Donato Iacovazzo1, Eivind Carlsen2, Francesca Lugli2, Sabrina Chiloiro2, Serena Piacentini2, Antonio Bianchi2, Antonella Giampietro2, Marilda Mormando2, Andrew J Clear2, Francesco Doglietto2, Carmelo Anile2, Giulio Maira2, Libero Lauriola2, Guido Rindi2, Federico Roncaroli2, Alfredo Pontecorvi2, Márta Korbonits3, Laura De Marinis2. 1. EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK. 2. EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK. 3. EndocrinologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKPathologySTHF, N-3710 Skien, NorwayEndocrinologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyHaemato-OncologyBarts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, UKNeurosurgeryUniversità di Brescia, 25121 Brescia, ItalyNeurosurgeryUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyNeurosurgeryHumanitas, 20089 Milan, ItalyPathologyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyBrainBehaviour and Mental Health, University of Manchester, M13 9PT Manchester, UK m.korbonits@qmul.ac.uk.
Abstract
AIM: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. PATIENTS AND METHODS: SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. RESULTS: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04). CONCLUSION: The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.
AIM: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. PATIENTS AND METHODS: SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. RESULTS: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04). CONCLUSION: The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.
Authors: Amy A Swanson; Dana Erickson; Diane Mary Donegan; Sarah M Jenkins; Jamie J Van Gompel; John L D Atkinson; Bradley J Erickson; Caterina Giannini Journal: Pituitary Date: 2020-10-19 Impact factor: 4.107