体细胞营养肿瘤形态功能特征和第一代体生长激素受体配体治疗效果的预测因素

E. Pronin, V. Pronin, M. Antsiferov, A. V. Petryaykin, T. M. Alexeeva, A. Lapshina, L. Urusova, A. Khoruzhaya, S. Tamaeva
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引用次数: 0

摘要

导言。及时鉴别诊断稠密和稀疏颗粒的体细胞滋养性肿瘤可以预测肢端肥大症病程的最可能情况、肿瘤细胞的受体表型和增殖潜力、术后继续生长的风险以及计划使用第一代体生长激素受体配体进行药物治疗的疗效。验证细胞学、放射学和治疗预测因子,以评估体细胞营养肿瘤的形态功能组成,并预测对第一代体生长激素受体配体的敏感性。研究对象包括525名患者(153名男性),年龄为(60.2±14.0)岁,接受第一代体生长激素受体配体药物治疗的时间为(72.0±51.9)个月。根据 IGF-1 指数的最终水平(≤1)评估疗效,并与病理形态学检查(97 例)和重复放射学检查(53 例)的数据进行比较。研究还探讨了致密和稀疏颗粒状体细胞瘤的细胞组成对免疫组化和放射学特征的影响,并指定了体细胞瘤形态学鉴定的主要预测指标。此外,还提出了用于定量评估 T2、T1 和 (T2-T1) 加权磁共振成像上肿瘤信号相对强度的其他放射标记物,以对致密和稀疏肉芽肿瘤进行无创鉴别诊断,并确定最佳治疗策略。通过短期(3-6 个月)服用第一代体生长激素受体配体进行药物治疗测试,以评估受体和受体后机制的完好性,并选择最佳药物治疗方法的便捷性得到了证实。基于临床、放射学、病理形态学和功能学综合特征的精准方法可对肢端肥大症患者进行分层,以优化治疗效果。第一代体生长抑素受体配体药物治疗能否控制肢端肥大症取决于肿瘤体积及其激素活性、第二亚型体生长抑素受体的绝对和相对表达、破坏性变化的严重程度以及细胞组成特征。如果对第一代体生长抑素受体配体产生耐药性,则应尽快使用培维索孟。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Predictors of morphofunctional features of somatotrophic tumors and of the effectiveness of treatment with first-generation somatostatin receptor ligands
Introduction. Timely differential diagnosis between densely and sparsely granulated somatotrophic tumors allows predicting the most probable scenario of acromegaly course, receptor phenotype and proliferative potential of tumor cells, risk of continued postoperative growth, as well as the efficacy of planned drug therapy with first-generation somatostatin receptor ligands.Aim. To validate cytological, radiological and therapeutic predictors allowing to evaluate the morphofunctional composition of somatotrophic tumors and to predict sensitivity to first-generation somatostatin receptor ligands.Materials and methods. 525 patients (153 men) aged 60.2 ± 14.0 years receiving drug therapy with first-generation somatostatin receptor ligands for 72.0 ± 51.9 months were examined.Results. Treatment efficacy was evaluated according to the final level of IGF-1 index (≤1) and compared with the data of pathomorphologic (97 patients) and repeated radiologic (53 patients) examination. The influence of cellular composition of densely and sparsely granulated somatotrophic tumors on immunohistochemical and radiologic characteristics with the designation of leading predictors of morphologic identification of somatotrophic tumors was investigated. Additional radio markers for quantitative assessment of relative intensity of tumor signal on T2-, T1and (T2-T1)-weighted MRI for non-invasive differential diagnostics of densely and sparsely granulated somatotrophic tumors and determination of optimal treatment tactics were proposed. The expediency of using pharmacotherapeutic testing with short-term (3–6 months) first-generation somatostatin receptor ligands administration to assess the intactness of receptor and postreceptor mechanisms and to choose optimal drug therapy was substantiated.Conclusion. The precision approach based on comprehensive clinical, radiological, pathomorphological and functional characteristics allows stratification of patients with acromegaly to optimize treatment benefit. Achievement of acromegaly control in drug therapy with first-generation somatostatin receptor ligands depends on tumor volume and its hormonal activity, absolute and relative expression of the 2nd subtype of somatostatin receptors, severity of destructive changes and features of cellular composition. In case of refractoriness to first-generation somatostatin receptor ligands, the use of pegvisomant is expedient.
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