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免疫检查点抑制剂在实体瘤辅助治疗中的应用:当前进展、未来方向及在移植肿瘤学中的作用

英文原题:Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology.

PubMed 2023/02/23(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

在辅助治疗中使用免疫检查点抑制剂(ICIs)的理由是清除微转移灶,并最终延长生存期。

中文摘要

在辅助治疗中使用免疫检查点抑制剂(ICIs)的理论基础是清除微转移灶,并最终延长生存期。迄今为止,临床试验已证明,为期1年的辅助ICIs治疗可降低黑色素瘤、尿路上皮癌、肾细胞癌、非小细胞肺癌以及食管癌和胃食管交界处癌的复发风险。黑色素瘤已显示出总生存获益,而其他恶性肿瘤的生存数据尚未成熟。新出现的数据还表明,在肝胆恶性肿瘤的围移植期使用ICIs具有可行性。虽然ICIs通常耐受性良好,但慢性免疫相关不良事件(通常为内分泌病变或神经毒性)以及迟发性免疫相关不良事件的发生,要求进一步审视辅助治疗的最佳持续时间,并进行全面的风险-获益评估。基于血液的动态生物标志物,如循环肿瘤DNA(ctDNA)的出现,有助于检测微小残留病灶并识别可能从辅助治疗中获益的患者亚群。此外,TIL(肿瘤浸润淋巴细胞)、中性粒细胞与淋巴细胞比值以及经ctDNA校正的血液肿瘤突变负荷(bTMB)的特征分析,在预测免疫治疗反应方面也显示出前景。在更多前瞻性研究明确总生存获益的幅度并验证预测性生物标志物的应用之前,应将个体化、以患者为中心的辅助ICIs治疗策略常规纳入临床实践,包括对患者进行关于潜在不可逆不良事件的充分咨询。

展开英文摘要原文

The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk-benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.

论文信息

作者
Abboud K、Umoru G、Esmail A、Abudayyeh A、Murakami N、Al-Shamsi HO、Javle M、Saharia A
第一作者单位
Department of Pharmacy, Houston Methodist Hospital, Houston, TX 77030, USA.United States
通讯作者单位
Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA.United States
文献类型
综述
期刊
Cancers2023 Feb 23
原文标识
PubMed 36900226 · DOI 10.3390/cancers15051433