Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH producing adenomas

2020 ◽  
Author(s):  
Joan Gil ◽  
Montserrat Marqués‐Pamies ◽  
Mireia Jordà ◽  
Carmen Fajardo‐Montañana ◽  
Araceli García‐Martínez ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Molecular Determinants

Diverse Peptidyl Privileged Structures as Potent Somatostatin Receptor Ligands

2004 ◽  
Vol 1 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Alexander Pasternak ◽  
Yanping Pan ◽  
Ralph Mosley ◽  
Susan Rohrer ◽  
Elizabeth Birzin ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Privileged Structures

MRI follow‐up of patients with acromegaly treated after surgery with first‐generation somatostatin receptor ligands

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands

scholarly journals Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Odelia Cooper ◽  
Vivien Bonert ◽  
Ning-Ai Liu ◽  
Adam N. Mamelak
Keyword(s):  
Radiation Therapy ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Individualized Approach ◽  
Evidence Based Guidelines

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

scholarly journals Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide

2020 ◽  
Vol 105 (10) ◽  
pp. e3785-e3797 ◽  
Author(s):  
Susan L Samson ◽  
Lisa B Nachtigall ◽  
Maria Fleseriu ◽  
Murray B Gordon ◽  
Marek Bolanowski ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Control Measures ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Phase 3 ◽  
Double Blind ◽  
Somatostatin Receptor Ligands ◽  
End Of Treatment

Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.

scholarly journals Medical Therapy of Acromegaly

2012 ◽  
Vol 2012 ◽  
pp. 1-22 ◽  
Author(s):  
U. Plöckinger
Keyword(s):  
Medical Therapy ◽  
Mechanism Of Action ◽  
Present Status ◽  
Therapeutic Efficacy ◽  
Dopamine Agonists ◽  
Somatostatin Receptor ◽  
Postoperative Treatment ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Remission Criteria

This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs), dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

scholarly journals Preoperative treatment of growth hormone (GH) producing macroadenomas with somatostatin receptor ligands (SRLs) to improve surgical outcome: a critical analysis

2018 ◽  
Vol 12 (1) ◽  
pp. 7-18
Author(s):  
Ariel Barkan
Keyword(s):  
Growth Hormone ◽  
Surgical Outcome ◽  
Somatostatin Receptor ◽  
Preoperative Treatment ◽  
Receptor Ligands ◽  
Tumor Removal ◽  
Post Surgery ◽  
Randomized Studies ◽  
Somatostatin Receptor Ligands ◽  
Complete Tumor

Thirty years ago, a hypothesis stating that preoperative shrinkage of growth hormone (GH) producing macroadenomas with somatostatin receptor ligands (SRLs) may improve surgical outcome was put forward. Since then, multiple retrospective, non-randomized studies as well as four contemporary prospective, randomized studies have been performed to evaluate the validity of that hypothesis and are critically reviewed in this manuscript. With the exception of an occasional retrospective study the great preponderance of evidence could not confirm this hypothesis. Similarly, while all prospective studies suggested better surgical outcome for SRL-pretreated tumors 3 months post surgery, the differences in outcomes between pretreated and untreated control patients disappeared after 6–12 months. Thus, preoperative treatment of macrosomatotropinomas with SRLs should not be relied upon as a means to achieve complete tumor removal and cannot be recommended.

scholarly journals MON-320 Inter-Rater Reliability of T2 MRI Intensity of Somatotroph Adenomas; Endocrinologists vs. Neuroradiologist Pilot Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elena V Varlamov ◽  
José Miguel Hinojosa-Amaya ◽  
Dawn Lim Shao Ting ◽  
Maria Fleseriu ◽  
Joao Prola
Keyword(s):  
White Matter ◽  
Pilot Study ◽  
Medical Therapy ◽  
Somatostatin Receptor ◽  
Biochemical Response ◽  
Receptor Ligands ◽  
Rater Reliability ◽  
Post Surgery ◽  
Somatostatin Receptor Ligands ◽  
T2 Mri

Abstract Background MRI T2 hypointensity of growth hormone (GH) secreting pituitary adenomas (PA) has been associated with better biochemical response to somatostatin receptor ligands and has been suggested to be useful in selecting patients with expected favorable response for pre- and post-surgery medical therapy. However, in most imaging centers, T2 intensity measurement is not part of standard neuroradiologist (NR) reporting. Objective To assess whether endocrinologists (Es) can reliably measure PA T2 signal intensity by calculating inter-rater reliability between Es and NR. Methods Retrospective review of MRI in 20 patients with pituitary somatotroph macroadenoma randomly selected from an IRB-approved PA database who had preoperative MRI available. T2 MRI intensity of the solid portion of the PA was compared to the temporal gray matter (GM) and white matter (WM): hypo- (PA< WM), hyper- (PA> GM), and isointense (WM <PA <GM). Measurements were performed separately by a NR and by two Es trained to take measurements by the same NR. Statistics: SPSS 25; Cohen kappa (κ). Results Patient mean age was 47 ± 20 years, with 12 females; mean largest PA diameter was 22.6 mm (range 11-45 mm). NR measured 12 hyper-, 7 iso- and 1 hypo-intense PA. Agreement was moderate between NR and E#1 (κ 0.72, 95%CI 0.751-1.0, p<0.001) and NR and E#2 (κ 0.638, 95%CI 0.351-0976, p<0.001) and strong between E#1 and E#2 (κ=0.90, 95%CI 0.309-0.903, p=0.001). Hypointense PA (by NR) was read by both Es as isointense. One hyperintense PA (by NR) was read by both Es as isointense. One isointense PA was read by E#2 as hypointense. Overall adenomas were; 9 densely granulated GH, 5 sparsely granulated GH, 3 mixed GH and prolactin, 1 plurihormonal, 1 not classified, and 1 no surgical intervention. Discussion Inter-rater reliability between the 2 Es was strong, however, it was moderate between each E and the NR. Factors that likely contributed to difference in measurement are heterogeneity of the PA, MRI quality, selection bias in choosing “most appropriate” site to measure intensity of adenoma, gray and white matter. Es could be trained to interpret the T2 intensity, although reliability with NR is only moderate. Interestingly, in this sample majority of T2 PA were hyperintense, but densely granulated, suggesting that preoperative identification of densely granulated tumors, which are also predictive of favorable SRL response, might be limited. More studies are needed to assess T2 correlation with pathology. Conclusion As T2 intensity (hyper-, hypo- or iso-) on MRI might be predictive of biochemical response to medical therapy in some patients with PA, we recommend T2 intensity to be part of neuroradiology reporting protocol. Our pilot study showed that endocrinologists could read MRIs after adequate training, but there is only moderate correlation with neuroradiologists.

scholarly journals The future of somatostatin receptor ligands in acromegaly

2021 ◽  
Author(s):  
Monica R Gadelha ◽  
Luiz Eduardo Wildemberg ◽  
Leandro Kasuki
Keyword(s):  
Precision Medicine ◽  
First Generation ◽  
Somatostatin Receptor ◽  
New Drugs ◽  
Response To Treatment ◽  
Tumor Shrinkage ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Somatostatin Receptor Ligands ◽  
The Future

Abstract Currently, first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients’ adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.

Sign in / Sign up

Export Citation Format

Share Document