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


Journal

Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782

Informations de publication

Date de publication:
2021
Historique:
received: 08 03 2021
accepted: 19 04 2021
entrez: 24 5 2021
pubmed: 25 5 2021
medline: 24 12 2021
Statut: epublish

Résumé

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. 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 naïve acromegaly patients referred to a single tertiary center for pituitary diseases. 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. 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; 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. 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 naïve acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Sections du résumé

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 naïve 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; 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.
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 naïve acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Identifiants

pubmed: 34025586
doi: 10.3389/fendo.2021.677919
pmc: PMC8139627
doi:

Substances chimiques

IGF1 protein, human 0
Receptors, Somatostatin 0
Human Growth Hormone 12629-01-5
Insulin-Like Growth Factor I 67763-96-6

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

677919

Informations de copyright

Copyright © 2021 Nista, Corica, Castelletti, Khorrami, Campana, Cocchiara, Zoppoli, Prior, Rossi, Zona, Ferone and Gatto.

Déclaration de conflit d'intérêts

DF received grants and fees for lectures and participation to advisory boards for Novartis, Ipsen and Pfizer. F.G. received fees for lectures and/or participation to advisory boards for Novartis, AMCo, and IONIS Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Clin Endocrinol (Oxf). 2012 Mar;76(3):407-14
pubmed: 21848909
Nat Rev Endocrinol. 2018 Sep;14(9):552-561
pubmed: 30050156
Radiology. 2003 Aug;228(2):533-8
pubmed: 12819334
Endocr Relat Cancer. 2016 Nov;23(11):871-881
pubmed: 27649724
J Clin Endocrinol Metab. 2021 Mar 8;106(3):789-801
pubmed: 33236108
Eur J Endocrinol. 2013 Jul 15;169(2):217-23
pubmed: 23749849
J Clin Endocrinol Metab. 2013 Jan;98(1):E66-71
pubmed: 23118420
J Mol Endocrinol. 2014 Jun;52(3):R223-40
pubmed: 24647046
Gland Surg. 2019 Sep;8(Suppl 3):S150-S158
pubmed: 31559182
J Clin Endocrinol Metab. 2010 May;95(5):2334-42
pubmed: 20335450
J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51
pubmed: 25356808
Pituitary. 2018 Jun;21(3):310-322
pubmed: 29605877
Nat Rev Dis Primers. 2019 Mar 21;5(1):20
pubmed: 30899019
Arch Endocrinol Metab. 2019 Nov-Dec;63(6):618-629
pubmed: 31939487
J Endocrinol Invest. 2012 Jun;35(6):613-5
pubmed: 22776973
Trends Endocrinol Metab. 2013 May;24(5):238-46
pubmed: 23270713
Endocrine. 2016 Jun;52(3):451-7
pubmed: 26785848
Endocrine. 2016 Mar;51(3):524-33
pubmed: 25982150
Endocr Rev. 2004 Feb;25(1):102-52
pubmed: 14769829
J Clin Endocrinol Metab. 1999 Nov;84(11):3950-5
pubmed: 10566633
J Clin Endocrinol Metab. 2014 Apr;99(4):1282-90
pubmed: 24423301
N Engl J Med. 2020 Mar 5;382(10):937-950
pubmed: 32130815
Endocr Rev. 2011 Apr;32(2):247-71
pubmed: 21123741
Eur J Endocrinol. 2017 May;176(5):645-655
pubmed: 28246150
Clin Endocrinol (Oxf). 2009 Aug;71(2):166-70
pubmed: 19226264
Endocrine. 2016 Jul;53(1):327-30
pubmed: 26615593
Acta Neurochir (Wien). 2016 Apr;158(4):677-683
pubmed: 26821836
Growth Horm IGF Res. 2005 Jun;15(3):200-6
pubmed: 15935982
Endocr Relat Cancer. 2015 Apr;22(2):169-77
pubmed: 25556181
Eur J Endocrinol. 2005 Jul;153(1):67-71
pubmed: 15994747
Endocrine. 2019 Jan;63(1):120-129
pubmed: 30269264
Pituitary. 2020 Apr;23(2):171-181
pubmed: 31879842
Pituitary. 2013 Dec;16(4):490-8
pubmed: 23184260
Endocrine. 2016 May;52(2):333-43
pubmed: 26475495
Rev Endocr Metab Disord. 2020 Dec;21(4):667-678
pubmed: 32914330
J Clin Endocrinol Metab. 2019 Mar 1;104(3):856-862
pubmed: 30285115
Clin Endocrinol (Oxf). 2005 Mar;62(3):282-8
pubmed: 15730408
J Clin Endocrinol Metab. 2020 Sep 1;105(9):
pubmed: 32589751
Endocr Relat Cancer. 2020 Jun;27(6):375-389
pubmed: 32302973
Eur J Endocrinol. 2017 Feb;176(2):203-212
pubmed: 27932528
Endocr Rev. 2019 Feb 1;40(1):268-332
pubmed: 30184064
J Cell Mol Med. 2019 May;23(5):3088-3096
pubmed: 30843342
Eur J Endocrinol. 2007 Oct;157(4):399-409
pubmed: 17893253
Endocrine. 2018 Sep;61(3):533-541
pubmed: 29797214
Clin Endocrinol (Oxf). 2012 Jul;77(1):72-8
pubmed: 22066905
Pituitary. 2016 Jun;19(3):262-7
pubmed: 26792654
Ther Clin Risk Manag. 2020 May 05;16:379-391
pubmed: 32440136
J Clin Endocrinol Metab. 2010 Nov;95(11):4973-8
pubmed: 20739382
J Clin Endocrinol Metab. 2013 Nov;98(11):E1730-9
pubmed: 24092823
Pituitary. 2018 Aug;21(4):347-354
pubmed: 29460202
Pituitary. 2013 Mar;16(1):115-21
pubmed: 22481632
J Endocrinol Invest. 2012 Jun;35(6):616-8
pubmed: 22776974
Pituitary. 2016 Jun;19(3):235-47
pubmed: 26519143
Pituitary. 2017 Feb;20(1):116-120
pubmed: 28197813
Eur J Endocrinol. 2006 Feb;154(2):267-74
pubmed: 16452540

Auteurs

Federica Nista (F)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

Giuliana Corica (G)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

Lara Castelletti (L)

Department of Radiology, Tigullio Hospital, Lavagna, Italy.

Keyvan Khorrami (K)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

Claudia Campana (C)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

Francesco Cocchiara (F)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

Gabriele Zoppoli (G)

Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Alessandro Prior (A)

Division of Neurosurgery, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Diego Criminelli Rossi (DC)

Division of Neurosurgery, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Gianluigi Zona (G)

Division of Neurosurgery, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Diego Ferone (D)

Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Federico Gatto (F)

Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH