Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
BMC Med. 2022 Oct 24;20(1):403. doi: 10.1186/s12916-022-02609-5.
Although neoadjuvant anti-PD-1 immunotherapies have shown good efficacy in non-small cell lung cancer (NSCLC) patients, there is still a lack of effective predictive markers. We aimed to develop a pretreatment histologic scoring system to predict the efficacy of neoadjuvant immunotherapy.
One hundred forty NSCLC cases were evaluated in this study. Initially, surgical specimens from 31 squamous cell lung cancer patients treated with neoadjuvant anti-PD-1 therapy and their eligible paired pretreatment biopsies were used for pathologic evaluation and developing the pretreatment scoring system, immune-related histologic phenotype assessment criteria (irHPC). Three trained pathologists independently scored the haematoxylin-eosin (HE) slides of the pretreatment tumour biopsies according to irHPC. The follow-up was from 07 March 2018 to 31 December 2021, mainly focusing on disease-free survival (DFS) and overall survival (OS). Second, 109 biopsies of lung squamous cell carcinoma were evaluated to explore the relationship between eosinophils and PD-L1 expression.
Superior 2-year DFS rates and 2-year OS rates were observed in patients who achieved major pathologic response (MPR) (MPR vs. non-MPR: 92.9% vs. 78.6%; 100.0% vs. 93.3%). Whether necrosis was included in the calculation of the per cent of residual viable tumour (%RVT) or not had almost no effect on the consistency of pathologic assessment and the histological response grouping. The interpathologist variability in assessing %RVT with immune-activated phenotype was not statistically significant (P = 0.480). Four immune-related features of pretreatment biopsies were included for calculating the predictive score. The trained pathologist accurately predicted most cases according to irHPC. For interobserver reproducibility using "2 points" as the cutoff, the overall per cent agreement was 77.8%. The reliability between pathologists for a binary tumour evaluation showed "moderate" agreement (κ = 0.54). Patients with scores ≥ 2 points tended to have better 2-year DFS rates and 2-year OS rates than those with scores < 2 points (85.7% vs. 71.4%; 100.0% vs. 87.5%).
The irHPC scoring system reflecting the preexisting immune response could be used to predict pathologic response to neoadjuvant immunotherapy, possibly further predicting the long-term prognosis, but larger trials are needed for verification.
尽管新辅助抗 PD-1 免疫疗法在非小细胞肺癌（NSCLC）患者中显示出良好的疗效，但仍缺乏有效的预测标志物。我们旨在开发一种预处理组织学评分系统，以预测新辅助免疫治疗的疗效。
本研究评估了 140 例 NSCLC 病例。最初，对 31 例接受新辅助抗 PD-1 治疗的鳞状细胞肺癌患者的手术标本及其合格的预处理活检进行了病理评估，并制定了预处理评分系统，即免疫相关组织学表型评估标准（irHPC）。三名经过培训的病理学家根据 irHPC 独立评估预处理肿瘤活检的苏木精-伊红（HE）切片。随访时间为 2018 年 3 月 7 日至 2021 年 12 月 31 日，主要关注无病生存期（DFS）和总生存期（OS）。其次，评估了 109 例肺鳞状细胞癌活检，以探讨嗜酸性粒细胞与 PD-L1 表达的关系。
在达到主要病理缓解（MPR）的患者中观察到更高的 2 年 DFS 率和 2 年 OS 率（MPR 与非 MPR：92.9% vs. 78.6%；100.0% vs. 93.3%）。无论在计算残留活肿瘤百分比（%RVT）时是否包括坏死，对病理评估的一致性和组织学反应分组几乎没有影响。免疫激活表型评估 %RVT 的病理学家间变异性无统计学意义（P = 0.480）。将预处理活检的 4 个免疫相关特征纳入计算预测评分。经过培训的病理学家根据 irHPC 准确地预测了大多数病例。对于使用“2 分”作为截定点的观察者间重现性，总体百分一致率为 77.8%。用于二元肿瘤评估的病理学家之间的可靠性显示出“中等”一致性（κ=0.54）。评分≥2 分的患者的 2 年 DFS 率和 2 年 OS 率倾向于高于评分<2 分的患者（85.7% vs. 71.4%；100.0% vs. 87.5%）。
反映预先存在的免疫反应的 irHPC 评分系统可用于预测新辅助免疫治疗的病理反应，可能进一步预测长期预后，但需要更大规模的试验进行验证。
