PDF(Pubmed)
Abstract：
While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.
Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.
Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
摘要：
■虽然有报道称使用[177Lu]Lu-DOTA-TATE治疗的嗜铬细胞瘤/副神经节瘤（PPGL）患者出现与治疗相关的内分泌干扰和儿茶酚胺激增，在治疗后即刻(48小时内)的这些异常的范围以前没有被评估过,可能被低估了.
■研究人群包括参加2期治疗生长抑素受体（SSTR）-2+不可手术/转移性嗜铬细胞瘤/副神经节瘤的患者（≥18岁）[177Lu]Lu-DOTA-TATE（每个周期7.4GBq，共1-4个周期）。激素测量[促肾上腺皮质激素（ACTH），皮质醇,促甲状腺激素(TSH),游离甲状腺素（FT4），卵泡刺激素（FSH），黄体生成素(LH),睾丸激素，雌二醇,生长激素,催乳素]，儿茶酚胺,根据试验方案，每个周期在第1、2、3、30和60天获得间肾上腺素，并进行了回顾性分析。
■在27名患者中（年龄：54±12.7岁，48.1%的女性)接受荷尔蒙评估，低泌乳素血症（14.1%），FSH升高（13.1%），LH升高(12.5%)是所有4个周期中最常见的激素异常。关于纵向随访，i.ACTH显着减少，皮质醇没有相应的变化，Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.TSH,和FT4,以及iii.[177Lu]Lu-DOTA-TATE第30天或之前的催乳素。促性腺激素轴和GH水平未观察到显着变化。第60天的所有激素水平与第1天值没有显着差异，这表明了这些变化的暂时性。然而,两名患者发展为临床，持续性内分泌疾病（原发性甲状腺功能减退症：n=1男性；绝经早期：n=1女性）。与第1天相比，去甲肾上腺素显著增加，多巴胺,在[177Lu]Lu-DOTA-TATE给药后24小时观察到去甲肾上腺素水平，并在48小时内达到峰值。
■[177Lu]Lu-DOTA-TATE治疗与SSTR2+内分泌组织辐射暴露引起的内分泌功能改变有关。然而,这些变化有时可能表现为临床上显著的内分泌疾病.因此，在[177Lu]Lu-DOTA-TATE治疗期间定期评估内分泌功能非常重要，尤其是有症状的患者。
■https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1，标识符NCT03206060。
■研究人群包括参加2期治疗生长抑素受体（SSTR）-2+不可手术/转移性嗜铬细胞瘤/副神经节瘤的患者（≥18岁）[177Lu]Lu-DOTA-TATE（每个周期7.4GBq，共1-4个周期）。激素测量[促肾上腺皮质激素（ACTH），皮质醇,促甲状腺激素(TSH),游离甲状腺素（FT4），卵泡刺激素（FSH），黄体生成素(LH),睾丸激素，雌二醇,生长激素,催乳素]，儿茶酚胺,根据试验方案，每个周期在第1、2、3、30和60天获得间肾上腺素，并进行了回顾性分析。
■在27名患者中（年龄：54±12.7岁，48.1%的女性)接受荷尔蒙评估，低泌乳素血症（14.1%），FSH升高（13.1%），LH升高(12.5%)是所有4个周期中最常见的激素异常。关于纵向随访，i.ACTH显着减少，皮质醇没有相应的变化，Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.TSH,和FT4,以及iii.[177Lu]Lu-DOTA-TATE第30天或之前的催乳素。促性腺激素轴和GH水平未观察到显着变化。第60天的所有激素水平与第1天值没有显着差异，这表明了这些变化的暂时性。然而,两名患者发展为临床，持续性内分泌疾病（原发性甲状腺功能减退症：n=1男性；绝经早期：n=1女性）。与第1天相比，去甲肾上腺素显著增加，多巴胺,在[177Lu]Lu-DOTA-TATE给药后24小时观察到去甲肾上腺素水平，并在48小时内达到峰值。
■[177Lu]Lu-DOTA-TATE治疗与SSTR2+内分泌组织辐射暴露引起的内分泌功能改变有关。然而,这些变化有时可能表现为临床上显著的内分泌疾病.因此，在[177Lu]Lu-DOTA-TATE治疗期间定期评估内分泌功能非常重要，尤其是有症状的患者。
■https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1，标识符NCT03206060。
