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

Abstract

BackgroundFirst-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.ObjectiveWe 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 naïve acromegaly patients referred to a single tertiary center for pituitary diseases.MethodsUnivariable 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.ResultsFifty-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; β -0.533, p<0.0001), while a positive association was observed with both IGF-1 xULN levels at diagnosis (β 0.330, p=0.018) and the presence of a T2-hypointense pituitary tumor (β 0.466, p=0.019). All these variables were still significant predictors at multivariable analysis.ConclusionsDichotomized 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 naïve acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain

“…Younger age at diagnosis appears to be the most important determinant of not responding, and a significant inverse association was seen between GH concentration at diagnosis and absolute IGF-1 reduction after treatment. Recently, Nista et al (36) retrospectively evaluated the potential predictors of SRL response in a cohort of 55 naïve acromegaly patients aged 57 (IQR: 45-63) and found that dichotomized age, IGF1 ULN at diagnosis, and T2-hypointense MRI signal of the tumor were reliable predictors of SRL response. However, this study was not fully comparable to ours, as patients were much younger.…”

gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

“…We recently developed a machine learning based prediction model, including clinical (age and sex), biochemical (GH and IGF-I levels), and immunohistochemical (SST2 and SST5 expression and cytokeratin granulation pattern) features, that predicted response to fg-SRL with an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5% [ 42 ]. Another recent study evaluated clinical, biochemical, and imaging parameters, and found that age was negatively correlated with IGF-I reduction, whereas IGF-I levels at diagnosis and tumor T2 hypointensity at MRI were positively correlated [ 43 ].…”

Resistance to Somatostatin Analogs in Italian Acromegaly Patients: The MISS Study

“…The main clinical predictors of fg-SRL resistance recognized in the literature include: male sex [5,13,14], young age [5,[13][14][15][16][17] and tumor hyperintensity on T2-weighted magnetic resonance imaging (MRI) scans [1,7,13,15,16]; however, IGF-I and r-GH values at diagnosis also deserve to be taken into consideration [5,8,[13][14][15][16][17]. Furthermore, the most relevant histological and molecular characteristics identified so far are the following: the grade of expression of the type 2 somatostatin receptors (SSTR2) [1,7,8,15,18], the pathological classification based on cytoplasmic granulation and keratin pattern analyzed by the CAM5.2 antibody [1,7,8,15], the proliferation index Ki-67 [7,18,19] and the presence of aryl hydrocarbon receptor-interacting protein (AIP) gene mutation [8,20,21].…”