Grob Sydney, Mirsky David M, Donson Andrew M, Dahl Nathan, Foreman Nicholas K, Hoffman Lindsey M, Hankinson Todd C, Mulcahy Levy Jean M
Department of Pediatrics, University of Colorado Denver, Aurora, CO, United States.
The Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children's Hospital Colorado, Aurora, CO, United States.
Front Oncol. 2019 Aug 21;9:791. doi: 10.3389/fonc.2019.00791. eCollection 2019.
Adamantinomatous craniopharyngioma (ACP) makes up between 6 and 8% of pediatric brain tumors and is the most common pediatric tumor arising in the sellar/suprasellar region of the brain. The 10-year survival for patients diagnosed with craniopharyngioma ranges between 64 and 92%, but complicating factors such as location, common cyst formation, and potential hypothalamic infiltration cause significant morbidity in this population. There are a number of therapeutic options for children with ACP, including surgery, radiation, and cyst directed therapies such as interferon and bleomycin. Research has raised concerns regarding the efficacy and side effects associated with these conventional therapies, as well as with the difficulty in treating recurrent cystic ACP. Evidence from our group and others has shown that the cystic and solid tumor components of craniopharyngioma have high levels of IL-6R and IL-6, providing a potential target for therapy. Tocilizumab, a humanized monoclonal antibody, acts against soluble and membrane bound IL-6R, and has been widely utilized in pediatric patients. Two patients with recurrent cystic ACP were offered systemically administered tocilizumab or a combination of tocilizumab and bevacizumab on a compassionate use basis. Both patients' tumors had a significant response, with decreased cyst burden, supporting the assertion that tocilizumab with or without bevacizumab may be an option for patients suffering from cystic ACP.
成釉细胞瘤型颅咽管瘤（ACP）占儿童脑肿瘤的6%至8%，是起源于脑鞍区/鞍上区最常见的儿童肿瘤。被诊断为颅咽管瘤的患者10年生存率在64%至92%之间，但诸如肿瘤位置、常见的囊肿形成以及潜在的下丘脑浸润等复杂因素导致该人群出现显著的发病率。对于患有ACP的儿童有多种治疗选择，包括手术、放疗以及针对囊肿的治疗方法，如干扰素和博来霉素。研究引发了对这些传统疗法的疗效和副作用以及治疗复发性囊性ACP困难的担忧。我们团队和其他团队的证据表明，颅咽管瘤的囊性和实性肿瘤成分中白细胞介素-6受体（IL-6R）和白细胞介素-6（IL-6）水平较高，这为治疗提供了一个潜在靶点。托珠单抗是一种人源化单克隆抗体，作用于可溶性和膜结合型IL-6R，已在儿科患者中广泛应用。两名复发性囊性ACP患者在 compassionate use（可译为“基于人道考虑”等，此处可结合上下文准确理解其含义）的基础上接受了全身给药的托珠单抗或托珠单抗与贝伐单抗的联合治疗。两名患者的肿瘤均有显著反应，囊肿负担减轻，这支持了托珠单抗无论是否联合贝伐单抗可能是囊性ACP患者一种治疗选择的观点。
