Chan Angela My, Roldan Urgoiti Gloria, Jiang Will, Lee Sandra, Kornaga Elizabeth, Mathen Peter, Yeung Rosanna, Enwere Emeka K, Box Alan, Konno Mie, Koebel Martin, Joseph Kurian, Doll Corinne M
Precision Oncology Hub, Tom Baker Cancer Centre, Department of Oncology, University of Calgary, Calgary, AB, Canada.
Department of Oncology, University of Calgary, Calgary, AB, Canada.
Front Oncol. 2022 Oct 7;12:1000263. doi: 10.3389/fonc.2022.1000263. eCollection 2022.
Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS).
Ninety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS.
Of the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052.
Tumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.
程序性死亡配体1（PD-L1）表达已被证明在多种癌症类型中具有预后意义，并被用于考虑检查点抑制剂免疫治疗。然而，关于PD-L1在肛管鳞状细胞癌（ASCC）患者中的预后影响的数据非常有限且相互矛盾。本研究的目的是测量接受根治性放化疗（CRT）的ASCC患者中PD-L1和CD8的表达，并将肿瘤表达与无进展生存期（PFS）和总生存期（OS）相关联。
纳入2000年至2013年间在两个三级癌症中心接受原发性CRT治疗且有可用治疗前肿瘤样本的99例ASCC患者。对治疗前肿瘤标本的组织微阵列（TMA）进行PD-L1和CD8染色。使用HALO图像分析软件对肿瘤和基质中的PD-L1表达进行定量，并采用定量方法解释结果。由一名经过培训的病理学家使用0-4评分系统对肿瘤内CD8细胞的密度进行半定量解释。采用对数秩检验的Kaplan-Meier分析来确定肿瘤标志物与PFS和OS关联的显著性。采用Cox多变量分析来探索PFS和OS的独立预测因素。
99例患者中，63例（64%）有足够的肿瘤样本进行全面分析。63例中的32例（50.8%）记录为CD8高状态。88.9%的病例PD-L1表达呈阳性。约一半患者的肿瘤PD-L1≥5%。肿瘤PD-L1≥5%的患者与表达较低的患者相比，OS更好，HR=0.32（95%CI 0.11-0.87），p=0.027；10年总生存率：肿瘤PD-L1≥5%的患者为84%，而PD-L1<5%的患者为49%。PD-L1表达与PFS无关。多变量分析显示，肿瘤PD-L1≥5%对更好的OS有统计学意义的趋势，HR=0.55（95%CI 0.12-1.00），p=0.052。
肿瘤PD-L1≥5%与接受CRT治疗的ASCC患者的OS相关。使用这一独特切点的PD-L1表达状态在该疾病患者的预后评估中值得进一步验证。未来的研究需要确定基于PD-L1状态的替代治疗策略的益处。
