Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Dermatology Unit "Daniele Innocenzi", "A. Fiorini" Hospital, Terracina, Italy.
Clin Ter. 2024 Nov-Dec;175(6):374-377. doi: 10.7417/CT.2024.5141.
Melanoma brain metastases represents a significant clinical challenge, frequently associated with high morbidity and mortality. Recent advancements in neuroimaging, radiation therapy, and targeted systemic therapies, specifically BRAF and MEK inhibitors, have improved the management of this condition. Nevertheless, the optimal therapeutic approach for melanoma brain metastases remains a subject of ongoing debate, with no universally accepted treatment protocol. The combination of stereotactic radiosurgery with targeted therapy using encorafenib and binimetinib in patients harboring BRAF V600E mutation holds therapeutic promise but requires careful toxicity management to ensure both safety and efficacy.
A 61-year-old male with metastatic BRAF V600E-mutated melanoma presented with a 20 mm brain metastasis in the right occipital lobe, manifesting as acute-onset diplopia. The patient was undergoing systemic therapy with encorafenib and binimetinib for metastatic lung involvement. Brain MRI revealed a metastatic lesion with surrounding edema. To minimize the risk of overlapping toxicities, a treatment strategy was devised, combining stereotactic radiosurgery with a temporary cessation of targeted therapy. Stereotactic radiosurgery was administered at a total dose of 27 Gy in three fractions, with enco-rafenib and binimetinib paused 24 hours prior to, and resumed 24 hours following, the radiosurgery. Following treatment, the patient's diplopia resolved completely, and a follow-up MRI two months later demonstrated near-total regression of the brain metastasis. At 30 months post-treatment, the patient remained free from recurrence and continued systemic therapy with excellent tolerance and no reported adverse effects.
This case demonstrates the efficacy and safety of combining stereotactic radiosurgery with encorafenib and binimetinib for managing melanoma brain metastases with BRAF V600E mutation. This approach provided effective disease control, as evidenced by symptom resolution, near-complete regression on MRI, and sustained remission at 30 months, with no adverse effects observed. Further studies are needed to establish standardized protocols for optimizing outcomes in this patient population.
黑色素瘤脑转移是一个重大的临床挑战，常伴有高发病率和死亡率。神经影像学、放射治疗和靶向全身治疗的最新进展，特别是 BRAF 和 MEK 抑制剂，改善了这种疾病的治疗。然而，黑色素瘤脑转移的最佳治疗方法仍然是一个正在讨论的话题，没有普遍接受的治疗方案。对携带 BRAF V600E 突变的患者，立体定向放射外科联合 encorafenib 和 binimetinib 的靶向治疗具有治疗前景，但需要谨慎的毒性管理，以确保安全性和疗效。
一名 61 岁男性，患有转移性 BRAF V600E 突变黑色素瘤，右侧枕叶有一个 20 毫米的脑转移灶，表现为急性发作的复视。患者正在接受转移性肺受累的 encorafenib 和 binimetinib 全身治疗。脑部 MRI 显示转移性病变伴周围水肿。为了最大限度地降低重叠毒性的风险，设计了一种治疗策略，将立体定向放射外科与靶向治疗的暂时中断相结合。立体定向放射外科以 27 Gy 的总剂量分为三次进行，在放射外科前 24 小时和后 24 小时暂停 encorafenib 和 binimetinib。治疗后，患者的复视完全缓解，两个月后的随访 MRI 显示脑转移灶几乎完全消退。治疗后 30 个月，患者无复发，继续接受全身治疗，耐受性良好，无不良反应报告。
本病例证明了立体定向放射外科联合 encorafenib 和 binimetinib 治疗携带 BRAF V600E 突变的黑色素瘤脑转移的疗效和安全性。这种方法提供了有效的疾病控制，症状缓解、MRI 上几乎完全消退和 30 个月时持续缓解证明了这一点，没有观察到不良反应。需要进一步的研究来为这一患者群体制定优化治疗结果的标准化方案。
