Cacchione Antonella, Lodi Mariachiara, Carai Andrea, Miele Evelina, Tartaglia Marco, Megaro Giacomina, Del Baldo Giada, Alessi Iside, Colafati Giovanna Stefania, Carboni Alessia, Boccuto Luigi, Diomedi Camassei Francesca, Catanzaro Giuseppina, Po Agnese, Ferretti Elisabetta, Pedace Lucia, Pizzi Simone, Folgiero Valentina, Pezzullo Marco, Corsetti Tiziana, Secco Domitilla Elena, Cefalo Maria Giuseppina, Locatelli Franco, Mastronuzzi Angela
Department of Paediatric Haematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Neurosurgery Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Int J Cancer. 2021 May 15;148(10):2522-2534. doi: 10.1002/ijc.33438. Epub 2020 Dec 27.
Pediatric low-grade gliomas (pLGGs) are the most frequent brain tumor in children. Adjuvant treatment, consisting in chemotherapy and radiotherapy, is often necessary if a complete surgical resection cannot be obtained. Traditional treatment approaches result in a significant long-term morbidity, with a detrimental impact on quality of life. Dysregulation of the mitogen-activated protein kinase (MAPK) pathway is the molecular hallmark of pLGGs and hyperactivation of the downstream mammalian target of rapamycin (mTOR) pathway is frequently observed. We report clinical and radiological results of front-line treatment with everolimus in 10 consecutive patients diagnosed with m-TOR positive pLGGs at the Bambino Gesù Children's Hospital in Rome, Italy. Median duration of treatment was 19 months (range from 13-60). Brain magnetic resonance imaging showed stable disease in 7 patients, partial response in 1 and disease progression in 2. Therapy-related adverse events were always reversible after dose reduction or temporary treatment interruption. To the best of our knowledge, this is the first report of everolimus treatment for chemo- and radiotherapy-naïve children with pLGG. Our results provide preliminary support, despite low sample size, for the use of everolimus as target therapy in pLGG showing lack of progression with a manageable toxicity profile.
小儿低级别胶质瘤（pLGGs）是儿童中最常见的脑肿瘤。如果无法实现完整的手术切除，通常需要进行包括化疗和放疗在内的辅助治疗。传统治疗方法会导致显著的长期发病率，对生活质量产生不利影响。丝裂原活化蛋白激酶（MAPK）通路失调是pLGGs的分子标志，并且经常观察到下游雷帕霉素靶蛋白（mTOR）通路的过度激活。我们报告了在意大利罗马的 Bambino Gesù儿童医院，对 10 例连续诊断为 m-TOR 阳性 pLGGs 的患者进行依维莫司一线治疗的临床和放射学结果。中位治疗持续时间为 19 个月（范围为 13 - 60 个月）。脑磁共振成像显示 7 例患者疾病稳定，1 例部分缓解，2 例疾病进展。在剂量减少或暂时中断治疗后，治疗相关不良事件总是可逆的。据我们所知，这是首次关于依维莫司治疗未经化疗和放疗的 pLGG 患儿的报告。尽管样本量较小，但我们的结果为依维莫司作为 pLGG 的靶向治疗提供了初步支持，显示出无进展且毒性特征可控。
