Chae Young Kwang, Wang Si, Nimeiri Halla, Kalyan Aparna, Giles Francis J
Developmental Therapeutics Program of the Division of Hematology Oncology, Northwestern University, Chicago, Illinois, USA.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Oncotarget. 2017 Jun 3;8(34):57889-57897. doi: 10.18632/oncotarget.18361. eCollection 2017 Aug 22.
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden. Tumor regression was subsequently observed and patient has remained in stable disease. Despite the substantial radiological progression, the symptomatic improvement reported by the patient led us to the decision of treatment continuation based on the suspicion of pseudoprogression, illustrating the importance of clinical evaluation in medical decision making while managing patients on immunotherapy. Additionally, the patient's MSI-high status contributes to his good, maintained response to PD-L1 blockade. Our case provides a frame of reference for fluctuation in tumor burden associated with pseudoprogression. Here we also evaluate the incidence and scale of pseudoprogression across solid tumor types.
通过免疫检查点抗体规避肿瘤介导的免疫抑制已在特定实体瘤患者中显示出临床益处。接受免疫治疗的患者存在反应异质性,包括假性进展,即肿瘤负荷最初增加,随后下降至疾病得到控制。然而,假性进展的特征和机制仍知之甚少。我们在此报告一例微卫星高度不稳定(MSI-H)的转移性结直肠癌患者,接受OX40激动剂和程序性死亡配体1(PD-L1)拮抗剂联合治疗,出现假性进展,肿瘤负荷较基线增加了163%。随后观察到肿瘤消退,患者病情保持稳定。尽管有显著的影像学进展,但患者报告的症状改善使我们基于假性进展的怀疑决定继续治疗,这说明了在管理接受免疫治疗的患者时,临床评估在医疗决策中的重要性。此外,患者的MSI-H状态有助于其对PD-L1阻断治疗保持良好反应。我们的病例为与假性进展相关的肿瘤负荷波动提供了参考框架。在此,我们还评估了实体瘤类型中假性进展的发生率和程度。