T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly.
T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly.
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DOI：
10.1530/eje-19-0840
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发表时间：
2020-06-01
影响因子：
5.8
通讯作者：
Neggers, Sebastian J C M M
中科院分区：
文献类型：
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作者：
Coopmans, Eva C;Schneiders, Joppe J;Neggers, Sebastian J C M M
目的：T2 信号强度和生长抑素 (SST) 受体表达是肢端肥大症治疗反应的公认预测因子。我们研究了这些预测因子与长效帕瑞肽 (PAS-LAR) 治疗的激素和肿瘤反应之间的关系，并与第一代生长抑素受体配体 (SRL) 的反应进行了比较。设计：PAPE 研究是一项队列研究。方法：我们纳入了 45 名肢端肥大症患者，最初接受 SRL，随后接受联合治疗 培维索孟，最后是 PAS-LAR。我们评估了肿瘤体积缩小（较基线≥25%）、IGF-1 水平（表示为正常上限）以及腺瘤的 T2 加权 MRI 信号和 SST 受体表达。 结果：PAS-LAR 期间肿瘤显着缩小的患者在 PAS-LAR 期间表现出较高的 IGF-1 水平（平均值 (S.D.)：1.36 (0.53) vs 0.93 (0.43)，P = 0.020），第一代 SRL 后 IGF-1 减少较少（平均值 (S.D.)：0.55 (0.71) vs 1.25 (1.07)，P = 0.028），并且 SST2 受体表达较低（中位数 (IQR)：2.0 (1.0-6.0) vs 12.0 (7.5-12.0)，P = 0.040）。总体而言，与基线相比，T2 信号强度比有所增加（平均值 (S.D.)：1.39 (0.56) vs 1.25 (0.52)，P = 0.017），并且 PAS-LAR 期间较高的 T2 信号与较低的 IGF-1 水平相关（β：-0.29，95% CI：-0.56 至 -0.01，P = 0.045）。 T2 信号强度增加的 PAS-LAR 治疗患者亚群实现了 IGF-1 更大程度的降低（平均值 (S.D.)：0.80 (0.60) vs 0.45 (0.39)，P = 0.016）。结论：对 SST2 受体表达较低的 SRL 无反应的患者在 PAS-LAR 期间更容易实现肿瘤缩小。令人惊讶的是，肿瘤缩小并不伴随生化反应，而生化反应则伴随着更高的 T2 信号强度。
OBJECTIVE: T2-signal intensity and somatostatin (SST) receptor expression are recognized predictors of therapy response in acromegaly. We investigated the relationship between these predictors and the hormonal and tumoral responses to long-acting pasireotide (PAS-LAR) therapy, which were also compared with responsiveness to first-generation somatostatin receptor ligands (SRLs).DESIGN: The PAPE study is a cohort study.METHODS: We included 45 acromegaly patients initially receiving SRLs, followed by combination therapy with pegvisomant, and finally PAS-LAR. We assessed tumor volume reduction (≥25% from baseline), IGF-1 levels (expressed as the upper limit of normal), and T2-weighted MRI signal and SST receptor expression of the adenoma.RESULTS: Patients with significant tumor shrinkage during PAS-LAR showed higher IGF-1 levels during PAS-LAR (mean (S.D.): 1.36 (0.53) vs 0.93 (0.43), P = 0.020), less IGF-1 reduction after first-generation SRLs (mean (S.D.): 0.55 (0.71) vs 1.25 (1.07), P = 0.028), and lower SST2 receptor expression (median (IQR): 2.0 (1.0-6.0) vs 12.0 (7.5-12.0), P = 0.040). Overall, T2-signal intensity ratio was increased compared with baseline (mean (S.D.): 1.39 (0.56) vs 1.25 (0.52), P = 0.017) and a higher T2-signal was associated with lower IGF-1 levels during PAS-LAR (beta: -0.29, 95% CI: -0.56 to -0.01, P = 0.045). A subset of PAS-LAR treated patients with increased T2-signal intensity achieved greater reduction of IGF-1 (mean (S.D.): 0.80 (0.60) vs 0.45 (0.39), P = 0.016).CONCLUSIONS: Patients unresponsive to SRLs with a lower SST2 receptor expression are more prone to achieve tumor shrinkage during PAS-LAR. Surprisingly, tumor shrinkage is not accompanied by a biochemical response, which is accompanied with a higher T2-signal intensity.