Background: Previous studies indicate that PAS-LAR can achieve control of insulin-like growth factor I (IGF-I) levels and may reduce tumor size, however a subset of acromegaly patients responds poorly. T2-signal intensity, somatostatin receptor (SST) subtype 2 and 5 expression, and the response to first-generation somatostatin receptor ligands (SRLs) are recognized predictors of therapy response. Valid prediction of the response to PAS-LAR can alter treatment stratification.
Aim: To analyze T2-signal intensity and SST receptor expression in relation to the hormone and tumor response during PAS-LAR treatment, and to determine to what extent this equals SRLs responsiveness.
Methods: We included 45 patients initially receiving SRLs, followed by a combination therapy including pegvisomant, and finally treated with PAS-LAR. The hormone response to PAS-LAR was evaluated using IGF-I (x ULN) levels at 24 weeks. T2-weighted MRI signal intensity of the adenoma was visually assessed and quantified by region of interest measurement. A tumor volume change of ≥25% from baseline was considered significant. SST receptor expression in adenomas was evaluated in 13 out of 45 patients using a validated immunoreactivity score (IRS). The clinical characteristics and the hormone and tumor response to PAS-LAR were assessed using multivariable regressions.
Results: Patients with the lowest percentage IGF-I (x ULN) reduction during SRLs also showed weak IGF-1 (x ULN) control during PAS-LAR and, however, more significant tumor shrinkage (r=0.41, P=0.006; P=0.036). Lower IGF-I (x ULN) levels during PAS-LAR were associated with higher T2-signal intensity and less significant tumor shrinkage (ß=−0.29, P=0.045; ß=0.34, P=0.035). With regards to tumor response, adenoma volume at baseline was associated with higher random GH levels at diagnosis and greater absolute tumor shrinkage during PAS-LAR (ß=69, P=0.0018; ß=1.05, P=0.020). Significant tumor shrinkage was associated with female patients, higher IGF-I (x ULN) levels during PAS-LAR and borderline significant with non-hypointense adenomas at baseline (OR=6.35, 95% CI=1.4236.4; OR=13.2, 95% CI=2.14129.1; OR=5.97, 95% CI=0.9165.5 respectively). Lower IGF-I (x ULN) levels after PAS-LAR correlated with higher (r=−0.68, P=0.011; r=−0.52, P=0.083), while significant tumor shrinkage correlated with lower SST2 levels and SST2/SST5 ratio (P=0.040; P=0.024).
Conclusions: Patients not responding to somatostatin analogs with particularly large adenomas, low SST2 receptor expression and higher T2-signal intensity are more prone to show tumor shrinkage during PAS-LAR than patients with high SST2 receptor expression and T2-hypointense adenomas. Surprisingly, tumor shrinkage is not accompanied by lower IGF-I (x ULN) levels, which are associated with a high SST2 receptor expression and a higher T2-signal intensity.
18 - 21 May 2019
European Society of Endocrinology