Pedersen Sidsel, Johansen Emma Lund, Højholt Karen Louise, Pedersen Marie Wett, Mogensen Anne Mark, Petersen Søren Kjær, Haslund Charlotte Aaquist, Donia Marco, Schmidt Henrik, Bastholt Lars, Friis Rasmus, Svane Inge Marie, Ellebaek Eva
National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
Eur J Cancer. 2025 Feb 25;217:115253. doi: 10.1016/j.ejca.2025.115253. Epub 2025 Jan 21.
Advances in modern therapies have improved outcomes for patients with melanoma brain metastases (MBM), though prognosis remains poor. The optimal treatment strategy for patients who do not meet clinical trial inclusion criteria is unclear.
This study included all patients with MBM diagnosed in Denmark between 2015 and 2022, identified through the Danish Metastatic Melanoma Database (DAMMED) and local surgical and radiotherapy records. Data were collected from electronic patient records.
A total of 838 patients were included, with a median overall survival (OS) of 9.0 months. Of these, 112 (19.4 %) survived beyond 3 years post-diagnosis. Patients treated with immune checkpoint inhibitors (ICI) as first line treatment, specifically ipilimumab + nivolumab, demonstrated an intracranial overall response rate (icORR) of 46 % and a 2-year OS of 49 %. Those treated with BRAF/MEK inhibitors (BRAF/MEKi) had an icORR of 56 % but a 2-year OS of 20 %. Patients with leptomeningeal disease (LMD, n = 67) had a median OS of 8.4 months. Systemic therapy was associated with a superior OS for patients with LMD, though no survival benefit was seen with ICI compared to BRAF/MEKi. Among the 230 patients who underwent surgery, 30 received postoperative stereotactic radiosurgery (SRS); however, there was no difference in OS or intracranial progression-free survival between the groups.
A considerable proportion of patients with brain metastases diagnosed after 2015 survived more than 3 years. Patients with LMD appeared to obtain limited benefit of ICI with only few patients alive > 3 years post-diagnosis.
现代疗法的进步改善了黑色素瘤脑转移（MBM）患者的预后，尽管预后仍然很差。对于不符合临床试验纳入标准的患者，最佳治疗策略尚不清楚。
本研究纳入了2015年至2022年在丹麦诊断为MBM的所有患者，通过丹麦转移性黑色素瘤数据库（DAMMED）以及当地手术和放疗记录进行识别。数据从电子病历中收集。
共纳入838例患者，中位总生存期（OS）为9.0个月。其中，112例（19.4%）在诊断后存活超过3年。接受免疫检查点抑制剂（ICI）作为一线治疗，特别是伊匹木单抗+纳武单抗治疗的患者，颅内总缓解率（icORR）为46%，2年总生存率为49%。接受BRAF/MEK抑制剂（BRAF/MEKi）治疗的患者icORR为56%，但2年总生存率为20%。软脑膜疾病（LMD，n = 67）患者的中位总生存期为8.4个月。全身治疗与LMD患者的总生存期延长相关，尽管与BRAF/MEKi相比，ICI未显示出生存获益。在230例接受手术的患者中，30例接受了术后立体定向放射外科治疗（SRS）；然而，两组之间的总生存期或颅内无进展生存期没有差异。
2015年后诊断为脑转移的患者中有相当一部分存活超过3年。LMD患者似乎从ICI中获益有限，诊断后超过3年存活的患者很少。
