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Advances in Therapy Feb 2021Somatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and... (Review)
Review
Patient and Healthcare Provider Perspectives of First-Generation Somatostatin Analogs in the Management of Neuroendocrine Tumors and Acromegaly: A Systematic Literature Review.
INTRODUCTION
Somatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and lanreotide autogel/depot (LAN), are available. A systematic literature review (SLR) was conducted to investigate which characteristics beyond efficacy are most important in patient and healthcare practitioner (HCP) experience of LAN and OCT when used to treat acromegaly and NETs.
METHODS
MEDLINE, Embase, the Cochrane Library, and Database of Abstracts of Reviews of Effect were searched from database inception to January 2019 with terms for first-generation SSAs, NETs, acromegaly, preferences, decision-making, and human factors. Key congresses in 2016-2018 and SLR bibliographies were hand-searched. Two independent reviewers screened articles at title/abstract and full-text stage. Publications fulfilling pre-specified inclusion criteria reported patient or HCP perspectives of LAN or OCT, or any factors affecting treatment perspectives for NETs or acromegaly.
RESULTS
A total of 1110 unique records were screened, of which 21 studies were included, reporting from the perspectives of patients (n = 18) and/or HCPs (n = 9). Perspectives were collected using shared decision-making frameworks, questionnaires, informal patient opinion, and a Delphi panel. Where patient preference was specifically reported, LAN was preferred in 4/5 studies and OCT LAR in 1/5. Common factors underlying treatment experience included technical problems with injections and associated pain, emotional quality/anxiety of injections, time and convenience of treatment administration, and independence. Immediate aspects of injections appeared most important to patients, though the possibilities of extended dosing intervals and self-/partner-injection with LAN were also notable factors.
CONCLUSIONS
Study outcomes favored LAN in this SLR, with factors surrounding injection administration most influential in treatment experience. The findings of this SLR provide a basis that could inform development of decision-making criteria, with patient and HCP treatment perspectives considered. Future studies should utilize a common method to report preference and associated drivers.
Topics: Acromegaly; Health Personnel; Humans; Neuroendocrine Tumors; Octreotide; Somatostatin
PubMed: 33432541
DOI: 10.1007/s12325-020-01600-x -
The Journal of Clinical Endocrinology... Jan 2021Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.
METHODS
Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately.
RESULTS
Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased -2.3 points (95% CI, -1.3 to -3.3 points), and individual symptom scores decreased for paresthesia -0.9 (95% CI, -0.6 to -1.2), hyperhidrosis -0.4 (95% CI, -0.1 to -0.6), fatigue -0.3 (95% CI, -0.1 to -0.6), arthralgia -0.3 (95% CI, -0.1 to -0.5), headache -0.3 (95% CI, 0.0 to -0.6), and soft-tissue swelling -0.2 (95% CI, 0.0 to -0.4).
CONCLUSION
Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.
Topics: Acromegaly; Health Status; Humans; Prognosis; Quality of Life
PubMed: 33245343
DOI: 10.1210/clinem/dgaa868 -
Scientific Reports Oct 2019Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning... (Comparative Study)
Comparative Study Meta-Analysis
Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To assess current evidence of preoperative medical treatment, we performed a systematic review and meta-analysis of comparative studies. A literature search was conducted in Pubmed, Embase, and the Cochrane Library. Five randomized controlled trials (RCT) and seven non-RCT comparative studies were included. These studies mainly focused on pituitary macroadenomas though a small number of microadenoma cases were included. For safety, preoperative SSAs were not associated with elevated risks of postoperative complications. With respect to efficacy, the short-term cure rate was improved by preoperative SSAs, but the long-term cure rate showed no significant improvement. For invasive macroadenomas, the short-term cure rate was also improved, but the long-term results were not evaluable in clinical practice because adjuvant therapy was generally required. In conclusion, preoperative SSAs are safe in patients with acromegaly, and the favorable impact on surgical results is restricted to the short-term cure rate in macroadenomas and invasive macroadenomas. Further well-designed RCTs to examine long-term results are awaited to update the finding of this meta-analysis.
Topics: Acromegaly; Combined Modality Therapy; Growth Hormone-Secreting Pituitary Adenoma; Humans; Somatostatin; Treatment Outcome
PubMed: 31575930
DOI: 10.1038/s41598-019-50639-6 -
Endocrine Connections Jul 2019Machine learning methods in sellar region diseases present a particular challenge because of the complexity and the necessity for reproducibility. This systematic review...
INTRODUCTION
Machine learning methods in sellar region diseases present a particular challenge because of the complexity and the necessity for reproducibility. This systematic review aims to compile the current literature on sellar region diseases that utilized machine learning methods and to propose a quality assessment tool and reporting checklist for future studies.
METHODS
PubMed and Web of Science were searched to identify relevant studies. The quality assessment included five categories: unmet needs, reproducibility, robustness, generalizability and clinical significance.
RESULTS
Seventeen studies were included with the diagnosis of general pituitary neoplasms, acromegaly, Cushing's disease, craniopharyngioma and growth hormone deficiency. 87.5% of the studies arbitrarily chose one or two machine learning models. One study chose ensemble models, and one study compared several models. 43.8% of studies did not provide the platform for model training, and roughly half did not offer parameters or hyperparameters. 62.5% of the studies provided a valid method to avoid over-fitting, but only five reported variations in the validation statistics. Only one study validated the algorithm in a different external database. Four studies reported how to interpret the predictors, and most studies (68.8%) suggested possible clinical applications of the developed algorithm. The workflow of a machine-learning study and the recommended reporting items were also provided based on the results.
