Department of Diagnostic Radiology, M. D. Anderson Cancer Center, T. Boone Pickens Academic Tower, Houston, TX 77030, USA.
AJR Am J Roentgenol. 2011 Dec;197(6):W992-W1000. doi: 10.2214/AJR.10.6198.
Monoclonal antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4) used for treatment of metastatic melanoma produce inflammatory immune-related adverse events. The purpose of the current study was to retrospectively identify and characterize the radiologic manifestations of immune-related adverse events and to evaluate the possible association between these events and clinical responses to anti-CTLA-4 therapy.
We retrospectively reviewed the images and medical records of 119 patients with metastatic melanoma treated with anti-CTLA-4 at our institution and assessed the presence of radiologic manifestations of immune-related adverse events and the clinical responses to therapy. The responses were categorized as progressive or controlled disease. The controlled disease category included stable disease, partial response, and complete response according to the Response Evaluation Criteria in Solid Tumors, version 1.1.
Radiologic manifestations of immune-related adverse events were found in 20 patients (16.8%). Clinically evident manifestations included colitis, hypophysitis, thyroiditis, and arthritis. Clinically silent manifestations were benign lymphadenopathy and inflammatory changes in the soft tissues, such as myositis, fasciitis, and retroperitoneal fat haziness. There was a significant association between the incidence of radiologic manifestations of immune-related adverse events and clinical responses to anti-CTLA-4 therapy. The disease control rates were 18% for the entire group, 55% for the group with, and 10% for the group without radiologic manifestations of immune-related adverse events. In three patients (2.5%), lymphadenopathy related to radiologic manifestations of immune-related adverse events was interpreted as suspected metastasis but was proved benign at biopsy.
Radiologic manifestations of immune-related adverse events are associated with significant clinical benefit of anti-CTLA-4 therapy. In the era of developing immune checkpoint-targeted therapy for metastatic melanoma, radiologists should be alert to the possibility of these manifestations, which can mimic radiologic disease progression.
用于治疗转移性黑色素瘤的细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）单克隆抗体可引起炎症性免疫相关不良事件。本研究的目的是回顾性识别和描述免疫相关不良事件的影像学表现，并评估这些事件与抗 CTLA-4 治疗临床反应之间的可能关联。
我们回顾性地审查了在我们机构接受抗 CTLA-4 治疗的 119 例转移性黑色素瘤患者的图像和病历，并评估了免疫相关不良事件的影像学表现以及对治疗的临床反应。根据实体瘤反应评价标准 1.1，将反应分为进行性疾病或控制疾病。控制疾病类别包括稳定疾病、部分缓解和完全缓解。
在 20 例患者（16.8%）中发现了免疫相关不良事件的影像学表现。临床上明显的表现包括结肠炎、垂体炎、甲状腺炎和关节炎。临床上无症状的表现为良性淋巴结病和软组织的炎症性改变，如肌炎、筋膜炎和腹膜后脂肪混浊。免疫相关不良事件的影像学表现的发生率与抗 CTLA-4 治疗的临床反应之间存在显著关联。整个组的疾病控制率为 18%，有影像学表现的组为 55%，无影像学表现的组为 10%。在 3 例患者（2.5%）中，与免疫相关不良事件的影像学表现相关的淋巴结病被解释为疑似转移，但活检证实为良性。
免疫相关不良事件的影像学表现与抗 CTLA-4 治疗的显著临床获益相关。在开发转移性黑色素瘤的免疫检查点靶向治疗的时代，放射科医生应该警惕这些表现的可能性，这些表现可能模仿影像学疾病进展。
