生长激素分泌型垂体神经内分泌肿瘤治疗的现状与新进展

Current status and new advances in treatment of growth hormone-secreting pituitary neuroendocrine tumors

摘要:

生长激素分泌型垂体神经内分泌肿瘤（GH-PitNET）是一类以生长激素过量分泌为特征的垂体前叶来源肿瘤。最新共识指出，这类肿瘤患者激素缓解标准需要满足随机生长激素水平＜1 μg/L以及血清胰岛素生长因子1下降至与患者性别、年龄所匹配的范围。为达到上述治疗目标，近年来，新的手术、药物以及放射治疗方案的应用有效提高了肿瘤的控制率。神经内镜下的经鼻蝶手术由于具有近距离照明和广角视野的优势逐渐取代传统显微镜手术。术中的肿瘤假包膜外切除技术和选择性海绵窦内侧壁切除技术进一步提高了肿瘤的全切率。对于无法手术或术后激素未缓解的患者，口服生长抑素受体配体以及新型药物Paltusotine的出现提高了患者的依从性，多种药物的联合治疗也提高了激素的控制率。此外，贝伐珠单抗和免疫检查点抑制剂可能成为替莫唑胺外难治性垂体神经内分泌肿瘤的新选择。立体定向放射治疗具有精度高、剂量低的优点，是目前GH-PitNET的主要放疗手段，其有效性已被临床所证实。对于毗邻视神经的残余肿瘤组织，分次放疗技术可以有效减少视神经损伤风险的发生率，且不影响疗效。该文就GH-PitNET治疗的现状与新进展做一综述。

Abstract:

Growth hormone-secreting pituitary neuroendocrine tumor （GH-PitNET） are a group of anterior pituitary neoplasms characterized by excessive secretion of growth hormone （GH）. The latest consensus statements point out that biochemical remission in such tumor patients is defined as a random GH level of <1 μg/L and the reduction in serum insulin-like growth factor-1 to the range adjusted for age and sex. In order to achieve the above treatment goals， the application of new surgeries， drugs， and radiotherapy regimens in recent years has effectively improved tumor control rate. Neuroendoscopic endonasal transsphenoidal surgery has gradually replaced traditional microscopic procedures due to its superior visualization and illumination capabilities， and intraoperative pseudocapsule-based extracapsular resection and selective resection of cavernous sinus medial wall have further improved the total resection rate of tumor. For patients who are unsuitable for surgery or fail to achieve hormonal remission after surgery， oral administration of somatostatin receptor ligands and the development of the new drug Paltusotine can improve the compliance of patients， and combined treatment with multiple drugs can improve hormone control rate. In addition， bevacizumab and immune checkpoint inhibitors may become new options for pituitary neuroendocrine tumors refractory to temozolomide. Stereotactic radiotherapy has the advantages of high accuracy and low dose and has become the main radiotherapy regimen for GH-PitNET at present， and its efficacy has been confirmed in clinical practice. For residual tumor tissue near the optic nerves， fractionated radiotherapy can effectively reduce the incidence rate of optic nerve damage， without affecting treatment outcome. This article reviews the current status and new advances in the treatment of GH-PitNETs.