Anti-PD-1 Immunotherapy and Radiotherapy for Stage IV Intrahepatic Cholangiocarcinoma: A Case Report
Anti-PD-1 Immunotherapy and Radiotherapy for Stage IV Intrahepatic Cholangiocarcinoma: A Case Report
复制标题
DOI：
10.3389/fmed.2020.00368
复制
发表时间：
2020-08-28
影响因子：
3.9
通讯作者：
Kuang, Ming
中科院分区：
文献类型：
--
作者：
Liu, Ze-Long;Liu, Xin;Kuang, Ming
由于目前的预测性生物标志物在许多情况下的稳健性不理想，免疫治疗在治疗选择有限的晚期癌症（如IV期肝内胆管癌（ICC））中的应用非常普遍。因此，迫切需要提高免疫治疗效果或扩大潜在受益患者范围的策略。放射治疗与抗程序性死亡受体-1 （anti-programmed death receptor-1, PD-1）免疫治疗相结合是一种很有前景的治疗方法，因为在动物模型和少数患者中发现它们具有协同抗肿瘤作用。我们在此报告一位68岁的男性患者，患有化疗无法耐受的IV期ICC，其原发肿瘤PD-L1表达水平低，肿瘤微环境中缺乏CD8+细胞，微卫星不稳定性高（MSI），肿瘤突变负担高（TMB）。这些生物标志物对抗pd -1免疫治疗的治疗反应和临床获益的预测相互矛盾。采用抗pd -1免疫治疗联合放疗作为一线治疗。经过6个周期的免疫治疗后，原发性肝脏肿瘤和转移性淋巴结出现缩小，并伴有新的肺转移，这表明反应不一。然后对肝脏和肺部病变进行放疗，并伴随持续的免疫治疗。联合治疗最终导致原发肿瘤和所有转移瘤完全缓解，没有治疗相关的不良反应。该患者在联合治疗后存活了26个月，目前仍无肿瘤。该病例表明，在ICC中，免疫治疗反应生物标志物与免疫治疗和放疗的协同抗肿瘤作用高度不一致。
Due to the unsatisfactory robustness of current predictive biomarkers in many cases, application of immunotherapy in advanced cancers with limited treatment options, such as stage IV intrahepatic cholangiocarcinoma (ICC), was quite common. Hence, strategies to enhance the therapeutic effect of immunotherapy or to extend the scope of potential beneficial patients were urgently needed. Combination of radiotherapy and anti-programmed death receptor-1 (PD-1) immunotherapy was a promising one, since they were found to have a synergistic anti-tumor effect in animal models and a couple of patients. We here present a 68-years-old male with chemotherapy-intolerable stage IV ICC, whose primary tumor had low PD-L1 expression level, scarce CD8+ cells in tumor microenvironment, high microsatellite instability (MSI), and high tumor mutation burden (TMB). These biomarkers showed a conflicting prediction of the treatment response and clinical benefit of anti-PD-1 immunotherapy. Combination therapy of anti-PD-1 immunotherapy and radiotherapy was adopted as first-line treatment for the patient. After six cycles of immunotherapy, shrinkage of the primary liver tumor and metastatic lymph nodes happened, alongside with new lung metastasis, which indicated a mixed response. Radiotherapy was then administered to both the liver and lung lesions, accompanied with continued immunotherapy. The combined therapy eventually led to a complete response for both the primary tumor and all metastases without treatment-related adverse effects. The patient has survived for 26 months after the combined therapy and remains tumor-free currently. This case demonstrates the high inconsistency between immunotherapy response biomarkers and the synergetic anti-tumor effect of immunotherapy and radiotherapy in ICC.