[en] OBJECTIVE: T2-signal intensity and somatostatin (SST) receptor expression are recognized predictors of therapy response in acromegaly. We investigated the relationship between these predictors and the hormonal and tumoral responses to long-acting pasireotide (PAS-LAR) therapy, which were also compared with responsiveness to first-generation somatostatin receptor ligands (SRLs).
DESIGN: The PAPE study is a cohort study.
METHODS: We included 45 acromegaly patients initially receiving SRLs, followed by combination therapy with pegvisomant, and finally PAS-LAR. We assessed tumor volume reduction (≥25% from baseline), IGF-1 levels (expressed as the upper limit of normal), and T2-weighted MRI signal and SST receptor expression of the adenoma.
RESULTS: Patients with significant tumor shrinkage during PAS-LAR showed higher IGF-1 levels during PAS-LAR (mean (S.D.): 1.36 (0.53) vs 0.93 (0.43), P = 0.020), less IGF-1 reduction after first-generation SRLs (mean (S.D.): 0.55 (0.71) vs 1.25 (1.07), P = 0.028), and lower SST2 receptor expression (median (IQR): 2.0 (1.0-6.0) vs 12.0 (7.5-12.0), P = 0.040). Overall, T2-signal intensity ratio was increased compared with baseline (mean (S.D.): 1.39 (0.56) vs 1.25 (0.52), P = 0.017) and a higher T2-signal was associated with lower IGF-1 levels during PAS-LAR (β: -0.29, 95% CI: -0.56 to -0.01, P = 0.045). A subset of PAS-LAR treated patients with increased T2-signal intensity achieved greater reduction of IGF-1 (mean (S.D.): 0.80 (0.60) vs 0.45 (0.39), P = 0.016).
CONCLUSIONS: Patients unresponsive to SRLs with a lower SST2 receptor expression are more prone to achieve tumor shrinkage during PAS-LAR. Surprisingly, tumor shrinkage is not accompanied by a biochemical response, which is accompanied with a higher T2-signal intensity.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Coopmans, Eva C; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
Schneiders, Joppe J; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands
El-Sayed, Nour; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
Erler, Nicole S; Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands
Hofland, Leo J; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
van der Lely, Aart-Jan; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
Petrossians, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Potorac, Julia; Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, Liège, Belgium
Muhammad, Ammar; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
Neggers, Sebastian J C M M; Department of Medicine, Endocrinology Section, Pituitary Center Rotterdam, The Netherlands
Language :
English
Title :
T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly.
E C Coopmans, J J Schneiders, N El-Sayed, N S Erler, J Potorac, and A Muhammad have nothing to disclose. L J Hofland received investigator-initiated research grants from Novartis and 阀psen. P Petrossians received speakers and consulting fees from Novartis Pharma, 阀psen Pharma, and Pfizer. A J van der Lely is a consultant to Pfizer 阀nc. and Millendo Therapeutics and received grants from Pfizer 阀nc. S J C M M Neggers received research grants and speaker fees from 阀psen Pharma, Novartis Pharma, and Pfizer 阀nc. and consulting fees from Pfizer, Crinetics, and 阀psen Pharma.
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