Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
World Neurosurg. 2020 Jul;139:226-231. doi: 10.1016/j.wneu.2020.04.087. Epub 2020 Apr 21.
The use of targeted therapies and immune checkpoint inhibitors has drastically changed the management of patients with melanoma and brain metastases. Specifically, combination therapy with ipilimumab, a cytotoxic T-lymphocyte antigen 4 inhibitor, and nivolumab, a programmed cell death protein 1 inhibitor, has become a preferred systemic therapy option for patients with melanoma and asymptomatic brain metastases. However, the efficacy and toxicity profile of these agents in combination with brain-directed radiation therapy is not well described.
In this case series, we highlight a series of patients with melanoma demonstrating severe radiation necrosis immediately refractory to surgical resection following brain-directed stereotactic radiation therapy with concurrent ipilimumab and nivolumab. Three patients described in this series each received stereotactic radiation therapy to a dose of 30 Gy in 5 fractions to a melanoma brain metastasis. These areas developed radiographic evidence of necrosis, which was managed surgically and progressed immediately and rapidly after resection. Re-resection, bevacizumab, steroids, and/or discontinuation of nivolumab was used to mitigate further necrosis with varying efficacy.
Patients with metastatic melanoma receiving brain-directed radiation therapy with concurrent ipilimumab and nivolumab are at risk for developing severe, surgically refractory radiation necrosis and should be closely followed clinically and with imaging. The exact mechanism for such severe necrosis is unknown, and future studies are needed to better understand this pathophysiology and identify optimal treatment strategies.
靶向治疗和免疫检查点抑制剂的使用极大地改变了黑色素瘤和脑转移患者的治疗方法。具体来说，细胞毒性 T 淋巴细胞相关抗原 4 抑制剂伊匹单抗(ipilimumab)和程序性死亡蛋白 1 抑制剂纳武单抗(nivolumab)的联合治疗已成为黑色素瘤和无症状脑转移患者的首选全身治疗选择。然而，这些药物联合脑定向放射治疗的疗效和毒性特征尚未得到很好的描述。
在本病例系列中，我们重点介绍了一系列黑色素瘤患者，这些患者在接受伊匹单抗和纳武单抗联合脑定向立体定向放射治疗后，立即对脑转移灶进行手术切除，出现严重的放射性坏死。本系列中描述的 3 名患者均接受立体定向放射治疗，脑转移灶的剂量为 30Gy，共 5 次。这些区域出现了坏死的放射学证据，通过手术进行了治疗，但在切除后迅速且迅速进展。再次切除、贝伐单抗、类固醇和/或停用纳武单抗在不同程度上缓解了进一步的坏死。
接受脑定向放射治疗联合伊匹单抗和纳武单抗治疗的转移性黑色素瘤患者有发生严重、手术难治性放射性坏死的风险，应密切进行临床和影像学随访。这种严重坏死的确切机制尚不清楚，需要进一步的研究来更好地了解这种病理生理学，并确定最佳的治疗策略。
