抑制剂药物治疗。
Purpose: In a prior, retrospective study, 76% of patients with advanced neuroendocrine tumors undergoing 177Lu-DOTATOC molecular radiotherapy (MRT) showed their best response within 8 months from the first MRT cycle. In 24% of patients, latency was much greater up to >22 months after the first cycle, and long after near-complete decay of 177Lu from the last cycle. An immune response induced by MRT seems a likely explanation. As a crude measure of immunocompetence, the authors investigated whether blood cell counts (BCCs) may have predictive value for MRT outcome with 177Lu-DOTATOC. Methods: 56 Patients with neuroendocrine tumors (NET) were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) with median radioactivity of 7.0 GBq/cycle at 3-month intervals. Patients\' BCCs were evaluated for four responder categories: CR, PR, SD, and PD (RECIST 1.1). Furthermore, baseline BCCs were correlated with progression-free survival (PFS). Finally, BCCs of patients with (PMT+) and without prior medical therapy (PMT-) were compared. Results: Significant differences between responder categories were found for baseline hemoglobin (Hb), erythrocytes, neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and LEHN-score, integrating lymphocyte, erythrocyte, and neutrophil counts, and Hb level, but not for leukocytes and platelets. LEHN-score yielded an almost complete separation between CR and PD groups. In analogy, PFS times showed significant correlations with baseline Hb, erythrocytes, neutrophils, lymphocytes, NLR, PLR, and LEHN-score, the LEHN-score showing the strongest correlation, but not with leukocytes and platelets. For PMT- patients, median PFS was 34.5 months, compared with 20.8 months in PMT+ patients, with corresponding baseline lymphocyte (32.1 ± 9.6% vs. 24.5 ± 11.6%, p = 0.028) and neutrophil (54.9 ± 11.6% vs. 63.5 ± 13.7%, p = 0.039) counts. Conclusion: These findings emphasize the significance of an immune response to MRT for obtaining optimal therapy efficacy and support concepts to enhance the immune response of less immunocompetent patients before MRT. It seems advisable to avoid prior or concomitant immunosuppressant medical therapy.