Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

Background First-generation somatostatin receptor ligands (fg-SRLs) represent the first-line medical treatment for acromegaly, recommended in patients with persistent disease after neurosurgery, or when surgical approach is not feasible. Despite the lack of strong recommendations from guidelines and consensus statements, data from national Registries report an increasing use of medical therapy as first-line treatment in acromegaly. Objective We retrospectively evaluated the potential role of a large number of clinical and radiological parameters in predicting the biochemical response to 6-month treatment with fg-SRLs, in a cohort of naive acromegaly patients referred to a single tertiary center for pituitary diseases. Methods Univariable and multivariable logistic regression and linear regression analyses were performed. Biochemical response was defined based on IGF-1 levels, represented as both categorical (tight control, control, >50% reduction) and continuous (linear % reduction) variables. Results Fifty-one patients (33 females, median age 57 years) were included in the study. At univariable logistic regression analysis, we found that younger age (<= 40 years; OR 0.04, p=0.045) and higher BMI (OR 0.866, p=0.034) were associated with a lower chance of achieving >50% IGF-1 reduction. On the contrary, higher IGF-1 xULN values at diagnosis (OR 2.304, p=0.007) and a T2-hypointense tumor (OR 18, p=0.017) were associated with a significantly higher likelihood of achieving >50% IGF-1 reduction after SRL therapy. Of note, dichotomized age, IGF1 xULN at diagnosis, and T2-hypointense signal of the tumor were retained as significant predictors by our multivariable logistic regression model. Furthermore, investigating the presence of predictors to the linear % IGF-1 reduction, we found a negative association with younger age (<= 40 years; beta -0.533, p<0.0001), while a positive association was observed with both IGF-1 xULN levels at diagnosis (beta 0.330, p=0.018) and the presence of a T2-hypointense pituitary tumor (beta 0.466, p=0.019). All these variables were still significant predictors at multivariable analysis. Conclusions Dichotomized age, IGF-1 levels at diagnosis, and tumor T2-weighted signal are reliable predictors of both >50% IGF-1 reduction and linear % IGF-1 reduction after 6 month fg-SRL treatment in naive acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Automated summary

The study demonstrated that age, IGF-1 levels, and tumor T2-weighted signal are significant predictors of biochemical response to fg-SRL treatment in naive acromegaly patients. Younger age, lower IGF-1 levels, and absence of T2-hypointense signal in the tumor were associated with poorer treatment outcomes. These factors should be taken into consideration for individualized treatment of acromegaly patients.