Manne Ashish, Tounkara Fode, Min Eric, Samuel Paul, Benson Katherine, Noonan Anne M, Mittra Arjun, Hays John, Roychowdhury Sameek, Malalur Pannaga, Rahman Shafia, Jin Ning, Pitter Kenneth, Miller Eric, Diaz Alexandra, He Kai
Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Department of Biostatistics, The Ohio State University, Columbus, OH 432120, USA.
Gastroenterology Res. 2024 Dec;17(5-6):195-204. doi: 10.14740/gr1768. Epub 2024 Oct 2.
Immune checkpoint inhibitors (ICIs) have moved to the frontline in recent years to manage upper gastrointestinal (UGI) tumors, such as esophageal and gastric cancers. This retrospective review sheds light on real-world data on ICI-treated UGI tumors to identify risk factors (clinical and pathological) impacting the outcome other than traditional biomarkers (programmed cell death ligand 1 (PD-L1) or microsatellite instability status).
Patients with UGI tumors who received at least one dose of ICI for stage IV or recurrent disease between January 1, 2015, and July 31, 2021, at The Ohio State University were included in the study. The patients' baseline characteristics, labs, and blood counts (even at disease progression) were extracted with survival outcomes (progression-free survival (PFS) and overall survival (OS)). Descriptive statistics, log-rank test and Cox proportional hazard model for survival outcomes, Fisher exact test for categorical variables, were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC).
We had 64 patients (84% males) included in the study, with the racial distribution as follows: 88% Caucasian, 5% African American, 1% Asian, and 6% from other racial groups. Men and the use of ICI in third lines or more had a positive impact on PFS and OS. For OS, 1) history of surgery positively impacted the outcome, while bone metastases worsened it; 2) baseline red blood cell count (RBC), hemoglobin, and thyroid-stimulating hormone (TSH) negatively impacted the OS. For PFS, 1) PD-L1 positivity, baseline lymphocyte count, and aspartate transferase levels had a positive impact; 2) human epidermal growth factor receptor 2 (HER2) positivity, baseline RBC, TSH, alkaline phosphatase, and alanine transferase (AST) levels had a negative impact. A slight increase in white blood cell (WBC) count (by 1.54, P = 0.02) and a drop in lymphocyte count (by 0.1907, P = 0.003) was significantly associated with disease progression.
Baseline risk factors and monitoring blood counts can help predict outcomes in ICI-treated UGI tumors. We need larger studies to confirm this.
近年来，免疫检查点抑制剂（ICI）已成为治疗上消化道（UGI）肿瘤（如食管癌和胃癌）的一线用药。这项回顾性研究揭示了ICI治疗UGI肿瘤的真实世界数据，以确定除传统生物标志物（程序性细胞死亡配体1（PD-L1）或微卫星不稳定性状态）之外影响预后的风险因素（临床和病理方面）。
纳入2015年1月1日至2021年7月31日期间在俄亥俄州立大学因IV期或复发性疾病接受至少一剂ICI治疗的UGI肿瘤患者。提取患者的基线特征、实验室检查结果和血细胞计数（即使在疾病进展时）以及生存结局（无进展生存期（PFS）和总生存期（OS））。使用JMP Pro 16（SAS Institute Inc.，北卡罗来纳州卡里）进行描述性统计、生存结局的对数秩检验和Cox比例风险模型，以及分类变量的Fisher精确检验。
本研究纳入64例患者（84%为男性），种族分布如下：88%为白种人，5%为非裔美国人，1%为亚洲人，6%来自其他种族群体。男性以及三线或更晚使用ICI对PFS和OS有积极影响。对于OS，1）手术史对结局有积极影响，而骨转移则使其恶化；2）基线红细胞计数（RBC）、血红蛋白和促甲状腺激素（TSH）对OS有负面影响。对于PFS，1）PD-L1阳性、基线淋巴细胞计数和天冬氨酸转氨酶水平有积极影响；2）人表皮生长因子受体2（HER2）阳性、基线RBC、TSH、碱性磷酸酶和丙氨酸转氨酶（AST）水平有负面影响。白细胞（WBC）计数略有增加（增加1.54，P = 0.02）和淋巴细胞计数下降（下降0.1907，P = 0.003）与疾病进展显著相关。
基线风险因素和监测血细胞计数有助于预测ICI治疗的UGI肿瘤的预后。我们需要更大规模的研究来证实这一点。
