仇文涛, 李振辉, 焦一平, 王向学, 张深燕, 吴琳, 徐军. 自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效[J]. 中国肿瘤临床, 2023, 50(23): 1203-1210. DOI: 10.12354/j.issn.1000-8179.2023.20231107
引用本文: 仇文涛, 李振辉, 焦一平, 王向学, 张深燕, 吴琳, 徐军. 自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效[J]. 中国肿瘤临床, 2023, 50(23): 1203-1210. DOI: 10.12354/j.issn.1000-8179.2023.20231107
Wentao Qiu, Zhenhui Li, Yiping Jiao, Xiangxue Wang, Shenyan Zhang, Lin Wu, Jun Xu. Automated quantified tumor-stroma ratio predicts neoadjuvant chemotherapy response in gastric cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(23): 1203-1210. DOI: 10.12354/j.issn.1000-8179.2023.20231107
Citation: Wentao Qiu, Zhenhui Li, Yiping Jiao, Xiangxue Wang, Shenyan Zhang, Lin Wu, Jun Xu. Automated quantified tumor-stroma ratio predicts neoadjuvant chemotherapy response in gastric cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(23): 1203-1210. DOI: 10.12354/j.issn.1000-8179.2023.20231107

自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效

Automated quantified tumor-stroma ratio predicts neoadjuvant chemotherapy response in gastric cancer

  • 摘要:
      目的  探讨通过深度学习的方法来全自动定量评估术前活检标本的肿瘤-间质比(tumor-stroma ratio,TSR)是否可以预测胃癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效。
      方法  选取2013年3月至2020年3月在云南省肿瘤医院接受NAC治疗的胃癌患者的术前活检切片148张和手术切除切片43张。构建肿瘤区域分割模型和上皮-间质分割模型,使用手术切除切片训练和评估模型,在活检切片上预测,取二者预测结果的交集,根据TSR的定义得到TSR值。根据术后病理学肿瘤退缩分级(tumor regression grade,TRG)将所有患者分为反应良好者(TRG 0~1)和反应不良者(TRG 2~3)。采用单因素和多因素回归分析TSR与胃癌新辅助化疗疗效的相关性。
      结果  肿瘤组织分割模型的IOU(intersection over union)为0.94,上皮-间质分割模型的IOU为0.88。以44.93%和70.22%作为TSR的临界值,将患者分为低、中、高间质比组,三组之间反应良好者比例具有显著性差异(P<0.05)。多因素分析显示,TSR是治疗前对胃癌NAC反应的独立预测因子(OR=0.10,95%CI:0.03~0.32)。使用常规临床信息预测治疗响应的基础上,加入TSR三分类等级作为治疗响应的预测变量时,曲线下面积(area under curve,AUC)可从0.71提升至0.85。
      结论  该模型能够在病理切片上自动分割肿瘤区域、上皮区域和间质区域,并能够自动、准确的计算出TSR,同时发现基于此方法自动计算的TSR可以预测NAC疗效。

     

    Abstract:
      Objective  The tumor-stroma ratio (TSR) is considered an independent prognostic factor for gastric cancer. Traditionally, TSR assessments have relied on the visual evaluation of surgical specimens, which is a method that lacks objectivity. This study was conducted to investigate whether the TSR in preoperative biopsy specimens can be automatically quantified using deep learning methods and whether the TSR value can be used to predict the efficacy of neoadjuvant chemotherapy (NAC) in patients with gastric cancer.
      Methods  In total, 148 preoperative biopsy slides and 43 surgical resection slides from patients with gastric cancer who underwent NAC treatment at Yunnan Cancer Hospital between March 2013 and March 2020 were used in the study. Tumor region segmentation and epithelial-stromal segmentation models were developed. The surgical resection slides were used to trained and evaluate the model, and the biopsy slides were used to test their predictive abilities. The TSR values were determined on the basis of the intersection of predictions from both models. The postoperative pathological tumor regression grade (TRG) was used to categorize patients into good responders (TRG 0-1) and poor responders (TRG 2-3). Univariate and multivariate Logistic regression analyses were conducted to determine the correlation between the TSR value and the efficacy of NAC in gastric cancer.
      Results  The intersection over union (IOU) value was 0.94 for the tumor tissue segmentation model and 0.88 for the epithelial-stromal segmentation model. Using cutoff values of 44.93% and 70.22%, patients were classified into low, intermediate, and high TSR groups. The proportion of good responders was significantly different among these groups (P<0.05). Multivariate Logistic regression analysis indicated that the TSR was an independent predictor of NAC response in gastric cancer (OR=0.10, 95% CI: 0.03-0.32). When the TSR three-category classification was added as a predictor of treatment response alongside conventional clinical information, the area under curve (AUC) increased from 0.71 to 0.85.
      Conclusions  This deep learning model is capable of automatically segmenting tumor, epithelial, and stromal regions based on pathological slides, accurately calculating TSR value, and predicting the efficacy of NAC on the basis of the automatically computed TSR values.

     

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