Matsui Ayaka, Yoshida Taichi, Takahashi Yuya, Fukuda Koji, Shimazu Kazuhiro, Taguchi Daiki, Shinozaki Hanae, Kodama Naoaki, Kato Shunsuke, Waki Hironori, Nanjo Hiroshi, Shibata Hiroyuki
Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan.
Department of Metabolism and Endocrinology, Graduate School of Medicine, Akita University, Akita, Japan.
Int Cancer Conf J. 2025 Feb 14;14(2):163-170. doi: 10.1007/s13691-025-00752-3. eCollection 2025 Apr.
The immune checkpoint system suppresses T-cell activity. Unlike cytotoxic anticancer drugs that directly kill cells, immune checkpoint inhibitors (ICIs) are generally safer by stimulating tumor immunity. However, most clinical trials require patients to have a better performance status (PS), leaving limited evidence for those with poorer PS. In practice, patients may be classified with poor PS due to tumor-induced pain and motor dysfunction, even if major organs remain functional. Real-world data on non-small cell lung cancer has shown no safety difference between patients with PS 3/4 and those with lower PS. Approximately 20-30% of endometrial cancer cases show microsatellite instability-high (MSI-high), the highest among common malignancies. A 46-year-old patient with advanced, recurrent endometrial cancer resistant to standard chemotherapy, and PS of 4 from severe pelvic pain, was diagnosed with MSI-high. Pembrolizumab was initiated and continued for 19 courses, after which lesions had disappeared or calcified, leading to drug discontinuation. Now, 4 and a half years post-treatment, she has regained independent mobility and returned to work, and her PS has improved to approximately 1. Side effects included Grade 2 or lower thyroiditis, hypothyroidism, and hypoadrenalism, manageable with hormone replacement therapy and temporary pembrolizumab suspension. This case underscores the need to test for MSI-high/mismatch repair deficiency in endometrial cancer and to consider ICI therapy in patients with poor PS but no major organ dysfunction. In such cases, ICI can rapidly improve overall condition, a phenomenon known as a Lazarus-type response, as seen in other cancers such as non-small cell lung cancer.
The online version contains supplementary material available at 10.1007/s13691-025-00752-3.
免疫检查点系统会抑制T细胞活性。与直接杀死细胞的细胞毒性抗癌药物不同，免疫检查点抑制剂（ICI）通过刺激肿瘤免疫反应，通常更安全。然而，大多数临床试验要求患者具有较好的体能状态（PS），因此针对PS较差患者的证据有限。在实际临床中，即使主要器官功能尚好，患者也可能因肿瘤引起的疼痛和运动功能障碍而被归类为PS较差。非小细胞肺癌的真实世界数据显示，PS为3/4的患者与PS更低的患者之间在安全性上并无差异。大约20%-30%的子宫内膜癌病例表现为微卫星高度不稳定（MSI-H），这在常见恶性肿瘤中比例最高。一名46岁的晚期复发性子宫内膜癌患者，对标准化疗耐药，因严重盆腔疼痛导致PS为4，被诊断为MSI-H。开始使用帕博利珠单抗并持续治疗19个疗程后，病灶消失或钙化，遂停药。现在，治疗后四年半，她已恢复独立活动能力并重返工作岗位，PS改善至约1。副作用包括2级或以下的甲状腺炎、甲状腺功能减退和肾上腺功能减退，通过激素替代疗法和暂时停用帕博利珠单抗可控制。该病例强调了对子宫内膜癌进行MSI-H/错配修复缺陷检测的必要性，并考虑对PS较差但无主要器官功能障碍的患者进行ICI治疗。在这种情况下，ICI可以迅速改善整体状况，这种现象被称为拉撒路式反应，在非小细胞肺癌等其他癌症中也有出现。
在线版本包含补充材料，可在10.1007/s13691-025-00752-3获取。
