Predictors of Response to Treatment with First-Generation Somatostatin Receptor Ligands in Patients with Acromegaly

Marques-Pamies, Montserrat; Gil, Joan; Jordà, Mireia; Puig-Domingo, Manel

doi:10.1016/j.arcmed.2023.102924

Cited by 7 publications

(3 citation statements)

References 90 publications

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“…Secondly, PAS-LAR treatment in non-responder patients was withdrawn only after 6 months of ineffective therapy, which may have prevented us to observe a delayed response in some of the patients in whom treatment was discontinued. Finally, we were not able to provide data on the T2 intensity at magnetic resonance or granulation pattern at histopathology as predictors of response to Pas-LAR, which could have been more informative ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study

Favero,

Zampetti,

Carioni

et al. 2024

Front. Endocrinol.

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BackgroundAcromegaly is caused by excessive growth hormone (GH) and insulin-like growth factor 1 (IGF1). Medical therapy plays a role as a treatment option for persistent disease after non-curative surgery or as a first-line therapy when surgery is not feasible. Pasireotide-LAR (Pas-LAR) is recommended for patients with acromegaly as second-line treatment.AimTo evaluate the patients characteristics predictive of an adequate response to Pas-LAR and the long-term efficacy and safety of the Pas-LAR treatment.MethodsData from 19 patients with active acromegaly, who were and resistant or intolerant to first-line medical therapy and were switched to pas-LAR have been retrospectively collected. We compared the baseline clinical and biochemical characteristics of patients who were found to respond to Pas-LAR therapy (responders, n=14) with those of patients who did not respond (non-responders, n=5). We then evaluated the Pas-LAR efficacy and safety during long-term follow-up in responders.ResultsIGF1 normalization occurred in 71.4% of responders after one injection. IGF1 levels, [median(interquartile range) of the upper limit of the normal range (ULN) fold increase] were higher in non-responders compared to responders within the initial month of therapy [1.40(1.30-2.34) vs 0.70(0.55-1.25), respectively, p=0.009] and after three [1.77(1.74-2.29) vs 0.94(0.82-1.13), respectively, p=0.029] and six months [1.68(1.33-1.72) vs 1.00(0.65 -1.28), respectively, p=0.002]. Out of 6 patients with symptomatic headache (all in responder group), 5 and 1 reported the resolution and improvement of headache, respectively, already after the first injection. Median HbA1c levels tended to increase from baseline to 6 months both in responder (36 mMol/Mol to 42 mMol/Mol) and non-responder patients (45 mMol/Mol to 48 mMol/Mol). During long term follow up, in the responder group 2 new patients developed diabetes. Tumor shrinkage was observed in 6 out of 7 evaluated responders, with no cases of size increase during the long-term follow-up.ConclusionPas-LAR is effective and safe and the early identification of responders is possible just after the first administration.

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Section: Discussionmentioning

confidence: 99%

Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study

Favero,

Zampetti,

Carioni

et al. 2024

Front. Endocrinol.

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“…от начала МТ АС1 (AUC = 0,672, Se 57%, Sp 72%). Благоприятными для лечения гормональными показателями являются уровни ГР и ИФР-1 менее 8,8 и 461,5 нг/мл (AUC = 0,676, Se 65%, Sp 60% и AUC = 0,707, Se 65%, Sp 65% соответственно) [31][32][33].…”

Section: Discussionunclassified

“…К другим морфологическим биомаркерам, указывающим на наличие ПСО и РСО, относятся грануляционный рисунок низкомолекулярного цитокератина CAM 5.2 Таблица 11. Чувствительность к аналогам соматостатина 1-й генерации у пациентов с различными опухолевыми фенотипами Другие проблемы эндокринологии [31]. Напротив, снижение этих показателей и избыточное присутствие (более 70%) клеток с ФТ является отражением эпителиально-мезенхимального перехода (ЭMП), проявляющегося увеличенными размерами, агрессивным и инвазивным ростом опухоли с наклонностью к рецидивированию [41].…”

Section: Discussionunclassified

Predictors of morphofunctional features of somatotrophic tumors and of the effectiveness of treatment with first-generation somatostatin receptor ligands

Pronin,

Antsiferov

et al. 2024

Medicinskij sovet

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Introduction. Timely differential diagnosis between densely and sparsely granulated somatotrophic tumors allows predicting the most probable scenario of acromegaly course, receptor phenotype and proliferative potential of tumor cells, risk of continued postoperative growth, as well as the efficacy of planned drug therapy with first-generation somatostatin receptor ligands.Aim. To validate cytological, radiological and therapeutic predictors allowing to evaluate the morphofunctional composition of somatotrophic tumors and to predict sensitivity to first-generation somatostatin receptor ligands.Materials and methods. 525 patients (153 men) aged 60.2 ± 14.0 years receiving drug therapy with first-generation somatostatin receptor ligands for 72.0 ± 51.9 months were examined.Results. Treatment efficacy was evaluated according to the final level of IGF-1 index (≤1) and compared with the data of pathomorphologic (97 patients) and repeated radiologic (53 patients) examination. The influence of cellular composition of densely and sparsely granulated somatotrophic tumors on immunohistochemical and radiologic characteristics with the designation of leading predictors of morphologic identification of somatotrophic tumors was investigated. Additional radio markers for quantitative assessment of relative intensity of tumor signal on T2-, T1and (T2-T1)-weighted MRI for non-invasive differential diagnostics of densely and sparsely granulated somatotrophic tumors and determination of optimal treatment tactics were proposed. The expediency of using pharmacotherapeutic testing with short-term (3–6 months) first-generation somatostatin receptor ligands administration to assess the intactness of receptor and postreceptor mechanisms and to choose optimal drug therapy was substantiated.Conclusion. The precision approach based on comprehensive clinical, radiological, pathomorphological and functional characteristics allows stratification of patients with acromegaly to optimize treatment benefit. Achievement of acromegaly control in drug therapy with first-generation somatostatin receptor ligands depends on tumor volume and its hormonal activity, absolute and relative expression of the 2nd subtype of somatostatin receptors, severity of destructive changes and features of cellular composition. In case of refractoriness to first-generation somatostatin receptor ligands, the use of pegvisomant is expedient.

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Immunological signatures and predictive biomarkers for first-generation somatostatin receptor ligand resistance in Acromegaly

Luo,

Yu,

Tang

2024

J Neurooncol

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Predictors of Response to Treatment with First-Generation Somatostatin Receptor Ligands in Patients with Acromegaly

Cited by 7 publications

References 90 publications

Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study

Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study

Predictors of morphofunctional features of somatotrophic tumors and of the effectiveness of treatment with first-generation somatostatin receptor ligands

Immunological signatures and predictive biomarkers for first-generation somatostatin receptor ligand resistance in Acromegaly

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