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

ABSTRACT:

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.

SUBMITTER: Nista F

PROVIDER: S-EPMC8139627 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundQuality of life (QoL) in patients with acromegaly is reduced irrespective of disease state. The contributions of multifactorial determinants of QoL in several disease stages are presently not well known.ObjectiveTo systematically review predictors of QoL in acromegalic patients.MethodsMain databases were systematically searched using predefined search terms for potentially relevant articles up to January 2017. Inclusion criteria included separate acromegaly cohort, non-hereditary acromegaly, QoL as study parameter with clearly described method of measurement and quantitative results, N ≥ 10 patients, article in English and adult patients only. Data extraction was performed by two independent reviewers; studies were included using the PRISMA flow diagram.ResultsWe identified 1,162 studies; 51 studies met the inclusion criteria: 31 cross-sectional observational studies [mean AcroQoL score 62.7 (range 46.6-87.0, n = 1,597)], 9 had a longitudinal component [mean baseline AcroQoL score 61.4 (range 54.3-69.0, n = 386)], and 15 were intervention studies [mean baseline AcroQoL score 58.6 (range 52.2-75.3, n = 521)]. Disease-activity reflected by biochemical control measures yielded mixed, and therefore inconclusive results with respect to their effect on QoL. Addition of pegvisomant to somatostatin analogs and start of lanreotide autogel resulted in improvement in QoL. Data from intervention studies on other treatment modalities were too limited to draw conclusions on the effects of these modalities on QoL. Interestingly, higher BMI and greater degree of depression showed consistently negative associations with QoL. Hypopituitarism was not significantly correlated with QoL in acromegaly.ConclusionAt present, there is insufficient published data to support that biochemical control, or treatment of acromegaly in general, is associated with improved QoL. Studies with somatostatin receptor ligand treatment, i.e., particularly lanreotide autogel and pegvisomant have shown improved QoL, but consensus on the correlation with biochemical control is missing. Longitudinal studies investigating predictors in treatment-naive patients and their follow-up after therapeutic interventions are lacking but are urgently needed. Other factors, i.e., depression and obesity were identified from cross-sectional cohort studies as consistent factors associated with poor QoL. Perhaps treatment strategies of acromegaly patients should not only focus on normalizing biochemical markers but emphasize improvement of QoL by alternative interventions such as psychosocial or weight lowering interventions.

Project description:OBJECTIVE:The aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics. DESIGN AND METHODS:The SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls. RESULTS:In total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR)=3.38; 95% confidence interval (CI), 1.78-6.42; P=0.00016 and OR=2.41; 95% CI, 1.41-4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P<0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient ?=-10.4; P=0.002), increased body mass index (?=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014). CONCLUSIONS:Our results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.

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Project description:IntroductionSomatostatin 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.MethodsMEDLINE, 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.ResultsA 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.ConclusionsStudy 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.