Endocrine Abstracts

The control of acromegaly with drug therapy (DT) by fg-SRLs is achieved only in 40–50% of cases, due to the heterogeneous composition of somatotrophic tumors. In order to optimize DT stratification of clinical and immunophenotypic biomarkers which make it possible to predict the long-term effectiveness of fg-SRLs at early stages is required. The aim of the work was to assess the informativeness of pharmacotherapeutic testing (% of decrease of IGF-1 level after 3 and 6 months of treatment) for the prognosis of the receptor phenotype of a somatotrophic tumor and the rationality of DT by fg-SRLs.

Materials and methods: The comparative study included 33 and 47 patients with densely and sparsely granulated somatotroph tumors (DGST&SGST) who received postsurgical DT by fg-SRLs. Prolonged forms of lanreotide and octreotide were used. The duration of DT was 21.5±21.8 months. The adequacy of DT was assessed by the level of IGF-1 index (IGF-1/ULN) ≤1. The control points were the indicators of IGF-1 before DT, after 3,6,12 months of treatment and at the last visit.

Results: The percentage of decrease of IGF-1 level after 3&6 months of fg-SRLs treatment was correlated with the expression of the SSTR2 (r=0.44; r=0.36), as well as the difference and the ratio between the SSTR2&SSTR5 [r=0.46; r=0.46&r=0.41; r=0.43;(P<0.05)]. The final value of IGF-1 index in patients with DGST&SGST was 0.95±0.27 vs. 1.4±0.64, (P=0.0002). The magnitude of the decrease of IGF-1 level in the groups of patients with DGST and SGST after 3&6 months was 54.8±19.6 vs. 28.4±23.7% and 58.4±18.0 vs. 31.6±24.5%, respectively (P=0.0002). The presence of an inverse correlation between the percentage of decrease of IGF-1 level after 3&6 months of fg-SRLs treatment and the final value of IGF-1 index was revealed [r=−0.59; r=−0.72;(P<0.001)]. In the ROC analysis, the AUC was 0.841&0.853. The decrease of IGF-1 level after 3&6 months by 46 and 49% of the baseline level was the cut-off point of effective DT. The sensitivity of these markers was 63&75%, the specificity was 79&80%, respectively. With a decrease of IGF-1 level after 3&6 months, over or under 50%, the final IGF-1 index was 0.9±0.2 vs. 1.49±0.62(P=0.000).

Conclusions: 1. The magnitude of the decrease of IGF-1 level after 3&6 months of fg-SRLs treatment reflects the severity of the expression of the SSTR2, as well as the intact postreceptor mechanisms in tumor cells.

2. The results of pharmacotherapeutic testing can be used as an additional predictor of the effectiveness of fg-SRLs long-term treatment.