Abu Laban Dima, Alsharif Abeer, Al-Hussaini Maysa, Obeidat Mouness, Maraqa Bayan, Alzoubi Qasem, Musharbash Awni, Jaddoua Saad, Ramlawi Raed, Khaleifeh Kawther, Ibrahimi Ahmad Kh, Sarhan Nasim, Bouffet Eric, Amayiri Nisreen
Department of Diagnostic radiology, King Hussein Cancer Center, Amman, Jordan.
Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
Front Oncol. 2024 Sep 27;14:1417484. doi: 10.3389/fonc.2024.1417484. eCollection 2024.
Most pediatric low-grade-gliomas (LGG) and some high-grade-gliomas (HGG) have alterations in the RAS/MAPK pathway. Promising high tumor response rates were achieved using BRAF/MEK inhibitors, however data on their use in low-middle-income-countries (LMICs) are limited.
We retrospectively reviewed our Jordanian experience of using compassionate BRAF/MEK inhibitors in treating children with gliomas. We reviewed patients' clinical characteristics, tumor response, and side effects.
Twenty patients (13 males, 7 females) were identified. Median age at diagnosis was 8.3 years (0.3-18.9years). There were fifteen LGGs, three HGGs and two grade-2 pleomorphic xanthoastrocytoma (PXA-2). Fifteen tumors were supratentorial, three posterior fossa/brainstem, one diffuse-glioneuronal tumor (DLGNT) and one spinal. Five tumors were metastatic. Except for one patient with neurofibromatosis, ten patients underwent partial resection and nine had biopsy. All patients, except three, received BRAF/MEK inhibitors after initial standard chemo/radiotherapy. Seven LGGs had BRAF-mutation, six had BRAF-fusion, and two were empirically treated (one neurofibromatosis and one DLGNT). Fourteen LGGs were treated with 1-4 chemotherapy regimens before BRAF/MEK inhibitors' use; all had partial/stable response on targeted therapy at a median of 1.9 years (0.5-5.4years). Two patients with -mutated/ deleted PXA-2, had progression following resection, and experienced stable/partial response at 9 months of dabrafenib use. Two patients with HGGs had -mutation, and one had an FGFR-mutation. All three patients with HGG had temporary stable/partial response, two with significant clinical improvement. At a median of 2.7 years (1.3-3.2years), all patients experienced tumor progression, and two died. Eight patients (40%) developed acneiform rash, three (15%) paronychia, and one had significant panniculitis and fatigue. Six patients (30%) needed dose-reduction. Nine patients had temporary drug interruptions [due to side effects (5) and drug shortage (4)]. Two patients who stopped trametinib due to side effects (significant acneiform rash/paronychia and intracranial bleeding) did not experience progression.
Our experience with BRAF/MEK inhibitors' use was positive achieving response in all LGGs and provided sustained response with good quality of life for patients with HGG. Cost effectiveness analyses and patients' satisfaction comparisons with chemotherapy are needed to evaluate the routine use of these drugs in LMICs.
大多数儿童低级别胶质瘤（LGG）和一些高级别胶质瘤（HGG）的RAS/MAPK通路存在改变。使用BRAF/MEK抑制剂可实现较高的肿瘤缓解率，然而，关于其在低收入和中等收入国家（LMICs）使用的数据有限。
我们回顾性分析了约旦使用BRAF/MEK抑制剂治疗儿童胶质瘤的经验。我们回顾了患者的临床特征、肿瘤反应和副作用。
共纳入20例患者（男13例，女7例）。诊断时的中位年龄为8.3岁（0.3 - 18.9岁）。其中有15例LGG、3例HGG和2例2级多形性黄色星形细胞瘤（PXA - 2）。15例肿瘤位于幕上，3例位于后颅窝/脑干，1例为弥漫性神经胶质神经元肿瘤（DLGNT），1例位于脊髓。5例肿瘤有转移。除1例患有神经纤维瘤病的患者外，10例患者接受了部分切除术，9例进行了活检。除3例患者外，所有患者在初始标准化疗/放疗后接受了BRAF/MEK抑制剂治疗。7例LGG有BRAF突变，6例有BRAF融合，2例进行经验性治疗（1例神经纤维瘤病和1例DLGNT）。14例LGG在使用BRAF/MEK抑制剂前接受了1 - 4个化疗方案治疗；所有患者在靶向治疗中均有部分缓解/病情稳定，中位时间为1.9年（0.5 - 5.4年）。2例PXA - 2突变/缺失患者在切除术后病情进展，使用达拉非尼9个月后病情稳定/部分缓解。2例HGG患者有 - 突变，1例有FGFR突变。所有3例HGG患者均有暂时稳定/部分缓解，2例有显著临床改善。中位随访2.7年（1.3 - 3.2年）时，所有患者病情进展，2例死亡。8例患者（40%）出现痤疮样皮疹，3例（15%）出现甲沟炎，1例有严重脂膜炎和疲劳。6例患者（30%）需要减量。9例患者有暂时停药情况[原因包括副作用（5例）和药物短缺（4例）]。2例因副作用（严重痤疮样皮疹/甲沟炎和颅内出血）停用曲美替尼的患者未出现病情进展。
我们使用BRAF/MEK抑制剂的经验是积极的，所有LGG均有反应，HGG患者也获得了持续反应并具有良好的生活质量。需要进行成本效益分析以及与化疗的患者满意度比较，以评估这些药物在LMICs中的常规使用情况。
