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肢端肥大症的个性化医疗:ACROFAST研究。

Personalized Medicine in Acromegaly: The ACROFAST Study.

作者信息

Marques-Pamies Montserrat, Gil Joan, Sampedro-Nuñez Miguel, Valassi Elena, Biagetti Betina, Giménez-Palop Olga, Hernández Marta, Martínez Silvia, Carrato Cristina, Villar-Taibo Rocío, Araujo-Castro Marta, Blanco Concepción, Simón-Muela Inmaculada, Simó-Servat Andreu, Xifra Gemma, Vázquez Federico, Pavón Isabel, Rosado José Antonio, García-Centeno Rogelio, Zavala Roxana, Hanzu Felicia Alexandra, Mora Mireia, Aulinas Anna, Vilarrasa Nuria, Librizzi Soledad, Calatayud María, de Miguel Paz, Alvarez-Escola Cristina, Picó Antonio, Salinas Isabel, Fajardo-Montañana Carmen, Cámara Rosa, Bernabéu Ignacio, Jordà Mireia, Webb Susan M, Marazuela Mónica, Puig-Domingo Manel

机构信息

Department of Endocrinology and Nutrition, Hospital Municipal de Badalona, Badalona 08911, Spain.

Endocrine Research Unit, Germans Trias i Pujol Research Institute (IGTP), Badalona 08916, Spain.

出版信息

J Clin Endocrinol Metab. 2024 Dec 18;110(1):30-40. doi: 10.1210/clinem/dgae444.

Abstract

CONTEXT

Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response.

OBJECTIVE

Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.

METHODS

This was a prospective trial (21 university hospitals) comparing the effectiveness and time-to-control of 2 treatment protocols during 12 months: (A) a personalized protocol in which the first options were fgSRLs as monotherapy or in combination with pegvisomant, or pegvisomant as monotherapy depending on the short acute octreotide test (sAOT) results, tumor T2 magnetic resonance (MRI) signal or immunostaining for E-cadherin; and (B) a control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control.

RESULTS

Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, P < .05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI, 1.30-4.80). Patients from the personalized arm were controlled in a shorter period of time (P = .01).

CONCLUSION

Personalized medicine is feasible using a relatively simple protocol, and it allows a higher number of patients to achieve control in a shorter period of time.

摘要

背景

目前,肢端肥大症的医学治疗采用试错法,将第一代生长抑素受体配体(fgSRLs)作为一线药物,有效率约为50%,后续药物则通过临床判断来选用。一些生物标志物可预测fgSRLs的反应。

目的

在此,我们报告ACROFAST研究的结果,该研究是一项评估基于fgSRLs预测生物标志物方案的临床试验。

方法

这是一项前瞻性试验(21家大学医院参与),比较了两种治疗方案在12个月内的有效性和控制时间:(A)个性化方案,根据短程急性奥曲肽试验(sAOT)结果、肿瘤T2磁共振(MRI)信号或E-钙黏蛋白免疫染色,首选fgSRLs单药治疗或与培维索孟联合使用,或培维索孟单药治疗;(B)对照组,治疗始终从fgSRLs开始,在证明控制效果不佳后再使用其他药物。

结果

85名患者参与研究,其中个性化方案组45名,对照组40名。与对照组相比,个性化方案组有更多患者实现了激素控制(78%对53%,P<.05)。生存分析显示,经年龄和性别调整后,实现激素控制的风险比为2.53(置信区间,1.30 - 4.80)。个性化方案组的患者在更短时间内实现了控制(P = .01)。

结论

使用相对简单的方案实施个性化医疗是可行的,且能使更多患者在更短时间内实现控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f7b/11651705/da9e663ba853/dgae444f1.jpg

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