CONCLUSIONS
Machine learning methods were used to predict diagnosis and posttreatment outcomes in sellar region diseases. Though most studies had substantial unmet need and proposed possible clinical application, replicability, robustness and generalizability were major limits in current studies.
PubMed: 31234143
DOI: 10.1530/EC-19-0156 -
Journal of Research in Medical Sciences... 2019There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most... (Review)
Review
BACKGROUND
There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most published clinical trials involved only a few patients and their results are rather variable. We aimed to conduct a systematic review on available studies on the impact of these drugs on CV parameters.
MATERIALS AND METHODS
A literature search was conducted in MEDLINE (OVID), EMBase, Cochrane, and ISI Web of Science for citations published until April 30 2018 to identify studies on our objective that considered changes in CV parameters. For this search, we established a Boolean search strategy using keywords related to "acromegaly," "Somatostatin analog," and "cardiovascular diseases and parameters." All study types except for case reports or conference abstracts were included. Twenty-four studies ( = 558) fulfilled the inclusion criteria and were selected for final analysis.
RESULTS
In 12 studies ( = 350), decrease in heart rate (HR) and in 4 studies ( = 128), decrease in blood pressure (BP) was significant. In 15 studies ( = 320), left ventricular mass index (LVMi) changes were significant. In 9 studies ( = 202), the early diastole to peak velocity flow in late diastole (E/A ratio) was evaluated, and in 5 of them ( = 141), the improvement was significant. Eighteen studies ( = 366) examined changes in left ventricular ejection fraction (LVEF), 5 of which ( = 171) reported that these changes were significant. Decrease of left ventricular end-diastolic diameter was reported in only 2 studies ( = 27).
CONCLUSION
We found that first-generation SSAs have a beneficial effect on cardiac parameters such as HR and LVMi. For other parameters such as LVEF, BP, LV diameter, and E/A ratio, we were not able to draw a firm conclusion.
PubMed: 31143230
DOI: 10.4103/jrms.JRMS_955_18 -
Value in Health : the Journal of the... Jul 2018Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug treatments have been conducted.
OBJECTIVES
To conduct the first network meta-analysis simultaneously comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration recommendations (PROSPERO database under the registration number CRD42017059880). The electronic searches were conducted in PubMed (MEDLINE), Scopus, and Web of Science databases. Randomized controlled trials comparing any drug for the treatment of acromegaly head-to-head or versus placebo were included. Outcomes concerning the efficacy and safety of treatments were evaluated. The statistical analyses were performed using Aggregate Data Drug Information System version 1.16.8 (drugis.org, Groningen, The Netherlands).
RESULTS
The initial search retrieved 2059 articles. Of these, 10 randomized controlled trials were included in a qualitative analysis and 7 in a quantitative analysis. The network meta-analysis for the efficacy outcome (number of patients achieving insulinlike growth factor 1 control) showed that pegvisomant and lanreotide autogel were statistically superior to placebo (odds ratio [95% credible interval] 0.06 [0.00-0.55] and 0.09 [0.01-0.88]). No further differences were found. The probability rank indicated that pegvisomant and pasireotide have the highest probabilities (33% and 34%, respectively) of being the best therapeutic options. No major side effects were noted.
CONCLUSIONS
Pegvisomant is still a good option for acromegaly treatment, but pasireotide seems to be a promising alternative. Nevertheless, other important key factors such as drug costs and effectiveness (real-world results) should be taken into account when selecting acromegaly treatment.
Topics: Acromegaly; Adolescent; Adult; Aged; Aged, 80 and over; Female; Hormone Antagonists; Human Growth Hormone; Humans; Male; Middle Aged; Peptides, Cyclic; Receptors, Somatotropin; Somatostatin; Treatment Outcome; Young Adult
PubMed: 30005760
DOI: 10.1016/j.jval.2017.12.014 -
Acta Neurochirurgica Nov 2017The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal... (Comparative Study)
Comparative Study Review
PURPOSE
The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly.
METHODS
A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes.
RESULTS
Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively.
CONCLUSIONS
Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.
Topics: Acromegaly; Cerebrospinal Fluid Leak; Endoscopy; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hypopituitarism; Microsurgery; Pituitary Neoplasms; Postoperative Complications; Sphenoid Bone; Treatment Outcome
PubMed: 28913667
DOI: 10.1007/s00701-017-3318-6 -
Cancers Aug 2017Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by... (Review)
Review
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959-2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3-14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5-9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas.
PubMed: 28786923
DOI: 10.3390/cancers9080103 -
Neuroendocrinology 2017The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting.
OBJECTIVE
To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies.
DESIGN
A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of raw data from these studies was performed.
RESULTS
No significant effect of the d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results.
CONCLUSION
Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.
Topics: Acromegaly; Exons; Human Growth Hormone; Humans; Receptors, Somatotropin; Sequence Deletion
PubMed: 27513761
DOI: 10.1159/000448844 -
Frontiers in Endocrinology 2016PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA),... (Review)
Review
PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing's syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.
PubMed: 26869991
DOI: 10.3389/fendo.2016.00001