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年龄、生长激素/胰岛素样生长因子-1水平、肿瘤体积、T2低信号以及肿瘤亚型而非增殖和侵袭,都是肢端肥大症患者对生长抑素类似物治疗生化反应的可靠预测指标:一项临床病理研究。

Age, GH/IGF-1 levels, tumor volume, T2 hypointensity, and tumor subtype rather than proliferation and invasion are all reliable predictors of biochemical response to somatostatin analogue therapy in patients with acromegaly: A clinicopathological study.

作者信息

Durmuş Elif Tutku, Atmaca Ayşegül, Kefeli Mehmet, Çalışkan Sultan, Mete Ozgur, Aslan Kerim, Fidan Murat, Çolak Ramis, Durmuş Buğra

机构信息

Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey.

Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey.

出版信息

Growth Horm IGF Res. 2022 Dec;67:101502. doi: 10.1016/j.ghir.2022.101502. Epub 2022 Sep 9.

Abstract

PURPOSE

To determine whether biochemical responses to long-acting forms of first-generation somatostatin analogue (SSA) therapy in patients with acromegaly could be predicted from baseline and postoperative hormone concentrations, and tumor radiological and histopathological characteristics.

METHODS

A total of 68 patients with acromegaly for whom postoperative SSA therapy was started were categorized according to their responses to treatment (SSA-responders vs. non-responders). The patients were compared based on their demographic characteristics, hormone levels, magnetic resonance imaging (MRI), and histopathological findings. Receiver-operating-characteristic (ROC) curves were constructed using the predictive factors that were significant in the univariate analysis to determinate the optimal cut-off values.

RESULTS

The SSA-responders were significantly older (p = 0.041). Lower GH at diagnosis (p = 0.036), the postoperative 1st-week GH level (p = 0.027), baseline GH, insulin-like growth factor-1 (IGF-1) and IGF-1% upper limit of normal (ULN) (p = 0.001, p = 0.006, p = 0.023, respectively) were associated with biochemical response. T2-hypointensity and lower tumor volume were more common in the SSA-responders (p = 0.018, p = 0.03, respectively). Compared to sparsely granulated somatotroph tumors, densely granulated somatotroph tumors and other PitNETs causing GH excess including mammosomatotroph and mixed somatotroph and lactotroph tumors were more likely to respond to SSA therapy (p = 0.026, p = 0.03, respectively). The cut-off values generated by ROC curve analysis were GH at diagnosis of ≤8.8 ng/mL, GH at baseline of ≤2.69 ng/mL, IGF-1 at baseline ≤461.5 ng/mL, IGF-1% ULN at baseline ≤180.4%, and tumor volume of ≤1.11 cm (all p < 0.05). There were no differences between the groups in terms of tumor invasiveness, proliferative activity (mitotic count per 2 mm and Ki-67 labeling index) and quantitative analyses of T2-weighted MRI.

CONCLUSION

This study underscores that advanced age, low baseline GH and IGF-1 at diagnosis, low tumor volume, densely granulated tumor subtype, and T2 hypointensity may help predict biochemical response to SSA therapy in cases of acromegaly. These variables should be assessed with utmost attention for all patients prior to SSA treatment. In cases of possible resistance to SSA therapy, therapeutic activity should be monitored more closely and other therapies should be administered immediately in the event of poor response.

摘要

目的

确定能否根据基线和术后激素浓度、肿瘤的放射学和组织病理学特征,预测肢端肥大症患者对第一代长效生长抑素类似物(SSA)治疗的生化反应。

方法

共有68例开始接受术后SSA治疗的肢端肥大症患者,根据其对治疗的反应分为SSA反应者和无反应者。根据患者的人口统计学特征、激素水平、磁共振成像(MRI)和组织病理学结果进行比较。使用单因素分析中有显著意义的预测因素构建受试者工作特征(ROC)曲线,以确定最佳临界值。

结果

SSA反应者年龄显著较大(p = 0.041)。诊断时较低的生长激素(GH)水平(p = 0.036)、术后第1周的GH水平(p = 0.027)、基线GH、胰岛素样生长因子-1(IGF-1)和IGF-1%正常上限(ULN)(分别为p = 0.001、p = 0.006、p = 0.023)与生化反应相关。SSA反应者中T2低信号和较小的肿瘤体积更为常见(分别为p = 0.018、p = 0.03)。与稀疏颗粒型生长激素细胞肿瘤相比,密集颗粒型生长激素细胞肿瘤以及其他导致GH分泌过多的垂体神经内分泌肿瘤(PitNETs),包括乳腺生长激素细胞肿瘤和混合性生长激素细胞及催乳激素细胞肿瘤,对SSA治疗的反应更可能良好(分别为p = 0.026、p = 0.03)。ROC曲线分析得出的临界值为:诊断时GH≤8.8 ng/mL、基线GH≤2.69 ng/mL、基线IGF-1≤461.5 ng/mL、基线IGF-1% ULN≤180.4%以及肿瘤体积≤1.11 cm(所有p < 0.05)。两组在肿瘤侵袭性、增殖活性(每2 mm的有丝分裂计数和Ki-67标记指数)以及T2加权MRI定量分析方面无差异。

结论

本研究强调,高龄、诊断时低基线GH和IGF-1水平、小肿瘤体积、密集颗粒型肿瘤亚型以及T2低信号可能有助于预测肢端肥大症患者对SSA治疗的生化反应。在对所有患者进行SSA治疗前,应极其关注这些变量。对于可能对SSA治疗耐药的病例,应更密切地监测治疗效果,若反应不佳应立即给予其他治疗。

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